LUPUS: A GP Guide to Diagnosis
The Joints and Lupus
Introduction
Lupus arthritis is defined as a non-erosive arthritis, involving two or more peripheral joints, which is characterised by tenderness, swelling and/or effusion. Arthritis is one of the 1982 ACR revised classification criteria for lupus.
Prevalence
The musculoskeletal system is the most commonly involved system in lupus patients, with 50-95% of patients being affected. Joint pain is the most common initial symptom, being the presenting problem in 50%. Fortunately, despite its frequency, joint disease is rarely serious and only 10% of lupus patients develop significant joint deformities. There are some risk factors for a deforming arthropathy which include secondary Sjögren's syndrome, an anti-Ro antibody, an elevated C-reactive protein (CRP) and positive rheumatoid factor (RF).
Histopathology
The joint deformities in lupus are usually due to a tenosynovitis rather than synovial hypertrophy. The synovium of patients with lupus has not been studied extensively but synovial membrane hyperplasia, microvascular changes, fibrin deposition and perivascular infiltrates have been documented. Interestingly, there is little cartilage or bone destruction, which reflects the altered cytokine profile, particularly reduced levels of IL 1 and 1L 6. The low cytokine levels within the joint mean that there is little circulating pro-inflammatory cytokine and, therefore, the liver is not stimulated to produce an elevated CRP. Thus, a common differentiation between lupus and rheumatoid arthritis is that lupus usually has a normal CRP whereas RA has an elevated CRP.
Symptoms
Patients with lupus arthritis typically suffer from stiffness, pain and swelling. These are usually worse in the morning. These symptoms reflect active inflammation. It is notable that some patients may experience joint pains for a considerable time without objective physical signs. This may delay diagnosis and can make treatment difficult. The arthritis or arthralgia may be persistent, intermittent or flitting from joint to joint, but is typically symmetrical. The metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints are the most commonly affected. Other joints frequently involved include the wrists, knees, ankles, elbows and shoulders.
The hand
The patient with lupus may have rheumatoid-like deformities including ulnar deviation, swan neck deformities and subluxation of the thumb, MCP and PIP joints - see figures 1 - 3. This is sometimes called Jaccoud's arthropathy. In some instances, the changes are reversible and so the patients do not usually require or benefit from surgery. Importantly, X-rays of the hands of lupus patients rarely (approx. 4%) show erosions - see figure 4.
 Figure 1. MCP swelling. Z thumbs and swan necking in a lupus arthritis patient |
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 Figure 2. Subluxation of MCPs and ulnar deviation |
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| Figure 3. Reversibility of lupus arthritis: | |
 a) voluntary induction of deformities |
 b) returning to almost normality |
 Figure 4. X-ray of hands of lupus patient showing non-erosive arthropathy including Z thumbs |
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The foot
The common deformities seen in the foot are hallux valgus, metatarsal phalangeal subluxation and hammer toes.
The neck
Atlanto-axial subluxation can rarely occur in lupus patients. When it does it is associated with corticosteroid use, longer disease duration, Jaccoud's arthropathy and chronic renal failure.
Extra-articular associations
There is an increased prevalence of median nerve compression in lupus patients as in other inflammatory arthropathies. Nodules occur infrequently in lupus patients. They are typically found in the small joints of the hand but also in the more characteristic areas for RA e.g. the extensor surface of the elbow.
Calcinosis occurs but is less frequent compared with systemic sclerosis or dermatomyositis. This feature is often only evident on X-rays.
Table 1 - Arthritis and its associated features in SLE and RA
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Practical issues - lupus should be considered in the differential diagnosis in a patient presenting with persistent inflammatory symmetrical arthritis. RA can also present in a similar way. Table 1 summarises the differences. A history of a photosensitive rash, mouth ulcers, alopecia and Raynaud's is in keeping with a diagnosis of lupus.
Monoarthritis in a lupus patient
If a lupus patient has one particularly active, i.e. hot, swollen and tender joint relative to the other joints then a septic arthritis should be considered. The joint should be aspirated urgently and the synovial fluid sent for urgent microscopy, culture and staining for alcohol and acid fast bacilli. Staphylococcus and streptococcus are the two most common causes of septic arthritis, but mycobacterium tuberculosis and nontuberculous mycobacterial infections are becoming more prevalent and should be borne in mind.
Isolated hip pain
This should raise the suspicion of avascular necrosis (also known as aseptic necrosis or ischaemic necrosis of bone). It occurs in 4-9% of lupus patients. Most cases are associated with corticosteroid use but it also occurs more commonly in lupus patients with Raynaud's, small vessel vasculitis, fat emboli and secondary antiphospholipid syndrome. The radiological changes are best detected on an MRI. It is treated by limiting weight-bearing, adequate pain relief, e.g. NSAIDs, and, for a selected group of patients, by surgery. There is controversy over the value of core decompression for early lesions but hip arthroplasty clearly has a place for end stage lesions.
