clinical Polymyalgia rheumatica

Oliver van Hecke Diagnosis and management

There are occasional familial cases and there is Background a clear north to south gradient with the highest Polymyalgia rheumatica (PMR) is a common inflammatory rheumatic disease and an prevalence in Scandinavian countries and in indication for long term treatment with oral steroids. Its incidence rises progressively parts of the USA that have a population of a beyond the age of 50 years. For the most part, PMR is managed in primary care. similar ethnic background, a lower prevalence Objective in Mediterranean countries and the lowest This article highlights the main points in the British Society for Rheumatology and the prevalence in Arabian and Asian countries.7 British Health Professionals in Rheumatology guidelines that may be useful to general Studies report a cyclical yearly pattern of practitioners in the primary care setting. incidence and seasonal variations in incidence, Discussion which might suggest an environmental infectious Different levels of awareness of the condition between practitioners, and a lack of uniform aetiology.7 Polymyalgia rheumatica is twice as diagnostic criteria may impede correct diagnosis and management of PMR. Updated common in women as in men and is related to international guidelines produced by the British Society for Rheumatology and the British arteritis (GCA), although the precise Health Professionals in Rheumatology can aid diagnosis and direct treatment and disease relationship between the two conditions remains monitoring. unknown. Polymyalgia rheumatica is 2–3 times Keywords: polymyalgia rheumatica; general practice; primary care more common than GCA.7 Clinical features Polymyalgia rheumatica affects the shoulder Polymyalgia rheumatica (PMR) is a and hip girdles causing aching and morning common rheumatic disease that affects stiffness related to synovitis of proximal joints patients middle aged and older. Its and of extra-articular synovial incidence increases progressively beyond structures.8 Patients may complain of difficulty the age of 50 years.1 The reported annual getting out of bed or standing from the seated incidence in Europe and the United position. Typically, morning stiffness lasts for 30 States of America varies between 1.3 minutes or more. The onset is often abrupt and and 11.3 per 10 000 individuals aged symptoms are usually symmetrical. Pain can also over 50 years.2–5 This wide variation may involve the neck, upper arms, lower back and reflect differing levels of awareness of thighs. Distal musculoskeletal manifestations the condition between practitioners, or may include carpal tunnel syndrome and a lack of uniform criteria used to make nonerosive, asymmetrical peripheral arthritis the diagnosis. A United Kingdom study6 (affecting the knees and small joints of the hands demonstrated that general practitioners and feet) and are seen in about half of patients.9 do not always use established criteria Atypical presentations involving asymmetrical to diagnose PMR. This may result in proximal joint symptoms or younger patients may unnecessary further investigation and occasionally occur. needlessly expose patients to the risks Examination findings may be minimal and associated with long term steroid use. include painful restriction of active and passive movements of the shoulder and hip joints, usually While the aetiology of PMR remains elusive, without detectable proximal joint swelling. both environmental and genetic risk factors Muscle strength is usually normal, although are thought to contribute to its development.7 interpretation may be difficult because of pain.

