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 arteritis (GCA, also known as Horton disease, Horton giant cell arteritis, and temporal arteritis); 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 arteritis" and "Diagnosis of giant cell arteritis" and "Treatment of giant cell 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 .
PMR is relatively common. The lifetime risk of developing PMR has been estimated at 2.43 percent for women and 1.66 percent for men and is second only to rheumatoid arthritis (RA) as a systemic rheumatic disease in adults . Women are affected two to three times more often than men. Cases of familial aggregation are rare, but recognized .
The annual incidence varies geographically and is highest in Scandinavian countries and in people of northern European descent . 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 Latin American populations, though all racial and ethnic groups can be affected.
Association with GCA — PMR is two to three times more common than giant cell arteritis (GCA) and occurs in approximately 50 percent of patients with GCA . 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 arteritis (GCA), there are pathogenic similarities (see "Pathogenesis of giant cell 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) . 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, T helper 17 (Th17) cells are increased and regulatory T (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 . However, unlike in 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, implying possible environmental infectious triggers . 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, in particular, the periarticular structures (bursae and tendons) that are mainly affected in PMR, as has been demonstrated by ultrasonography, magnetic resonance imaging (MRI), computed tomography (CT), and 18F fluorodeoxyglucose (FDG) positron emission tomography (PET) [15-22]. (See 'Imaging findings' below.)
Imaging findings at the shoulders include subdeltoid/subacromial bursitis and biceps tenosynovitis. 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 . At the hips, PET studies have demonstrated increased uptake of 18F FDG at the greater trochanters and ischial processes, attributed to bursitis, iliopectineal and iliopsoas bursitis, and hamstring tendinitis. MRI and PET CT have shown evidence for interspinous bursitis in the cervical and lumbar spine (image 1). Glenohumeral and hip joint effusions are less frequently observed.
Upper-extremity symptoms in PMR thus result from biceps tenosynovitis, subdeltoid/subacromial bursitis, cervical interspinous bursitis, and, to a lesser extent, glenohumeral synovitis, while pelvic girdle symptoms arise from involvement of various bursae about the hip, hamstring tendinitis, lumbar interspinous bursitis, and hip synovitis.
Additional MRI studies have suggested a potential role for capsular inflammation and involvement of the entheses (the insertions of tendons, ligaments, and capsules) in the pathogenesis of PMR [23,24].
A synovitis characterized by macrophages and CD4+ T lymphocytes has been described in synovial membranes from involved joints .
Clinical features — 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 – Bilateral shoulder pain is the presenting manifestation in nearly all patients (70 to 95 percent), while the neck and the hip girdle are involved in approximately 70 and 50 percent of patients, respectively. 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. As described above, the proximally distributed aching and stiffness represent referred symptoms from the joints and periarticular structures of the shoulders and hips. (See 'Pathogenesis and pathophysiology' above.)
Distal symptoms, generally mild, accompany the characteristic proximal symptomatology in approximately 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 . 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 gelling phenomenon, coupled with proximal stiffness, can be such that patients may 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 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 'Assessment for GCA' below and 'Differential diagnosis' below and "Diagnosis of giant cell arteritis".)
Laboratory findings — Acute phase reactants are elevated in virtually all patients with PMR. Head-to-head studies of the diagnostic value of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are few, but in clinical experience, the CRP is a more useful index of inflammation.
●The traditional laboratory finding in PMR is an elevated ESR, which ranges from mildly to markedly increased. In one study, 20 percent of patients had ESR values over 104 mm/hour . Conversely, several studies have found that in approximately 5 to 20 percent of patients with PMR, the ESR is less than 40 mm/hour [28-30].
●The CRP is nearly always elevated in PMR. In two reports, 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) [27,31]. In another study, only 1.5 percent of patients with clinically diagnosed PMR 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 . The range of the CRP in PMR, like the ESR, is wide. A diagnostic cut-off value for elevations of the CRP (ie, below which the diagnosis is ruled out) has not been established, but practically speaking, a normal CRP effectively excludes the diagnosis of PMR.
