Introduction
Background
Polymyalgia rheumatica (PMR) is a relatively common clinical syndrome of unknown etiology. It is characterized by proximal myalgia of the hip and shoulder girdles with accompanying morning stiffness that lasts for more than one hour. Approximately 15% of patients with polymyalgia rheumatica develop giant cell arteritis (GCA), and approximately 50% of patients with giant cell arteritis have associated polymyalgia rheumatica.
Pathophysiology
The cause of polymyalgia rheumatica is unknown. HLA-DR4 is found with increased frequency in patients with polymyalgia rheumatica and in those with giant cell arteritis. Systemic monocyte activation is characteristic of both conditions. Both diseases show a sequence polymorphism encoded within the second hypervariable region of the HLA-DRB1 gene. The pattern of T-cell–derived cytokines distinguishes the 2 patient populations. Patients with polymyalgia rheumatica often have an elevated interleukin-2 (IL-2) and interleukin-6 (IL-6) levels.
One hypothesis holds that in a genetically predisposed patient, an environmental factor, possibly a virus, causes monocyte activation, which helps determine the production of cytokines that induce manifestations characteristic of polymyalgia rheumatica and giant cell arteritis. The prevalence of antibodies to adenovirus and respiratory syncytial virus was reportedly higher in patients with polymyalgia rheumatica.1,2
Occurrence in siblings suggests a genetic role in the pathophysiology of the disease.
Frequency
United States
The average annual incidence is 52.5 cases per 100,000 persons aged 50 years and older. The prevalence is approximately 0.5-0.7%.
International
The frequency varies by country; highest rates occur in northern Europe. For example, in Italy, the incidence is 12.7 cases per 100,000 persons.
Mortality/Morbidity
With appropriate treatment, the survival rate is similar to that of unaffected persons of the same age; however, some reports document increased mortality from vascular disease among men with polymyalgia rheumatica after the initial 2 years following diagnosis.
Polymyalgia rheumatica is self-limited and often remits in 1-3 years. Untreated patients, however, often feel unwell and have an impaired quality of life.
Race
Polymyalgia rheumatica almost always affects whites but is also occasionally reported in African American persons.
Sex
Polymyalgia rheumatica is twice as common in females.
Age
The incidence increases with advancing age. Polymyalgia rheumatica rarely affects persons younger than 50 years. The median age at diagnosis is 72 years.
Clinical
History
Patients are often in good health prior to disease onset, which is abrupt in about 50% of patients. In most patients, the shoulder girdle is first to become symptomatic. In the remainder, the hip or neck is involved at onset. At presentation, symptoms may be unilateral but usually become bilateral within a few weeks.
Criteria for diagnosis are as follows:
* Age 50 years or older at onset
* Bilateral aching and morning stiffness for at least 1 month and involving at least 2 of 3 areas: neck or torso, shoulders or arms, hips or thighs
* Westergren erythrocyte sedimentation rate (ESR) 40 mm/h or greater
* Prompt response of symptoms to corticosteroids (15 mg/d)
Systemic findings are as follows:
* Low-grade fever and weight loss
* Malaise, fatigue, and depression
* Difficulty rising from bed in the morning
* Difficulty getting up from the toilet
* Difficulty completing daily life activities
* High, spiking fevers (rare)
Musculoskeletal findings are as follows:
* Morning stiffness for more than 1 hour, often more prolonged
* Muscle stiffness after prolonged inactivity
* Carpal tunnel syndrome (in about 15% of patients)
* Distal extremity swelling (uncommon)
* Possible development of arthralgia and myalgia up to 6 months after onset of systemic symptoms
Physical
Polymyalgia rheumatica is a clinical diagnosis based on the complex of presenting symptoms and exclusion of the other potential diseases.
General symptoms are as follows:
* Fatigued appearance
* Low-grade temperature
* Distal extremity swelling with pitting edema
Musculoskeletal symptoms are as follows:
* Normal muscle strength
* Pain in the shoulder and hip with movement without significant clinical swelling
* Transient synovitis of the knee, wrist, and sternoclavicular joints
* Tenderness to palpation with decreased active range of motion in the proximal hip/leg and/or shoulder/arm girdle musculature
* In later stages: Disuse muscle atrophy with proximal muscle weakness and even contractures of the shoulder capsule may lead to limitation of passive and active movement.
