Rheumatology

Diffuse connective tissue diseases (DCTD) under which umbrella come systemic lupus erythematosus,
scleroderma, inflammatory disease of muscle and rheumatoid arthritis. Each of these may be associated
with Sjögren’s syndrome.

The WHO has categorized rheumatological disorders into four major categories

1. Back pain (48%)

2. Osteoarthritis (31%)

3. Soft tissue rheumatism (12%)

4. Inflammatory rheumatic diseases (9%).

Laboratory Investigations

A. Erythrocyte sedimentation rate (ESR): It is common to find very high ESR, often exceeding 100
mm/hour in active rheumatoid disease (RA), systemic lupus erythematosus (SLE) and infective
arthritis
B. C-reactive protein (CRP): This is a beta globulin which is absent in normal plasma but appears in the
presence of different types of inflammatory arthritis. CRP is an acute phase serum protein that is
synthesized by hepatocytes. This protein is capable of reacting with the capsule of pneumococci,
and hence this name. The CRP levels rise by up to 100 folds during infection, tissue injury and
inflammation. Though the physiological role of CRP is not known, it may contribute to innate
immunity and suppression of autoimmune processes. Estimation of CRP level is a reliable
investigation to identify inflammatory processes and follow up their progress. The test can be
quantitated. CRP is more expensive than ESR.
The advantages of CRP over ESR
1. More rapid procedure; only a few minutes.
2. CRP is positive even before ESR starts rising.
3. CRP can be quantified by serial dilution.
4. It helps to distinguish between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
In RA it is elevated, whereas in uncomplicated SLE it is not.

Sjögren’s syndrome, polymyositis, dermatomyositis, liver cirrhosis, sarcoidosis and several chronic
infections including tuberculosis, leprosy, kala-azar and filariasis may lead to elevation of CRP.
Tobacco smoking, obesity, diabetes mellitus and hypertension lead to mild elevation of CRP
baseline. Higher levels of CRP have been associated with increased risk of myocardial infarction
Both ESR and CRP are non-specific markers of joint inflammation and connective tissue diseases. In
a case where diagnosis has been made, changes in ESR can be estimated for treatment and follow-
up.
 C. Serological markers
1. Rheumatoid factor (RF): This consists of different types of immunoglobulins and it is seen most
frequently in rheumatoid arthritis. Their presence is detected by several tests such as sheep red cell
agglutination test (Rose Waaler), latex fixation test and other slide agglutination tests. RF is present
in a smaller proportion of patients with systemic lupus erythematosus (SLE), progressive systemic
sclerosis (PSS), mixed connective tissue (MCT) disease and others. Based on the demonstrable
presence of RF, arthritis can be broadly classified into seropositive and seronegative types.

2. Antistreptolysin-O titer (ASO titer): ASO is the antibody produced against streptolysin produced
by Streptococcus hemolyticus. Presence of ASO titer in excess of 400 Todd units should suggest
active or recent infection by Streptococcus.

3. Antinuclear factors (ANF): These are also known as antinuclear antibodies (ANA). Several
components of the nucleus elicit antibody response in the host and detection of these components
help to diagnose different rheumatic diseases. ANAs are immunoglobulins, directed against nuclear
components such as DNA, RNA, histones centromere and others. Identification and estimation of
levels of ANA are of great diagnostic help.

4. Serum complement levels: Components of the complement system such as C3 and C4 are
consumed during antigen-antibody reaction and so levels of C3 and C4 may be reduced generally or
selectively.

5. Lupus erythematosus (LE) cell phenomenon: This is a test to detect phagocytosis of nuclear
material by neutrophils seen in active SLE. Rarely the test is positive in RA and allergic states.

6. Antineutrophil cytoplasmic antibodies (ANCAs) These are antibodies directed against the
granules present in the cytoplasm of neutrophils and monocytes. Based upon their pattern and
immunofluorescence they have been classified into three types.
1. Cytoplasmic—cANCA—directed against proteinase 3
2. Perinuclear—pANCA—directed against myeloperoxidase
3. Atypical—xANCA—antigen specificity not clear

7. Anti-phospholipid antibodies (APLA): These are acquired antibodies which are heterogeneous,
directed against plasma proteins bound to phospholipids.

8. Serological test for syphilis: False-positive VDRL may be obtained in SLE, especially in those cases
showing the presence of anticardiolipin antibody.

