2015 Issue 2

Seminars in Orthodontics
EDITOR -IN-CHIEF
Elliott M. Moskowitz, DDS, MSd
EDITORIAL BOARD
EDITOR-IN-CHIEF EMERITUS
P. Lionel Sadowsky, DMD, BDS, DipOrth, MDent
Mani Alikhani, New York, NY (2017) Peter Ngan, Morgantown, WV (2015)

Rolf G. Behrents, St. Louis, MO (2017) Perry M. Opin, Milford, CT (2017)
S. Jay Bowman, Portage, MI (2017) Jae Hyun Park, Mesa, AZ (2017)
James Caveney, Wheeling, WV (2015) Sheldon Peck, Newton, MA (2014)
John Grubb, Chula Vista, CA (2015) C.B. Preston, Buffalo, NY (2017)
Greg Huang, Seattle, WA (2014) William R. Proffit, Chapel Hill, NC (2015)
Robert J. Isaacson, Edina, MN (2015) Eugene Roberts, Indianapolis, IN (2015)
Laurance Jerrold, Brooklyn, NY (2017) Emile Rossouw, Rochester, NY (2017)
Lysle E. Johnston, Jr., Eastport, MI (2015) David L. Turpin, Federal Way, WA (2017)
Donald R. Joondeph, Bellevue, WA (2015) James L. Vaden, Cookeville, TN (2015)
Robert G. Keim, Los Angeles, CA (2017) Robert L. Vanarsdall, Jr., Philadelphia, PA (2015)
Richard Kleefield, Norwalk, CT (2015) Katherine Vig, Columbus, OH (2017)
Steven J. Lindauer, Richmond, VA (2015) Christos Vlachos, Homewood, AL (2014)
James A. McNamara, Jr., Ann Arbor, MI (2017) Timothy T. Wheeler, Gainesville, FL (2015)
Ravindra Nanda, Farmington, CT (2017) Leslie A. Will, Boston, MA (2017)
INTERNATIONAL
Adrian Becker, Jerusalem, Israel (2017) Rakesh Koul, Lucknow, India (2017)
Jose´ Alexandre Bottrel, Rio de Janeiro, Brazil (2015) Birte Melsen, Aarhus, Denmark (2017)
Theodore Eliades, Nea Ionia, Greece (2014) Antony McCollum, Bryanston, South Africa (2015)
W.G. Evans, Johannesburg, South Africa (2017) Eliakim Mizarahi, Ilford, England (2015)
Jorge Faber, Brasilia, Brazil (2017) Bjørn Øgaard, Oslo, Norway (2017)
Joseph Ghafari, Beirut, Lebanon (2017) Nikolaos Pandis, Corfu, Greece (2017)
Vicente Hernandez, Alicante, Spain (2017) Pratik K. Sharma, London, UK (2017)
Nigel Hunt, London, England (2015) George Skinazi, Paris, France (2015)
Haluk Iseri, Ankara, Turkey (2017) John C. Voudouris, Toronto, Canada (2017)
Roberto Justus, Mexico City, Mexico (2015) William A. Wiltshire, Winnipeg, Canada (2015)
Sanjivan Kandasamy, Midland, WA, Australia (2017) Björn U. Zachrisson, Oslo, Norway (2015)
VOL 21, NO 2 JUNE 2015
Juvenile Idiopathic Arthritis and Temporomandibular Joint

Involvement: An Interdisciplinary Approach
Bjørn Øgaard, DDS, Dr Odont
Guest Editor
■ Introduction 71
Bjørn Øgaard
■ Juvenile idiopathic arthritis: A frequent cause for chronic joint inflammation in

childhood 72
Marinka Twilt and Nikolay Tzaribachev
■ Juvenile idiopathic arthritis characteristics: Etiology and pathophysiology 77

Lynn Spiegel, Kasper Dahl Kristensen, and Troels Herlin
■ Craniofacial growth and dento-alveolar development in juvenile idiopathic arthritis

patients 84
Timo Peltomäki, Sven Kreiborg, Thomas Klit Pedersen, and Björn Ogaard
■ Clinical craniofacial examination of patients with juvenile idiopathic arthritis 94

Peter Stoustrup and Bernd Koos
■ TMJ imaging in JIA patients—An overview 102

Tore A. Larheim, Andrea S. Doria, Eva Kirkhus, Dimitri A. Parra,
Christian J. Kellenberger, and Linda Z. Arvidsson
■ Magnetic resonance imaging of temporomandibular joints in juvenile idiopathic

arthritis 111
Christian J. Kellenberger, Linda Z. Arvidsson, and Tore A. Larheim
■ 3D digital surface imaging for quantification of facial development and asymmetry

in juvenile idiopathic arthritis 121
Tron A. Darvann, Per Larsen, Nuno V. Hermann, and Sven Kreiborg
■ Systemic and intra-articular anti-inflammatory therapy of temporomandibular joint

arthritis in children with juvenile idiopathic arthritis 125
Matthew L. Stoll, Randy Q. Cron, and Rotraud K. Saurenmann
■ Functional and orthopedic treatment in developing dentofacial growth deviation in

juvenile idiopathic arthritis 134
Thomas Klit Pedersen and Carlalberta Verna
■ Jaw surgery for correction of dentofacial anomalies caused by JIA 140

Sven Erik Nørholt, Tore Bjørnland, and Thomas Klit Pedersen
VOL 21, NO 2 JUNE 2015
Introduction
J uvenile idiopathic arthritis (JIA) affects chil-

dren and adolescence, and is the most com-
mon rheumatic disease in children with a
established in Oslo with more than 40 partici-
pants from 10 countries. Since then meetings
have been held in Zürich, Kiel, Utrecht, Aarhus,
reported prevalence in the Western world of and the last meeting in 2014 in Tampere with
about 1 per 1000 children. There has recently about 150 participants.
been increased focus on the temporomandibular Four working groups reflecting the inter-
joints (TMJs) that are more frequently affected disciplinary aspects between medicine and den-
than many of the other joints in JIA patients. tistry, has been established with clinical and/or
Severe craniofacial growth disturbances may gen-environmental leaders in (1) etiology,
occur when the TMJs are affected leading to a immunology, and molecular biology; (2) diag-
typical craniofacial morphology characterized by nostics, examination, and imaging; (3) treat-
mandibular retrognati and even asymmetries. ment; and (4) guidelines and policy statements.
There is currently no cure for the disease, There is a need for a more complete over-
which is of autoimmune nature. There is minor view of the current status for the disease
consensus regarding optimal treatment of JIA regarding its effect on the craniofacial complex,
patients, even if modern treatment with metho- diagnostics, and treatment. Therefore, leading
trexate and biologicals appear to have reduced scientist on JIA within the fields of rheumatol-
the occurrence and severity of the disease. ogy, molecular biology, maxillofacial radiology,
Remission of severely affected TMJ in JIA patients orthodontics, and oral surgery were invited to
has been reported. All is discussed in the present expertly review the literature in their particular
issue of Seminars in Orthodontics. field and point at shortcomings in the current
Due to the relative low prevalence of the knowledge.
disease, its complex nature and several subtypes, I hope these articles will provide more insight
international multicenter studies are mandatory. into the complex nature of the JIA disease in the
In 2010, an international research network, craniofacial area, and be of value for future mul-
EurotmJoint (European interdisiplinary network ticenter studies and hence for the JIA patients.
for research, diagnostics, and treatment of cra-
niofacial anomalies in Juvenile Idiopatic Arthritis Bjørn Øgaard, DDS, Dr Odont
patients (JIA) (http://eurotmj.com) for JIA was Guest Editor
& 2015 Elsevier Inc. All rights reserved.

http://dx.doi.org/10.1053/j.sodo.2015.02.001
Seminars in Orthodontics, Vol 21, No 2 (June), 2015: p 71 71

Juvenile idiopathic arthritis: A frequent cause
for chronic joint inflammation in childhood
Marinka Twilt, and Nikolay Tzaribachev
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in

childhood. JIA is divided in seven different subtypes based on different
inclusion and exclusion criteria. The long-term prognosis has changed over
the last 20 years due to new medical treatments available. (Semin Orthod
2015; 21:72–76.) & 2015 Elsevier Inc. All rights reserved.
Introduction cular JIA, psoriatic arthritis, enthesitis-related

arthritis, and undifferentiated arthritis.2 All
J uvenile idiopathic arthritis (JIA) is the most
common childhood rheumatic disease in the
subsets have their own inclusion and exclusion
criteria (Table). Extended oligoarticular JIA is
Western world, affecting approximately 1 per
found in the patient who presented with only a
1000 children overall.1 It is characterized by
few affected joints during the first 6 months of
persistent inflammation of the joints for at least 6
disease onset but subsequently developed a poly-
weeks, with an onset prior to the age of 16 years.2
articular course. Psoriatic arthritis was previously
JIA is a diagnosis of exclusion, and other causes
thought to be a separate disease; however, now it
of joint inflammation (e.g., infections, etc.)
has also been included in the JIA classification
should be excluded.
scheme. Enthesitis-related arthritis was formerly
Multiple names have been associated with this
known as seronegative enthesopathy and
illness, including Juvenile Chronic Arthritis
arthropathy or spondyloarthropathy or spondy-
(JCA) and Juvenile Rheumatoid Arthritis (JRA).
loarthritis. Undifferentiated arthritis represents
Currently, the disease is classified according to
the group of patients who either do not fulfill the
the International League of Associations for
criteria for one of the other subsets or fulfill the
Rheumatology (ILAR) revised classification,
criteria for more than one.
referring to the disease as JIA.2 The primary aim
The present criteria rely on clinical and lab-
for the reclassification of JIA was to define rela-
oratory features, but as the immunological basis
tively homogeneous, exclusive subsets of arthritis
of JIA becomes better understood, classification
for both prognostic and research purposes. This
may be defined by genetic predispositions for
classification consists of seven heterogeneous
gene expression and cytokine profiles. Mono-
subgroups (Table) based predominantly on clini-
nuclear cells in peripheral blood display different
cal manifestations and laboratory features within
gene expression profiles among the different JIA
the first 6 months of the disease.2 The new
subtypes, and further understanding of the
classification includes systemic-onset, oligoarticu-
pathophysiology of the disease may lead to more
lar (formerly pauciarticular,) and polyarticular
specific disease patterns and subsequent tailored
subsets, which were also represented in the old
treatment.
JRA and JCA criteria. However, the new ILAR
classification expanded further to include other
sub-classifications, such as extended oligoarti- Epidemiology
JIA is the most common form of childhood
Department of Rheumatology, Aarhus University Hospital, rheumatic disease with a prevalence of 1 in 1000
Skejby, Aarhus, Brendstrupgaardsvej 100 8200, Denmark; PRI children.3 The incidence of JIA in populations
Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany. from Europe and North America varies between
Corresponding author at: Department of Rheumatology,
1.3 and 22.6 per 100,000 person-years.4,5 Com-
Brendstrupgaardsvej 100, 8200 Aarhus, Denmark. E-mail: martwi
@rm.dk parison of these studies is difficult due to the use
of different terminology, diagnostic criteria, and
1073-8746/15/1801-$30.00/0 study designs. Children from European descents
http://dx.doi.org/10.1053/j.sodo.2015.02.002 were associated with a higher risk in a multiethnic
Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 72–76 72

Juvenile idiopathic arthritis 73
Table. ILAR classification of juvenile idiopathic arthritis

Systemic arthritis Arthritis with or preceded by at least 2 weeks of daily fever, with at least 3 days of quotidian fever.
Plus one of the following:
Evanescent, non-fixed erythematous rash
Generalized lymph node enlargement
Hepatomegaly, splenomegaly, or both
Exclusion:
Psoriasis or a history of psoriasis in a first-degree relative
Arthritis in an HLA B27-positive male beginning after his sixth birthday
History of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease,
reactive arthritis, or acute anterior uveitis in a first-degree relative
IgM rheumatoid factor positive on two or more occasions, at least 3 months apart
Oligoarticular JIA Persistent: arthritis of four or fewer joints throughout the disease course
Extended: arthritis of four or fewer joints in the first 6 months followed by arthritis of five or more joints
Exclusion:
Diagnosis of systemic juvenile idiopathic arthritis
Polyarticular Arthritis of five or more joints during the initial 6 months of the disease. Rheumatoid factor positive on two
RF-positive JIA or more occasions, at least 3 months apart.
Exclusion:
Polyarticular Arthritis of five or more joints during the initial 6 months of the disease. Rheumatoid factor negative.
RF-negative JIA Exclusion:
Psoriatic arthritis Arthritis and psoriasis
Or
Arthritis and two of the following:
Dactylitis
Nail pitting or onycholysis
Psoriasis in a first-degree relative
Exclusion:
Enthesitis-related Arthritis and enthesitis
arthritis OR
Arthritis OR enthesitis and two of the following:
Sacroiliac joint tenderness or inflammatory lumbosacral pain
HLA B27 positive
Arthritis in a male over 6 years of age
Acute anterior uveitis
Exclusion:
74 Twilt and Tzaribachev
Table. (continued )
Undifferentiated Fulfils none of the above subsets

arthritis OR
Fulfils more than one of the above subsets
cohort analysis.1 The distribution of JIA subtypes disease course is usually polyarticular.
differs significantly between different ethnic Inflammatory markers such as ESR and CRP are
backgrounds, confirming findings for the often markedly elevated. A life-threatening com-
prevalence and incidence of the different plication in sJIA is the development of macro-
subtypes in different countries across the world.1 phage activation syndrome.7 Both uveitis and
autoantibodies are not typically part of the
features of sJIA, and, in contrast to the other JIA
Clinical features subtypes, cells and cytokines of the innate immune
The diagnosis of JIA cannot be made based on response are involved, suggesting that sJIA may be
specific laboratory or radiological features. Joint considered an autoinflammatory disease.
swelling, reduced range of motion in a joint, or
warmth over an individual joint is a cardinal Oligoarticular JIA
feature of arthritis; however, they do not denote Oligoarthritis affects girls more than boys, and
the underlying pathology. As mentioned before, the age at onset distribution is characterized by a
other causes of chronic joint inflammation, such peak incidence between 1 and 2 years of age.
as infection, malignancy, trauma, hemarthrosis, Oligoarthritis accounts for 50–70% of all chil-
and other rheumatic diseases (e.g., sarcoidosis dren with chronic arthritis.1,4,5 Oligoarthritis is
and Sjogren syndrome), can present identically. defined by the involvement of four or less joints.
Typical inflammatory arthritis symptoms include If the total count of affected joints after the first 6
morning stiffness and more prominent limping months exceeds four, the disease is defined as
and pain in the morning or after periods of oligoarticular extended, while if no more than
inactivity; these features can be provided by a four joints are involved during the total disease
good history of symptoms. course, it is classified as persistent.2 Oligoarthritis
The different subsets of JIA do display a tends to affect mainly the joints in the lower
predilection for arthritis in different joints, extremities, with approximately 50% of
although in theory any joint can be affected in monoarthritis, usually of the knee. As an extra-
any of the subtypes. articular disease manifestation, uveitis may occur
in up to 20% of these children and is usually
Systemic arthritis (sJIA) asymptomatic. Antinuclear antibody testing is
positive in 65–85% of children with oligoarthritis,
This subtype affects both girls and boys (1:1) and
particularly in girls with associated uveitis.8
can occur at any age but with peak onset at 2 years
of age. sJIA is characterized by systemic features
Polyarticular JIA
often preceding the arthritis. The daily fever has to
be present for at least 2 weeks, with at least 3 days JIA affecting more than four joints within the first
of documented quotidian spikes (4391C).2 6 months of onset is defined as polyarthritis. Two
Besides the fever, at least one or more criteria subtypes are recognized: polyarticular rheuma-
need to be present (Table). The typical rash seen toid factor-negative JIA and polyarticular rheu-
in sJIA is an evanescent, non-fixed salmon-colored matoid factor-positive disease.2 Polyarticular JIA
erythematous rash, usually present when the fever accounts for approximately 20% of JIA, and
spikes. The generalized lymph node enlargement approximately 85% of these children are
can be very significant and lead to the suspicion of rheumatoid factor negative.1,4,5 Polyarticular
an underlying malignancy. The distribution of RF-negative JIA more frequently affects boys than
arthritis seen in sJIA includes both small and large girls and displays two phases in the age dis-
joints.6 Monoarthritis is uncommon and the tribution, with one peak at 1–3 years of age and
Juvenile idiopathic arthritis 75
another later in childhood and adolescence. In due to the introduction of methotrexate (MTX)
RF-negative disease, knees, ankles, and wrists are and biologics. In children with multiple joints
the most commonly involved joints early in the involved and/or uveitis, DMARDs are introduced
disease course. Small joints can be involved at early in the disease course. Anti-TNF alpha
disease onset. The distribution of affected joints therapy (etanercept, adalimumab, infliximab,
is more commonly asymmetric, compared to RF- and certolizumab) is increasingly used in JIA and
positive polyarthritis. In RF-positive polyarthritis, is shown to be very effective and safe.11,12
girls outnumber the boys, and the mean age of Unfortunately, none of the systemic treatments
onset is 9–11 years. are extensively evaluated for the treatment of
TMJ arthritis. In the study with improvement of
Enthesitis-related arthritis (ERA) the condyles over time, only systemic treatments
were used, indicating that systemic treatment
ERA is the only subset in which boys tend to be does influence TMJ arthritis, although this could
more frequently involved than girls. ERA affects also be based on the natural course of the dis-
mostly the lower extremities and eventually the ease.13 Although systemic treatment of JIA has
axial skeleton. It is typically associated with HLA improved significantly, TMJ arthritis still develops
B27 positivity.2 ERA accounts for approximately during the disease course, even if patients are
1–7% of all JIA cases.9 The onset can be insidious, treated with biologics.14 More directed and
characterized by musculoskeletal pain and specific treatment for TMJ arthritis might be
stiffness. Lower extremities are most commonly indicated.
affected together with enthesitis at one or more
sites around the knee or foot.
Intra-articular therapies (IAS)
Juvenile psoriatic arthritis (jPsA) Initial treatment with IAS is very physician
dependent, such that in some centers, children
The diagnosis of jPsA is complicated by the fact receive multiple joint injections on multiple
that the diagnosis of psoriasis in a young child occasions, while other centers, only occasionally
might be subtle, atypical, and transient. This fact inject locally. IAS are proven to be a safe and
has been taken into account in the new classi- effective treatment for peripheral joints in JIA.15
fication system, as patients do not always have IAS are used in the treatment of TMJ
classic psoriasis with arthritis. The reason for the involvement; however, concerns have risen after
link between psoriasis and arthritis is still reports suggested a potential risk in inflammatory
unknown. jPsA has a biphasic age distribution and non-inflammatory conditions.16
with one peak during preschool years and
another one in late childhood. It is slightly more
frequent in girls than boys. jPsA is clinically Conclusion
heterogeneous. The younger children tend to
JIA is the most common childhood rheumatic
be female, ANA positive, and develop dacty-
disease and consists of multiple subsets with
litis. The arthritis involves the wrists and small
several inclusion and exclusion criteria. Treat-
joints of the hands and the feet and progresses to
ment of JIA has changed dramatically over the
polyarticular disease in the absence of treatment.
last decades due to new therapeutic options.
In older children, the gender ratio is closer to
Long-term data on safety and efficacy seems
1:1, with a tendency to enthesitis and axial
promising. These long-term studies are necessary
skeleton involvement, resembling adult Psoriatic
to develop a more tailored treatment for the
Arthritis.10
different JIA subtypes.
Systemic treatment
References
Systemic treatment of JIA is based on subtype,
disease course, and associated co-morbidities. 1. Saurenmann RK, Rose JB, Tyrrell P, et al. Epidemiology
of juvenile idiopathic arthritis in a multiethnic cohort.
Historically, initial treatment included physi- Arthritis Rheum. 2007;56:1974–1984.
otherapy and NSAIDs. Therapeutic approaches 2. Petty RE, Southwood TR, Manners P, et al. International
have changed substantially in the last 2 decades League of Associations for Rheumatology classification of
76 Twilt and Tzaribachev
juvenile idiopathic arthritis: second revision, Edmonton, 10. Southwood TR, Petty RE, Malleson PN, et al. Psoriatic
2001. J Rheumatol. 2004;31:390–392. arthritis in children. Arthritis Rheum. 1989;32:1007–1013.
3. Gewanter HL, Roghmann KJ, Baum J. The prevalence of 11. Prince FH, van Suijlekom-Smit LWA. Cost of biologics in
juvenile arthritis. Arthritis Rheum. 1983;26:599–603. the treatment of juvenile idiopathic arthritis: a factor not
4. Laaksonen AL. A prognostic study of juvenile rheumatoid to be overlooked. Paediatr Drugs. 2013;15:271–280.
arthritis. Analysis of 544 cases. Acta Paediatr Scand 12. Tzaribachev N. CZP is effective in polyJIA patients not
1966:1–163. responsive to other TNF alpha antagonists. Ann Rheum
5. Prieur AM, Le Gall E, Karman F, Edan C, Lasserre O, Dis. 2011;71:435.
Goujard J. Epidemiologic survey of juvenile chronic 13. Twilt M, Schulten AJ, Verschure F, Wisse L, Prahl-
arthritis in France. Comparison of data obtained from Andersen B, van Suijlekom-Smit LWA. Long-term fol-
two different regions. Clin Exp Rheumatol. 1987;5:217–223. lowup of temporomandibular joint involvement in
6. Schneider R, Lang BA, Reilly BJ, et al. Prognostic juvenile idiopathic arthritis. Arthritis Rheum. 2008;59:
indicators of joint destruction in systemic-onset juvenile
546–552.
rheumatoid arthritis. J Pediatr. 1992;120:200–205.
14. Stoll ML, Morlandt AB, Teerawattanapong S, Young D,
7. Ravelli A, Grom AA, Behrens EM, Cron RQ. Macrophage
Waite PD, Cron RQ. Safety and efficacy of intra-articular
activation syndrome as part of systemic juvenile idiopathic
infliximab therapy for treatment-resistant temporoman-
arthritis: diagnosis, genetics, pathophysiology and treat-
dibular joint arthritis in children: a retrospective study.
ment. Genes Immun. 2012;13:289–298.
8. Saurenmann RK, Levin AV, Feldman BM, et al. Preva- Rheumatology. 2013;52:554–559.
lence, risk factors, and outcome of uveitis in juvenile 15. Stoustrup P, Kristensen KD, Verna C, Kuseler A,
idiopathic arthritis: a long-term followup study. Arthritis Pedersen TK, Herlin T. Intra-articular steroid injection
Rheum. 2007;56:647–657. for temporomandibular joint arthritis in juvenile idio-
9. Symmons DP, Jones M, Osborne J, Sills J, Southwood TR, pathic arthritis: a systematic review on efficacy and safety.
Woo P. Pediatric rheumatology in the United Kingdom: Semin Arthritis Rheum. 2012;43:63–70.
data from the British Pediatric Rheumatology Group 16. Ringold S, Thapa M, Shaw EA, Wallace CA. Heterotopic
National Diagnostic Register. J Rheumatol. 1996;23:1975– ossification of the temporomandibular joint in juvenile
1980. idiopathic arthritis. J Rheumatol. 2011;38:1423–1428.
Juvenile idiopathic arthritis characteristics:
Etiology and pathophysiology
Lynn Spiegel, Kasper Dahl Kristensen, and Troels Herlin
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic

condition during childhood, which may result in disabilities that can continue
into adulthood. JIA, with its onset before the age of 16 years and with a
chronic arthritis lasting more than 6 weeks, should present without any
known cause. Despite the definition, this does not exclude a number of
different etiological candidates for the pathogenesis of JIA. The advances in
molecular medicine and pivotal role of cytokine network for the regulation of
inflammatory processes in JIA and other chronic arthritides have greatly
improved our understanding of the disease. This has contributed to the
advances of clinical care of JIA with the advent of biological drugs, first and
foremost anti-TNF-alpha therapies, and recently, the use of anti-IL-1 and anti-
IL-6 drugs. We are still faced with a number of difficulties translating this
knowledge at the molecular level into the concert of new therapeutic targets
for JIA, and especially regarding the temporomandibular joint. We discuss
current knowledge of the etiopathogenesis of JIA on joint destruction and its
impact on the therapeutic possibilities. (Semin Orthod 2015; 21:77–83.) &
2015 Elsevier Inc. All rights reserved.
Introduction families, a concordance rate of 25% for JIA was

found in monozygotic twins3 and siblings of those
J uvenile idiopathic arthritis is a heterogeneous
group of diseases characterized by arthritis of
unknown origin and with the onset before the age
affected by JIA have a 15- to 30-fold increase of
prevalence of JIA.4 Strong evidence supports for
the role of HLA Class I and II alleles in the
of 16. The etiology is not completely understood
pathogenesis of different subtypes of JIA. The
but it is considered as multifactorial with an
earliest report for HLA Class I was the association
essential role of both genetic and environmental
of HLA-B27 and JIA with inflammation in the
factors. Within recent years, a number of studies
axial skeleton.5,6 A number of HLA studies have
have led to a substantial progress in the under-
been performed showing that the Class II anti-
standing of the pathogenic mechanisms leading to
gens HLA-DRB1n11 (a subtype of HLA-DR5) and
new and essential treatment possibilities.
HLA-DRB1n08 are strongly associated to early
onset oligoarticular JIA.7,8 HLA-DRB1n08 is also
Genetic associations in JIA associated with RF-negative polyarticular arthri-
tis.9 RF-positive polyarticular JIA is immunoge-
The genetics of JIA have recently been netically similar to adult rheumatoid arthritis
reviewed.1,2 In a Finnish study of JIA multicase (RA) with a confirmed association with HLA-
DR4. However, the HLA variants explain only
Division of Rheumatology, Hospital for Sick Children, University part of the genetic susceptibility to JIA, and it has
of Toronto, Toronto, Canada; Department of Orthodontics, Aarhus
been estimated that HLA-DR accounts for only
University, Aarhus, Denmark; TkVest Rogaland, Specialist Oral
Health Center for Western Norway, Stavanger, Norway; Department about 17% of the genetic burden of JIA.10 Within
of Pediatrics, Aarhus University Hospital, DK-8200, Aarhus N, the recent years, a number of confirmed
Denmark. associations between JIA and non-HLA candi-
Corresponding author at: Department of Pediatrics, Aarhus date genes have been presented from genome-
University Hospital, DK-8200, Aarhus N, Denmark. E-mail:
troeherl@rm.dk
wide association studies (GWAS), case–control
studies, and meta-analysis. Most of the non-HLA
1073-8746/15/1801-$30.00/0 loci belong to the immune related genes. Hinks
http://dx.doi.org/10.1053/j.sodo.2015.02.003 et al.11 analyzed more than 2800 oligoarticular

