Rheumatology & Autoimmune Diseases
1. What this chapter covers, and how NEET PG actually tests it
Stems give a joint distribution with a rash or systemic feature, an autoantibody panel, or a synovial fluid analysis.
The organising principle is that the pattern diagnoses and the antibody confirms.
Antibodies are used to support a diagnosis already suspected clinically, because almost all of them appear in healthy people and in other diseases, so a positive result without a compatible picture is far more often a false lead than a discovery.
The first division is between inflammatory and mechanical pain.
| Feature | Inflammatory | Mechanical |
|---|---|---|
| Morning stiffness | Prolonged, over half an hour | Brief |
| Effect of activity | Improves | Worsens |
| Night pain | Common | Uncommon |
| Swelling | Present | Absent or bony |
The second division is the distribution itself: how many joints, which ones, and whether the involvement is symmetrical.
2. Rheumatoid arthritis and osteoarthritis
| Feature | Rheumatoid arthritis | Osteoarthritis |
|---|---|---|
| Joints involved | Metacarpophalangeal, proximal interphalangeal, wrist | Distal interphalangeal, proximal interphalangeal, knee, hip |
| Joints spared | Distal interphalangeal | Metacarpophalangeal |
| Pattern | Symmetrical, additive | Asymmetrical, use-related |
| Systemic features | Present | Absent |
The two diseases are separated by which row of finger joints is affected. Rheumatoid arthritis attacks the metacarpophalangeal and proximal interphalangeal joints and spares the distal row; osteoarthritis does the reverse, producing Heberden nodes distally and Bouchard nodes proximally.
Anti-cyclic citrullinated peptide antibody is far more specific than rheumatoid factor and appears earlier, while rheumatoid factor is found in Sjogren syndrome, chronic infection and healthy older people.
Extra-articular disease includes nodules, interstitial lung disease, scleritis, vasculitis and secondary amyloidosis, and it tracks with disease severity and seropositivity.
Atlantoaxial subluxation is the complication that matters before any operation, because neck extension during intubation can cause cord compression, so the cervical spine is imaged before general anaesthesia in longstanding disease.
Methotrexate remains the first-line disease-modifying drug, and biological agents are added when it fails, with the principle being to suppress inflammation early before erosion occurs.
Folic acid is co-prescribed with methotrexate to reduce mucositis, cytopenia and hepatotoxicity without reducing efficacy, and omitting it is a frequent avoidable cause of intolerance.
Methotrexate is given weekly rather than daily, and inadvertent daily dosing has caused fatal marrow suppression, which is why the frequency is written out in words on the prescription.
Tuberculosis must be screened for before any tumour necrosis factor inhibitor, because these agents reactivate latent infection, and in a high-prevalence country that reactivation is common and can be disseminated.
Non-steroidal anti-inflammatory drugs and corticosteroids relieve symptoms but do not prevent joint destruction, which is why disease-modifying therapy is started at diagnosis rather than after failure of symptomatic treatment.
3. The spondyloarthropathies
These share axial involvement, enthesitis, dactylitis, anterior uveitis and an association with a particular tissue antigen, and they are seronegative for rheumatoid factor.
| Condition | Distinguishing feature |
|---|---|
| Ankylosing spondylitis | Sacroiliitis, reduced spinal flexion, bamboo spine |
| Psoriatic arthritis | Distal interphalangeal involvement, nail pitting, pencil-in-cup deformity |
| Reactive arthritis | Follows gastrointestinal or genitourinary infection, with urethritis and conjunctivitis |
| Enteropathic arthritis | Accompanies inflammatory bowel disease |
Inflammatory back pain in a young adult that improves with exercise and worsens with rest is the presentation of ankylosing spondylitis, and it is the reverse of mechanical back pain.
Extra-articular features of ankylosing spondylitis include apical pulmonary fibrosis, aortic regurgitation and anterior uveitis.
Psoriatic arthritis is the one inflammatory arthritis that attacks the distal interphalangeal joints, which places it alongside osteoarthritis in distribution while behaving as an inflammatory disease.
The skin disease can be minimal or hidden in the scalp, natal cleft or umbilicus, so those sites are examined specifically when an inflammatory arthritis appears seronegative.
Nail changes correlate with distal joint involvement, because the nail bed and the distal joint share an enthesis, which is why pitting and onycholysis are looked for.
Dactylitis, the diffuse swelling of an entire digit rather than of individual joints, arises from inflammation of the whole tendon sheath and is characteristic of this whole group.
