Polymyalgia rheumatica

Musculoskeletal problems related to degenerative diseases, such as osteoarthritis and degenerative disk disease, are common among older adults and for the most part, irreversible. In contrast, the inflammatory diseases are potentially reversible. Teasing apart the diagnoses of the inflammatory diseases can be a challenge, even for seasoned clinicians, but making the correct diagnosis is mandatory because effective treatments are available for inflammatory diseases that occur in geriatric patients.

One of the more common inflammatory disease seen in older adults is polymyalgia rheumatica (PMR). (1) The condition results in severe stiffness and pain in the muscles of the neck, shoulders, lower back, buttocks, and thighs. The muscles of the forearms, hands, calves of the legs, and the feet are usually not affected.

Since patients who have PMR almost invariably have coexistent osteoarthritis, the clinician must be careful when confronted with an older patient with musculoskeletal complaints not to attribute the systemic disease to underlying osteoarthritis. Thus, if an 80-year-old woman presents acutely with severe pain in her neck and upper arms and legs, and is found on x-ray to have narrowing of the C5-C6 disk space, it is far more likely that PMR is causing her symptoms than the cervical spondylosis found on x-ray. If the x-ray had been performed before the symptoms occurred, the findings would likely have been the same.

Careful attention to the patient's history with PMR would typically reveal marked morning stiffness and major fatigue. Physical examination might show muscle tenderness in the upper and lower extremities, and laboratory analysis would reveal evidence of inflammation and possible anemia. None of these are features of cervical osteoarthritis. The patient with PMR, moreover, could be returned to a more normal existence with appropriate treatment.

This article discusses polymyalgia rheumatica; next month's article will focus on cranial arteritis and will include discussion of co-existing polymyalgia rheumatica and cranial arteritis. The articles represent the authors' experience with more than 2,000 patients diagnosed with PMR and more than 450 patients with biopsy-proven cranial arteritis.

Clinical picture of PMR

Polymyalgia rheumatica is primarily a disease of older adults, although it can occur at a younger age; it occurs approximately twice as often in women as in men.

Onset of PMR is usually acute. Pain begins most commonly in the neck and upper arms, although it may occasionally begin in the pelvic girdle. Typically, the pain generally evolves to involve the pelvic and pectoral girdles. Accompanying the pain is easy fatigability; severe morning stiffness is characteristic. Low-grade fever may occur but is not common. Swelling of the joints is not typical, although swelling of the knees may be present on occasion.

Nocturnal pain, particularly in the shoulder, makes sleep difficult. The patient often awakens when attempting to turn in bed. Patients with severe symptoms often report sleeping in a chair, as recumbency may be intolerable.

The "gelling" phenomenon, defined as great difficulty when trying to stand after sitting for a while, or when getting out of a car or bathtub, is also an important symptom.

Getting dressed, particularly in the morning, is difficult, especially when the patient attempts to put on a sweater or jacket. Combing the hair is often impossible. In general, the worst pain occurs at night and in the early morning. Usually the morning pain and stiffness subside to some degree after a few hours, only to increase in the late afternoon and evening and become worse at night. Fatigue, malaise, and depression often accompany the pain of PMR. Raynaud's phenomena or skin rash are not features of the disease.

Physical examination

There are no specific physical findings unique to PMR. The patient may have limited motion in the neck, shoulders, and hips. The limitation is related to pain rather than structural change or muscle weakness. There may be tenderness in the upper arms and thighs. Muscle weakness is not usually present, although evaluating the strength of the muscles is quite difficult as the pain may make it hard for the patient to complete a test. Clinical evaluation of muscle strength is basically a subjective observation. If the patient has pain, is afraid of pain, or does not quite understand the instructions, the examination becomes difficult to interpret.

Overt joint inflammation is not characteristic of PMR, but on occasion knee effusions are seen. When synovitis of the wrists and hands, and diffuse swelling of the hands and feet occur, the diagnosis is most likely rheumatoid arthritis (RA). Distinctions between PMR and seronegative RA of older adults may well be semantic. In patients who have a significant degree of synovitis, we prefer to diagnose them with RA rather than PMR. The vast majority of older patients often have osteoarthritic changes that are not germane to the diagnosis of PMR.

