REVIEW Salman Bin Mahmood, MBBS Elizabeth Nelson, MD Jessica Padniewski, DO Rawad Nasr, MD Department of Medicine, Hennepin Healthcare, Department of Medicine, Hennepin Department of Medicine, Hennepin Rheumatology Division Director, Minneapolis, MN Healthcare, Minneapolis, MN Healthcare, Minneapolis, MN Department of Medicine, Hennepin Healthcare, Minneapolis, MN Polymyalgia rheumatica: An updated review ABSTRACT olymyalgia rheumatica (PMR) is eas- P ily recognized when it presents classically, Polymyalgia rheumatica should be suspected in older ie, in an older woman with pelvic girdle stiff- patients with bilateral shoulder and hip stiffness that is ness that improves over the day, elevated in- worse in the morning and improves with use. An array fl ammatory markers, and a rapid response to of nonspecifi c musculoskeletal complaints, constitutional prednisone therapy. But its presentation often symptoms, and elevated serum infl ammatory markers overlaps with that of other rheumatologic and may be present, so other conditions should also be con- infl ammatory syndromes. sidered. Prolonged glucocorticoids with patient-tailored This article provides guidance on the eval- dosing and duration are the mainstay of treatment. uation and management of PMR and discusses Corticosteroid-sparing therapy with adjunctive metho- current and emerging therapies. trexate may benefi t select patients. ■ OLDER ETHNIC EUROPEANS KEY POINTS MOST AFFECTED Rheumatoid arthritis, late-onset spondyloarthritis, and PMR typically presents in people over age 50, RS3PE (remitting seronegative symmetrical synovitis with incidence increasing with age. Annual in- with pitting edema) are important mimics of polymyalgia cidence varies from 12 to 60 cases per 100,000 rheumatica. in different populations, with the highest rate in those of Northern European descent.1,2 Women are more often affected than men. Diagnosis usually requires either an elevated erythrocyte PMR’s etiology is not well understood. Ge- sedimentation rate (> 30 or 40 mm/h) or C-reactive pro- netic and infectious associations have been in- tein level (> 6 mg/dL). vestigated without conclusive results.3,4 Stud- ies in various geographic regions have revealed Ultrasonographic evidence of infl ammation, especially increased numbers of certain polymorphisms subacromial bursitis, increases diagnostic specifi city. for genes involved in the immune system, but they have not been consistently found across Patients should be evaluated at diagnosis and periodi- different populations of patients with PMR.3 cally for the development of giant cell arteritis. ■ PROXIMAL BILATERAL MORNING STIFFNESS To help avoid relapse, therapy should continue until symptoms resolve, followed by slow tapering. The cardinal feature of PMR is proximal girdle pain associated with restricted range of motion and stiffness. Shoulders are affected in up to 95% Preliminary studies show possible benefi t from tocilizu- of cases5; the neck and pelvic girdle can also be mab, an interleukin-6 receptor antibody, as monotherapy involved. Patients often report being unable to or for refractory cases. stand up from a chair, get out of bed without as- doi:10.3949/ccjm.87a.20008 sistance, or lift their arms to comb their hair. CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 87 • NUMBER 9 SEPTEMBER 2020 549 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. POLYMYALGIA RHEUMATICA Bilateral symptoms should particularly ed C-reactive protein (CRP) (> 6 mg/dL),12 raise suspicion for PMR. In some cases, symp- indicating an ongoing infl ammatory process. toms are unilateral at onset, but quickly be- While uncommon, it is possible for levels to be come bilateral and often develop rapidly over normal; in such cases, rheumatology referral is a few days.4 indicated if PMR is otherwise suspected.13 Symptoms are characteristically worse in Conversely, elevated levels alone do not the morning and with inactivity. Morning establish the diagnosis, as ESR and CRP in- stiffness tends to last an hour or more. Pain crease with a variety of conditions, including can also be strikingly severe at night and can normal aging. affect sleep. Other tests may be abnormal ■ INFLAMMATION MAY BE WIDESPREAD Other laboratory fi ndings consistent with an ongoing infl ammatory process and commonly Symptoms are related to infl ammation of the seen in PMR include normochromic anemia, articular and extra-articular structures, caus- thrombocytosis, and leukocytosis.4,14 Liver en- ing synovitis and bursitis of the shoulder, hip, zymes, particularly alkaline phosphatase, may and neck.6 also be elevated.14 Distal joint arthritis may also occur. It is often asymmetric and most commonly affects ■ PMR HAS MANY MIMICS the