Rheumatology (Greek rheuma—river) is the study of rheumatic conditions involving the joints, soft tissues, bones, connective tissue disorders, vasculitides, and a number of autoimmune conditions.
• Crystal arthritis: gout and calcium pyrophosphate disease (CPPD)
• Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA)
• Systemic lupus erythematosus (SLE)
• Antiphospholipid antibody syndrome
• Polymyositis and dermatomyositis
• Mixed connective tissue disease/overlap syndromes.
Rheumatology is a specialty driven by pattern recognition. Disease labels often describe a constellation of associated and overlapping features. This can make accurate diagnosis very difficult. The first question is usually ‘Is this inflammatory disease?’ The cardinal sign of inflammatory disease is stiffness, particularly in the morning, of at least 30–45 min duration which contrasts with the few minutes of stiffness reported in OA.
There is no one feature that distinguishes between inflammatory and non-inflammatory conditions. The diagnosis is often led by clinical experience taking into account the whole clinical picture (see Table 31.1).
Table 31.1 Inflammatory versus non-inflammatory disease
| Favours inflammatory disease | Favours non-inflammatory disease |
| Early morning stiffness >45 min | Short-lived stiffness |
| Worse in morning (and sometimes evening as well) | Worse after exertion/in the evening |
| Systemic symptoms (malaise, fatigue, fevers, sweats, anorexia, weight loss) | No systemic symptoms |
| Raised inflammatory markers (depends on stage of disease and joints involved—normal inflammatory markers do not exclude inflammatory disease), normocytic anaemia, thrombocytosis | Normal inflammatory markers (erythrocyte sedimentation rate (ESR) and CRP) |
| Widespread symptoms (caution in pain syndromes, e.g. fibromyalgia) | Regional symptoms (but see text, e.g. monoarthritis) |
Reproduced from NICE CKD Guidelines 2014. Adapted from Kidney Disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease, Kidney Intern. Suppl. Vol 3:1 (1.Jan.2013) pp 1–150.
Regional symptoms suggest regional aetiology—unilateral shoulder pain and restriction is far more likely to be due to ‘frozen shoulder’ or cervical nerve root irritation than primary muscle disease.
• Monoarthritis: suggests crystal arthritis (hot, red, very painful), septic/infective (hot, red, very painful) spondyloarthropathy/seronegative arthritis, monoarticular presentation of polyarticular disease (e.g. rheumatoid, lupus, vasculitis).
• Oligoarthritis (≤4 joints): spondyloarthropathy, rheumatoid, infections, sarcoid, Behçet’s disease.
• Polyarthritis: RA, seronegative inflammatory arthritis, SLE.
• Location of involved joints: first metatarsophalangeal joint (MTPJ) involvement is most likely to be due to gout. First carpometacarpal joint involvement is typical of osteoarthritis. Distal interphalangeal joint involvement is most likely due to osteoarthritis, psoriatic arthritis, or gout.
• Symmetrical: most likely rheumatoid.
• Asymmetrical: psoriatic arthritis, other spondyloarthropathy/seronegative arthritis.
Most rheumatological diseases are treated with a predictable stepwise series of anti-inflammatory and immunosuppressive treatments:
• NSAIDs: a class of drugs with a self-explanatory name.
• Disease-modifying anti-rheumatoid drugs (DMARDs): methotrexate, azathioprine, mycophenolate mofetil, hydroxychloroquine, sulfasalazine, leflunomide.
• Biological agents: anti-TNF, e.g. infliximab.
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Inappropriate prescribing of methotrexate has led to deaths. It is only given weekly for rheumatological disease and should never be co-prescribed with trimethoprim and co-trimoxazole. The risk is of bone marrow suppression and subsequent sepsis.
There are hundreds of rheumatological diseases, but the good news is that you can complete a whole medical career without knowing much about most of them. However, there are a small number of extremely important diseases that you will encounter throughout your career. For this reason, they are high yield both for medical school assessments and afterwards.
RA is the most common autoimmune inflammatory joint disease, and is characterized by a synovitis, which unchecked 
limitation of movement, joint damage, deformity, and destruction, with subsequent loss of function. It is a symmetrical polyarthropathy (affecting multiple joints), usually affecting the small joints first, and is associated with elevated rheumatoid factor/anticitrullinated protein antibody.
