Polymyositis

antibodies. Tests that detect immune complex-bound C3 will also reveal those complexes that can activate complement by the alternative pathway. False-positive results can be induced in a number of different ways. First of all, IgG aggregated by repeated freezing and thawing, by heat inactivation, and by storage may interact in most of the tests described; endotoxin, DNA, and low-molecularweight polyanions can react with Clq. In addition, immune complexes not binding Clq, or of insufficient size to precipitate will remain undetected. Lymphocytotoxic antibodies may bind to Raji cells and should be adsorbed from the serum prior to testing. It has been shown that assays do not necessarily correlate with one another. For example, using the Raji cell assay, higher levels of immune complexes are found in SLE than in rheumatoid arthritis, while the opposite is observed using the Clq binding assay or the monoclonal RF inhibition assay. At the present time, there are no simple techniques for detecting circulating complexed 19A and IgE antibodies, but it is anticipated they will

be developed in the near future. The clinical usefulness of the detection of CIC is currently under study. It appears that their detection may be useful in management of SLE, rheumatoid arthritis and bacterial endocarditis (3, 5, 9), yet no uniformity of opinion has been reached. It is hoped that these tests will provide new insights into the pathogenesis, diagnosis and management of immune complex disease. References 1. Cochrane, C. G., and F. J. Dixon. 1976. Antigen-antibody complex induced disease, p. 137. In P. A. Meischer, and H. J. Muller-Eberhard (eds.), Textbook of immunopathology, 2nd ed., vo!. 1. Grune & Stratton, New York. 2. Dixon, F. J., J. J. Vasquez, W. O. Weigle, and C. G. Cochrane. 1958. Pathogenesisof serum sickness. Arch. Patho!. Lab. Med. 65:18-27. 3. Espinoza, L. R., S. W. Gaylord. F. B. Vasey, B. F. Germain, and C. K. Osterland, 1980. The "active" rosette test in rheumatoid arthritis: Correlation with disease activity. Clint Immuno!. lmrnunopathol.

Clinical, pathologic, immunologic, and therapeutic considerations. Ann. Intern. Med. 89(Part 1):660676. 5. Frank, M. M., M. I. Hamburger, T. J. Lawley, R. P. Kimberly, and P. H. Plotz. 1979. Defective reticu-

loendothelial system Fc-recepror function in systemic lupus erythematosus. N. Eng!. J. Med. 300: 518-523. 6. Germuth, F. G. 1953. A comparative

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4. Fauci, A. S. 1978. Pathophysiology and immunologic mechanisms, pp. 660-662. In A. S. Fauci (moderator), The spectrum of vasculitis.

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histologic and immunologic study in rabbits of induced hypersensitivity of the serum sickness type. J. Exp. Med. 97:257-268. Lambert, P. H., et al, 1978. A WHO collaborativestudy for the evaluation of eighteen methods for detecting immune complexes in serum. J. Clint Lab. Immuno!. 1:1-15. McDuffie, F. C. 1978. Immune complexes in the rheumatic diseases. J. Allergy Clin. Immunol. 62:37-43. Pussell, B. A., C. M. Lockwood, D. M. Scott, A. J. Pinching, and D. K. Peters. 1978. Valueof immunecomplex assays in diagnosis and management. Lancet 11:359-364. Theofilopoulos, A. N., C. B. Wilson, and F. J . Dixon. 1976. The Raji cell radioimmunoassay for detecting immune complexes in human sera. J. C1in. Invest. 57:169-182 . Zubler, R. H., and P. H. Lambert. 1978. Detection of immune complexes in human diseases. Prog. Allergy 24:1-48.