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.
●Autoantibodies, including rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) antibodies, are usually negative in PMR, and if positive, an alternative diagnosis of late-onset rheumatoid arthritis (RA) should be considered. On the other hand, it should be borne in mind that approximately 10 percent of the older adult population has a positive RF (usually at a low titer) without evidence of RA.
Imaging findings — As discussed above, characteristic features of periarticular structures (eg, bursitis and tenosynovitis) can be seen on ultrasonography, MRI, and positron emission tomography (PET) (see 'Pathogenesis and pathophysiology' above), but imaging studies are not required to confirm the diagnosis of PMR. (See 'Diagnosis' below.)
While bilateral subdeltoid/subacromial bursitis is a typical imaging feature of PMR, it is not specific and is seen in patients with other inflammatory diseases (such as RA and spondyloarthritis) and other noninflammatory shoulder pathology . (See 'Pathogenesis and pathophysiology' above.)
However, in patients older than 50 years with new-onset pain and morning stiffness in the shoulders, ultrasound (US) or MRI evidence of bilateral subacromial/subdeltoid bursitis and tenosynovitis of the long head of the biceps, especially if bilateral, can be supportive of the diagnosis of PMR. PET findings include increased fluorodeoxyglucose (FDG) uptake in the shoulders, hips, and spinous processes of the cervical and lumbar spine (image 1).
Evaluation for PMR — The initial evaluation of patients with suspected polymyalgia rheumatica (PMR) includes a complete history and physical, as well as selected laboratory testing (algorithm 1). Many features of PMR may predispose the unwary clinician to diagnostic error.
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 45 minutes' duration; joint pain and swelling; disruption of sleep; systemic symptoms, such as fever and weight loss; and symptoms suggestive of giant cell arteritis (GCA), such as new headache, jaw claudication, scalp tenderness, visual change, fever, or cough. (See 'Assessment 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 "Diagnosis of giant cell arteritis".)
●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. A few important aspects of the physical examination are as follows:
•Joint examination – Range of motion about the shoulders, 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 approximately 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 [26,32,34,35]. 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 seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome (picture 2 and picture 3). 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 testing — Laboratory testing should include a complete blood count (CBC) and platelet count, erythrocyte sedimentation rate (ESR) and C-reactive protein (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 (RF), and anticyclic citrullinated peptide (anti-CCP) antibodies. Additional laboratory tests may be helpful to exclude other disorders that can mimic the disease in the appropriate clinical setting.
Imaging in selected patients — If there is diagnostic uncertainty, MRI or ultrasound (US) may be helpful to assess whether there is underlying bursitis or other local pathology, such as rotator cuff disease. Plain radiographs are not indicated unless another diagnosis that could be confirmed or excluded by such studies is under consideration. (See 'Imaging findings' above.)
Patients with PMR do not routinely need to be imaged for large vessel vasculitis. However, in selected cases in which concomitant GCA is suspected, an evaluation for GCA with imaging (chest/abdomen) such as magnetic resonance angiography (MRA), CT angiography (CTA), or positron emission tomography (PET) may be indicated (see 'Assessment for GCA' below). Furthermore, in atypical and difficult cases of suspected PMR, imaging (MRA, CTA, or PET) may help to rule out other diseases that can mimic PMR (such as malignancies and infections) .
PET scanning has demonstrated underlying vascular involvement in a subset of patients with PMR. Increased fluorodeoxyglucose (FDG) vascular uptake compatible with vasculitis on PET scan has been reported in approximately one-third of consecutive patients with a new diagnosis of PMR . In most patients, vascular uptake was seen in the subclavian arteries, but uptake intensity was less intense than that observed in GCA .