D. Biochemical tests: Serum uric acid is elevated in gout. Blood glucose examination: It is important
to exclude diabetes mellitus since it is a very common cause of nonarticular rheumatism

E. Synovial fluid examination: Synovial fluid should be examined for its mucus content, cells, crystals
and viscosity. Diagnostic findings are obtained in different types of arthritis.
 F. Arthroscopy and synovial biopsy: Several joints can be inspected by direct arthroscopy. Diagnostic
findings are present in many cases. Biopsy and several surgical procedures can be done through the
arthroscope.

G. Determination of HLA status: Several rheumatological disorders show strong HLA associations, e.g.
ankylosing spondylitis (AS) and other seronegative spondyloarthropathies show high prevalence of HLA
B27. Except HLAB27, which is present in over 75% of cases of AS no other laboratory test is diagnostic of
the condition.

H. Imaging procedures: X-ray examination of the bones an joints.

CT Scanning and MRI :CT scanning and MRI have become very specific investigations in rheumatological
disorders. CT scan can reveal the anatomical details particularly in the vertebral column, skull bones and
in joints. MRI is very useful to bring out the details of cartilage inside joints, especially the semilunar
cartilages inside the knees.

Rheumatoid Arthritis:
Pathology

Articular lesions: Most marked changes are seen in the joints. The earliest change is in the synovial
membrane which shows congestion, infiltration by mainly CD4+ lymphocytes, plasma cells and
macrophages. Synovial effusion occurs. Muscles around the joint also show mononuclear cell infiltration.
Synovium shows fibrinoid degeneration surrounded by infiltration with fibroblasts and mononuclear
cells. The synovial membrane is thickened, hyperemic, and edematous lesions. It proliferates to form
villi which fill the joint. Later, vascular proliferation invades the articular cartilage to form a pannus.
Irreversible destruction of cartilage occurs in the later stages of the disease. The proliferated synovial
membrane which invades cartilage, ligaments and subchondral bone centripetally liberates proteolytic
enzymes which aggravate the destructive process.

Extra-articular lesions: Other tissues are affected to varying degrees. Basic pathology is the same as in
the synovium. Lesions are seen in the skin, lungs, heart, liver, nervous system, and eyes. The small blood
vessels may be affected. They show intimal hyperplasia, perivascular round cell infiltration, and
occasionally necrotizing panarteritis. Subcutaneous nodules consist of a central areas of fibrinoid
necrosis surrounded by mononuclear cells arranged in a palisade manner.

Articular involvement: The onset is generally insidious and the disease presents as a chronic
symmetrical polyarthritis. Less common presentations include: (1) acute polyarthritis, (2) oligoarthritis,
(3) acute monoarticular arthritis, (4) chronic monoarticular arthritis, and (5) systemic disease with fever,
sweating, leukocytosis and pleural effusion in addition to arthritis

Any diarthrodal joint may be inflamed. Arthralgia, arthritis, muscle wasting, tendonitis, tendon rupture,
and deformities constitute the main lesions. The affected joints are warm, painful, and swollen.
Movements are restricted, especially in the morning after sleep (morning stiffness) and after periods of
resting. Classic lesions are in the joints of the hands and feet. Metacarpophalangeal,
metatarsophalangeal , and proximal interphalangeal joints are inflamed most frequently. Wasting of the
small muscles of hand may develop due to disuse and direct muscle involvement.

In the hands, there is the typical ulnar deviation of the metacarpophalangeal joints. Sometimes, there is
anterior subluxation of metacarpal heads and medial dislocation of the extensor tendons. Swan neck
deformity of the fingers consists of hyperextension of the proximal interphalangeal joints and flexion of
the distal interphalangeal joints. This deformity impairs effective hand grip. Sometimes, the extensor
expansion overlying the proximal interphalangeal joint ruptures resulting in the dorsal protrusion of the
head of the proximal phalanx. This leads to flexion of the proximal interphalangeal joint and
hyperextension of the distal interphalangeal joint (boutonnière or button hole) deformity. The extensor
tendons may undergo attrition, these result in loss of extension of the fingers (dropped fingers). The
thumb may show a ‘Z’-shaped deformity (Hitch-hiker’s thumb). Large joints like the knees, wrists,
ankles, elbows, and shoulders may also be involved. Tense synovial effusions may develop in the knees.
Baker’s cysts are tense cysts developing in the popliteal fossae as a result of collection of synovial fluid.
These may occasionally rupture giving rise to a painful and tender swelling on the calf. Lateral
subluxation of the knee joint is also very common. Chronic arthritis develops which leads to permanent
deformities.

Deformities are also common in the feet. Hammer toe is flexion at the proximal interphalangeal joint
and hyperextension at the metatarsophalangeal joint. Hallux valgus (lateral deviation of the big toe) may
develop. The arches of the feet may be lost due to affection of the joints and ligaments.