Radiological features include LESS (loss of joint space, erosions, soft tissue swelling, soft bones [osteopenia]), panniculitis, and chondrolysis (see Fig. 31.1). Extra-articular features (lung fibrosis, pleural effusion, vasculitis, scleritis/scleromalacia) are rare at presentation. Long-term complications are disability, cardiovascular disease, amyloid, and myelopathy from atlanto-axial subluxation.
Fig. 31.1 The pathology of rheumatoid arthritis: normal joint (left) and rheumatoid joint (right). Reproduced with permission from Warrell, D. et al, Oxford Textbook of Medicine, 2010, Oxford University Press
The last two decades have seen a paradigm shift in treatment of RA, both in the use of the DMARDs that were previously available and the introduction of new biological therapies. Methotrexate is the first-line drug, and may be combined with sulfasalazine and/or hydroxychloroquine. If a patient does not respond to these first-line DMARDs then the next step is biological therapies (anti-TNF, rituximab, tocilizumab, abatacept). NSAIDs are also helpful adjuncts for short-term flare-ups, as are steroids.
The spondyloarthropathies are a group of conditions characterized by seronegativity (i.e. rheumatoid factor negative) in the presence of inflammatory arthritis involving the spine (spondylo-), peripheral joints, and entheses (site of ligament, tendon, and capsule insertion into the bone). They can be classified as axial or peripheral, and include:
• ankylosing spondylitis (AS) & Non-radiographic spondylarthritis
• arthritis/spondylitis associated with IBD (enteropathic)
• undifferentiated spondyloarthropathy.
AS is the typical disease of the spondyloarthropathies, affecting the sacroiliac joints and spine resulting in progressive joint stiffness. AS was typically associated with HLA-B27 affecting mainly men in their 30s who present with persistent lower back or alternating buttock pain (sacroiliitis), and early morning/inactivity stiffness which improve with exercise but not with rest. These patients are often described as having a ‘question mark’ posture, and the best students will spot this typical posture from the bedside. If you are shown a plain radiograph of a spine in the rheumatology clinic the answer may well be bamboo spine with syndesmophytes (new bone formation) of AS. Non-radiographic SpA includes patients with inflammatory back pain that have MRI changes not visible on plain radiographs. Treatment is similar to RA in the form of exercise, NSAIDs, DMARDs, and anti-TNF-α agents to reduce symptoms and improve function, but they do not prevent bony progression.
Typically includes a personal or family history of psoriasis (not essential), nail changes, dactylitis, and/or radiological evidence of new bone formation in the hands or feet. There are a number of clinical patterns of psoriatic arthritis described, including distal interphalangeal joint disease, symmetrical polyarthritis similar to RA, asymmetrical oligoarthritis, spondylitis, and arthritis mutilans. The pattern may alter with time.
Reactive arthritis is an aseptic arthritis triggered by an infectious agent outside the joint, usually occurring 1–4 weeks following urethritis (Chlamydia, Ureaplasma spp.) or dysentery (Campylobacter, Salmonella, Shigella, or Yersinia spp.). There may be polyarticular features, mucocutaneous lesions, conjunctivitis, and enthesitis. Attempts should be made to identify the causative organism including the aspiration and culture/histopathological evaluation of an involved joint to guide antibiotic treatment.
These occur with concomitant ulcerative colitis and Crohn’s disease, and can manifest as peripheral or axial disease, enthesitis, mucocutaneous disease, and anterior uveitis.
The most common cause of inflammatory arthritis, associated with the deposition of monosodium urate crystals within joints and soft tissues. Most commonly presents as recurrent, self-limiting attacks of acute, severe arthritis.
Onset within a few hours (often overnight) of a hot, red, swollen, very painful, and tender joint. The first MTPJ is the most common site (but can affect other limb joints). Look for (and aim to correct) common triggers: heavy alcohol intake, dehydration (especially with diuretic use), joint trauma, surgery, other medical illness, and high-purine diet (beer, spirits, meat, seafood, sugary drinks, fructose). Address metabolic factors (BP, diabetes etc.).
Temperature can be raised in severe attack. One or more warm, red, tender joints. Check for gouty tophi (chalky deposits of urate crystals found on the pinna of the ear or overlying the joints).
Gold standard is the finding of negatively birefringent, needle-shaped crystals under polarized light microscopy, in a sample of tissue or synovial fluid for cytology. Serum urate may be normal or low during an acute attack, so normal levels do not exclude an attack. Gout and joint sepsis may be clinically indistinguishable, so a sample should be sent for Gram stain and culture as well.
