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Clinical manifestations and diagnosis of polymyalgia rheumatica
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Clinical manifestations and diagnosis of polymyalgia rheumatica
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Literature review current through: Aug 2017. | This topic last updated: Sep 01, 2017.

INTRODUCTION — Polymyalgia rheumatica (PMR) is an inflammatory rheumatic condition characterized clinically by aching and morning stiffness about the shoulders, hip girdle, and neck. It can be associated with giant cell (temporal) arteritis (GCA); the two disorders may represent different manifestations of a shared disease process.

When the diagnosis of PMR is considered, two main issues arise:

How is the diagnosis established and distinguished from other disorders that can produce similar symptoms?

Does the patient also have GCA?

The major features of PMR, with emphasis on clinical manifestations and diagnosis, will be reviewed here. Issues related to the treatment of PMR and to the diagnosis and treatment of GCA are discussed separately. (See "Treatment of polymyalgia rheumatica" and "Clinical manifestations of giant cell (temporal) arteritis" and "Diagnosis of giant cell (temporal) arteritis" and "Treatment of giant cell (temporal) arteritis".)

EPIDEMIOLOGY — Polymyalgia rheumatica (PMR) is almost exclusively a disease of adults over the age of 50, with a prevalence that increases progressively with advancing age. The peak incidence of PMR occurs between ages 70 and 80 [1].

PMR is relatively common. The lifetime risk of PMR is second only to rheumatoid arthritis (RA) as a systemic rheumatic disease in adults [2]. Women are affected two to three times more often than men. Cases of familial aggregation are recognized [3].

The annual incidence varies geographically and is highest in Scandinavian countries and in people of northern European descent [4]. In Europe, for example, the incidence rates for the population ≥50 years are highest in northern regions (113 per 100,000 per year in Norway) and much lower in southern areas (13 per 100,000 per year in Italy) [5,6]. In Olmsted County, Minnesota, where the population is predominantly of Scandinavian descent, the incidence is 63.9 per 100,000 per year, with a prevalence of 701 out of 100,000 [7-9]. PMR is distinctly less common in Asian, African-American, and Latino populations, though all racial and ethnic groups can be affected.

Polymyalgia rheumatica and giant cell (temporal) arteritis — PMR is two to three times more common than giant cell (temporal) arteritis (GCA) and occurs in about 50 percent of patients with GCA [10]. The percentage of patients with PMR who experience GCA at some point varies widely in reported series, ranging from roughly 5 to 30 percent [1,11,12]. A figure of 10 percent seems most consistent with clinical practice. PMR can precede, accompany, or follow GCA.

PATHOGENESIS AND PATHOPHYSIOLOGY — The cause of polymyalgia rheumatica (PMR) is unknown.

In addition to the frequent clinical association between PMR and giant cell (temporal) arteritis (GCA), there are pathogenic similarities (see "Pathogenesis of giant cell (temporal) arteritis"). Both PMR and GCA are associated with specific alleles of human leukocyte antigen (HLA)-DR4. There is also a sequence polymorphism within the hypervariable region of the HLA-DRB1 gene that maps to the antigen-binding cleft of the HLA-DR molecules, suggesting an important role for antigen selection and presentation. Patients with GCA and PMR share this sequence polymorphism, which is not found in patients with rheumatoid arthritis (RA) [13]. Studies of the immunogenetics of PMR contain somewhat limited numbers and need validation in larger patient cohorts.

Other immunologic abnormalities shared by PMR and GCA include a similar distribution of circulating CD4+ T-cell subsets; in both conditions, Th17 cells are increased and Treg cells are decreased. The proinflammatory cytokine interleukin (IL)-6 is elevated in the peripheral blood of patients with PMR and GCA and is thought to be responsible for their constitutional manifestations.

Evidence of subclinical arterial inflammation, including activated dendritic cells, IL-1, and IL-6 can be detected in the temporal arteries of some patients with PMR who have no clinical evidence of GCA [14]. However, unlike GCA, interferon gamma-producing T cells are not prominent.

