REVIEWS

Oesophageal dysphagia: manifestations

and diagnosis
Frank Zerbib and Taher Omari
Abstract | Oesophageal dysphagia is a common symptom, which might be related to severe oesophageal
diseases such as carcinomas. Therefore, an organic process must be ruled out in the first instance by
endoscopy in all patients presenting with dysphagia symptoms. The most prevalent obstructive aetiologies
are oesophageal cancer, peptic strictures and eosinophilic oesophagitis. Eosinophilic oesophagitis is one of
the most common causes of dysphagia in adults and children, thus justifying the need to obtain oesophageal
biopsy samples from all patients presenting with unexplained dysphagia. With the advent of standardized high-
resolution manometry and specific metrics to characterize oesophageal motility, the Chicago classification
has become a gold-standard algorithm for manometric diagnosis of oesophageal motor disorders. In addition,
sophisticated investigations and analysis methods that combine pressure and impedance measurement
are currently in development. In the future, these techniques might be able to detect subtle pressure
abnormalities during bolus transport, which could further explain pathophysiology and symptoms. The degree
to which novel approaches will help distinguish dysphagia caused by motor abnormalities from functional
dysphagia still needs to be determined.
Zerbib, F. & Omari, T. Nat. Rev. Gastroenterol. Hepatol. advance online publication 18 November 2014; doi:10.1038/nrgastro.2014.195

Introduction
Oesophageal dysphagia is defined as a sensation of dif- dysphagia should be differentiated from dyspeptic symp-
ficult passage of solids or liquids in the oesophageal toms such as early satiety or bloating in patients ­reporting
body. Oesophageal dysphagia is a remarkably common a sensation of delayed food bolus in the epigastrium.
symptom; the most recent study in 2008 reported that up Distinguishing between whether dysphagia symptoms
to 16% of a random sample of 1,000 healthy individuals are due to a predominantly oropharyngeal or oesophageal
from Sydney, Australia, had a history of some form of body cause can be difficult. Oropharyngeal dysphagia
dysphagia at some time in their life,1 with the incidence symptoms usually occur immediately after swallowing
increasing with age.2 Dysphagia is considered to be an and can be associated with various symptoms such as
important alarm symptom as it might be related to severe choking and coughing, drooling and nasal regurgita-
oesophageal disorders such as oesophageal carcinoma. tion. Oesophageal dysphagia is indicated when passage
However, the prevalence of serious organic disease is of the food bolus is delayed in the chest or epigastrium;
low 2 and most patients will eventually prove to have however, the ability of an individual to accurately identify
dysphagia related to benign obstructive disorders or the location where a food bolus is sticking varies. Patients
motility disorders. localizing the site of bolus hold up to the cervical area or
mid-chest often do not prove to have a cause in this area,
Clinical presentation whereas those complaining of more distal dysphagia are
In a patient with swallowing complaints, a careful accurate in 80% of cases.4 Oesophageal dysphagia is also
Gastroenterology interview is mandatory to confirm dysphagia, to dif- more often associated with heartburn, regurgitation and
and Hepatology ferentiate (as best possible) whether the dysphagia is of chest pain than oropharyngeal dysphagia.
Department,
Saint André Hospital,
a predominantly oesophageal or oropharyngeal nature Dysphagia symptoms in relation to ingestion of solids
Centre Hospitalier and to provide a first impression regarding the potential are widely considered to suggest a mechanical obstruc-
Universitaire de underlying mechanism or aetiology (Box 1). Dysphagia tion. Dysphagia that occurs in relation to both solids and
Bordeaux, 1 Rue Jean
Burguet, F‑33075 should not be confused with a globus sensation, which is liquids suggests an underlying oesophageal motility dis-
Bordeaux, France (F.Z.). defined, according to the Rome III definition, as a non- order. However, both our own clinical experience and a
Medical Science
and Technology, School
painful sense of a lump, a retained food bolus or tight- systematic study 5 have demonstrated that the utility of
of Medicine, Flinders ness in the throat, which frequently improves with eating such a symptomatic differentiation seems to be limited.
University, Sturt Road, and is therefore not associated with dysphagia.3 Similarly, There­fore, an organic process must be ruled out with
Bedford Park, SA 5042,
Australia (T.O.). appropriate investigations in all patients presenting
with dysphagia symptoms.
Correspondence to: F.Z. Competing Interests
frank.zerbib@ F.Z. is a consultant and speaker for Given Imaging. T.O. holds Taking a careful history can be helpful to provide
chu-bordeaux.fr patents on pressure-flow analysis methods. cues for several organic disorders. Alcohol abuse and/or

