Rheumatology — Long Cases

16 Rheumatology—IL.ong Cases Chak-Sing Lau, Carmen Ho, Temy Mo-Yin Mok, and Raymond Woon-Sing Wong 16.1 Back pain for two years (ankylosing spondylitis) History A 26-year-old manager complained of on-and-off back pain for 2 years. On several occasions he was woken from sleep by back pain. He did not recall any back injuries. There was stiffness in the early morning, which improved during the day. He had also been having right knee and left ankle pains on and off in the last 6 months. He was a non-smoker and non-drinker. His bowel and urinary habits were unremarkable, and there was no history of urethral discharge or eye problems. There was no family history of joint pains. Physical examination There was decrease in the range of movement of the lumbar spine (in all directions) and tenderness over the left Achilles’ tendon. Chest expansion was normal. There was no peripheral arthritis, pitting of the nails or skin psoriasis lesions. His blood pressure was 150/70 mmHg and an aortic regurgitation murmur was detected. ~N

238 Problem-Based Medical Case Management Case 16.1 Important investigations Complete blood picture was normal, but ESR was raised (45 mm/ hour). C-reactive protein was increased to 2.4 mg/dL (normal < 0.7). Chest X-ray showed no cardiomegaly. Lumbar spine and pelvic X-rays revealed widened sacroiliac joints with an irregular outline and periarticular sclerosis, bilaterally. Echocardiogram revealed mild aortic regurgitation. Questions 1. What are the two important types of back pain in clinical practice and what are the major differences between them? * Back pain may be mechanical or inflammatory in nature. * Simple mechanical back pain is by far the most common cause of lower back pain. It may be idiopathic or associated with minor self-limited injuries such as lifting a heavy object, a fall or a sudden deceleration (as may occur in an automobile acci- dent). The pain is often acute, confined to the lower back, and relieved by rest. The patient may assume unusual postures related to spasm of the sacrospinalis muscles. The diagnosis of - simple mechanical back pain depends upon the description of the injury, localization of the pain, the finding of localized ten- derness, and the augmentation of pain when tension is exerted . on the involved structures. The patient is otherwise well. , + Inflammatory lower back pain is often due to ankylosing spondylitis and related syndromes, collectively known as spon- dyloarthritis. These syndromes have specific characteristics including male predominance, young age of onset, marked . early morning stiffness and pain relieved by exercise and non- steroidal anti-inflammatory drugs. Additionally, often there is peripheral joint involvement and enthesopathies such as plantar fasciitis and Achilles’ tendonitis. Pain is often located in the lower back, with diffuse radiation to the buttock and occasion- _ ally to the lower hamstrings bilaterally. This contrasts with sci- atica, which often radiates beyond the knee level and is usually unilateral.

Case 16.1 Rheumatology 239 2. What are the important extra-articular features to look for in assessing a patient with inflammatory back pain? + In spondylitis there may be: — Evidence of skin psoriasis (scalp, behind ears, periumbilical, natal cleft, as well as in the common sites such as extensor aspects of the elbows and knees and the trunk) and some- times nail dystrophy. — Reiter’s syndrome, with urethritis and painless urethral discharge. - Eye involvement (conjunctivitis and iritis), which is common to all forms of seronegative spondylitis. - Cardiovascular system derangement (aortic incompetence). * Pulmonary restriction resulting from chest wall involvement and lung fibrosis (< 3% of cases) may also ensue. 3. What genetic marker may be helpful for investigating a patient with back pain? * Although HLA B-27 is often found in patients with spondy- loarthritis (> 90% with ankylosing spondylitis, 50-75% with psoriatic spondylitis, and 70% with Reiter’s syndrome), it is not a diagnostic test for any of these conditions. The sensitivity and specificity depend on the relative prevalence of HLA B-27 and spondyloarthritis in different populations. For example, in Chinese, the frequency of HLA B-27 is 6-8%, whilst the prevalence of all spondyloarthritis is between 0.2-0.4%. Thus, HLA B-27 is not useful in diagnosing ankylosing spondylitis or related syndromes. However, a negative test may help for the purpose of exclusion. 4. What is the management strategy for ankylosing spondylitis? Ankylosing spondylitis is a chronic condition, for which coun- selling and patient education are important. Physiotherapy is particularly appropriate, especially back exercises and hydro- therapy. Pain control can usually be achieved by regular use of non-steroidal anti-inflammatory drugs. For patients with periph- eral arthritis, sulphasalazine may be effective. Methotrexate has also been tried, but results are inconclusive. Recently, it has been shown that treatments that target tumour necrosis factor-o and the interleukin-23 / interleukin-17 axis can greatly improve