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Systemic such as low grade Table 1. Polymyalgia rheumatica: core inclusion criteria (all these criteria are , depression, fatigue, anorexia, and weight required for a diagnosis) loss may occur in up to 40% of patients.7 • Bilateral shoulder or pelvic girdle aching – or both Diagnosis • Morning stiffness longer than 45 minutes There are no specific diagnostic tests • Age older than 50 years for polymyalgia rheumatica. The British • Duration >2 weeks Society for Rheumatology and the British • Evidence of an acute phase response (raised ESR/CRP) Health Professionals in Rheumatology have published joint guidelines on the diagnosis and management of polymyalgia rheumatica.9 Table 2. Conditions that may mimic polymyalgia rheumatica Good scientific evidence is currently lacking • Active cancer (eg. multiple myeloma, lymphoma, leukaemia) and most of the recommendations for diagnosis • Infections: viral or bacterial and treatment included in these guidelines are • Giant cell arteritis graded at level B or C. The guidelines recommend • Rheumatic diseases a stepped diagnostic and management process –– late onset rheumatoid arthritis (symmetrical peripheral synovitis, positive with diagnosis involving identification of core rheumatoid factor and anticyclic citrullinated peptide antibodies, joint erosions, inclusion criteria and exclusion of conditions extra-articular manifestations) that may mimic PMR – exclusion criteria (Table –– remitting seronegative symmetrical synovitis with pitting oedema (RS3PE 1, 2). Inclusion and exclusion criteria should be syndrome) documented in the patient’s medical record. –– late onset spondyloarthopathy (peripheral enthesitis, dactylitis, anterior uveitis, HLA-B27, and radiological evidence of sacroiliitis) Suspected giant cell arteritis –– late onset systemic lupus erythematosus, other connective disease Regardless of the presence of PMR, if the –– polymyositis (proximal muscular weakness rather than pain, increased muscle with or without creatine kinase, myopathic electromyogram changes) acute phase reactants are elevated and this is –– pseudogout associated with new headache or an unexplained –– fibromyalgia (younger, absence of typical joint stiffness, normal inflammatory pain located above the neck, it is important to markers) consider a diagnosis of GCA. Features of this • Hypothyroidism condition include headache, jaw claudication and • Drug induced (eg. statin myopathy) visual symptoms. If GCA is suspected, commence treatment with high dose steroids immediately • Chronic pain syndrome (osteoarthritis of neck or shoulder, fibromyalgia) and refer the patient to a hospital emergency • Local shoulder or hip pathology department without delay.10 The Therapeutic 10 Guidelines: rheumatology13 suggest steroids and Adapted from Gonzalez-Gay et al urgent ophthalmology referral. cases (range 7–20%).11 C-reactive protein is a imaging (eg. scintigraphy, magnetic resonance Investigations more sensitive indicator of disease activity than imaging, ultrasonography) to detect synovitis in So long as there are no features that suggest ESR in PMR as it is less affected by extraneous proximal joints and periarticular structures. GCA, urgent institution of steroid therapy is not factors such as increasing age.11 Patients in necessary, and treatment can be delayed to whom evidence of inflammation on blood testing Management enable further investigation. Suggested initial is equivocal should be referred for specialist Corticosteroids laboratory investigations in PMR are listed in assessment.9 Patients with PMR may have a Table 3. normochromic, normocytic anaemia and raised Once the diagnosis is established, the patient Laboratory test findings in PMR are alkaline phosphatase but creatinine kinase is should be commenced on low dose steroid nonspecific and usually indicate the presence invariably normal (in contrast to elevated levels therapy. The dose is then gradually tapered over of inflammation with elevated erythrocyte in polymyositis, hypothyroidism and other muscle time. It is important to counsel the patient about sedimentation rate (ESR) and C-reactive protein diseases). potential risk factors associated with long term (CRP). However, the presence of PMR can be The extent of further investigations steroid therapy (Table 4). established in the setting of a normal ESR if there will depend on the level of certainty of the Osteoporotic risk with long term steroid is a classic clinical picture and a good response diagnosis. Secondary investigations may include therapy can be minimised by using the minimum to steroids; this occurs in up to one-fifth of autoantibody screening, muscle biopsy and effective steroid dose. A recent meta-analysis