Some studies of PMR and GCA have suggested a cyclical pattern in incidence and seasonal variation, indicating a possible environmental infectious trigger [4]. Results of studies of several viruses as potential triggers have been inconclusive.

The term polymyalgia rheumatica implies a myopathic process, but the muscle in PMR is histopathologically normal. It is in fact the proximal articular and periarticular structures (joints, bursae, and tendons) that are mainly affected in PMR, as has been demonstrated by scintigraphy, ultrasonography, magnetic resonance imaging (MRI), and positron emission tomography (PET) [15-18] (see 'Imaging' below). Findings at the shoulders include subdeltoid/subacromial bursitis, biceps tenosynovitis, and glenohumeral synovitis. Bilateral subdeltoid/subacromial bursitis is an imaging hallmark of PMR; a meta-analysis of four ultrasound (US) studies found this abnormality in 66 percent (95% CI 36-87 percent) of patients [19]. Trochanteric bursitis and synovitis at the hips can be seen, as well as iliopsoas bursitis [20,21].

Proximal upper-extremity symptoms in PMR thus arise from glenohumeral synovitis, biceps tenosynovitis, and subdeltoid/subacromial bursitis, while pelvic girdle symptoms result from hip synovitis and bursitis.

MRI has also shown evidence for interspinous bursitis in the cervical and lumbar spine [22,23] and tenosynovitis at the hands [24]. Additionally, MRI studies have suggested a potential role for capsular inflammation and involvement of the enthesis (the insertions of tendons, ligaments, and capsules) in the pathogenesis of PMR [19,25].

A synovitis characterized by macrophages and CD4+ T lymphocytes has been described in synovial membranes from involved joints [26].

CLINICAL MANIFESTATIONS

History — Polymyalgia rheumatica (PMR) is characterized by symmetrical aching and stiffness about the shoulders, hip girdle, neck, and torso, worst on arising in the morning, of recent onset, in a patient over the age of 50 (figure 1).

Onset – It is typically a recent, discrete change in musculoskeletal symptoms that prompts the patient with PMR to seek medical attention. The onset can be abrupt, sometimes startlingly so, seeming to occur almost overnight. A story of longstanding stiffness and aching does not suggest a diagnosis of PMR.

Pattern of symptoms – Symptoms in PMR involve aching and stiffness about the upper arms, posterior neck, pelvic girdle, and/or lumbar region; they can initially be unilateral but soon become symmetrical. Bilateral achiness about the upper arms with limitation of active shoulder abduction is particularly common and often commands the clinical presentation. Pelvic girdle symptoms manifest as pains about the groin and lateral aspects of the hips and are frequently reported as radiating to the posterior aspects of the thighs. The proximally distributed aching and stiffness represent referred symptoms from the joints and periarticular structures of the shoulders and hips.

Distal symptoms, generally mild, accompany the characteristic proximal symptomatology in about one-half of patients, most commonly at the wrists and metacarpophalangeal joints, and occasionally at the knees, but not the feet and ankles. Carpal tunnel syndromes, due to wrist involvement, can be found in 10 to 15 percent of patients [27]. Occasionally, distal symptoms at the hands and wrists are of explosive onset and exuberant extent. (See 'Differential diagnosis' below.)

Morning stiffness and the gel phenomenon – Gelling, or stiffness with inactivity, is a hallmark of synovitis in the systemic rheumatic diseases in general, but in PMR this phenomenon can be notably severe. Morning stiffness in PMR is invariable; its absence excludes a diagnosis of PMR. In untreated PMR, morning stiffness can last into the late morning or afternoon. After inactivity, such as after a longer car ride, stiffness can recur. Nocturnal pain is common.

Functional limitations – Proximal stiffness can result in difficulties with activities of daily living, such as pulling on a shirt or coat, hooking a bra in the back, donning socks and shoes, or transferring from the supine or seated position to standing. The intensity of the gel phenomenon, coupled with proximal stiffness, can be such that patients require assistance with morning dressing.

