Recognising polymyalgia rheumatica
Polymyalgia rheumatica (PMR) is an inflammatory disease which causes pain and
stiffness in the shoulder and pelvic girdle. The incidence of PMR varies, but in the UK, recent reviews have suggested an age adjusted incidence rate of 8.4/10,000 patient years, with a female to male ratio of 2:11. The aetiology remains unclear. Both environmental and familial clustering have been reported. Susceptibility to PMR has been associated with HLA-DRB12. A number of viral and bacterial agents have been implicated, including Mycoplasma pneumoniae3 and Chlamydia pneumoniae4. However, other studies have not confirmed this.5,6,7
PMR affects the elderly, rarely occurring in those aged 50–59 years but increasing in each decade over 60 years. It presents with proximal girdle pain and early morning stiffness (EMS), often acutely and usually bilaterally; tenderness may also occur. Power may be restricted by pain, but true weakness is not apparent. Systemic features such as fatigue, fever, loss of appetite and weight loss are common and may be the dominant features. Patients may report difficulty with daily activities, such as getting out of bed in the morning and getting into the bath. Transient peripheral synovitis of the wrists, knees and sternoclavicular joints has been documented.
PMR is linked with giant cell arteritis (GCA), an inflammatory process affecting the temporal and other extracranial arteries. This disease causes headaches, scalp tenderness, jaw claudication, visual symptoms and systemic upset. Approximately 25 per cent of PMR patients have features of GCA. However, PMR or GCA can also occur in isolation, and PMR is more common than GCA.
There are a number of diagnostic criteria sets available (see table 1, page 43). Most of these include age, proximal stiffness, ESR, constitutional symptoms and response to glucocorticoids. The Bird criteria appear to be the easiest to use in a clinical setting, requiring three of the seven criteria to be present. The test, in the original studies, returned a sensitivity of 92 per cent and a specificity of 80 per cent. Further studies comparing the sensitivity of all available diagnostic criteria have a demonstrated sensitivity of 99.5 per cent8. A number of conditions may respond to glucocorticoids, and the response in PMR is not always dramatic and rapid, so its use as a diagnostic criterion may be limited.
PMR is a clinical diagnosis, without a ‘gold standard' serological or histological test. Conditions which may mimic PMR, therefore, must be excluded. These include both inflammatory and non-inflammatory disorders. Table 2 (page 44) outlines the main differential diagnoses. Osteoarthritis is common in the elderly, and a combination of this with a systemic problem such as intercurrent infection may appear to be PMR. The most important differential is late onset rheumatoid arthritis (LORA), which often has a polymyalgic onset. Rheumatoid factor is present in approximately 12 per cent of healthy over 60-year-olds9 and may therefore be unhelpful in distinguishing between the two diseases. However, a study comparing PMR patients with LORA patients found that high titre rheumatoid factor at first presentation is an indicator of underlying RA even in the absence of clinical arthritis10. Importantly, this group also found that those with true LORA had persistent synovitis despite steroids and progressed to erosive disease. Anti-cyclic citrullinated peptide antibody (anti-CCP2) may help in distinguishing the two diseases. The test has a sensitivity of 80 per cent and a specificity of 98 per cent for rheumatoid arthritis. In addition, 40 per cent of rheumatoid factor negative patients with RA are positive for anti-CCP211. Lopez-Hoyos et al 12 showed that 65 per cent of the LORA cohort were anti-CCP positive, whereas all PMR patients were anti-CCP negative.
When there are peripheral signs present in patients with PMR (approximately
10 per cent), an important differential diagnosis is RS3PE (Remitting Seronegative Symmetrical Synovitis with Pitting (O)Edema). This syndrome presents in the elderly with symmetrical peripheral signs, absent rheumatoid factor, raised inflammatory markers and a good response to glucocorticoids, making it difficult to distinguish between these two diseases. MRI studies have shown similarities in the two groups, with tenosynovitis being the predominant finding13.
Laboratory investigations are outlined in table 3 (page 44). An inflammatory response is almost always present, with raised ESR, plasma viscosity (PV) or CRP. A normochromic anaemia and raised alkaline phosphatase are common. Occasionally the ESR or CRP is normal14 but the clinical presentation should be classical, and other mimics excluded.