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Bone protection Table 3. Suggested initial laboratory investigation in polymyalgia rheumatica The decision about the use of a bone sparing • Full blood count agent (eg. oral biphosphonate) for bone • ESR/plasma viscosity and/or CRP protection when initiating steroids for PMR • Urea and electrolytes depends on the clinical risk of developing • Liver function tests • Calcium, phosphate, albumin, alkaline phosphatase glucocorticoid induced osteoporosis. A recent • Protein electrophoresis (also consider urinary Bence Jones protein) review suggests that osteoporotic risk in • Thyroid stimulating hormone PMR varies widely, from 3.6–27%, and from • Creatine kinase 58–91%.12 However, all individuals with PMR • Rheumatoid factor (antinuclear antibody and anticyclic citrullinated peptide should commence calcium and vitamin D antibodies may be considered) supplementation and receive advice about weight • Dipstick urinalysis bearing exercise. In patients deemed at high fracture risk clinically (eg. prior fragility fracture, showed that starting prednisolone doses of 15 • 10–20 mg orally, daily in the morning initially high steroid dose) or following dual energy X-ray mg/day or lower was associated with lower for 2–4 weeks absorptiometry (DXA) scan, a bone sparing agent cumulative steroid dosages than higher starting • then reduce the daily dose by 2.5 mg every (eg. oral biphosphonate) should be considered. doses and that higher doses of corticosteroids 2–4 weeks until the daily dose is less than Medicare rebates are available for patients were associated with more adverse effects.12 In 10 mg having DXA scan who are currently on prolonged addition, higher doses may mask those conditions • then decrease the daily dose by 1 mg every glucocorticoid therapy (such as equivalent to or whose symptoms mimic PMR (Table 2). 4–8 weeks. greater than 7.5 mg prednisolone daily for a for a There is no consistent evidence for an ideal Intramuscular methylprednisolone (intramuscular period anticipated to last for at least 4 months).16 steroid regimen that is suitable for all patients. depomedrone) may be used in milder cases Some bisphosphonates are available on the Therefore, the approach to treatment must be and may reduce the risk of steroid related Pharmaceutical Benefits Scheme for: 'Treatment flexible and tailored to the individual. Dose complications. Initial dose is 120 mg every 3–4 as the sole PBS subsidised anti-resorptive agent adjustment may be required for disease severity, weeks, reducing by 20 mg every 2–3 months.14 for corticosteroid induced osteoporosis in a comorbidity, side effects and patient wishes. The The addition of nonsteroidal anti- patient currently on long term (at least 3 months), British Society for Rheumatology and the British inflammatory drugs to glucocorticoid regimens high dose (at least 7.5 mg per day prednisolone Health Professionals in Rheumatology consensus for the treatment of patients with PMR has or equivalent) corticosteroid therapy with a bone regimen suggests using:9 shown no advantage over steroids alone in terms mineral density (BMD) T-score of –1.5 or less.'17 • daily prednisolone: 15 mg for 3 weeks of duration of therapy or daily or cumulative Follow up and monitoring • then 12.5 mg for 3 weeks prednisone doses, but produced more adverse • then 10 mg for 4–6 weeks events.15 In specialist settings, glucocorticoid Early follow up is vital to evaluate response to • then reduction by 1 mg every 4–8 weeks sparing agents such as methotrexate and other initial therapy and to confirm the diagnosis.18 or alternate day reductions (eg. 10/7.5 mg biological and nonbiological agents may be A patient reported global improvement of alternate days). considered. ≥70% within 1 week of commencing steroids is The Therapeutic Guidelines rheumatology group 13 suggest a similar regimen: Table 5. Indications for referral in polymyalgia rheumatica