Systemic signs and symptoms – Patients with PMR can experience nonspecific systemic signs or symptoms, including malaise, fatigue, depression, anorexia, weight loss, and low-grade fever. The high spiking fever that can accompany giant cell (temporal) arteritis (GCA), however, is rare in patients who have only PMR. In general, the occurrence of any fever in suspected PMR should prompt a search for underlying GCA or other pathology, especially infection. (See 'Evaluation for GCA' below and 'Differential diagnosis' below and "Diagnosis of giant cell (temporal) arteritis".)

Physical examination — As PMR is a disorder of the joints and bursae, the critical part of the physical examination is the joint examination.

Joint examination – Range of motion about the shoulder, cervical spine, and hips can be limited. Restricted shoulder motion is especially common; a classic finding in PMR is the inability to actively abduct the shoulders past 90 degrees (picture 1). In about one-half of patients, distal findings can be identified. Clinical synovitis can occur at the peripheral joints, especially at the wrists and metacarpophalangeal joints, and is usually mild [27-30]. Minor knee effusions can be found. The feet and ankles are never affected.

An unusual manifestation of distal involvement is the puffy edematous hand syndrome, or remitting symmetrical synovitis with peripheral edema (RS3PE) syndrome (picture 2). In this presentation, distal symptoms and signs can appear explosively and abruptly and often dominate the clinical situation. (See 'Differential diagnosis' below.)

Neurologic examination – The muscles are normal in PMR, and though patients may complain of subjective weakness, and though the motor examination can be problematic in an older adult who is in pain, careful neurologic evaluation will demonstrate normal muscle strength. Tenderness to muscle palpation is a nonspecific sign, and what tenderness there may be about the shoulders relates to articular or bursal involvement.

Laboratory findings — The erythrocyte sedimentation rate (ESR) can be normal, mildly elevated, or even markedly elevated:

The characteristic laboratory finding in PMR is an elevated ESR, with occasional patients having values that can exceed 100 mm/hour. In one study, for example, 20 percent of patients had ESR values over 104 mm/hour [31].

Conversely, studies have found that approximately 5 to 20 percent of patients with PMR have ESRs less than 40 mm/hour [32-34].

Some evidence suggests that an elevated serum C-reactive protein (CRP) level is more common than a high ESR. In two reports from the same group, an elevated ESR (greater than 30 mm/hour) was noted in 92 to 94 percent of patients at the time of diagnosis of PMR, while 99 percent of such patients had an increased serum CRP level (greater than 5 mg/L) [31,35]. In one of these studies, 9 of the 10 patients with a normal ESR at time of diagnosis had an elevated CRP (median 14 mg/L, range 7 to 47 mg/L), although mean values tended to be lower in these patients than in the PMR group as a whole (19 versus 68 mg/L). In another study, only 1.5 percent of patients had an ESR and CRP within normal limits (defined as less than 20 mm/hour and 10 mg/L, respectively) at the time of diagnosis [29].

Other laboratory findings are nonspecific:

A normocytic anemia may be present, and the white blood cell and platelet counts are usually normal, though thrombocytosis can occur as part of a general acute inflammatory response.

Serologic tests, such as antinuclear antibodies, rheumatoid factor, and cyclic citrullinated peptide antibodies are typically negative. The prevalence of positive assays for antinuclear antibody and rheumatoid factor rises with age.

Liver function tests, especially alkaline phosphatase, are occasionally elevated, although these abnormalities are more common in patients with GCA than isolated PMR. The creatine kinase (CK) is always normal.

Imaging — As discussed above, there are characteristic features of periarticular structures (eg, bursitis and tenosynovitis) that can be seen on ultrasonography, magnetic resonance imaging (MRI), and positron emission tomography (PET) (see 'Pathogenesis and pathophysiology' above). Routine radiographs do not show abnormalities in patients with PMR.

Ultrasound (US) and MRI can demonstrate synovitis of the glenohumeral and hip joints and frequent involvement of extraarticular structures, especially the subacromial/subdeltoid bursa, long head of the biceps, and trochanteric bursa. While subdeltoid/subacromial bursitis is a characteristic imaging feature of PMR, it is not specific and is seen in patients with rheumatoid arthritis (RA) and other shoulder pathology [16]. (See 'Pathogenesis and pathophysiology' above and "Bursitis: An overview of clinical manifestations, diagnosis, and management", section on 'Subacromial bursitis'.)

