Polymyalgia rheumatica (PMR)was first described by Bruce in

18881 and is the commonestinflammatory rheumatological dis-order affecting older people.2 Ithas an incidence of 8.4 per 10 000patient years in the UK3 and carriesa lifetime risk of 2.4 per cent inwomen and 1.7 per cent in men.4

With an ageing population,5 thenumber of patients with PMR is setto increase.

Clinical courseNo gold-standard diagnostic testexists for PMR and so accuratediagnosis can be challenging.Patients are typically over 50 yearsof age and present classically withbilateral shoulder and hip girdlepain and morning stiffness.6

Additionally typical cases haveraised inflammatory markers and

respond markedly to low-dose cor-ticosteroids. An initial dose of 15mgprednisolone is recommended inUK PMR guidelines.6,7 A graduallytapered dose of prednisoloneremains the cornerstone of treat-ment, which is often needed for 18months or more. As such, regularmonitoring, screening and, ifappropriate, prophylaxis for poten-tial corticosteroid-associated side-effects and complications form apivotal part of on-going manage-ment.

An essential aspect of diagnosisshould be directed towards exclud-ing other disorders that can mimicPMR (see Table 1). Accurate diag-nosis is essential as some of thesedisorders may also respond initiallyto low-dose corticosteroids thatmay in turn result in inappropriateprolonged treatment or a delayed

diagnosis of the true underlyingpathology.

A full physical examination aswell as additional laboratory tests,as highlighted in the latest BritishSociety for Rheumatology/BritishHealth Professionals in Rheum -atology (BSR/BHPR) PMR guid-ance,6 should be undertaken torule out other causes of symptoms.

A low threshold for early refer-ral for specialist review should besought where there is diagnosticuncertainty.

CausesThe cause of PMR remains elusive.Shoulder synovial membranesexhibit mild synovitis charac-terised by macrophages and CD4+T lymphocytes.8 Links betweenPMR and an infective agentremain controversial.9 However,

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Prescribing in practice

Recommended management of

polymyalgia rheumaticaToby Helliwell MRCGP, Samantha Hider PhD, FRCP and Christian Mallen PhD, MRCGP

The authors describe the

causes, diagnosis and rec-

ommended management of

polymyalgia rheumatica, the

commonest rheumatological

disorder in the elderly.

Figure 1. Corticosteroids, usually prednisolone, are the mainstay of treatment in poly -

myalgia rheumatica; the dose is gradually tapered over up to 18 months

an association between patientswith PMR and HLA-DRB1 allelesin certain populations has beenshown.10

Role of the GPPatients with PMR are managedlargely in general practice: over 80per cent of patients with PMR are

managed exclusively by their GP.11

Early specialist review is should besought for diagnostic confirmationin cases of uncertainty, atypical clin-ical presentations, multiple relapsesor treatment conundrums.6

General practice is therefore inti-mately involved in the identifica-tion, diagnostic work-up, treatmentand on-going monitoring ofpatients with PMR.

A practice with 10 000 patientswill expect to have 20 with PMRconsulting over a 12-monthperiod,12 although this is depend-ent on the practice’s demographiccomposition and geographicallocation.3

Role of the specialistAccurate PMR diagnosis is essentialto prevent inappropriate long-termsteroid use. In patients presentingwith atypical features (eg no shoul-der symptoms), normal or veryraised inflammatory markers or

diagnostic uncertainty, specialistreferral should be considered.Indications for specialist referralare summarised in Table 2.

TreatmentCorticosteroidsThe first-line and mainstay of treat-ment for PMR is corticosteroids,usually oral prednisolone in a start-ing dose of 15mg daily.6

The mechanism of action ofcorticosteroids in PMR is not fullyunderstood, although it has beenhypothesised that their anti-inflam-matory and immune-modulatoryeffects reduce inflammatory medi-ators and cytokine production.13

Although there is no consistentevidence for the ideal steroid regi-men, the BSR/BHPR guidelines6

advocate a steroid dose-reducingregimen of:• daily prednisolone 15mg forthree weeks• then 12.5mg for three weeks• then 10mg for four to six weeks• then reduction by 1mg every fourto eight weeks or alternate-dayreductions, eg 10/7.5mg alternatedays, etc.

Studies suggest7 that pred-nisolone starting doses of >15mgdaily are associated with a higherrate of adverse events with no addi-tional benefit. Dose adjustmentmay be required for disease sever-ity, co-morbidity and adverseevents.

Although other steroids such asdeflazacort (Calcort)14 and dexa -methasone are available, evidencesupporting their use over oral pred-nisolone in PMR is lacking.7

Further studies are needed to accu-rately define the appropriatesteroid dose, formulation and tim-ing of administration.