Case Report Polymyositis Mahadevappa Vagesh, M.D. Frank B. Vasey, M.D. Luis R. Espinoza, M.D. Bernard F. Germain, M.D. Department of Internal Medicine College of Medicine University of South Florida Tampa. Florida 33612

Polymyositis (PM) is a disorder of striated muscle characterized by diffuse inflammatory and degenerative changes resulting in symmetrical weakness and, to a lesser degree, muscle atrophy. The term dermatomyositis (OM) is applied in the presence of typical skin lesions. The first recorded case of PM was described by Wagner in 1863, but until recently this condition has received comparatively little atten-

tion. The more dramatic subgroup, OM, was first outlined by Unverricht in 1887. OM held the spotlight for more than fifty years as the predominant inflammatory myopathy. For the past two decades it has been recognized that patients with myositis may lack the typical skin lesions. A 62-year-old male developed proximal muscle weakness six weeks prior to admission to the hospital in April 1980. The patient initially developed difficulty in climbing stairs and rising from a chair. This pelvic girdle muscle weakness was followed by weakness of the shoulder girdle muscle, which caused difficulty combing his hair and lifting objects. The muscle weakness gradually progressed over the next few weeks, causing the patient to become nonambulatory. He also complained of

proximal myalgia, malaise, anorexia and a 15-lb weight loss during the six weeks prior to admission. He did not have Raynaud's phenomenon, oral Ulcers, arthralgia, arthritis, sclerodactyly or skin rashes. Examination revealed severe weakness and atrophy of the proximal muscles of the upper and lower extremities. Laboratory studies revealed markedly elevated muscle enzymes (creatine phosphokinase (CPK), aldolase, transaminases), negative antinuclear antibody test (ANA), and an abnormal electromyogram that showed a myopathic pattern. A muscle biopsy revealed marked infiltration of acute and chronic inflammatory cells, necrosis, noticeable variation of muscle fiber size and atrophy. The erythrocyte sedimentation rate was 49 mm/hr, 7

and thyroid function studies were normal. Diagnostic studies for malignancy, which included an upper gastrointestinal series, barium enema, colonoscopy and intravenous pyelogram, were normal. Treatment with prednisone (60 rug/day) resulted in improvement over the next several weeks. This case demonstrates typical clinical and laboratory features of polymyositis. Approximately onehalf of the cases are associated either with a malignancy or a connective tissue disease (scleroderma, systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, polyarteritis modosa), and the other half of the cases occur as isolated primary myopathies or in combination with a skin lesion. The frequency of PM among the inflammatory myopathies has been estimated to be approximately 35%; and that of DM to be approximately 300/0 (I, 2). PM and DM can occur at any age, but most cases occur during the fifth and sixth decades of life (I). PM occurs most commonly in females, with a male to female ratio of 1:2; the ratio is nearly equal in patients with DM (5). Constitutional symptoms of fever, anorexia, weight loss, and malaise are particularly common in acute cases. Proximal muscle weakness is the most common presenting feature and is present in nearly all patients with PM. In its absence, the diagnosis cannot be made with assurance. Typically, initial weakness of pelvic girdle muscles is observed followed by weakness of the shoulder girdle muscles. The onset of muscle weakness can be acute, progressing over weeks and months or gradually progressing over a period of years. The muscle weakness may show periods of remission and exacerbation. In some cases the weakness may be extreme and the patient becomes bedridden or confined to a wheel chair. Muscle pain, tenderness and induration are present in few cases. Shortening and contracture of muscles rarely occur and atrophy of muscles is usually a late event. Calcinosis of muscles may occur after severe myositis, especially in children.

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Weakness of anterior neck muscles and respiratory muscles can occur. Distal muscle strength is usually well maintained, however, and facial muscles are typically uninvolved. Raynaud's phenomenon is seen in about 300/0 of patients with PM, particularly in patients with an associated connective tissue disease (1,2), and somewhat less commonly in those with isolated PM and OM. Its occurrence is usually not severe. Transitory arthralgia or arthritis develops in about one-third of the patients with PM (l, 2). It usually involves the small joints of the hands, wrists and knees and appears identical to early rheumatoid arthritis (5). Marginal erosive changes and deforming arthritis of the hands have been reported. Visceral manifestations of PM and DM are rare but have been described as affecting almost every organ. Interstitial lung disease, manifested clinically as cough, dyspnea, hypoxemia and interstitial infiltrates, has been described (6). Dysphagia due to involvement of the posterior pharyngeal muscles and esophagus, and small bowel involvement causing abdominal bloating, constipation and malabsorption can occur. Involvement of cardiac muscle can also occur, and patients may have cardio-