PET scanning — PET scanning can also identify bursitis [36]. This modality has been of additional interest in the investigation of underlying vascular involvement. In a series of 13 patients with suspected PMR who underwent 18-fluorodeoxyglucose PET scanning prior to initiation of glucocorticoid therapy, 12 had increased uptake in vascular regions as assessed by visual inspection of the images and by a computer-aided quantitative analysis [37]. Another study of PET scanning demonstrated increased uptake in the subclavian arteries in one-third of 35 patients with PMR, though less intense than that observed in GCA [18]. While increased uptake of radiolabeled glucose is suggestive of large-vessel vasculitis, histologic examination of the aorta and large arteries is obviously not feasible.

The practical implications of subclinical inflammation of the great vessels in PMR is unclear, and further study is needed to determine whether the findings on PET scanning are of prognostic or therapeutic consequence. It is unusual for patients with PMR without clinical features of GCA to develop large-vessel complications such as stenoses or aneurysms.

DIAGNOSIS

General approach — There is no pathognomonic test or established diagnostic criteria for polymyalgia rheumatica (PMR). We use the presence of all of the following empirically formulated criteria for the clinical diagnosis of PMR in whom another disease to explain the findings is not present [28,38-40]:

Age 50 years or older at disease onset.

Proximally and bilaterally distributed aching and morning stiffness (lasting at least 30 minutes or more) persisting for at least two weeks. The stiffness should involve at least two of the following three areas: neck or torso, shoulders or proximal regions of the arms, and hips or proximal aspects of the thighs.

Erythrocyte sedimentation rate (ESR) ≥40 mm/hour.

Rapid resolution of symptoms with low-dose glucocorticoids. Symptoms are generally 50 to 70 percent better within three days in patients with PMR started on prednisone at a dose of 10 to 20 mg/day, and almost all patients respond completely within three weeks of beginning treatment. The lack of response to initial therapy strongly suggests an alternative diagnosis. Symptomatic improvement with low-dose glucocorticoid treatment can also be seen in patients with rheumatoid disease, psoriatic arthritis, and other inflammatory arthritides.

Although classification criteria for PMR have been proposed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR), they should not be used as diagnostic criteria [41]. It is important to emphasize that the proposed criteria are designed as a research tool to distinguish PMR from other conditions and are not intended for the diagnosis of an individual patient [42].

Atypical presentations — In atypical presentations, such as patients with asymmetric symptoms or an ESR less than 40 mm/hour, establishing the diagnosis is more difficult [32-34,43]:

In younger patients, inflammatory rheumatic diseases that can mimic PMR warrant careful consideration of other diagnoses. (See 'Differential diagnosis' below.)

Symptoms can be asymmetric early in disease, beginning in one shoulder or hip, but soon become bilateral.

As noted above, a small percentage of patients with bona fide PMR have lower ESRs at the time of diagnosis. Although there is less experience with use of serum C-reactive protein (CRP) testing to establish the diagnosis of PMR, it is reasonable to substitute an elevated serum CRP (above the upper limit of normal for the testing laboratory) as a criterion for PMR if the ESR is less than 40 mm/hour. A normal or modestly elevated ESR by itself should not deter consideration of a diagnosis of PMR in the appropriate clinical setting, but the combination of a normal ESR plus a normal CRP renders the diagnosis much less likely. (See 'Laboratory testing' below.)

Evaluation for PMR — The initial evaluation of patients with suspected PMR includes a complete history and physical, as well as selected laboratory testing.

History and physical examination — The initial history and physical examination should be comprehensive, with specific attention to the following:

History of stiffness and pain of the hips and shoulders and proximal upper and lower extremities; morning stiffness of more than 30 minutes' duration; joint pain and swelling; disruption of sleep; systemic symptoms, such as fever and weight loss; and symptoms suggestive of giant cell (temporal) arteritis (GCA), such as new headache, jaw claudication, scalp tenderness, visual change, fever, or cough. (See 'Evaluation for GCA' below.)