78 Spiegel et al
and polyarticular JIA patients and confirmed two after demonstrating persistent rubella virus
known non-HLA risk loci (PTPN22 and PTPN2) infection in the peripheral blood and/ or
and identified 14 new susceptibility loci for JIA in synovial fluid, in a small series of JIA patients.
an Immunochip array study. In addition to However, Frenkel et al.19 were unable to confirm
PTPN22 and PTPN2, the loci IL2RA, STAT4, IL2- these findings. A number of studies link evidence
IL21, ANKRD55, and SH2B3-ATXN2 have been of a previous Parvovirus B19 infection and parvo
confirmed in other cohorts as well.1,2 There have B19 viral persistence with the development of JIA
been small candidate gene studies, which have and the presence of active disease.20–23 Enteric
focused on specific subcategories of JIA. Thus, and genitourinary tract organisms may play a
ERAP1 with the enthesitis related arthritis and triggering role in ERA, though none have been
IL23R with the juvenile psoriatic arthritis.12 A proven. Masi and Walsh24 studied ERA patients
SNP at position 173 of the MIF gene is with evidence of active synovitis. A significant
associated to the systemic JIA.13 The genetic number showed a lymphoproliferative antigenic
susceptibility to temporomandibular joint (TMJ) response to enteric bacteria in synovial fluid,
arthritis has to our knowledge not been suggesting that enteric bacteria could be a trigger
specifically addressed. Since arthritis in the for disease exacerbation.
TMJ is observed in all subcategories of JIA,14 Another mechanism to explain how infections
the genetic association would presumably reflect may serve as a trigger for JIA is molecular mimicry.
the differences observed in the respective This model proposes that microbial antigens share
subcategories. Most of the genetic research similar structural properties to a self (host) anti-
have to date aimed to identify genetic variants gen, leading to the stimulation and expansion of
that affect the risk of developing JIA. However, cross-reactive autoimmune cells. Massa et al.25
the genetic research has also focused on different described sequence homologies between EBV
outcome responses, e.g., in a Canadian study, the proteins and alleles associated with oligoarticular
IL6 genotype 174 G/G was associated with JIA, suggesting that an EBV infection may activate
pain, and change in the TGF-beta1 gene (codon cross-reactive T-cells, thus triggering stimulation of
25 G/G) was associated with a protective effect pro-inflammatory pathways.
against joint space narrowing on radiographs.15 It is speculated that immunizations may trig-
ger autoimmune disease through molecular
mimicry or general activation of the immune
Environmental triggers of JIA
system. The hygiene hypothesis has also been
The fact that development of JIA does not occur in proposed, where reduced exposure to infections
100% of concordant twins, who share identical in childhood may alter the immune environ-
genetic make-up at a DNA sequence level, suggests ment, leading to a reduction in healthy regu-
a role for environmental factors.16 There are a latory T-cell responses. Post vaccination arthritis
number of studies that suggest infectious triggers has been reported after routine immunizations,
and several mechanisms have been proposed. One including Diptheria–Pertussis–Tetanus and
such mechanism, persistent antigenic stimulation, Measles–Mumps–Rubella vaccines.26 Weibel and
hypothesizes that a microbial antigen triggers a pro- Benor27 reported cases of chronic JIA developing
inflammatory response in genetically susceptible after the rubella vaccine, however another study
individuals. Although a number of organisms have did not replicate this finding.28 To date,
been investigated as potential triggers, little or no epidemiologic studies have not provided a
evidence exists for a single infectious agent-causing clear link between immunizations and JIA.29
JIA. Some of the microbes that have been studied A number of epidemiological studies have
include mycoplasma, rubella virus, Parvovirus B19, looked to see if onset of JIA is more prevalent
and a number of enteric organisms. during certain seasons. Lindsley showed that
A Canadian center showed that peaks in there was a higher incidence of SJIA onset in
mycoplasma infection correlated with peak onset Kansas between the spring and fall, with a lower
of JIA. This was most evident in the oligoarticular incidence of onset during the winter.30 They
and polyarticular subtypes, and less common in postulated that a virus could be a trigger for
systemic JIA patients.17 Chantler et al.18 suggested disease onset. A larger multi-center Canadian
that rubella has a role in disease pathogenesis study found similar seasonal peaks in SJIA onset
Juvenile idiopathic arthritis characteristics 79
in the Prairie Provinces but not in the rest of females were at increased risk to develop JIA if their
Canada. They speculated that the prairies are in mothers smoked Z10 cigarettes/day during
close geographic proximity to Kansas, possibly pregnancy.40 However, the small sample size
suggesting a common seasonal trigger.31 Uziel made it challenging to draw definitive conclu-
et al.32 showed no seasonal pattern for onset of sions. Ellis et al.37 found that tobacco smoke expo-
SJIA but did show that those patients with a more sure in utero or during the perinatal period was not
severe disease course tended to have disease associated with an increased incidence of JIA.
onset in the winter.
The timing and nature of environmental
Dysregulation of the cytokine network in
exposures in susceptible individuals may modify
JIA
the risk of autoimmune inflammatory disease. A
large Swedish nationwide study found that hos- Immunological studies have revealed differences
pitalization for any infection during the first year between the systemic JIA and the other sub-
of life was associated with a risk of later devel- categories of the disease preferentially activating
opment of JIA.33 A Danish study identified four the innate and the adaptive immunity, respec-
independent socioeconomic risk factors for the tively.41 Systemic JIA with the absence of
development of JIA: no siblings, high income autoantibodies and regulating T-cells is charac-
parents, living in urban vs a farm setting, and terized by the overproduction of pro-
living in single vs a multi-unit family dwelling.34 inflammatory cytokine IL-642 and with a
The hygiene hypothesis was one possible unique IL-1 signature.43 The importance of IL-
explanation offered, where the immune system 1 and IL-6 for the development of systemic JIA
was modulated by reduced childhood infections has also been delineated by the successful
because of improved hygiene and increased treatment recently described by specifically
immunizations. blocking these cytokines with canakinumab and
A number of studies have looked at the role of tocilizumab, respectively.44,45 Regulation of the
breast feeding and the development of JIA; monocyte-derived cytokines plays an important
however, the results are inconclusive. An early role in the inflammatory process and has been
study suggested a protective effect of breast subject of intense research. IL-6 but not IL-1 has
feeding.35 However, Rosenberg36 did not find a been directly measured elevated in serum. IL-18,
significant relationship between absence of belonging to the IL-1 family, stimulates a variety
breast feeding and subsequent development of of inflammatory immune responses and has been
JIA. A large Australian study reported that found elevated in serum in systemic JIA.46,47 Pro-
commencement or duration of breast feeding inflammatory cytokines include IL-1, IL-6, and
did not seem to be associated with an increased TNF-alpha, which have direct effect on the
risk of developing JIA.37 synovial tissue by enhancing the inflammatory
The role of vitamin D in JIA has been studied. response.48 Impaired balance between the pro-
The active form of vitamin D (1, 25- inflammatory cytokines (IL-1, IL-6, and TNF-
dihydroxyvitamin D3) seems to play an impor- alpha) and their regulating anti-inflammatory
tant role in modulating the immune system in antagonists [IL-1RA, sIL-6R, and soluble TNF-
several ways including up-regulating anti- receptor (sTNFR)] has been found in both
inflammatory cytokines and down-regulating synovial tissue and serum.42,43,49 IL-10 is a potent
pro-inflammatory cytokines. A systematic review suppressor of pro-inflammatory cytokines like
of 19 articles looking at vitamin D levels and IL-6 and in systemic JIA, the IL-10 suppression of
supplementation in JIA concluded that there is IL-6 production is diminished compared to
no clear evidence to support a link between controls.50 Soluble TNFR and sIL-2R are sensitive
vitamin D deficiency and JIA nor is there good markers of disease activity especially in oli-
evidence that vitamin D supplementation pre- goarticular JIA.51 In systemic JIA, IL-6, IL-18, and
vents or improves JIA.38 IL-1RA are correlated with disease activity.47,52 In
Numerous studies have shown that smoking is a JIA, the inflamed joints are enriched with IL-17-
risk factor for rheumatoid arthritis in adults.39 producing T-cells, and high levels of IL-17 have
Attempts have been made to establish a similar been detected in both serum and synovial fluid
association in JIA. A Finnish study showed that from patients with polyarticular JIA.53 The
80 Spiegel et al
pathophysiological mechanism behind TMJ destruction, the matrix metalloproteinases

arthritis in JIA is not completely understood (MMPs), are controlled by c-Fos/AP-1.66,67 The
but a number of studies suggest the role of local effects of MMPs are inhibited by their physio-
dysregulation of inflammatory cytokines.54,55 The logical inhibitors tissue inhibitor of metal-
pro-inflammatory cytokines IL-1beta and TNF- loproteinases (TIMP) and if the ratio between
alpha as well as serotonin have been associated MMPs and TIMPs increases as in arthritic con-
with TMJ pain and destructive changes in carti- ditions, the MMPs will be overrepresented
lage and bone tissue in adults with rheumatoid leading to tissue destruction.67 Some of the most
arthritis.56–58 It is therefore conceivable that important degrading MMPs are produced in the
better control of the impaired regulation of the synovial lining cells and are up-regulated by pro-
cytokine network both locally and systemically inflammatory cytokines (e.g., TNF-α and IL-1β)
will have an important implication on the and are present in large amounts in the pannus
inflammatory response in TMJ arthritis. causing cartilage destruction.68 MMP-3 is
expressed in both JIA and normal synovial tissue,
in synovial fluid, and its expression correlates
Effect of chronic synovitis on cartilage and
with the degree of inflammation.69,70 Generally,
bone turn-over
joint destruction usually occurs later in the dis-
Although not the same disease, the synovial ease course of childhood than in RA in adults.59
histopathological features of JIA are similar to Unfortunately, this is not the case for the TMJ.
those described in rheumatoid arthritis (RA) in The TMJ is a secondary joint due to its
adults.59 However, studies on cytokine levels and embryonic origin. The cartilage is fibrous and not
mRNA levels reveal that distinct differences are hyaline. It has an articular disc that divides the
present, both between JIA and RA, and between joint into two distinct joint spaces, and the con-
the different JIA subgroups.48,60,61 Initially, the dylar fibrocartilage provides a chondrogenic
sub-synovial connective tissue reacts with both an growth-site essential for mandibular development.
increased vascularity and an inflammatory cell The mandibular condyles provide a regional
infiltrate. The synovial lining demonstrates vil- adaptive growth by endochondral ossification and
lous hyperplasia and hypertrophy. Histopatho- are primarily responsible for vertical ramus
logical studies of the synovium in JIA reveal growth.71 Because of this intraarticular localization
prominent infiltration with lymphocytes, plasma of the growth site, both bone remodeling and
cells, and macrophages, as well as proliferation of modeling occur in close proximity to the
both fibroblast- and macrophage-like synovio- intraarticular environment and inflammatory
cytes. Synovial infiltration with inflammatory cells changes herein can alter both. If a pannus
does not appear to be homogeneous: lightly destroys the condylar cartilage, normal modeling
infiltrated areas alternate with areas of heavy cell and growth cannot take place as the cartilaginous
aggregates.62 Synovitis and pannus formation can hyperplastic layer where the endochondral growth
lead to progressive erosion and articular cartilage originates is destroyed. However, in the majority of
destruction and, later, of subjacent bone patients, some vertical ramus growth is seen
erosion.63 In RA, the synovial fibroblast-like suggesting that the cartilage is not completely
cells degrade cartilaginous matrix under the destroyed, but rather that the chemical
pannus by clinging tightly to the articular surface composition and joint function is changed
of cartilage and penetrating into cartilage and resulting in a less optimal potential for growth.
bone from the area between the margin of car- Homeostatic bone remodeling is conducted by
tilage and synovial insertion by changing their the bone metabolic unit with osteoclasts and
shape into macrophage-like cells.64 Such synovial osteoblasts, where osteoclasts remove bone and
mesenchymal cells are up-regulated by the osteoblasts rebuild it in a timed and coordinated
transcription factors c-Fos/AP-1 in RA, which sequence. If these timed events are altered by
release IL-1β, and causes synovial overgrowth.65 cytokine or hormonal factors, the bone metabolism
That c-Fos/AP-1 is an important transcription is changed resulting in an unbalance between
factor was shown as inhibition of c-Fos/AP-1 not removal and apposition of bone. These actions are
only reduces arthritis but also resolves arthritic controlled by many different mechanisms, but the
joint destruction as the main enzyme for tissue main mediator is the nuclear factor κβ ligand
(RANKL) and osteoprotegerin (OPG) ratio, 2. Cobb JE, Hinks A, Thomson W. The genetics of juvenile
which are largely controlled by the pro-infl- idiopathic arthritis: current understanding and future
prospects. Rheumatology (Oxford). 2014;53:592–599.
ammatory cytokines TNF-α and IL-1β. TNF-α 3. Saila HM, Savolainen HA, Kotaniemi KM, Kaipiainen-
may promote osteoclastogenesis indirectly thr- Seppanen OA, Leirisalo-Repo MT, Aho KV. Juvenile
ough the induction of the expression of RANKL idiopathic arthritis in multicase families. Clin Exp Rheu-
and colony stimulating factor-1 in bone marrow matol. 2001;19:218–220.
stromal cells and bone-lining cells72 and directly 4. Prahalad S, O'brien E, Fraser AM, et al. Familial
aggregation of juvenile idiopathic arthritis. Arthritis
on the osteoclast precursor to promote osteoclast Rheum. 2004;50:4022–4027.
differentiation. Therefore, osteoclastogenesis is 5. Rachelefsky GS, Terasaki PI, Katz R, Stiehm ER. Increased
largely up-regulated in inflammatory conditions prevalence of W27 in juvenile rheumatoid arthritis. N Engl
thereby linking inflammation and bone destruc- J Med. 1974;290:892–893.
6. Berntson L, Nordal E, Aalto K, et al. HLA-B27 predicts a
tion. Treatment using denusomab, a fully human
more chronic disease course in an 8-year followup cohort
IgG2 monoclonal antibody that binds human of patients with juvenile idiopathic arthritis. J Rheumatol.
RANKL, will effectively inhibit progression of 2013;40:725–731.
bone damage in RA. However, it does not affect 7. Glass D, Litvin D, Wallace K, et al. Early-onset pauciar-
the amount of inflammation present.73 The ticular juvenile rheumatoid arthritis associated with
RANKL/OPG and MMP-3/TIMP ratios are human leukocyte antigen-DRw5, iritis, and antinuclear
antibody. J Clin Invest. 1980;66:426–429.
increased in JIA, especially in polyarticular JIA.70 8. Haas JP, Nevinny-Stickel C, Schoenwald U, Truckenbrodt
Wnt-mediated signals are crucial for bone H, Suschke J, Albert ED. Susceptible and protective major
remodeling in both physiological and patho- histocompatibility complex class II alleles in early-onset
logical conditions. It is beyond the scope of this pauciarticular juvenile chronic arthritis. Hum Immunol.
article to fully elucidate the different Wnt- 1994;41:225–233.
9. Fernandez-Vina MA, Fink CW, Stastny P. HLA antigens in
signaling pathways, but this is reviewed in juvenile arthritis. Pauciarticular and polyarticular juvenile
Maeda et al.74 In RA, Wnt5a is up-regulated and arthritis are immunogenetically distinct. Arthritis Rheum.
through Dickkopf 1 (Dkk1)-overexpression bone 1990;33:1787–1794.
formation and resorption is unbalanced causing 10. Prahalad S, Ryan MH, Shear ES, Thompson SD, Giannini
EH, Glass DN. Juvenile rheumatoid arthritis: linkage to
bone resorption. Wnt5a inhibition using the
HLA demonstrated by allele sharing in affected sibpairs.
decoy receptor glutathione S-transferase-soluble Arthritis Rheum. 2000;43:2335–2338.
Ror2 (GST-Ror2 fusion protein) abrogated bone 11. Hinks A, Cobb J, Marion MC, et al. Dense genotyping of
destruction due to suppression of osteoclast immune-related disease regions identifies 14 new sus-
formation in experimental arthritic joints and ceptibility loci for juvenile idiopathic arthritis. Nat Genet.
may prove an effective strategy for reducing joint 2013;45:664–669.
12. Hinks A, Martin P, Flynn E, et al. Subtype specific
destruction and inflammation reduction.74,75 genetic associations for juvenile idiopathic arthritis:
ERAP1 with the enthesitis related arthritis subtype and
IL23R with juvenile psoriatic arthritis. Arthritis Res Ther.
Conclusion 2011;13:R12.
13. Donn RP, Shelley E, Ollier WE, Thomson W, British
In conclusion, a number of environmental factors Paediatric Rheumatology Study Group. A novel 5'-flank-
can likely be implicated in both triggering the onset ing region polymorphism of macrophage migration
of JIA and maintaining an inflammatory response inhibitory factor is associated with systemic-onset juvenile
in genetically susceptible individuals. However, to idiopathic arthritis. Arthritis Rheum. 2001;44:1782–1785.
14. Pedersen TK, Jensen JJ, Melsen B, Herlin T. Resorption of
date, studies have provided conflicting evidence.
the temporomandibular condylar bone according to
Further research is necessary to clarify the con- subtypes of juvenile chronic arthritis. J Rheumatol.
tributing role that genetics and environment play 2001;28:2109–2115.
in the onset and disease course of JIA, in particular 15. Oen K, Malleson PN, Cabral DA, et al. Cytokine genotypes
regarding the pathogenic mechanisms leading to correlate with pain and radiologically defined joint
damage in patients with juvenile rheumatoid arthritis.
the development of TMJ arthritis.
Rheumatology (Oxford). 2005;44:1115–1121.
16. Prahalad S. Genetic analysis of juvenile rheumatoid
arthritis: approaches to complex traits. Curr Probl Pediatr
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Craniofacial growth and dento-alveolar
development in juvenile idiopathic arthritis
patients
Timo Peltomäki, Sven Kreiborg, Thomas Klit Pedersen, and Björn Ogaard
Mandibular condyles/condylar cartilages can be considered as major growth

sites of the mandible. Condylar affection by arthritis may therefore have an
impact on craniofacial growth and development and joint function. In JIA
patients with TMJ involvement, up to 70% show some form of craniofacial
growth disturbance, which may be due to an adverse inflammatory effect on
the condylar cartilages, reducing their normal growth potential and/or real
destruction of the condyles. Craniofacial morphology in JIA patients has been
classically described as “bird-face” outlook with micrognathic/retrognathic
mandible with posterior rotation in relation to the cranial base, large lower
anterior facial height, and anterior open bite in patients with insufficient dento-
alveolar compensational growth. Impaired masticatory function is known to
have an impact on the mandibular growth in normal circumstances. Therefore,
it is plausible that impaired masticatory function further worsens growth
capacity of the mandibular condyle in JIA. Variability in craniofacial morphol-
ogy in JIA patients with TMJ affection depends on the severity of arthritis,
onset age, and individual genetic variability influencing growth and respon-
siveness to treatment. Thanks to early diagnosis and proper medication, the
prevalence of “bird-face” appearance of JIA patients is decreasing. (Semin
Orthod 2015; 21:84–93.) & 2015 Elsevier Inc. All rights reserved.
Normal craniofacial growth and dento- During postnatal craniofacial growth, differ-
alveolar development ent stages (infantile, juvenile, pubertal, post-
pubertal, and adulthood) can be recognized with
nderstanding of craniofacial and dento-
U alveolar growth and development is
essential to diagnose and treat skeleto-dental
different annual growth amounts and velocities.
In the co-ordinated growth, maxilla and man-
dible are displaced predominantly in the
malocclusions in healthy persons, and it is even
forward-downward direction in relation to the
more important in those with deviating growth
cranial base. This means that the spatial position
due to a disease or trauma.1
of the maxilla and the mandible changes during
growth, with great individual variation. In some
individuals, mandibular displacement occurs in
Field of Dentistry, School of Medicine, University of Tampere, P. the vertical direction and in some others in the
O. Box 2000, FI-33521 Tampere, Finland; Oral and Maxillofacial horizontal direction.2 Maxillary and mandibular
Unit, Tampere University Hospital, Tampere, Finland; Department displacement is closely linked and related to
of Pediatric Dentistry and Clinical Genetics, School of Dentistry, adaptive occlusal development.
University of Copenhagen, Panum Instituttet, Nørre Allé 20, 2200
Copenhagen, Denmark; Department of Maxillofacial Surgery, Aarhus
Facial proportions also change during growth.
University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark; While the growth of brain tissue and cranial vault
Department of Orthodontics, Faculty of Dentistry, University of Oslo, is completed early (about 10 years), facial growth
P.O. Box 1109 Blindern, 0317 Oslo, Norway. may continue up to 20 years of age. Facial growth
Corresponding author at: Field of Dentistry, School of Medicine, in different directions also differs in terms of
University of Tampere, P.O. Box 2000, FI-33520 Tampere, Finland.
E-mail: timo.peltomaki@pshp.fi
amount and cessation. In the transversal
dimension, only moderate postnatal growth takes
1073-8746/15/1801-$30.00/0 place. Mandibular condyle–condyle dimension
http://dx.doi.org/10.1053/j.sodo.2015.02.004 does not increase after about 10 years. In