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REVIEWS

Key points choking and airway changes secondary to aspira-

tion.10 Premature and newborn babies with dysphagia
■■ An organic process must be ruled out by endoscopy in all patients presenting
might fail to demonstrate adequate progression to full
with dysphagia symptoms
■■ Eosinophilic oesophagitis is one of the most prevalent causes of dysphagia
oral feeding due to immaturity of the complex control
in adults and children mechanisms responsible for suck, swallow and breath-
■■ Oesophageal biopsy samples should be obtained in all patients with ing coordination.11 Many of the typical causes of adult
unexplained dysphagia symptoms p­resentations of dysphagia might have an early-life onset
■■ High-resolution manometry is the gold-standard investigation for diagnosis and can therefore manifest in the paediatric population.11
of oesophageal motor disorders Examples of disorders for which dysphagia is a second-
■■ According to the Chicago classification algorithm, major oesophageal motor ary symptom include neurological disease, GERD, atopic
disorders are achalasia, oesophagogastric junction outflow obstruction,
disease and primary motor disorders, particularly acha-
diffuse oesophageal spasm, hypercontractile ‘jackhammer’ oesophagus and
absent peristalsis lasia. Oesophageal dysmotility and dysphagia have a high
■■ Sophisticated investigations (for example integrated pressure impedance prevalence in children who have undergone surgical
analysis and impedance planimetry) could reveal subtle abnormalities and help repair for congenital abnormalities, including oesopha-
distinguish between neuromechanical dysfunction and functional dysphagia geal atresia and diaphragmatic hernia.11 Current knowl-
edge in relation to upper gastrointestinal motility in the
paediatric population has been the topic of an extensive
Box 1 | Aetiologies of oesophageal dysphagia review 11 and therefore will not be discussed further here.
Obstructive
Malignant strictures Endoscopy
■■ Adenocarcinoma Upper gastrointestinal endoscopy enables direct visu-
■■ Squamous cell carcinoma alization of the oesophagus (as well as the stomach and
■■ Extrinsic compression
duodenum) and the opportunity to obtain oesophageal
Benign strictures
■■ Peptic stenosis mucosa biopsy samples. Endoscopy is a crucial first-
■■ Schatzki ring line investigation for evaluating patients for structural
■■ Oesophageal web causes of oesophageal dysphagia. Endoscopy can easily
■■ Drug-induced stricture identify tumours, compression by extrinsic structures,
■■ Caustic stricture strictures, webs and mucosal inflammatory changes
■■ Oesophagitis dissecans superficialis related to GERD (peptic oesophagitis and stenosis), as
Eosinophilic oesophagitis
well as caustic and drug-induced stenosis frequently
Complications after surgery
■■ Postfundoplication
located at the level of mid-oesophagus. Endoscopy can
■■ Anastomosis stricture also demonstrate the presence of a severe oesophageal
Nonobstructive
motor disorder, such as achalasia, if oesophageal stasis
Motility disorders in a dilated oesophagus associated with a ‘spastic’ (tight)
■■ Achalasia oesophagogastric junction (EGJ) is present (Figure 1). An
■■ Diffuse oesophageal spasm oesophagus with a ‘normal’ appearance in a patient with
■■ Absent peristalsis dysphagia should lead the endoscopist to search for subtle
■■ Hypercontractile ‘jackhammer’ oesophagus mucosal changes, such as mild oesophageal stenosis or
■■ Oesophagogastric junction outflow obstruction Schatzki ring, which can be easily overlooked.12 In our
Functional dysphagia
own experience, a slightly dilated oesophagus and/or a
paucity of oesophageal contractions could also suggest
smoking are risk factors for oesophageal carcinoma. the presence of an oesophageal motor disorder; however,
GERD-related dysphagia might be suspected if heart- early stage achalasia is frequently missed at endoscopy
burn and/or regurgitation are present. Dermatological because the changes are subtle. Looking for endoscopic
disorders might be associated with oesophagitis or stric- oesophageal features of eosinophilic oesophagitis such as
tures. Oesophagitis owing to an acid or caustic cause is concentric rings (trachealisation), exudates (white spots),
fairly easy to diagnose. Oesophagitis of a drug-induced furrows or oedema (Figure 1) is important.13 How­ever, as
nature can occur in relation to use of NSAIDs, potas- the endoscopic appearance of the oesophageal mucosa
sium chloride and bisphosphonates; however, it is more might be normal in 10–25% of patients with eosinophilic
difficult to detect from a patient’s history because of oesophagitis, oesophageal biopsies should be performed
potential lack of awareness from physicians and patients.6 in all patients with unexplained dysphagia.7,14 If slough-
A longstanding history of mild dysphagia in young adult ing of large fragments of oesophageal mucosa occurs
males with atopic disorders and one or several episodes during biopsy or after passage of the scope, oesophagitis
of food impaction is very suggestive of eosinophilic dissecans is indicated,15 which can be either idiopathic
oesophagitis. 7 Specific and validated questionnaires or secondary to various bullous skin disorders16 and
such as EAT‑108 and MDQ‑309 can be used to assess the lichen planus.17
initial level of disability and monitor treatment progress
in adults. Fluoroscopy and timed barium transit
Dysphagia is also prevalent in the paediatric popu- Videofluoroscopic examination of oesophageal transit
lation and can lead to failure to thrive, feed refusal, (barium swallow) is usually performed with the patient