Review of systems to elicit a history that could suggest another disorder to explain the symptoms. (See 'Differential diagnosis' below.)

Evaluation of comorbidities, especially diabetes mellitus, hypertension, and osteoporosis, which could be adversely impacted by glucocorticoid treatment.

Complete physical examination to evaluate for signs indicative of comorbidities or alternative diagnoses. The cardiovascular examination should include assessment for asymmetry of blood pressures, abnormalities of the temporal arteries, and vascular bruits, which could point to the presence of GCA. (See 'Differential diagnosis' below and 'Physical examination' above.)

Detailed musculoskeletal examination to determine range of motion of the axial joints (shoulders and hips), peripheral joints, neck, and low back and to assess for evidence of peripheral synovitis.

Laboratory testing — Laboratory testing should include a complete blood count (CBC) and platelet count, ESR, and CRP levels, and documentation of other tests as a baseline prior to initiation of treatment, including glucose, creatinine, liver function tests, and calcium. Depending upon the patient's symptoms, physical findings, and other diagnoses under consideration, additional testing may be required, including serum thyroid-stimulating hormone (TSH), creatine kinase (CK), vitamin D, rheumatoid factor, anticyclic citrullinated peptide (anti-CCP) antibodies, and antinuclear antibody (ANA).

Imaging in selected patients — If there is diagnostic uncertainty, magnetic resonance imaging (MRI) or ultrasound (US) may be helpful to assess whether there is underlying bursitis or other evidence for inflammation. Plain radiographs are not required, unless another diagnosis that could be confirmed or excluded by such studies is under consideration. (See 'Imaging' above.)

Evaluation for GCA — Patients with clinically "pure" PMR lack the classic findings of GCA, eg, temporal artery tenderness, headache, jaw pain, visual symptoms, and other evidence of ischemia such as arm claudication. In the absence of symptoms or signs, we do not routinely perform a temporal artery biopsy, since a positive result is rare [29,44]. (See "Diagnosis of giant cell (temporal) arteritis".)

GCA can manifest at any point during the clinical course of PMR, including at presentation, during treatment with glucocorticoids, or after treatment has been discontinued. Risk factors for the clinical expression of GCA in patients with PMR have not been clearly established. In patients on 20 mg of prednisone/day, the persistence of constitutional symptoms (such as fever) or significantly elevated acute phase reactants prompts consideration for underlying GCA or an alternative diagnosis.

At every follow-up visit, patients with PMR should be monitored for symptoms or physical findings suggestive of GCA, and, if warranted, further diagnostic evaluation should be pursued (see "Diagnosis of giant cell (temporal) arteritis", section on 'Evaluation for large vessel GCA'). The presence of low-dose glucocorticoid therapy will not affect the yield of temporal artery biopsy [45]. Biopsy can be negative if there is large artery involvement by GCA, the diagnosis of which requires imaging of the vascular tree.

DIFFERENTIAL DIAGNOSIS — The most challenging consideration in the differential diagnosis of polymyalgia rheumatica (PMR) is seronegative rheumatoid arthritis (RA) presenting in older adults. A variety of other disorders can usually be easily distinguished clinically from PMR [43,46,47]. Limited laboratory testing may be helpful depending on the specific clinical presentation.

Rheumatoid arthritis – In younger patients in their early fifties, especially those with some degree of peripheral arthritis, the possibility of classic, seropositive RA must be considered. In these situations, measurement of rheumatoid factor and antibodies to cyclic citrullinated peptide (anti-CCP) is mandatory. Patients with RA commonly have symmetric polyarthritis of the small joints of the hands and feet, which is persistent and only partially responsive to low doses of prednisone. In PMR, fewer joints are swollen, and swelling subsides completely in response to low-dose prednisone. (See "Clinical manifestations of rheumatoid arthritis" and "Use of glucocorticoids in the treatment of rheumatoid arthritis".)

