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Polymyositis and Dermatomyositis
Polymyositis and Dermatomyositis FRANK M. HOWARD, JR., M.D. JUERGEN E. THOMAS, M.D.
POLYMYOSITIS, at one time considered to be a rare disease, is now recognized as the most common primary myopathy in adults. In the majority of the cases the diagnosis can be made on clinical grounds alone. Confirmation by electromyographic observation and muscle biopsy, however, is always desirable, and indeed, at times these two procedures are indispensable for accurate diagnosis. Polymyositis should be considered in any patient with weakness of the muscles of the proximal part of the extremities. In the past some patients with childhood and "menopausal" dystrophy have been reported as having recovered from their disease. It is now felt that these cases most likely were misdiagnosed and in reality were cases of polymyositis. The establishment of the diagnosis of myositis is important from the standpoint of prognosis and therapy. Progressive muscular dystrophy follows a relentless course and does not respond to any known treatment, whereas polymyositis is a disease from which some patients may recover either spontaneously or under the influence of steroid therapy. It is the intention of this report to summarize the clinical and differential diagnostic aspects of myositis. Wagner, in 1863, is generally given credit for describing the first case and introducing the term "polymyositis." Unverricht, in 1887, was the first to recognize the frequent association of cutaneous lesions and called the disease "dermatomyositis." Sporadic reports mentioned that polymyositis may mimic muscular dystrophy, and in 1953 Adams and associates stressed the distinguishing features of these diseases. In 1954, Eaton reported 17 cases of polymyositis from his personal experience and emphasized the importance of this clinical entity. An excellent summary on this disease and the pertinent literature was presented by Walton and Adams in their book published in 1958. At this point it seems best to define some of the terms often used in discussing primary disease of muscle. The term "myopathy" is nonspecific and implies only a disease that has its primary pathologic change
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in the muscle itself. Involvement of the muscle secondary to neurogenic disease should never be classed as myopathy. For clinical purposes polymyositis may be defined as a disease characterized by weakness of the proximal muscles of the extremities without evidence of involvement of the nervous system; the disease is usually insidious in onset and is associated with characteristic changes discernible in the electromyogram and on microscopic examination of the muscle biopsy. It presents a varied clinical picture with many additional findings as will be discussed later, but there is no one pathognomonic feature or laboratory test. If the condition is associated with characteristic cutaneous lesions, the term "dermatomyositis" is preferred. Aside from the presence of skin lesions, dermatomyositis and polymyositis present similar symptomatology and course. There is still disagreement as to whether they represent two different entities or are the same disease. From the clinical point of view it seems justified to discuss them under the collective term, "myositis." ETIOLOGY
The cause of myositis is unknown. Heredity does not seem to be a factor since a positive family history of muscle disease is usually lacking. We have seen two patients each of whom had another member of his family diagnosed at the Clinic as having the same disease, but such a familial relationship is merely incidental. Hypersensitivity appears to be the favorite etiologic theory at present although there is no definite evidence to confirm this. This mechanism has been invoked as an explanation for the cases that are alleged to follow sensitivity to drugs, beauty aids, minor infections, exanthems and malignant lesions. A history of allergy is seldom obtained. INCIDENCE
Polymyositis and dermatomyositis may occur at any age but are slightly more prevalent in the fifth and sixth decades. Our youngest patient was 18 months old, and we have seen several patients older than 70 years when symptoms began. In childhood, polymyositis is rare, whereas dermatomyositis is almost as common as muscular dystrophy. In adults, myositis is the most common primary myopathy, and most conditions previously diagnosed as menopausal dystrophy are now recognized to be examples of chronic polymyositis. Polymyositis and dermatomyositis occur in Negroes as well as Caucasians and affect females twice as often as males. In pseudohypertrophic muscular dystrophy, males are afflicted almost exclusively. The sex,
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therefore, may be an important differential diagnm,tic point in childhood myopathy. CLINICAL PICTURE
The clinical picture varies considerably from patient to patient, and this is an outstanding feature of the disease. Acute fulminating polymyositis has been described in which the onset is abrupt, with rapid development of muscular weakness and the presence of marked constitutional symptoms such as fever, malaise and generalized muscular aching. This condition usually is accompanied by myoglobulinuria due to massive necrosis of muscle and invariably terminates fatally within one week. Although such cases are well documented,1° we have not seen this syndrome. Most often the onset of the disease is insidious. In polymyositis the most common initial manifestation is weakness of the muscles of the pelvic girdle. The patient may state that he first noticed difficulty on arising from a sitting position or on climbing stairs. Because of weakness of the pelvic girdle he may have a waddling gait, and the presence of this sign may lead to confusion with muscular dystrophy. Less often weakness of the shoulder girdle is the initial symptom. In dermatomyositis the most common initial manifestation is a cutaneous lesion, although girdle weakness even in this group is not infrequently the first symptom. Occasionally there are other initial eomplaints in both groups, such as Raynaud's phenomenon, dysphagia, symptoms referable to joints and muscular pain. Muscular weakness is ultimately pronounced ill almo~t all patients, although