Craniofacial growth and dento-alveolar development 85
contrast, in the sagittal direction, considerable on the mandibular growth.8–10 Furthermore, the
growth occurs postnatally—mandible outgrows mandibular condyle is subject to significant age-
maxilla, which leads to decrease in the facial related changes in size and shape during child-
convexity.3 The greatest amount of postnatal hood,11 probably related to development of
growth occurs in the vertical dimension seen as occlusion and use of the masticatory apparatus.
an increase of the mandibular ramus height and Uneven growth on the right and left condyles seen
adaptive eruption of teeth and as an increase in as normally occurring mandibular/facial asym-
the dento-alveolar arches. Mandibular growth metry is probably also a reflection of uneven
ceases later than maxillary growth, particularly masticatory function.12 In extreme cases, canting
in males. of the maxillary occlusal plane is a consequence.
In addition to displacement, the shape of
bones is changed, i.e., remodeling takes place on
the bone surfaces. Local resorption–apposition Craniofacial and dento-alveolar growth
of the nasal roof leads to lowering of the nasal and development in children with JIA
floor concomitantly, with the displacement of the of the TMJ
entire maxillary complex. Mandibular pro- The condyles can thus be considered as major
portions change during displacement; there is growth sites of the mandible, and condylar
more growth in height (ramus growth) than in affection by arthritis may therefore significantly
length or width. affect craniofacial growth and development and
Over the past century, sometimes, even a mandibular function.13–18 In JIA patients with
heated debate has been made over the driving TMJ involvement, 70% show some form of cra-
force(s) that cause maxillary and mandibular niofacial growth disturbances.17 Small erosions to
displacement. The mandible has been consid- nearly complete deformation of the condylar
ered to be like a bent long bone, with displace- heads have been reported.19 Even if moderate
ment force originating from active growth in the growth disturbances could probably appear
condylar cartilages. Functional matrix hypoth- before radiological visible lesions are detec-
esis4 represents an opposite concept—growth of table,20 radiographical examination of the TMJ
condylar cartilages is adaptive to secure joint is crucial in craniofacial longitudinal growth
integrity, while the displacement force is created studies to differentiate between JIA patients
by increase in the oral–nasal airway volume. In with and without TMJ involvement.
this debate, it has often been forgotten that the Temporomandibular joints are among the
endochondral bone formation cascade must take most frequently affected joints in JIA patients.
place in the condylar cartilage in an ordered Arvidsson et al.21 observed that TMJ involvement
fashion to create/accommodate the mandibular in JIA patients progressed with age from about
displacement. In the condylar cartilage, the 40% at the initial examination at the age of 9
endochondral bone formation mechanism lies years to 75% at 27 years later. Disease onset age,
beneath the outer, articular layer, while in the duration, disease subtype and activity, and the
long bones, separate cartilages exist for number of joints affected have shown a signifi-
articulation and growth. This difference cant relationship to radiographic TMJ involve-
between mandibular condylar cartilage and ment22,23 and growth disturbances.17,18,24 Twilt
long bone articular and epiphyseal cartilages et al.25 observed that with low disease activity,
causes the difference in response in case of condylar lesions may not progress and even
inflammation or injury. Experimental in vitro and regenerate. Since JIA commonly has intermit-
transplantation studies have shown condylar tent periods of activity, longitudinal craniofacial
cartilage to possess some tissue-separating growth studies are important.
capacity like other cartilages.5,6 At the same
time, growth of the condylar cartilage can,
Craniofacial morphology in subjects with JIA of
however, be affected by environmental factors,
the TMJ
i.e., its growth is adaptive due to the nature of this
secondary cartilage.7 Craniofacial morphology in JIA patients has
Lowered masticatory function due to soft diet or been classically described as “bird-face” outlook
muscular disease has been shown to have an impact with micrognathic/retrognathic mandible and
86 Peltomäki et al
posterior rotation in relation to the cranial base change and reduced vertical condylar growth lead
and the maxilla (Fig. 1A and B), especially if TMJ to a posterior rotation of the mandible, mandibular
arthritis is severe and has an early onset. Due to retrognathia, and malocclusion. During period of
the posterior rotation of the mandible, lower dysplastic mandibular growth, apposition of bone
anterior facial height may be large, and anterior gradually takes place at the gonial angle, leading to
open bite may develop with insufficient dento- antegonial notching.2,27 As a consequence, growth
alveolar compensational growth. of the posterior height of the maxilla may also
The inflammatory destruction of the man- become reduced. The short and severely posteri-
dibular condylar cartilage/condyle, the articular orly inclined mandible often results in a charac-
eminence, and probably the disc seem to lead to a teristic soft tissue facial profile, with a receding chin
change in mandibular position, with more anterior and a double chin; the oropharyngeal airway may
position of the condyle in the glenoid fossa,26,27 become restricted, and the child extends the head
and to reduced vertical growth of the mandibular in relation to the cervical column to secure open
condyles.2,27 Both the condyle–fossa positional airway.
Figure 1. (A) A 14-year-old girl with untreated JIA. Note typical “bird face” with receding chin. (B) Lateral
cephalogram of the patient. Posterior rotation of the mandible and typical antegonial notching. Reduced posterior
and increased anterior facial heights.
Twilt et al.28 reported higher prevalence's of TMJ involvement or healthy control subjects.
retrognathia (82%) and posterior rotation of the Larheim and Haanaes29 speculated that
mandible (58%) in JIA patients with the interferences with mandibular growth in JIA
presence of TMJ involvement compared to no patients could be due to a combination of
TMJ involvement (55% and 47%, respectively) in direct effect by the arthritis on the TMJ and
accordance with many other studies.14,17,29–33 It restricted function. However, Stabrun et al.24
was further reported that mandibular retro- found that TMJ abnormalities were the
gnathia occurred more often in the polyarticular dominating factors for mandibular length
type (75%) than in the oligoarticular (68%) and association when several disease factors were
systemic disease (64%) JIA patients. The corre- examined.
sponding observations for posterior rotation of The prevalence of micrognathia in recent
the mandible were systemic (93%), polyarticular studies of JIA patients has been reported to be
(65%), and oligoarticular subtypes (63%). around 25%. Micrognathia occurs in patients
with bilateral TMJ involvement only, and about
40% of these patients have a micrognathic
Mandibular growth deviation mandible and 70% of the patients have some
Experimentally induced TMJ arthritis in rabbits kind of growth disturbance.17
offers a possibility to study and describe histo- Damm et al.27 presented an illustrative
pathology of the inflamed TMJ.34 In a later longitudinal follow-up of a girl with polyarticular
cephalometric study, diminished dimensions of JIA without initial TMJ affection (Figs. 3 and 4). She
the mandible were found in arthritic animals.35 had been diagnosed with JIA affecting the
These findings were confirmed by Stoustrup et al. extremities at the age of 4 years and was
studying growing rabbits with induced TMJ continuously followed up and treated for this by
arthritis using medical computed tomography the pediatric rheumatologists. At the age of 8 years
(CT).36 The images of the CT scans were and 11 months, the girl was referred to School of
superimposed, and the difference between Dentistry in Copenhagen because of malocclusion
normal and abnormal growth caused by TMJ (bilateral cross-bite) without any clinical signs of
arthritis was visualized (Fig. 2). TMJ affection. Her orthopantomographic and
A relationship between radiographical TMJ cephalometric films obtained at this time and
involvement due to arthritis and micrognathic again at 10 years and 2 months of age, in relation to
development of the mandible is well estab- her orthodontic treatment, showed no signs of TMJ
lished.29 Stabrun et al.24 and Fjeld et al.33 showed affection. Mandibular morphology and growth
that TMJ abnormalities were significantly related were normal during this period. However, at
to mandibular growth inhibition, and bilateral follow-up 2 years later, it was observed that she
TMJ involvement reduced mandibular had bilateral TMJ affection with marked destruc-
dimensions (total length, height of ramus, and tion of the mandibular condyles and anterior open
corpus length) compared to JIA patients without bite malocclusion. The cephalometric analysis
Figure 2. Difference in mandibular growth of a healthy and TMJ arthritis model rabbit. Note the difference in
condylar height and the development of subangular notch in the arthritis rabbit.
88 Peltomäki et al
Figure 3. Tracings of lateral cephalograms of longitudinal follow-up (from 8 years 11 months to 17 years) of a girl
with polyarticular JIA without initial TMJ affection.
revealed that the position of the mandible had rotation of the mandible seen in the “long face
changed: the condylar position in the glenoid fossa sequence” (Fig. 5A and B). In the long face
was more anterior. The mandible had undergone a sequence, vertical lowering of the maxillary
posterior rotation both in relation to the anterior molars exceeds the vertical component of
cranial base and to the maxilla, with hypomochlion condylar growth, leading to posterior rotation
at the last molar causing the anterior open bite. of the mandible with downward growth of the
There were no signs of antegonial notching at this symphysis (Fig. 5A). In children with moderate to
stage (Fig. 3). It was decided to follow the jaw severe destruction of the TMJ by arthritis, the
development till the end of growth and to perform joint collapses, the articular eminence and the
orthognathic surgery at adult age. The condylar head become flattened, and the
cephalometric analysis from 12 years and 2 condyle moves forward in the fossa. Thereby,
months of age till 17 years of age revealed a the mandible rotates posteriorly; the hypo-
dysplastic pattern of mandibular development with moklion is at the posterior maxillary molars,
further flattening and anterior position of the which are, subsequently, lowered less than
condyles leading to an extreme posterior rotation normal (Fig. 5B).30
of the mandible and with gradual development of The pattern of mandibular growth rotation in
antegonial notching. At the same time, the chin JIA patients is, however, probably more complex
became progressively receding, and the head than generally described and is related to the
position in relation to the cervical column progress of the disease. Fjeld et al.18 compared
became more extended to protect the airway JIA patients with bilateral and no TMJ
(Fig. 4). involvement after almost 30 years of follow-up
It should be emphasized that the posterior and noted that mandibular growth displacement
rotation of the mandible in JIA children with TMJ in non-TMJ-affected patients was similar to
affection differs from the posterior growth healthy control subjects, i.e., mainly in an
Figure 4. Cephalometric analysis from 12 years 2 months of age till 17 years of age reveals dysplastic mandibular
development with gradual development of antegonial notching. At the same time, the chin became progressively
receding and extended head position to protect the upper airway.
anterior direction. Also, in the abnormal TMJ A posterior growth pattern was also related to
group, the average mandibular growth pattern mandibular function and progressing detri-
was, contrary to most previously reported longi- mental joint morphology. Thus, improved joint
tudinal studies, in a slight anterior direction. morphology was related to improved condylar
However, 20% of the patients with a consistently translation and a favorable mandibular growth
progressing or stable disease course showed a pattern, and the more progressive the TMJ dis-
posterior mandibular growth rotation, and 40% ease course, the more likelihood for reduced
of the patients with improving disease course mandibular function and a posterior growth
showed an anterior mandibular growth rotation. rotation pattern. The same authors also noted
Figure 5. (A) In long face sequence, lowering of the maxillary molars exceeds vertical growth of the condyle,
leading to posterior rotation of the mandible and downward growth of the symphysis. (B) In moderate to severe
destruction of the TMJ by arthritis, the joint collapses, the articular eminence, and the condylar head becomes
flattened, and the condyle moves forward in the fossa. As a consequence, the mandible rotates posteriorly; the
hypomochlion is at the posterior maxillary molars, which are lowered less than normally.
90 Peltomäki et al
that even in patients with early severe TMJ cause of growth deviation, little is known about
affection, improvement in the disease course the interaction between inflammatory sub-
resulted in a favorable growth rotation, in stances, bone formation, and condylar growth.
accordance with Twilt et al.16 This shows the Future research should therefore be directed
dynamics of mandibular growth rotation and the against a possible limitation of the inflammatory
potential for normal growth development if the effect.
arthritis is controlled at an early age. Medical treatment in the form of anti-
Unilateral TMJ involvement may result in inflammatory therapy may positively influence
mandibular asymmetry with underdevelopment mandibular growth. Systemic use or local injec-
of the affected side and chin deviation tions of corticosteroids in the joints have been
(Fig. 6).15,24,37 Compensatory appositional shown to reduce inflammation but also to
growth in the gonial region may camouflage a adversely affect craniofacial growth and man-
steep mandibular plane angle, resulting in dis- dibular growth in particular.24,38,39 Stoustrup
tinct antegonial notching (Fig. 1B). However, et al.20 reported mandibular growth retardation
compensatory jaw growth may not be able to after intra-articular corticosteroid injection in
adjust for the large difference in condylar growth rabbits and concluded in a recent systematic
between the two sides. Larheim and Haanaes29 review that there is a need for well-designed
pointed out that unilateral TMJ involvement may prospective clinical studies on this topic and that
become symmetrical with progressing disease current knowledge on the long-term effect of
activity, and Huntjens et al.19 reported that TMJ injections is currently insufficient for clinical
condylar growth asymmetry may not necessarily recommendations.40 New medical agents such as
develop into facial asymmetry. disease-modifying methotrexate and biological
Research focus in the recent decades has been agents may on the other hand prevent condylar
directed towards describing the variety of destruction and thereby craniofacial growth
deformities developing in the TMJ, con- disturbances.15 Therefore, studies conducted
sequences at the maxillary and dento-alveolar prior to modern biological treatment regimens
levels, and progress of the condition. While were implemented may not necessarily be
inflammation of the TMJ is undoubtedly the relevant for the present situation and should
Figure 6. Facial asymmetry as a consequence of arthritic changes of the left TMJ. The left ramus is shorter than the
right, and occlusal plane is inclined to the left with shorter dento-alveolar height on this side.
be the subject of further investigations. Classical Dento-alveolar compensations

“bird-face” appearance of JIA patients is today
In skeletal growth anomalies, dento-alveolar
relatively rarely seen if early diagnosis and proper
adaptations occur in a variety of ways to com-
medication has been introduced.
pensate for a deviating maxillo-mandibular
relation and bring the teeth into a more opti-
Maxillary growth deviation
mal position and allow masticatory function.44
In JIA, mandibular growth deviation is consid- The decreased dento-alveolar posterior height
ered as the primary consequence followed by can be seen as such, as a compensation for the
change in maxillary growth and develop- short ramus in JIA patients. The sagittal insuffi-
ment.2,20,23,30 Larheim and Haanaes29 reported ciency of the mandible will be compensated with
no significant differences in the size and position proclination of the lower incisors in an attempt to
of the maxilla in JIA children, whereas Rönning contact the upper incisors. These two types of
et al.31 found a shorter maxillary dimension in compensations are frequently seen in JIA
younger TMJ-affected patients compared with patients with TMJ involvement.
non-affected patients. They also found a reduced Posterior mandibular growth rotation may lead
posterior height of the maxilla, an observation to an anterior open bite. Compensatory eruption
also done in unilateral affected cases developing of incisors and concomitant vertical alveolar
an inclination of the occlusal plane (Fig. 6), growth may occur in the anterior part of the
indicating a possible constraining effect of the mandible to camouflage the mandibular growth
reduced posterior ramus height on the maxilla.23 pattern.14 Fjeld et al.33,45 did not find a difference
The failure in maxillary posterior development in the lower anterior facial height and the prev-
complies with the posterior (clockwise) alence of anterior open bite in an unselected JIA
rotational pattern of the mandibular group compared to healthy subjects, supporting
development described by Björk and Skieller2 the findings by Larheim and Haanaes 29 and
and thereby the development of a steep occlusal Rönning et al.31 They found that anterior open
plane. Jämsä and Rönning41 observed the maxilla bites may occur in JIA patients with both
to be smaller vertically with a posteriorly elevated abnormal and normal condylar morphology.
occlusal plane due to subnormal eruption of An increased frequency of anterior open bite in
maxillary molars.
Soft tissue reaction

Disturbance in the joint function is thought to
have an adverse effect on the soft tissues and
muscles related to the joint. Reduced muscle
strength of the anterior tibial muscle has been
found together with change in muscle immu-
nology in JIA patients.42 In JIA children, maximal
bite force and endurance of masticatory muscles
have been found to be reduced, indicating
functional hypotrophy of the masticatory
muscles.30,43 As mentioned above, lowered mas-
ticatory function has been shown to have an
impact on the mandibular growth in normal
circumstances. Therefore, it is plausible that
lowered masticatory function further worsens the
growth capacity of the mandibular condyle in
JIA, but unfortunately, no studies seem to have
addressed this topic. In any case, a shorter
Figure 7. An MR image of a JIA patient with chronic
masseter muscle with less volume is a clinical arthritis in the right TMJ. The image demonstrates
observation in patients with severe growth devi- atrophied right masseter and medial pterygoid muscles
ation (Fig. 7). compared to the left side.
92 Peltomäki et al
JIA patients has, however, been observed by 4. Moss ML, The functional matrix. In: Kraus BS, Riedel RA,
Kreiborg et al.46 and Karhulahti et al.47 eds. Vistas in Orthodontics. Philadelphia: Lea & Febiger;
1962:85–98.
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Tissue-separating capacity of growth cartilages. Eur J
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Acta Odontol Scand. 2009;67:153–160. Dent Res. 1990;98:17–26.
Clinical craniofacial examination of patients
with juvenile idiopathic arthritis
Peter Stoustrup, and Bernd Koos
Clinical craniofacial examination plays an essential role in assessing the

general health of individuals diagnosed with juvenile idiopathic arthritis. The
aim of the present article is to present recommendations for the clinical
orofacial examination based on the current knowledge related to character-
istic clinical signs, symptoms, and craniofacial morphology of patients with
juvenile idiopathic arthritis and temporomandibular joint involvement.
(Semin Orthod 2015; 21:94–101.) & 2015 Elsevier Inc. All rights reserved.
Introduction The aim of the present article is to present the

current knowledge related to characteristic
linical craniofacial examination plays an
C essential role in assessing the general health
of individuals diagnosed with juvenile idiopathic
clinical signs, symptoms, and craniofacial mor-
phology of patients with JIA and TMJ involve-
ment. Herein, we also propose recommendations
arthritis (JIA). Particular attention to the tem-
for aspects that should be included in the clinical
poromandibular joint (TMJ) and the associated
examination of this particular patient group.
structures is advocated, since TMJ inflammation
can have detrimental effects on craniofacial
growth and function.1–5 TMJ involvement in TMJ arthritis in JIA—a temporomandibular
patients with JIA is a common phenomenon, with disorder
a reported prevalence of up to 87%.6
Accurate diagnosis of TMJ arthritis and the Temporomandibular joint arthritis is a sub-
associated comorbidities requires a combination diagnosis of the more general umbrella term
of clinical examination and contemporary temporomandibular disorders (TMD). TMD
imaging modalities. Prompt diagnosis of TMJ covers a broad variety of clinical orofacial find-
arthritis is important to establish an early inter- ings—ranging from mild TMJ crepitus and
ventional strategy. However, it is equally impor- clicking to disc displacement and more severe
tant to monitor craniofacial function and growth conditions like myalgia, headache, TMJ arthral-
through post-diagnostic clinical follow-up exa- gia, and degenerative joint diseases. The orofa-
minations. Clinical examination of the craniofacial signs and symptoms seen in patients with TMJ
cial structures in patients with JIA includes; a rou- arthritis are comparable to those encountered in
tine assessment of signs, symptoms of craniofacial other TMD subsets.7,8 Therefore, differential
abnormalities, TMJ and muscular functionality, TMD diagnoses are important clinical consid-
and craniofacial morphology. The examination erations in patients with JIA who present orofa-
serves two equally important general purposes— cial signs and symptoms. In addition to the
the diagnosis of TMJ arthritis; and the assessment functional and structural pathologic changes,
of craniofacial growth and the progression of there are multiple psychosomatic aspects related
signs and symptoms in patients who are diag- to TMD diagnoses.
nosed with TMJ involvement. TMD is understood as a multifactorial con-
dition that encompasses both functional dis-
orders and autoimmune etiologies. The
Section of Orthodontics, Aarhus University, Vennelyst Boulevard disorders may have the same radiological/clin-
9-11, Aarhus C DK-8000, Denmark; Department of Orthodontics, ical appearance but diverse etiologies; e.g., TMJ
University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-
disc displacement without reduction is a func-
Heller-St 3, Haus 26, Kiel 24105, Germany.
Corresponding author. E-mail: pstoustrup@odont.au.dk tional disorder where suboptimal disc function
can lead to capsulitis of the joint capsule and
1073-8746/15/1801-$30.00/0 osteoarthritic tissue degeneration.9 In contrast,
http://dx.doi.org/10.1053/j.sodo.2015.02.005 TMJ arthritis associated with JIA may also lead to

Clinical craniofacial examination 95
tissue degeneration but occurs due to a synovial the masticatory muscles, and the interaction of
reaction caused by an autoimmune disease joint function and discus articularis inside the
process. Indeed this underlines the fact, that TMJ. The analysis and summary of the complete
future research faces the challenge of finding DC/TMD procedure leads to a specific and
methods to effectively differentiate between the unique TMD diagnosis varying from physiologic
etiologies behind JIA-related TMJ arthritis and disc clicking to complex functional disturbances
other subgroups of TMD-induced TMJ de- with or without psychosomatic involvement. The
generation. areas of focus of the DC/TMD are orofacial
During TMJ examination, it is important to be function and pain assessment, with no assess-
aware of the complex anatomy and function of ments of craniofacial morphology (e.g., facial
this joint. The TMJ is divided into two separate profile and symmetry) or growth evaluation. This
joint spaces with two different functions by the is a significant and crucial drawback to these
discus articularis. While the upper joint space recommendations in relation to JIA patients.
allows the whole complex of the disc and man- For historical purposes another index, The
dibular condyle to slide forward, the lower part Helkimo Index7, should also be mentioned. This
allows the condyle to synchronously rotate dur- index is comparable in magnitude and com-
ing the sliding movement. Normal TMJ function plexity to the RDC/TMD and the DC/TMD and
is only allowed when this optimal joint interplay has previously been used in the orofacial
occurs, as seen in mouth-opening procedures in assessment of patients with JIA.
healthy subjects. In cases of TMJ disc displace- Both of the above-mentioned diagnostic
ment, the dysfunction can provoke severe indices facilitate the attainment of complex
arthralgia caused by poor joint function. Such information about TMJ functional status; how-
pathological findings can occur in patients ever, their complexity likely limits their use to
diagnosed with JIA, but may not necessarily be specialists with a dental educational background.
caused by the autoimmune-induced inflamma- At this point there exists no specific validated and
tion of JIA. evidence based recommendations for orofacial
examination of patients with JIA.
Diagnosis of TMJ arthritis
Indices for the diagnosis of TMJ arthritis
There are several validated examination tools
TMJ arthritis-related signs and symptoms
and questionnaires available for orofacial
in patients with JIA
examination, but none have been tested within
the context of JIA. These tools vary widely TMJ arthritis can interfere with optimal joint and
regarding their complexity and the required time muscle function and cause orofacial signs and
for completion. In 1992, an expert-based classi- symptoms.12–16 Both cross-sectional and longi-
fication and diagnostic system was proposed, tudinal observational studies have consistently
called the Research Diagnostic Criteria for TMD reported higher prevalences of limited jaw
(RDC/TMD) (Table 1).10 In 2014, the RDC/ function and orofacial pain complaints in
TMD was revised and renamed as the Diagnostic patients with JIA compared to matched healthy
Criteria (DC/TMD).11 They comprise a dual-axis controls.12–14 Patients with all JIA subtypes can
system including a specific examination and exhibit mild to severe TMJ arthritis-related signs
questionnaire protocol for the functional and and symptoms, which can severely influence the
psychosocial examination (Table 1). The RDC/ quality of life.14,17 TMJ arthritis-related signs and
TMD and the DC/TMD have been validated and symptoms appear to be related to the severity of
published in several languages and the DC/TMD the general disease activity, and the duration of
criteria are currently considered the golden active JIA and pain on jaw opening have been
standard of TMD classification and diagnosis. reported as predictors of future incidence of
The DC/TMD include a questionnaire for orofacial signs and symptoms.12,17 Till date, there
history and epidemiological background, a is no distinction between acute and chronic TMJ
pain anamnesis, and a physical examination arthritis-related signs and symptoms among
consisting of an in-depth analysis of the TMJ, patients with JIA.
96 Stoustrup and Koos
Table 1. RDC/TMD Classifications as Published by Dworkin et al. in 199210

Axis I: Clinical Diagnosis
Group Diagnosis
Group I la Myofascial pain
lb Myofascial pain with limited opening
Group II lla Disc displacement (DD) with reduction
llb DD without reduction with limited opening
llb DD without reduction without limited opening
Group III llla Arthralgia
llb Osteoarthritis
lllc Osteoarthrosis
Axis II: Assessment of Psychological Status and Level of tmd-r elated Psychosocial Disability
Group Diagnosis
Graded chronic pain Grade 0, no pain within the last 6 months
Grades I–IV, increasing levels of chronic pain severity
Scale items Depression
Nonspecific physical symptoms (pain items included)
Nonspecific physical symptoms (pain items excluded)
Symptoms most consistently used in studies related to TMJ

arthritis diagnosis and management.23 Such
TMJ arthritis involves more than only the TMJ
studies have used mouth-opening capacity as
itself, and thus special attention must be paid to
an indirect outcome variable reflecting the cur-
both the TMJ and the surrounding structures
rent functional status of the TMJ, with increased
during clinical examination. Orofacial symptoms
post-treatment mouth-opening capacity inter-
are most common in the TMJ area and the
preted as a treatment-induced improvement in
masseter muscle region (Fig. 1A).12,13,16,22 Con-
TMJ function.23 The predictive value of reduced
stant orofacial symptoms are rare; the majority of
mouth-opening capacity and early TMJ arthritis
patients with pain complaints experience pain
has been examined in cross-sectional studies
during jaw functioning on a weekly basis. TMJ
regarding early diagnosis of TMJ arthritis. These
and masticatory muscle symptoms most com-
studies have shown that mouth-opening capacity
monly occur during mastication and maximal
has only a limited predictive value when using
mouth-opening procedures, and TMJ morning
standardized cut-off reference values of normal/
stiffness is also a frequent complaint (Fig. 1B).16
abnormal mouth-opening capacity (e.g., abnor-
The symptoms typically fluctuate over time and
mal if less than 40 mm).21 This could be due to
the average pain intensity, if present, is
the fact that mouth-opening capacity is generally
moderate; however, great variation is seen in
associated with a large inter-individual variation
this parameter.16 Table 2 illustrates the typical
(approximately 18 mm between the 10th and the
complaints associated with JIA.
90th percentiles),24 and that the reproducibility
of duplicate mouth-opening measurements is
Clinical signs
limited. Future prospective longitudinal studies
Among patients with JIA, reduced mandibular are needed to elucidate the predictive value of
range of motion and asymmetric mouth opening standardized mouth-opening measurements
are the two most common clinical signs reported when age-related mouth-opening references
to be associated with TMJ involvement.18–22 from healthy individuals are taken into consi-
Throughout the literature, several other clin- deration.
ical signs have been associated with TMJ arthritis Mandibular deviation at maximal mouth
(Table 2). opening is another important clinical examina-
The most consistently reported clinical sign of tion variable in patients with JIA. Asymmetric
TMJ arthritis is reduced mandibular mouth- mandibular position at maximal opening posi-
opening capacity, although this clinical finding tion, in relation to the facial vertical midline, may
is not specific to arthritis.18–22 Mouth-opening indicate TMJ arthritis in the side of devia-
capacity is also the clinical outcome measure tion.18,21,22 Another clinical finding associated
Figure 1. (A) Relative frequency distribution of self-reported orofacial pain localization. Pain solely from the TMJ
area is rare. Symptoms most often occur in the TMJ area in combination with the masseter muscle region. (B)
Typical self-reported main complaints in patients with juvenile idiopathic arthritis and TMJ involvements. Patients
often report several complaints. Data from Stoustrup et al.16 Reproduced with permission from the Journal of
Rheumatology.
with TMJ involvement is a lack of condylar and discussed in detail in other articles in the
translation, such that the joint only displays a present issue of Seminars in Orthodontics.
rotational movement during mouth opening.20,22 Therefore, here we will only briefly discuss the
association between imaging methods and
clinical examination. No x-ray-based imaging
Limited association between MRI and orofacial methods are capable of showing inflammation,
signs/symptoms but they are important in analyzing craniofacial
The classical signs of inflammation are rubor, structures and evaluating the possible destructive
calor, dolor, tumor, and function laesa. However, course of the disease to improve the selection or
these signs are not always present in JIA patients adaption of necessary treatment options.25–27
with TMJ involvements; therefore, their absence Contrast-enhanced MRI is considered a highly
may only account for a limited specificity of TMJ sensitive method to detect TMJ inflammation,
inflammation in children and adolescents with although von Kalle et al.28 recently questioned
JIA.21 The sensitivity of TMJ arthritis diagnosis the validity of a positive MRI finding, since they
can be improved with the use of different found that MRI contrast enhancement is a
imaging techniques, each with its own benefits normal finding in the soft tissue and the
and limitations. These techniques are introduced condyle of the TMJ in non-arthritic children
Table 2. Temporomandibular Joint Arthritis-Related Orofacial Signs and Symptoms Described Across the Literature
TMJ Arthritis-Related Signs and Symptoms
Symptoms Signs
Pain/difficulties during mastication Reduced mouth-opening

