Polymyalgia Rheumatica (PMR)

Definition, Etiology, PathogenesisTop

Polymyalgia rheumatica (PMR) is an inflammatory disease of unknown etiology that affects individuals aged >50 years, women 4 times more frequently than men, with an incidence of 20 to 50 cases per 100,000 persons. It is characterized by pain and stiffness of the muscles of the neck, shoulder girdle, and/or pelvic girdle.

Clinical Features and Natural HistoryTop

Pain in the muscles of the shoulder girdle, pelvic girdle, and neck, sometimes worsening at night, along with morning stiffness lasting ≥30 minutes are the classic symptoms of PMR. Initially the pain may be unilateral, but later it involves both sides symmetrically and can make it difficult or impossible for the patient to elevate the upper extremities. Arthritis is often present, most frequently involving the knees, sternoclavicular joints, and hips. Other symptoms may include pitting edema of the hands and feet as well as muscle weakness, which in more advanced disease may be followed by muscle atrophy and contractures. General symptoms may include low-grade fever, weight loss, and depression. In ~20% of patients PMR coexists with giant cell arteritis.

In the majority of cases symptoms resolve with treatment. Relapses are rare.

DiagnosisTop

Diagnostic Tests

1. Blood tests: Elevated erythrocyte sedimentation rate (ESR) (usually >100 mm after 1 hour, very rarely normal or only slightly elevated), elevated acute-phase protein levels (C-reactive protein [CRP], fibrinogen), moderate normochromic or hypochromic anemia, thrombocytosis, eosinophilia, and/or mildly elevated serum liver enzyme levels (particularly alkaline phosphatase).

2. Imaging studies: Ultrasonography and magnetic resonance imaging (MRI) may reveal synovitis of the involved joints, bursitis, and inflammation of the tendon sheaths.

Diagnostic Criteria

Healey criteria for the diagnosis of PMR: All of the following are required for diagnosis:

1) Pain persisting for ≥1 month at ≥2 of the following sites: neck, shoulders, pelvic girdle.

2) Morning stiffness lasting >1 hour.

3) Prompt response to prednisone (20 mg/d).

4) Exclusion of other conditions that may account for symptoms (see Differential Diagnosis, below).

5) Age >50 years.

6) ESR >40 mm/h.

Differential Diagnosis

Differential diagnosis should include early stages of rheumatoid arthritis (especially in elderly patients, absence of rheumatoid factor and anti–citrullinated peptide antibody may be helpful, although not conclusive) and other types of arthritis, systemic connective tissue diseases (differentiated by multiorgan involvement, specific autoantibodies), polymyositis, and other myopathies (distinguished by muscle weakness and elevated muscle enzyme levels). Other considerations include fibromyalgia (ESR and CRP are not elevated), malignancy, osteoarthritis, neurologic disorders (eg, parkinsonism), bone diseases, infections, hypothyroidism, myalgia due to muscle overuse, and depression.