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in the supine position and then upright. Visualization of a b

a swallowed bolus as it is propelled along the oesopha-
geal lumen can determine anatomical abnormalities (for
example, oesophageal diverticuli), luminal narrowing
and/or obstruction (stricture, webs and rings) and hiatus
hernia. Achalasia and other motor abnormalities (such
as diffuse oesophageal spasm, stasis due to peristaltic
failure or EGJ obstruction) can be detected. However,
an oesophageal manometry test (see later) enables better c d
understanding and characterization of these anatomical
abnormalities than videofluoroscopic examination. Semi-
solid boluses, solid boluses and radio-opaque tablets can
also establish oesophageal bolus transport function in
relation to the increased work load (that is, with a solid
bolus). The timed barium oesophagram test can assess
passive drainage of the oesophagus in patients with acha-
Figure 1 | Endoscopic features of dysphagia. Features
lasia. During this test, the height and maximum width
of oesophageal achalasia a | oesophageal stasis
of the barium column (above the EGJ ‘bird’s beak’) are and b | ‘tight’ EGJ. Features of eosinophilic oesophagitis
taken at 1, 2 and 5 min after ingestion of ~250 ml of liquid c | longitudinal furrows and d | concentric rings. Abbreviation:
barium. This test determines how effectively the oesopha- EGJ, oesophagogastric junction.
gus empties, which is useful for measuring the success of
therapy to improve oesophageal outflow.18,19
typical GERD symptoms. Three EGJ pressure morphol-
Oesophageal manometry ogy subtypes have been defined, which are primarily
Methodologies for performing diagnostic pressure distinguished by the extent of separation between the
measurements within the gut have evolved considerably crural diaphragm and the lower oesophageal sphincter.22
during the last 20 years. Advances in catheter technol- Current diagnostic criteria used by the Chicago clas-
ogy now offer improved reliability, recording fidelity sification algorithm are based on a standardized protocol
and spatial resolution of measurements. Catheter diam- of 10 × 5 ml liquid bolus swallows performed in a supine
eter has also reduced, enabling motility investigations posture.19 However, in our experience, most patients who
in children to become routine. Oesophageal manom- develop dysphagia owing to a primary motor disorder
etry is a short, well-tolerated procedure, which can be experience symptoms in relation to solids rather than
very useful for diagnosing the presence of a primary liquids and, indeed, often report no symptoms during
oesophageal motor disorder that might explain dyspha- performance of a manometric test. EPT metrics also do
gia symptoms. Manometry testing utilizes an indwell- not seem to correlate with the intensity of bolus percep-
ing catheter to measure the pressures generated during tion experience during the test.23 Considerable debate
transport of a swallowed bolus from pharynx to stomach. has surrounded the issue of the potential added value
This approach provides an objective measurement of of testing using a more physiological posture (that is,
the resting and relaxation pressures of the oesophageal upright) and with solid bolus challenges or a meal in
sphincters and the pressures generated by oesopha- order to precipitate symptoms and to characterize the
geal peristaltic contraction. Intrabolus pressures within adaptive response of the oesophagus to an increased
the lumen of the distal oesophagus can also be measured. work load; notably, this adaptive response has been
High-resolution manometry (HRM) is the current state- shown to be diminished in patients with erosive GERD.24
of-the-art for this measurement method and typically Data from studies assessing the normative range in the
involves recording of intraluminal pressure using a large upright posture and with solid bolus challenges for
array of closely spaced pressure sensors (typically 32–36 EPT metrics are emerging and could potentially lead to
sensors at 1 cm spacing). High-resolution pressures are expansion of the range of swallow protocols upon which
displayed over time by way of spatiotemporal pressure a diagnosis using the Chicago classification algorithm
plots (also called oesophageal pressure topography [EPT] can be based.25
or Clouse plots). EPT plots can be quantitatively evalu- In the paediatric setting, the spectrum of motility dis-
ated for diagnosis through the derivation of EPT metrics, orders that can be classified by HRM resembles that seen
of which five are currently in routine use (Figure 2). in adults.26 However, implementation of HRM for use in
Derivation of EPT metrics has been made both objec- the paediatric population is challenging owing to the lack
tive and reliable using interactive software. Interpretation of data on paediatric normative ranges for EPT metrics.
of the EPT results is then guided through application of The age and size of the patient also affects some HRM
the Chicago classification diagnostic algorithm.20 HRM metrics26,27 and paediatric studies are more challenging to
can reveal residual pressure at the crural diaphragm perform, meaning that studies often have fewer than the
or elevated intrabolus pressure proximal to the EGJ.21 requisite 10 liquid swallows and the scope for provoca-
Hiatus hernia might cause an EGJ outflow obstruction, tive testing is limited. Multiple swallowing, movement
particularly in patients with dysphagia, but without and crying can also produce pressure artefacts.