it may be minimal when the diagno~is is first established. The pattern is one of involvement of the proximal muscles of the extremitie~. Harely the weakness i~ primarily di~tal, and at times there is diffuse weakness of the extremities. An important differential diagnostic feature is uniform involvement of the girdle muscles as contrasted to that of muscular dystrophy in which weakness in the same distribution is often spotty. Dysphagia is present in roughly half of the patients while in muscular dystrophy it rarely, if ever, occurs. In more advanced cases the respiratory muscles may be involved, resulting in dyspnea. This is a grave prognostic sign. Occasionally other muscle groups are affected including the facial muscles, muscles of phonation and extraocular muscles. The cardiac muscle may be involved although clinical cardiac symptomatology is rare. Frequently weakness is accompanied by muscular atrophy, and contractures may develop. On rare occasions pseudohypertrophy of the muscles may occur. Some patients mention that the muscular weakness is more pronounced after exercise and somewhat improved by rest. This superficially suggests
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myasthenia gravis. Only very rarely have we seen myasthenic features in the electromyogram, and in those patients on whom we have performed pharmacologic tests with edrophonium chloride (Tensilon), neostigmine (Prostigmin) and curare, the results have uniformly been negative. Tenderness of muscles although usually considered a characteristic symptom is frequently absent in our experience, especially in polymyositis. As a result of weakness and atrophy of muscles, the stretch reflexes are commonly reduced proportionate to the degree of weakness of the muscle involved in the reflex arc. The reflexes are never hyperactive and pathologic reflexes are not seen. The remainder of the neurologic examination is normal except in the occasional case in which pressure neuropathies occur. Although some patients may mention mild paresthesia, objective sensory loss is found only rarely. CUTANEOUS LESIONS
The cutaneous lesions of dermatomyositis are of many different types and may appear before or after the onset of muscular weakness. Edema of the face especially in the periorbital regions is one of the earliest manifestations, and generalized edema may be present occasionally. Associated with the edema there is usually some degree of erythema of the skin. A heliotropic suffusion of the eyelids should immediately alert the physician to the possibility of dermatomyositis. This heliotropic tinge is due to the presence of tiny telangiectatic vessels. At a later date changes in the skin occur over the joints at the knuckles, elbows, knees and ankles. These small, shiny erythematous plaques may persist indefinitely or disappear, leaving an atrophic area. The chronic stage of the disease is characterized by the presence of poikiloderma. This is most prevalent over the face, neck and upper part of the chest and consists of atrophy, pigmentation and telangiectasia of the skin. At this stage the changes in the skin often cannot be differentiated from those of lupus erythematosus. Both alopecia and hypertrichosis may occur. Stomatitis and ulceration of the mucous membranes of the mouth are occasionally seen. Calcinosis may be found and involves the muscles that show maximal weakness. Muller, Winkelmann and Brunsting have stressed that this can be anticipated in most children who survive the acute phase of the disease but that the incidence in adults is low. They found that calcinosis usually develops two to three years after the onset of the disease. Occasionally there are recurrent ulcerations of the buttocks, thighs and bony prominences with extrusion of calcified debris and a marked systemic reaction. Hypercalcemia is not associated, and healing without the need for surgical intervention is the rule.
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In about a third of the adult patients with dermatomyositis, Raynaud's phenomenon occurs and may be the initial manifestation of the disease. It is seen less often in polymyositis. ELECTROMYOGRAPHIC EXAMINATION
The laboratory procedures which contribute the most toward confirmation of the diagnosis are the electromyogram and muscle biopsy. In performing electromyography we routinely test the conduction velocities of several peripheral nerves in the upper and lower extremities. In polymyositis conduction velocities are within the normal range except when a pressure neuropathy, such as a tardy ulnar palsy, a crossed-leg peroneal palsy or a carpal tunnel syndrome, is associated. Needle electrode examination of the muscle itself reveals certain findings typical of myopathy but does not always permit the differentiation into specific muscle disease entities. In the usual case of myositis, however, the findings are sufficiently characteristic to confirm the diagnosis. Fibrillation potentials are common in the resting muscle and, in fact, may be numerous in clinically active cases. They appear to be identical to those seen in lower motor neuron disease. Whether, in myositis, they are produced by degeneration of the intramuscular nerve endings or fibrillary contraction of the diseased muscle fiber is still unsettled. With regard to the voluntary innervation of the muscle the picture is identical in progressive muscular dystrophy and polymyositis. The number of motor-unit potentials relative to the strength of contraction is increased. There is a decrease in amplitude of the motor-unit potentials and an increased proportion of polyphasic potentials and of sharp potentials of short duration. The appearance of the motor-unit action potentials on voluntary contraction of the muscle enables one to differentiate the myopathic from the neuropathic diseases, whereas the distinguishing feature between polymyositis and progressive muscular dystrophy is the presence of frequent fibrillation potentials in polymyositis. As with any laboratory procedure, the finding on electromyographic examination must be correlated with the clinical history and examination. MUSCLE BIOPSY