Acute attack: NSAIDs (contraindications: elderly, CV disease, kidney disease, GI bleed)/colchicine/oral, IM or intra-articular steroids. Recurrent or chronic gout: urate-lowering drug e.g. allopurinol (xanthine oxidase inhibitor). Co-prescribe colchicine (for up to 6 months) or NSAIDs (e.g. naproxen for 6 weeks) when initiating urate-lowering therapy. You should remember that urate-lowering drugs can precipitate/exacerbate an acute flare of gout, therefore they should not be started during an acute flare.
Pseudogout has a similar presentation to gout, the difference is biochemical, with positively birefringent analysis on crystal analysis.
Osteoporosis is the most common metabolic bone disease, in which low bone mass and alteration of bone architecture fractures. Bone is a dynamic tissue, with a turnover of up to 10% at any one time; this process is driven by osteoblasts which lay down the bone matrix and mineralize it, and osteoclasts which promote resorption. Risk factors can be non-modifiable (age, female, family history, collagen disorders), or modifiable (smoking, alcohol, early menopause, steroids).
Osteoporosis is clinically silent until a fracture occurs. Particularly with vertebral fractures, it is important to check for other causes of fragility fracture such as malignancy or metabolic bone disease. The five ‘B’s describe some of the most common cancers which metastasize to bone—‘Breast, Bronchus, B(k)idney, B(t)hyroid, B(p)rostate’. Prostate are more likely to be sclerotic while myeloma are classically the lytic tumours. Osteoporosis is categorized by the presence or absence of fracture, and the T-score reported on a dual-energy X-ray absorptiometry (DXA) scan (see Table 31.2). The T-score reflects the patient’s bone mass density (BMD) compared to bone mass at peak density, while the Z-score reflects BMD compared to age- and sex-matched controls. In younger patients, the Z-score is used. Treatment is based on identifying patients at risk prior to development of osteoporosis/fracture, e.g. DEXA scans for patients on long-term steroids, modifying risk factors, and using antiresorptive bisphosphonates (e.g. oral alendronate, IV zoledronate). See Table 31.2.
Table 31.2 WHO definitions for osteoporosis—postmenopausal women and men ≥50 years old
| Definition | Bone mass density measurement | T-score |
| Normal | BMD within 1 SD of the mean bone density for young adult women | ≥ –1 |
| Low bone mass (osteopenia) | BMD 1–2.5 SD below the mean for young-adult women | Between –1 and –2.5 |
| Osteoporosis | BMD ≥2.5 SD below the normal mean for young-adult women | ≤ –2.5 |
| Severe or ‘established’ osteoporosis | BMD ≥2.5 SD below the normal mean for young-adult women in a patient who has already experienced ≥1 fractures | ≤ –2.5 (with fragility fractures) |
SD, standard deviation.
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These may cause marked hypocalcaemia; ensure that the patient is calcium and vitamin D replete prior to treatment. Osteonecrosis of the jaw has also been reported with bisphosphonates. Long-term bisphosphonate use (>5 years) has been linked with an 
risk of atypical (subtrochanteric) femoral fractures.
PMR, the most common inflammatory rheumatic disease in the elderly, is characterized by widespread muscle pain and stiffness, particularly affecting the shoulder and hip girdle. The overwhelming majority of patients are treated with steroids. If the patient does not report a rapid improvement (≥70% improvement within 1 week), then the diagnosis is something else. DMARDs are reserved for refractory cases.
GCA is a granulomatous large/medium vessel vasculitis which classically affects the extracranial arteries, hence the alternative name, temporal arteritis. GCA can result in permanent blindness if untreated. For this reason it is important, both because you must not miss the diagnosis as a doctor, and you are likely to be grilled on the subject as a medical student. It is characterized by headache, jaw claudication, visual disturbance, and scalp tenderness (e.g. pain on brushing hair, usually in an elderly lady). The most important thing to know is that GCA should be treated (with steroids) as soon as it is suspected and certainly before investigation (e.g. positive biopsy or ESR >50). There is also an association with PMR.