Causes
Exact causes are unknown. The disease is more common among northern Europeans, which may indicate a genetic predisposition.
An autoimmune process may play a role in polymyalgia rheumatica development. Polymyalgia rheumatica is associated with the HLA-DR4 haplotype. High levels of IL-2 are associated with polymyalgia rheumatica, and high serum levels of IL-6 correlate with increased disease activity.
Many investigators believe that nonerosive synovitis and tenosynovitis are responsible for many symptoms of polymyalgia rheumatica.Differential Diagnoses
Amyloidosis, AA (Inflammatory)
Osteoarthritis
Depression
Paraneoplastic Syndromes
Fibromyalgia
Polymyositis
Giant Cell Arteritis
Rheumatoid Arthritis
Hypothyroidism
Multiple Myeloma
Other Problems to Be Considered
Acute or chronic infection
Bursitis/tendinitis
Cervical spondylosis
Endocarditis
Malignancy
Parkinson disease
RS3PE
Shoulder disorders, including shoulder synovitis, rotator cuff tendinitis, and subdeltoid bursitis
Vasculitis
Workup
Laboratory Studies
Erythrocyte sedimentation rate findings are as follows:
* ESR is the most sensitive diagnostic study for polymyalgia rheumatica, although it is not specific.
* The ESR is frequently elevated and greater than 40 mm/h, but the rate can exceed 100 mm/h.
* In 20% of patients, the ESR is mildly elevated or, occasionally, normal, which may occur in patients with limited disease activity. In these cases, diagnosis is based on rapid positive response to low-dose oral corticosteroids (10-15 mg/d).
C-reactive protein findings are as follows:
* The C-reactive protein level is often elevated and may parallel the ESR.
* Longitudinal studies suggest that it may be a more sensitive test than ESR for the diagnosis of PMR.
CBC count with differential findings are as follows:
* CBC count reveals mild normocytic, normochromic anemia.
* The WBC count may be normal or mildly elevated. Platelet counts are often increased.
Other laboratory test results are as follows:
* Liver function tests reveal normal transaminase enzyme levels, the alkaline phosphatase may be mildly increased. Serum albumin levels may be slightly decreased.
* The creatine kinase level is normal and helps differentiate the disease from polymyositis and other primary myopathic disorders.
* Antinuclear antibodies and rheumatoid factor levels are usually normal.
* Serum IL-6 levels are elevated and often closely parallel inflammatory activity of the disease.
Imaging Studies
Radiographs of the painful joints rarely show abnormalities such as osteopenia, joint space narrowing, or erosions.
MRI is not necessary for diagnosis. MRI of the shoulder reveals subacromial and subdeltoid bursitis and glenohumeral joint synovitis in the vast majority of patients. MRI of the hands and feet demonstrates inflammation of the tendon sheaths in many patients.
Bursa ultrasonography may reveal an effusion within the shoulder bursae. The ultrasonography findings and those of MRI usually correlate well. Ultrasonography is very operator-dependent and may be useful when the diagnosis is uncertain.
Procedures
Occasionally, synovitis with effusions may be observed. In these cases, synovial fluid analysis reveals signs of mild inflammation, including poor mucin clotting. WBC counts are usually 1000-20,000 cells/µL, with 40-50% polymorphonuclear leukocytes.
Temporal artery biopsy (TAB) has a very low yield in patients with isolated polymyalgia rheumatica and is therefore usually unnecessary in patients with polymyalgia rheumatica without symptoms of giant cell arteritis. TAB is not indicated in patients with mild symptoms of polymyalgia rheumatica that is of recent onset or in patients who have remained stable over a long period (1 y or longer without current or previous clinical evidence of arteritis).
Patients should be monitored for symptoms or signs of arteritis after treatment initiation because low-dose corticosteroids do not prevent progression of polymyalgia rheumatica to giant cell arteritis. If clinical signs of vasculitis develop, TAB should be performed.
TAB may also be warranted in patients with polymyalgia rheumatica who are receiving low-dose corticosteroids if the clinical response is incomplete or if the ESR remains elevated or rises despite symptom resolution on corticosteroid therapy. Low-dose corticosteroids do not appear to affect biopsy yield.