Ideally muscle biopsy should be performed after the electromyographic examination, as a muscle then may be selected that is known to be involved by the disease process and is, therefore, most likely to show microscopic abnormalities. A generous portion of muscle should be removed and longitudinal and cross sections should be obtained. On microscopic examination the most conspicuous finding is degeneration of muscle fibers. Individual fibers are undergoing vacuolar and
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granular degeneration. At times only a portion of the fib er may be involved. The degenerating fiber may be surrounded by inflammatory cells with some of the celb containing phagocytized necrotic material. There is usually an increase in the interstitial fibrous tissue and fat in cases of long standing. R.egenerating muscle fibers, as evidenced by basophilic cytoplasm, and centrally placed nuclei are commonly seen. In chronic polymyositis the inflammatory reaction may be minimal, thereby making pathologic differentiation from progressive muscular dystrophy difficult. The presence of a definite inflammatory reaction along with the presence of regenerating muscle fibers distinguishes polymyositis from muscular dystrophy. OTHER LABORATORY TESTS
TRANSAMINASE AND ALDOLASl<; IN SERUM. Glutamic-oxalacetic transaminase is usually present in elevated concentrations in the blood serum in the myopathies, and the amount present serves as a rough indicator of the activity of the disease. In neuropathies it is present in normal amounts. Since the concentration is elevated in both muscular dystrophy and polymyositis, the test for transaminase is not helpful in distinguishing these two conditions. Administration of steroids to patients with myositis usually will result in a decrease in the serum transaminase. The determination of serum aldolase also may be used, but the results parallel those of the transaminase tests. We no longer use creatine-creatinine determinations. 3 SEDIMENTATION RATE. It should be emphasized that the sedimentation rate is normal (less than 20 mm. in one hour; Westergren) in 40 per cent of the patients with dermatomyositis and polymyositis even when the disease process is very active. In approximately half of the patients the sedimentation rate is moderately elevated. If it exceeds 80 mm. in one hour, the possibility of an associated collagen disease or a malignant lesion must be considered. Lupus ERYTHEMATOSUS CLOT TEST (L.E. CLOT TEST). This test almost invariably gives negative results in polymyositis. In a few patients with systemic lupus erythematosus and a positive L.E. clot test, muscle involvement compatible with polymyositis has been seen. BASAL METABOLIC RATE AND R.ELATED TESTS. The basal metabolic rate is within normal limits in the majority of these patients. When abnormal, it is invariably elevated. The results of the radioactive iodine and protein-bound iodine tests are, however, within normal limits in this disease. SEROLOGIC AND HEMATOLOGIC TESTS AND URINALYSIS. Tests for syphilis usually give no reaction, although rarely a false positive reaction may occur. Erythrocyte and leukocyte counts are rarely abnormal unless
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other complicating diseases exist. Except for slight traces of albumin, urine usually is normal. CEHEBROSPINAL FLUID. The cerebrospinal fluid is almost always normal. In the vast majority of patients we do not test it. In two of our patients the value for protein in the spinal fluid was elevated to 90 mg. per 100 ml. We do not know the significance of this finding, and the clinical course of these patients has not been unusual. ROENTGENOLOGIC FINDINGS. Roentgenograms of the involved muscles may reveal calcinosis. In patients with dysphagia, when the esophagus is examined fluoroscopically after ingestion of barium, abnormalities consisting of pooling of barium in the hypopharynx and a dilated atonic esophagus showing poor peristalsis may be seen. DIFFERENTIAL DIAGNOSIS
The main entity to be considered in the differential diagnosis of polymyositis is muscular dystrophy. At times it is impossible to distinguish muscular dystrophy from polymyositis, but in most cases this can be accomplished. Progressive muscular dystrophy is a disease of childhood and adolescence affecting males predominantly. Myositis on the other hand can begin at any age but has its peak incidence from 40 to 60 years and affects females twice as often as males. In addition the course is more rapid in myositis. Although both diseases produce weakness of the proximal muscles of the upper and lower extremities, the involvement is more uniform in polymyositis. Muscular dystrophy most often causes selective muscle weakness, that is, not all muscles in anyone area are involved, and at times only a portion of an individual muscle may be affected. Late in the course of dystrophy diffuse weakness may be present. Marked weakness of the musculature of the neck, while common in polymyositis, is infrequent in progressive muscular dystrophy. Dysphagia in our experience is a common symptom in myositis and occurs in roughly half of the cases. If muscular pain and tenderness are present, they further support the diagnosis of myositis. Both diseases produce reduction of stretch reflexes in proportion to the degree of muscle weakness. The course is generally more rapid in polymyositis, but remissions may occur. Cutaneous lesions, so typical of dermatomyositis, are not seen in muscular dystrophy. Likewise, Raynaud's phenomenon, fever and arthralgia are not a part of the dystrophies. Among the laboratory procedures most helpful in differential diagnosis are electromyography and muscle biopsy. The differential diagnostic features of these two diseases are compared in Table 1. Other important diseases to be considered in the differential diagnosis are myasthenia gravis, neuronitis, progressive muscular atrophy, thyro-
1008 Table 1.
FRANK
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HOWARD, JR., JUERGEN
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THOMAS
Differential Diagnostic Features of Polymyositis and Progressive Muscular Dystrophy PROGRESSIVE MUSCULAR DYSTROPHY
POLYMYOSITIS
Age at onset. Sex ... Hereditary ... Main weakness ..... Type of muscular involvement .................. Weakness of muscles of neck Muscular tenderness. . . Pseudohypertrophy of muscles .... Muscular pain .. Dysphagia. Fever ..... . Skin changes ..... Raynaud's phenomenon .. Atrophy of muscles. Course .....