Pain with maximal mouth opening Mandibular deviation at maxima mouth openinga
TMJ morning stiffness Reduced translation
Tiredness of the jaws Reduced protrusion/laterotrusion
Headache Asymmetric protrusion
Neck pain TMJ crepitation
Others Pain/tenderness on palpation: TMJ and masticatory muscles
Reduced bite-force
a
Corrected mandibular position at maximal mouth opening is not considered a deviation.
and adolescents. Additionally, MRI examination also further discussed elsewhere in this edition of
also has the drawbacks of limited availability and Seminars in Orthodontics. It is important to recognize
high cost. that there are no pathognomonic dental signs/
Some research has focused on the association traits for early TMJ arthritis diagnosis. Long-term
between MRI findings and clinical signs and TMJ arthritis in patients during growth may lead to
symptoms, with the purpose of establishing clin- mandibular growth deficiencies resulting in a
ical predictors to aid early diagnosis of TMJ hyperdivergent jaw base relationship that tends to
arthritis. However, less attention has been paid to develop into a skeletal Class II pattern.34
the association between MRI findings and clinical
findings in patients who already present chronic
TMJ arthritis-related clinical signs and symptoms. Recommendation of clinical craniofacial
Based on the current literature, MRI is consid- examination in patients with JIA
ered the golden standard in detection of early Regular orofacial evaluations of JIA patients have
TMJ arthritis in patients with JIA.29 In contrast, been recommended by several studies.12,14,16
routine MRI is of less clinical value in patients Based on the existing knowledge on TMJ
with TMJ arthritis-related signs and symptoms, arthritis in patients with JIA the following general
since only a limited association is shown between aspects are recommended to be elucidated in the
orofacial symptoms and TMJ MRI findings.20,30–33 clinical orofacial examination:
Supporting this, Arabshahi et al.31 found no
association between clinical improvements in Patient symptoms
maximal mouth-opening capacity and reso- Clinical signs
lution of MRI effusion at follow-up after TMJ Craniofacial morphology and growth pattern
arthritis treatment with intra-articular steroid
injections. From a clinical point of view, this
means that patients with TMJ arthritis-related The clinical examination must foremost
orofacial signs and symptoms may present no address the clinical characteristics of JIA patients
MRI indications of TMJ inflammation. Inversely, with TMJ involvement, as described in Tables 2
it is also possible that MRI signs of TMJ inflam- and 3. An example of a short clinical examina-
mation may be found in a clinically asymptomatic tion could be as follows:
patient. Furthermore, anti-inflammatory treat-
ment modalities leading to resolution of MRI Questions about the subjective pain intensity,
signs of inflammation may not necessarily be duration, and frequency.
followed by improvement in signs and symptoms Clinical examination of the lateral TMJ pole
in patients with JIA. These findings underline the and masticatory muscles (e.g., the masseter
mutual relationship between MRI and clinical and the temporalis muscles).
examination, and suggest that both types of Clinical functional examination of the jaw and
examination should be considered when dealing TMJ movement in terms of mouth-opening
with patients with JIA. capacity, and lateral deviations of the chin
during the opening movement.
Craniofacial morphology in patient Table 3. Craniofacial Characteristics of Patients with

with JIA TMJ Arthritis-Induced Growth Disturbances
Craniofacial Characteristics of Patients with TMJ Arthritis
The presence of TMJ arthritis is known to alter
craniofacial development in children.1–5,34 Skeletal Class 2 appearance
Inflammation within the TMJ affects the con- Increased ML/NSL angle
dylar cartilage that forms the basis for the endo- Increased ANB angle
Increased anterior face height
chondral ossification process that is partly Retruded and inclined mandible
responsible for mandibular growth.35–37 The Short mandibular ramus height
location of this growth zone within the TMJ is a Appositional growth in the gonion area
Craniofacial asymmetry
unique characteristic of this joint. Table 3 and Steep/canted occlusion plane
Fig. 2 show the abnormalities that result from TMJ Proclination of lower incisor
inflammation in growing individuals, which are Anterior open bite
Figure 2. Clinical photo of a 13-year-old girl with juvenile idiopathic arthritis and TMJ arthritis involvement. (A)
Frontal view: obvious facial asymmetry with a lip line canting toward the right side. Reduced vertical development of
the right side of the face compared to the left side. (B) Lateral view: skeletal Class 2 appearance with increased
anterior face height and a concave profile.
It is important to recognize that TMJ arthritis- dental educational background for the results to
related orofacial symptoms often fluctuate and be reliable and valid. In many countries, routine
are most often present in situations where spe- orofacial examinations of JIA patients are
cific functional demands trigger the symptoms conducted by pediatric rheumatologists without
(e.g., during masticatory activity and maximal a dental educational background. Therefore, on
mouth opening), which can make it difficult to a global basis, it is important to develop a JIA-
recall during the clinical examination. During specific validated examination protocol that
routine clinical assessment, this issue can be pediatric rheumatologists can use to identify
addressed by the introduction of a standardized potential TMJ arthritis candidates and to refer
patient questionnaire in which the patient these patients for further craniofacial examina-
reports their orofacial symptoms within the last tion carried out by specially trained dentists. A
2–4 weeks. This procedure is recommended standardized examination protocol would
since it allows for a more meticulous and accu- improve the chances of diagnosing a sudden
rate description of symptoms of each individual reduction in TMJ function and/or a detrimental
patient. However, no specific questionnaire orofacial growth pattern, which could then be
currently exists for JIA patients, and no stand- met with increased future attention, and opti-
ardized guidelines have been established for mized patient referral.
clinical assessment. The sensitivity/specificity of a the clinical
Diagnostic tools and indices, such as the orofacial examination in relation to TMJ arthritis
Helkimo index7 and the RDC/TMD,10 have been diagnosis has been debated, and is strongly
used in studies with JIA patients; however, their influenced by factors such as time available for
sensitivities have not yet been established in each patient, profession and educational back-
relation to this specific group of patients. As ground of the examiner, and general knowledge
mentioned above, another drawback is that these and practice of the clinic. No standardized
tools must be performed by someone with a guidelines exist regarding the interval between
regular routine clinical examinations in JIA 3. Mericle PM, Wilson VK, Moore TL, et al. Effects of
patients. Therefore, this interval should be polyarticular and pauciarticular onset juvenile rheuma-
toid arthritis on facial and mandibular growth. J Rheu-
decided individually based on conditions such as matol. 1996;23:159–165.
presence of TMJ involvement, patient pain 4. Sidiropoulou-Chatzigianni S, Papadopoulos MA, Koloki-
complaints, clinical signs, craniofacial growth thas G. Dentoskeletal morphology in children with
pattern, JIA subtype, general disease activity, and juvenile idiopathic arthritis compared with healthy
age at JIA onset. The future craniofacial growth children. J Orthod. 2001;28:53–58.
5. Twilt M, Schulten AJ, Nicolaas P, et al. Facioskeletal
potential in relation to the current age should changes in children with juvenile idiopathic arthritis. Ann
also be a decisive factor in determining the Rheum Dis. 2006;65:823–825.
interval, since TMJ arthritis can obviously have a 6. Kuseler A, Pedersen TK, Herlin T, et al. Contrast
larger impact on craniofacial development if enhanced magnetic resonance imaging as a method to
diagnose early inflammatory changes in the temporo-
onset occurs before or during the pubertal
mandibular joint in children with juvenile chronic
growth spurt. arthritis. J Rheumatol. 1998;25:1406–1412.
7. Helkimo M. Studies on function and dysfunction of the
masticatory system. II. Index for anamnestic and clinical
Future recommendations dysfunction and occlusal state. Sven Tandlak Tidskr.
At the time of writing this article, a task force 1974;67:101–121.
8. List T, Wahlund K, Wenneberg B, et al. TMD in children
within the EuroTMJoint research network is and adolescents: prevalence of pain, gender differences, and
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JIA. The presently described clinical character- changes link retrognathic mandibular growth to TMJ disc
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2011;40:621–627.
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in 2015 published in 2015-16 on the webpage of temporomandibular joint disorders: Review, criteria,
the euroTMJoint network (www.eurotmj.com). examinations and specifications, critique. J Craniomandib
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11. Schiffman E, Ohrbach R, Truelove E, et al. Diagnostic
Criteria for Temporomandibular Disorders (DC/TMD)
Conclusion for clinical and research applications: Recommendations
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in the general health assessment of individuals function, and temporomandibular disorders in women
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TMJ imaging in JIA patients—An overview
Tore A. Larheim, Andrea S. Doria, Eva Kirkhus, Dimitri A. Parra,
Christian J. Kellenberger, and Linda Z. Arvidsson
Involvement of the TMJ in children with JIA may lead to facial growth
disturbances, pain, and/or impaired jaw function. For the prevention of such
complications, early diagnosis of TMJ arthritis is paramount and a
prerequisite for early treatment. Since clinical signs and symptoms from
the TMJs frequently are absent, imaging plays a major role in diagnostic
assessment. In earlier studies, conventional methods were applied, predom-
inantly panoramic radiography. In the last decade, MRI has become the new
standard for examining these joints because both joint inflammation and
joint damage can be evaluated. This review will briefly focus on imaging
modalities to assess JIA in the TMJ, imaging manifestations of JIA in the
TMJ, frequency of TMJ involvement on imaging, clinical predictors of TMJ
involvement, relationship between TMJ involvement on imaging and facial
growth disturbance, longitudinal TMJ studies, image-guided intra-articular
injections, differential diagnoses, and future need for research. (Semin
Orthod 2015; 21:102–110.) & 2015 Elsevier Inc. All rights reserved.
Introduction radiography3–11 or magnetic resonance imaging

(MRI).12–19
he definition of juvenile idiopathic arthritis
T (JIA) is based on clinical cardinal signs of
inflammation: “Swelling within a joint, or limi- Imaging modalities to assess JIA in the
tation in the range of joint movement with joint TMJ
pain or tenderness”.1 However, this definition
frequently cannot be applied to the TMJ because In early years, a number of imaging modalities
joint swelling in particular, but other symptoms have been used to assess TMJ arthritis in patients
as well, is seldom reported. As a consequence, the with JIA. Panoramic radiography was by far the
TMJ has been dubbed “the forgotten joint” in most frequently applied method, but others
pediatric rheumatology,2 and diagnostic imaging include transcranial examination,20,21 conven-
is considered mandatory to assess JIA tional tomography,22 and a combination of
involvement. During the last four decades, this panoramic, transcranial, and tomographic
has been emphasized in a number of studies methods,5,6,23 and later, computed tomography
using conventional methods, usually panoramic (CT)24,25 and cone beam CT.26,27 Ultrasound has
also been investigated.14,16,28,29
Although studies continue to be published
using panoramic radiography because of its
Department of Maxillofacial Radiology, Institute of Clinical
availability and simplicity, MRI has become the
Dentistry, University of Oslo, Oslo, Norway; Institute of Clinical
Dentistry, University of Tromsö (UiT The Arctic University of new standard for examining these joints because
Norway), Tromsö, Norway; Department of Medical Imaging, The both joint inflammation and joint damage can be
Hospital for Sick Children, University of Toronto, Toronto, Ontario, evaluated. It is frequently used to evaluate
Canada; Department of Radiology, Oslo University Hospital, treatment with corticosteroid injections.30–35
Rikshospitalet, Oslo, Norway; Department of Diagnostic Imaging,
University Children's Hospital Zürich, Zürich, Switzerland.
Corresponding author at: Department of Maxillofacial Radiology,
Imaging manifestations of JIA in the TMJ
Institute of Clinical Dentistry, University of Oslo, P.O. Box 1109,
Blindern 0317, Oslo, Norway. E-mail: t.a.larheim@odont.uio.no X-rays
1073-8746/15/1801-$30.00/0 Most studies have focused on the osseous TMJ
http://dx.doi.org/10.1053/j.sodo.2015.02.006 components, in particular the mandibular

TMJ imaging in JIA patients 103
condyle. Various degrees of flattening are typically about 1 year of age.40 No obvious changes in this
reported; the condyle may be completely absent. morphology could be observed between 1 and 4
Although destruction, erosion, and resorption are years of age, giving the TMJ an early adult-like
frequently used expressions for the bone damage, appearance, although the joint continues to grow
it is our experience that this is frequently a into adulthood. With severe JIA involvement, the
remodeling of the condyle with both bone- TMJ has been found to resemble normal infan-
destructive and bone-productive changes. The tile TMJs in radiographic appearance. It was
abnormal bone shape could be considered a form postulated that the eminence flattening could be
of growth disturbance within the TMJ as a response due to lack of normal development early in life
to the inflammatory activity (Fig.). As discussed by rather than joint destruction, due to the
Arvidsson et al.,36 a deformed joint with an inflammation.40
apparently intact cortical outline might even be An important aspect of JIA is the impaired
the result of a previous erosion or destruction with TMJ function. In healthy children, the condylar
subsequent “healing.” Surely, evident cortical translation is very good, and at maximally
erosions similar to those occurring in adult opened mouth, the condyle is located entirely
rheumatoid arthritis may also be seen in the anterior to the “apex” of the eminence as seen
TMJ, and such changes have been demonstrated on transcranial radiography.38 In both children
in children within a 6-month period, even with and adults with JIA, the maximal condylar
conventional radiography.37 translation was less than half of that observed
Also the temporal bone (articular fossa/emi- in healthy controls.4,41 In the adults, the trans-
nence) may be involved by JIA (Fig.), although it lation constituted only 37–42% of the trans-
cannot be evaluated with panoramic lation in the control subjects, whereas the
radiography. The typical flattening can be maximal mouth-opening capacity constituted
visualized with conventional transcranial and about 57%.4 Thus, the impaired function was
tomographic methods both in small children clearly more severe assessed by radiography
and adults.38–40 In a radiographic study of nor- than by clinical assessment; a patient could
mal TMJ development, the articular eminence have a mouth-opening capacity of more than
developed from a flat form in newborns to an 40 mm but still have a reduced condylar
evident S-shaped appearance in infants already at translation.
Figure. Panoramic radiography of 11-year-old girl with supplementary cone beam CT at 2-year follow-up showing
facial asymmetry and deformed (flattened and remodeled) condyle and fossa/eminence with intact cortical
outline, indicating sequel of arthritis in the right TMJ. She had no jaw symptoms.
104 Larheim et al
MRI JIA children and healthy controls indicated that

it was useful as a screening method.29 However,
With the advent of MRI, pathology of all joint
when compared to MRI as gold standard for
components can be visualized, as well as
detecting TMJ synovitis, the sensitivity was low
inflammatory activity. The first non-enhanced
and US was not recommended for TMJ
TMJ study on a series of children with JIA was
evaluation.14,16 A recent study on US and
published in 1993.13 Flattening of the disc was a
MRI is far more positive and suggested that US
frequent abnormality, supporting observations in
“could become one of the leading instruments
the first two non-enhanced MR imaging studies
for the evaluation of TMJ involvement in JIA.”51
of adult rheumatic TMJ disease.42,43
US is a very operator-dependent method and we
The value of contrast-enhanced MRI to assess
suppose many will argue against such a
inflammation was demonstrated in the first series
statement.
of children published in 1998,12 a few years after
synovial contrast enhancement was visualized in
adult rheumatic TMJ disease,44 as a signal
increase on post-Gd T1-weighted images com- What is the frequency of TMJ
pared to pre-Gd images. involvement in JIA on imaging?
The frequency of contrast enhancement has
The wide range of frequencies is repeatedly
varied substantially, 87–93% in early studies12,45
mentioned in the literature with the figures 17–
and 73–80% in subsequent studies.14,18,46 These
87%. However, the 87% was based on only 15
figures are in contrast to the significantly smaller
selected patients,12 and when this group was
percentages reported in larger series of children,
followed for 2 years, the frequency raised to
29% (64 of 223 patients) by Cannizzaro et al.17
93%.45 Regarding the 17%, the article referred to
and 31% (116 of 370 joints in 185 patients) by
claims the frequency to vary between 5% and
Stoll et al.19 It should be emphasized that
17%,52 without reference to any patient series or
contrast enhancement of the TMJ has been
other study. All investigations since the 1970s
reported also in healthy children.47,48
focusing on the TMJ show that the involvement is
Joint effusion is another manifestation of
at least 29%.3 Several studies are reporting
inflammatory activity and again the frequency
frequencies of 50% or more with conventional
has varied significantly, from about 13%18,19 to
radiography, 50%,53 62%,8 50–72%,54 57–77%,11
23%,17,45 and up to 65%.46 In a study
and 78%.10 In a longitudinal study of 103
investigating the utility of corticosteroid
children, the frequency of TMJ involvement
injections, joint effusion was reported in 57%
increased from 42% at baseline to 67% at 4-
(13 of 23 joints) in 14 patients at the time of the
year follow-up.50
first injection.30 Joint fluid may also be found in
As might be expected, the percentage of
the TMJ in healthy individuals, as reported by
patients with TMJ involvement has been higher
Kellenberger et al.49
using MRI than using conventional radiographic
Bone marrow edema is a third manifestation
methods. A frequency of 63% was reported by
of inflammatory activity, observed in 17 % of 48
Müller et al.,16 80% by Aziez et al.,46 87% by
patients by Abramowicz et al.18
Küseler et al.,12 91% by Weiss et al.,14 93% by
Long-standing TMJ involvement demonstrates
Küseler et al.,45 and 96% by Abramowicz et al.18 It
bone deformation, frequently with secondary
should be noted that these reports included less
osteoarthritis and rather frequently with mild
than 50 patients.
contrast enhancement.36,50
Interestingly, in two more recent studies of
MR imaging findings in the healthy and arthritic
large series of children examined by MRI, con-
TMJ are thoroughly discussed elsewhere.49
siderably lower frequencies than earlier are
reported. TMJ abnormalities were found in 39%
Ultrasound
of 223 children by Cannizzaro et al.17 and in 43%
High-resolution (US) with linear probes (12-17 of 187 children by Stoll et al.19 These figures are
MHz) is routinely used to detect synovitis in a surprisingly similar to those reported in large
number of joints and was applied in a pilot TMJ series of children examined with conventional
study in 2007.28 A later work comparing US in panoramic radiography, around 40%.5–7,9,50,55–57
Most of these studies are based on consecutively bilateral TMJ involvement.59,68 In a study
examined patients. by Larheim and Haanaes4 on 20 adult JIA
Unilateral TMJ involvement is frequently patients with evident micrognathia determined
found with conventional radiographic methods by clinical examination and defined by cepha-
mostly between 40% and 45%.5,8,53,55 In studies lometric analysis, bilateral TMJ abnormalities
using MR imaging, the proportion of patients were identified in all. In a 27-year follow-up
with unilateral TMJ involvement seems to be study of 60 JIA patients, 27% had developed
smaller.14,18,19 This is to be expected since MR micrognathia based on cephalometry, and all of
imaging is more sensitive than panoramic radi- those had bilateral TMJ involvement.67 Of all
ography.58 Unilaterality also seems to decrease the patients with TMJ involvement, 70% had
with age and disease duration; it changed from some form of facial growth disturbance.
40% at baseline in childhood to 18% in Thus, 30% of the patients with radiographic
adulthood.50 TMJ involvement, the majority from childhood,
had not developed facial growth disturbance.67
This supports some earlier studies that
Clinical predictors of TMJ involvement
suggested that TMJ involvement seen on x-ray
Direct comparison of the frequencies of TMJ not necessarily leads to facial growth dis-
involvement reported in the different studies turbance.7,21,55 On the other hand, it has been
should be made with caution because TMJ stated that “untreated, TMJ arthritis leads to
involvement is associated with a number of var- micrognathia.”69 Some authors have claimed
iables. Some clinical predictors of TMJ involve- that even minimal TMJ involvement may inhibit
ment in earlier studies using conventional the growth.10
radiographic methods5,8,9,11,59 and in more More interestingly, it has been suggested that
recent studies using MRI15,17 are: young age at the growth to some extent may be regained in
onset (o4 years), long disease duration, systemic patients with improved TMJ arthritis. In a long-
or polyarticular disease subtype, and extended term study, a progressing TMJ arthritis course
disease course. Absence of HLA-B27 has also was related to posterior mandibular growth
been associated with TMJ involvement.8,17 TMJ rotation, i.e., a worsening growth pattern,
involvement occurs in all JIA subtypes although whereas an improving disease course was related
the rate may differ significantly17 and is more to anterior rotation, i.e., an improving growth
prevalent in children with extended pattern,70 supporting a study with a shorter
pauciarticular disease than in those with follow-up.71 In the first group of patients, this
polyarticular disease.17,59 Impaired mandibular happened without the use of modern medication
function assessed clinically as limited mouth- and steroid injections.70
opening capacity or opening with deviation or
reduced condylar translation is strongly asso-
Longitudinal TMJ studies
ciated with TMJ involvement on imaging in a
number of studies.4,5,7,9,19,58 Rather few studies are available, and most are based
on conventional radiography. Progression of con-
dylar abnormalities was observed within a 6-month
Relationship between TMJ involvement
period in a study that compared different medi-
on imaging and facial growth disturbance
cation regimens in children.37 Progression was also
In addition to pain and functional problems, the reported in a 6-year and in 27-year follow-up
most important reason to focus on the TMJ study.50,60 A yearly incidence of 7.1% of new con-
arthritis is the facial growth disturbance. dylar lesions has been found.72
TMJ involvement has been considered the More interestingly, improvement of the con-
most important cause of this abnormal dylar condition is also documented,60,73 even
growth.4,10,20,21,60–67 Facial asymmetry has been complete normalization of the condyle.74 However,
found to be strongly related to unilateral using advanced imaging, the joint was never
TMJ involvement.59 On the other hand, normalized completely in a long-term follow-
mandibular underdevelopment (micrognathia up,36 although signs of improvement were clearly
and retrognathia) has been strongly related to seen.50
106 Larheim et al
MRI has also been applied in follow-ups. modalities. MRI-guided injections show promis-
In a study, 15 patients examined four times ing results and probably will become frequently
at 6-month intervals, an important observation used in the future.33
was that synovial contrast enhancement, effu- The procedure is performed using conscious
sion, and marrow edema fluctuated over sedation or general anesthesia, a strict sterile
time.45 This supports a 15-month follow-up technique, 25 gauge needles, and the steroid
study of an adult psoriatic arthritis patient, in triamcinolone hexacetonide. The medication is
whom both fluid and marrow edema changed determined by the referring rheumatologist
from normal through increased to decreased (usually 5–10 mg) and is followed by the injection
signal intensity on T2-weighted images, of a small volume of local anesthetic (lidocaine
indicating exacerbation and subsidence of 1%). This procedure is performed routinely in
inflammation.75 many centers, reporting excellent clinical results
Follow-up studies using MRI are usually short- and a very low complication rate.31,76
term, evaluating the effect of intra-articular There is, however, a concern that the current
injections. Corticosteroid injections have level of evidence allows only very limited con-
resulted in substantial reduction or resolution of clusions on the effect of steroid injections in JIA
joint effusion and/or synovial contrast patients with TMJ arthritis as shown in a sys-
enhancement in about half or more of the tematic review on efficacy and safety.78
treated joints.30,31,34 In a study, a TNF antagonist Moreover, experimental animal studies do not
(infliximab) agent was injected in TMJs that were indicate a positive effect on the mandibular
resistant to corticosteroids.35 Although growth by the use of steroid injection in the TMJ
resolution of inflammation was observed in a as an early treatment of inflammation.79 The
few joints, the progression of bone abnormalities effect on mandibular growth in humans is
was more substantial. Development of bone not known.
abnormalities is also reported in some of the
other studies.31,34 Thus, the effect of intra-
Differential diagnoses
articular injections based on MRI findings may
so far be questioned. Also, the “normal” fluctu- TMJ involvement on imaging may be quite typ-
ation of inflammatory activity,45,75 and the fact ical, in particular in patients with long-standing
that most patients were re-examined several TMJ arthritis. However, in patients with a mean
months after the last injection will add to the age of 35 years, Arvidsson et al.50 occasionally
uncertainty of the effect of intra-articular injec- observed TMJ conditions that could not be
tions reported. distinguished from osteoarthritis. In this age
group, TMJ dysfunction is quite common in
the general population, and the dysfunction is
Image-guided treatment of TMJ arthritis
frequently related to disc displacement and
Image-guided intra-articular steroid injection is a osteoarthritis.80,81 Similar observations are
treatment possibility for TMJ arthritis in children. made in the pediatric age group.82,83 In adults,
Different imaging modalities can be used to adolescents, and children such TMJ dysfunction
advance a needle into the joint space such as a may be a differential diagnostic challenge to JIA
combination of US and CT76 or C-arm CT,77 TMJ involvement.73 It should be noted that a
using the lowest radiation dose possible. US displaced disc is also found in 10–33% of
provides an excellent view of the superficial asymptomatic volunteers and in preorthodontic
portion of the joint as well as the adjacent adolescents,84 but as a non-reducing condition
vascular structures, which should be avoided only in patients and not in volunteers.85
during the injections. The needle is advanced TMJ fluid is also found in patients with dys-
into the joint space under direct US visualization. function but has been observed in more than half
To determine the final needle position, of adult volunteers as well.86 In children, a
anatomical landmarks in CT76 or C-arm CT are minority has shown prominent amount of
used. Based on the imaging findings, this posi- fluid, and even discrete synovial contrast
tion may be adjusted prior to the injection, which enhancement.48 However, excessive amount of
is the rational for combining the two imaging fluid is pathologic and was reported in a non-
rheumatic child with TMJ arthritis, reactive to 3. Rönning O, Väliaho ML, Laaksonen AL. The involvement
lymphadenitis, and aseptic meningitis.87 of the temporomandibular joint in juvenile rheumatoid
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factorial origin. In a study of 38 patients younger dibular joint changes and dental occlusion in juvenile
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Magnetic resonance imaging of
temporomandibular joints in juvenile
idiopathic arthritis
Christian J. Kellenberger, MD, Linda Z. Arvidsson, DDS, PhD, and
Tore A. Larheim, DDS, PhD
Magnetic resonance imaging (MRI) is considered essential for diagnosing