A chest X-ray is important to exclude malignancy.
PMR is treated primarily with glucocorticoids. The dose, length of treatment and rate of reduction are based largely on observational studies. An initial dose of 15mg of prednisolone daily appears effective. Lower doses are associated with relapse, and higher doses with side-effects. There should be a dramatic response within a few days, with around 80 per cent improvement. A less optimal response should prompt the clinician to seek an alternative diagnosis. Rapid tapering is associated with relapse20, therefore 15mg should be maintained for 3–4 weeks. This should be followed by 12.5mg daily for 3–4 weeks, 10mg daily for 4–6 weeks and then a gradual reduction of 1mg every 4–8 weeks. The rate of reduction should be adjusted depending on the individual patient's response, with the clinical picture rather than blood tests determining the regimen used. Therapy can be withdrawn in around 50 per cent of patients after two years20,21, and in the remainder within four years. A small group of patients may need to continue a daily 2 or 3mg dose for a number of years.
An alternative to oral prednisolone is intramuscular methylprednisolone acetate. A regimen of 120mg every 3–4 weeks was used for the first 12 weeks, followed by monthly injections with a dose reduction of 20mg every three months. Dasgupta et al documented a lower incidence of glucocorticoid-related side-effects when methylprednisolone was used in preference to oral prednisolone22.
The response to glucocorticoid therapy is based on the physician's global assessment of disease activity and the inflammatory response. Newer disease activity scores are being tested in clinical practice23,24 but are not yet generally accepted. The calculation includes CRP (mg/dl) + VAS patient (0-10) + VAS physician (0-10) + morning stiffness (minutes x 0.1) + ability to elevate shoulders (3-0).
Relapses are common in PMR, with approximately a third to half of all patients relapsing, especially in the first year of treatment or at the time of glucocorticoid reduction. A small increase in glucocorticoid dose to a level where disease control was adequate is normally sufficient to regain control. The ESR may not always be raised during a flare and in one study was shown to be normal in 50 per cent of cases25. For patients who relapse frequently or those who cannot reduce their glucocorticoid dose below 10mg per day, a more gradual reduction should be attempted. This may be done using alternate day doses of 10mg and 9mg for a month with a similar ongoing reduction pattern. Concomitant low dose NSAIDs, such as ibuprofen, or simple analgesics such as paracetamol or co-codamol may also enable successful withdrawal of steroids. Failing this, disease-modifying antirheumatic drugs (DMARDS) such as methotrexate or azathioprine should be considered for use as steroid sparing agents, though the evidence for these is not clear cut. Novel agents such as the biologics have been used to treat resistant PMR and GCA. Although isolated case reports have shown biologics to be effective,26,27,28 as yet there has been no trial evidence to support this.
Criteria for referral
The majority of PMR patients are successfully managed in primary care. The following situations should prompt the primary care physician to consider referral to secondary care.
• A sub-optimal response to glucocorticoids leading to doubt regarding diagnosis
• Inability to reduce the glucocorticoid dose below 10mg or less within one year and/or development of steroid side-effects
• Development of symptoms to suggest GCA for temporal artery biopsy and higher steroid doses
• Atypical PMR – asymmetrical symptoms, young age of onset, peripheral joint involvement
As most of these patients are likely to need glucocorticoid therapy for at least three months, concomitant bisphosphonate and calcium/vitamin D therapy should be prescribed from the onset of glucocorticoid treatment. In addition, proton pump inhibitors should be considered in those patients with known peptic ulcer disease or previous upper gastrointestinal bleeds.
PMR is relatively common in the elderly. It is characterised by symmetrical proximal stiffness. An initial 15mg daily glucocorticoid dose produces a rapid improvement. Patients are likely to remain on therapy for at least two years and should be on a daily steroid dose of less than 10mg after a year. Steroid related side-effects are common when doses above 30mg per day are used, and relapses are common in those patients where steroids are rapidly reduced. Prophylactic therapy with bisphosphonates, calcium/vitamin D is mandatory and proton pump inhibitors should be considered in higher risk populations.
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