Any age. Most common 40 to 60 yr. Females twice as often as males Never Usually proximal muscles of extremities
Childhood and adolescence predominantly Males almost exclusively Often Usually proximal muscles of extremities
Uniform (global) Common Common
Selective (spotty) Unusual Rare
Uncommon but occurs Common May be present Rare Common Rare May occur Never Present in dermatomyositis Never Common Never Common Common Exacerbations and remis- Never any remissions; steady slow progression sions; more rapid progress initially N ever occurs Complete functional recovery May occur Elevated Elevated Serum transaminase. . . . Sedimentation rate. . Elevated in 60 per cent of Rarely elevated cases Electromyogram, fibrillation potentials. . . . Frequent in active cases Usually few or none Muscle biopsy: Rare Inflammatory cells. . . .. Numerous Regenerating muscle fibers Common Rare Treatment. . . . . . . Steroid therapy of benefit No effective treatment in some cases
toxic myopathy, and the myasthenic syndrome associated with pulmonary malignancy. COURSE AND PROGNOSIS
Since the course of the disease is unpredictable, caution must be exercised in discussing the prognosis with the patient and family. Some generalizations are possible, but the individual case must be judged on its own features. The rare cases of acute fulminating polymyositis with myoglobulinuria terminate fatally within one week. The majority of patients with myositis, however, do not succumb but seem to reach a plateau and the dis-
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ease becomes inactive. The peak of activity is usually reached in one to two years. Significant residual disability is the rule, although complete functional recovery sometimes occurs. The highest mortality is among patients with the rare fulminating polymyositis and among patients with coexisting malignant disease or other collagen disease. The long-standing chronic form of the disease has a better prognosis for life. }\Iuller and associates reported a mortality rate of 26 per cent in their group of 31 children. It was unusual for a child to die after the stage of calcinosis had been reached, but marked residual disability usually persisted. One of the most ominous signs is dyspnea, although fortunately this is uncommon. Another poor prognostic sign is failure of the active phase of the disease to respond to steroid therapy. In addition to clinical improvement, a decrease in the abnormalities seen in the electromyogram is the best indication of a satisfactory response to treatment. When death occurs, it is usually due to respiratory complications, to disseminated malignant lesions, or to the coexisting collagen disease. Other causes of death are myocarditis and complications of steroid therapy. Patients in whom the disease is of recent onset are more likely to regain strength than those with chronic disease. When significant muscular atrophy and contractures have developed, the outlook for return of muscular strength is unfavorable. Physical therapy is extremely important, and the intensity with which this is carried out has a considerable bearing on the degree of functional recovery. TREATMENT
The benefits derived from various types of treatment for any disease whose natural course may be one of remissions and exacerbations are difficult to assess. Over the years many drugs have been employed but have failed to produce consistent benefit. Among the most widely used were vitamin E, antibiotics, testosterone and the antimalarials. At present, steroid therapy appears to be the most promising. We believe that every patient in the active stage of the disease should be treated with steroids on a trial basis. The most effective dosage has not been established definitely, but we generally favor the initial use of large doses. To adults we give 200 to 300 mg. of hydrocortisone or 30 to 50 mg. of prednisone daily in divided doses. After a period of about five days this is gradually tapered to a maintenance dose. An attempt is always made to discontinue this treatment, but the disease frequently flares and must again be brought under control by means of steroids. At times in the acute stages the administration of steroids appears to be life-saving and dramatic remissions may occur. Its effect on the over-all course of the disease has not had an adequate evaluation. Unfortunately,
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there itl no way other than a trial of steroid therapy to prediet whieh patients respond favorably. Certainly patients in the ehronie "burnedout" stage do not derive significant benefit. Hypereortisonism frequently oeeum, and the patient must be closely supervised in an attempt to minimize the effects of this complication. The administration of antacids and supplementary potassium itl often required. Occasionally triamcinolone and fiudrocortisone have been reported 4 , 6 to have the undesirable tlide effect of producing muscular weaknestl and atrophy. Although thitl complication seemtl to be reversible the use of these compounds in the treatment of myositis should best be avoided, All patienttl should undergo extensive physical therapy in an attempt to prevent eontraetures and to inerease muscle strength, Adequate periods of rei:lt are etlselltial. At timetl when there is all aHsociated malignant lesion, muscle strength may improve when the neoplasm is removed. ASSOCIATION WITH MALIGNANT LESIONS AND COLLAGEN DISEASES
Polymyositis and dermatomyositis are generally grouped with the collagen diseases. ThiH seems aceeptable if the term "collagen" is used in the broad sense of meaning "collneetive tissue," The most common collagen disease assoeiated with polymyositis is acrosclerosis. Infrequently there is an association with rheumatoid arthritis and periarteritis, and we have seen polymyositis in patients who definitely had lupus erythematosus, although this is rare. This blending of the various collagen diseases suggests the possibility of a common etiologic factor which at. present is unknown. vVhen myositis occurs in older individuals, a careful search for coexisting malignant disease must be made. Malignant lesions occur in approximat.ely 7 per cent of patienti:l with myositis 2 and affect predominantly the older age groups. Despite this age factor, the incidence appears to be higher than in the general population. The neoplasm may be detected before or after the onset of myositis. The reason for this coexistence is unknown. In our experience, the malignant lesiontl most commonly associated are those arising in the breast, rectum or colon, cervix, ovary and lung. Other sites are the kidney, prostate, gallbladder and hypophysis. The tumors are usually carcinomas although occasional lymphomas have been reported, SUMMARY
Polymym;itis seems to be the most common primal'Y myopathy, It should be considered in any patient with weakness of the proximal mus-
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cles of the extremities. In certain cases the diagnosis can be made on the basis of the history and clinical examination, but, if possible, it should be confirmed by electromyographic examination and muscle biopsy. The cause is unknown; the course is often characterized by remissions and exacerbations, and the prognosis generally is guarded. Administration of steroids in conjunction with physical therapy seems to be the most effective treatment at this time. Except for the presence of cutaneous lesions, there is little to distinguish dermatomyositis from polymyositis. The incidence of other collagen diseases and malignant lesions among these patients is high. REFERENCES 1. Adams, R. D., Denny-Brown, D. and Pearson, C. M.: Diseases of Muscle: A Study in Pathology. New York, P. B. Hoeber, 1953,556 pp. 2. Christianson, H. B., Brunsting, L. A. ond Perry, H. 0.: Dermatomyositis: Unusual Features, Complications, and Treatment. A.M.A. Arch. Dermal,. 74: 581-589 (Dec.) 1956. 3. Christianson, H. B., O'Leary, P. A. and Power, M. H.: Urinary Excretion or Creatine and Creatininc in Dermatomyositis. J. Invest. Dermat. 27: 431441 (Dec.) 1956. 4. Dubois, E. L.: Evaluation of Steroids in Systemic Lupus Erythematoms with Particular Emphasis on Triamcinolone and Methylprednisolone. Metaholism 7: 509-525, 1958. 5. Eaton, L. M.: The Perspective of Neurology in Regard to Polymyositis: A Study of 41 Cases. Neurology 4: 245-263 (April) 1954. 6. MacLean, Kenneth and Schurr, P. H.: Reversible Amyotrophy Complicating Treatment with Fludrocortisonc. Lancet 1: 701-703 (April 4) 1959. 7. Muller, S. A., Winkelmann, R. K. and Brunsting, L. A.: Calcinosis in Dermatomyositis: Observations on Course of Disease in Children and Adults. A.M.A. Arch. Dermat. 79: 669-673 (June) 1959. 8. Unverricht, H. T. V.: Polymyositis acuta progressiva. Ztschr. klin. Med. 12: 533-549, 1887. 9. Wagner, E.: Fall einer seltnen Muskelkrankheit. Arch. Heilk. 4: 282, 1863. 10. Walton, J. N. and Adams, R. D.: Polymyositis. Baltimore, Williams & Wilkins Company, 1958, 270 pp.