early involvement of the temporomandibular joint (TMJ) in children with
juvenile idiopathic arthritis (JIA). Assessment of the soft tissue joint
components and contrast enhancement allows diagnosing and grading
the severity of TMJ arthritis. An MRI grading system for synovial inflamma-
tion and deformity of the TMJ in children with JIA is proposed. Normal and
arthritic MRI findings are illustrated. (Semin Orthod 2015; 21:111–120.) & 2015
Elsevier Inc. All rights reserved.
Introduction The condylar contour is rounded with a

straight condylar neck in a young child up to
n children with juvenile idiopathic arthritis
I (JIA), imaging is fundamental to assess the
frequent involvement of the temporomandibular
about 5 years of age. With increasing age and
growth, the condylar neck gets anteriorly tilted
and the condylar contour more squared (Fig. 1).6
joint (TMJ). While various radiological methods
In coronal-oblique plane the normal mandibular
show the osseous components of the TMJ well,1
condyle has an ovoid shape usually with a convex
magnetic resonance imaging (MRI) offers the
upper contour.
unique opportunity to also investigate the soft
The bone marrow of the temporal and man-
tissues without exposure to ionising radiation.2,3
dibular bones contains varying proportions of
Contrast-enhanced MRI allows an early diagnosis
red haematopoietic marrow depending on age.7
of TMJ arthritis4 and is also valuable for monitoring
In an infant (Fig. 2) bone marrow signal intensity
the degree of synovitis and bony deformities under
is low (isointense to muscle) on T1-W images and
treatment.5 In this article we discuss and illustrate
intermediate (hyperintense to muscle) on fluid-
the MRI appearance of normal and arthritic TMJs.
sensitive sequences; T2-W fast spin echo (FSE)
with fat-saturation or short tau inversion recovery
(STIR). With older age and decreasing propor-
Normal MRI appearance of TMJ in
tion of red marrow, the amount of fatty marrow
children
will increase (Fig. 3), eventually becoming iso-
Osseous components intense in signal intensity to subcutaneous fatty
tissue on all sequences.
The temporal articular surface consists of the
glenoid or mandibular fossa posteriorly and the
articular eminence anteriorly giving it an s-shaped Articular disk
configuration in sagittal-oblique imaging plane.
The normal articular disk is well visualised on
Department of Diagnostic Imaging, University Children’s Hospi-
FSE images as a biconcave structure with homo-
tal Zürich, Zürich, Switzerland; Department of Maxillofacial geneous low signal intensity interposed between
Radiology, Institute of Clinical Dentistry, University of Oslo, Oslo, the mandibular condyle and the articular surface
Norway. of the temporal bone (Figs. 4 and 5), dividing the
Address correspondence to Christian J. Kellenberger, MD
TMJ in a larger upper and smaller lower com-
Kinderspital Zürich, Steinwiesstr 75, CH 8032 Zürich, Switzerland.
E-mail: christian.kellenberger@kispi.uzh.ch partment. The fibrocartilaginous disk consists of
a thicker triangular anterior and posterior band
1073-8746/15/1801-$30.00/0 joined by a thinner intermediate zone. With the
http://dx.doi.org/10.1053/j.sodo.2015.02.007 mouth closed, the mandibular condyle is seated

112 Kellenberger et al
Figure 1. Four different children at different ages with normal TMJs. Sagittal-oblique gradient echo images show
increase of the articular eminence height and deepening of the fossa with increasing age.
in the mandibular fossa with the posterior band of secreted by the synovium located in the
the disk located at an 11–12 o’clock position in recesses.10 Detection of fluid by MRI depends on
relation to the condyle. However, both in healthy the orientation, spatial resolution and type of
children, adolescents,8 and in healthy adults9 up to sequence used.7 TMJ fluid has been reported in
one-third of subjects have an anteriorly displaced about half of 62 healthy adults examined with
disk. When the mouth is open, both the condyle T2-W images.11 In a series of 27 children without
and disk are located under the articular eminence, TMJ disease, Kottke et al.7 found hyperintense
with the intermediate zone of the disk at a 12 intra-articular fluid in 31% of the joints on T2-W
o’clock position in relation to the condyle (Fig. 4). FSE images and in 83% of the joints when fat-
saturation was added. Therefore, small hyper-
intense dots or lines of fluid in the joint recesses
Joint fluid
can be considered a normal amount of joint fluid
Every TMJ contains a small amount of synovial on highly fluid-sensitive sequences (T2-W FSE
fluid derived from plasma by dialysis and with fat-saturation or STIR) (Figs. 3 and 4).
Figure 2. A 2-year-old girl with normal bone marrow. Sagittal-oblique images show marrow signal intensity of the
mandible and temporal bone iso- to slightly hyperintense to muscle (n) or hypointense to subcutaneous fatty tissue
(nn) on T1-W image (A), mildly hyperintense to muscle on fat-saturated T2-W image (B), and isointense to muscle
on contrast-enhanced fat-saturated T1-W image (C).
Magnetic resonance imaging of temporomandibular joints 113
Figure 3. A 16-year-old girl with normal TMJ. Sagittal-oblique T1-W gradient echo (A), fat-saturated T2-W FSE (B)
and contrast-enhanced fat-saturated T1-W FSE (C) images. The subchondral bone is seen as hypointense line on all
sequences. Signal intensity of condylar bone marrow is consistent with a large proportion of fatty marrow still
containing some red marrow, with similar signal intensities on the T2-W (A) and contrast-enhanced (B) images.
Bone marrow signal intensities of temporal bone, mandibular condyle and mandibular ramus are similar. There is
a small amount of joint fluid in the anterior inferior joint recess (arrows in B and C) with high signal intensity on
the fat-saturated T2-W image (B) and contrast-enhanced fat-saturated T1-W image (C).
Contrast enhancement further steady increase beyond 6 min after contrast

administration. While signal intensity of vascula-
Following intravenous administration of gadolinium- rised tissues (veins, muscle, and synovium) decreases
based contrast agents, all vascularised tissues show again within minutes as the intravascular gadolinium
higher signal intensity on T1-W images than on pre- concentration falls, diffusion of the contrast agent
contrast images. Such contrast-enhancement has into the joint compartment continues and the high
been demonstrated in the normal TMJs in children signal intensity of fluid is retained for at least 1 h.13
by dynamic contrast-enhanced gradient echo Because contrast diffusion into the small TMJ
imaging.12 The joint compartment, consisting of is immediate, any T1-W image shows strong
synovial lining and small amounts of fluid, shows a enhancement of normal amounts of joint fluid.
strong enhancement within the first minute and a Even on T1-W FSE sequences acquired within
Figure 4. A 16-year-old boy with normal TMJ. Open mouth images show expanded retrodiskal venous plexus (n)
with high signal intensity on fat-saturated T2-W image (A) and strong contrast-enhancement on fat-saturated T1-W
image (B). Note small effusion with small amounts of enhancing joint fluid in all joint recesses (arrows).
Figure 5. A 8-year-old boy with moderate inflammation and mild osseous deformity of TMJ. T2-W fat-saturated
image shows small hyperintense effusion anteriorly in both joint compartments (A). Contrast-enhanced T1-W
image shows hyperintense signal intensity (isointense to vessels) in the entire joint space (B). The condyle is mildly
flattened and shows bone marrow oedema (normal marrow of ramus not shown on this slice).
4 min after contrast administration, the areas of bone marrow oedema and increased joint en-
the joint compartment containing a visible hancement as described for any other synovial
amount of fluid (as determined on fluid-sensitive joint.
sequences) will show intense enhancement with The increased enhancement in synovitis can
signal intensity similar to that of veins (Figs. 3 and be explained by hyperaemia, hypervascularity
4).7 Areas without detectable joint fluid maintain and increased permeability of the synovial mem-
signal intensities similar to that of muscle on early brane due to inflammation. On fat-saturated
sequences, but may increasingly enhance on T1-W images obtained immediately following
sequences acquired later on. Bone marrow contrast injection, we consider joint enhance-
enhancement of the temporal bone and mandi- ment as increased when high signal intensity
bular condyle is less intense with signal intensity (similar to that of veins) is seen in upper or lower
being isointense to that of mandibular ramus joint compartments exceeding areas of normal
marrow and surrounding muscles (Fig. 2).7 joint fluid (as seen on T2-W images) (Fig. 10),
If the condyle is in an anterior position in involves the entire joint compartments (Figs. 5
relation to the mandibular fossa such as in open and 7), or expands them (Figs. 8 and 9).
mouth position, the retrodiskal tissue (bilaminar Synovial hyperplasia is first evident as a
zone) containing a venous plexus will be dis- thickened lining of a joint recess with inter-
tended and visible as hyperintense structure on mediate signal intensity on T2-W images and
T2-W images and as intense enhancement on high signal intensity on contrast-enhanced T1-W
contrast-enhanced T1-W images (Fig. 4).14 This images (Figs. 6 and 7). Normal synovium is too
distended venous plexus should not be mistaken thin to be visualised. Differentiation between
for enhancing synovium or pannus. enhancing synovium and joint fluid may be
impossible in a small joint like the TMJ. With
increasing synovial hyperplasia the entire joint
MRI findings in TMJ arthritis compartment can be filled and expanded. We
define such soft tissue as pannus showing low or
Active inflammation
intermediate signal intensity on T2-W images and
The MRI signs of active TMJ inflammation (syno- variable degrees of contrast enhancement
vitis) are joint effusion, synovial hyperplasia, and (Figs. 8 and 9).
Figure 6. A 10-year-old girl with severe inflammation and severe osseous deformity of TMJ. Lateral fat-saturated
T2-W (A) and contrast-enhanced T1-W (B) images show moderate, strongly enhancing effusion in the upper
compartment. The anterior recess of the lower joint compartment is filled with intermediate intense (arrowheads
in A) soft tissue which also enhances (arrowheads in B). Central images show the upper compartment mostly
containing intermediate intensity soft tissues (“synovial thickening”) (C) which also enhances strongly (arrows)
(D). The disk is flattened but appears intact. The mandibular fossa is moderately flattened. The condyle shows
severe flattening with irregularities of the joint surface (small erosions).
Joint effusion is seen as hyperintense signal sensitive sequences, as well as increased contrast-
intensity area (isointense to that of cerebrospinal enhancement (Figs. 5 and 10).
fluid) on fluid-sensitive sequences in the upper The degree of synovial inflammation can be
or lower joint compartments exceeding the graded by qualitative assessment of the extension
normal tiny amount of joint fluid (Figs. 5 and 6). of joint enhancement, presence of synovial
Small joint effusions usually enhance strongly on thickening on T2-W images, and pannus for-
contrast-enhanced images, but large effusions mation. The following progressive score has been
expanding the joint compartments may show a developed at the University Children’s Hospital
peripheral enhancing rim (thickened synovium Zürich2,16 and is based on sagittal-oblique fluid-
and adjacent contrast diffused into the joint) on sensitive images and fat-saturated T1-W images
early images with gradual signal intensity increase acquired immediately following contrast
of the central portion over time, as demonstrated injection:
by Smith et al.15
Bone marrow oedema can be seen in the – Grade 1: Mild inflammation. Extension of joint
mandibular condyle but also in the temporal enhancement exceeds that of the normal joint
bone. The marrow shows signal hyperintense to fluid but does not involve the entire joint
that of mandibular ramus on fat-saturated fluid- space (Fig. 10).
Figure 7. A 17-year-old girl with severe inflammation and moderate osseous deformity of TMJ. Fat-saturated T2-W
(A) and contrast-enhanced fat-saturated T1-W (B) images show diffuse synovial thickening and joint
enhancement. The mandibular fossa is mildly flattened and the condyle is moderately flattened with small
erosions best seen in the gradient echo image (small arrows in C).
– Grade 2: Moderate inflammation. Joint

Validation of this and other grading sys-
enhancement involves the entire joint space tems5,17 is currently underway by working groups
or there is an enhancing joint effusion (Fig. 5). of OMERACT and EuroTMjoint.
– Grade 3: Severe inflammation. Detectable
synovial thickening in addition to increased
joint enhancement/effusion (Figs. 6 and 7).
Joint deformation
– Grade 4: The joint space is filled with and Deformation of the arthritic TMJs in children can be
enlarged by pannus (Figs. 8 and 9). due to altered growth, destruction by the
Figure 8. A 16-year-old girl with TMJ filled with pannus. The joint space is enlarged by intermediate intensity (A)
and enhancing (B) soft tissue. The condyle and articular eminence show bone marrow oedema (n in A). There is a
large erosion of the condyle and small erosions of the eminence (seen in B). Gradient echo image obtained more
laterally shows new bone formation extending from the articular eminence to the mandibular fossa (nn) (C).
Figure 9. A 8-year-old girl with destroyed TMJ. T2-W image showing a small amount of fluid (n), (A) surrounded
by hypo- to intermediate intense pannus expanding the joint space (arrows) and showing some enhancement (B).
On the 3D gradient echo image multiple globular hypointense calcifications/ossifications (arrowheads) are seen
within the pannus (C).
inflammatory process and probably, therapeutic erosions (Figs. 6–8). Progressive destruction of the
interventions. Both the temporal component and mandibular condyle may lead to bony fragmenta-
the mandibular condyle may typically show flat- tion, seen as discrete corpuscular structures with low
tening of variable degrees (Figs. 5–7, 10 and 11). signal intensity located within the joint compart-
The articular surfaces may reveal irregularities or ment. Intra-articular calcification (heterotopic bone
breaks in the subchondral bone considered to be formation) has a similar appearance (Fig. 9) and
Figure 10. A 10-year-old boy with mild inflammation and moderate osseous deformity of TMJ. There is bone
marrow oedema of the condyle with increased signal on fat-saturated T2-W image (A) compared to bone marrow
of the mandibular ramus (n). Joint enhancement (arrow in B) exceeds that of visible normal joint fluid (arrows in
A). Both the condyle and mandibular fossa are moderately flattened. Note centrally ruptured disk with only
peripheral hypointense remnants visualised.
Figure 11. Three TMJs from different children. Sagittal-oblique T1-W 3D gradient echo images showing
increasing degrees of flattening of the mandibular condyle: mild (A), moderate (B) and severe (C). The shape of
the mandibular fossa is normal in (A), mildly flattened in (B) and moderately flattened in (C).
has been described developing in the – Grade 3: Severe osseous deformity: severe
inflammatory pannus.18 In our experience, flattening of the condyle with loss of height,
intra-articular calcification and bone formation and/or completely flat temporal bone and/or
seem to occur with a higher frequency following the presence of small erosions (Figs. 6 and 7).
intra-articular corticosteroid injection. Further, – Grade 4: “Destroyed” TMJ: presence of large
remodelling of the TMJ may occur; bone appo- erosions (Fig. 8), and/or fragmentation of the
sition in the mandibular fossa, at the articular condyle, intra-articular ossifications, bone
eminence (Fig. 8) or of the mandibular condyle. apposition on condyle or temporal bone.
The articular disk may typically obtain a flat,
attenuated shape (Figs. 6 and 7) or in more
TMJ findings in long-standing JIA
advanced cases, perforate centrally (Fig. 10). The
disk can also dislocate in front of the mandibular There are few imaging studies on the adult TMJ
condyle. in JIA,21–25 and only one applying computed
Bony deformity of the TMJ can be graded in a tomography (CT) and MRI.26 In a group of 47
similar fashion as has been described for con- JIA patients (32 women, mean age 35 years and
ventional radiography and orthopantomog- mean disease duration 30 years) who all
raphy.19–21 We assess the osseous joint compo- underwent both CT and MRI of the TMJs, 33
nents for their shape, deformities and presence (70%) patients showed TMJ involvement and all
of erosions or destruction mainly on sagittal- but 4 had bilateral involvement.26 In most joints
oblique T1-W gradient echo images.16 Hypo- deformities of the condyle and fossa had been
intense corpuscular lesions within the joint present for at least 20 years, as shown by earlier
compartment are considered either bony conventional radiographs. Ruptured, fragmen-
fragments of the condyle or intra-articular cal- ted or absent disks were seen in more than 90%
cifications/ossifications (Fig. 9). Hypointense of the involved TMJs. Although disk abnor-
layers in continuity with the bony joint surfaces malities have been reported less frequently in
are considered as new bone formation (Fig. 8). children with TMJ involvement with only few
The severity of osseous deformity is graded destroyed or absent disks,27,28 the disk seems to
progressively in 4 grades (Fig. 11): be vulnerable to the disease from early on with
increasing severity of the abnormalities over
– Grade 1: Mild osseous deformity: mild flat- time. Bony sclerosis and osteophytes (secondary
tening of the condyle and/or temporal bone. osteoarthritis) were also more frequent in
– Grade 2: Moderate osseous deformity: moder- patients with long-standing disease (47% of the
ate flattening of the condyle and/or involved joints) than has been reported in
temporal bone. younger children with TMJ involvement.
Slight to moderate contrast enhancement 9. Larheim TA, Westesson P-L, Sano T. Temporomandib-
indicating mild synovitis was seen in about a third ular joint disk displacement: comparison in asymptomatic
volunteers and patients. Radiology. 2001;218:428–432.
of the affected joints (42% of the patients). Bone 10. Alomar X, Medrano J, Cabratosa J, et al. Anatomy of the
marrow oedema and joint effusion were very rare temporomandibular joint. Semin Ultrasound CT MR.
and hardly observed at all in the adult patients.26 2007;28:170–183.
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together with minor bone abnormalities, effusion Moss ME. MR evidence of temporomandibular joint fluid
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Fukuda J. Changes in temporomandibular disc position tion in patients with juvenile idiopathic arthritis followed
during growth in young Japanese. Dentomaxillofac Radiol. from childhood to adulthood. Pediatr Rheumatol Online J.
2007;36:397–401. 2010;8:13.
24. Larheim TA, Haanaes HR, Dale K. Radiographic tempor- 28. Abramowicz S, Cheon JE, Kim S, Bacic J, Lee EY.
omandibular joint abnormality in adults with micro- Magnetic resonance imaging of temporomandibular
gnathia and juvenile rheumatoid arthritis. Acta Radiol joints in children with arthritis. J Oral Maxillofac Surg.
Diagn (Stockh). 1981;22:495–504. 2011;69:2321–2328.
25. Larheim TA, Haanaes HR, Ruud AF. Mandibular growth, 29. Katzberg RW, Tallents RH, Hayakawa K, Miller TL, Goske
temporomandibular joint changes and dental occlusion MJ, Wood BP. Internal derangements of the tempor-
in juvenile rheumatoid arthritis. A 17-year follow-up study. omandibular joint: findings in the pediatric age group.
Scand J Rheumatol. 1981;10:225–233. Radiology. 1985;154:125–127.
26. Arvidsson LZ, Smith HJ, Flato B, Larheim TA. Tempor- 30. Suenaga S, Hamamoto S, Kawano K, Higashida Y,
omandibular joint findings in adults with long-standing Noikura T. Dynamic MR imaging of the temporoman-
juvenile idiopathic arthritis: CT and MR imaging assess-
dibular joint in patients with arthrosis: relationship
ment. Radiology. 2010;256:191–200.
between contrast enhancement of the posterior disk
27. Taylor DB, Babyn P, Blaser S, et al. MR evaluation of the
attachment and joint pain. Am J Roentgenol. 1996;166:
temporomandibular joint in juvenile rheumatoid arthri-
1475–1481.
tis. J Comput Assist Tomogr. 1993;17:449–454.
3D digital surface imaging for quantification of
facial development and asymmetry in juvenile
idiopathic arthritis
Tron A. Darvann, Per Larsen, Nuno V. Hermann, and Sven Kreiborg
3D digital surface imaging (digital stereophotogrammetry or “3D photog-

raphy”) is becoming an increasingly popular tool for quantification of the
face, in clinical contexts as well as for research. The modality is easy to apply
and is free from motion artifacts and harmful radiation. It is an obvious choice
for comprehensive documentation and analysis of facial development and
treatment progression and outcome in individuals with juvenile idiopathic
arthritis (JIA). An acquisition protocol for 3D digital surface imaging of
children and adolescents with JIA using a 3dMDtrio stereophotogrammetric
system is presented. Methodology for processing and analysis of the
acquired surfaces is presented and applied to two patient cases in order
to illustrate quantification of facial development and asymmetry progression.
It is concluded that surface imaging is a powerful technique for monitoring of
facial development and treatment outcome, and it is proposed that the
method would be suitable for multi-center comparisons of treatment
outcomes. (Semin Orthod 2015; 21:121–124.) & 2015 Elsevier Inc. All rights
reserved.
3D digital surface acquisition systems have

become reliable and accurate, and
provide detailed shape and color representation
may be stored as documentation or conveniently
allow measurement of the face after the patient
has left the clinic, for use in e.g., diagnostics,
of objects in many contexts, including dentistry treatment planning, or treatment outcome eval-
and medicine.1 Systems based on stereophoto- uation. A fairly large body of literature published
grammetry are very fast (less than 2 ms for an on measurement of the face using surface imaging
acquisition) thus avoiding motion artifacts. The deals with population studies,2–5 demonstrating
result is a spatially detailed polygonal mesh with beyond doubt the usability of 3D surface imaging
color texture (a color photo “pasted” onto the for these purposes. Of these, one study carried out
surface) that provides a sub-millimeter accurate by our research group investigates the facial
representation of the subject's face. The surface asymmetry in a population of children with JIA in
the temporomandibular joint (TMJ) and com-
pares them to a control population that has no
3D Craniofacial Image Research Laboratory (School of Dentistry,
University of Copenhagen; Centre of Head and Orthopaedics, TMJ involvement.4 The study also proposes a
Copenhagen University Hospital Rigshospitalet; and DTU Compute, method of comparison of the asymmetry in a
Technical University of Denmark), Copenhagen, Denmark; Depart- single individual with JIA to the mean asymmetry
ment of Oral and Maxillofacial Surgery, Copenhagen University in the control population, thus providing a clinical
Hospital Rigshospitalet, Copenhagen, Denmark; Pediatric Dentistry tool for measurement in the individual. Several
and Clinical Genetics, School of Dentistry, Faculty of Health and
Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
studies show the use of surface imaging in a clinical
Department of Clinical Genetics, Copenhagen University Hospital context with convincing results.6–8 Main sources of
Rigshospitalet, Copenhagen, Denmark. error that typically influence the measurement are
Correspondence to: Tron A. Darvann, MSc, PhD, 3D Cranio- (1) the imaging device itself (system accuracy and
facial Image Research Laboratory, School of Dentistry, University of
reproducibility),9 (2) the process of landmarking
Copenhagen, Nørre Alle 20, DK 2200, Copenhagen N, Denmark. E-
mail: trd@sund.ku.dk
(the capability of recognizing and marking
particular anatomical landmarks on the surface,
1073-8746/15/1801-$30.00/0 either directly (manually) by a human operator
http://dx.doi.org/10.1053/j.sodo.2015.02.008 or by some automatic algorithm),10,11 (3)