myopathy, manifested as abnormal electrocardiographic findings, in the absence of overt myocardial inflam_ rnatory disease. The most common abnormality is nonspecific ST-T changes (5). Histologically proven myocarditis has been reported in patients with PM. The typical skin rash of OM seen in about 30070 of patients with PM (1, 2) consists of a dusky erythematous eruption on the face in a butterfly distribution, over the periorbital areas, occasionally on the forehead, neck, shoulders, upper chest, and proximal and distal portions of the upper extremities. The heliotrope rash consisting of lilac discoloration of upper eyelids with periorbital edema is considered to be pathognomonic of OM. Erythematous, scaling eruption, with and without atrophy, and dusky red patches or linear streaks over the knuckles, elbows, knees, and medial malleoli of the ankles can also be present.

Laboratory abnormalities Most routine laboratory studies are normal except for occasional elevation of the erythrocyte sedimentation rate and alteration of acute-phase reactants. Leukocytosis may occur, especially in acute cases; anemia is rare. A positive ANA in up to 250/0

Editors: Herman Friedman, Mano Escobar, and Noel Rose Editorial Committee: Charles D. Graber. Ph D.• Medical University of South Carolina; John R. Kateley, Ph.D., Edward W. Sparrow Hospital Assoc.; Bruce S. Rabin. M.D., Ph.D., University of Pittsburgh School of Medicine; Robert F. Ritchie, M.D., Foundation for Blood Research. Maine; John L. Sever, M.D., Ph.D., National Instil ute of Neurological and Communicative Disorders and Stroke. National Institutes of Health; Steven Specter. Ph.D., University of South Florida College of Medicine; Roy W. Stevens. Ph.D., New York Health Department Laboratories; Norman Talal, M.D .• VA Hospital and University of California Medical Center at San Francisco; Eng M. Tan. M.D., University of Colorado Medical Center; Gabriel Virella, M.D., Ph.D., Medical University of South Carolina. Subscription Rates in U.S. and Canada: one year 546.50; two years 589.00; three years $127.50. All other countries: one year $53.50; two years $102.50; three years 5146.50. Single copies are $2.00 in U.S. and Canada, $2.65 all other countries. Single issues are available in quannty (prices available upon request). All subscriptions are payable in advance. Foreign subscriptions are sent guaranteed air mail. First class postage paid in U.S. and Canada. Address correspondence regarding subscription to: Clinical Immunology Newsletter. G. K. Hall & Co., 70 Lincoln St., Boston. Massachusetts 02111. Please include zip code in subscription address. The Clmical Immunology Newsletter is published twice monthly. All rights, including that of translation into other languages, reserved. Photomechanical reproduction (photocopy, microcopy) of this newsletter or parts thereof without special permission of the publisher is prohibited.