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REVIEWS

such pressures are often difficult to measure and tend

to be ignored unless unequivocally elevated. The meas-
UES urement of intraluminal impedance could help guide
intrabolus pressure measurements as it has been con-
firmed that the lowest level of impedance (nadir imped-
ance) defines maximum bolus distension in space and
time.32 Hence, the pressures measured at nadir imped-
DCI
ance define intrabolus distension and emptying pressures
during bolus transport.30,35 Such pressures in and around
CFV
the bolus being transported might have physiological and
pathophysiological relevance and seem to correlate with
symptoms.35,36 Finally, impedance measurements might
give the potential to assess oesophageal passive drain-
DL age in patients with achalasia.37,38 When combined with
pressure measurements of the EGJ, impedance meas-
LES IRP
urements could provide a broader scope of mechanistic
information than that currently available using a timed
barium oesophagram test and have a greater role in the
diagnosis of dysphagia than originally envisaged.
Figure 2 | Oesophageal pressure topography Clouse plots of a normal water
swallow on high-resolution manometry. The two bands of high pressure correspond
to the UES and LES. The IRP is the lowest average pressure for four noncontiguous Impedance planimetry
seconds, defining LES relaxation. The UES relaxes at the start of the swallow, and Some aspects of oesophageal function are not readily
the LES relaxes as the contraction front traverses the oesophageal body. The CDP appreciable using HRM techniques alone. Most evident
(black dot) is the inflexion point in the contractile front propagation. The CFV are the mechanical properties of the gut wall, which
corresponds to the slope of the tangent line to the initial portion of the contraction. alter oesophageal compliance and therefore bolus flow-
The distal latency is measured from the onset of swallow (dashed vertical line)
resistance along the oesophageal body and through the
to the CDP. The DCI corresponds to the volume of the contraction between the first
pressure trough and the distal trough. Abbreviations: CDP, contractile deceleration
upper and lower oesophageal sphincters. Oesophageal
point; CFV, contractile front velocity; DCI, distal contractile integral; DL, distal compliance can reduce in concert with a disease process,
latency; IRP, integrated relaxation pressure; LES, lower oesophageal sphincter; which leads to loss of neuromechanical function (for
UES, upper oesophageal sphincter. example, achalasia) and tissue remodelling (eosinophilic
oesophagitis). Repeated therapy such as dilation can also
lead to fibrosis and subsequent complications. The tech-
Intraluminal impedance nique of impedance planimetry, by way of a functional
Manometry results can be inconclusive or even normal luminal imaging probe (FLIP), could provide compliance
despite a clinical history suggesting an underlying oesoph- information. Comprising of a compliant bag, an array of
ageal motility disorder.23 Such findings might dictate the impedance electrodes and a pressure sensor, the FLIP
need for further corroborative evidence of abnormal bolus can quantify the distensibility of surrounding structures
transport, such as from fluoroscopy (as mentioned pre- based on the relationship between bag cross-sectional
viously) or intraluminal impedance measurement. The area and intra-bag pressure and/or volume. FLIP has
measurement of electrical impedance along a catheter by already been applied in two key areas and could have
way of an electrode array is now a standard add-on feature great diagnostic relevance. First, FLIP has been used to
of oesophageal manometry systems. Impedance meas- predict treatment success by assessing EGJ distensibility,
urements detect movement and clearance of a conduc- particularly in relation to achalasia.39 Second, FLIP has
tive bolus. Although this approach provides physiological been used to predict bolus impaction risk by assessment
insights, the additional yield of measuring impedance in of oesophageal distensibility in relation to eosinophilic
relation to understanding pathophysiology is limited. The oesophagitis (Figure 3).40
analysis of impedance recordings remains fairly simplistic Although an important determinant of treatment
and does not go beyond the detection of bolus transport strategies, distinguishing patients with hypersensitivity
failure, which is already highly predictable with the use from those with true motor dysfunctions is not always
of HRM results.28,29 New and different ways of analysing straightforward, even when state-of-the-art HRM is used.
impedance waveforms through integration with pressure Oesophageal perception can be evoked by graded disten-
measurement are now being explored, with studies sug- sions applied using the impedance planimetry balloon,
gesting that impedance can be used to track subtle vari- thus enabling the direct correlation of wall tension and
ations in bolus movement,30 quantify luminal diameter sensory thresholds. Patients with hyper­sensitivity (for
changes31–33 and time the period of bolus flow across the example patients with noncardiac chest pain) demonstrate
EGJ.34 Further research is needed to determine whether lower tension thresholds to elicit sensation than patients
these additional insights have clinical utility. with true motor dysfunctions.41 Impedance plani­metry of
Intrabolus pressure captured during HRM is gener- the oesophagus could also have a role in detecting subtle
ally considered to be a definitive correlate of increased mechanical dysfunction that might explain symptoms
flow resistance as measured by manometry; however, of dysphagia.42