240 Problem-Based Medical Case Management Case 16.2 symptoms as well as quality of life. However, use of this group of drugs is limited by their high cost and the liability of treated patients to develop tuberculosis and other infectious diseases. Pitfalls and tips = Do not miss subtle signs of psoriasis (lesions in perianal and infra-mammary areas and nail changes). 16.2 A woman with multiple problems (systemic lupus erythematous) History A 35-year-old lady was diagnosed to have systemic lupus erythe- matosus 3 years ago when she presented with polyarthritis, malar rash, and lupus nephritis. She had been treated with corticoster- oid and immunosuppressive agents. She was admitted this time because of fever, chills, and vertigo for 5 days. She also had left-sided chest pain, which was exacerbated by deep breathing. However, there was no history of cough or shortness of breath. Nor was there any dysuria or urinary frequency. She also volunteered that she had increasing joint pains affecting her hands for 1 month, and that her right hip was particularly painful on climbing stairs for the past 6 months. She was taking prednisolone 10 mg/day and azathioprine 100 mg/day. Physical examination She was Cushingoid, febrile (38.2°C), and tired-looking. There was a mild malar rash, and cutaneous vasculitic lesions were detected on both palms. She had tenderness of metacarpophalan- geal and proximal interphalangeal joints of both hands without swelling or increase in temperature. Abduction and adduction of the right hip was limited. There was mild suprapubic discomfort -

Case 16.2 Rheumatology 241 and a pleural rub was audible over the left lower chest posteriorly. There was no organomegaly and central nervous system examina- tion was normal. Urine examination was 2+ for protein and 1+ for red blood cells. Important investigations Complete blood count: anaemia (9.8 g/dL), low white cells (3.2 x 10°/L) and thrombocytopenia (101 x 10°/L). Her serum creatinine level was 120 umol/L and her serum albumin was low (29 g/L). Questions 1. What are the possible causes of fever in this patient? * This patient’s fever may be related to relapse of her underlying systemic lupus condition. However, an infection must be con- sidered and excluded, as the patient is immunocompromised (presently taking prednisolone and azathioprine treatment) and systemic lupus erythematosus itself is an immunocompromis- ing disorder. Finally, coexistence of disease relapse and an underlying infection is not uncommon. 2. What are the possible causes of this patient’s chest pain? * The characteristics of the chest pain suggest a form of serositis, which may be a manifestation of lupus or secondary to a chest infection. Pulmonary embolism with or without infarct may also give rise to pleuritic chest pains, but this complication is less common. 3. What further investigations would you undertake for this patient? * To delineate an underlying infection: a thorough septic workup, including chest X-ray, blood cultures x 2, sputum, urine, and any other secretions as appropriate for microbiological €xamination. To delineate possible disease relapse: serology for anti-double stranded DNA antibodies, serum complement (C3 & C4), Coomb’s test and haemolysis screen.

242 Problem-Based Medical Case Management Case 16.2 4. To determine if there was a renal relapse: urine microscopy and 24-hour urine protein and creatinine estimation, and renal biopsy. ; How should this patient be treated if her problem was sec- ondary to disease relapse alone? 7. complement and/or high anti-dsDNA antibody levels) who is . otherwise asymptomatic? The immunosuppressive drugs need to be augmented (increased steroid dosage and azathioprine may need to be substituted by a more potent agent—e.g., cyclophosphamide, cyclosporine A, mycophenolic acid—particularly if renal relapse is confirmed). Biologic agents such as anti-B cell stimulating factor and anti-CD20 antibodies may be considered. ' . What is the likely cause of this patient’s right hip pain? Bone necrosis of the right femoral head is the most likely, which could be related to chronic steroid use. Alternatively, active lupus itself may also cause this condition as a result of an underlying vasculitis (especially when the patient is in receipt of steroids). . . How would you control this patient’s right hip pain? Physiotherapy is important and non-steroidal anti-inflamma- tory drugs may be used to relieve symptoms. Referral to an orthopaedic surgeon for consideration of surgery is anotherf'L option. Finally, the use of steroid should be judicious and the . dosage kept to the minimum, in order to prevent necrosis of the other hip. Would you treat a patient with active serology (low serum It is important to look for evidence of renal disease, which is often asymptomatic during the early stage. Otherwise, treat- ment in clinically asymptomatic patients should not be esca- lated based solely on stable or persistent serological activity.

