JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Copyright 0 1976 by the American Geriatrics Society
Vol. XXIV. No. 2 Printed in U S A .
Polymyalgia Rheurnatica EDWARD S. McCABE, MD, FACP*
Presbyterian Hospital-University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
ABSTRACT: Polymyalgia rheumatica should be considered when a syndrome of constitutional symptoms, especially weight loss, low-grade fever, weakness, wasting proximal muscles, fatigue, malaise and depression, is seen in the elderly. Giantrcell arteritis plays a part later in the course. Thus the need for biopsy of a long segment of the temporal artery to help in determining diagnosis and therapy. An elevated erythrocyte sedimentation rate (ESR)is an important clue. The usual high value is about 80 mm/hour; if it is over 100 mm/hour, giantrcell arteritis should be suspected. Salicylates, indomethacin, phenylbutazone and hydroxychloroquine produce some clinical improvement but do not lower the high ESR; moreover, the patients are prone to experience relapses. Prednisone, however, not only produces clinical improvement but lowers the high ESR. Potassium paminobenzoate may be useful in maintaining the remission. The laboratory data showed a normal level of serum uric acid, negative results with the latex fixation test, and an erythrocyte sedimentation rate (ESR) of 26 mmhour. X-ray findings were suggestive of gout. The patient did not drink alcohol. He responded slowly to indomethacin (Indocin) and the disturbance subsided. His mind was occupied with the illness of the school teacher. The following year, superficial thrombophlebitis developed in the saphenous system of the left leg. He was admitted to Presbyterian Hospital and was treated with an anticoagulant (Hedulin), an antibiotic, heat, rest, and elevation of the leg. X-ray examination revealed a polyp of the sigmoid, which was removed in a sigmoidoscopy procedure. The ESR during the remission was 22 mm/hour. Then, in the several months during which he functioned well, the school teacher had a relapse and died. The patient became somewhat depressed and was asked to take a tranquilizer-antidepressant (Triad). Instead, he closed the house and went to Puerto Rico. On returning, after he had spent the winter there, he stated that he had had a virus infection and had stayed in his room a lot. He noticed that his upper arm and shoulder muscles seemed to be atrophying; then they became painful. He obtained relief by keeping his elbows flexed; he now had contractures and could not straighten them out beyond 140 degrees. He
Barber (1) in 1957 apparently was responsible for renewing interest in a syndrome that has constitutional symptoms of a protean but nonspecific nature. Among the more prominent are low-grade fever, weakness, fatigue, malaise, weight loss, anorexia, myalgia, pseudo arthralgia, bursitis, and depression (2). Usually the syndrome occurs in patients over 50 years of age and remains chronic until some acute episode intervenes, e.g., transient blindness or intermittent claudication of the jaw muscles. Bruce (3) in 1888 described in England “senile rheumatic gout,” stating that it was half as common as rheumatoid arthritis and just as common as gout. The sex ratio was 60 percent males to 40 percent females. The cases of 3 patients (2 men and 1 woman) recently seen in my practice seemed worth reporting: CASE REPORTS
Patient 1 An 82-year-old white man, who was engaged in looking after a retired school teacher of the same vintage, was in good health until three years previously. His right wrist had become swollen, hot and painful. He underwent some dental work. *Staff Physician. Address for correspondence: Edward S. McCabe, MD, 512 Anthwyn Road, Merion Station, PA 19066.
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noticed what seemed to be ganglions forming a t the left wrist (tenosynovitis). When he returned to Philadelphia his right leg became swollen and he called a physician, as he felt it was a flare-up of the thrombophlebitis; instead, it was diagnosed as suprapatellar bursitis. He had emphysema, but ventilation studies showed pulmonary function to be surprisingly good. He also had mild arteriosclerotic heart disease. He would not permit aspiration of the knee joint. The serum uric acid level was normal and the latex fixation test gave negative results, but the ESR was 78-85 mm/ hour. He was treated with indomethacin (Indocin) and he improved clinically. His appetite increased and he gained a pound a day. His mood improved, but the ESR remained high. Then phenylbutazone (Butazolidin) was started; this also produced clinical improvement, but the ESR did not change. He refused temporal artery biopsy. Since he had not complained of headache and no gross changes were evident, he was given prednisone, 5 mg every 8 hours. Within five days the ESR had dropped to 40 mm/hour and he remarked that he had never felt better. On discharge he was taking the same dosage of prednisone; supportive stockings were recommended. If the ESR dropped to 22 mm/hour, the dosage of prednisone was to be reduced to 5 mg every 12 hours and eventually tapered off. Then a three-day-per-month schedule was contemplated, or K p-aminobenzoate (Potaba) daily, to maintain remission.