Histologic Findings
Synovitis is histologically mild and is characterized by a predominance of macrophages and CD4+ helper cells.Treatment
Medical Care
Polymyalgia rheumatica is a chronic, self-limited disorder. Therapy is based on empiric experiences because few randomized clinical trials are available to guide treatment decisions. The therapeutic goals are to control painful myalgia, to improve muscle stiffness, and to resolve constitutional features of the disease.
Corticosteroids are considered the treatment of choice because they often cause complete or near-complete symptom resolution and reduction of the ESR to normal. However, no definite evidence demonstrates that corticosteroids (or any other therapy) alter the natural history of polymyalgia rheumatica. The low-dose corticosteroids used in polymyalgia rheumatica are almost certainly ineffective in the prevention of vasculitis progression.
Nonsteroidal anti-inflammatory drugs (NSAIDs) can be administered to some patients with mild symptoms; however, most patients require corticosteroids for total control of symptoms. NSAIDs may be helpful in later stages of corticosteroid dosage tapering. NSAIDs generally have no effect on ESR.
Methotrexate, azathioprine, and other immunosuppressive drugs have been used in some centers in an effort to limit dosage and duration of corticosteroid therapy. At present, no clear-cut data suggest that any of these drugs is superior to corticosteroid therapy. They are seldom indicated for the vast majority of patients with polymyalgia rheumatica who do not have giant cell arteritis because these patients generally respond to low doses of corticosteroids. In fact, symptomatic palliation of pain with analgesic therapy alone may be preferable in situations of corticosteroid intolerance (eg, uncontrolled diabetes mellitus, severe symptomatic osteoporosis, psychosis).
Consultations
Diagnosis and treatment involve the primary care physician and rheumatologist. Ophthalmologists, pathologists, and surgeons may be consulted on an as-needed basis. In coordination with the primary care physician, the rheumatologist plays an important role in diagnosis, treatment, and follow-up care. Consult with an ophthalmologist if concomitant giant cell arteritis may be causing decreased vision. In order to perform TAB, a consultation with a surgeon is essential if the presence of giant cell arteritis is in doubt.
Diet
Ensure adequate calcium and vitamin D intake with corticosteroid use.
Activity
Generally, activity restriction is unnecessary.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Corticosteroids
Oral corticosteroids are the first line of treatment. These agents cause profound and varied metabolic effects. The exact mechanism of action in polymyalgia rheumatica is not well-known, although the disease may be caused by general anti-inflammatory and immunomodulatory effects. In addition, corticosteroids down-regulate cytokine production.
Prednisone (Sterapred)
Has the capacity to dramatically reduce inflammatory manifestations for the following reasons: (1) inhibition of the function of leukocytes and tissue macrophages, which diminishes their ability to respond to antigens and mitogens; (2) inhibition of phospholipase A2, resulting in decreased prostaglandin and leukotriene synthesis; (3) inhibition of cyclooxygenase II expression, which may be the enzyme more involved in the inflammatory effects of eicosanoids; and (4) decreased activity of kinins and decreased histamine release by basophils, leading to decreased capillary permeability.
Controversy remains regarding dose and duration of treatment. Dose depends on patient's weight and severity of symptoms. Expect relief of symptoms in 24-72 h. Dose should be increased if symptoms are not well controlled within 1 wk, and a diagnosis of giant cell arteritis may need to be pursued. Tapering should be guided by clinical response. Normalization of laboratory values are helpful but should not set the guidelines for decreasing or stopping the treatment. In contrast to other rheumatic diseases, alternate-day administration of corticosteroids in polymyalgia rheumatica has been largely unsuccessful.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
0.2-0.3 mg/kg/d PO (10-15 mg/d) initial; maintain effective dose for 2-4 wk after patient becomes asymptomatic; generally, effective dose can be lowered by 1-2.5 mg/d q2-4wk to find the minimum dose needed to maintain symptom suppression; once 10-mg dose is reached, taper by 1 mg/d decrements q4wk
Pediatric
Not applicable
* Dosing
* Interactions
* Contraindications
* Precautions
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics; decreases effects of salicylates and toxoids (for immunizations)
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use; aspirin should be used cautiously in conjunction with corticosteroids in patients with hypoprothrombinemia
Nonsteroidal anti-inflammatory drugs
These agents can be administered to some patients with mild symptoms; however, most patients require corticosteroids for total control of symptoms. NSAIDs may be helpful in later stages of corticosteroid dosage tapering. NSAIDs generally have no effect on ESR.
