9 Rheumatological disease

Approach to the patient

Bone, joint, muscle and soft-tissue structures all produce pain. This can be regional, when it is usually due to a local problem, or widespread, when it may be a manifestation of systemic disease. Clinical assessment is often all that is required for a diagnosis.

Management

Management of all rheumatological conditions is multi-disciplinary and involves allied health professionals including physiotherapists, podiatrists, occupational therapists, as well as drug therapy and local injections.

Drugs in rheumatology

Simple and compound analgesic agents

Agents such as paracetamol (acetaminophen), aspirin (acetylsalicylic acid) or codeine compounds (or combination preparations), used when necessary or regularly, relieve pain and improve function. The side-effects are relatively infrequent, although drowsiness and constipation occur with codeine preparations and are worse in the elderly. Examples are paracetamol 500–1000 mg 6-hourly, paracetamol with codeine 1–2 tablets 6-hourly, and paracetamol with dihydrocodeine 1–2 tablets every 6–8 hours.

Non-steroidal anti-inflammatory drugs (NSAIDs) (Table 9.1)

NSAIDs and paracetamol have comparable analgesic activities when given in single doses. However, with long-term use, NSAIDs also have an anti-inflammatory effect and therefore are more appropriate to use than either paracetamol or opioid analgesics in, for example, inflammatory arthritides such as rheumatoid arthritis. NSAIDs can also be used in osteoarthritis for soft-tissue problems or back pain. Paracetamol is preferred in the elderly for long-term usage.

Table 9.1 Commonly used non-selective non-steroidal anti-inflammatory drugs (NSAIDs)

The anti-inflammatory activity of individual NSAIDs is broadly similar but there is much variation in patient response and tolerance. Most (60%) will respond to a single NSAID, another can be tried if there is no response after 2 weeks. The analgesic effect will be achieved sooner than an anti-inflammatory effect, which may take up to 3 weeks.

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.

If the use of NSAIDs cannot be avoided in patients at high risk of gastrointestinal side-effects (those over 65 years of age, past history of peptic ulcer/bleed, concomitant steroid or warfarin use, or presence of serious comorbidity), use a non-selective NSAID combined with a PPI, e.g. omeprazole 20 mg daily. This is preferred to COX-2 inhibitors (see above). Misoprostol 200 mcg 2–3 times daily can also be used as a cytoprotective agent but causes diarrhoea.

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.

• Hydrocortisone 50–250 mg IV is given short-term when oral prednisolone cannot be taken.

• 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.

Local corticosteroids

Steroids are often given intra-articularly in non-septic inflammatory monoarthritis and in osteoarthritis, particularly when associated with an effusion. Additionally, local soft-tissue injections are often indicated for patients with tenosynovitis, bursitis, enthesitis and carpal tunnel syndrome. In patients with an effusion, joint aspiration is required first.

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.

• ‘Normal’ fluid is clear and non-inflammatory fluid is straw colour (high viscosity).

• 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.

1 Decide on the site to insert the needle and mark it

2 Clean the skin and your hands scrupulously; remove rings and wristwatch. Put on gloves

3 Draw up local anaesthetic (and corticosteroid if it is being used) and then use a new needle

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

5 If fluid is obtained, change syringes and aspirate fully

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

N.B. Aspiration and injection of joints can be painful!

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.

• Methylprednisolone acetate (40 mg/mL or 10 mg/mL) 0.5–2 mL, is often used for intra-articular injections.

• Triamcinolone acetate (40 mg/mL) 0.25–1 mL is an alternative to methylprednisolone acetate.

• Contraindications. These include infection over the site of needle insertion (absolute), and coagulopathy or bacteraemia (relative).

• Complications. Infection following procedure is rare but a serious complication (< 0.1%).

N.B. No more than three injections per joint should be performed in 1 year.

Disease-modifying anti-rheumatic drugs (DMARDs)

See p. 309 and Table 9.2.

Table 9.2 Disease-modifying anti-rheumatic drugs (DMARDs)

Osteoarthritis (OA)

Clinical features

This is a disorder of synovial joints characterized by degeneration of articular cartilage with reactive new bone formation at the articular margins. Clinical features are activity-related pain, stiffness, bony swelling, crepitus and deformity. Most patients are > 50 years of age. The most common joints involved are distal and proximal interphalangeal joints of the hands, cervical and lumbar spine, hips, knees and first metatarsophalangeal joint (‘bunion’). In the knees there may be an effusion.

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.

• NSAIDs are beneficial (topical or oral) for short-term pain relief.

• 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.

• Arthroscopy and washouts have no proven benefit.

Inflammatory arthritis

Rheumatoid arthritis (RA)

Clinical features

RA is a chronic, systemic, inflammatory disorder of unknown aetiology. Any age can be affected but onset is generally between 30 and 60 years of age, with women affected three times more commonly than men.

• 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.

Fig. 9.3 X-ray of early rheumatoid arthritis. Typical erosions are seen at the thumb and middle MCP joints (arrowed) and at the ulnar styloid (white arrow on right).

Management

This requires a multi-disciplinary approach based on early aggressive treatment with non-drug measures and drug therapy. The main aims are to reduce inflammation, maintain joint function, and prevent or slow the advancement of arthritis and deformity.

• 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:

a) to settle a disease flare; options are a short course of oral prednisolone < 20 mg daily, IM methylprednisolone 80–120 mg, intra-articular injections or IV methylprednisolone pulses of 500 mg

b) as an adjunct to DMARDs (see combination therapy below)

c) as the sole treatment when the risks of DMARD therapy outweigh potential benefit (e.g. in the very elderly) at a dose of prednisolone 5–10 mg daily. Doses > 7.5 mg may slow radiographic progression.

• 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.

• Sulfasalazine (SSZ) is a commonly prescribed agent. Radiological progression is reduced. Mild side-effects are common (30%), most occurring in the first 6 months. SSZ should not be used in glucose-6-phosphate dehydrogenase (G6PD) deficiency. There is a theoretical risk of neonatal haemolysis if it is used in pregnancy and folate supplements should be given.

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