Rheumatology — Short Cases

15 Rheumatology—Short Cases Chak-Sing Lau, Carman Ho, Temy Mo-Yin Mok, and Raymond Woon-Sing Wong Overview When presented with a patient with arthritis, a detailed examina- tion is essential to ascertain the diagnosis and to determine the severity of the disease and the nature and extent of the investiga- tions to undertake. General observation provides much information; the patient may have difficulty sitting on or rising from a chair, have an abnor- mal gait or show reluctance to shake hands for fear of pain. The number and the distribution of joints affected are impor- tant, for example: * Gout and septic arthritis tend to present as a monoarthritis (one joint). * Spondyloarthritis including ankylosing spondylitis and entero- pathic arthritides are oligoarticular (4 or fewer joints involved). * Rheumatoid arthritis and systemic lupus erythematosus are polyarticular (affecting 5 or more joints). A proximal and symmetrical distribution suggests rheumatoid arthritis and other connective tissue disorders. An asymmetrical presentation favours the diagnosis of spondyloarthritis. In spondyloarthritis, there may also be axial joint involvement with spinal and lower back pain, and dactylitis.

220 Problem-Based Medical Case Management To assess joint function ask simple questions about: difficulty dressing, washing unaided, working in the kitchen, climbing up and down stairs, getting in and out of a car, etc. On inspection of any joint: look for erythema, swelling, muscu- lar atrophy resulting from disuse and deformity. The range of active movement should be assessed, so that limi- tation of joint movement is noted before palpation. On palpation, joint tenderness should be noted. An increase in skin temperature indicates active inflammation. The type of swelling may be appreciated (thickened synovium has a boggy feeling; osteophytes feel hard and irregular). Joint effusion may be demonstrated and crepitation can be felt (palpable crepitation caused by bone and cartilage irregularities). Grip strength can be assessed either by asking the patient to squeeze the examiner’s second and third digits or with a modi- fied sphygmomanometer. Deformities are classified as either fixed or reducible, and in accordance with their deviation from the normal anatomical position (e.g., valgus, varus, ulnar, radial, flexion, etc.) A comprehensive and systemic examination should also be carried out to reveal extra-articular features such as: Episcleritis, nodules, and vasculitis in rheumatoid arthritis. Skin and nail lesions of psoriasis. Iritis, mucocutaneous lesions, and cardiac complications in ankylosing spondylitis. . Conjunctivitis and urethritis in Reiter’s syndrome. Tophus deposition in gout. Septic vesicular lesions (pustules) in gonococcal arthritis. In suspected connective tissue disorders, a thorough examina-. tion of all systems including urinalysis is necessary, as many are multisystem conditions. The following features are particularly noteworthy: .

Case 15.1 Rheumatology 221 + Though patients may present with joint pain, synovitis and joint deformities are not commonly encountered. + The classical malar rash of systemic lupus erythematosus is found on exposed areas of the patient’s face and is commonly known as “butterfly rash”, having two “wings” on the malar areas and its “body” on the nasal bridge. The nasolabial fold is often spared. + Many patients have small vessel vasculitis, commonly at the following sites: Ulnar aspect of the elbow. Nail fold, bed and edge. Lower limbs. - Fundi. * Vaculitic purpuric lesions are palpable and may be tender and associated with limb oedema. Note: thrombocytopenic purpuric lesions are macular and non-tender. * Raynaud’s phenomenon and acrocyanosis are common. * Serositis is common in systemic lupus erythematosus. Keratoconjunctivitis sicca is common in most connective tissue disorders. 15.1 Dermatomyositis Classical signs . Heliotrope (lilac colour) facial rash Periorbital oedema Photosensitive rash on sun-exposed areas, e.g., the “V” neck sign Gottron’s patches: scaly erythematosus, violaceous rash on the dorsal aspects of the metacarpophalangeal and proximal inter- phalangeal joints Nail fold vessel dilatation Nail edge vasculitic lesions/digital vasculitis Raynaud’s phenomenon Calcinosis cutis Muscle tenderness is not always present, and wasting occurs late. .