Atypical features Table 4. Risks of long term steroid therapy • Age younger than 60 years • Chronic onset more than 2 months • Osteoporosis • Lack of shoulder involvement • Weight gain • Lack of inflammatory stiffness • Skin bruising • Prominent systemic features, weight loss, night pain, neurological signs • Raised blood pressure • Features of other rheumatic disease • Impaired blood glucose • Normal or extremely high acute phase response • Depression • Cardiac failure Treatment dilemmas • Increased risk of infection • Incomplete, poorly sustained or nonresponse to corticosteroids • Cataracts • Inability to reduce corticosteroids • Glaucoma • Contraindications to corticosteroid therapy • Cushing syndrome • Prolonged corticosteroid therapy (more than 2 years)

Reprinted from Australian Family Physician Vol. 40, No. 5, May 2011 305 clinical Polymyalgia rheumatica – diagnosis and management consistent with a diagnosis of PMR. Inflammatory • Suspect PMR in the elderly patient with Polymyalgia rheumatica: a disorder of extraar- ticular synovial structures? J Rheumatol markers usually normalise within 4 weeks. A bilateral shoulder ache and stiffness. 1999;26:517–21. lesser response should prompt a search for an • Document inclusion and exclusion criteria 9. Dasgupta B, Borg F, Hassan N, et al. BSR and BHPR guidelines for the management of polymy- alternative condition. If a relapse of PMR is in the medical record. algia rheumatica. Oxford: Oxford University Press, suspected as the steroid dose is being tapered, • Use the minimum effective steroid dose 2009. the steroid dose can be increased to the initially (15 mg/day prednisolone or less). 10. Gonzalez-Gay M. The diagnosis and management of patients with giant cell arteritis. J Rheumatol previously effective dose level and dose reduction • Taper steroids gradually (<1 mg/month); 2005;32:1186–8. recommenced from that level.13 relapses are common. 11. Cantini F, Salvarani C, Olivieri I, et al. Erythrocyte Each follow up encounter with the GP should • Assess the need for bone sparing agents sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in try to explore the following: and institute osteoporosis prophylaxis polymyalgia rheumatica: a prospective follow-up • response to treatment – degree of reduction early, if required. study. Semin Arthritis Rheum 2000;30:17–24. in proximal pain, fatigue and morning • Atypical features and treatment dilemmas 12. hernandez-Rodrıguez J, Cid M, Lopez-Soto A, et al. Treatment of polymyalgia rheumatica: stiffness warrant referral. a systematic review. Arch Intern Med • complications of disease including symptoms 2009;169:1839–59. Resource 13. Rheumatology Expert Group. Polymyalgia rheu- of GCA (eg. headaches, jaw claudication and matica and giant cell arteritis. In: Therapeutic large vessel disease) The stepped diagnostic and management Guidelines: rheumatology. Melbourne: • steroid related adverse events process recommended by the British Society Therapeutic Guidelines, 2010. 14. Dasgupta B, Dolan AL, Fernandes L, et al. An • atypical features or other mimicking for Rheumatology and the British Health initially double-blind controlled 96 week trial of conditions Professionals in Rheumatology is available depot methylprednisolone against oral predniso- • laboratory monitoring (full blood count, ESR/ at http://rheumatology.oxfordjournals.org/ lone in the treatment of polymyalgia rheumatica. Brit J Rheumatol 1998;37:189–95. CRP, urea and electrolytes, glucose) every 4–6 content/49/1/186/F2.large.jpg. 15. Gabriel S, Sunku J, Salvarani C, et al. Adverse weeks. outcomes of antiinflammatory therapy among Author patients with polymyalgia rheumatica. Arthritis Duration of treatment can vary from 1–3 years, Oliver van Hecke MBChB, MRCGP, FRACGP, Rheum 1997;40:1873–8. and some patients will require small doses of is Lecturer, Department of General Practice, 16. Australian Government Department of Health steroids beyond 3 years.7 Slow prednisolone dose Monash University, Melbourne, Victoria. oliver. and Ageing. Medicare Benefits Schedule - Note D1.27. Available at www9.health.gov.au/mbs/ tapering (<1 mg/month) is important as slower [email protected]. fullDisplay.cfm?type=note&qt=NoteID&q=D1.27. tapering regimens are associated with fewer 17. Australian Government Department of Health relapses and earlier glucocorticoid treatment Conflict of interest: none declared. and Ageing. Pharmaceutical Benefits Scheme. Available at www.pbs.gov.au/browse/body- 12 cessation than faster tapering regimens. system?depth=4&codes=m05ba. Steroids may be stopped when the patient is References 18. Dasgupta B, Salvaran I, Schirmer M, et al. 1. 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