The practical implications of subclinical inflammation of the great vessels in PMR is unclear, and further studies are 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 (ie, "pure" PMR) to develop severe cranial ischemic complications such as blindness and stroke at diagnosis and large vessel stenoses or aneurysms during follow-up . However, close observation should be maintained over the entire course of the disease, since typical features of cranial GCA, including ischemic events, may develop during follow-up in these patients . Furthermore, isolated aortitis has been occasionally found at aneurysm surgery in patients with a history of "pure" PMR . Although in our clinical practice we do not treat patients with "pure" PMR who are found to have asymptomatic large vessel involvement on imaging with the higher dose of prednisone used for GCA, and we do not recommend imaging follow-up, this is a controversial area, since patients with PMR and large vessel involvement were included in GCA clinical trials and treated as GCA . However, evidence that higher prednisone doses are able to prevent the development of vascular damage, in particular of the ascending aorta aneurysm, and of late cranial GCA is lacking. (See "Clinical manifestations of giant cell arteritis", section on 'Large vessel involvement'.)
Assessment for GCA — A clinical assessment for the presence of giant cell arteritis (GCA) is a key consideration in the evaluation of the patient with suspected or diagnosed PMR.
All patients with PMR should be counseled about symptoms that could suggest GCA, especially new-onset headache, visual impairment, or jaw pain with mastication, and instructed to notify the clinician promptly if such symptoms arise. At presentation and at each follow-up visit, patients with PMR should be assessed for symptoms or physical findings referable to GCA, as GCA can manifest at any point during the clinical course of PMR, at presentation, during treatment with glucocorticoids, or after treatment has been discontinued. (See 'Association with GCA' above.)
Clinically, patients with "pure" PMR lack the classic findings of GCA, such as temporal artery tenderness, headache, jaw pain, visual symptoms, and other evidence of ischemia (eg, arm claudication). In the absence of these symptoms or signs, we do not routinely pursue temporal artery biopsy or large imaging for GCA. However, in selected cases of PMR that incur repeated relapses, have persistently increased acute phase reactants, and appear relatively resistant to glucocorticoids, an evaluation for GCA with large vessel imaging may be indicated .
Risk factors for the clinical expression of GCA in patients with PMR have not been clearly established. In patients on active treatment with prednisone, the persistence of constitutional symptoms (such as fever) or significantly elevated acute phase reactants warrants consideration for underlying GCA or an alternative diagnosis.
A positive temporal artery biopsy in PMR patients with no symptoms of GCA has been described but is rare [32,43].
Diagnosis — There is no pathognomonic test or established diagnostic criteria for PMR. We use the presence of all of the following empirically formulated criteria for the clinical diagnosis of PMR when another disease to explain the findings is not present (algorithm 1) [34,44-46] (see 'Differential diagnosis' below):
●Age 50 years or older at disease onset.
●Bilateral shoulder and/or pelvic girdle aching (lasting longer than 45 minutes) 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.
●Elevated acute phase reactants (eg, ESR and/or CRP).
●Rapid resolution of symptoms with low-dose glucocorticoids (eg, prednisone 15 to 25 mg/day or its equivalent). The lack of response to initial therapy strongly suggests an alternative diagnosis (see 'Differential diagnosis' below). Symptomatic improvement with low-dose glucocorticoid treatment can also be seen in patients with rheumatoid arthritis (RA), psoriatic arthritis, and other inflammatory arthritides.
The International PMR Classification Criteria Group, endorsed by the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR; formerly known as European League Against Rheumatism), endorse a stepwise approach for the diagnosis of PMR, which is also consistent with our approach [47,48].
Classification criteria for PMR have been proposed by EULAR and the ACR but should not be used as diagnostic criteria (table 1) [49,50]. The proposed criteria are designed as a research tool to differentiate PMR from other conditions and are not intended for the diagnosis of an individual patient .
In atypical presentations, such as patients with asymmetric symptoms or with minimally elevated acute phase reactants, establishing the diagnosis is more difficult [28-30,51]:
●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 published experience with use of CRP testing to establish the diagnosis of PMR, an elevated serum CRP (above the upper limit of normal for the testing laboratory) can serve as a criterion for PMR. 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 findings' above.)
Differential diagnosis — Several disorders can mimic PMR (table 2). The most challenging consideration in the differential diagnosis of PMR is seronegative RA presenting in older adults. A variety of other disorders can usually be easily distinguished clinically from PMR [51-53]. Limited laboratory testing may be helpful depending on the specific clinical presentation.