222 Problem-Based Medical Case Management Case 15.1 * Proximal muscle weakness affecting the shoulders and pelvic girdle. Patients have difficulty getting out of a chair or bed, rising from a squatting position, and lifting the upper limbs (e.g., combing of hair). » Cardiac dysrhythmias » Aspiration pneumonia due to oesophageal dysmotility * Pulmonary fibrosis * Signs of an associated connective tissue disorder * Signs of an underlying malignancy Causes * Dermatomyositis exists in two forms: juvenile and adult. » Peak age of onset is bimodal; 10-15 and 45-55 years. * Female-to-male ratio is 3:1. » The majority of cases are idiopathic. * Some cases have an associated underlying connective tissue disorder such as systemic lupus erythematosus. e About 10-15% of adult cases are associated with a malignancy (e.g., carcinomas of the nasopharynx, lung, stomach, pancreas, breast, cervix, ovary and prostate, and Hodgkin’s lymphoma). « Nasopharyngeal carcinoma is the most commonly associated underlying malignancy in some parts of China and Asia. Important differential diagnoses » Few differential diagnoses if patient presents with dermatomyositis. ! « For polymyositis without skin manifestations, the differential diagnosis includes: drug and toxin induced myopathies (e.g., statin-induced myositis), rhabdomyolysis, metabolic myopathies such as hypo- or hyperthyroidism, acromegaly, and infective myositis. .

Case 15.1 Rheumatology 223 Important investigations Serum creatine kinase level, often > 2000 Iu/L. Other muscle enzyme levels (aspartate transaminase and lactate dehydrogenase) are often increased. Electromyography may show spontaneous polyphasic motor- unit action potentials of low amplitude and of short duration. Muscle biopsy may show lymphocytic infiltration and muscle NEcrosis. Magnetic resonance imaging of the muscles may show only non-specific inflammatory changes. Tests for anti-nuclear antibodies may be positive, but are non-specific. Anti-Jo-1 antibodies are found in 20-30% of patients, and are associated with pulmonary fibrosis. Anti-melanoma differentiation-associated protein 5 (Anti- MDA) antibodies have been reported in up to 20% of several Asian populations. They are often associated with amyopathic dermatomyositis and progressive interstitial lung disease. Pitfalls and tips The skin rashes are characteristic and seldom cause confusion. Muscle tenderness is not a prerequisite. An underlying malignancy should be looked for in all adult patients. High dose corticosteroid, e.g., prednisolone 1 mg/kg/day is needed. Clinical monitoring of disease activity is more important than blood biochemistry. Skin rashes take up to 2-3 months to disappear. A rise in creatinine kinase without significant deterioration of muscle power does not always warrant augmentation of the Steroid dosage. In patients with malignancy associated dermatomyositis/poly- myositis, any relapse of the skin and/or muscle disease should alert the physician to possible recurrence of the malignancy.

224 Problem-Based Medical Case Management Case 15.2 15.2 Gout Classical signs Acute monoarthritis is common; typically, the joint is red, warm, swollen, excruciatingly painful, and tender. The first metatarsophalangeal joint is the most commonly involved. Other peripheral joints such as the ankle and knee may also be affected. Desquamation of the skin overlying the affected joint may develop a few days after onset of the acute arthritis. Tophus deposition (cream-coloured nodules on the ear lobes, interphalangeal, and metatarsophalangeal joints) Stigmata of chronic alcohol intake (parotid swelling, liver palms, etc.) Features of uraemia Causes Under-excretion of uric acid: primary or secondary to renal impairment or drugs (e.g., diuretics, pyrazinamide). Overproduction of uric acid: primary or secondary to excessive dietary intake, particularly alcohol use, lymphoproliferative disorders, psoriasis, and treatment with cytotoxic agents. Important differential diagnoses For gouty tophi: — Rheumatoid nodules: both gouty tophi and rheumatoid nodules may be found at the extensor surface of the elbow. However, rheumatoid nodules are often firmer, more discrete and smaller in size, and there may be associated vasculitic lesions. : — Xanthomata: these lesions are usually found over large tendons such as the Achilles’ tendon. For acute arthritis:

Case 15.2 Rheumatology 225 — Septic arthritis: clinically, the two conditions are almost indistinguishable. Microbiological examination is a must in cases of doubt. — Traumatic arthritis: a careful history of trauma to the affected joint is useful, though acute gout may also be precipitated by trauma. Important investigations + Blood tests: uric acid, renal function tests, and a complete blood picture « Joint fluid: cell count, culture, and microscopy. Synovial fluid white cell count is markedly increased (> 50 x 10°/L) with neu- trophil predominance. Polarized microscopic examination may reveal negatively birefringent needle-shaped crystals, some of which may be engulfed by a neutrophil. Gram stain and culture are needed to exclude septic arthritis. * X-ray of the relevant joints: soft tissue swelling may be the only abnormal sign in cases of acute gout. Punched out erosive lesions may be seen in chronic recurrent gout with tophaceous deposition. Discussion * How do you manage this patient during an acute episode? Acute gout is one of the most painful medical conditions known. Adequate pain control is essential and may be achieved with full doses of non-steroidal anti-inflammatory drugs. However, if non-steroidal anti-inflammatory drugs are contraindicated (e.g., due to renal failure or recent peptic ulceration), oral col- chicine (loading dose no longer recommended) or intralesional steroid injection may be considered. Adequate hydration is also important. How do you manage this patient in the long term? Removal of the underlying cause is important. Thus, alcoholic patients should be discouraged from drinking, and diuretics should be discontinued. Referral to a dietitian for advice on a

226 Problem-Based Medical Case Management Case 15.2 low-purine diet is useful. Uric acid lowering drugs (e.g., allopu- rinol) should only be considered if there is tophaceous disease, gout occurring > 2 times per year, coexistent renal impairment or past history or urolithiasis, with a view to preventing uric acid uropathy. Allopurinol treatment is sometimes associated with a potentially life-threatening systemic allergic reaction and patients in receipt of this drug should be closely monitored. Febuxostat, a non-purine xanthine oxidase inhibitor, may be considered. Uricosuric agents such as probenecid should be avoided in patients with renal impairment. Pitfalls and tips Acute gout may be precipitated by trauma, dietary excess, alcohol, and starvation. Remember to ask about alcohol intake and the use of diuretics. Serum uric acid should not be relied on as a diagnostic investi- gation, as it may be normal during an acute gouty attack. Patients often give a history of previous similar acute episodes of arthritis. Demonstration of characteristic uric acid crystals in the syno- vial fluid is the gold-standard diagnostic test. Chronic knee pain and hyperuricaemia are NOT consistent with gout. Joints near the core of the body, e.g., shoulder, spine, and hip are not affected. Septic arthritis and acute gout can coexist. Septic synovial fluid can also contain monosodium urate crystals. Therefore, all synovial fluid from suspected gouty joints should be sent for microscopy and culture. Treatment for sepsis should also be instituted whenever there is doubt regarding the diagnosis.

Case 15.3 Rheumatology 227 15.3 Nodal osteoarthritis Classical signs The prevalence increases with age, and females are slightly more commonly affected. Herberden’s nodes: bony articular nodules located on the distal interphalangeal joints Bouchard’s nodes: bony articular nodules located on the proxi- mal interphalangeal joints The nodules are bony and firm without much signs of inflammation. The nodules may be tender on palpation. There may be restriction of joint movement. Osteoarthritis may also be commonly found at the first carpo- metacarpal joint, first metatarsophalangeal joint, knee, and the cervical and lumbar spine. Hip osteoarthritis is uncommon in Chinese. Coarse crepitations may be elicited in the knee. No specific extra-articular manifestations apart from other pathologies related to ageing. Causes Idiopathic Associated with ageing Chronic use, e.g., chopstick arthropathy which is probably related to chronic use of the affected joints (second and third proximal and distal interphalangeal joints). Important differential diagnosis Rheumatoid arthritis: rheumatoid arthritis is a symmetrical inflammatory proximal polyarthritis. Distal interphalangeal joints are seldom affected in rheumatoid arthritis while osteo- arthritis seldom affects the metacarpophalangeal joints and wrists.