SLE is a multisystem connective tissue disease, characterized by immune complex formation and deposition. It is one of the ‘great imitators’ as it can present in countless ways and affect many organ systems. Constitutional symptoms (malaise, fatigue, weight loss, etc.) are extremely common. Textbook signs of SLE include malar rash, discoid rash, photosensitivity, oral ulcers, neuropsychiatric features, and a positive ANA. Other types of lupus (not SLE) include discoid (chronic skin disorder), drug induced (similar symptoms to SLE but reversible), and neonatal (associated with complete heart block).
Typically this presents as recurrent miscarriages in young females. It is a hypercoagulable state that may be diagnosed by a single clinical event and positive blood tests (anticardiolipin, lupus anticoagulant) on 2 occasions at least 12/52 apart. Treatment is with anticoagulation, e.g. warfarin (not in pregnancy—causes craniofacial defects), LMWH, and aspirin.
Vasculitis (literally ‘inflammation of blood vessels’) is an umbrella term covering a group of heterogeneous multisystem diseases.
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The Chapel Hill Consensus Conference (1994) classified vasculitides by vessel size, although there may be overlap between sizes of affected vessels:
• Large vessel: e.g. Takayasu’s arteritis, GCA.
• Medium vessel: polyarteritis nodosa, Kawasaki disease.
• Small vessel: microscopic polyangiitis (MPA), granulomatous polyangiitis (GPA, previously known as Wegener’s granulomatosis), eosinophilic granulomatous polyangiitis (EGP, previously known as Churg–Strauss syndrome), immunoglobulin A vasculitis (Henoch–Schönlein purpura), and antineutrophil cytoplasmic antibody-associated vasculitis.
• Variable vessel: Behçet’s disease can affect any size of vessel
There is significant variability in severity, from isolated skin rash to multiorgan failure and death, even within groups of patients with the same disease. The consequences of vasculitis are vascular stenosis which may progress to occlusion, and aneurysmal dilatation, with subsequent vessel rupture. Treatment is stepwise immunosuppression.
These are poorly understood connective tissue diseases characterized by inflammatory changes within skeletal muscles causing myalgia and muscle weakness. Classical symptoms of dermatomyositis include skin rash (heliotrope periorbital rash, Gottron’s papules on the knuckles), and symmetrical proximal muscle weakness. Polymyositis has a similar constellation of features without the skin signs. Investigations include an elevated CK and autoimmune antibodies (anti-Jo-1), and attempts should also be made to exclude a concurrent malignancy.
SSc is a multisystem connective tissue disease, in which vascular endothelial damage and subsequent fibroblast proliferation and accumulation occur. SSc is classified into limited SSc and diffuse SSc (involving GI, cardiovascular, respiratory, renal systems). Limited SSc has previously been known as CREST because of a constellation of Calcinosis, Raynaud’s, (o)Esophageal dysmotility, Sclerodactyly, and Telangiectasia. In an exam the characteristic appearance plus blood tests showing anaemia should prompt consideration of GI telangiectasiae (microcytic) or bacterial overgrowth (macrocytic).
Often found in middle-aged females, who will have dry mucous membranes and various other glandular and MSk symptoms. Autoantibody associations (e.g. anti-Ro/La), but definitive diagnosis is biopsy. These patients have a 5–10% lifetime risk of lymphoma and this might be an opportunity to practise your lymph node examination.
The most likely scenario in a history taking station will be of a new-onset inflammatory arthritis. Use the principles outlined at the start of this chapter to establish the presence of inflammatory disease, and then drill down to what type. PMR or GCA may also be found in history stations.
‘SOCRATES’ is useful (see 
p. 148–149), but be prepared to ask about stiffness (duration, timing, etc.) If back pain is reported, again try to differentiate inflammatory from non-inflammatory pain; ask about radiation—alternating buttock pain is the classical description of sacroiliitis. If back pain is present then always check for ‘red flag’ symptoms—bladder/bowel dysfunction, saddle anaesthesia, progressive neurology, night pain, history of malignancy or immunosuppression, systemic symptoms.
Ask about psoriasis or skin problems that might suggest psoriasis, even if the patient has not had a diagnosis. Check for inflammatory bowel symptoms, uveitis (‘Have you ever had a red, painful eye?’). Think about connective tissue disease and ask about thrombosis, miscarriage, photosensitivity, rashes, and migraine. Take a travel and sexual history if reactive arthritis is possible.
Try to discern whether this is inflammatory or degenerative. Patients often do not distinguish between OA and RA although the distinction is important. They will often know OA as ‘wear and tear’ arthritis. If inflammatory arthritis is being queried, ask specifically about family history of psoriasis.
