9 Rheumatological disease
Approach to the patient
Clinical features in musculoskeletal assessment
• Articular disorders cause limitation of generalized movement (both active and passive) and joint line tenderness.
• Inflammatory articular disorders cause early morning joint stiffness (> 30 mins), warmth ± redness and boggy joint swelling. There may be a rapid response to anti-inflammatory drugs.
Drugs in rheumatology
Non-steroidal anti-inflammatory drugs (NSAIDs) (Table 9.1)
NSAIDs are inhibitors of both cyclo-oxygenase 1 and 2 isoenzymes and thereby inhibit the prostaglandin pathway (Fig. 9.1). Typical agents used for rheumatological disorders are shown in Table 9.1, although there are many others.
• Side-effects (Box 9.1) are common, particularly in the elderly. Indigestion and gastric erosions occur and occasionally gastrointestinal haemorrhage. The risk increases from ibuprofen (low) to, for example, diclofenac, indometacin and piroxicam (intermediate/high). Piroxicam should therefore not be used as a first-line drug and the dose should not exceed 20 mg. Bronchospasm and urticaria occur due to type 1 hypersensitivity from release of leucotrienes. Fluid retention and an increase in blood pressure can occur. Although there is a reduction in renal blood flow, acute kidney injury is rare. Avoid in pregnancy and with breast feeding, even though the amounts in the milk are small. NSAIDs should not be used if a patient is on anticoagulants, unless a proton pump inhibitor (PPI) is also given.
• Cyclo-oxygenase-2 specific agents (COX-2 inhibitors) are equal in efficacy to naproxen or diclofenac. These agents include celecoxib 200–400 mg daily in divided doses and etoricoxib 30–120 mg daily. They reduce the risk of gastrointestinal side-effects by 50% but there have been reports of an increased rate of cardiovascular events; two agents (rofecoxib and valdecoxib) have already been withdrawn but this may be a class effect. As a consequence, COX-2 inhibitors should not be given in the presence of cardiovascular or cerebrovascular disease. COX-2 inhibitors are also relatively contraindicated in those with vascular risk factors (e.g. smoking, diabetes, hypertension, hypercholesterolaemia).
Fig. 9.1 Arachidonic acid metabolism and the effect of drugs. The sites of action of NSAIDs (e.g. aspirin, ibuprofen) are shown. The enzyme cyclo-oxygenase occurs in three isoforms: COX-1 (constitutive), COX-2 (inducible) and COX-3 (in brain). BLT, B leukotriene receptor; cysLT, cysteinyl leukotriene receptor; PG, prostaglandin.
NSAID should be used for the shortest possible time at the lowest effective dose.
Glucocorticoids
Systemic corticosteroids
These are potent anti-inflammatory agents.
• Prednisolone in doses up to 60 mg daily is used in many systemic rheumatic conditions, preferably taken in the morning after breakfast.
• Methylprednisolone 0.5–1 g IV for 3 days is used in severe organ-threatening disease in vasculitis, and 80–120 mg IM for acute flares of inflammatory arthritis, particularly rheumatoid.
• Side-effects of steroids are many (Box 9.2) and include:
• Insomnia, weight gain, thinning of the skin, bruising, hypertension, sodium retention, hyperglycaemia, cataracts and glaucoma.
• Osteoporosis. This is a long-term problem, developing within 6 months on doses above 7.5 mg daily. It should be monitored with dual energy X-ray absorptiometry (DEXA scanning), which guides treatment with calcium 1–1.5 g/day and vitamin D 400 U daily, and a weekly bisphosphonate (p. 324). A proximal myopathy and avascular necrosis (often of the femoral head) can also occur.
• Steroid reduction. Patients who have taken low doses of prednisolone for less than 3 weeks may stop the drug immediately, as adrenal suppression will not have occurred in this time frame. Other patients, however, require a gradual reduction in the dosage, which can be fairly rapidly decreased to 20 mg and then more slowly down to 7.5 mg, equivalent to a physiological steroid dose.
Joint aspiration and injection for diagnosis and therapy (Box 9.3)
Aspiration
Aspiration should always be performed in patients with unexplained large joint effusions to obtain a diagnosis; for symptomatic relief in a patient with known arthritis; and to monitor response to treatment in an infected joint.
• Inflammatory and septic fluids are yellow and can be translucent or opaque. Opaque fluid suggests a high protein content and high white cell count, is of low viscosity and may clot.
• The fluid should be sent to the laboratory for a cell count, Gram strain and microscopic examination for crystals and culture.
Box 9.3 Joint aspiration
This is a sterile procedure, which should be carried out in a clean environment.
Explain the procedure to the patient; obtain consent.