228 Problem-Based Medical Case Management Case 15.4 Spondyloarthritis including psoriatic arthritis: spondyloarthritis is an inflammatory arthropathy. Many patients are young or middle-aged. Often there is associated spondylitis. Important investigations No specific diagnostic blood test X-rays show loss of joint space, periarticular sclerosis, osteo- phyte formation, and subchondral cysts. Pitfalls and tips Nodal osteoarthritis may be deforming, but unlike rheumatoid - arthritis, the metacarpophalangeal joints, wrists, ankles, and 2nd to 5th metatarsal phalangeal joints are not affected. Radiological abnormalities correlate poorly with clinical symptoms. Lack of signs of inflammation excludes active rheumatoid arthritis. Lack of skin psoriasis and nail changes excludes psoriatic arthritis. False positive rheumatoid factor is not uncommon in the elderly. A positive rheumatoid factor test in a patient with non- inflammatory nodal osteoarthritis is not diagnostic of rheuma- toid arthritis. | False positive rheumatoid factor test is often low level. , Disease-modifying anti-theumatoid arthritis drugs are not needed. . 15.4 Psoriatic arthritis Classical signs Spinal disease (sacroiliitis and spondylitis): ~5% Predominantly distal interphalangeal joint disease: ~10% Symmetrical/asymmetrical polyarthritis: ~35%

Case 15.4 Rheumatology 229 « Asymmetrical oligoarthritis: ~50% « Look for signs of inflammation: redness, soft tissue swelling, warmth, and tenderness. + Cutaneous psoriasis: extensor surfaces of limbs, scalp, peri- umbilicus, lower back + Pitting nail lesions with or without hyperkeratosis + Dactylitis + Tendonitis, e.g., Achilles’ tendonitis + Uveitis Causes + About 10-15% of patients with cutaneous psoriasis have arthritis. * Familial predisposition: family members of patients with psori- atic arthritis have up to 50 times increased risk of arthritis. + About 50-75% of patients with spondylitis and/or sacroiliitis are HLA B27 positive. Important differential diagnoses * Rheumatoid arthritis; presentation ~ with symmetrical polyarthritis Ankylosing spondylitis; presentation with spondylitis and/or sacroiliitis, or oligoarthritis Inflammatory bowel disease associated arthritis. Important investigations No specific diagnostic test The finding of skin psoriasis and an inflammatory arthritis con- firms the diagnosis, though coexistence of skin psoriasis and theumatoid arthritis cannot be excluded. X-rays may show relative absence of periarticular osteoporosis, erosion of terminal tufts, bone osteolysis, and asymmetric and skip spondylitis.

230 Problem-Based Medical Case Management Case 15.5 Discussion Most patients are middle-aged (35-50 years old). Juvenile cases may present as early as age 9-12 years. For patients presenting with peripheral arthritis, there is equal sex ratio. For patients with spinal involvement, male-to-female ratio is approximately 3:1. Pitfalls and tips In about one-third of patients, arthritis precedes skin psoriasis. Skin lesions may be subtle; look for them actively, particularly on the scalp, lower back and periumbilical region. Pitting nail lesions alone are not diagnostic of nail psoriasis, though the diagnosis should be seriously entertained if > 5 pits are evident. Psoriatic arthritis is an inflammatory arthritis. Beware of coex- isting skin psoriasis and osteoarthritis. Degenerative arthritis in a patient with skin psoriasis does not require disease-modifying drug treatment. There is no relationship between the severity of skin disease and that of the arthritis. Systemic steroid, if tapered rapidly, may exacerbate skin psoriasis. Rarely, anti-malarials such as hydroxychloroquine may exacer- bate skin lesions. 15.5 Scleroderma Classical signs Face: smooth, shiny, and tight skin, telangiectasia and hyper- pigmentation, beaked nose, microstomia Hands: smooth, shiny, and tight skin, sclerodactyly, atrophic finger pulps and nails, active digital ulcers or scars, periungal erythema, Raynaud’s phenomenon, nodules of calcinosis