There is, however, considerable overlap between PMR and seronegative RA in older adults who present with peripheral synovitis. Such patients have also been referenced under the rubrics of "late-onset rheumatoid arthritis" and "elderly-onset rheumatoid arthritis." The following are illustrative:

In a report of 159 patients with PMR, seronegative RA, or features of both, who were followed for at least 30 months, recurrent synovitis was observed in 57 patients [48]. During follow-up, 20 of the 57 patients had episodes of symptoms and signs consistent with PMR and, on other occasions, those resembling RA. All patients responded to prednisone. Twenty-four of the patients later developed giant cell (temporal) arteritis (GCA): 19 had been given the diagnosis of PMR and 5 of RA. (See "Diagnosis and differential diagnosis of rheumatoid arthritis".)

A prospective study including 116 patients found that after one year of follow-up, the diagnosis was changed to RA in 20 percent of patients initially diagnosed with PMR [49].

No clinical and laboratory findings consistently separate PMR from seronegative RA in the older adult; ultimately, the differentiation between the two rests on vigilant clinical follow-up [49,50]. Measurement of anti-CCP will identify the older adult with classically seropositive RA [51].

In situations where PMR cannot be clinically distinguished from seronegative RA, we treat with glucocorticoids in the doses used for PMR and carefully monitor the clinical response. It can take several months to differentiate PMR from rheumatoid disease with certainty. Patients who respond well are continued on this treatment regimen, and glucocorticoids are tapered accordingly. Treatment for RA should be instituted if symptoms of arthritis respond incompletely or evolve into a pattern more characteristic of RA. (See "Treatment of polymyalgia rheumatica".)

RS3PE syndrome – The RS3PE syndrome [52] refers to Remitting Seronegative Symmetrical Synovitis with Pitting Edema, also described as the puffy edematous hand syndrome or distal extremity swelling with pitting edema (picture 3). In this syndrome, distal symptoms and signs, often of sudden onset, are pronounced, though careful musculoskeletal examination will usually also disclose some degree of limited range of motion about the shoulders. Swelling, which is usually pitting, extends over the dorsa of the wrists to the metacarpophalangeal joints, producing the appearance of a "boxing glove," with limited range of motion of the hands and wrists. Assays for rheumatoid factor and anti-CCP are negative [53]. Ultrasound (US) and magnetic resonance imaging (MRI) demonstrate prominent extensor tenosynovitis of the extensor tendon of the forearms and hands, with lesser amounts of flexor tenosynovitis and synovitis of the metacarpophalangeal and proximal interphalangeal joints [54]. An association with solid tumors and hematologic disorders has also been reported, but in clinical practice such an occurrence is rare [55,56].

Multifocal local musculoskeletal disease – Symptoms and signs at the shoulders in PMR can be similar to those that result from subacromial/subdeltoid bursitis without PMR or from rotator cuff tendinitis. Local pathology of this sort is common in older adults, can be bilateral, and, when combined with symptoms and signs of degenerative disc disease at the cervical spine and/or osteoarthritis at the hips, could suggest PMR. In such patients, however, morning stiffness is brief, constitutional symptoms are absent, and the acute phase reactants are not elevated. (See 'Imaging' above.)

Bone disease – The differential diagnosis of diffuse achiness in an older adult includes osseous disease. Multiple myeloma can present with bone pain and an elevated ESR, thereby simulating PMR. Such patients can be identified by the presence of a monoclonal protein in the serum or urine (see "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma"). Widespread skeletal metastases can present with diffuse pain, so details of a prior history of malignancy should not be overlooked. Hyperparathyroidism can present with proximal stiffness and aching, often in older patients, usually in the context of hypercalcemia and elevated parathyroid hormone (see "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation"). Osteomalacia, with multiple microfractures, can be associated with widespread musculoskeletal pain.

Drug-induced myalgias or myositis – Statins can be associated with a variety of myopathic syndromes, including statin-related myopathy and myalgias. Explicit myopathy causes weakness and elevations of the serum creatine kinase levels, which are not features of PMR. Statin-related myalgias can usually be distinguished from PMR by the absence of prominent morning stiffness and by the lack of proximally and symmetrically distributed symptoms. (See "Statin myopathy".)