Do you take any medications? Do you have any allergies? Ask what drugs the patient has tried for their symptoms.
Smoking, alcohol, and impact on life (how do you get around normally? How has this affected you day to day? What sort of things are you struggling to do at home or at work?). Functional status is very important to the patient. The easiest way to assess function is to ask the patient what they can do—it is surprising what people with marked hand deformities are still able to do!
Hands are the most common joint in medical school exams, and knees are also common, but you may be asked to examine any joint. If faced with an unfamiliar joint, return to first principles—look, feel, move (active first, then passive), and ‘special tests’, e.g. anterior draw test or McMurray’s test for knees. There are many different systems for examining the hands; the smoothest and most professional of these approaches is described as follows. As with all physical examinations there is a theatrical component, and you should rehearse the steps with colleagues and patients as many times as is necessary for fluency.
Inspect as you approach the patient—look for signs of systemic disease, e.g. the facial changes of SSc or obvious psoriatic plaques.
Ensure the patient is exposed enough for you to see the area of interest (many people use the ‘expose up to one joint above and one joint below’ approach). In any hand examination, make a show of examining the elbows and then resting the patient’s hands on a pillow (ask your examiner for one), and ask whether they are comfortable—this is the first of your communication marks in case you forget to win some more later on.
Inspection is an important part of examining the hands—do not be worried about looking at all aspects of the hands (including elbows) as the examination will be over very quickly if you do otherwise. One systematic method is to work distally to proximally on each hand. First inspect the hand as a whole and look for gross bony deformities (symmetrical/asymmetrical, fixed/reversible). Then look in turn at nails (pitting, onycholysis, nail bed infarcts), distal interphalangeal joints (DIPJs) (Heberden’s nodes, gouty tophi), proximal interphalangeal joints (PIPJs) (Bouchard’s nodes), metacarpophalangeal joints (MCPJs), and muscle wasting (Fig. 31.2). Check for skin changes (scleroderma, telangiectasiae, vasculitic lesions, steroid purpura).
Fig. 31.2 Patient with RA presenting with a radial deviation (right wrist), swan-neck deformity with hyperextension of the PIPJs and flexion of DIPJs (digits 3 right and 5 on both sides) and boutonnière deformity with flexion of the PIP and hyperextension of DIP joints (digit 2 right). Reproduced from Richard A. Watts, Oxford Textbook of Rheumatology (4 ed.), 2013, Oxford University Press.
Feel the joint with the back of your hand—is it warm (if so, likely to be tender, so proceed carefully), beginning from DIPJ, PIPJ, dorsum of hand, and wrist. Then palpate each of the joints distally to proximally for structural abnormalities and tenderness. Make a request to the patient that you wish to turn their hands over as you gently supinate their hands. Inspect first for muscle wasting (thenar, hypothenar eminences reflecting median or ulnar nerve deviation respectively) and carpal tunnel scar (longitudinal scar across the wrist). Depending on the case you could consider special tests for carpal tunnel syndrome (e.g. Tinel’s). Inspect the patient’s forearm up to the elbows (extensor rash of psoriasis, rheumatoid nodules).
You should then check the following movements. Wrist flexion/extension, finger flexion/extension/abduction, and thumb abduction/opposition (feeling for thenar muscle bulk for wasting). Finally, you should perform a functional assessment of grip strength (around your middle and index finger), pincer grip (around index finger), and ask them to pick up a small object such as a coin. Finish off your exam by offering to perform a full neurovascular exam.
Once you have finished, think about the examination in context. If the patient has Raynaud’s and digital ulceration, are there any other signs of SSc or SLE? Does the patient with apparently rheumatoid hands have any nail dystrophy or psoriasis that might alter your differential diagnosis? Most students are easily able to recognize RA, but often struggle to describe it; if you can produce a smooth, sequential presentation supporting your diagnosis, you will please the examiner.
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(See Fig. 31.2.) The most likely case is a rheumatoid hand. Students are very good at identifying a rheumatoid hand (severe cases are obvious) but often struggle to describe its features. Learn a list of features which are almost always present together and mentally check these when examining the patient. Once you have confirmed all are present, you can recite the clinical signs confidentially and firmly. Clinical signs include:
• Heberden's nodes (DIPJ, first MCPJ)