●Rheumatoid arthritis – In younger patients in their early 50s, especially those with some degree of peripheral arthritis, the possibility of classic, seropositive RA must be considered. In these situations, measurement of RF and antibodies to 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. The presence of joint erosions differentiates RA from PMR. PMR-related peripheral arthritis is nonerosive, seronegative, and highly responsive to low doses of glucocorticoids . (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. Follow-up is often needed to establish the correct diagnosis, and in up to 30 percent of patients initially diagnosed with PMR, the disease is eventually reclassified as "late-onset" or "elderly onset" RA . 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 . 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 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 .
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 [56,57]. Measurement of anti-CCP will identify the older adult with classically seropositive RA . The presence of joint erosions on plain radiographs at diagnosis or their development during follow-up differentiates RA from PMR .
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 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 RF and anti-CCP are negative . US and 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 . An association with solid tumors and hematologic disorders has also been reported, but in clinical practice such an occurrence is rare [62,63].
●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 bilateral 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 findings' 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 "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis"). 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 CK 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 muscle-related adverse events".)
●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 experience widespread musculoskeletal pain, stiffness, aching, and fatigue. Although such patients are often younger than 50 years, fibromyalgia can be seen in older patients. Patients with fibromyalgia have symptoms of longstanding duration, in contrast to PMR, where symptoms are of recent, acute, or subacute onset. Physical examination in fibromyalgia discloses no abnormalities, apart from characteristic tender points, and unlike patients with PMR, those with fibromyalgia 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 left-sided 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 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 , 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 [64-66]. 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 . 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 with 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 . (See "Toxicities associated with immune checkpoint inhibitors", 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 . 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 "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis".)
•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 2). Symptomatic relief is obtained with nonsteroidal antiinflammatory drugs (NSAIDs) or colchicine [71,72].
•Spondyloarthropathy – Proximal symptoms similar to PMR have been described in occasional patients with late-onset spondyloarthropathy , 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, spondyloarthropathy 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".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Giant cell arteritis and polymyalgia rheumatica".)
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●Beyond the Basics topics (see "Patient education: Polymyalgia rheumatica and giant cell arteritis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definition and epidemiology – 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 arteritis (GCA, also known as Horton disease, Horton giant cell arteritis, and temporal arteritis). 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. (See 'Epidemiology' above and 'Association with GCA' above.)
●Clinical features – Proximal joint and neck symptoms are worst with inactivity, resulting in nocturnal pain and prominent morning stiffness. Morning stiffness, which can be severe and 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. (See 'Clinical features' above.)
Physical examination can demonstrate decreased passive range of motion of the shoulders, neck, and hips. Muscle strength is normal when carefully tested. (See 'History and physical examination' above.)
●Laboratory findings – The characteristic laboratory finding is an elevation of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP; acute phase reactants). The range of these values is wide. The ESR occasionally exceeds 100 mm/hour but can also be less than 40 in a minority (5 to 20 percent) of patients. The CRP is nearly always raised and clinically is more sensitive than ESR for the diagnosis. (See 'Laboratory findings' above.)
•Age 50 years or older at onset of symptoms.
•Bilateral aching and morning stiffness (lasting 45 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.
•Elevated acute phase reactants (eg, ESR and/or CRP).
•Prompt response of symptoms to low-dose glucocorticoids (eg, prednisone 15 to 25 mg/day or its equivalent).
●Assessment for GCA – Patients must routinely be monitored for signs and symptoms suggestive of GCA. (See 'Assessment for GCA' above.)
Diagnostic evaluation for GCA (temporal artery biopsy, temporal artery ultrasound [US], positron emission tomography [PET], CT scanning) is not required in the absence of signs or symptoms referable to GCA but should be pursued if indicated. (See 'Assessment for GCA' above.)
●Differential diagnosis – 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 (table 2). (See 'Differential diagnosis' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William P Docken, MD, who contributed to an earlier version of this topic review.
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