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a b 500 a transient nature during the immediate postoperative

Oesophageal distensibility
Healthy patient period. However, persistent and troublesome dysphagia is
EGJ distensibility
Oesophagus less common, affecting 8–12% of patients in randomized
400
Control
controlled trials, and leads to dilation and/or surgical re-
EGJ intervention in up to 7% of patients.50,51 A meta-analysis
of randomized controlled trials showed that the preva-
Stomach Narrowest SCA (mm2) 300 lence of postoperative dysphagia was lower (8.6%) after
laparoscopic anterior (180°) fundoplication than after ‘full
30 ml wrap’ laparoscopic Nissen (360°) fundoplication (13.5%),
Eosinophilic
200 oesophagitis with a similar effect on control of reflux symptoms.50
Patient with achalasia Control Whether the occurrence of postoperative dysphagia can
Oesophagus be predicted by oesophageal motility testing performed
100 preoperatively remains a matter of debate. However, some
EGJ encouraging data suggest that subtle, subclinical dys-
Untreated functions of motility, detectable by combined pressure-
Stomach achalasia impedanc­e analysis52,53 and/or multiple rapid swallow
0
0 10 20 30 40 50 60 testing,54 could predict susceptibility to postoperative dys-
30 ml Bag pressure (mmHg) phagia. Although these data are preliminary, they suggest
Figure 3 | Impedance planimetry to assess distensibility of the oesophagus and the potential for an individual patient’s risk for dysphagia
EGJ. a | FLIP measurement panels showing the diameter profile across the EGJ in to be better quantified than is currently possible. Such
a healthy person and a patient with achalasia. b | Distensibility curves for the distal a change might enable improved determination of risks
oesophagus, in controls and patients with eosinophilic oesophagitis and for the versus benefits of surgery and/or decision making with
EGJ in control individuals and patients with untreated achalasia. This figure was respect to optimal operative approach.
constructed based on published findings. Abbreviations: EGJ, oesophagogastric
junction; FLIP, functional luminal imaging probe. Permission obtained from
Elsevier Ltd. © Rohof, W. O. et al. Gastroenterology 143, 328–335 (2012)39 and
Eosinophilic oesophagitis
Nicodeme, F. et al. Clin. Gastroenterol. Hepatol. 11, 1101–1107 (2013).40 Over the past 15 years, eosinophilic oesophagitis has
become recognized as one of the most prevalent causes
of oesophageal dysphagia in adults,55 probably because of
Diagnosis of oesophageal dysphagia an increased awareness of both endoscopists and pathol-
GERD-related dysphagia ogists.56 Eosinophilic oesophagitis is an allergic disorder
Dysphagia is a common symptom of GERD and might defined by symptoms related to oesophageal dysfunc-
be related to oesophagitis, peptic stricture, oesopha- tion and characterized by an eosinophil-predominan­t
geal carcinoma or GERD-related oesophageal motility inflammation on analysis of oesophageal biopsy
disorders. 43 Erosive oesophagitis, which develops in samples.7 Mucosal eosinophilia is usually isolated to
patients with chronic GERD, is defined by the presence the oesophagus, characteristically consisting of a peak
of mucosal breaks in the oesophageal mucosa at the EGJ value of ≥15 eosinophils per high-power field. Other
and is best classified according to the Los Angeles clas- causes of oesophageal eosinophilia such as vasculitis,
sification.44 Reflux oesophagitis is present in 10–30% eosinophilic gastroenteritis, hypereosinophilic syn-
of patients with reflux symptoms and approximately drome, acute infections, Crohn’s disease or connective
one-third of patients with oesophagitis report non- tissue diseases should be excluded. The pathogenesis of
troublesome dysphagia that resolves with PPI therapy.45 eosinophilic oesophagitis involves genetic susceptibil-
According to the Montreal definition, “troublesome ity 57 and dysregulated immunity directed at food anti-
dysphagia is present when patients need to alter eating gens as demonstrated by the efficacy of elementary or
patterns or report food impaction”43 and is considered elimination diets in improving symptoms.58,59 GERD and
as an alarm symptom indicative of serious oesophageal eosinophilic oesophagitis might be related diseases as
pathology such as peptic stricture or oesophageal cancer up to 50% of patients with an eosinophilic oesophagitis
that warrants further investigation. Indeed, GERD phenotype respond to PPI therapy both clinically and
symptoms are not singularly associated with oesopha- histologically,60 leading to the concept of ‘PPI-responsive
geal carcinoma;46 having dysphagia has been reported to oesophageal eosinophilia’. A 2014 study has shown
increase the likelihood of having oesophageal cancer.47 that oesophageal permeability was increased in both
The prevalence of oesophageal strictures is low (<5% eosinophilic oesophagitis and PPI-responsive oesopha-
in population-based studies) and has declined as PPI geal eosinophilia, which enabled transepithelial trans-
therapy has become widespread. 48 GERD-associated port of food antigens.61 PPI therapy can at least partially
motility disorders such as hypotensive or failed peri­ restore mucosal integrity in PPI-responsive oesopha-
stalsis usually increase in parallel with reflux severity geal eosinophilia but not in eosinophilic o­esophagitis.61
and might be responsible for nonobstructive dysphagia Dysphagia can be related to oesophageal stricture,
in patients with GERD.49 obser­ved in approximately one-third of patients with
Dysphagia is also a common symptom in patients eosinophilic oesophagitis,13 or to oesophageal motility
who undergo antireflux surgery (for example, Nissen disorders secondary to oesophageal mucosal infiltra-
fundoplication). Many patients experience dysphagia of tion of the oesophageal wall. However, as most patients