POLYMYOSITIS, at one time considered to be a rare disease, is now recognized as the most common primary myopathy in adults. In the majority of the cases the diagnosis can be made on clinical grounds alone. Confirmation by electromyographic observation and muscle biopsy, however, is always desirable, and indeed, at times these two procedures are indispensable for accurate diagnosis. Polymyositis should be considered in any patient with weakness of the muscles of the proximal part of the extremities. In the past some patients with childhood and "menopausal" dystrophy have been reported as having recovered from their disease. It is now felt that these cases most likely were misdiagnosed and in reality were cases of polymyositis. The establishment of the diagnosis of myositis is important from the standpoint of prognosis and therapy. Progressive muscular dystrophy follows a relentless course and does not respond to any known treatment, whereas polymyositis is a disease from which some patients may recover either spontaneously or under the influence of steroid therapy. It is the intention of this report to summarize the clinical and differential diagnostic aspects of myositis. Wagner, in 1863, is generally given credit for describing the first case and introducing the term "polymyositis." Unverricht, in 1887, was the first to recognize the frequent association of cutaneous lesions and called the disease "dermatomyositis." Sporadic reports mentioned that polymyositis may mimic muscular dystrophy, and in 1953 Adams and associates stressed the distinguishing features of these diseases. In 1954, Eaton reported 17 cases of polymyositis from his personal experience and emphasized the importance of this clinical entity. An excellent summary on this disease and the pertinent literature was presented by Walton and Adams in their book published in 1958. At this point it seems best to define some of the terms often used in discussing primary disease of muscle. The term "myopathy" is nonspecific and implies only a disease that has its primary pathologic change
1001
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FRANK
M.
HOWARD, JR., JUERGEN
E.
THOMAS
in the muscle itself. Involvement of the muscle secondary to neurogenic disease should never be classed as myopathy. For clinical purposes polymyositis may be defined as a disease characterized by weakness of the proximal muscles of the extremities without evidence of involvement of the nervous system; the disease is usually insidious in onset and is associated with characteristic changes discernible in the electromyogram and on microscopic examination of the muscle biopsy. It presents a varied clinical picture with many additional findings as will be discussed later, but there is no one pathognomonic feature or laboratory test. If the condition is associated with characteristic cutaneous lesions, the term "dermatomyositis" is preferred. Aside from the presence of skin lesions, dermatomyositis and polymyositis present similar symptomatology and course. There is still disagreement as to whether they represent two different entities or are the same disease. From the clinical point of view it seems justified to discuss them under the collective term, "myositis." ETIOLOGY
The cause of myositis is unknown. Heredity does not seem to be a factor since a positive family history of muscle disease is usually lacking. We have seen two patients each of whom had another member of his family diagnosed at the Clinic as having the same disease, but such a familial relationship is merely incidental. Hypersensitivity appears to be the favorite etiologic theory at present although there is no definite evidence to confirm this. This mechanism has been invoked as an explanation for the cases that are alleged to follow sensitivity to drugs, beauty aids, minor infections, exanthems and malignant lesions. A history of allergy is seldom obtained. INCIDENCE
Polymyositis and dermatomyositis may occur at any age but are slightly more prevalent in the fifth and sixth decades. Our youngest patient was 18 months old, and we have seen several patients older than 70 years when symptoms began. In childhood, polymyositis is rare, whereas dermatomyositis is almost as common as muscular dystrophy. In adults, myositis is the most common primary myopathy, and most conditions previously diagnosed as menopausal dystrophy are now recognized to be examples of chronic polymyositis. Polymyositis and dermatomyositis occur in Negroes as well as Caucasians and affect females twice as often as males. In pseudohypertrophic muscular dystrophy, males are afflicted almost exclusively. The sex,
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therefore, may be an important differential diagnm,tic point in childhood myopathy. CLINICAL PICTURE
The clinical picture varies considerably from patient to patient, and this is an outstanding feature of the disease. Acute fulminating polymyositis has been described in which the onset is abrupt, with rapid development of muscular weakness and the presence of marked constitutional symptoms such as fever, malaise and generalized muscular aching. This condition usually is accompanied by myoglobulinuria due to massive necrosis of muscle and invariably terminates fatally within one week. Although such cases are well documented,1° we have not seen this syndrome. Most often the onset of the disease is insidious. In polymyositis the most common initial manifestation is weakness of the muscles of the pelvic girdle. The patient may state that he first noticed difficulty on arising from a sitting position or on climbing stairs. Because of weakness of the pelvic girdle he may have a waddling gait, and the presence of this sign may lead to confusion with muscular dystrophy. Less often weakness of the shoulder girdle is the initial symptom. In dermatomyositis the most common initial manifestation is a cutaneous lesion, although girdle weakness even in this group is not infrequently the first symptom. Occasionally there are other initial eomplaints in both groups, such as Raynaud's phenomenon, dysphagia, symptoms referable to joints and muscular pain. Muscular weakness is ultimately pronounced ill almo~t all patients, although it may be minimal when the diagno~is is first established. The pattern is one of involvement of the proximal muscles of the extremitie~. Harely the weakness i~ primarily di~tal, and at times there is diffuse weakness of the extremities. An important differential diagnostic feature is uniform involvement of the girdle muscles as contrasted to that of muscular dystrophy in which weakness in the same distribution is often spotty. Dysphagia is present in roughly half of the patients while in muscular dystrophy it rarely, if ever, occurs. In more advanced cases the respiratory muscles may be involved, resulting in dyspnea. This is a grave prognostic sign. Occasionally other muscle groups are affected including the facial muscles, muscles of phonation and extraocular muscles. The cardiac muscle may be involved although clinical cardiac symptomatology is rare. Frequently weakness is accompanied by muscular atrophy, and contractures may develop. On rare occasions pseudohypertrophy of the muscles may occur. Some patients mention that the muscular weakness is more pronounced after exercise and somewhat improved by rest. This superficially suggests
1004
FRANK
M.