Enthesitis at the Achilles insertion or plantar fascia is the same process at a different site, and it distinguishes spondyloarthropathy from rheumatoid disease, which inflames synovium rather than entheses.
That single mechanistic difference, synovium against enthesis, explains why the two groups affect entirely different structures and respond to different biological agents.
4. Systemic lupus erythematosus
Antinuclear antibody is sensitive but not specific, so it functions as a screening test and a negative result makes lupus very unlikely.
| Antibody | Value |
|---|---|
| Antinuclear | Sensitive, poorly specific, used to screen |
| Double-stranded DNA | Specific, correlates with activity and nephritis |
| Smith | Highly specific, does not track activity |
| Histone | Drug-induced lupus |
| Ro and La | Sjogren syndrome, neonatal lupus and congenital heart block |
| Antiphospholipid | Thrombosis and recurrent fetal loss |
Complement falls during active disease because it is consumed by immune complexes, so a low complement with a rising double-stranded DNA antibody indicates a flare.
Renal involvement determines prognosis and is silent until advanced, which is why urinalysis is performed at every visit rather than only when the patient feels unwell.
Renal biopsy establishes the class of nephritis, and the class rather than the creatinine determines whether immunosuppression is needed, since a patient with proliferative disease may still have normal function.
The disease disproportionately affects young women of reproductive age, so contraception, pregnancy planning and drug safety in pregnancy are part of routine management rather than occasional considerations.
Pregnancy is timed for a period of quiescence, because conception during active disease markedly increases the risk of flare, pre-eclampsia and fetal loss.
Cyclophosphamide and mycophenolate are teratogenic and must be changed before conception, while hydroxychloroquine and azathioprine are continued.
Drug-induced lupus spares the kidney and central nervous system, carries antihistone antibodies, and resolves on stopping the drug, with hydralazine, procainamide and isoniazid the classic culprits.
Anti-Ro antibody crosses the placenta and can cause congenital complete heart block, so a woman with these antibodies needs fetal cardiac monitoring during pregnancy.
Hydroxychloroquine is continued in essentially every patient with lupus, including through pregnancy, because it reduces flares, organ damage and mortality with an unusually favourable safety profile.
Its one significant long-term risk is retinal toxicity, which is why annual ophthalmological screening is arranged after several years of use rather than at the outset.
4.1 Antiphospholipid syndrome
The syndrome is defined by thrombosis or recurrent pregnancy loss together with persistently positive antibodies, and the antibodies must be confirmed on a repeat sample after an interval.
Repeat testing is required because transient antibodies appear after infection and carry no thrombotic risk, so a single positive result during an acute illness proves nothing.
It occurs alone or secondary to lupus, and it is the reason a young patient with an unexplained arterial or venous thrombosis is investigated for an autoimmune cause.
Warfarin rather than a direct oral anticoagulant is used in the high-risk triple-positive patient, since the direct agents performed worse in trial in this specific group.
5. Other connective tissue diseases
5.1 Systemic sclerosis
| Feature | Limited | Diffuse |
|---|---|---|
| Skin involvement | Distal to elbows and knees, plus face | Proximal as well, including trunk |
| Antibody | Anticentromere | Anti-topoisomerase |
| Major complication | Pulmonary arterial hypertension | Interstitial lung disease and renal crisis |
| Onset of organ disease | Late | Early |
Scleroderma renal crisis presents with accelerated hypertension and acute kidney injury, and it is treated with an angiotensin-converting enzyme inhibitor even when the creatinine is rising.
That is a deliberate exception to the usual caution about these drugs in renal impairment, because the crisis is driven by renin and the inhibitor is disease-modifying rather than merely antihypertensive.
5.2 Sjogren syndrome and inflammatory myopathy
Sjogren syndrome causes dry eyes and mouth from lymphocytic infiltration of exocrine glands, carries Ro and La antibodies, and confers a markedly increased risk of lymphoma.
Inflammatory myopathy presents with symmetrical proximal weakness rather than pain, with a raised creatine kinase and characteristic changes on electromyography and biopsy.
Dermatomyositis adds a heliotrope rash and Gottron papules over the knuckles, and it carries a significant association with underlying malignancy that warrants a search in adults.
Weakness rather than pain is the presenting complaint in myositis, and patients describe difficulty rising from a chair or combing hair rather than aching muscles.