Lab, radiographic findings

There are no laboratory or radiographic findings specific to the diagnosis of PMR, however some findings are characteristic. Most commonly there is an elevation of sedimentation rate, considered by some to be essential to the diagnosis. Usually the elevation is >50 mm/hr, although at times the sedimentation rate is much higher. Some PMR patients, although usually at a younger age, may never have an elevated sedimentation rate. We have investigated the mechanism of the elevated sedimentation rate, and it appears to be related to the presence of fibrinogen.

Mild anemia (ie, 11 to 13 grams/%) is frequently found. The anemia is normochromic and normocytic. Iron deficiency, hemolysis, and bone marrow suppression are not seen. If they are present, the anemia is not due to PMR.

White blood cell count and platelets are usually normal, although they may be elevated reflecting the inflammatory state. Chemistries are normal except for those relating to any co-morbidities that may be present. Kidney and liver function are normal. On rare occasions an elevated alkaline phosphatase may be present, particularly if cranial arteritis co-exists.

Autoantibodies are not found in any greater frequency among patients with PMR than in patients of the same age without PMR. It is well known that rheumatoid factor and antinuclear antibodies are present in a significant percentage of older adults.

Protein electrophoresis may demonstrate some decrease in albumin, elevation of alpha-2, and an increase of polyclonal gamma globulin. Monoclonal gammopathy is not a feature of PMR. Thyroid function tests are normal, as are tests of adrenal function. There is no elevation of CK and aldolase, such as would be found in diseases of muscle.

X-ray imaging and CT will demonstrate degenerative changes and possibly osteoporosis. MRI of the pelvic and pectoral girdles may reveal synovitis of the shoulders but may also show inflammation in the surrounding soft tissues. This finding is not specific, but may offer an explanation as to the cause of pain in PMR.

Differential diagnosis

The clinical picture of diffuse myalgia and an elevated sedimentation rate is rather nonspecific. Other diagnostic possibilities include infection, neoplasia, endocrine disease, fibromyalgia, and other diffuse connective tissue diseases.

Although viral infection may simulate PMR, most viral infections are of short duration and improve spontaneously in a matter of days or weeks.

If endocarditis is suspected, blood cultures and echocardiograms could establish the correct diagnosis.

AIDS may, at times, present with muscle pain and systemic symptoms. If suspected on the basis of the clinical findings, AIDS can be confirmed by HIV testing.

Hepatitis A, B, and C can present with myalgia, but abnormal liver function tests and serologic testing would help clarify the diagnosis.

In hyperthyroid myopathy, weakness, rather than pain, is a major complaint. TSH testing would clarify the diagnosis. Rarely, hyperparathyroidism may present with muscle pain, although weakness would tend to be more prominent. Calcium, and, if necessary, PTH testing, could be diagnostic.

On occasion, patients with adrenal insufficiency may present with weakness and achiness. Usually the presence of hyponatremia or hyperkalemia would confirm this diagnosis. Appropriate testing would be indicated. Moreover, in contrast to PMR, where response to glucocorticoids is dramatic, one would not expect this to occur in Addison's disease, where replacement of both glucocorticoids and mineralocorticoids is necessary.

Rarely, myeloma or lymphoma can present with fatigue, achiness, and an elevated sedimentation rate. In myeloma, a serum immunofixation should reveal a monoclonal spike, which would not be characteristic of PMR. More significantly, PMR responds dramatically to small doses of glucocorticoids, whereas neither myeloma nor lymphoma will respond to the lower doses used in PMR. At times high doses of glucocorticoids are helpful in treating myeloma and lymphoma, although the response would generally be transient. Occult malignancy would also not respond well to low doses of glucocorticoids.

Many of the connective tissue diseases may initially present as a diffuse pain syndrome with an elevated sedimentation rate. Patients with apparent PMR may eventually evolve clinical features characteristic of RA, lupus, or scleroderma. Thus, continued observation of the patient is important as these entities would eventually become manifest. Serologic studies may be helpful in this regard, but be aware that the various connective tissue diseases are defined clinically and not serologically. Thus, a positive rheumatoid factor does not necessarily indicate RA, nor does a positive antinuclear antibody establish the diagnosis of systemic lupus. Other serologies, such as anti-double stranded DNA, anti-RNP, and hypocomplementemia are more specific to various connective tissue diseases, and their presence should alert the clinician to alternate diagnoses.