HOWARD, JR., JUERGEN
E.
THOMAS
myasthenia gravis. Only very rarely have we seen myasthenic features in the electromyogram, and in those patients on whom we have performed pharmacologic tests with edrophonium chloride (Tensilon), neostigmine (Prostigmin) and curare, the results have uniformly been negative. Tenderness of muscles although usually considered a characteristic symptom is frequently absent in our experience, especially in polymyositis. As a result of weakness and atrophy of muscles, the stretch reflexes are commonly reduced proportionate to the degree of weakness of the muscle involved in the reflex arc. The reflexes are never hyperactive and pathologic reflexes are not seen. The remainder of the neurologic examination is normal except in the occasional case in which pressure neuropathies occur. Although some patients may mention mild paresthesia, objective sensory loss is found only rarely. CUTANEOUS LESIONS
The cutaneous lesions of dermatomyositis are of many different types and may appear before or after the onset of muscular weakness. Edema of the face especially in the periorbital regions is one of the earliest manifestations, and generalized edema may be present occasionally. Associated with the edema there is usually some degree of erythema of the skin. A heliotropic suffusion of the eyelids should immediately alert the physician to the possibility of dermatomyositis. This heliotropic tinge is due to the presence of tiny telangiectatic vessels. At a later date changes in the skin occur over the joints at the knuckles, elbows, knees and ankles. These small, shiny erythematous plaques may persist indefinitely or disappear, leaving an atrophic area. The chronic stage of the disease is characterized by the presence of poikiloderma. This is most prevalent over the face, neck and upper part of the chest and consists of atrophy, pigmentation and telangiectasia of the skin. At this stage the changes in the skin often cannot be differentiated from those of lupus erythematosus. Both alopecia and hypertrichosis may occur. Stomatitis and ulceration of the mucous membranes of the mouth are occasionally seen. Calcinosis may be found and involves the muscles that show maximal weakness. Muller, Winkelmann and Brunsting have stressed that this can be anticipated in most children who survive the acute phase of the disease but that the incidence in adults is low. They found that calcinosis usually develops two to three years after the onset of the disease. Occasionally there are recurrent ulcerations of the buttocks, thighs and bony prominences with extrusion of calcified debris and a marked systemic reaction. Hypercalcemia is not associated, and healing without the need for surgical intervention is the rule.
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In about a third of the adult patients with dermatomyositis, Raynaud's phenomenon occurs and may be the initial manifestation of the disease. It is seen less often in polymyositis. ELECTROMYOGRAPHIC EXAMINATION
The laboratory procedures which contribute the most toward confirmation of the diagnosis are the electromyogram and muscle biopsy. In performing electromyography we routinely test the conduction velocities of several peripheral nerves in the upper and lower extremities. In polymyositis conduction velocities are within the normal range except when a pressure neuropathy, such as a tardy ulnar palsy, a crossed-leg peroneal palsy or a carpal tunnel syndrome, is associated. Needle electrode examination of the muscle itself reveals certain findings typical of myopathy but does not always permit the differentiation into specific muscle disease entities. In the usual case of myositis, however, the findings are sufficiently characteristic to confirm the diagnosis. Fibrillation potentials are common in the resting muscle and, in fact, may be numerous in clinically active cases. They appear to be identical to those seen in lower motor neuron disease. Whether, in myositis, they are produced by degeneration of the intramuscular nerve endings or fibrillary contraction of the diseased muscle fiber is still unsettled. With regard to the voluntary innervation of the muscle the picture is identical in progressive muscular dystrophy and polymyositis. The number of motor-unit potentials relative to the strength of contraction is increased. There is a decrease in amplitude of the motor-unit potentials and an increased proportion of polyphasic potentials and of sharp potentials of short duration. The appearance of the motor-unit action potentials on voluntary contraction of the muscle enables one to differentiate the myopathic from the neuropathic diseases, whereas the distinguishing feature between polymyositis and progressive muscular dystrophy is the presence of frequent fibrillation potentials in polymyositis. As with any laboratory procedure, the finding on electromyographic examination must be correlated with the clinical history and examination. MUSCLE BIOPSY
Ideally muscle biopsy should be performed after the electromyographic examination, as a muscle then may be selected that is known to be involved by the disease process and is, therefore, most likely to show microscopic abnormalities. A generous portion of muscle should be removed and longitudinal and cross sections should be obtained. On microscopic examination the most conspicuous finding is degeneration of muscle fibers. Individual fibers are undergoing vacuolar and