Patient 2 A 78-year-old white man, a retired railroad executive, had a febrile illness (“grippe”) and shortly afterward complained of pain in the left shoulder on the outside of the arm; he had difficulty raising his arm. X-ray examination showed no calcification and he was given an injection of prednisolone, which helped for two weeks. Then he had more discomfort, especially a t night, and the other shoulder bothered him. He lost a great deal of weight in six months (20-30 pounds), yet he claimed that he ate adequately. The laboratory studies a t Presbyterian Hospital showed the ESR to be 110-110 mm/hour. He had a minor degree of pancreatic functional impairment, but x-ray films of the upper and lower intestines did not show any abnormalities. A liver scan was normal but the pancreas could not be visualized. Thus pancreatic carcinoma was sus90
pected. Laparotomy was not performed because clinical improvement occurred during indomethacin (Indocin) therapy. Mood, appearance and weight improved, yet the high ESR did not change. He complained of headache but it responded to indomethacin and no abnormality of the temporal artery was found clinically. The patient was discharged after a 10-pound weight gain; the serum uric acid level was normal and the latex fixation test gave negative results. However, the symptoms recurred on attempting to reduce the dosage of indomethacin, and he was seen by another physician who substituted hy droxychloroquine therapy. The patient improved but the ESR did not decrease. The symptoms returned on attempting to reduce drug dosage, but they improved again when prednisolone (5 mg twice daily) was added to the regimen. In retrospect, biopsy of the temporal artery should have been performed and prednisolone should have been given in large doses. Based on experience with disseminated lupus, it would be recommended that the remission be maintained with K p-aminobenzoate (Potaba), 12 gm daily. Before indomethacin therapy, there was evidence of slight hemolysis (4), negative findings with the Coombs test, and no reticulocyte response. However, this condition improved along with improved nutrition.
Patient 3 A 53-year-old white woman had experienced a three-month period of fever, with soreness and stiffness in the pectoral girdle muscles. Suddenly, blindness of the left eye developed. Biopsy of the temporal artery revealed giant-cell arteritis. The ESR was 102 mmhour. She was given 60 mg of prednisone daily, and the active disease was suppressed. On attempting to reduce the dosage of prednisone, the ESR started to rise again, and left hemiparesis suddenly appeared. This seemed to respond to resumption of the larger dosage of prednisone. However, another reduction in dosage was followed by cardiac failure, probably myocarditis with arrhythmia, and death. There was no evidence of the aortic arch syndrome mimicking Takayasu’s disease. Autopsy was not permitted.
DISCUSSION Characteristic of this clinical syndrome is the marked elevation of the ESR (usually about 60 mm/hour) despite only a mild hypochromic
February 1976
POLYMYALGIA RHEUMATICA
anemia refractory to iron. A possible explanation is an elevation of the levels of fibrinogen, globulin and &globulin (chiefly of fibrinogen). X-ray studies show either normal joints or only mild degenerative changes. The synovial fluid may contain several thousand leukocytes per cu mm, and be sterile. Although salicylates, indomethacin, phenylbutazone or hydroxychloroquin do not reverse the ESR, prednisone will. Giant-cell arteritis ( 5 ) , especially of the temporal artery, occurs in 40 percent of the cases but may be delayed in onset. One clue is when the ESR rises to 20-40 mm/hour, or visual or neurologic symptoms emerge. A normal-appearing artery does not obviate biopsy; preferably a long segment should be examined by serial sections. In two-thirds of patients in whom biopsy findings are positive, the vessels are normal by physical examination. In Bruk’s series (5), 40 percent of 33 patients with polymyalgia rheumatica had giantcell arteritis. In the study of Hamilton et a1 (6), biopsy revealed: 1) predominance of mononuclear inflammatory cells, lymphocytes, plasma cells and macrophages, and an increase in eosinophils; 2) the entire thickness of the artery is usually affected, and thrombosis and canalization are common; 3) giant cells are a constant feature, especially in the region of the internal elastic lamina; 4) elastic fibers, sometimes calcified, are seen in the cytoplasm of the giant cells, but there is no fibrinoid necrosis; and 5) the electron microscope shows that the initial lesion is in the smooth muscle of the artery.