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of patients and a positive rheumatoid supports a possible role for cellhas been reported, is exceptional. factor (RF) in up to 40010 of patients .mediated immunity directed against Several large series have failed to have been reported. The 24-hour show familial occurrence. Increased the patients' muscle cells (4). Lymphofrequency of HLA-B8 has been urinary creatine excretion will be cytes from patients with active PM elevated in the majority of the have been shown to produce cytotoxic reported, but the role of the HLA patients with active PM. Myoglobin system in the pathogenesis of this effects on cultured muscle cell lines of disease is not clear. has been detected in the serum of up both chick embryo (3) and human to 70% of patients and in the urine of origins. Evidence for altered humoral Treatment 20% of patients. immunity is meager. The presence Corticosteroids are generally conElevation of muscle enzymes in the of antimyosin antibodies, which are sidered beneficial in the treatment of serum (CPK, aldolase, transaminot cytotoxic to muscle cells, have polymyositis (4). Those patients who nases, and LDH) are of the greatest been reported not only in PM but in fail to respond to corticosteroids in help diagnostically and in following other neurogenic and dystrophic months should full doses over several the clinical course and response to processes. Vascular deposition of be considered for immunosuppressive treatment (4). The serum enzymes will IgG, IgM and C3 has been reported, agents, which appear to have a steroid be elevated at some time in almost all particularly in patients with childsparing effect. Significant clinical patients with active myositis. The hood OM. It has been postulated that improvement has been reported in CPK is most reliable and sensitive and one of the mechanisms leading to correlates best with the clinical course more than 75% of patients treated muscle injury may be vascular abwith methotrexate, the most comand other parameters of activity. normalities mediated through deposimonly used immunosuppressive Occasionally patients may have only tion of immunoglobulins and C3, agent. one muscle enzyme elevated with the possibly in the form of immune others remaining normal. Muscle complexes (7). enzymes usually return to normal as Newly discovered antinuclear References the myopathic process responds to antibody systems distinct from those I. Barwic, D. D., and J. N. Walton. treatment with steroids. The CPK described in other diseases have been 1963. Polymyositis. Am. J. Med., normalizes in the majority of patients reported to be specific for PM. The 35:646. antigen involved (PM-I) is most in two to four months, and its decline 2. Bohan, A., J. B. Peter, R. L. Bowman. and C. M. Pearson. 1977. A comusually precedes any significant easily detected by precipitin reactions puter assisted analysis of 153 patients improvement in muscle strength by in gel. Antibody to it is present in with polymyositis and dermatomyothree to four weeks. more than 50% of PM sera tested, sitis. Medicine (Baltimore) 56:255. Abnormalities of the electroand none is found in control sera. 3. Dawkins. R. L•• and F. L. Mastaglia. myogram (EMG) suggestive of PM However, the pathogenetic signifi1973. Cell-mediated cytotoxicity to muscle in polymyositis. N. Engl. J. have been reported to occur in a cance of the above is unknown. The Med. 288:434. majority of patients. A completely association between PM and OM and 4. Pearson, C. M. 1979. Polymyositis normal EMG may be seen in about malignancy is generally accepted. and dermatomyositis, pp. 742-761. 10070 of patients. Small-amplitude, PM-OM in cancer may represent In D. J. McCarty (ed.), Arthritis and short-duration. polyphasic motorautosensitivity to malignancy. In allied conditions, 9th ed. Lea and unit potentials are the most comFebiger, Philadelphia. some patients with a malignancy and 5. Schumacher. H. R., et al. 1979. monly seen abnormalities (2). myositis, tissue extract of tumor was Articular manifestations of polyTypical changes on muscle biopsy found to cause immediate skin-test myositis and dermatomyositis. Am. occur in most patients. A completely reactivity that could then be passively J. Med. 67:287. normal muscle biopsy is seen in about transferred. Circulating antibodies 6. Schwartz, M. I., et al. 1976. Inter10% of patients (2). The most frestitial lung disease in polymyositis ana against the tumor have been found. dermatomyositis. Analysis of six cases quent abnormalities are degeneration A variety of precipitating environand review of literature . Medicine of the muscle fibers, inflammation mental factors have been suggested. (Baltimore) 55:89. with chronic inflammatory cells Photosensitivity is common in DM. 7. Whitaker, J. N•• and W. K. Engel. and exposure to sunlight can initiate usually near or surrounding blood 1972. Vascular deposits of immunoglobulin and complement in idiopathic an eruption on the arms, face, and vessels. and cross-sectional diameter inflammatory myopathy. N. Eng\. J. legs. Viral infections have received variation of muscle fibers. Necrosis. Med., 286:333. particular attention. Severe transient regeneration, fibrosis, phagocytosis myositis in children following inand vasculitis occur less frequently fluenza has been documented. (2). Electron-microscopic studies by a number of workers have demonEtiology and Pathogenesis of PM strated nuclear and cytoplasmic Mechanisms causing muscle structures resembling viruses. destruction in the inflammatory Familial occurrence of PM, which myopathies are unresolved. Evidence 9