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December 2007: Early diagnosis crucial in polyarthralgia

What investigations are useful in assessing polyarthralgia?

Which patients should be referred and when?

Which treatments should be started in primary care?

What investigations are useful in assessing polyarthralgia?

Which patients should be referred and when?

Which treatments should be started in primary care?

Polyarthralgia is a common presentation in primary care. While the true incidence is unknown, 35% of a large UK community cohort aged over 55 years reported pain in more than one joint.1 Polyarthralgia is more common in women and with increasing age.

Patients often present a diagnostic and management challenge. However, early assessment and diagnosis is important, as there is increasing evidence of the benefit of early intervention in patients with inflammatory arthritis. A window of opportunity exists where the benefits of early treatment may be significant and long-lasting.2

Monoarthritis is widely recognised as requiring urgent evaluation because of the risk of septic arthritis, gout or rare bone tumours. However, patients with polyarthritis should also receive prompt assessment. While some forms of polyarthritis may have a single finding that is diagnostic (such as uric acid crystals in joint aspirate for gout), the diagnosis of most polyarticular diseases requires a constellation of historical and clinical findings.

Polyarthritis is generally defined as pain affecting five or more joints, while a patient with 2-4 joints involved would be said to have oligoarticular disease. In this article, ‘polyarthralgia' is defined as more than one painful joint.

Diagnosis

In patients with symptoms in multiple joints, it is important to decide whether the condition is inflammatory or mechanical in nature. This is a pragmatic simplification, as mechanical forces, such as weight bearing, may exacerbate most inflammatory arthritides, and osteoarthritis has a variable inflammatory component.

Polyarthralgia has a wide range of differential diagnoses (see table 1, attached) and diagnosis is often not straightforward. However, history and physical examination should establish a diagnosis in at least 75% of patients.3 Laboratory investigations and imaging studies may be indicated to aid diagnosis.

History

Early morning stiffness

It is vital to ask about prolonged early morning stiffness (EMS). It is the key feature suggesting inflammation. In patients with inflammatory arthritis, EMS typically lasts for more than one hour; in contrast, patients with osteoarthritis may find their joints become less stiff in only 5-10 minutes.

Do not forget to ask about inflammatory symptoms that affect the back, such as an insidious onset of back pain, without a history of trauma, in a patient under 40 years of age and which is associated with morning stiffness of more than one hour's duration.4

Pattern of joint involvement

Symmetrical joint pain may suggest an inflammatory problem, such as rheumatoid arthritis (RA) or polymyalgia rheumatica.

The involvement of the distal and proximal interphalangeal joints of the hands suggests osteoarthritis, whereas involvement of metacarpophalangeal and metatarsophalangeal joints suggests inflammatory arthritis.

Features suggesting systemic illness

Fever may suggest infective arthritis, systemic lupus erythematosus or crystal-associated arthritis. GPs should ask about extra-articular symptoms, such as eye symptoms, hair loss, mouth ulcers, Raynaud's phenomenon and photosensitive rashes, as these may indicate seronegative arthritis or connective tissue disease.

Fatigue may be a symptom of inflammatory arthritis, but if associated with sleep disturbance or lack of refreshing sleep and widespread pain then consider fibromyalgia.

Features suggesting associated disease

It is vital to enquire about preceding infections, particularly bowel or genitourinary infections, as these are often not volunteered by the patient and may suggest a reactive arthritis or indicate a post-infectious aetiology.

The presence of psoriasis or thyroid disease should be considered.

Family history

Family history may give a useful clue to the possible diagnosis, although many patients are not clear about what type of arthritis their relatives have.

Finally, the impact of the disease and effect on function should be documented.

Examination

There is no consensus on a standard joint examination. However, the GALS (gait, arms, legs and spine) assessment (see box 1,attached)5 followed by a more focused examination is unlikely to miss any significant musculoskeletal pathology. The assessment is a simple and brief screening examination, which should take less than two minutes. It involves observing a patient's gait and posture, examining for the presence of joint swelling and assessing the range of joint movement. It is highly sensitive in detecting significant abnormalities of the musculoskeletal system and can be used to highlight body regions that require a more complete examination.

Patients with suspected inflammatory arthritis should be examined for synovitis, indicated by synovial thickening (a soft, boggy feeling at the joint line), and effusion. However, synovitis and effusion can also occur in arthritides that are not primarily inflammatory.

GPs should assess patients for tenosynovitis, which is commonly found in overuse problems and inflammatory arthritides. Range of movement of any affected joint should be assessed.

An important aspect of examination is to differentiate between articular pain and pain caused by periarticular pathology; usually, nonarticular pathology does not produce overt joint swelling.6 Tendinitis, for example, may mimic polyarthritis, but the tenderness and swelling associated with this condition will be localised to the tendon sheaths and bursae on one side of, or adjacent to, the affected joint.

Another clue as to whether pain is arising from a periarticular source may come from examination. Pain will be associated with a particular directional movement of the joint, such as shoulder abduction in subacromial bursitis, rather than movement in any direction, which suggests intra-articular pathology. Similarly, diabetes and Dupuytren's contracture can be associated with tendon and subcutaneous thickening, leading to painful contractures without any primary joint involvement.

Muscle strength should be assessed, as muscle weakness is a hallmark of polyarthralgia. A vicious cycle of disuse because of joint pain, leading to muscle weakness and increased arthralgia can develop. In the absence of inflammatory joint disease, treatment is aimed at muscle reconditioning rather than treatment of any underlying joint pathology. Muscle weakness in the presence of inflammatory disease should not be neglected.

Investigations

The role of investigation will depend on the diagnosis being considered.

No investigation will exclude inflammatory arthritis in a patient with the appropriate history and findings on examination. Conversely, all rheumatologic investigations are subject to false positives.