4 Warn the patient. Insert the needle, injecting local anaesthetic as it advances; if a joint effusion is suspected, attempt to aspirate as you advance the needle
6 Examine the fluid in the syringe and decide whether or not to proceed with a corticosteroid injection (if fluid clear)
7 Cover the injection site and advise the patient to rest the affected area for a few days. Warn patients that the pain may increase initially but to report urgently if the pain persists beyond a few days, if the swelling worsens, or if they become febrile, since this might indicate an infected joint
Joint injection
• Glucocorticoids. There are several preparations available; the dosages are variable and should be checked with the product literature. The ‘volume’ injected varies with the size of the joint, e.g. small joints (hands and feet) 0.25–0.5 mL, larger joints (knees, shoulder) 1–2 mL. Lidocaine 1% solution can be mixed with the steroid in the syringe to make up to 1–10 mL depending on joint size.
• Hydrocortisone acetate (25 mg/mL) 0.5–1 mL, can be used for soft tissue injections and is the least likely to cause skin atrophy or depigmentation, as it is a short-acting preparation.
• Contraindications. These include infection over the site of needle insertion (absolute), and coagulopathy or bacteraemia (relative).
N.B. No more than three injections per joint should be performed in 1 year.
Osteoarthritis (OA)
Investigations
• Blood tests are not usually helpful. Inflammatory markers, e.g. ESR, are normal but high-sensitivity CRP may be raised.
Management
• General measures. These are underused and include education and weight loss. Refer to physiotherapy for exercises (aerobic and muscle strengthening) and joint protection (e.g. lateral heel wedges for medial knee OA, patella taping, knee braces, shock-absorbing insoles and walking stick). Acupuncture is also used.
• Drug therapy. Drugs are overused.
• Paracetamol up to 1 g 4 times daily should be trialled in all patients before trying alternative drugs.
• Capsaicin ointment 0.025% topically has shown benefit for hand and knee OA but the full effect may take up to 4 weeks.
• Glucosamine sulphate 1500 mg or chondroitin sulphate 800 mg daily have been used for hip and knee OA. Their value is unproven but some patients derive benefit.
• Intra-articular steroid injection is often worthwhile in knee OA (particularly if there is an effusion) and in thumb-base OA.
• Hyaluronic acid injections, provided as pre-filled syringes and given weekly for 3–5 weeks, are available for mild–moderate knee OA and can give a longer-lasting effect (up to 6 months) compared to steroid injections (up to 2 months).
• Total replacement arthroplasty has transformed the management of severe OA. The safety of hip and knee replacement is now equal, with a rate of complications of about 1%; loosening and latent blood-borne infection are the most serious of these. Total hip or knee replacement reduces pain and stiffness, and greatly increases function.
Inflammatory arthritis
Rheumatoid arthritis (RA)
Clinical features
• The characteristic feature is persistent (> 6 weeks) symmetrical polyarthritis affecting the hands (metacarpal phalangeal joints (MCPs), proximal interphalangeal joints (PIPs) and wrists) and feet (metatarsal phalangeal joint (MTPs)), although any synovial joint can be involved.
• Common extra-articular features include soft-tissue lesions, subcutaneous nodules, pleural effusions, carpal tunnel syndrome (CTS), systemic symptoms and Sjögren’s syndrome.
• RA causes progressive damage, with > 90% having joint erosions within 3 years (Fig. 9.3). Early aggressive treatment is therefore warranted. Poor prognostic factors include extra-articular manifestations, poor scores on functional assessment, high inflammatory markers, a positive rheumatoid factor and early erosions on imaging.
Investigations
Management
• General measures. Give education with reassurance; physiotherapy, i.e. exercises to maintain joint range and power; occupational therapy to help maintain normal function through the use of joint splints, gadgets and mobility aids; and podiatry for foot care.
• Drug therapy. In the first 6–12 weeks after disease onset, around 50% of patients will have negative auto-antibodies and normal X-rays. It may be difficult to differentiate RA from self-limiting post-viral arthritis during this time. One approach to treatment is to give an IM injection of methylprednisolone 120 mg (or 80 mg if < 60 kg), along with an NSAID, and review at week 12; a self-limiting polyarthropathy will have settled by this time. Persisting disease requires use of a DMARD (see below), the most common being sulfasalazine or methotrexate.
• Glucocorticoids are potent anti-inflammatory drugs, which are used:
• DMARDs (Table 9.2) reduce inflammation (as reflected by a reduction of joint swelling and fall in plasma acute-phase reactants), slow the development of joint erosions and prevent irreversible damage. They act slowly and achieve disease remissions in up to 70% of patients. Combinations of 2–3 drugs may be necessary. These drugs are potentially dangerous in pregnancy and contraception should be used; manufacturer’s advice should be followed.