Data suggest that up to 30 percent of patients remain on pred-nisolone at three years.7 Given therisks of osteoporosis with long-termsteroid use,15 BSR guidance advo-

38 Prescriber 19 March 2013 www.prescriber.co.uk

Prescribing in practice

Table 1. Disorders that can mimic PMR

Inflammatory

late-onset rheumatoid arthritis, spondyloarthritides, psoriatic arthritis, SLE,

scleroderma, Sjögren’s syndrome, vasculitis, inflammatory myopathies

Noninflammatory

osteoarthritis, rotator cuff disorders, frozen shoulder

fibromyalgia

endocrine disorders, eg hypo/hyperthyroidism, hypo/hyperparathyroidism

drug-induced myalgia, eg statins

Parkinson’s disease

pain syndromes, eg complex regional pain and chronic pain syndrome

lymphoma, myeloma, leukaemia, solid tumours and metastases, eg prostate,

bowel, lung, breast, renal

TB, bacterial endocarditis, osteomyelitis, septic arthritis, other infections, eg UTI

Rheumatological

Infection

Malignancies

Other

Table 2. Indications for referral and on-going specialist

management6

• younger patients (less than 60 years old)

• long duration of onset (more than 2 months)

• absence of shoulder symptoms

• absence of inflammatory stiffness

• systemic features, weight loss, night pain, neuro -

logical signs

• possibility of other rheumatic disease

• normal or very high acute-phase response

• incomplete, poorly sustained or nonresponse to

corticosteroids

• inability to reduce corticosteroids

• contraindications to corticosteroid therapy

• the need for prolonged corticosteroid therapy (>2 years)

cates all patients being given adviceregarding weight-bearing exerciseand calcium and vitamin D supple-mentation.6

Oral bisphosphonates shouldbe considered in those at high riskof fracture (age >65 years or withprior fragility fracture) or requiringa higher initial steroid dose or witha T score on dual-energy X-rayabsorptiometry (DEXA) of <-1.5.6

Other risk stratification scores, egWHO Fracture Risk AssessmentTool (FRAX), may be employed tohelp evaluate the need for addi-tional bone protection.

Assessment of symptom relapseshould be clinically based and man-aged by increasing the dose of cor-ticosteroid to the previous dose thatcontrolled symptoms.6 Higherdoses may be required to regainsymptom control and in these cir-cumstances specialist review shouldbe strongly considered.6

Steroid cards should be carriedby all patients treated with long-term corticosteroids and especiallyin patients with PMR as the hypo-thalamic-pituitary-adrenal (HPA)axis is suppressed in this condi-tion16 meaning patients may beunable to mount an adequatestress response to intercurrent ill-ness, infection or if undergoingsurgery.

Long-term use of cortico -steroids is associated with numer-ous side-effects and complications(see Table 3). Gastric events (dys-phagia and dyspepsia) are the sec-ond most commonly reportedside-effects after psychological dis-turbances.18 The management ofPMR must therefore involve regu-lar monitoring and screening forassociated side-effects and compli-cations, and appropriate prophy-laxis should be provided whenindicated.

Second-line treatmentoptionsMethylprednisoloneTwo studies19,20 have evaluatedmethylprednisolone in the treat-ment of PMR. However, oral prednisolone controlled symp-toms more rapidly and hadhigher steroid discontinuationrates and therefore methylpred-nisolone is only advocated inmilder cases.6

MethotrexateMethotrexate may be considered asa steroid-sparing agent at a dose of10–15mg weekly either when thereare complications with steroidtreatment or a failure to respond tosteroids alone.

Use of methotrexate seems toreduce the cumulative steroid dose,although superiority of combina-tion treatment compared to steroidtreatment alone has not yet beenfully established.21

Failure to reduce the steroiddose should prompt specialist refer-ral for consideration of methotrex-ate, which should not be initiatedin primary care.

Biological agentsA study using infliximab as an ini-tial steroid-sparing agent in newlydiagnosed PMR cases found no dif-ference in the duration and cumu-lative steroid dose or number ofrelapses at 12 months in thosetreated.22

Similarly etanercept had only amodest effect on steroid-naïve PMRpatients, suggesting that the role oftumour necrosis factor (TNF) isminor.23

The effect of newer biologicalagents including the interleukin-6(IL-6) inhibitor tocilizumab has yetto be established.24