In particular, rheumatoid factor is not a screening test for RA; there are other conditions, such as infection, where rheumatoid factor may be elevated. The test should only be performed in patients with a high likelihood of inflammatory arthritis. In patients with an inflammatory history, an elevated rheumatoid factor level makes a diagnosis of RA more likely.

Elevation of inflammatory markers (CRP, ESR, plasma viscosity) is also non-specific, but taken in context can indicate inflammatory arthritis. Therefore, both inflammatory markers and rheumatoid factor should be checked before referral.

Other investigations, such as x-rays, are unnecessary. In inflammatory arthritis, x-rays are likely to be normal or to show equivocal changes, such as periarticular osteopaenia early in the disease, and in non-inflammatory conditions, such as osteoarthritis, imaging is not required to make a diagnosis.

The antinuclear antibody (ANA) test is only useful in patients with a high likelihood of connective tissue disease on history and examination. It is not a good screening tool because of the risk of false-positive results with low titres.

Anti-cyclic citrullinated peptide (anti-CCP) antibodies have similar sensitivity but increased specificity compared with rheumatoid factor for the diagnosis of RA.7 An elevated anti-CCP antibody level can be found in patients in whom the rheumatoid factor test is negative, and can aid diagnosis. Anti-CCP is present in 50-60% of patients with early RA (within 3-6 months of onset of any symptoms).8

Anti-CCP testing may be helpful in the evaluation of undifferentiated arthritis (in patients whose symptoms suggest RA but do not meet the diagnostic criteria). Approximately 95% of these patients who go on to develop RA are reported to be positive for anti-CCP antibodies.9 However, the usefulness of anti-CCP testing in primary care is yet to be evaluated.

This test is currently not widely available and costs more than a rheumatoid factor test. However, its high specificity and low false positive rate suggest its usefulness in primary care needs to be evaluated.

If reactive arthritis is suspected, screening for chlamydia is highly important.

Joint aspirate for the presence of infection or crystals may be useful, as polyarticular gout may often evolve from monoarthritic gout to a polyarthritis which can affect the knees, wrists or small joints of the hands.

Referral

The UK has no national guideline on rheumatology referral. Therefore, referral will depend to a certain extent on local care pathways. In general, GPs should refer any patient considered to have a moderate to high risk of inflammatory polyarthritis, or obvious inflammatory arthritis.

Many cities in the UK have established early arthritis clinics aimed at early diagnosis and treatment. Patients should be referred on suspicion so that no time is lost in subsequent treatment. The absence of abnormal investigations in a patient with inflammatory symptoms should not be a barrier to referral.

Patients with polyarthralgia should be referred if:

• There is diagnostic uncertainty and the clinician or patient is concerned

• The impact of joint symptoms on quality of life is substantial

• Multidisciplinary assessment is required

• The ‘rule of three' has been broken (the patient has presented for the same problem three times).

Referral to specialties other than rheumatology may also need to be considered. Many areas have musculoskeletal services that work closely with rheumatology and orthopaedic colleagues, and local guidelines will indicate which patients are suitable for referral along this pathway. Pain management services have a role where mainstream physical and drug therapies have failed.

Treatment

Standard treatment of polyarthralgia is a combination of nonpharmacological and pharmacological therapies.

First-line treatment is with a simple analgesic, such as paracetamol, with treatment for mechanical problems, such as upper and lower limb strengthening exercises; this may require referral to physiotherapy. NSAIDs are useful in patients without contraindications, and topical NSAIDs have fewer serious side-effects. Opioid analgesics may also be useful. Lifestyle interventions such as weight loss should be considered.

In many patients, diagnosis and management will be straightforward and treatment should not be delayed. For example, polymyalgia rheumatica can often be managed with prednisolone and appropriate bone protection.

An acute episode of polyarticular gout is usually treated with NSAIDs or colchicine (the latter at an appropriate, tolerated dose).

Multiple mechanical joint pains or fibromyalgia can be managed with muscle strengthening and aerobic exercise programmes and drug therapy.

In patients with inflammatory polyarthritis, treatment with disease-modifying antirheumatic drugs (DMARDs) should be instituted in secondary care, where the evolution of both the disease process and modern DMARD use (including biological therapy) can be evaluated. Patients on DMARD therapy will usually remain under follow up in secondary care where the need for escalation (or reduction) in therapy can be assessed. However, shared care with the GP with regard to drug monitoring requirements is usually appropriate, when local guidelines are in place.

Patients with suspected inflammatory polyarthritis should be promptly referred to a rheumatologist for assessment. Ideally, waiting times should be short enough that treatment with a corticosteroid, which will mask clinical features, is not required pre-referral. However, patients should not be denied adequate pain relief or NSAIDs while awaiting an appointment.

Summary

Polyarthralgia is a common problem with a wide range of differential diagnoses. Clinical assessment is the most important factor in making a diagnosis. History and examination should help to differentiate mechanical from inflammatory disorders, and investigations play a small role.

Early intervention, regardless of aetiology, is the key to successful management. Treatment is likely to be a combination of lifestyle modification, physical therapy and medication, and this combined approach is most likely to negate the disability and chronic ill-health traditionally seen in patients with polyarthralgia.

Key points Table 1: Causes of polyarthralgia Box 1: The GALS screening assessment Authors

Dr Robert Ley
MB BCh MRCP
specialist registrar in rheumatology, Yorkshire Deanery, University of Leeds

Professor Philip G Conaghan
MB BS PhD FRACP FRCP
Professor of Musculoskeletal Medicine, academic section of musculoskeletal disease, University of Leeds, and
honorary consultant rheumatologist, Leeds Teaching Hospitals NHS Trust

Polyarthralgia

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