I
Elastin (7) is made by mesenchymal cells and is a polymerized tetra peptide with cross-linkage that makes it relatively insoluble. Destruction of that cross-linkage because of copper deficiency, impaired calcium binding or hydrophobic ligands will increase solubility and act as a stimulus for giant-cell formation. Recently the opposite process has been reported, i.e., ductal-cell carcinoma of the breast which by induction increased production of insoluble elastin so that there was reduplication of internal elastic lamina. It would seem worth while to perform trace metal studies on copper excretion when polymyalgia rheumatica is suspected. The dye, congo red, solubilizes the collagen elastin. Possibly a sex-linked defect is involved. REFERENCES 1. Barber HA: Myalgia syndrome with constitutional effects: polymyalgia rheumatica, Ann Rheum Dis 16, 230, 1957. 2. Wilske KR and Healey LA: Polymyalgia rheumatica, a manifestation of systemic giant cell arteritis, Ann Int Med 66:,77, 1967. 3. Bruce W: Senile rheumatic gout, Brit Med J 2: 811, 1888. 4. Flanagan P, McCraken AW, Jones FR et al: Necrotizing arteritis with giant cells associated with haemolytic anemia, J Clin Path 18: 588, 1905. 5. Bruk MI: Articular and vascular manifestations of polymyalgis rheumatica, Ann Rheum Dis 26: 103, 1967. 6. Hamilton CR Jr, Shelley WM and Tumulty PA: Giant cell arteritis, including temporal arteritis and polymyalgia rheumatica, Medicine 50: 1, 1971. 7. Gray WR: Molecular model for elastin structure and function, Nature 246: 461, 1973.
91
Vol. XXIV. No. 2 Printed in U S A .
Polymyalgia Rheurnatica EDWARD S. McCABE, MD, FACP*
Presbyterian Hospital-University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
ABSTRACT: Polymyalgia rheumatica should be considered when a syndrome of constitutional symptoms, especially weight loss, low-grade fever, weakness, wasting proximal muscles, fatigue, malaise and depression, is seen in the elderly. Giantrcell arteritis plays a part later in the course. Thus the need for biopsy of a long segment of the temporal artery to help in determining diagnosis and therapy. An elevated erythrocyte sedimentation rate (ESR)is an important clue. The usual high value is about 80 mm/hour; if it is over 100 mm/hour, giantrcell arteritis should be suspected. Salicylates, indomethacin, phenylbutazone and hydroxychloroquine produce some clinical improvement but do not lower the high ESR; moreover, the patients are prone to experience relapses. Prednisone, however, not only produces clinical improvement but lowers the high ESR. Potassium paminobenzoate may be useful in maintaining the remission. The laboratory data showed a normal level of serum uric acid, negative results with the latex fixation test, and an erythrocyte sedimentation rate (ESR) of 26 mmhour. X-ray findings were suggestive of gout. The patient did not drink alcohol. He responded slowly to indomethacin (Indocin) and the disturbance subsided. His mind was occupied with the illness of the school teacher. The following year, superficial thrombophlebitis developed in the saphenous system of the left leg. He was admitted to Presbyterian Hospital and was treated with an anticoagulant (Hedulin), an antibiotic, heat, rest, and elevation of the leg. X-ray examination revealed a polyp of the sigmoid, which was removed in a sigmoidoscopy procedure. The ESR during the remission was 22 mm/hour. Then, in the several months during which he functioned well, the school teacher had a relapse and died. The patient became somewhat depressed and was asked to take a tranquilizer-antidepressant (Triad). Instead, he closed the house and went to Puerto Rico. On returning, after he had spent the winter there, he stated that he had had a virus infection and had stayed in his room a lot. He noticed that his upper arm and shoulder muscles seemed to be atrophying; then they became painful. He obtained relief by keeping his elbows flexed; he now had contractures and could not straighten them out beyond 140 degrees. He
Barber (1) in 1957 apparently was responsible for renewing interest in a syndrome that has constitutional symptoms of a protean but nonspecific nature. Among the more prominent are low-grade fever, weakness, fatigue, malaise, weight loss, anorexia, myalgia, pseudo arthralgia, bursitis, and depression (2). Usually the syndrome occurs in patients over 50 years of age and remains chronic until some acute episode intervenes, e.g., transient blindness or intermittent claudication of the jaw muscles. Bruce (3) in 1888 described in England “senile rheumatic gout,” stating that it was half as common as rheumatoid arthritis and just as common as gout. The sex ratio was 60 percent males to 40 percent females. The cases of 3 patients (2 men and 1 woman) recently seen in my practice seemed worth reporting: CASE REPORTS
Patient 1 An 82-year-old white man, who was engaged in looking after a retired school teacher of the same vintage, was in good health until three years previously. His right wrist had become swollen, hot and painful. He underwent some dental work. *Staff Physician. Address for correspondence: Edward S. McCabe, MD, 512 Anthwyn Road, Merion Station, PA 19066.