6. Vasculitis
Classification by vessel size determines the presentation, because the size of the vessel determines which tissue is deprived.
| Size | Conditions |
|---|---|
| Large | Giant cell arteritis, Takayasu arteritis |
| Medium | Polyarteritis nodosa, Kawasaki disease |
| Small, antibody-associated | Granulomatosis with polyangiitis, eosinophilic granulomatosis, microscopic polyangiitis |
| Small, immune complex | Immunoglobulin A vasculitis, cryoglobulinaemic vasculitis |
Giant cell arteritis presents in the elderly with headache, scalp tenderness, jaw claudication and visual loss, and it is associated with polymyalgia rheumatica.
Corticosteroid is started immediately on clinical suspicion, before biopsy, because vision lost to this disease does not return and the biopsy remains informative for a week or two afterwards.
Takayasu arteritis affects young women, classically of Asian origin, producing absent pulses and blood pressure differences between limbs.
Polyarteritis nodosa affects medium vessels, is associated with hepatitis B, and characteristically spares the lungs, which separates it from the antibody-associated group.
Granulomatosis with polyangiitis affects upper airway, lung and kidney together and carries antibodies to proteinase 3, while eosinophilic granulomatosis is preceded by asthma and eosinophilia.
The combination of pulmonary haemorrhage with glomerulonephritis defines a pulmonary-renal syndrome, and the differential is short: the antibody-associated vasculitides, anti-glomerular basement membrane disease and lupus.
Anti-glomerular basement membrane disease is separated by a linear rather than granular pattern on immunofluorescence, reflecting antibody bound uniformly along the basement membrane rather than lumpy immune complex deposits.
Immunoglobulin A vasculitis is the commonest vasculitis of childhood, presenting with a palpable purpuric rash over the buttocks and extensor surfaces, abdominal pain, arthritis and nephritis.
Palpable purpura is itself a physical sign of small vessel vasculitis, because inflammation of the vessel wall produces both leakage and the surrounding infiltrate that makes the lesion raised.
A non-blanching rash that can be felt therefore prompts a search for renal and pulmonary involvement rather than reassurance, whatever the patient's age.
7. Crystal arthropathy and the hot joint
| Feature | Gout | Pseudogout |
|---|---|---|
| Crystal | Monosodium urate | Calcium pyrophosphate |
| Shape | Needle | Rhomboid |
| Birefringence | Negative | Positive |
| Typical joint | First metatarsophalangeal | Knee and wrist |
Every acutely hot swollen joint is aspirated to exclude septic arthritis, because gout and infection can look identical and can coexist, and an untreated septic joint is destroyed within days.
Serum urate is frequently normal during an acute attack of gout, because urate precipitates into the joint, so a normal level does not exclude the diagnosis and a raised one does not confirm it.
Urate-lowering therapy is not started during an attack without anti-inflammatory cover, because any abrupt change in urate concentration in either direction can precipitate or prolong an attack.
Established urate-lowering therapy is never stopped during an acute attack for the same reason, and stopping it is a common error made in the belief that the drug is causing the flare.
Pseudogout is associated with haemochromatosis, hyperparathyroidism and hypomagnesaemia, so a young patient with calcium pyrophosphate deposition warrants a search for one of these.
Chondrocalcinosis on a knee radiograph, a thin line of calcification within the cartilage, is the radiological signature of calcium pyrophosphate deposition.
8. The whole-body autoimmune presentations
Several conditions present with fatigue, aches and a positive antinuclear antibody, and separating them prevents both overdiagnosis and missed disease.
Polymyalgia rheumatica causes proximal girdle pain and stiffness in the elderly with a very high inflammatory response but a normal creatine kinase and no true weakness.
The distinction from myositis is that polymyalgia hurts while myositis is weak, and the creatine kinase settles it: markedly raised in myositis and normal in polymyalgia.
Fibromyalgia produces widespread pain with fatigue and unrefreshing sleep, normal inflammatory markers and no objective swelling, and it responds to exercise and centrally acting agents rather than to anti-inflammatory drugs.
A positive antinuclear antibody in a patient with fibromyalgia is common and usually meaningless, since a low titre is found in a substantial proportion of healthy people.
That is the practical reason the antibody is not ordered as a screening test for tiredness: applied to a low-probability population it generates far more false positives than diagnoses, exactly as any test does at low prevalence.
Adult-onset Still disease presents with quotidian spiking fever, an evanescent salmon-coloured rash appearing with the fever, arthritis and a strikingly raised ferritin.
The rash is easily missed because it comes and goes with the temperature spike, so a patient examined between spikes appears to have an unexplained fever with nothing to find.