122 Darvann et al
deformation of the face due to facial expres-

sion,12,13 (4) spatial orientation of the face, and (5)
determination of detailed point correspondence
(interpolation between landmark locations; nec-
essary in order to obtain values of e.g., develop-
ment and asymmetry at every spatial location
across the face). Error sources (4) and (5) have
been less studied but are very dependent on the
application. Reproducibility may be assessed by
repeated measurement and accuracy by compar-
ison with visual assessment.14,15 Methodology of
particular relevance for assessment of soft tissue
development may be found in references.16–18 Figure 1. 3D digital surface imaging using the
3dMDtrio stereophotogrammetric system. Compare
Table. Letters C indicate cameras (two cameras for
Surface acquisition protocol geometry and one for color texture in each of the
three camera housings), F indicate flashes, M is the
Our experience since 2007 with surface imaging monitor showing live images, and S is the system
of children and adolescents with JIA has led to an computer.
acquisition protocol as presented in the Table.
The protocol is for a 3dMDtrio system (3dMD, high, while the side cameras are mounted lower
Atlanta, GA, USA) which has three camera pairs: in order to avoid occlusion in the chin area and
one located in front of the patient and two on in order to get good ear coverage. The computer
either side (Fig. 1). The front camera is mounted screen showing live images from the cameras is
mounted in front of the patient such that he/she
Table. Protocol for 3D Surface Imaging at School of can assist in adjustment of head orientation
Dentistry, Faculty of Health and Medical Sciences, according to vertical/horizontal grid lines
University of Copenhagen, Denmark, March 2015 superimposed on the screen.
System 3dMDtrio stereophotogrammetric system
with projection of random light pattern
Space 3.0 3.0 m Surface processing and analysis
requirement
Room lighting Ordinary roof lighting In broad terms, the pipeline of the data handling
Hardware 3dMD factory setup could be described as consisting of (1) ori-
setup entation, (2) segmentation, and (3) analysis. The
Screen The central camera window should be
windows positioned at the central bottom of the screen main purpose of orientation is to assure that two
Calibration Every day (or more) surfaces (e.g., at different time points)
Patient chair Chair with electric up/down function; 3601 have a similar and valid overall relative ori-
rotation capability; arm and head rest
Patient Date of birth, date of acquisition, body entation and is typically carried out by a rigid
information height, and weight should be recorded at registration based on landmarks or surface
each time of image acquisition patches. The validity of the relative orientation is
Patient No clothing around neck; no glasses or
preparation jewelry; head band to control hair achieved through selection of landmarks or
Patient Natural upright sitting position with the chair surface patches that are “stable” (i.e., fairly
positioning in a low position. Natural head to neck unaffected by the temporal progression one
posture. The chair is raised to the level where
the patient's eyes coincides with the wishes to uncover). The main purpose of seg-
horizontal central grid line in the central mentation is to assign anatomical knowledge to
camera window on the screen, and the particular points or regions on the surface. One
midline of the face should be adjusted
according to the vertical grid line in the particular type of segmentation is the process of
central camera window achieving detailed point correspondence19
Facial The patient is instructed to maintain a between the involved surfaces, resulting in all
expression relaxed facial expression, light contact on the
posterior teeth, and lips in light contact points in the face surfaces having a known
Exposures It is recommended that several exposures are correspondence in all other face surfaces. In
made (and reviewed) in the same position, particular, if detailed point correspondence is
especially when imaging young children
also known between the surfaces and an already
3D digital surface imaging 123
segmented reference surface (called an atlas),

the atlas segmentation may be automatically
transferred to the individual surface. In the
analysis step, measurements and analysis may
now be carried out meaningfully since, due to the
detailed point correspondence, arithmetic (e.g.,
for surface comparisons) may be carried out
point-wise across all involved surfaces.
Examples of quantification of
development and asymmetry
Case 1 is a girl with JIA and a radiographic Figure 3. Progression of facial asymmetry of Case 1.
Top images: 3D facial surfaces in a frontal view, color
diagnosis of unilateral involvement of the TMJ,
coded according to magnitude of asymmetry in mm,
where surface imaging had taken place at four are shown for four different time points in the same
examinations approximately 1 year apart (age at individual with unilateral involvement of the TMJ. Red
first surface acquisition 11 years 7 months). A and blue parts of the color table are being used on
modification of the above pipeline (4,14,15,20–22) opposite sides of the face. Plot: Star symbols indicate
the mean value of asymmetry across the entire face
was created that included a relative alignment23
region, shown with vertical bars corresponding to 1 SD.
of the four surfaces using a “mask” (Fig. 2) Filled circles indicate chin asymmetry. (For interpreta-
representing a noiseless, temporally stable region. tion of the references to colour in this figure legend,
Deformation vectors between temporally the reader is referred to the web version of this article.)
corresponding points were computed and
visualized.24 Fig. 2 shows deformation vectors deviation of asymmetry as a function of time.
between first and last examination in Case 1. In Clear differences in the pattern of development
addition, Fig. 2 shows a result of the same method may be seen between Case 1 and the control, in
applied to a control subject (a girl with JIA particular in the direction of deformation vectors
without radiographic signs of TMJ affection). in the chin region that has a large transverse
Fig. 3 shows the progression of asymmetry in component in Case 1, while it is very vertical in
Case 1, with a plot of the mean and standard the control. The pattern of asymmetry in Case 1 is
similar at all the examinations, but with a
magnitude increasing with time.
Conclusion
A methodology, including an acquisition proto-
col, suitable for quantification of development
and asymmetry in the face of individuals with
TMJ disorders due to JIA was presented. 3D
Figure 2. Left: The “mask” defining the region used surface imaging seems like a tool that is useful for
for rigid alignment of surfaces of the same individual
longitudinal monitoring of facial development in
over time. Middle: Mean facial surface of Case 1 with
deformation vectors superimposed demonstrating the individuals with JIA, and could also be expected
development between the first and last examination to be an effective tool for comparison of treat-
(age at first examination: 11 years 7 months; time span ment outcomes between treatment centers.
4 years 1 month). Color and direction of vectors
indicate amount and direction of development,
respectively. Blue to red range of the color bar
corresponds to ranging from no change to develop- References
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surface of the control subject with deformation vectors dimensional surface acquisition systems for the study of
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3 years 8 months). surgery. Int J Med Robot. 2007;3:97–110.
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4. Demant S, Hermann NV, Darvann TA, et al. 3D analysis of superimposition and measurement model for 3D sagittal
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Caucasian and African American facial morphologies in a stereophotogrammetry: a practical guide to facial image
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Systemic and intra-articular anti-inflammatory
therapy of temporomandibular joint arthritis in
children with juvenile idiopathic arthritis
Matthew L. Stoll, MD, PhD, Randy Q. Cron, MD, PhD, and
Rotraud K. Saurenmann, MD, PhD
Juvenile idiopathic arthritis (JIA) is a leading cause of acquired disability and

malformation in childhood. Although virtually any joint can be affected, one
of the most commonly involved yet least frequently recognized joints is the
temporomandibular joint (TMJ).1 Persistent arthritis can result in pain,
growth problems, cosmetic defects, and poor function, underscoring the
necessity of obtaining early control of TMJ arthritis. While the therapy of JIA
as a whole has benefitted enormously from the introduction of novel
therapeutic agents,2 it remains uncertain to what extent these therapies
benefit the TMJ specifically. Thus, many practitioners use intra-articular
therapy for refractory TMJ arthritis, although concerns about their long-term
safety have been raised.3 Herein, we will review the data on systemic and
local anti-inflammatory therapy of TMJ arthritis. (Semin Orthod 2015;
21:125–133.) & 2015 Elsevier Inc. All rights reserved.
Overview of juvenile idiopathic arthritis regarding the perceived frequency of TMJ arthritis
among JIA patients.9 However, centers that perform
J IA (previously referred to as JRA, juvenile
rheumatoid arthritis) is defined by the pres-
ence of arthritis in one or more joints with onset in
routine screening of TMJ arthritis by magnetic
resonance imaging (MRI) report frequencies of
40–80%.10–12 Although symptoms of TMJ involve-
a child under the age of 16 years, lasting at least 6
ment and abnormal physical exam findings (e.g., jaw
weeks, with no identifiable cause (e.g., lupus and
deviation and small oral aperture) appear to have a
infection).4 Diagnosis and classification of JIA are
high predictive value in identifying TMJ arthritis,11,12
discussed herein5 and elsewhere in this series.6
the absence of these findings is by no means reas-
suring, necessitating MRI screening to identify
TMJ involvement in JIA asymptomatic cases. In addition, these clinical
findings are late in the disease process when bony
The TMJ is one of the most infrequently recognized changes and growth disturbances have already fre-
yet commonly involved joints in JIA, hence its quently taken place. Complicating the matter is that,
moniker, “The forgotten joint.”1 Indeed, several while MRI abnormalities in patients with clinically
studies documenting the frequency of involved joints active arthritis were shown to reflect inflammatory
in JIA patients have completely excluded the TMJ,7,8 infiltrates on histopathologic examination,13
and there is enormous variation among centers increased T2 signal and even contrast uptake
can occur for a prolonged period of time during
The Department of Pediatrics and the Division of Rheumatology, the healing process after tissue injuries, potentially
The University of Alabama at Birmingham, CPP N 210 M, 1600 7th
reflecting ongoing reparative processes.14 Thus, in
Ave South, Birmingham, AL 35233-1711; The Department of
Pediatrics and the Division of Rheumatology, Direktorin DKJ, the absence of functional loss or progressive
Kinderklinik, Brauerstr. 15, Postfach 834, Winterthur CH-8401, destructive changes, a single MRI finding may
Switzerland. be of uncertain clinical significance.
Corresponding author at: The University of Alabama at
Birmingham, 1600 7th Avenue South, CPP N 210 M, Birmingham,
AL. E-mail: mstoll@peds.uab.edu Therapy of JIA
1073-8746/15/1801-$30.00/0 The last 10 years have witnessed an explosion of
http://dx.doi.org/10.1053/j.sodo.2015.02.009 therapeutic options for the management of JIA,

126 Stoll et al
such that the routine and prolonged use of non- has less suppression of endogenous CS as
steroidal anti-inflammatory drugs and systemic compared to other preparations, including TA.22
corticosteroids is now the exception rather than the There have also been scattered reports of IA
rule.2,15 A detailed discussion of the safety and delivery of TNFi to treat inflammatory arthritic
efficacy of the multiplicity of agents currently used conditions, including JIA. For example, Bello
to treat JIA is beyond the scope of this review but is et al.26 reported on 5 adults with psoriatic
available for the interested reader.2 Broadly arthritis who responded to IA infliximab, and
speaking, the therapeutic agents can be classified Conti et al.27 reported good responses in 9 of 10
as conventional versus biologic disease-modifying subjects with rheumatoid or psoriatic arthritis
anti-rheumatic drugs (DMARDs). One conventional receiving IA infliximab. Unlike IACS, the TNFi
DMARD, methotrexate, is by far the most widely were not designed for depot injections; indeed,
used in children due to its long track record and its improvements in systemic symptoms and
overall favorable safety and efficacy profile.16 inflammatory markers have also been observed
Multiple categories of biologics exist, targeting with local TNFi injections.26,28 The comparative
different inflammatory pathways, with the most effectiveness of IA TNFi versus IACS is unclear. A
frequent first-line therapies being the tumor RCT comparing IA etanercept to IA betame-
necrosis factor inhibitors (TNFi).16 Although largely thasone showed etanercept to be superior,29
safe and well tolerated, they are associated with a risk while a comparison of IA etanercept and IA
of rare but serious infections, including tuberculosis; methylprednisolone showed equivalence.30 To
there also remains an uncertain association with an our knowledge, IA TNFi have not been
increased risk of malignancies.17–19 compared directly to the preferred IACS agent
Despite all the advancements in treatment TH; there have been reports of patients who
options, locally delivered therapy, typically in the responded well to IA TNFi after failing IACS
form of long-acting intra-articular corticosteroids therapy, although the specific IACS agent used in
(IACS), remains a frequently used therapeutic these reports was not specified.27,31–33 These
option in the management of children with JIA. injections have largely been well tolerated. Nev-
Typically, IACS are used in subjects with oli- ertheless, there is a case report of a Chinese
goarticular disease, thus sparing them the risks patient with JIA who developed miliary tuber-
and inconveniences of long-term systemic culosis 1 month after a dose of IA etanercept.
immunosuppressive therapy.20,21 They can also However, it is unclear from the report whether
be used as adjunctive therapy in children with the patient had tuberculosis all along.34 Use of IA
polyarticular JIA with a limited number of par- infliximab to treat TMJ arthritis will be
ticularly troublesome joints. The preferred discussed below.
agents are triamcinolone hexacetonide (TH)
and triamcinolone acetonide (TA); these agents
Systemic therapy of TMJ arthritis
have relatively low water solubility and therefore
remain within the joint space for a significantly Although systemic immunosuppressive therapy is
longer period of time as compared to other CS clearly of tremendous benefit in the manage-
preparations.22 Retrospective as well as ment of JIA as a whole,2 there is very little data
randomized controlled trials in children with addressing its effect specifically on TMJ arthritis.
bilateral knee arthritis have shown TH to be There is only a single randomized or prospective
more effective than TA at inducing remission study that evaluated the effects of systemic
and to result in a longer-lasting remission as therapy on TMJ involvement in JIA, and
well.23,24 The duration of therapeutic effect is although this was a well-designed study lasting
variable, averaging close to 1 year.23 IACS are 50 weeks, the trial unfortunately evaluated 2
associated with a very rare risk of infections in medicines that are no longer in use to treat JIA, D-
adults, with the most common adverse events penicillamine and sodium aurothiomalate.35
being localized injection-site hypopigmentation Stoll et al.12 reported that abnormal TMJ MRI
and/or subcutaneous atrophy.25 There is also a images could be seen in subjects with otherwise
risk of systemic CS effects, as systemic absorption quiescent disease, even in the face of aggressive
occurs with all forms of IACS, although management with biologic and non-biologic
pharmacokinetic studies demonstrate that TH DMARDs. The reasons for this apparent
Systemic and intra-articular anti-inflammatory therapy 127
discrepancy in response to systemic therapy are In contrast, studies of more recently diagnosed
unclear. It may reflect differences in the anat- patients provide some cause for optimism. Twilt
omy, biochemistry, and development of the TMJ et al.47,48 performed baseline and 5-year evaluations
compared to all of the other articulations.36 of subjects with JIA. During the intervening period,
Alternatively, it may reflect observations the patients received unspecified systemic immu-
discussed above that MRI findings of acute nosuppressive medications; none received IA
inflammation are indistinguishable from therapy for TMJ arthritis. Of the original 97 par-
reparative processes,14 or findings reported in ticipants, 84 were available at the 5-year follow-up
adults with mechanical causes of TMJ pain of point. Orthopantomogram (OPT) of those 84
apparent inflammatory changes on MRI.37,38 subjects revealed TMJ involvement in 49% at
Nevertheless, a retrospective study involving 96 baseline, compared to 40% at 5 years. At the level
children who underwent contrast MRI of the of the individual condyle, the number without any
brain revealed TMJ abnormalities in only 6%, all abnormalities increased from 106 (63%) at base-
of which were mild findings.39 line to 124 (74%) at follow-up. The number of
Despite the absence of direct evidence, the condyles showing improvement dwarfed the
preponderance of data appears to show that number showing worsening (43 versus 15), find-
systemic immunosuppressive therapy benefits ings that are in stark contrast to those of the study
TMJ arthritis. This possibility was first proposed by Arvidsson et al.46 Additionally, clinical evaluation
by Ince et al.,40 who observed retrospectively showed decreased incidence of posterior rotation
decreased radiographic evidence of arthritis of the mandible. There is, therefore, reason to
among 18 polyarticular JRA patients taking believe that the mandibular condyle has a high
methotrexate, compared to 9 who were not. regenerative and reparative potential once the
Historically, children diagnosed with JRA in the inflammatory process is stopped.
1970s to early 1980s, for whom there were Stoll et al.12 provided additional indirect
minimal therapeutic options, often rapidly evidence on potential benefits of systemic
developed arthritis severe enough to be readily immunosuppressive therapy on TMJ arthritis.
detected on plain radiography. Larheim et al.41 The authors reported on the results of TMJ MRI
evaluated 100 randomly selected JIA patients, in 187 patients with JIA who were screened by
finding definite TMJ abnormalities on plain MRI at a range of 0.3–17 years (mean ¼ 2.5) after
radiography in 41 and possible abnormalities diagnosis. In this study, only 43% had active
in an additional 11. Subsequent work by this arthritis, and only 24% had chronic changes.
group confirmed that these radiographic These rates of TMJ arthritis in a cohort largely
abnormalities are directly related to receiving MTX and TNFi are far below that
mandibular size and asymmetrical growth.42 at disease onset among subjects screened by
Karhulahti et al.43 studied 121 JRA patients MRI, as well as by studies of children diag-
who were 15 years old, finding condylar nosed in the pre-biologic era,11,43 and suggest
flattening in 65 (55%) as well as decreased some benefit of systemic therapy for TMJ
oral aperture in patients compared to healthy arthritis. As further evidence of a benefit of sys-
15-year-old children. Important findings in sev- temic immunosuppressive therapy, multivari-
eral of these and other studies is that the risk of able analysis revealed that a prolonged disease
TMJ arthritis evident by radiography increases duration was a protective factor against TMJ
with prolonged disease duration, consistent with arthritis.12 Importantly, however, as noted above,
a cumulative effect of unopposed inflamma- the authors did observe TMJ arthritis in 36
tion.44,45 This was illustrated most dramatically by subjects who had clinically quiescent disease in
Larheim and colleagues, who re-evaluated 60 of all of the other joints despite frequent use of
the original 103 subjects at a mean follow-up of conventional and often high doses of biologic
27 years.46 This follow-up study showed arthritis DMARDs.12
changes on plain radiography in 45/60 (75%) at
follow-up, compared to 25 (42%) at baseline.
Local therapy of TMJ arthritis
These subjects were more likely to develop new
or worsening changes, compared to showing To date, there have been 8 studies on the use of
improvement over time. IACS as treatment of TMJ arthritis in JIA.11,49–55
128 Stoll et al
One of them was largely a methods article with All 4 reported improvements in mean MIO,
overlapping subjects from a previous study by the ranging from 2.7 to 6.6 mm.11,50,51,55 Additional
group,49 so 7 studies are included (Tables 1 and 2). observations included frequent normalization of
Most of the studies required advanced imaging low MIOs55 and that younger patients were also
[MRI or computed tomography (CT)] evidence of more likely to show improvements.11,51 Impor-
TMJ arthritis,11,50,51,54,55 although 2 of them did not tantly, all of the studies that evaluated MIO did so
specify.52,53 Either TH or TA was the drug used in within a few months after the initial injection,
the 6 studies that documented selection of agent, thus preventing significant MIO increases
although the dose varied by study, ranging from 5 simply due to natural growth. The one study
to 20 mg of TH and 5 to 40 mg of TA per injection. that reported on jaw deviation documented
In addition, 2 of the studies used anatomic local- improvement in 13/14 subjects.54 Finally, ima-
ization to guide the CS injection,50,55 2 used CT ging as an outcome measure was used in 3 of the
guidance,11,51 2 used ultrasound (US) guidance (1 studies. The one that used CT, which by its nature
with53 and 1 without54 CT confirmation), and 1 can only show chronic changes, had largely
used MRI guidance.52 negative findings, with worsening in 10/15
The studies also varied in their outcome subjects and improvement in only 2 subjects50;
measures. One study did not report any effec- another limitation of this study is that follow-up
tiveness measures,52 while several reported CT scans were only performed on patients with
multiple effectiveness measures, categorized in unsatisfactory clinical responses, potentially
Table 2 according to symptomatic relief, changes biasing the outcome. In contrast, both studies
in physical exam findings, and improved imaging that reported on MRI changes demonstrated
findings. Of the 4 studies that reported on benefit—Arabshahi et al.51 showed improved
symptomatic relief, all reported generally effusions in 67% of TMJs over 14 subjects, and
positive results. For example, decreased TMJ Stoll et al.55 showed improved findings in 24/62
pain was reported in 17/17 subjects by Habibi TMJs, with worsening in only 8/62 subjects. An
et al.54 and in 10/13 subjects by Arabshahi et al.51 example of a positive imaging outcome following
Ringold et al.50 reported improvement in IACS is demonstrated in Fig. 1(A and B). Overall,
multiple symptoms, with overall findings that IACS appeared beneficial in terms of joint
the number of patients with one or more TMJ- function and symptomatology.
related symptoms (pain, stiffness, difficulty eat- In terms of safety of IACS, 6 of 7 studies
ing, and clicking) decreased from 60% to 28%. reported on short-term safety events.50–55 For a
Finally, Parra et al.53 reported a “good” response total of 255 subjects in these 6 studies, many of
in the majority, although this was not defined. whom underwent bilateral and, in some cases,
The most common physical exam finding multiple rounds of IACS, no serious adverse
assessed was the maximal incisal opening events (SAEs) were reported. The only events at
(MIO), which was assessed in 4 of the studies. all were transient localized Cushing syndrome in
Table 1. Methods used for TMJ CS injections

Study n Diagnosis of TMJ arthritis Localization of CS CS preparation and dose
Arabshahi 23 MRI CT guidance TA 40 mg (n ¼ 16); TH 20 mg

et al.51 (n ¼ 7)
Ringold 25 CT (n ¼ 24); Symptoms Anatomic localization TA 20–40 mg; TH 10–20 mg
et al.50 (n ¼ 1)
Weiss et al.11 21 MRI CT guidance TH 10 mg
Fritz et al.52 22 therapeutic ND MRI guidance ND
injections
Parra et al.53 83 ND US guidance with CT TH 5–10 mg
confirmation TA 5–10 mg
Habibi 39 MRI US guidance TH 10–20 mg (depending upon
et al.54 body weight)
Stoll et al.55 63 MRI 60 Anatomic localization TH 5–10 mg
CT 2
Abbreviations: ND ¼ not documented, TA ¼ triamcinolone acetonide, TH ¼ triamcinolone hexacetonide.
Table 2. Outcome measures and results