Inflammatory myopathy – Patients with dermatomyositis or polymyositis present with symmetric proximal muscle weakness, and shoulder and hip pain is not as prominent as in PMR. Elevated muscle enzymes, abnormal electromyography, abnormal MRI, and evidence of myositis on muscle biopsy establish the diagnosis of an inflammatory myopathy. (See "Clinical manifestations of dermatomyositis and polymyositis in adults".)

Fibromyalgia – Patients with fibromyalgia syndrome (FM) experience widespread musculoskeletal pain, stiffness, aching, and fatigue. Although such patients are often younger than 50 years, FM can be seen in older patients. Patients with FM have symptoms of longstanding duration, in contrast to PMR, where symptoms are of recent, acute, or subacute onset. Physical examination in FM discloses no abnormalities, apart from characteristic tender points, and unlike patients with PMR, those with FM have a normal ESR, CRP, and hematocrit. (See "Clinical manifestations and diagnosis of fibromyalgia in adults".)

Infection – The occurrence of fever in suspected PMR is always of concern and warrants consideration for infection, as endocarditis and other infectious diseases can occasionally mimic PMR. Polyarthralgias occurring in the context of fever and a heart murmur require blood cultures and evaluation for infectious endocarditis (see "Clinical manifestations and evaluation of adults with suspected native valve endocarditis"). Patients with early, localized, or disseminated Lyme disease can present with nonspecific constitutional symptoms that include myalgias and arthralgias.

Other – Other conditions whose initial presentations can occasionally prompt diagnostic concern for PMR include:

Parkinson disease – Parkinson disease can present with stiffness in an older adult but is commonly accompanied by abnormalities on neurologic examination, including tremor and rigidity. (See "Diagnosis and differential diagnosis of Parkinson disease".)

Hypothyroidism – Patients with hypothyroidism can present with aching, stiffness, and arthralgias. Slow relaxation of deep tendon reflexes, a low serum thyroxine (T4) concentration, and an elevated serum thyroid-stimulating hormone (TSH) concentration are characteristic of hypothyroidism and are not seen in PMR. (See "Clinical manifestations of hypothyroidism", section on 'Musculoskeletal symptoms' and "Diagnosis of and screening for hypothyroidism in nonpregnant adults".)

Malignancy – Though there are rare anecdotes of malignancy presenting with muscle and joint pains that resemble PMR [43], the overall risk of malignancy in PMR is not increased. Contradictory findings have been reported from earlier studies, which identified no such risk, on the one hand, and subsequent studies based on large administrative data sets, which suggested an excess malignancy risk in the first 6 to 12 months after the diagnosis, on the other [57-59]. A population-based cohort study, however, found no difference in the cumulative risk of malignancy after 10 years of follow-up in patients with PMR compared with comparator subjects. A malignancy workup is thus not required for a patient with an uncomplicated presentation of PMR. The presence of atypical clinical features (eg, fever, adenopathy, pulmonary infiltrate), however, must be carefully assessed before a diagnosis of PMR can be endorsed.

Myelodysplastic syndromes can be associated with a variety of rheumatologic manifestations, among which are symptoms and signs typical of PMR [60]. The therapeutic response to low-dose glucocorticoids is usually brisk, as in PMR. The finding of leukopenia or thrombocytopenia in a patient with otherwise typical PMR should lead to further hematologic evaluation. (See "Malignancy and rheumatic disorders", section on 'Malignant diseases: Musculoskeletal manifestations'.)

PMR (and GCA) have been observed in the context of the use of ipilimumab for immunotherapy of malignant melanoma, and cases of PMR have now been seen with the use of other checkpoint inhibitors [61-63]. (See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Rheumatologic and musculoskeletal'.)

Vasculitis – Vasculitic disorders other than GCA can present with arthralgias and an elevated ESR. In a retrospective study of 86 patients with systemic vasculitis affecting small vessels, 11 (13 percent) were thought to have PMR prior to the recognition of renal involvement [64]. All 11 were found to have antineutrophil cytoplasmic antibodies (ANCA). Clinical and laboratory features that suggest ANCA-associated vasculitis include symptoms of upper respiratory tract involvement, pulmonary hemorrhage, renal disease, neuropathy, and positive ANCA. (See "Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis".)