A ferritin many times the upper limit narrows an undiagnosed fever considerably, since very few conditions raise it that far, and the short list is Still disease, haemophagocytic syndromes and severe liver injury.
Sarcoidosis deserves mention here because it mimics several rheumatological diseases, producing arthritis, uveitis, erythema nodosum and a raised inflammatory response together.
The combination of bilateral hilar lymphadenopathy, erythema nodosum, fever and arthritis has its own name and carries a good prognosis, usually resolving without treatment.
9. Worked examples
Example 1. A patient has symmetrical swelling of the metacarpophalangeal joints with sparing of the distal interphalangeal joints. What is the diagnosis?
Rheumatoid arthritis. The distribution alone establishes it, since osteoarthritis affects the distal row and spares the metacarpophalangeal joints, which is the reverse pattern.
Example 2. An elderly patient has a new headache with jaw claudication and blurred vision. What is the first action?
Start corticosteroid immediately. Biopsy can follow within a week or two and remains informative, whereas vision lost while awaiting confirmation does not return.
Example 3. A patient with lupus has a rising double-stranded DNA antibody and a falling complement. What does this indicate?
An active flare. Complement is consumed by immune complexes during activity, and this antibody tracks disease activity and correlates with renal involvement, unlike the Smith antibody.
Summary
The pattern diagnoses and the antibody confirms, never the reverse.
Inflammatory pain has prolonged morning stiffness and improves with activity; mechanical pain does the opposite.
Rheumatoid arthritis takes the metacarpophalangeal and proximal rows and spares the distal interphalangeal joints.
Osteoarthritis takes the distal row and spares the metacarpophalangeal joints.
Anti-cyclic citrullinated peptide is more specific and earlier than rheumatoid factor.
Rheumatoid factor also occurs in Sjogren syndrome, chronic infection and healthy older people.
Image the cervical spine before anaesthesia in longstanding rheumatoid disease.
Methotrexate is first-line, and suppressing inflammation early prevents erosion.
The spondyloarthropathies share axial disease, enthesitis, dactylitis and uveitis, and are seronegative.
Psoriatic arthritis is the inflammatory arthritis that attacks distal interphalangeal joints.
Ankylosing spondylitis adds apical fibrosis, aortic regurgitation and anterior uveitis.
Antinuclear antibody screens; double-stranded DNA and Smith antibodies confirm.
Double-stranded DNA tracks activity and nephritis; Smith does not track activity.
Falling complement with rising double-stranded DNA indicates a lupus flare.
Lupus nephritis is silent until advanced, so urinalysis is done at every visit.
Drug-induced lupus carries antihistone antibodies and spares kidney and brain.
Anti-Ro crosses the placenta and can cause congenital heart block.
Limited sclerosis has anticentromere antibodies and pulmonary hypertension.
Diffuse sclerosis has anti-topoisomerase antibodies, lung fibrosis and renal crisis.
Renal crisis is treated with an angiotensin-converting enzyme inhibitor despite rising creatinine.
Sjogren syndrome carries a markedly increased lymphoma risk.
Myositis presents with proximal weakness rather than pain, and dermatomyositis warrants a malignancy search.
Vessel size determines the vasculitis presentation.
Start steroids in giant cell arteritis before biopsy, because lost vision does not return.
Polyarteritis nodosa spares the lungs, unlike the antibody-associated vasculitides.
Gout crystals are needle-shaped and negatively birefringent; pseudogout crystals are rhomboid and positive.
Aspirate every acutely hot joint, because gout and sepsis look alike and can coexist.
Serum urate is often normal during an acute attack of gout.
Never stop established urate-lowering therapy during a flare, and co-prescribe folic acid with methotrexate.
Methotrexate is weekly, not daily, and inadvertent daily dosing has caused fatal marrow suppression.
Screen for tuberculosis before any tumour necrosis factor inhibitor.
Polymyalgia rheumatica hurts with a normal creatine kinase; myositis is weak with a raised one.
A low-titre antinuclear antibody is common in healthy people and is not a screening test for fatigue.
Pulmonary haemorrhage with glomerulonephritis has a short differential, and linear immunofluorescence identifies basement membrane disease.
Palpable purpura means small vessel vasculitis and prompts a search for renal and lung involvement.
Hydroxychloroquine is continued in almost all lupus including pregnancy, with retinal screening after years of use.
Antiphospholipid antibodies must be confirmed on a repeat sample, since transient positives follow infection.
Spondyloarthropathy inflames entheses while rheumatoid disease inflames synovium, which is why they affect different structures.