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granular degeneration. At times only a portion of the fib er may be involved. The degenerating fiber may be surrounded by inflammatory cells with some of the celb containing phagocytized necrotic material. There is usually an increase in the interstitial fibrous tissue and fat in cases of long standing. R.egenerating muscle fibers, as evidenced by basophilic cytoplasm, and centrally placed nuclei are commonly seen. In chronic polymyositis the inflammatory reaction may be minimal, thereby making pathologic differentiation from progressive muscular dystrophy difficult. The presence of a definite inflammatory reaction along with the presence of regenerating muscle fibers distinguishes polymyositis from muscular dystrophy. OTHER LABORATORY TESTS
TRANSAMINASE AND ALDOLASl<; IN SERUM. Glutamic-oxalacetic transaminase is usually present in elevated concentrations in the blood serum in the myopathies, and the amount present serves as a rough indicator of the activity of the disease. In neuropathies it is present in normal amounts. Since the concentration is elevated in both muscular dystrophy and polymyositis, the test for transaminase is not helpful in distinguishing these two conditions. Administration of steroids to patients with myositis usually will result in a decrease in the serum transaminase. The determination of serum aldolase also may be used, but the results parallel those of the transaminase tests. We no longer use creatine-creatinine determinations. 3 SEDIMENTATION RATE. It should be emphasized that the sedimentation rate is normal (less than 20 mm. in one hour; Westergren) in 40 per cent of the patients with dermatomyositis and polymyositis even when the disease process is very active. In approximately half of the patients the sedimentation rate is moderately elevated. If it exceeds 80 mm. in one hour, the possibility of an associated collagen disease or a malignant lesion must be considered. Lupus ERYTHEMATOSUS CLOT TEST (L.E. CLOT TEST). This test almost invariably gives negative results in polymyositis. In a few patients with systemic lupus erythematosus and a positive L.E. clot test, muscle involvement compatible with polymyositis has been seen. BASAL METABOLIC RATE AND R.ELATED TESTS. The basal metabolic rate is within normal limits in the majority of these patients. When abnormal, it is invariably elevated. The results of the radioactive iodine and protein-bound iodine tests are, however, within normal limits in this disease. SEROLOGIC AND HEMATOLOGIC TESTS AND URINALYSIS. Tests for syphilis usually give no reaction, although rarely a false positive reaction may occur. Erythrocyte and leukocyte counts are rarely abnormal unless
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other complicating diseases exist. Except for slight traces of albumin, urine usually is normal. CEHEBROSPINAL FLUID. The cerebrospinal fluid is almost always normal. In the vast majority of patients we do not test it. In two of our patients the value for protein in the spinal fluid was elevated to 90 mg. per 100 ml. We do not know the significance of this finding, and the clinical course of these patients has not been unusual. ROENTGENOLOGIC FINDINGS. Roentgenograms of the involved muscles may reveal calcinosis. In patients with dysphagia, when the esophagus is examined fluoroscopically after ingestion of barium, abnormalities consisting of pooling of barium in the hypopharynx and a dilated atonic esophagus showing poor peristalsis may be seen. DIFFERENTIAL DIAGNOSIS
The main entity to be considered in the differential diagnosis of polymyositis is muscular dystrophy. At times it is impossible to distinguish muscular dystrophy from polymyositis, but in most cases this can be accomplished. Progressive muscular dystrophy is a disease of childhood and adolescence affecting males predominantly. Myositis on the other hand can begin at any age but has its peak incidence from 40 to 60 years and affects females twice as often as males. In addition the course is more rapid in myositis. Although both diseases produce weakness of the proximal muscles of the upper and lower extremities, the involvement is more uniform in polymyositis. Muscular dystrophy most often causes selective muscle weakness, that is, not all muscles in anyone area are involved, and at times only a portion of an individual muscle may be affected. Late in the course of dystrophy diffuse weakness may be present. Marked weakness of the musculature of the neck, while common in polymyositis, is infrequent in progressive muscular dystrophy. Dysphagia in our experience is a common symptom in myositis and occurs in roughly half of the cases. If muscular pain and tenderness are present, they further support the diagnosis of myositis. Both diseases produce reduction of stretch reflexes in proportion to the degree of muscle weakness. The course is generally more rapid in polymyositis, but remissions may occur. Cutaneous lesions, so typical of dermatomyositis, are not seen in muscular dystrophy. Likewise, Raynaud's phenomenon, fever and arthralgia are not a part of the dystrophies. Among the laboratory procedures most helpful in differential diagnosis are electromyography and muscle biopsy. The differential diagnostic features of these two diseases are compared in Table 1. Other important diseases to be considered in the differential diagnosis are myasthenia gravis, neuronitis, progressive muscular atrophy, thyro-
1008 Table 1.
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Differential Diagnostic Features of Polymyositis and Progressive Muscular Dystrophy PROGRESSIVE MUSCULAR DYSTROPHY
POLYMYOSITIS
Age at onset. Sex ... Hereditary ... Main weakness ..... Type of muscular involvement .................. Weakness of muscles of neck Muscular tenderness. . . Pseudohypertrophy of muscles .... Muscular pain .. Dysphagia. Fever ..... . Skin changes ..... Raynaud's phenomenon .. Atrophy of muscles. Course .....