89
Val. XXIV
EDWARD S McCABE
noticed what seemed to be ganglions forming a t the left wrist (tenosynovitis). When he returned to Philadelphia his right leg became swollen and he called a physician, as he felt it was a flare-up of the thrombophlebitis; instead, it was diagnosed as suprapatellar bursitis. He had emphysema, but ventilation studies showed pulmonary function to be surprisingly good. He also had mild arteriosclerotic heart disease. He would not permit aspiration of the knee joint. The serum uric acid level was normal and the latex fixation test gave negative results, but the ESR was 78-85 mm/ hour. He was treated with indomethacin (Indocin) and he improved clinically. His appetite increased and he gained a pound a day. His mood improved, but the ESR remained high. Then phenylbutazone (Butazolidin) was started; this also produced clinical improvement, but the ESR did not change. He refused temporal artery biopsy. Since he had not complained of headache and no gross changes were evident, he was given prednisone, 5 mg every 8 hours. Within five days the ESR had dropped to 40 mm/hour and he remarked that he had never felt better. On discharge he was taking the same dosage of prednisone; supportive stockings were recommended. If the ESR dropped to 22 mm/hour, the dosage of prednisone was to be reduced to 5 mg every 12 hours and eventually tapered off. Then a three-day-per-month schedule was contemplated, or K p-aminobenzoate (Potaba) daily, to maintain remission.
Patient 2 A 78-year-old white man, a retired railroad executive, had a febrile illness (“grippe”) and shortly afterward complained of pain in the left shoulder on the outside of the arm; he had difficulty raising his arm. X-ray examination showed no calcification and he was given an injection of prednisolone, which helped for two weeks. Then he had more discomfort, especially a t night, and the other shoulder bothered him. He lost a great deal of weight in six months (20-30 pounds), yet he claimed that he ate adequately. The laboratory studies a t Presbyterian Hospital showed the ESR to be 110-110 mm/hour. He had a minor degree of pancreatic functional impairment, but x-ray films of the upper and lower intestines did not show any abnormalities. A liver scan was normal but the pancreas could not be visualized. Thus pancreatic carcinoma was sus90
pected. Laparotomy was not performed because clinical improvement occurred during indomethacin (Indocin) therapy. Mood, appearance and weight improved, yet the high ESR did not change. He complained of headache but it responded to indomethacin and no abnormality of the temporal artery was found clinically. The patient was discharged after a 10-pound weight gain; the serum uric acid level was normal and the latex fixation test gave negative results. However, the symptoms recurred on attempting to reduce the dosage of indomethacin, and he was seen by another physician who substituted hy droxychloroquine therapy. The patient improved but the ESR did not decrease. The symptoms returned on attempting to reduce drug dosage, but they improved again when prednisolone (5 mg twice daily) was added to the regimen. In retrospect, biopsy of the temporal artery should have been performed and prednisolone should have been given in large doses. Based on experience with disseminated lupus, it would be recommended that the remission be maintained with K p-aminobenzoate (Potaba), 12 gm daily. Before indomethacin therapy, there was evidence of slight hemolysis (4), negative findings with the Coombs test, and no reticulocyte response. However, this condition improved along with improved nutrition.