Case 15.5 Rheumatology 231 Flexion contracture; if skin tightening involves region crossing ajoint Look for whitish/bluish discoloration of finger-tips especially in a cold room. Palpate the skin over fingers and face to feel for thickening and tightening. Ask the patient to open his/her mouth to look for a reduced oral aperture. Examine joints for any arthritis or limitation in range of movement. If there is associated pulmonary fibrosis, auscultation of the chest may yield bi-basal coarse crepitations. Important differential diagnoses Other causes of Raynaud’s phenomenon, e.g., dermato/polymy- ositis, vibration-induced white finger syndrome, atherosclero- sis, Buerger’s disease. Overlap syndromes with systemic sclerosis: look for clinical features of other autoimmune diseases. Important investigations Anti-nuclear antibodies: positive in high titre. Anti-extractable nuclear antigen antibody: anti-Scl 70 is present in 25-40% of patients with diffuse systemic sclerosis. Chest X-ray: may show reticular and/or honeycomb changes at both lung bases. Lung function tests: may reveal a restrictive pattern with reduc- tion in forced expiratory velocity and forced vital capacity, increased residual volume, and diminished transfer factor. Barium swallow: may show oesophageal dysmotility and/or reflux.

232 Problem-Based Medical Case Management Case 15.5 Discussion The triphasic colour changes of Raynaud’s phenomenon result from ischaemia (white: vasoconstriction), cyanosis (blue: veno- constriction) and reactive hyperaemia (red: vasodilatation). Some patients present with sclerodermatous skin changes, namely, severe Raynaud’s phenomenon and lupus serology including anti-RNP. The latter patients were formerly known as having the “mixed connective tissue disease”. It is now realized that most of their clinical manifestations eventually become polarized into those of systemic sclerosis or systemic lupus . erythematosus. Such patients are therefore referred to as having undifferentiated connective tissue disease. Severe Raynaud’s phenomenon leads to digital ulceration which may cause superimposed bacterial infection that heals with scarring. Patients with limited forms of systemic sclerosis have sclero- dermatous skin changes affecting the fingers distal to the meta- carpophalangeal joints only. Diffuse cutaneous systemic sclerosis is more often complicated by major organ disease and is thus associated with a poorer prognosis. Treatment is largely symptomatic: vasodilators for Raynaud’s phenomenon, non-steroidal anti-inflammatory drugs for arthritis, proton pump inhibitors for reflux oesophagitis etc.; immunosuppressive drugs may be used to treat inflammatory complications such as low-grade myositis and pulmonary fibrosis. Pitfalls and tips Raynaud’s phenomenon may manifest even if the patient is not exposed to cold. B-blockers exacerbate digital ischaemia and should be avoided - in such patients. It is important to monitor the blood pressure; a sudden increase - may be an early indication of scleroderma renal crisis.