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REVIEWS

IRP ≤ upper limit of normal Yes Category 1 wave, transition zone, and relaxation and movement of
and absent peristalsis ■ Achalasia (subtypes I, II and III) the EGJ. HRM can also evaluate pharyn­geal (tongue base
No pressure) and upper oesophageal sphincter relaxation
during swallowing. To date, the major focus of HRM
IRP ≤ upper limit of normal Yes
Category 2 studies for the investigation of oesophageal dysphagia
and some instances of intact ■ EGJ outflow obstruction
or weak peristalsis Achalasia variant versus mechanical obstruction has been the identification of disordered peristalsis
and/or high EGJ pressures. Pharyngeal propulsion also
No helps facilitate bolus transport so that the more effec-
tive the swallowing force, the less work the oesophagus
IRP is normal Category 3
and absent peristalsis Yes ■ Absent peristalsis will need to do to finalize transport of the bolus into
or reduced DL or
DCI >8,000 mmHg•s•cm
■ Diffuse oesophageal spasm the stomach.30
≥20% of swallows with reduced DL (<4.5 s)
■ Hypercontractile ‘jackhammer’ oesophagus
The present Chicago classification algorithm is highly
≥20% of swallows with DCI >8,000 mmHg•s•cm useful to the clinician because it provides a unified HRM
No and normal DL
and consensus-based framework enabling recognition of
specific oesophageal dysfunctions.19 These dysfunctions
IRP is normal Yes Category 4 might cause failure of transport along the oesophagus
and minor peristaltic ■ Rapid contraction
≥20% of swallows with rapid CFV (>9 cm/s)
(for example weak propulsion), pain symptoms (such
abnormalities
and normal DL as hypercontractility or spasticity) or impede bolus flow
■ Hypertensive peristalsis through the EGJ (obstruction). The evolving Chicago
≥20% of swallows with DCI >5,000 mmHg•s•cm
and normal DL classification algorithm is the current best-practice for
No ■ Weak peristalsis manometric diagnosis of oesophageal motor disor-
≥30% of swallows with small (2–5 cm) breaks
in the 20 mmHg IBC ders and characterizes oesophageal motor dysfunction
≥20% of swallows with large (>5 cm) breaks into four main categories in order of severity: achalasia
in the 20 mmHg IBC
■ Frequent failed peristalsis (Category 1); EGJ outflow obstruction (Category 2);
Normal ≥30% of absent swallows disorders never observed in healthy individuals such as
Figure 4 | Flow diagram illustrating the hierarchical analysis of patient EPT findings absent peristalsis, diffuse oesophageal spasm or hyper-
according to the Chicago classification.20 Abbreviations: CFV, contractile front contractile oesophagus (Category 3); and motor patterns
velocity; DCI, distal contractile integral; DL, distal latency; EGJ, oesophagogastric outside the normal range, for example weak peri­stalsis,
junction; EPT: oesphageal pressure topography; IBC, isobaric contour; IRP, frequent failed peristalsis, hypertensive peristalsis or
integrated relaxation pressure. rapid contraction (Category 4, Figure 4). To arrive at a
specific Chicago classification diagnosis, five different
with eosinophilic oesophagitis have normal oesophageal EPT metrics are calculated for each swallow (Figure 2):
motility,62 decreased oesophageal distensibility has been first, the 4 s integrated relaxation pressure (which defines
suggested to cause dysphagia.63 EGJ relaxation pressures); second, the largest size of
Eosinophilic oesophagitis is most frequently observed breaks in the peristaltic contractile front (break size;
in young adult males, during the third or fourth decade which defines peristaltic integrity over distance based
of life64 and is frequently (>75%) associated with other on the 20 mmHg isocontour); third, the velocity of the
allergic disorders such as asthma, atopic rhinitis or contractile front (which defines peristaltic contraction
eczema.65 Dysphagia is the most frequent symptom in rate); fourth, the integral of pressure generated by con-
adults with eosinophilic oesophagitis; other symptoms traction of the distal oesophagus (which defines strength
include chest pain, heartburn and abdominal pain.65 or weakness of contractility); and fifth, the time latency
Food impaction requiring endoscopic bolus removal from swallow onset to the contractile deceleration point
frequently leads to diagnosis and occurs in 30–50% of (which signifies the time of transition of oesophageal
patients.66 In children, dysphagia is less prevalent than in emptying into the stomach). Distal latency is the latest
adults with pain, vomiting or feeding difficulties being metric to be added to the Chicago classification and is
the most frequent clinical manifestations. As outlined thought to describe contractions of abnormally early
above, the most frequently observed endoscopic features onset and rapid onset better than the contractile front
of eosinophilic oesophagitis are rings, furrows, exsudates velocity. The physiological and pathological basis under-
and strictures (Figure 2) but normal endoscopic appear- pinning the utility of the five metrics is well supported by
ance can be observed in up to 25% of patients (adults published evidence.20,67,68
and children) with eosinophilic oesophagitis, thus justi- As previously mentioned, defining ‘normal’ oesopha-
fying the need to obtain oesophageal biopsy samples in geal motility is just as important as determining a motor
all patients with unexplained dysphagia.13 For accurate disorder. A normal manometry study could identify a
diagnosis, at least four biopsy samples from two different patient whose symptoms might be caused by visceral
locations (that is in the distal and proximal oesophagus) hypersensitivity (see section on functional dysphagia).
should be taken.7 A reliable measurement of EGJ pressures is also critical
because the diagnostic algorithm purposefully empha-
Primary oesophageal motor disorders sizes the identification of EGJ dysfunction as a key diag-
Oesophageal manometry can reveal manometric features nostic parameter to confirm or exclude achalasia. Among
of bolus swallowing such as the oesophageal peristaltic the various diagnostic categories, Category 1 disorders