The swollen calf: a ruptured Baker's cyst versus a deep vein thrombosis (DVT)
Both diagnoses can occur in lupus patients. Baker's cysts are more prevalent with any inflammatory arthropathy and the prevalence of DVTs is increased in lupus patients due to the increased prevalence of the secondary antiphospholipid syndrome. The two conditions require different treatments and potential complications can occur if the wrong treatment is given e.g. haemorrhage into the calf, causing a compartment syndrome if a patient with a ruptured Baker's cyst is inadvertently anti-coagulated. Diagnosis is aided by performing an early ultrasound examination. The patient with a ruptured Baker's cyst should receive an intra-articular corticosteroid knee injection and the patient with a DVT should be anti-coagulated.
Tendon rupture
This tends to occur in the weight bearing areas e.g. the infra-patella tendon of the knee and the Achilles tendon of the ankle. This complication is associated with trauma, long-term therapy with oral corticosteroids, intra-articular steroid injections, Jaccoud's arthropathy, long disease duration and males.
Treatment
General
The priority is to provide adequate pain relief and, therefore, maintain normal function.
Non-pharmacological
Education from the physiotherapists and occupational therapists regarding joint protection and exercises is valuable in preventing joint deformity and maintaining muscle strength. Swimming, walking and cycling should be encouraged, however, rest is important during times of marked joint inflammation. The topical application of heat or cold often provides symptomatic relief to a particularly active joint. Localised severe pain may also be helped by the application of a TENS (transcutaneous electrical nerve stimulation) unit. Splints can be useful in correcting joint deformities. Corrective tendon surgery and joint replacement may be necessary on rare occasions in very severe cases.
Pharmacological
Simple analgesics and non-steroidal anti-inflammatory drugs
Simple analgesics e.g. paracetamol, co-dydramol, and non-steroidal anti-inflammatory drugs (NSAIDs) provide symptomatic relief and are the first line of therapy. There are numerous NSAIDs and most doctors tend to become familiar with just a few. Choosing an NSAID with a relatively long half-life or modified release formulation has advantages for the control of chronic inflammatory pain. It reduces early morning stiffness and provides better symptomatic relief and compliance. If the optimal dose of an NSAID does not produce a significant improvement after three to four weeks, then a different NSAID should be tried. A patient presenting with new onset synovitis may experience complete relief of their symptoms after taking an NSAID, thus confirming the presence of an inflammatory arthritis.
Many patients develop gastro-intestinal (GI) side effects with NSAIDs. These can be improved by the co-prescription of H2 antagonists e.g. ranitidine, proton pump inhibitors e.g. omeprazole, or a prostaglandin analogue e.g. misoprostol. NSAIDs act by blocking the enzyme cyclo-oxygenase. It is now known that there are two isoforms of cyclo-oxygenase, COX-1 and COX-2. COX-1 is associated with 'housekeeping' functions and COX-2 is associated with inflammatory mediation. Some NSAIDs e.g. nabumetone and meloxicam are more selective, with predominantly COX-2 inhibition. These COX-2 selective inhibitors tend to have a better side effect profile including a reduction in GI side effects. Renal toxicity can also occur secondary to NSAIDs. It is important to screen for this in lupus patients. The COX-2 selective inhibitors are less nephrotoxic, they do not reduce GFR although they probably still result in sodium and fluid retention.
Secondary fibromyalgia
The control of pain can be very difficult in lupus patients, particularly if a patient has secondary fibromyalgia. One approach is to develop stress management strategies with an exercise regime and prescribe low dose amitriptyline to modify the pain pathway in addition to prescribing analgesics.
Corticosteroids - Intra-articular, intra-muscular and/or oral corticosteroids treat lupus arthritis effectively. If only one joint is affected, an intra-articular injection is probably the most appropriate mode of administration. Intra-muscular long-acting corticosteroids can tide a patient through a flare. If they are required regularly then the background lupus therapy should be reviewed and a change in second-line drug considered or an additional drug added. Steroids should be used at the lowest effective dose in combination with NSAIDs, antimalarials or other second line drugs. Secondary osteoporosis is a significant risk and should be monitored with DEXA scans and preventative therapy considered.
Hydroxychloroquine is effective in treating the arthritis associated with lupus, as well as the skin manifestations - see 'Drug Therapy of Lupus'.
Other drugs
Azathioprine and methotrexate are both effective in lupus arthritis and are steroid-sparing - see 'Drug Therapy of Lupus'. Patients taking these drugs require regular monitoring for drug toxicity, namely marrow suppression and liver inflammation. The British Society of Rheumatology (BSR) has published recommended blood monitoring guidelines.
Prof. Paul Emery |
Dr. Bridget Griffiths |