Patient 3 A 53-year-old white woman had experienced a three-month period of fever, with soreness and stiffness in the pectoral girdle muscles. Suddenly, blindness of the left eye developed. Biopsy of the temporal artery revealed giant-cell arteritis. The ESR was 102 mmhour. She was given 60 mg of prednisone daily, and the active disease was suppressed. On attempting to reduce the dosage of prednisone, the ESR started to rise again, and left hemiparesis suddenly appeared. This seemed to respond to resumption of the larger dosage of prednisone. However, another reduction in dosage was followed by cardiac failure, probably myocarditis with arrhythmia, and death. There was no evidence of the aortic arch syndrome mimicking Takayasu’s disease. Autopsy was not permitted.
DISCUSSION Characteristic of this clinical syndrome is the marked elevation of the ESR (usually about 60 mm/hour) despite only a mild hypochromic
February 1976
POLYMYALGIA RHEUMATICA
anemia refractory to iron. A possible explanation is an elevation of the levels of fibrinogen, globulin and &globulin (chiefly of fibrinogen). X-ray studies show either normal joints or only mild degenerative changes. The synovial fluid may contain several thousand leukocytes per cu mm, and be sterile. Although salicylates, indomethacin, phenylbutazone or hydroxychloroquin do not reverse the ESR, prednisone will. Giant-cell arteritis ( 5 ) , especially of the temporal artery, occurs in 40 percent of the cases but may be delayed in onset. One clue is when the ESR rises to 20-40 mm/hour, or visual or neurologic symptoms emerge. A normal-appearing artery does not obviate biopsy; preferably a long segment should be examined by serial sections. In two-thirds of patients in whom biopsy findings are positive, the vessels are normal by physical examination. In Bruk’s series (5), 40 percent of 33 patients with polymyalgia rheumatica had giantcell arteritis. In the study of Hamilton et a1 (6), biopsy revealed: 1) predominance of mononuclear inflammatory cells, lymphocytes, plasma cells and macrophages, and an increase in eosinophils; 2) the entire thickness of the artery is usually affected, and thrombosis and canalization are common; 3) giant cells are a constant feature, especially in the region of the internal elastic lamina; 4) elastic fibers, sometimes calcified, are seen in the cytoplasm of the giant cells, but there is no fibrinoid necrosis; and 5) the electron microscope shows that the initial lesion is in the smooth muscle of the artery.
I
Elastin (7) is made by mesenchymal cells and is a polymerized tetra peptide with cross-linkage that makes it relatively insoluble. Destruction of that cross-linkage because of copper deficiency, impaired calcium binding or hydrophobic ligands will increase solubility and act as a stimulus for giant-cell formation. Recently the opposite process has been reported, i.e., ductal-cell carcinoma of the breast which by induction increased production of insoluble elastin so that there was reduplication of internal elastic lamina. It would seem worth while to perform trace metal studies on copper excretion when polymyalgia rheumatica is suspected. The dye, congo red, solubilizes the collagen elastin. Possibly a sex-linked defect is involved. REFERENCES 1. Barber HA: Myalgia syndrome with constitutional effects: polymyalgia rheumatica, Ann Rheum Dis 16, 230, 1957. 2. Wilske KR and Healey LA: Polymyalgia rheumatica, a manifestation of systemic giant cell arteritis, Ann Int Med 66:,77, 1967. 3. Bruce W: Senile rheumatic gout, Brit Med J 2: 811, 1888. 4. Flanagan P, McCraken AW, Jones FR et al: Necrotizing arteritis with giant cells associated with haemolytic anemia, J Clin Path 18: 588, 1905. 5. Bruk MI: Articular and vascular manifestations of polymyalgis rheumatica, Ann Rheum Dis 26: 103, 1967. 6. Hamilton CR Jr, Shelley WM and Tumulty PA: Giant cell arteritis, including temporal arteritis and polymyalgia rheumatica, Medicine 50: 1, 1971. 7. Gray WR: Molecular model for elastin structure and function, Nature 246: 461, 1973.
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