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a
i ii iii mmHg
0
150
5
100
10

15 50
No pressurization
20 CFV = 42 cm/s 0
25
Length along the oesophagus (cm)

DL = 3.0 s
30

IRP = 18.4 mmHg 5s IRP = 33.7 mmHg 5s IRP = 26.4 mmHg 5s

35
b
i ii iii
0
150
5

10 DCI = 16,305 mmHg•s•cm

100
15
CFV = 17 cm/s
20
50
25 DL = 3.0 s
20
30
0
35 5s 5s 5s

Figure 5 | Examples of major oesophageal motility disorders never seen in healthy individuals. a | The three achalasia
subtypes, (i) type I no compression (ii) type II with compression (arrow) (iii) type III (spastic achalasia). b | Examples of non-
achalasic major motor disorders. (i) oesophageal spasm (premature contraction, short distal latency) (ii) hypercontractile
‘jackhammer’ oesophagus (DCI >8,000 mmHg.s.cm (iii) absent peristalsis. Abbreviations: CFV, contractile front velocity;
DCI, distal contractile integral; DL, distal latency; IRP, integrated relaxation pressure.

(achalasia subtypes) are considered most important.19 recordings.71 Hence, patients meeting criteria for EGJ
HRM criteria can be used to distinguish three predomi- outflow obstruction, but who do not demonstrate evi-
nant achalasia subtypes (Figure 5), namely classic (type I) dence of distal compartmentalized pressurization (or
achalasia without compression, type II (achalasia) other evidence of interrupted trans-EGJ flow) might not
with compression and type III (spastic achalasia).69,70 have obstruction even though they have been classified
Importantly, achalasia subtyping in this way seems to be as such. Finally, in the case of patients with Category 3
predictive of response to interventions designed to ablate and 4 disorders, corroboratory evidence of symptom
flow resistance at the EGJ.70 association with motor patterns (for example, chest
If an achalasia subtype is not seen then a Category 2 pain with spasm or hypercontractility of the oesopha-
disorder, such as EGJ outflow obstruction, needs to be gus) or corroborative abnormalities (such as symptoms
excluded. Category 2 disorders include a subgroup of of hold-up or evidence of extreme bolus retention with
patients with some preserved peristalsis and typically frequent failed peristalsis) might be needed to classify
distal compartmentalized pressurization, which is a them as being clinically meaningful. Motor patterns in
marker of abnormal pressurization of the bolus ‘sand- Category 4, such as weak peristalsis with large breaks and
wiched’ between the advancing contractile front and bolus retention, are seen in control cohorts,72 therefore,
the EGJ. This subgroup of patients has been suggested the clinical significance of these patterns in i­solation
to represent an achalasia variant or early manifestation is unclear.
of achalasia.69
Beyond the achalasia subtypes and variants the clini- Functional dysphagia
cal significance of abnormal Chicago classification According to the Rome III classification, functional
findings might be less clear. The mechanisms that gen- dysphagia is defined by “a sensation of abnormal bolus
erate EGJ pressure are complex and the 4 s integrated transit through the oesophageal body after exclusion
relaxation pressure measurement reflects the composite of structural lesions, GERD and histopathology-based
effects of pressure generated by both the intrinsic lower oesophageal motor disorders”.3 The definition requires
oesophageal sphincter and the extrinsic crural dia- exclusion of organic stricture, eosinophilic oesophagi-
phragm sphincter.19 Importantly, the complexity of pres- tis and well-characterized primary oesophageal motil-
sure generation can produce erroneous high pressure ity disorders by appropriate investigations such as