Case 15.6 Rheumatology 233 + Pulmonary function tests are used to monitor lung disease but high-resolution CT scan of the chest is the gold standard for the investigation of possible secondary pulmonary fibrosis. 15.6 Sjogren’s syndrome Classical signs + Dry eyes, with a gritty sensation or feeling of sand therein; they may be complicated by infections. + Positive Schirmer’s test: a sterile strip of filter paper is hooked onto the temporal side of the lower eyelid for 5 minutes. The test is abnormal if the moisture on the filter paper extends less than 5 mm. * Dry mouth: classically, patients complain of difficulty swallow- ing dry food (e.g., crackers), hence the Cracker sign; related complications include: angular cheilitis, dental caries, peri- odontitis, oral candidiasis. * Synovitis of metacarpophalangeal and proximal interphalan- geal joint ¢ Lymphadenopathy * Post-auricular mass, parotid, and submandibular gland swelling * Raynaud’s phenomenon * Rheumatoid arthritis occurs in 50% of affected patients. Important differential diagnoses * Lymphoma * Amyloidosis * Parotid tumour Important investigational findings * Complete blood picture (low white cell and lymphocyte counts) * Raised erythrocyte sedimentation rate

234 Problem-Based Medical Case Management Examination case * Electrolyte changes, e.g., hypokalaemia due to secondary renal tubular acidosis ¢ Elevated serum globulin level ¢ Immune markers in the serum, including: anti-nuclear antibod- ies, anti-Ro and anti-La antibodies, and rheumatoid factor ¢ Hyper-gammaglobulinaemia « Abnormal salivary duct scintigraphy * Abnormal salivary gland biopsy * Abnormalities revealed by fine needle aspiration of parotid/ submandibular mass Pitfall and tips Failure to recognize keratoconjunctivitis sicca complex « Often, the symptoms of eye dryness and itchiness are wrongly attributed to conjunctivitis or allergic symptoms. * Erosive arthritis may mimic rheumatoid arthritis. e Parotid enlargement may be mistaken as lymphoma or carcinoma. » Sjogren’s syndrome may transform into a lymphoma. Recent parotid gland enlargement or lymphadenopathy in a patient with Sjogren’s syndrome should alert the physician of this pos- sibility. Coincidentally, there may also be a drop in the serum levels of rheumatoid factor. Examination case scenarios i. Examine this woman who complains of purplish discolouration of her fingers. Important signs * Tight skin ¢ Small mouth * Sclerodactyly * Thickened skin

Examination case Rheumatology 235 Diagnosis Systemic sclerosis Questions 1. What tests will you do to confirm diagnosis? Antinuclear antibodies: may be positive and in high titre. Anti-extractable nuclear antigen antibody; anti-Scl 70 (present in 25-40% of diffuse systemic sclerosis). Chest X-ray: searching for bilateral basal reticular and/or honeycomb changes. Lung function tests: may reveal a restrictive pattern with reduced forced expiratory velocity and forced vital capacity, increased residual volume, and diminished transfer factor. Barium swallow: may show oesophageal dysmotility and/or reflux. What are the complications? Raynaud’s phenomenon; digital infarcts if severe. Cutaneous ulcers. Calcinosis cutis and secondary infection. Oesophageal dysmotility, reflux oesophagitis, and aspiration pneumonia. Low grade myositis. Pulmonary fibrosis. Pulmonary hypertension. Cardiac arrhythmia. Renal crisis.

236 Problem-Based Medical Case Management Examination case ii. Look at this pair of hands. Important signs ¢ Wasting of hand muscles * Synovial swelling » Ulnar deviation e Swan neck deformity * Z-shaped thumb ¢ Rheumatoid nodule Failure to unbutton clothes Diagnosis Rheumatoid arthritis Question What are your differential diagnoses? * Polyarticular gout and elbow gouty tophi and/or bursitis. However, ulnar deviation, Z-thumb, and swan neck deformities are not found in gout. * Nodular osteoarthritis. However, metacarpo-phalangeal joint and wrist involvement are not found. Further, nodular lesions are not a feature. * Psoriatic arthritis. There may be associated skin psoriatic lesions. Subcutaneous nodules are not a feature of psoriatic arthritis. e Jaccoud’s arthritis of systemic lupus erythematosus but the presence of rheumatoid nodules is against this diagnosis. Jaccoud’s disease is non- erosive, so X-rays of the hand will not show any erosive lesions.