TreatmentTop

1. Glucocorticoids: Oral prednisone 15 to 20 mg/d (or another glucocorticoid at an equivalent dose) should be administered, with clinical improvement expected within a few days (resolution of pain and stiffness, normalization of ESR and CRP levels).Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the small sample size of randomized trials and heterogeneity of study designs. Hernández-Rodríguez J, Cid MC, López-Soto A, Espigol-Frigolé G, Bosch X. Treatment of polymyalgia rheumatica: a systematic review. Arch Intern Med. 2009 Nov 9;169(20):1839-50. doi: 10.1001/archinternmed.2009.352. Review. PubMed PMID: 19901135. Kyle V, Hazleman BL. Treatment of polymyalgia rheumatica and giant cell arteritis. I. Steroid regimens in the first two months. Ann Rheum Dis. 1989 Aug;48(8):658-61. PubMed PMID: 2782975; PubMed Central PMCID: PMC1003842. In exceptional cases, when no improvement has been observed after a week, the glucocorticoid may be continued for another week at a dose of 30 mg/dEvidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of studies and sparse data. Hutchings A, Hollywood J, Lamping DL, et al. Clinical outcomes, quality of life, and diagnostic uncertainty in the first year of polymyalgia rheumatica. Arthritis Rheum. 2007 Jun 15;57(5):803-9. PubMed PMID: 17530680.; however, if the patient still does not improve, the diagnosis should be reevaluated. Once symptoms begin to resolve, continue the treatment with prednisone, gradually tapering the dose down on an individual basis by monitoring clinical disease activity and decreasing ESR and CRP levels.Evidence 3 Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of studies. Hernández-Rodríguez J, Cid MC, López-Soto A, Espigol-Frigolé G, Bosch X. Treatment of polymyalgia rheumatica: a systematic review. Arch Intern Med. 2009 Nov 9;169(20):1839-50. doi: 10.1001/archinternmed.2009.352. Review. PubMed PMID: 19901135. Hutchings A, Hollywood J, Lamping DL, et al. Clinical outcomes, quality of life, and diagnostic uncertainty in the first year of polymyalgia rheumatica. Arthritis Rheum. 2007 Jun 15;57(5):803-9. PubMed PMID: 17530680. Cantini F, Salvarani C, Olivieri I, et al. Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia rheumatica: a prospective follow-up study. Semin Arthritis Rheum. 2000 Aug;30(1):17-24. PubMed PMID: 10966209. For instance, after 2 to 3 weeks reduce the daily dose by 2.5 mg every 2 weeks down to 10 mg, and then to 7.5 mg, 5 mg, and 2.5 mg every 2 to 4 weeks to discontinuation. In patients with recurrent symptoms, return to the previous dose until remission is achieved, and subsequently taper the dose down less rapidly. Treatment may last ≥1 year and may commonly be extended to 2 years.Evidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of studies and risk of bias. Kremers HM, Reinalda MS, Crowson CS, Zinsmeister AR, Hunder GG, Gabriel SE. Relapse in a population based cohort of patients with polymyalgia rheumatica. J Rheumatol. 2005 Jan;32(1):65-73. PubMed PMID: 15630727. Narváez J, Nolla-Solé JM, Clavaguera MT, Valverde-García J, Roig-Escofet D. Longterm therapy in polymyalgia rheumatica: effect of coexistent temporal arteritis. J Rheumatol. 1999 Sep;26(9):1945-52. PubMed PMID: 10493675. Note the importance of prophylaxis of osteoporosis in patients with PMR (see Osteoporosis).Evidence 5Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Homik J, Cranney A, Shea B, et al. Bisphosphonates for steroid induced osteoporosis. Cochrane Database Syst Rev. 2000;(2):CD001347. Review. Update in: Cochrane Database Syst Rev. 2016 Oct 05;10: CD001347. PubMed PMID: 10796432. Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P. Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev. 2000;(2):CD000952. Review. PubMed PMID: 10796394. Grossman JM, Gordon R, Ranganath VK, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). 2010 Nov;62(11):1515-26. doi: 10.1002/acr.20295. Epub 2010 Jul 26. Review. Erratum in: Arthritis Care Res (Hoboken). 2012 Mar;64(3):464. PubMed PMID: 20662044.

2. In patients with contraindications to long-term glucocorticoid treatment and/or ≥2 relapses, some authors suggest the use of methotrexate 10 mg once weekly.Evidence 6Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the small size of randomized controlled trials, inconsistency, and lack of reduction in adverse events due to glucocorticoids. Mahr AD, Jover JA, Spiera RF, et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum. 2007 Aug;56(8):2789-97. PubMed PMID: 17665429.Hernández-Rodríguez J, Cid MC, López-Soto A, Espigol-Frigolé G, Bosch X. Treatment of polymyalgia rheumatica: a systematic review. Arch Intern Med. 2009 Nov 9;169(20):1839-50. doi: 10.1001/archinternmed.2009.352. Review. PubMed PMID: 19901135.

3. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be useful and used in patients with persistent mild musculoskeletal symptoms in spite of a completed glucocorticoid treatment.Evidence 7Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of studies and indirectness. Gabriel SE, Sunku J, Salvarani C, O'Fallon WM, Hunder GG. Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica. Arthritis Rheum. 1997 Oct;40(10):1873-8. PubMed PMID: 9336424. Hernández-Rodríguez J, Cid MC, López-Soto A, Espigol-Frigolé G, Bosch X. Treatment of polymyalgia rheumatica: a systematic review. Arch Intern Med. 2009 Nov 9;169(20):1839-50. doi: 10.1001/archinternmed.2009.352. Review. PubMed PMID: 19901135.

Follow-UpTop

Monitor the patient for:

1) Efficacy of the glucocorticoid therapy and occurrence of adverse effects (monitor the blood pressure, blood glucose, and electrolyte levels).

2) Symptoms of giant cell arteritis (often temporal arteritis; see Giant Cell Arteritis). The patient should be advised to immediately seek medical help upon observing any symptoms of visual disturbances, headache, scalp tenderness, or claudication of the jaw, as PMR coexists with giant cell arteritis in ~20% of patients.