Case 16.3 Rheumatology 243 16.3 Recurrent right shoulder pain (rheumatoid arthritis) History A 40-year-old housewife was admitted with right shoulder pain for 2 days. She had a history of multiple symmetrical joint pains of her hands associated with morning stiffness, going back 18 years. The proximal finger joints were particularly affected, her hands were deformed and she could not cook for the family for the last 2 years. She had been on steroid and disease-modifying anti-rheumatic drugs for about 10 years. There was no injury to her shoulder and she did not have any fever. Physical examination She was Cushingoid and there was a buffalo hump. She was afebrile. Her right shoulder was mildly swollen and tender. The range of passive right shoulder flexion/extension was 160°/40°, and active range was 70°/30°, compared to 150°/30° and 130°/30° on the left side. Muscle power was grade 4. There was bilateral ulnar deviation of the metacarpophalangeal joints and swan neck deformity of right index and little fingers. Thenar and intrinsic hand muscle wasting was noted. There was also pes planus (flat foot) and bilateral hallux valgus. Subcutaneous nodules were Present on the ulnar border of both elbows. Important investigations Complete blood count showed normochromic normocytic anacmia (10.1 g/dL), and a raised platelet count of 570 x 10°/L. The ESR was increased to 95 mm/h, and C-reactive protein to 3.8 g/dL (normal < 0.7). The serum albumin was depressed (32 g/L). X-rays of the right shoulder showed soft tissue swelling around the gle- Nohumeral joint.

244 Problem-Based Medical Case Management Case 16.3° Questions 1. 3. arthritis? 5. arthritis. . What are the complications of long-term use of steroid? What are the possible differential diagnoses for this case? ::5 Septic arthritis and ruptured rotator cuff tendon should be excluded because of acute onset. . . What investigations should be performed immediately? Shoulder joint tapping. Synovial fluid should be sent for cell count, gram smear, and culture. Ultrasound for rotator cuff integrity should be performed. . What are the complications of long-standing rheumatoi Tendon rupture, joint deformities, and septic arthritis. . Complications from chronic use of immunosuppressive agents: infection, blood dyscrasia. Amyloidosis, rarely (secondary to long-standing mflamrnatwn) ] Neurological manifestations: mononeuritis (vasculitic), entra c ment neuropathies. Lung complications: pleural effusion, nodules, and fibrosing alveolitis. Increased risk of cardiovascular thrombosis. Others, including: pericarditis, lymphadenopathy and splen: megaly, anaemia, Raynaud’s phenomenon, keratoconjunctiviti Cushingoid features: acne, hirsutism, buffalo hump, and centr: obesity. Others: diabetes, hypertension, cataract, glaucoma, and suscep tibility to infections; gastritis/peptic ulcer, osteoporosis, an avascular necrosis of the hip. . Explain the non-drug measures for treating rheumatoi Provision of necessary counselling and education to panen and relatives about rheumatoid arthritis as a chronic painfl disorder of the joints. Physiotherapy: appropriate exercises to maintain full joir movement and strengthen weak muscles; wax baths, ice pack ultrasound, and weak electrical current stimulation (interferen tial therapy) to alleviate some joint symptoms.

Case 16.3 Rheumatology 245 + Occupational therapy: to provide joint protection by way of aids and appliances which allow sufferers to be independent; chiropodists can advise footwear and provide metatarsal bars to alleviate foot involvement. 6. Describe the types of drugs used to treat rheumatoid arthri- tis patients, and their complications. + Two main types of drug treatment are used: — Non-steroidal anti-inflammatory drugs: These are the main- stay of treatment to relieve symptoms but do not modify the underlying pathology and may produce upper gastrointesti- nal side effects. - Disease-modifying anti-theumatic drugs. These include: methotrexate, sulphasalazine, leflunomide, hydroxychlo- roquine, gold in injectable form, penicillamine and cyclo- sporine A. They induce remission of the arthritis but are associated with numerous potential side effects, including bone marrow suppression, nephrotoxicity, and hepatotox- icity. Early treatment of rheumatoid arthritis with disease- modifying drugs is now advocated, particularly for patients with features predictive of a poor prognosis. The latter include: the presence of rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies, shared epitope positivity and large number of joints involved, extra-articular disease, persistently elevated ESR or CRP, radiographic erosions, and education status. While some patients do well on mono- therapy, others might need a combination of anti-rheumatic drugs for optimal control. Recently, biological agents like inhibitors of tumour necrosis factors-cy, interleukin-6, CD20, and T-cell costimulation have been ?hOWn to be useful and successful in controlling the disease activ- 1ty of patients resistant to multiple disease modifying drugs singly and in combination. Recent evidence also suggests that these bio- logic agents may indeed induce true remissions if they are used ppropriately and early on during the disease.

246 Problem-Based Medical Case Management Case 16.3 Pitfalls and tips Missing the diagnosis of rotator cuff tendon rupture (supraspi- natus tendon) Missing pes planus and deformities of foot: foot arthritis is common, disabling, and often overlooked by physicians.