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© 2014 Macmillan Publishers Limited. All rights reserved
REVIEWS

Dysphagia standard 10 × 5 ml liquid protocol. Solid swallows or

ingestion of a standardized meal during manometry
Oropharyngeal dysphagia might demonstrate a link between the onset of bolus
hold-up symptoms and failure of the oesophageal
Oesophageal dysphagia
body to physiologically compensate for an increasing
workload for effective bolus transport. Such findings
would again be consistent with a primary motor dis-
Upper gastrointestinal endoscopy and biopsies order and not functional dysphagia. 25,73 Similarly, in
Fluoroscopy
patients with dysphagia who have oesophageal motil-
ity determined to be ‘normal’ on manometric criteria,
Abnormal Normal
sophisticated investigations that combine and integrate
Obstructive dysphagia Nonobstructive dysphagia
oesophageal pressure and impedance recordings seem to
reveal subtle pressure-flow and mechanical abnormali-
ties, which could explain symptoms.35,36,74,75 Impedance
Malignant stricture Oesophageal manometry plani­metry 42 might also improve detection of subtle
Benign stricture (EPT)
Eosinophilic oesophagitis abnormalities. Although subtle, such findings argu-
Extrinsic compression ably suggest a neuromechanical dysfunction and not
n­ecessarily f­unctional dysphagia.
Achalasia Minor motility disorders*
Diffuse oesophageal spasm Functional dysphagia Conclusion
Absent peristalsis
Hypercontractile ‘jackhammer’ oesophagus Oesophageal dysphagia is a common symptom that
EGJ outflow obstruction encompasses a wide spectrum of aetiologies, from neo-
Figure 6 | Diagnosis algorithm for oesophageal dysphagia. *Minor motor disorders plasia to functional disorders. A thorough patient history
are rapid contractions, weak peristalsis, frequent failed peristalsis and and endoscopy with oesophageal biopsies are the two
hypertensive ‘nutcracker’ oesophagus. Abbreviations: EGJ, oesophagogastric most important first steps for diagnosis (Figure 6).
junction; EPT, oesophageal pressure topography. Fluoroscopy might be useful to evaluate rings, webs and
hiatal hernia. Once obstructive dysphagia has been ruled
out, oesophageal manometry is the key investigation,
endoscopy and biopsy, barium swallow and oesopha- best performed with HRM to characterize oesophageal
geal manometry (HRM with oesophageal pressure motility. Major oesophageal motor disorders detected
topography). Some degree of oesophageal dysmotility, can be defined according to the Chicago classification.
combined with increased intraoesophageal sensory The clinical relevance of other motility disorders remains
perception, could be involved in the pathogenesis of questionable. Whether more sophisticated investigations
functional dysphagia. 3 However, if a primary motor than the ones currently in use will improve detection of
disorder, such as achalasia, EGJ outflow obstruction, subtle abnormalities in bolus transport and perception
diffuse oesophageal spasm, absent peristalsis or hyper- and thus help to identify a subgroup of patients with
contractile ‘jackhammer’ oesophagus, is seen then this functional dysphagia needs to be determined.
finding would be inconsistent with functional dyspha-
gia. As the clinical significance of minor oesophageal
motor abnormalities such as weak peristalsis (peristaltic Review criteria
breaks), frequent failed peristalsis, rapid contractions For the purpose of this Review, articles were selected in
and hypertensive ‘nutcracker’ oesophagus is less clear, PubMed database among full-text papers published in the
then these so-called abnormalities might not necessar- past 15 years in English that were identified using
ily exclude functional dysphagia.19 Provocative meas- the search terms “dysphagia”, “functional dysphagia”,
ures such as multiple rapid swallows or solid swallows “eosinophilic oesophagitis”, “oesophageal motor
disorders” and “achalasia”.
could reveal a motor dysfunction missed using the

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