Crowned dens syndrome – "Crowned dens" refers to the radiologic appearance of the dens resulting from soft-tissue calcifications of the periodontoid tissues, presumably due to hydroxyapatite crystals or calcium pyrophosphate deposition disease. The accompanying clinical syndrome can be acute and severe and include shoulder girdle stiffness, fever, and elevations of the acute phase reactants. Plain films may or may not show calcifications. CT examination of C1/C2 is necessary to confirm the periodontoid localization of calcification (image 1). Symptomatic relief is obtained with nonsteroidal antiinflammatory drugs (NSAIDs) or colchicine [65,66].

Spondyloarthropathy – Proximal symptoms similar to PMR have been described in occasional patients with late-onset spondyloarthropathy (SpA) [67], including axial skeletal involvement, oligoarthritis, distal pitting edema, and constitutional symptoms such as fever, anorexia, and weight loss, along with an elevated ESR. In these patients, SpA can be differentiated from PMR by the presence of enthesitis, dactylitis, anterior uveitis, or sacroiliitis on imaging and by a high prevalence of human leukocyte antigen (HLA)-B27. (See "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults" and "Overview of the clinical manifestations and classification of spondyloarthritis".)

Depression – Depression, which occurs in some patients with PMR, can be associated with weight loss and somatic symptoms, including aching and stiffness. Patients with depression do not have typical proximal aching and protracted morning stiffness. (See "Unipolar depression in adults: Assessment and diagnosis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Polymyalgia rheumatica and giant cell arteritis (The Basics)")

Beyond the Basics topics (see "Patient education: Polymyalgia rheumatica and giant cell (temporal) arteritis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Polymyalgia rheumatica (PMR) is an inflammatory rheumatologic condition characterized clinically by aching and morning stiffness about the shoulders, hip girdle, neck, and torso. It can be associated with giant cell (temporal) arteritis (GCA). PMR is almost exclusively a disease of adults over the age of 50; the incidence increases progressively with advancing age. The average age at diagnosis is over 70 years.

Proximal joint and neck symptoms are worst with inactivity, resulting in nocturnal pain and prominent morning stiffness. Morning stiffness, which can be protracted, is invariable. Symptomatology involving the shoulders and upper arms is especially common and can produce a characteristic clinical finding, that of restricted active range of motion at the shoulders, especially abduction.

Physical examination can demonstrate decreased passive range of motion of the shoulders, neck, and hips. Muscle strength is normal when carefully tested. (See 'Physical examination' above.)

The characteristic laboratory finding is an elevation in the erythrocyte sedimentation rate (ESR), occasionally exceeding 100 mm/hour, but which can also be less than 40 in a minority (5 to 20 percent) of patients. Elevated serum C-reactive protein (CRP) may be more sensitive than ESR for the diagnosis. (See 'Laboratory testing' above.)

The diagnosis of PMR can be made in patients with the following features, in whom another disease to explain the findings is not present (see 'General approach' above):

Age 50 years or older at onset of symptoms.

Bilateral aching and morning stiffness (lasting 30 minutes or more) persisting for at least two weeks and involving at least two of the following three areas: neck or torso, shoulders or proximal regions of the arms, and hips or proximal aspects of the thighs.

ESR increased to 40 mm/hour or more. Although there is less experience with use of serum CRP testing to establish the diagnosis of PMR, it is reasonable to substitute an elevated serum CRP as a criterion for PMR if the ESR is less than 40 mm/hour.

Prompt response of symptoms to low-dose glucocorticoids.

Patients must routinely be monitored for signs and symptoms suggestive of GCA. (See 'Evaluation for GCA' above.)

Temporal artery biopsy is not required in the absence of signs or symptoms of GCA. Evaluation, including biopsy, should be performed if symptoms of GCA develop, even if patients are under treatment with glucocorticoids. (See 'Evaluation for GCA' above.)

Early seronegative rheumatoid arthritis (RA) can initially be difficult to differentiate from PMR. The differential diagnosis also includes a variety of other disorders that can usually be distinguished from PMR on clinical grounds. (See 'Differential diagnosis' above.)

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