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Vasculitis might present with severe diffuse muscle pain. However, diseases such as polyarteritis would not usually respond to low doses of glucocorticoids and would require much higher doses or immunosuppressives. Furthermore, as time evolves other manifestations of vasculitis, such as renal disease, abdominal pain, or neuropathy would appear.

Polymyositis and dermatomyositis usually appear with muscle weakness, although pain may also be a feature. In these diseases, evidence of muscle disease would be manifested by elevation of CK, aldolase, or both. Further work-up with electrodiagnostic studies and muscle biopsy would usually be diagnostic. Certainly the presence of the characteristic rash of dermatomyositis would rule out PMR.

The distinction between polymyositis and PMR is important to make. Whereas PMR is a benign entity, polymyositis may have a poor prognosis and requires more aggressive treatment. Moreover, polymyositis may reflect an underlying occult malignancy.

Patients on "statin" drugs may present with myalgias, with or without muscle weakness. Before diagnosing PMR, discontinuation of these agents is warranted to see if the pain remits.

The most difficult entity to differentiate from PMR is fibromyalgia. Fibromyalgia is a syndrome of diffuse musculoskeletal pain, sleep disturbance, and no objective findings other than "tender points." Since an elevated sedimentation rate is commonly found in older adults, its presence does not rule out fibromyalgia. Usually people with fibromyalgia have a long history of widespread pain and fatigue. They do not necessarily have morning stiffness, and there is a sleep problem that may predate the pain syndrome. In PMR, the sleep disturbance seems to relate to the presence of the pain. Also in PMR, the pain tends to be limited to the upper arms and thighs, whereas in fibromyalgia, the tenderness is more diffuse, and "tender points" are found in the medial scapulae, occiput, elbows, and medial knees as well as sacroiliac joints. Although the sedimentation rate may be elevated for reasons not related to fibromyalgia, it is usually normal and anemia is not present. In addition, fibromyalgia is far more common in younger persons, particularly women.

At times, the diagnosis cannot be made based on the clinical examination, and a trial of low-dose glucocorticoids is helpful. Patients with PMR by definition have a dramatic response both subjectively and objectively to glucocorticoid treatment. Fibromyalgia usually would not respond in such a dramatic fashion.

RA in older adults can present as a bilateral shoulder-hand syndrome or symmetrical synovitis and peripheral edema, and both of these tend to respond to small doses of corticosteroids and have a good prognosis. Their relationship to PMR is unclear, but for the present it would be useful to separate these entities from PMR. It is indeed possible that as more information becomes available, these syndromes may be found to be closely related.

Treatment

Patients with PMR respond dramatically to relatively low doses of glucocorticoids. Prednisone, 15 mg/d, or an equivalent dose of another glucocorticoid is typically used. Quite often, the pain that may have been present for weeks to months despite use of nonsteroidal anti-inflammatory drugs and narcotics may be gone within days and, at times, within hours. The pain subsides, stiffness decreases, and a sense of well-being returns. Usually the sedimentation rate decreases to normal levels, and anemia resolves within a matter of weeks.

Some patients with PMR have a "classic" clinical picture but fail to respond adequately to prednisone, 15 mg/d. Before discarding the diagnosis, switch to an equivalent dose of methylprednisolone (ie, 12 mg/d). We have seen a number of patients with PMR who fail to respond to prednisone, [greater than or equal to]15 mg/d, but respond dramatically to methylprednisolone, 12 mg/d. To find a mechanism for this disparity, we tested patients to see if they lack the ability to convert prednisone to prednisolone (to be effective, prednisone must be so converted). However, in a group of 5 patients manifesting this phenomena, we could not demonstrate any defect in hydroxylation. Thus, this remains a clinical observation, which, at this point, is unexplained. On the basis of this experience, however, we often use methylprednisolone, 12 mg/d, as initial treatment rather than prednisone.

If PMR has been present for a long period of time, patients may experience residual limitation of motion of the shoulders and hips. This will usually improve with a physical therapy program aimed at active range-of-motion exercises. Patients who have been chair- or bed-bound before treatment may require a conditioning physical therapy program. Excepting these situations, there is usually no need for physical therapy in patients with PMR. Patients are encouraged to resume normal daily activities as tolerated.