Ibuprofen (Ibuprin, Motrin)
DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d
Pediatric
Not applicable
* Dosing
* Interactions
* Contraindications
* Precautions
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy
Naproxen (Anaprox, Aleve, Naprosyn, Naprelan)
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
500 mg PO followed by 250 mg q6-8h; not to exceed 1.25 g/d
Pediatric
Not applicable
* Dosing
* Interactions
* Contraindications
* Precautions
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug
Ketoprofen (Orudis, Oruvail, Actron)
For relief of mild to moderate pain and inflammation. Small dosages are initially indicated in small and elderly patients and in those with renal or liver disease. Doses of more than 75 mg do not increase therapeutic effects. Administer high doses with caution and closely observe patient for response.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
25-50 mg PO q6-8h prn; not to exceed 300 mg/d
Pediatric
Not applicableFollow-up
Further Outpatient Care
Polymyalgia rheumatica is typically treated in an outpatient setting. Objective means of determining prognosis and decisions concerning duration of treatment remain empiric and often need careful supervision.
Calcium and vitamin D supplementation should be initiated in all patients with polymyalgia rheumatica who are starting corticosteroid therapy. Osteopenia or osteoporosis discovered with a bone mineral density study (eg, dual-energy x-ray absorptiometry [DEXA] scan) is an indication to start antiresorptive therapy.
An isolated increase of ESR without symptoms during the course of treatment is not a valid reason to increase corticosteroid dose; however, a temporary delay in dosage reduction may be necessary.
Because relapses are more likely to occur during the initial 18 months of therapy and within 1 year of corticosteroid withdrawal, all patients should be monitored for symptom recurrence throughout corticosteroid tapering and until 12 months after cessation of therapy.
Approximately 50-75% of patients can discontinue corticosteroid therapy after 2 years of treatment.
Inpatient & Outpatient Medications
If not contraindicated, NSAIDs may provide supplemental pain relief. They may be used alone in the treatment of patients with mild symptoms.
Methotrexate and other immunosuppressive therapies are seldom used in polymyalgia rheumatica treatment. Occasionally, they may be considered in patients with corticosteroid intolerance or as corticosteroid-sparing agents.
Deterrence/Prevention
No method or strategy is known to be effective in preventing polymyalgia rheumatica.
Complications
Polymyalgia rheumatica usually has a limited course of several months to 5 years. Untreated patients often feel unwell and have an impaired quality of life. Generally, polymyalgia rheumatica is not associated with serious complications. Patients treated with corticosteroids are at risk for long-term complications of corticosteroid therapy.
Relapses are common and may occur in up to 25% of all treated patients. Arteritic relapse in a patient who presented exclusively with polymyalgia rheumatica is unusual.
Every patient should be considered at risk for giant cell arteritis. Additionally, several cases of systemic amyloidosis-associated polymyalgia rheumatica have been reported.
Prognosis
Polymyalgia rheumatica is usually self-limited. With prompt diagnosis and adequate therapy, the condition has an excellent prognosis.
Patient Education
Inform the patient about the potential benefits and risks of corticosteroid treatment and encourage the patient to participate in choosing the treatment plan. Emphasize the importance of healthy dietary habits and ensure adequate calcium and vitamin D supplementation. Emphasize compliance with long-term treatment plans and follow-up care in order to prevent relapses, flares, and subsequent morbidity secondary to corticosteroid therapy. Advise patients to immediately seek medical care if symptoms recur.
For patient education resources, visit eMedicine's Muscle Disorders Center. Also, see eMedicine's patient education article Chronic Fatigue Syndrome.
Miscellaneous
Medicolegal Pitfalls
Consider the following medicolegal pitfalls:
* Failure to consider giant cell arteritis in atypical cases of polymyalgia rheumatica
* Failure to consider alternative causes of systemic illness with an elevated ESR
* Failure to fully inform the patient about potential risks secondary to prolonged corticosteroid therapy
* Failure to arrange timely follow-up care
Special Concerns
Patients with polymyalgia rheumatica should be monitored regularly and carefully for symptoms and signs suggestive of giant cell arteritis development.
