This site is intended for healthcare professionals as a useful source of information on the diagnosis, treatment and support of patients with lupus and related connective tissue diseases.

Introduction

Arthralgia is a frequent symptom in patients with lupus and is often the presenting symptom. Not all patients with arthralgia will progress to a true arthritis. However, arthritis is included as an item in the 1982 American College of Rheumatology (ACR) revised classification criteria for lupus and is defined as a non-erosive arthritis, involving two or more peripheral joints, which is characterised by tenderness, swelling and/or effusion.

Prevalence

The musculoskeletal system is the most commonly involved system in patients with lupus. Different cohorts report the prevalence to be between 50-95%. Joint pain is the commonest initial symptom, being the presenting problem in 50% patients. Fortunately, despite its frequency, joint disease is rarely serious and only 10% of lupus patients develop significant joint deformities.The known risk factors for patients with lupus developing a deforming arthropathy include secondary Sjögren’s Syndrome, the presence of a positive anti-Ro antibody, an elevated Creactive protein (CRP) and a positive rheumatoid factor (RF). Approximately 2-3% of patients who are classified as having lupus and have erosive disease will also meet the ACR criteria for rheumatoid arthritis (RA). It is important to screen for extra-articular manifestations associated with a connective tissue disease so that the correct diagnosis is made.

Pathogenesis

The joint deformities in lupus are usually due to tenosynovitis, particularly of the flexor tendons, rather than intra-articular synovial hypertrophy and bony erosions and loss of joint space due to cartilage destruction, as in patients with RA. In lupus patients, there is also ligament laxity combined with muscle imbalance which contributes to the development of the deformity. Musculoskeletal ultrasound and MRI scans are more sensitive at detecting joint abnormalities compared with conventional radiography. MRI findings reported in lupus patients include tenosynovitis, capsular swelling, joint effusions and, sometimes, erosions. As in patients with RA, an MRI scan is more sensitive at detecting erosions in patients with lupus compared with conventional radiography. In some studies, a high proportion of patients with established lupus had erosions on MRI scan compared with 4% on conventional X-rays.

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 1L1 and 1L6. 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. A common differentiation between lupus and rheumatoid arthritis is that lupus patients usually have a normal CRP and elevated ESR whereas RA patients have both an elevated CRP and ESR.

Symptoms

Patients with lupus arthritis typically suffer from stiffness, pain and swelling. These symptoms are usually worse in the morning and reflect active inflammation. It is notable that some patients may experience inflammatory-sounding joint pains for a considerable time without objective physical signs of inflammation i.e. without swelling. 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, elbows and shoulders.

The hand

A 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 pattern of deformity is characteristic of Jaccoud’s arthropathy. The changes are usually reversible since they are due to tendon involvement rather than synovial damage and so the patient does not usually require or benefit from joint 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


Figure 2. Subluxation of MCPs and ulnar deviation


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

The foot

The common deformities seen in the foot are hallux valgus, metatarsal phalangeal subluxation and hammer toes.

The neck

Atlanto-axial subluxation can occur as a rarity in lupus patients. It has been 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 producing carpal tunnel syndrome in lupus patients, as in other patients with 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 also occurs in patients with lupus but is less prevalent compared with patients with systemic sclerosis or dermatomyositis. Calcinosis is often only evident on X-ray.

Table 1 - Arthritis and its associated features in Lupus and RA

Feature
Peripheral symmetrical polyarthritis
Erosions
PV/ESR
CRP
Nodules
RF
ANA
dsDNA
SLE
Present
Usually absent (present 4%)
Increased
Usually normal
Usually absent
Positive in minority
Positive in (>)90%
Positive in (>)80%
RA
Present
Often present (up to 100%)
Increased
Increased
Present in up to 30%
Positive in 70%
Positive in 20%
Negative

Practical Issues

Making the diagnosis

Lupus should be considered in the differential diagnosis in a patient presenting with a persistent inflammatory symmetrical arthritis. RA can also present in a similar way. Table 1 summarises the differences. A history of extra-articular manifestations e.g. 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 particular 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 also 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 high corticosteroid use and can occur within 3 months of starting prednisolone. It is also more common 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 weightbearing, adequate pain relief e.g. NSAIDs and, for a selected group of patients, by surgery. There is controversy over the value of the core decompression for early lesions but hip arthroplasty clearly has a place for end-stage lesions. Osteonecrosis also commonly occurs in the knees, in the tibial plateau and the humeral head in lupus patients.

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 in patients with an inflammatory arthropathy and the prevalence of DVTs is increased in lupus patients due to the increased prevalence of the secondary antiphospholipid syndrome.

See page – The Antiphospholipid (Hughes) 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/Doppler examination. The patient with a ruptured Baker’s cyst should receive an intraarticular corticosteroid injection and the patient with a DVT should be anticoagulated.

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 physiotherapist and occupational therapist regarding joint protection and exercise 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 machine (transcutaneous electrical joint stimulation) unit. Splints may occasionally 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. Cox 2 selective NSAIDs can be used provided there are no contra-indications e.g. hypertension, ischaemic heart disease. Renal toxicity can also occur secondary to NSAIDs and so renal function needs to be carefully monitored, particularly as these patients are prone to renal impairment per se. Choosing a 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 a 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 a NSAID, thus confirming the presence of an inflammatory arthritis.

Hydroxychloroquine is effective in treating the arthritis associated with lupus as well as the skin manifestations and, therefore, represents the cornerstone of treatment in patients with lupus.

See page - Drug Therapy of Lupus

Corticosteroids

Intra-articular, intra muscular and/or oral corticosteroids treat lupus arthritis effectively. If only one joint is affected then an intra-articular injection is probably the most appropriate mode of administration. Intra-muscular long-acting corticosteroids are very effective in treating a flare. If corticosteroids 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 and/or other second line drugs e.g. azathioprine, methotrexate, mycophenolate. Secondary osteoporosis is a particular risk in patients taking regular oral prednisolone and should be monitored with DEXA scans and preventative therapy with a bisphosphonate should be considered according to guidelines.

Other drugs

Azathioprine and methotrexate are both effective in lupus arthritis and are corticosteroid-sparing. Patients taking these medications require regular monitoring for drug toxicity, namely marrow suppression and liver inflammation. The British Society of Rheumatology (BSR) has published recommended blood monitoring guidelines.

See page - Drug Therapy of Lupus

Secondary fibromyalgia

Fibromyalgia is a syndrome of widespread pain and the presence of many tender points and is associated with a poor sleep pattern. Patients with lupus can develop secondary fibromyalgia.The control of pain can be very difficult in lupus patients, particularly if secondary fibromyalgia has developed. One approach is to develop stress management/coping strategies with an exercise regime and prescribe low dose amitriptyline to modify the pain pathway, in addition to prescribing analgesics.
Dr Bridget Griffiths
Consultant Rheumatologist
Freeman Hospital
Newcastle upon Tyne
NE7 7DN
Prof Paul Emery
arc Professor of Rheumatology
Academic Section of Musculoskeletal Disease
Chapel Allerton Hospital
Leeds LS7 4SA