Assessment
Study time Subjective change Physical exam change Imaging change Safety
Arabshahi 6–12 Resolution of pain MIO increase of 4.8 mm Improved acute findings on Transient Cushing
et al.51 Months in 10/13 subjects MRI in 467% of TMJs (14 syndrome in 2 pts
subjects)
Ringold Mean ¼ Decreased MIO increase of 6.6 mm CT: worsening changes in Subcutaneous atrophy in
et al.50 26 months incidence of one or after first injection (n ¼ 10, no change in 3, and 1
(5–52) more TMJ 19); incidence of jaw improvement in 2 subjects
symptoms (60% to deviation decreased from
28%) 40% to 16%
Weiss 6 Months ND Improved MIO in 9/16 Decreased effusions on ND
et al.11 subjects; the rest were enhancement in 5/6
normal at baseline subjects
Fritz 15 Months ND ND ND Skin atrophy in 1 patient
et al.52 (6–36)
Parra ND “Good” response in ND ND Skin atrophy in 1 patient
et al.53 80/99 subjects,
“Partial” response in
10, and “Poor”
response in 9
Habibi 6–8 Weeks Improved pain in Improved jaw deviation in ND Scar in 1 patient
et al.54 17/17 subjects and 13/14 subjects
chewing
dysfunction in 5/7
subjects
Stoll 5 Months ND Increased MIO by 2.7 mm Improved MRI findings in Minor adverse events in 3
et al.55 (n ¼ 55) 24/62 TMJs, 30 stable subjects: localized
findings (including all 15 swelling, fever 2 weeks
normal at baseline), and 8 post-operatively, and
TMJs worsened hypopigmentation
Abbreviations: MIO ¼ maximal incisal opening, ND ¼ not documented, TMJ ¼ temporomandibular joints.
2, subcutaneous atrophy in 3, and 1 each with The impression one is left with is that the
scarring, localized swelling, fever 2 weeks after weight of the evidence indicates that IACS of the
the injection, and hypopigmentation. Thus, IACS TMJ are likely to be effective in the management
of the TMJs in children with JIA appeared safe in of associated arthritis. The effectiveness of IACS
the short term. is also well established for multiple other small
Figure 1. Post-contrast parasagittal images of the TMJ. (A) A 16-year-old girl with polyarticular JIA; and (B) the
same patient following IACS. (C) A 17-year-old girl with Sjogren syndrome following 3 rounds of IACS; and (D) the
same patient as in (C), following 2 doses of intra-articular infliximab. The asterisks indicate the condylar heads.
130 Stoll et al
and large joints,25 and there is no a priori reason calls to limit or avoid TMJ IACIs absent long-term
why this joint would respond differently. safety data in pediatric subjects.3,48
Additionally, the above studies almost As documented above, multiple studies have
uniformly demonstrated improvements in both reported on use of IA TNF inhibitors in
subjective and objective measures of TMJ peripheral joints. Additionally, there are 2
arthritis. Although the mean improvements in reports of IA infliximab injection (IAII) specifi-
MIO were below the threshold of 5 mm, which is cally to the TMJ. One is a case report of an adult
said to represent the smallest detectable with psoriatic arthritis, who underwent 7 rounds
difference,56 mean values reflect a wide range over 36 months of IA infliximab (5 mg/injec-
of changes, many of which will fall over the tion), with improvement seen after the first
threshold. Furthermore, many of the subjects dose.64 The other was a retrospective review of 24
had normal MIO at baseline and thus might not children with JIA who underwent 1 or 2 rounds of
be expected to demonstrate much improvement. IAII (5–10 mg/injection) in children refractory
Stoustrup et al.3 reviewed the IACS literature, to IACS.65 This study largely demonstrated the
identifying limitations of these studies. These safety of the approach. Effectiveness data was
limitations include retrospective design, absence limited, not unexpectedly, in light of arthritis in
of blinding in interpretation of the imaging these subjects being refractory to systemic
studies, absence of a control group, absence of biologic therapy in 23/24, in addition to 1–3
standardized endpoints, and absence of long- rounds of IACS. However, IAII did result in
term safety data. Additionally, while the short- resolution of the arthritis in 6 TMJs (5 subjects).
term safety profile in these studies was generally An example of a positive imaging outcome
reassuring, there are some reports suggesting following IACS is demonstrated in Fig. 1(C and
adverse long-term effects of IACS into the TMJ. D). Although this was from patients with Sjogren
In an animal model of experimental TMJ syndrome, who are also at risk of TMJ arthritis,66
arthritis, IACS resulted in decreased mandibular there have been similar responses in children
growth as compared to untreated or placebo- with JIA.65 Whether or not IAII should be used
treated animals.57,58 Additionally, a retrospective prior to IACS is another open question.
study evaluating mandibular growth in JIA One final treatment option for refractory TMJ
patients who had received a total of 133 IACS arthritis has been suggested—dexamethasone
injections into the TMJ revealed mandibular iontophoresis (DIT).67 As the authors explained
growth impairment.59 To address whether this it, low-grade electrical currents result in the
was due to the injections rather than the ionization of hydrophilic (polar) molecules, such
inflammatory process itself, the authors as dexamethasone. The medicine is placed on
compared subjects who received intra-articular the skin overlying the TMJ, and the electrical
versus extra-articular placement of the CS, as current polarizes the drug and forces it into
assessed by MRI performed immediately after the deeper tissues, including the TMJ. In their ret-
injection; they found improved resolution of the rospective study, 32 subjects were enrolled, of
inflammation but negative growth in a steroid- whom 27 completed the 8 episodes of DIT.
dose dependent manner in those who had Decreased pain was reported in 11/15 subjects
received IA delivery of the CS. Finally, there are with pain at baseline, improved MIO was
reports of heterotopic bone formation and even reported in 19/28, and improved maximal lateral
rapid condylar destruction associated with joint excursion in 11/16 subjects. Transient erythema
ankylosis occurring in patients who had received was common, but no SAEs were reported. This is
repeated IACS into the TMJ as therapy for the only report along these lines.
inflammatory or degenerative arthritis.60–63
Although it remains unclear how much of the
Summary
heterotopic bone formation is secondary to the
IACS versus the ongoing chronic inflammation, TMJ arthritis in children with JIA is common and
the occurrences of rapid condylar destruction can lead to destructive changes.1 This can lead to
following administration of a potent and long- impaired growth of the jaw, poor function, and
lasting corticosteroid (TA or TH in all cases) obvious cosmetic changes.68 With the systemic
raises safety concerns. Thus, there have been therapies used to treat JIA that were unavailable a
generation ago, rheumatologists appear to be separate category in the classification of juvenile idio-
able to modulate the course of TMJ arthritis, pathic arthritis. Arthritis Rheum. 2011;63:267–275.
8. Burgos-Vargas R, Vazquez-Mellado J. The early clinical
treating the inflammatory component and recognition of juvenile-onset ankylosing spondylitis and
possibly even reversing damage. Although its differentiation from juvenile rheumatoid arthritis.
these changes are very welcome, there is Arthritis Rheum. 1995;38:835–844.
clearly room for improvement, thus the 9. Foeldvari I, Tzaribachev N, Cron RQ. Results of a
ongoing search for additional treatment multinational survey regarding the diagnosis and treat-
ment of temporomandibular joint involvement in juve-
options. There is evidence that IACS are nile idiopathic arthritis. Pediatr Rheumatol Online J.
effective in many patients with TMJ arthritis, 2014;12:6.
and although their short-term safety profile has 10. Muller L, Kellenberger CJ, Cannizzaro E, et al. Early
been well established, there remain concerns diagnosis of temporomandibular joint involvement in
juvenile idiopathic arthritis: a pilot study comparing
about long-term effects on mandibular growth.
clinical examination and ultrasound to magnetic reso-
However, these potential adverse effects must be nance imaging. Rheumatology (Oxford). 2009;48:680–685.
weighed against the known detrimental effects of 11. Weiss PF, Arabshahi B, Johnson A, et al. High prevalence
uncontrolled arthritis, particularly in patients of temporomandibular joint arthritis at disease onset in
who are already receiving therapeutic doses of children with juvenile idiopathic arthritis, as detected by
systemic immunosuppressive therapies. Clearly, magnetic resonance imaging but not by ultrasound.
Arthritis Rheum. 2008;58:1189–1196.
well-designed prospective studies evaluating dif- 12. Stoll ML, Sharpe T, Beukelman T, Good J, Young D, Cron
ferent treatment options, including IACS, IA RQ. Risk factors for temporomandibular joint arthritis in
infliximab, and possibly iontophoresis, or even children with juvenile idiopathic arthritis. J Rheumatol.
observation, are needed. Until these are com- 2012;39:1880–1887.
pleted, the risks must be weighed against the 13. Jimenez-Boj E, Nobauer-Huhmann I, Hanslik-Schnabel B,
et al. Bone erosions and bone marrow edema as defined
benefits of IACS for individual JIA patients based by magnetic resonance imaging reflect true bone marrow
in part upon the severity and functional con- inflammation in rheumatoid arthritis. Arthritis Rheum.
sequences of the arthritis, the systemic therapies 2007;56:1118–1124.
already in place, and additional patient- or 14. Kroschinsky F, Kittner T, Mauersberger S, et al. Pelvic
magnetic resonance imaging after bone marrow harvest
provider-specific factors.
—a retrospective study in 50 unrelated marrow donors.
Bone Marrow Transplant. 2005;35:667–673.
15. Mannion ML, Xie F, Curtis JR, Beukelman T. Recent
trends in medication usage for the treatment of juvenile
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Functional and orthopedic treatment in
developing dentofacial growth deviation in
juvenile idiopathic arthritis
Thomas Klit Pedersen, and Carlalberta Verna
Dentofacial growth in juvenile idiopathic arthritis (JIA) patients with

temporomandibular joint (TMJ) arthritis will lead to deviations related to
the joints, mandible, maxilla, and dentoalveolar parts, resulting in abnormal
jaw relations and morphology caused by the inflammatory interaction with
the growth process. One treatment modality of the deviating growth and
development has been the use of functional or orthopedic appliances,
traditionally used for the correction of limited growth deviations in normal
growing individuals within the broad sense of variation.
Although, the evidence for functional/orthopedic treatment in JIA is
limited, existing publications and personal clinical experience suggests the
use of functional/orthopedic appliances in the treatment of dentofacial
growth deviations in JIA.
The aim of the present article is to give a summary of treatment with
functional/orthopedic appliance from the current literature. (Semin Orthod
2015; 21:134–139.) & 2015 Elsevier Inc. All rights reserved.
Introduction disorder or by a general disease, such as
T
juvenile idiopathic arthritis (JIA), the com-
he dentofacial development has a vast var-
plexity of the growth pattern increases. In
iation in normal growing individuals, and in
particular, the lack of vertical growth of the
the orthodontic profession focus has for decades
mandibular ramus leads to a posterior rotation
been set on mandibular growth and develop-
pattern with a consequent effect on the sagittal
ment. Both genetic and environmental factors
and vertical relationships, which gives, in
contribute to the facial morphology.1,2 Devia-
extreme cases, the typical facial appearance
tions in mandibular growth pattern constitute a
also known as “bird face.”5,6
majority of malocclusions and dentofacial
Functional or orthopedic appliance is rou-
anomalies. Mandibular growth pattern has,
tinely used for treating mandibular insufficiency,
according to Bjork and Skieller,3 roughly been
together with orthodontic-induced dentoalveolar
classified as anterior (counter clockwise) or
compensations although only few studies has
posterior (clockwise), and the issue of difficult
demonstrated a skeletal effect in growing indi-
treatable cases caused by insufficient mandibular
viduals with deviating growth and development.7
growth and development are well-known in the
Despite the lack of evidence in abnormal growing
orthodontic field.4 In case of an additionally
individuals functional/orthopedic appliance
growth disturbance caused by a congenital
has been suggested to address the growth
deviation based on experience with insufficient
Department of Oral and Maxillofacial Surgery, Aarhus Uni-
versity Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark; Section
or deviating growth of the mandible in children
of Orthodontics, Aarhus Dental School, Aarhus University, Aarhus with JIA.8 Since no data is available concerning
C, Denmark; Department of Orthodontics and Pediatric Dentistry, the tissue reaction of condylar tissue to
School of Dental Medicine, University of Basel, Basel, Switzerland. mechanical loading in JIA, one could speculate
Corresponding author at: Department of Oral and Maxillofacial whether the effect of functional appliance is to
Surgery, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus
C, Denmark.. E-mail: thompede@rm.dk
support dentoalveolar development during a
difficult growth pattern where development of
1073-8746/15/1801-$30.00/0 the occlusion and the mandible is mutually
http://dx.doi.org/10.1053/j.sodo.2015.02.010 uncoordinated.

Functional and orthopedic treatment 135
Definition of functional–orthopedic relevant regarding the skeletal changes. They

appliances also emphasized the large variation in growth in
both treatment and control groups.12 Even
Functional appliance has been described for a
though small skeletal changes are found, the
century in the orthodontic literature.9 The term
treatment success of FOA is most likely due to
“functional” aims to describe a possible approach
dentoalveolar compensations.7,13 However, the
to influence the soft tissue function and mandi-
growth pattern in JIA patients is more compli-
bular functional position in order to support
cated and difficult compared to the treatment
normal growth and development. Furthermore,
groups in the above-mentioned studies. The
a stimulating, enhancing, modifying, or support-
pattern is not only characterized by a decrease in
ing effect of the appliance in relation to the
mandibular length, but also by a decreased ratio
amount of mandibular growth as well as a change
between the posterior and the anterior face
in growth pattern have been anticipated. Since
height, due to a failure in the vertical growth of
this implies an orthopedic effect, the name
the condyles.14 This will result in a posterior
functional–orthopedic appliance (FOA)10 is a
(clockwise) mandibular rotation and open bite.
more appropriate description of such devices.
The favorable effect of FOA in JIA cases is
A FOA (Fig. 1) can be described as a remov-
therefore, besides advancing the mandible, an
able appliance tooth- or soft-tissue borne, pre-
anterior (counter clockwise) rotation with a
venting a negative influence of soft tissue on
possible increase of the posterior face height, if
mandibular growth, stretching muscles, training
possible. The efficacy of the FOA in the
a favorable mandibular position and introducing
correction of open bite has been demonstrated
mechanical environmental forces to possibly
by Ibitayo et al.,15 although a review only found
influence bone formation. Furthermore, a FOA
weak evidence for the effect of FOA.16
allows for the control of tooth eruption and
thereby of the vertical development of the den-
toalveolar process. The following text is focusing Functional–orthopedic appliances and
on the possible treatment of mandibular insuf- possible effect on skeletal deviation and
ficient growth and development in JIA patients, malocclusion developing in JIA
considering also the benefit on mandibular
function. Different types of appliances have been sug-
gested in early treatment of skeletal deviations of
JIA patients and FOA treatment is recommended
although evidence of effect and efficacy are
Functional–orthopedic treatment, the
sparse.8–13,15–17 Kjellberg et al.18 treated a group
effect and level of evidence
of JIA patients with a Bow activator. This
The efficacy of treatment with FOA appliances to particular FOA was a modified twin-block
enhance mandibular growth has been discussed (Fig. 2) where the two parts were connected
extensively. Only a few randomized clinical trials with an elastic wire allowing the mandible lateral
have been conducted to demonstrate correction movements. The activator positioned the
in skeletal deviations. Tulloch et al.11 found mandible mainly forward in order to correct
favorable change of mandibular length as a the sagittal insufficiency. Vertically, the activator
result of functional appliance, although the was in contact with the teeth in cases of open bite
differences were small and barely clinically passively to prevent eruption of the teeth
Figure 1. A simple FOA appliance, an Ergenzinger activator, used for correction of a retrognathic mandible.
136 Pedersen and Verna
skeletal improvement was limited and the occlu-

sion was improved by dentoalveolar compensa-
tions. Pedersen et al.19 recommended the use of
a distraction splint to support posterior vertical
development. A distraction splint (Fig. 3) is a
FOA covering the occlusal surface gradually
increased in posterior height, aiming at a
change in the inclination of the occlusal plane
and preventing posterior collapse.20 The effect of
the distraction splint implies that the growth of
the condyle takes place in periods, and that
changes of the condylar morphology in JIA are
Figure 2. Bow activator ad modum Schwarz used in rather a growth disturbance than a degenerative
the study of Kjellberg et al.18 The upper and lower part
is connected by a flexible bow allowing transverse breakdown. Fig. 4 demonstrates the growth of the
movements of the mandible. (Courtesy: Dr. Heidrun condyle from a severe deformity in the age of 13
Kjellberg, Gothenburg, Sweden). to an almost normal condyle when growth has
ceased in a case of JIA treated with FOA. Dis-
posteriorly. The treated JIA group was compared traction splint treatment has lasted for several
cephalometrically with an untreated group of JIA years. In order to control the dentoalveolar deve-
patients: a group of healthy children treated for a lopment and the inclination of the occlusal plane
similar malocclusion and a group of non-treated, the eruption of the upper dentition is allowed as
healthy children without malocclusions. They part of the treatment. The treatment with a
found a satisfying treatment result although distraction splint is therefore not focused on
Figure 3. The principle of a distraction splint used for unilateral distraction. (A) The splint is increased vertically
gradually on the affected side. (B) Patient occluding lightly on the splint in the affected side resulting in a slight
open bite between upper teeth and splint. (C and D) While the occlusion is the same on the splint in the affected
side (C), muscular forces enables occlusion on the normal side (D). This results in a slight rotation of the mandible
according to a horizontal axis in the coronal plane.
occlusion stability and to decrease TMJ pain

typical of JIA activity.22 The use of an activator is
the often chosen continuation of the treatment.
Farronato et al.17 used a modified distraction
splint designed as an activator with a protrusive
position of the mandible combined with the
posterior vertical increase. They reported an
anterior (counter clockwise) rotation of the
mandible during treatment with FOA. A case
report, demonstrating acceptable results, exists
treating a JIA patient with a protrusive fixed
herbst appliance.23
The patient groups treated in the above-
mentioned reports are giving impression of
chronic arthritic TMJ deformities, and little is
known concerning interaction of the active
inflammatory process and exogenous bio-
mechanical forces. For comfort reasons for the
patient, FOA will in most cases be planned when
arthritis activity is low but no evidence exist
against applying FOA in cases of active joints.
Clinical observations do not give reason to
believe in a negative effect of FOA during active
arthritis although anti-inflammatory agents in
early TMJ arthritis probably are of great impor-
tance for success of FOA treatment.
In case of JIA with involvement of the TMJ, the
FOA can be classified as sagittal or vertical acti-
Figure 4. CBCT scanning of the right condyle of a JIA vators, according to the principal activation
patient at the age of 13.3 years and at the end of growth
pattern. Among the former, bite-jumping appli-
(18.3 years). Severely flattening of the condyle was
seen at the age of 13.3 years. Treatment with a ances are also used in the patients affected by JIA.
distraction splint was carried out for several years. However, it has to be observed, whether activa-
Arrow depicts final condylar length which is close to tors, as for example the one described by Kjell-
normal. berg et al.18 or with bite-jumping devices, has a
compensatory effect on the dentoalveolar proc-
sagittal advancement of the mandible, but rather ess. The dentoalveolar compensations, in case of
on the reestablishment of the vertical support need for further orthognathic surgical treatment,
undermined by the decreased growth of the will need a de-compensation phase which will
condyles. Fig. 5 depicts the dentofacial develop- increase treatment length and the burden of
ment of a JIA patient with bilateral TMJ treatment for the patient. Decompensations
involvement. In spite of extended condylar defor- would not be needed if the FOA is performed via
mities the dentofacial development is close to a distraction splint, where no dentoalveolar
normal. However, the contribution of a favorable compensation of the sagittal relationships
genetic inheritance cannot be neglected in case takes place.
of optimal treatment result with FOA. The dis- In open bite cases, vertical control related to
traction splint seems to be effective in limiting FOA as an extraoral traction could be considered
the development of asymmetries in cases of but the nature of the open bite has to be kept in
unilateral involvement of the TMJ. Stoustrup mind. In JIA cases, the open bite is due to the
et al.21 found a possibility to maintain symme- short posterior face height and the steep occlusal
try and control normal development in JIA plane; extraoral forces such as high-pull head-
patients with unilateral involvement. The splint gear will tend further to occlusal plane steeping
therapy seems, moreover, to improve functional and prevent skeletal counter clockwise
138 Pedersen and Verna
Figure 5. Dentofacial development of a patient with JIA and bilateral TMJ involvement treated with a distraction
splint. (A) Clinical development of profile and occlusion, 8.9–12.3 years. (B) CBCT depicting the lateral
development and the images of the condyles, 8.9–12.5 years.
improvement. Also, a cervical headgear should rather be maintained during growth since the
be avoided not to increase the open bite. day JIA is diagnosed in the TMJ.
Indications for functional–orthopedic Orthodontic treatment follow-up

treatment in JIA patients
After treatment with FOA most patients will need
FOA treatment is indicated when the TMJ an orthodontic treatment in order to establish a
involvement starts altering the growth. Since functional occlusion. This will be achieved with
such treatment cannot be expected to treat a fixed appliance therapy associated to bite-
severe malformation of the mandible developed jumping therapy. The use of skeletal anchor-
over a long period only limited growth dis- age in the orthodontic treatment can be a choice
turbances can be accepted. Therefore, early in order to avoid development of vertical side
diagnosis and early treatment of the TMJ arthritis effects and compensatory lower incisor procli-
becomes mandatory. A better result in patients nation. Only in a limited number of cases
who inherently have a positive and uncompli- orthognathic surgery will be an option, but if
cated growth pattern can be anticipated. needed, care should be taken to avoid dental
Patients’ cooperation and the burden of compensations during initial treatment.
treatment have to be considered. FOA treat- Although, not substantiated by randomized
ments must be expected to have duration of clinical trials, in case of need for orthognathic
several years, since the FOA treatment are not surgery, the functional treatment can be planned
significantly able to accelerate or generate sig- to avoid compensations and the possible effect
nificant more growth than what is genetically on the soft and hard tissue might allow for more
determined. The nature of TMJ arthritis will stable results and successful surgery.
affect the mandibular growth throughout the
active growth period and, still after condylar
Discussion and conclusion
growth has ceased, changes can occur.24
Therefore, the FOA in JIA patients should not Application of FOA in treatment of the growth
be started close to the pubertal growth spurt, as deviation caused by arthritis of the TMJ in JIA
suggested for non-JIA patients, but it should patients is recommendable. Care must be taken
to aim for skeletal changes by the use of FOA and 12. Tulloch JF, Proffit WR, Phillips C. Influences on the
avoid compensations until it is apparent whether outcome of early treatment for Class II malocclusion. Am J
Orthod Dentofacial Orthop. 1997;111:533–542.
the deviation can be solved by the following 13. O’Brien K, Wright J, Conboy F, et al. Effectiveness of early
orthodontic treatment alone or by a combined orthodontic treatment with the Twin-block appliance: a
orthodontic–surgical treatment. multicenter, randomized, controlled trial. Part 1: dental
The variation in individual growth pattern and skeletal effects. Am J Orthod Dentofacial Orthop.
combined with the nature of the disease is vari- 2003;124:234–243.
14. Peltomäki Timo, Kreiborg Sven, Pedersen Thomas Klit,
ables that make the research related to FOA Ogaard Björn. Craniofacial growth and dentoalveolar
treatment of JIA patients particularly challeng- development in juvenile idiopathic arthritis. Semin Orthod
ing, and therefore at present insufficiently sup- 2015; [this issue].
portive. Evidence for effect and efficacy for such 15. Ibitayo AO, Pangrazio-Kulbersh V, Berger J, Bayirli B.
Dentoskeletal effects of functional appliances vs bimax-
treatments are still inconclusive and randomized
illary surgery in hyperdivergent Class II patients. Angle
multicentre studies are strongly recommended. Orthod. 2011;81:304–311.
16. Lentini-Oliveira D, Carvalho FR, Qingsong Y, et al.
Orthodontic and orthopaedic treatment for anterior
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Am J Dis Child. 1949;78:728–743. and mandibular growth of children with temporoman-
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toid arthritis. A longitudinal study of lateral 21. Stoustrup P, Kuseler A, Kristensen KD, Herlin T,
cephalographs. Eur J Orthod. 1991;13:423–434. Pedersen TK. Orthopaedic splint treatment can reduce
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McNamara JA Jr. Long-term treatment effects of the FR-2 mandibular involvement in juvenile idiopathic arthritis.
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Eur J Orthod. 2014;36:192–199. 22. Stoustrup P, Kristensen K, Kuseler A, Verna C, Herlin T,
8. von Bremen J, Ruf S. Orthodontic and dentofacial Pedersen T. Management of temporomandibular joint
orthopedic management of juvenile idiopathic arthritis: arthritis-related orofacial symptoms in juvenile idiopathic
a systematic review of the literature. Orthod Craniofac Res. arthritis by the use of a stabilization splint. Scand J
2011;14:107–115. Rheumatol. 2014;43:137–145.
9. Bishara SE, Ziaja RR. Functional appliances: a review. Am J 23. Kitai N, Kreiborg S, Bakke M, et al. Three-dimensional
Orthod Dentofacial Orthop. 1989;95:250–258. magnetic resonance image of the mandible and masti-
10. Von den Hoff JW, Delatte M. Interplay of mechanical catory muscles in a case of juvenile chronic arthritis
loading and growth factors in the mandibular condyle. treated with the Herbst appliance. Angle Orthod.
Arch Oral Biol. 2008;53:709–715. 2002;72:81–87.
11. Tulloch JF, Phillips C, Koch G, Proffit WR. The effect of 24. Arvidsson LZ, Flato B, Larheim TA. Radiographic TMJ
early intervention on skeletal pattern in Class II maloc- abnormalities in patients with juvenile idiopathic arthritis
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Orthop. 1997;111:391–400. Radiol Endod. 2009;108:114–123.
Jaw surgery for correction of dentofacial
anomalies caused by JIA
Sven Erik Nørholt, Tore Bjørnland, and Thomas Klit Pedersen
In a number of patients with juvenile idiopathic arthritis with involvement of

the temporomandibular joint, a growth disturbance of the mandible and
consequently the facial skeleton will occur. If orthopedic and orthodontic
treatment cannot provide a sufficient normalization of the jaw relations and
occlusion, a surgical treatment can be indicated. The aim of the surgical
treatment is to relieve or prevent functional symptoms, provide an improve-
ment of the facial morphology, and, if possible, normalize the masticatory
function. A variety of surgical treatment principles can be applied to these
patients, and in this article, we describe the various options and the rationale
for their use. In particular, the timing of treatment is important to obtain
optimal and predictable results. Conventional osteotomy techniques as well
as distraction osteogenesis can be used in these treatments. It is essential to
initiate early, long-term planning and involve the patient and his/her parents
in the treatment options and the possible complications and relapse related
to these. (Semin Orthod 2015; 21:140–147.) & 2015 Elsevier Inc. All rights
reserved.
Introduction treatment procedures during growth could
A
generate acceptable results.
major challenge in orthognathic surgery is
For patients in whom the JIA affection of the
treatment of mandibular micrognathia.
TMJ has led to an alteration of growth, the first
Patients with juvenile idiopathic arthritis (JIA)
step is usually to initiate a functional treatment
and involvement of the temporomandibular joint
with an occlusal splint or other type of functional
(TMJ) are at risk of developing micrognathia or a
appliance5,6 to reduce the loading of the joints
condition of deviating jaw relations.1–3 Although
and to support normal growth by vertical stabi-
improved medical treatment has diminished the
lization of the posterior face height. If this
number of patients in need of surgical correc-
therapeutic measure does not provide normal-
tions, this is still indicated in case of larger growth
ization of the growth, the next step could be a
deviations. In a cohort study of 60 JIA patients,
surgical correction of the skeletal growth defect.
Arvidsson et al.4 found that 27% had developed
Growth deviations in JIA patients primarily
micrognathia, and six of the 60 patients went
involve the mandible. However, the maxilla, the
through orthognathic surgery. Furthermore,
dentoalveolar development, and the soft tissue
they found that orthopedic and orthodontic
are also influenced by the TMJ arthritis.7
Department of Oral and Maxillofacial Surgery, Aarhus Uni- Issues in JIA concerning orthognathic
versity Hospital, Aarhus Aarhus, Denmark; Department of Oral surgery
Pathology and Maxillofacial Surgery, Aarhus Dental School, Aarhus
University, Aarhus, Denmark; Department of Oral Surgery and Oral
The growth deformity in patients with JIA has
Medicine, Institute of Clinical Dentistry, Faculty of Dentistry, specific mandibular characteristics such as short
University of Oslo, Oslo, Norway; Section of Orthodontics, Aarhus ramus and corpus length,8,9 subangular notch-
Dental School, Aarhus University, Aarhus, Denmark. ing,8 and large mandibular plane angle.10
Corresponding author at: Department of Oral and Maxillofacial
Furthermore, mandibular asymmetry is a
Surgery, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus
C, Denmark. E-mail: svenoe@rm.dk frequent finding.9 As a consequence of the
skeletal changes, the development of the soft
1073-8746/15/1801-$30.00/0 tissue and muscles is compromised, resulting in a
http://dx.doi.org/10.1053/j.sodo.2015.02.011 reduced length and volume.7 The soft tissue