After the patient has achieved an optimal clinical response, which usually occurs in approximately 2 weeks, the glucocorticoids are tapered slowly. Although initially a BID dose regimen may be used, eventually the aim is to consolidate to a single morning dose to minimize cushingoid changes and adrenal suppression.

Glucocorticoid taper must be individualized. We generally decrease prednisone to 12.5 mg/d after 2 weeks of 15 mg/d, and then slowly taper further to 10 mg/d. This tapering schedule depends upon the patient's clinical response and the presence of side effects. Once the patient is taking the equivalent of prednisone, 10 mg/d, the steroids can be tapered at a rate of approximately 1 mg/d per week to the lowest dose that keeps the patient slightly uncomfortable. Our dictum of treating patients with PMR is that if the patient has no symptoms he or she is taking too much steroids. The difference in steroid dose necessary to suppress all of the symptoms of PMR and that necessary to keep the patient reasonably comfortable may well be substantial. The relationship of steroid dose to potential side effects is roughly exponential rather than linear. The difference between 7.5 mg/d of prednisone and 15 mg/d in terms of side effects can be substantial.

Before beginning glucocorticoids, the patient should be evaluated for osteoporosis by DEXA scan, if possible. If bone mineral density (BMD) is normal, then supplemental calcium, 1,200 mg/d, and vitamin D, 400 to 800 IU/d, are recommended. The patient should also be encouraged to engage in weightbearing exercise; walking is usually sufficient. If there is any evidence of significant osteopenia or osteoporosis, the addition of an antiresorptive medication is indicated. Usually alendronate or risedronate are used. BMD should then be monitored on a yearly basis.

Blood glucose should be measured before and monitored during glucocorticoid treatment. In some patients, treatment of hyperglycemia may be required.

Cholesterol elevation may also occur and may require treatment. Although statin drugs can cause myalgia, there is no evidence that their use would be contraindicated in patients with PMR.

Blood pressure and fluid retention must also be monitored. A common, but underestimated, complication of steroid therapy is myopathy. Patients with myopathy exhibit weakness, primarily of the lower extremities, but no evidence of muscle damage, such as elevated CK or abnormal EMG's (electromyography). Myopathy responds only to lowering the dose of steroids.

Duration of treatment is variable. Most patients require some doses of glucocorticoids for between 2 to 3 years.2 Some patients, however, are able to stop taking glucocorticoids within a matter of months, whereas others require small doses of steroids for as long as 20 years after diagnosis.

Prognosis

In general, the prognosis of PMR is excellent: typically, the pain and symptoms rapidly resolve with the use of corticosteroids. In contrast to RA, there is no residual joint damage, and patients live lives compatible with their general medical condition. With careful monitoring for steroid side effects and expectant treatment for bone loss and metabolic abnormalities, many side effects can be contained. Poor healing, skin bruising, and muscle weakness, however, often occur and respond only to lowering the dose of corticosteroids. Generally, on a dose of prednisone, 5 mg/d, or its equivalent, most steroid side effects tend to resolve.

Since glucocorticoids will suppress the hypothalamic-pituitary-adrenal axis, the patient and family must be aware that with medical or surgical stress, the patient may not be able to produce enough endogenous steroids to handle stress situations. Should such a situation arise while on glucocorticoids or up to 1 year after discontinuation, "stress steroids" may be indicated. If the treating doctor or surgeon is made aware of the current or recent use of glucocorticoids, he/she can decide if "stress steroids" should be administered.

As will be discussed in a future article, cranial arteritis may be associated with PMR. Patients must be aware of this possibility, and if symptoms of cranial arteritis appear, appropriate diagnostic studies and proper treatment should be instituted.

Summary

PMR is a clinical syndrome of pectoral and pelvic girdle pain requiring low doses of corticosteroids. The condition is reversible with treatment, and patients can return to their normal levels of functioning.

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References

(1.) Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998; 41(5):778-99.

(2.) Kyle V, Hazleman BL. Treatment of polymyalgia rheumatica and giant cell arteritis. II. Relation between steroid dose and steroid associated side effects. Ann Rheum Dis 1989; 48(8):662-6.

Dr. Robert Spiera is associate professor of clinical medicine at the Albert Einstein College of Medicine, New York City.

Dr. Harry Spiera is professor of clinical medicine at the Mount Sinai School of Medicine, New York City.

Disclosure: Neither author has any real or apparent conflicts of interest relating to the subject presented here.

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