knees and wrists, with the feet usually Symptoms of PMR may be nonspecifi c, and unaffected.6,7 Infl ammation may also involve many diseases present similarly (Table 1). periarticular structures, causing distal tenosy- Rheumatoid arthritis and spondyloar- novitis and carpal tunnel syndrome.8 Pitting thritis, which may be late-onset, are impor- edema affecting the distal extremities due to tant considerations. Both can present with regional tenosynovitis can occur and occa- distal arthritis, seen in up to half of patients sionally is a presenting feature.7 with PMR.5,15 As in PMR, joint involvement Constitutional symptoms (ie, low-grade in rheumatoid arthritis is usually bilateral and fever, anorexia, fatigue, and asthenia) are also PMR typically symmetric. However, serologic tests for rheu- common, occurring in up to half of patients.9,10 matoid factor and anticitrullinated peptide presents However, persistent high fever is uncommon antibody tend to be positive in rheumatoid ar- with isolated PMR and may signal the con- after age 50 thritis and spondyloarthritis, but not in PMR. currence or development of giant cell arteritis 11 Spondyloarthritides are associated with low (GCA). back pain and stiffness, as well as evidence of sacroiliitis on imaging, which are rare in PMR. ■ PHYSICAL EXAMINATION: RS3PE (remitting seronegative symmetri- PAIN, LIMITED RANGE OF MOTION cal synovitis with pitting edema) involves pit- On physical examination, active range of mo- ting edema in the distal extremities caused by tion is restricted due to pain, without actual extensor tendon synovitis, most commonly weakness, while passive range of motion may involving the dorsal surfaces of the hands be normal. Muscle tenderness may also be and wrists.16,17 Lower-extremity involvement present.10 is much less common. Like PMR, RS3PE re- sponds rapidly to glucocorticoids except when ■ LABORATORY TESTS FOR INFLAMMATION associated with a paraneoplastic syndrome, in Laboratory studies are helpful, as they may in- which case the underlying malignancy must 18,19 dicate an infl ammatory state consistent with be treated. PMR or, alternatively, suggest or help rule out Other medium-to-large-vessel vasculiti- another diagnosis. des, including GCA, may also present with unexplained fever and constitutional symp- Primary tests: ESR and CRP toms. Patients with symptoms of PMR should Most established diagnostic criteria for PMR always be evaluated for signs and symptoms of require either elevated erythrocyte sedimenta- GCA, including new-onset headache, scalp tion rate (ESR) (> 30 or 40 mm/h) or elevat- tenderness, tongue or jaw claudication, and 550 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 87 • NUMBER 9 SEPTEMBER 2020 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. MAHMOOD AND COLLEAGUES TABLE 1 Key features of polymyalgia rheumatica mimics Disease Features Infl ammatory diseases Rheumatoid arthritis Symmetrical joint involvement, autoantibody-positive, may see erosions on imaging in advanced disease Spondyloarthritis Low back involvement, sacroiliac joint tenderness, sacroiliitis on imaging RS3PE (remitting seronegative symmetrical Peripheral edema, extensor synovitis on imaging, may be paraneoplastic synovitis with pitting edema) Crystalline arthropathy Usually involvement of medium to large joints, intermittent symptoms, characteristic radiography and ultrasonographic fi ndings, synovial fl uid analysis positive for crystals Autoimmune myositis Muscle weakness and tenderness, elevated muscle enzymes Other connective tissue diseases Multiorgan involvement, specifi c autoantibodies may be positive, hypocomplementemia Noninfl ammatory diseases Osteoarthritis Pain exacerbated with use, normal infl ammatory markers, degenerative changes on imaging Fibromyalgia Fatigue, chronic pain with more generalized involvement Spinal spondylosis and stenosis Numbness, paresthesias, muscle weakness, normal infl ammatory markers Parkinson disease Muscle stiffness primary complaint, other symptoms typical of Parkinson disease including tremor and rigidity Infection Fever, heart murmur, leukocytosis, positive blood cultures Malignancy Weight loss, diffuse symptoms usually not limited to shoulder or pelvic girdle, and paraneoplastic syndromes lack of response to low-dose glucocorticoid therapy Drug-induced myopathy Lack of systemic symptoms, muscle weakness and tenderness, improvement (eg, statin, glucocorticoid, colchicine) with discontinuation of drug, elevated muscle enzymes, positive anti-HMG-CoA reductase antibody Thyroid and parathyroid disease Systemic symptoms typical of endocrinopathy; abnormal thyroid markers; abnormal calcium, phosphorus, or parathyroid levels vision changes. If GCA is suspected, temporal