Jaw surgery for correction of dentofacial anomalies 141
envelope surrounding the facial skeleton is thus a Treatment planning and timing of surgery
limiting factor in achieving an optimal and stable
The best chance of reaching an optimal treat-
result of surgical treatment, and therefore, these
ment is to detect any involvement of the TMJs as
features require specific considerations in the
early as possible and to initiate the necessary
orthognathic surgical treatment planning.
treatment. Pharmacological interventions in-
Ideally, in order to normalize the dentofacial
clude systemic and local medications, and these
morphology, the short posterior face height must
are often efficient in relieving symptoms and
be addressed, including the associated steep
restricting the development of degenerative
occlusal plane and the open bite. Other
changes in the joints.
important concerns are the reduced total
Orthopedic treatment with a functional
length and the frequent asymmetry of the
appliance in order to provide growth adaptation
mandible. Also, the question of stability of the
is often the first choice, and this may correct or
condyle is an issue, since relapse can occur as a
minimize the jaw deformity. If, however, a sur-
consequence of further condylar changes.
gical treatment appears to be indicated, timing of
this should be considered. The time of inter-
Indications for treatment vention can be in infancy, early and late ado-
lescence, or after the end of growth, depending
Abnormal growth of the dentofacial skeleton may
on which type of treatment could be relevant. It is
result in a number of symptoms and problems such
essential to outline a treatment plan, where the
as malocclusion, impaired chewing capacity,
different elements do not counteract each other.
unequal loading of the joints and muscles, insuf-
For instance, significant dentoalveolar compen-
ficient lip function, poor esthetics, and psychoso-
sations should not occur if these would require
cial malfunction.11 Furthermore, an inadequate
later decompensations.
respiratory ability could be a consequence.
An important factor is the local and general
Leksell et al.12 found TMJ-related pain in
disease activity and the need of medication for
approximately 80% of JIA patients, and this had
the arthritis.
an influence on daily life for approximately a
For the final treatment, mandibular growth
quarter of the patients. Temporomandibular
should have been ended and arthritic activity in
joint disorders are a frequent finding in adults
the TMJs should preferably be low in order to
with a history or a persistent JIA.13
establish stable results after orthognathic surgery
Several studies have found that various aspects
in patients with JIA.17
of quality of life, self-esteem, and psychosocial
function are negatively affected in children and
adolescents with JIA.14,15 In a Norwegian group of
Surgical treatment options
84 JIA patients followed up for 18 years after their
diagnosis, the physical abilities were impaired, but Although the temporomandibular joints are
psychosocially the patients were functioning well involved in JIA in the majority of cases,18 relatively
compared to the general population.16 few patients with JIA undergo orthognathic
The aim of the treatment is to relieve or surgery. In a study of mandibular osteotomies
prevent these problems according to the needs of in patients with JIA, only 16 were referred and
the patient. Regarding the burden of treatment, operated on between 1991 and 2000.17
it is important individually to consider a long- In a recent evaluation of JIA patients receiving
term treatment plan in case of early abnormal surgical treatment in three Scandinavian centers,
development. a total of 51 patients were treated surgically in a 6-
An important factor to consider when plan- year period (2008–2013). The treatments com-
ning a surgical treatment is the chance of prised distraction osteogenesis, conventional
obtaining a result that fulfills the expectations of orthognathic surgery, and alloplastic joint pros-
the patient and can be reached with a predictable theses (data under preparation). This indicates
and stable result. It is imperative to share the that some variation in treatment strategies exists
considerations with the family to ensure an and that there may be a trend of a more dif-
informed consent about the goal and possible ferentiated treatment protocol in selected
risks. patients.
142 Nørholt et al
The various types of surgical treatment The surgical technique of genioplasty includes
options including the planning of surgery will be an intra-oral incision in the buccal sulcus, and the
described in the following section. mental nerves are carefully freed, and the
osteotomy is placed below the mental foramina,
and with at least 5 mm distance from the apices
Orthognathic surgery
of the teeth. Cutting through the lingual cortical
Often, both the jaws are involved, and correction plate should be done carefully to avoid bleeding
thus requires advancement and management of from the sublingual area. The use of piezo-
asymmetries of the mandible and corresponding electric cutting of bone can nearly eliminate the
change of the vertical and transversal dimensions risk of damage to the sublingual vessels. After the
of the maxilla. The surgical methods are a osteotomy, the chin can be repositioned in a
bilateral sagittal split osteotomy (BSSO) in the straight advanced position or, in addition,
mandible and a Le Fort 1 osteotomy of the downward or upward, dependent on the need for
maxilla. changing the height of the lower face. The chin
In a study of craniofacial development in JIA may be advanced as far as the thickness of the
patients,1 significant differences were seen with symphysis. For osteosynthesis, titanium plates
regard to both vertical and mandibular and screws are used.
dimensions. Orthognathic surgery in JIA patients The surgical advancement of the mandible is
may therefore often include mandibular advan- performed by a BSSO after established cri-
cement with or without genioplasty. If maxillary teria.19,20 However, the splitting of the mandible
surgery should be needed, intrusion of the may be difficult in the angle of the mandible due
posterior part of the maxilla may be indicated to to the angular notching in patients with JIA.
improve occlusion, mastication, speech, res- Another difficulty may be in securing the con-
piration, and esthetics. dyles in the fossa due to flattening of the articular
In some patients, an anterior rotation of the fossa and deformation of the condyle.18 In
maxillomandibular complex is needed to addition to improvement of occlusion,
improve the airways and obtain the maximum mastication, and esthetics, advancement of the
projection of the chin prominence. Whether this mandible and chin may improve the airways in
is possible is partly depending on the soft tissue JIA patients.
envelope as the limiting factor, and it should be
considered if distraction osteogenesis is the most
Distraction osteogenesis
predictable treatment option. Fig. 1 illustrates
bimaxillary orthognathic surgical of a JIA Distraction osteogenesis (DO) of the mandible
patient. was first described by McCarthy et al.21 in 1992.
In a study of orthognathic surgery of 16 Since then, DO has been demonstrated to be
patients with JIA, six patents had an isolated performed in JIA patients without detrimental
genioplasty performed, six had a combination effects on their TMJ and without worsening of
of genioplasty and BSSO, three had only functional symptoms.22 The rationale for
BSSO, and just one patient had bimaxillary performing DO is to regain the lost vertical
surgery.17 dimension of the mandibular ramus and to
Intubation may be very challenging in normalize the occlusion, which in most
patients with JIA due to arthritic involvement of patients will provide the possibility for an
the cervical spine. Tracheotomy may therefore improved function of the jaws.
be indicated before orthognathic surgery can To obtain a predictable result of DO, a cal-
be performed. Nowadays, with the development culation of the vector of distraction should be
of advanced anesthesiological methods performed. Suggestions for considerations
including intubation guided by a fiberoptic regarding vector planning were described by
scope, most patients can be intubated by a Pedersen and Nørholt.23
normal nasoendotracheal tube. Genioplasty is a The surgical technique of vertical ramus DO
procedure that might be performed with only with internal devices includes an intra-oral inci-
use of a pharyngeal mask to secure airways sion made along the anterior border of the
during surgery. ascending ramus followed by exposure of the
Figure 1.
144 Nørholt et al
entire lateral surface of the ramus, with the therefore, overcorrection by the DO procedure
patient under general anesthesia. Sufficient is recommended. In case of performing dis-
space is created by bluntly stretching the soft traction osteogenesis before growth has ceased,
tissue. The distraction device is applied on the further growth and development can be nor-
lateral surface of the ramus and through a trocar malized due to continuous growth in the den-
entrance fixed loosely with one cortical screw. An toalveolar area.23
indicator rod is fixed perpendicular to the dis- An early surgical treatment with DO is indi-
traction device, the surgical guide is placed on cated in two categories of JIA patients: (1) where
the teeth, and the correct vector of distraction is it is expected that the bone lengthening followed
ensured by rotating the distraction device around by orthodontic and orthopedic treatment can
the first screw until the rod and the wire are provide the definite treatment with no further
parallel. A second screw is inserted to secure the surgery and (2) where severity of the deformity is
position of the distraction device. The remaining expected to require repeated surgeries and an
screw holes are drilled and the distraction device early improvement of facial morphology is
is removed to allow for osteotomy of the ramus by desired.
use of a piezoelectric device. The lingual peri-
osteum is kept attached to the bone, and the
fracture is completed. Free mobility across the
DO in infancy combined with later
osteotomy is mandatory. The distraction device is
orthognathic surgery
reinserted and fixated in the pre-drilled screw
holes. The device is activated to ensure move- In cases of unilateral involvement, it is rarely
ment without bony adherences of the lingual indicated to perform early DO if it is not
cortex, and the wounds are sutured. After 4–7 expected to finish treatment without further
days, the distraction process is initiated by acti- surgery. However, if micrognathia is developing
vations of 1 mm per day until the planned as a consequence of both TMJs being affected by
elongation of bone is obtained. A consolidation arthritis, the growth deficiency is likely to require
period of 2–3 months passes before the devices definite surgery when growth has ended. Nev-
are removed. In Fig. 2, DO of the right ertheless, an early elongation of the mandibular
mandibular ramus in a JIA is illustrated by rami by use of DO is an option in order to obtain
radiographs. improvement of function and esthetics at a young
The treatment protocol varies with the age of age. Orthopedic and orthodontic treatment fol-
the patient, and the principles adapted at various lows in order to maintain the position of the
stages are described in the following sections. mandible, stimulate further growth, and establish
good occlusion. It must be anticipated that a
second surgical treatment may be indicated at a
DO in infancy combined with
later stage; however, it will be less extensive
orthodontics and orthopedics
compared to a situation where no primary
The surgical procedure of DO is relatively gentle treatment was done.
and can be performed in all ages. Thus, if the
condition is identified at a young age and the
condition of the TMJ is stable, it is possible to
DO in adolescence combined with
perform an early elongation of the mandibular
orthodontics and orthopedics
ramus and thereby “catching up” with the
insufficient growth. This procedure is followed For JIA patients in late adolescence in whom
by orthopedics and orthodontic treatment in orthopedic treatment turns out to be insufficient,
order to support the position of the mandible DO followed by orthodontic adjustment is an
and to secure the development of a normal option. The possibility to finish the treatment
occlusion. A valid evaluation of the growth stage orthodontically requires that the malocclusion
of the patients is important because of after completion of DO is mainly of dentoal-
dependence on sufficient dentoalveolar growth veolar origin. If a skeletal component is present,
after DO. In unilateral distractions, there is still the option described in the following section is
remaining growth in the healthy side, and usually chosen.
Figure 2.
DO in adolescents or adults combined results have been published in a Swedish study.24

with Le Fort 1 and/or genioplasty Alternatively, an alloplastic joint prosthesis
including both a condylar and a fossa element
If the mandibular position is corrected by DO,
can be applied for reconstruction. The technique
the remaining deviation of the maxilla usually
and results have been described by Gianna-
requires a surgical correction to ensure a stable
kopoulos et al.,25 and stable results can be
occlusion. The maxillary osteotomy can correct
obtained. The treatment is quite extensive and
deviations in all three dimensions and is planned
is often regarded as the last option when more
to be performed either at the same surgical
conservative alternatives have been considered.
procedure as the distraction device is removed or
at a later stage. Additionally, the chin projection
is often compromised in bilateral cases and can Stability, risks, and complications
be improved by a genioplasty when removing the
Patients with sequel related to JIA of the tem-
distraction devices.
poromandibular joints may have increased risk of
relapse and joint symptoms following jaw surgery.
Orthognathic surgery in these patients is known
Condylar process reconstruction
to have tendency for relapse, and therefore, it
Major destructive condylar processes are rare in might be considered if it is safer to divide the
JIA. In most cases, a condylar growth disturbance treatment of severe malformations into several
is seen in contrast to adult rheumatoid arthritis, smaller and more predictable procedures, e.g.,
where extensive erosions occur. However, treatment with DO.
severely affected joint function and ankylosis can, Relapse after mandibular osteotomies in JIA
although in rare cases, develop and joint patients has been reported to be 0–8 mm.17 This
reconstructive procedures are infrequent. may be caused by continuous arthritic activity in
Reconstruction can be performed with a the TMJs or the tendency of relapse after
costochondral graft, and the technique and orthognathic surgery in general.26,27 The
146 Nørholt et al
relapse is mainly due to two factors: firstly, 4. Arvidsson LZ, Fjeld MG, Smith HJ, Flato B, Ogaard B,
extensive surgical movements of the bone seg- Larheim TA. Craniofacial growth disturbance is related to
temporomandibular joint abnormality in patients with
ments in patients with micrognathia might juvenile idiopathic arthritis, but normal facial profile was
challenge the soft tissue limits, resulting in a also found at the 27-year follow-up. Scand J Rheumatol.
partly reversion to former morphology and sec- 2010;39(5):373–379.
ondly, instability of the TMJ, i.e., the condyle, can 5. Farronato G, Carletti V, Maspero C, Farronato D,
result in further displacement of the mandible, Giannini L, Bellintani C. Craniofacial growth in children
affected by juvenile idiopathic arthritis involving the
leading to recurrence of the sagittal and vertical temporomandibular joint: functional therapy manage-
malformations. ment. J Clin Pediatr Dent. 2009;33(4):351–357.
The patient satisfaction is very high after 6. Pedersen TK, Gronhoj J, Melsen B, Herlin T. Condylar
advancement genioplasty with or without condition and mandibular growth during early functional
treatment of children with juvenile chronic arthritis. Eur J
BSSO,17 and 15 of 16 patients reported that the
Orthod. 1995;17(5):385–394.
surgery had a positive impact on their lives. The 7. Peltomäki T, Kreiborg S, Pedersen TK, Ogaard B.
complication rate is usually low, but neuro- Craniofacial growth and dento-alveolar development in
sensory disturbance of the mental nerves was juvenile idiopathic arthritis patients. Semin Orthod. 2015;
reported as the most uncomfortable compli- 21(2):84–93.
cation after the operations.17 Following DO of 8. Ronning O, Barnes SA, Pearson MH, Pledger DM.
Juvenile chronic arthritis: a cephalometric analysis of
the mandible, the occurrence of permanent the facial skeleton. Eur J Orthod. 1994;16(1):53–62.
neurosensory impairment was 1.5% in a series 9. Stabrun AE, Larheim TA, Hoyeraal HM, Rosler M.
of 131 patients.28 Reduced mandibular dimensions and asymmetry in
juvenile rheumatoid arthritis. Pathogenetic factors. Arthri-
tis Rheum. 1988;31(5):602–611.
10. Billiau AD, Hu Y, Verdonck A, Carels C, Wouters C.
Conclusion Temporomandibular joint arthritis in juvenile idiopathic
Although only a small group of JIA patients will arthritis: prevalence, clinical and radiological signs, and
relation to dentofacial morphology. J Rheumatol. 2007;34
need orthognathic surgical correction, these (9):1925–1933.
patients are severely disabled concerning their 11. Mericle PM, Wilson VK, Moore TL, et al. Effects of
orofacial function. Surgical treatment is a chal- polyarticular and pauciarticular onset juvenile rheuma-
lenge in JIA patients because of the specific toid arthritis on facial and mandibular growth. J Rheu-
limitations and the risk of relapse resulting from matol. 1996;23(1):159–165.
12. Leksell E, Ernberg M, Magnusson B, Hedenberg-
their primary disease. It is recommendable to Magnusson B. Orofacial pain and dysfunction in children
elaborate individual treatment plans taking into with juvenile idiopathic arthritis: a case–control study.
account the disease activity, joint stability, risk of Scand J Rheumatol. 2012;41(5):375–378.
relapse, and burden of treatment. Additionally, 13. Bakke M, Zak M, Jensen BL, Pedersen FK, Kreiborg S.
considerations regarding dividing procedures Orofacial pain, jaw function, and temporomandibular
disorders in women with a history of juvenile chronic
into smaller and predictable steps should be arthritis or persistent juvenile chronic arthritis. Oral Surg
taken. Research should focus on the efficacy, risk, Oral Med Oral Pathol Oral Radiol Endod. 2001;92
and stability of the treatment regime chosen. (4):406–414.
14. Bomba M, Meini A, Molinaro A, et al. Body experiences,
emotional competence, and psychosocial functioning in
juvenile idiopathic arthritis. Rheumatol Int. 2013;33
Reference (8):2045–2052.
1. Fjeld MG, Arvidsson LZ, Stabrun AE, Birkeland K, 15. Muller-Godeffroy E, Lehmann H, Kuster RM, Thyen U.
Larheim TA, Ogaard B. Average craniofacial develop- Quality of life and psychosocial adaptation in children
ment from 6 to 35 years of age in a mixed group of and adolescents with juvenile idiopathic arthritis and
patients with juvenile idiopathic arthritis. Acta Odontol reactive arthritis. Z Rheumatol. 2005;64(3):177–187.
Scand. 2009;67(3):153–160. 16. Ostile IL, Johansson I, Aasland A, Flato B, Moller A. Self-
2. Kjellberg H, Fasth A, Kiliaridis S, Wenneberg B, rated physical and psychosocial health in a cohort of
Thilander B. Craniofacial structure in children with young adults with juvenile idiopathic arthritis. Scand J
juvenile chronic arthritis (JCA) compared with healthy Rheumatol. 2010;39(4):318–325.
children with ideal or postnormal occlusion. Am J Orthod 17. Oye F, Bjornland T, Store G. Mandibular osteotomies in
Dentofacial Orthop. 1995;107(1):67–78. patients with juvenile rheumatoid arthritic disease. Scand J
3. Stabrun AE. Mandibular morphology and position in Rheumatol. 2003;32(3):168–173.
juvenile rheumatoid arthritis. A study on postero-anterior 18. Arvidsson LZ, Flato B, Larheim TA. Radiographic TMJ
radiographs. Eur J Orthod. 1985;7(4):288–298. abnormalities in patients with juvenile idiopathic arthritis
followed for 27 years. Oral Surg Oral Med Oral Pathol Oral 24. Svensson B, Adell R. Costochondral grafts to replace
Radiol Endod. 2009;108(1):114–123. mandibular condyles in juvenile chronic arthritis patients:
19. Epker BN. Modifications in the sagittal osteotomy of the long-term effects on facial growth. J Craniomaxillofac Surg.
mandible. J Oral Surg. 1977;35(2):157–159. 1998;26(5):275–285.
20. Trauner R, Obwegeser H. The surgical correction of 25. Giannakopoulos HE, Sinn DP, Quinn PD. Biomet Micro-
mandibular prognathism and retrognathia with consid- fixation Temporomandibular Joint Replacement System:
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genia and distoclusion. Oral Surg Oral Med Oral Pathol. 2005. J Oral Maxillofac Surg. 2012;70(4):787–794.
1957;10(8):787–792. 26. Hoppenreijs TJ, Freihofer HP, Stoelinga PJ, Tuinzing DB,
21. McCarthy JG, Schreiber J, Karp N, Thorne CH, Grayson van't Hof MA. Condylar remodelling and resorption after
BH. Lengthening the human mandible by gradual Le Fort I and bimaxillary osteotomies in patients with
distraction. Plast Reconstr Surg. 1992;89(1):1–8. anterior open bite. A clinical and radiological study. Int J
22. Norholt SE, Pedersen TK, Herlin T. Functional changes Oral Maxillofac Surg. 1998;27(2):81–91.
following distraction osteogenesis treatment of asym- 27. Mobarak KA, Espeland L, Krogstad O, Lyberg T.
metric mandibular growth deviation in unilateral Mandibular advancement surgery in high-angle and
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long-term follow-up. Int J Oral Maxillofac Surg. 2013;42 responses. Am J Orthod Dentofacial Orthop. 2001;119
(3):329–336. (4):368–381.
23. Pedersen TK, Norholt SE. Early orthopedic treatment 28. Norholt SE, Jensen J, Schou S, Pedersen TK. Complica-
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Future Issues
Vol 21 No 3 (September 2015)
ACCELERATED ORTHODONTICS
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Recent Issues
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ALL ROADS LEAD TO ROME: NEW DIRECTIONS FOR CLASS II
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Vol 18 No 2 (June 2012)
MAXILLARY EXPANSION AND MANDIBULAR WIDENING: TREATMENT METHODS AND STABILITY
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Seminars in Orthodontics

Mani Alikhani, New York, NY (2017) Peter Ngan, Morgantown, WV (2015)

Juvenile Idiopathic Arthritis and Temporomandibular Joint

■ Juvenile idiopathic arthritis: A frequent cause for chronic joint inflammation in

■ Juvenile idiopathic arthritis characteristics: Etiology and pathophysiology 77

■ Craniofacial growth and dento-alveolar development in juvenile idiopathic arthritis

■ Clinical craniofacial examination of patients with juvenile idiopathic arthritis 94

■ TMJ imaging in JIA patients—An overview 102

■ Magnetic resonance imaging of temporomandibular joints in juvenile idiopathic

■ 3D digital surface imaging for quantification of facial development and asymmetry

■ Systemic and intra-articular anti-inflammatory therapy of temporomandibular joint

■ Functional and orthopedic treatment in developing dentofacial growth deviation in

■ Jaw surgery for correction of dentofacial anomalies caused by JIA 140

J uvenile idiopathic arthritis (JIA) affects chil-

& 2015 Elsevier Inc. All rights reserved.

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: p 71 71

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in

Introduction cular JIA, psoriatic arthritis, enthesitis-related

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 72–76 72

Table. ILAR classiﬁcation of juvenile idiopathic arthritis

Undifferentiated Fulﬁls none of the above subsets

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic

Introduction families, a concordance rate of 25% for JIA was

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 77–83 77

pathophysiological mechanism behind TMJ destruction, the matrix metalloproteinases

Mandibular condyles/condylar cartilages can be considered as major growth

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 84–93 84

be the subject of further investigations. Classical Dento-alveolar compensations

Soft tissue reaction

Clinical craniofacial examination plays an essential role in assessing the

Introduction The aim of the present article is to present the

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 94–101 94

Table 1. RDC/TMD Classiﬁcations as Published by Dworkin et al. in 199210

Symptoms most consistently used in studies related to TMJ

Pain/difﬁculties during mastication Reduced mouth-opening

Craniofacial morphology in patient Table 3. Craniofacial Characteristics of Patients with

Introduction radiography3–11 or magnetic resonance imaging

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 102–110 102

MRI JIA children and healthy controls indicated that

Magnetic resonance imaging (MRI) is considered essential for diagnosing

Introduction The condylar contour is rounded with a

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 111–120 111

Contrast enhancement further steady increase beyond 6 min after contrast

– Grade 2: Moderate inﬂammation. Joint

3D digital surface imaging (digital stereophotogrammetry or “3D photog-

3D digital surface acquisition systems have

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 121–124 121

deformation of the face due to facial expres-

segmented reference surface (called an atlas),

Juvenile idiopathic arthritis (JIA) is a leading cause of acquired disability and

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 125–133 125

Table 1. Methods used for TMJ CS injections

Arabshahi 23 MRI CT guidance TA 40 mg (n ¼ 16); TH 20 mg

Table 2. Outcome measures and results

Dentofacial growth in juvenile idiopathic arthritis (JIA) patients with

Introduction disorder or by a general disease, such as

Seminars in Orthodontics, Vol 21, No 2 (June), 2015: pp 134–139 134

Deﬁnition of functional–orthopedic relevant regarding the skeletal changes. They