DiscussionIncreased awareness of this com-mon disorder, complemented by

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Prescribing in practice

Table 3. Complications and side-effects of corticosteroids17

Gastrointestinal

dyspepsia, pancreatitis, peptic ulceration and perforation, oesophageal

ulceration and candidosis

Musculoskeletal

muscle weakness, osteoporosis, vertebral/long bone fracture, tendon rupture,

avascular necrosis

Endocrine

diabetes, menstrual irregularities, hirsutism, weight gain, raised cholesterol,

hyperlipidaemia, Cushing’s syndrome

increased susceptibility to infections

Neuropsychiatric

psychological dependence, insomnia, confusion, hypomania, depression,

raised intracranial pressure, aggravation of schizophrenia and epilepsy

Ophthalmic

glaucoma, papilloedema, cataracts, ophthalmic viral or fungal disease, raised

intraocular pressure

Additional

impaired healing, ecchymosis, urticaria, hyperhidrosis, skin atrophy, bruising,

myocardial rupture post recent MI, congestive cardiac failure, leucocytosis,

headache, vertigo

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Prescribing in practice

robust evidence-based diagnosticand management guidance, isessential to improve the manage-ment and outcomes for patientsdiagnosed with PMR.

This needs to be comple-mented with regular follow-up andscreening to avoid the potentiallyserious complications and side-effects of current suggested treat-ments.

Oral corticosteroids remain thecornerstone of treatment.

The future of improved symp-tomatic control may lie in novelmodified-release corticosteroiddelivery systems that are being tri-alled with good effect in patientswith rheumatoid arthritis where,like PMR, morning symptoms pre-dominate.25

Declaration of interestsNone to declare.

References1. Bruce W. Br Med J 1888;2:811.2. Michet CJ, et al. Br Med J 2008;336:765–9.3. Smeeth L, et al. Ann Rheum Dis 2006;65(8):1093–8. 4. Crowson CS, et al. Arthritis Rheum2011;63:633–9. 5. Christensen K, et al. Lancet 2009;374:1196–208.6. Dasgupta B, et al. Rheumatology2010;49:186–90. 7. Hernández-Rodríguez J, et al. ArchIntern Med 2009;169:1839–50. 8. Meliconi R, et al. Arthritis Rheum1996;39:1199–207.9. Nuti R, et al. J Rheumatol 2005;32:200–1.10. Gonzalez-Gay MA, et al. SeminArthritis Rheum 2003;33:38–48.11. Barraclough K, et al. Family Practice2008;25:328–33. 12. Musculoskeletal Matters. Bulletin 2.www.keele.ac.uk/research/pchs/pcmrc/dissemination/bulletin/pdf/MusculoskeletalMatters2.pdf.13. Dasgupta B. Br J Rheumatol 1998;

37:102.14. Cimmino MA, et al. Ann Rheum Dis1994;53:331–3.15. Mazzantini M, et al. J Rheumatol2012;39:552–7.16. Demir H, et al. Scandinavian J Rheum2006;35:217–23.17. BNF.org.18. Hoes JN, et al. Ann Rheum Dis2009;68(12):1833–819. Salvarani C, et al. Rheumatol 2000;27:1470–6.20. Dasgupta B, et al. Br J Rheumatol1998;37:189–95.21. Spies CM, et al. Clin Exp Rheumatol2010;28(Suppl 61):S172–7.22. Salvarani C, et al. J Rheumatol 2003;30:760–3.23. Kreiner F, et al. Arthritis Res Ther2010;12:R176. Epub 2010.24. Unizony S, et al. Arthritis Care Res(Hoboken) 2012;64:1720–9.25. Buttgereit F, et al. Ann Rheum Dis2013;72:204–10.

Dr Helliwell is an NIHR In PracticeFellowship researcher, Dr Hider is sen-ior lecturer and honorary consultantrheumatologist and Christian Mallenis professor of general practice,Arthritis Research UK Primary CareCentre, Primary Care Sciences, KeeleUniversity

This article includes independentresearch arising from an In-PracticeFellowship supported by theNational Institute for HealthResearch. The views expressed arethose of the authors and not neces-sarily those of the NHS, the NationalInstitute for Health Research or theDepartment of Health.

• accurate diagnosis is key and early specialist referral should be sought in

diagnostic and treatment uncertainty

• initiating dose of prednisolone is 15mg/day

• all patients on corticosteroids should receive calcium and vitamin D supple-

mentation with high-risk patients receiving additional osteoporosis prophyl -

axis

• if treating with long-term corticosteroids, offer osteoporosis prophylaxis to

high-risk patients, otherwise arrange DEXA scan

• consider gastric prophylaxis

• treat clinical relapse by increasing prednisolone to the previous dose that

controlled symptoms

• second-line treatment, eg methotrexate, should only be initiated by a

hospital specialist

Key prescribing points