Any age. Most common 40 to 60 yr. Females twice as often as males Never Usually proximal muscles of extremities
Childhood and adolescence predominantly Males almost exclusively Often Usually proximal muscles of extremities
Uniform (global) Common Common
Selective (spotty) Unusual Rare
Uncommon but occurs Common May be present Rare Common Rare May occur Never Present in dermatomyositis Never Common Never Common Common Exacerbations and remis- Never any remissions; steady slow progression sions; more rapid progress initially N ever occurs Complete functional recovery May occur Elevated Elevated Serum transaminase. . . . Sedimentation rate. . Elevated in 60 per cent of Rarely elevated cases Electromyogram, fibrillation potentials. . . . Frequent in active cases Usually few or none Muscle biopsy: Rare Inflammatory cells. . . .. Numerous Regenerating muscle fibers Common Rare Treatment. . . . . . . Steroid therapy of benefit No effective treatment in some cases
toxic myopathy, and the myasthenic syndrome associated with pulmonary malignancy. COURSE AND PROGNOSIS
Since the course of the disease is unpredictable, caution must be exercised in discussing the prognosis with the patient and family. Some generalizations are possible, but the individual case must be judged on its own features. The rare cases of acute fulminating polymyositis with myoglobulinuria terminate fatally within one week. The majority of patients with myositis, however, do not succumb but seem to reach a plateau and the dis-
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ease becomes inactive. The peak of activity is usually reached in one to two years. Significant residual disability is the rule, although complete functional recovery sometimes occurs. The highest mortality is among patients with the rare fulminating polymyositis and among patients with coexisting malignant disease or other collagen disease. The long-standing chronic form of the disease has a better prognosis for life. }\Iuller and associates reported a mortality rate of 26 per cent in their group of 31 children. It was unusual for a child to die after the stage of calcinosis had been reached, but marked residual disability usually persisted. One of the most ominous signs is dyspnea, although fortunately this is uncommon. Another poor prognostic sign is failure of the active phase of the disease to respond to steroid therapy. In addition to clinical improvement, a decrease in the abnormalities seen in the electromyogram is the best indication of a satisfactory response to treatment. When death occurs, it is usually due to respiratory complications, to disseminated malignant lesions, or to the coexisting collagen disease. Other causes of death are myocarditis and complications of steroid therapy. Patients in whom the disease is of recent onset are more likely to regain strength than those with chronic disease. When significant muscular atrophy and contractures have developed, the outlook for return of muscular strength is unfavorable. Physical therapy is extremely important, and the intensity with which this is carried out has a considerable bearing on the degree of functional recovery. TREATMENT
The benefits derived from various types of treatment for any disease whose natural course may be one of remissions and exacerbations are difficult to assess. Over the years many drugs have been employed but have failed to produce consistent benefit. Among the most widely used were vitamin E, antibiotics, testosterone and the antimalarials. At present, steroid therapy appears to be the most promising. We believe that every patient in the active stage of the disease should be treated with steroids on a trial basis. The most effective dosage has not been established definitely, but we generally favor the initial use of large doses. To adults we give 200 to 300 mg. of hydrocortisone or 30 to 50 mg. of prednisone daily in divided doses. After a period of about five days this is gradually tapered to a maintenance dose. An attempt is always made to discontinue this treatment, but the disease frequently flares and must again be brought under control by means of steroids. At times in the acute stages the administration of steroids appears to be life-saving and dramatic remissions may occur. Its effect on the over-all course of the disease has not had an adequate evaluation. Unfortunately,
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there itl no way other than a trial of steroid therapy to prediet whieh patients respond favorably. Certainly patients in the ehronie "burnedout" stage do not derive significant benefit. Hypereortisonism frequently oeeum, and the patient must be closely supervised in an attempt to minimize the effects of this complication. The administration of antacids and supplementary potassium itl often required. Occasionally triamcinolone and fiudrocortisone have been reported 4 , 6 to have the undesirable tlide effect of producing muscular weaknestl and atrophy. Although thitl complication seemtl to be reversible the use of these compounds in the treatment of myositis should best be avoided, All patienttl should undergo extensive physical therapy in an attempt to prevent eontraetures and to inerease muscle strength, Adequate periods of rei:lt are etlselltial. At timetl when there is all aHsociated malignant lesion, muscle strength may improve when the neoplasm is removed. ASSOCIATION WITH MALIGNANT LESIONS AND COLLAGEN DISEASES
Polymyositis and dermatomyositis are generally grouped with the collagen diseases. ThiH seems aceeptable if the term "collagen" is used in the broad sense of meaning "collneetive tissue," The most common collagen disease assoeiated with polymyositis is acrosclerosis. Infrequently there is an association with rheumatoid arthritis and periarteritis, and we have seen polymyositis in patients who definitely had lupus erythematosus, although this is rare. This blending of the various collagen diseases suggests the possibility of a common etiologic factor which at. present is unknown. vVhen myositis occurs in older individuals, a careful search for coexisting malignant disease must be made. Malignant lesions occur in approximat.ely 7 per cent of patienti:l with myositis 2 and affect predominantly the older age groups. Despite this age factor, the incidence appears to be higher than in the general population. The neoplasm may be detected before or after the onset of myositis. The reason for this coexistence is unknown. In our experience, the malignant lesiontl most commonly associated are those arising in the breast, rectum or colon, cervix, ovary and lung. Other sites are the kidney, prostate, gallbladder and hypophysis. The tumors are usually carcinomas although occasional lymphomas have been reported, SUMMARY
Polymym;itis seems to be the most common primal'Y myopathy, It should be considered in any patient with weakness of the proximal mus-
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cles of the extremities. In certain cases the diagnosis can be made on the basis of the history and clinical examination, but, if possible, it should be confirmed by electromyographic examination and muscle biopsy. The cause is unknown; the course is often characterized by remissions and exacerbations, and the prognosis generally is guarded. Administration of steroids in conjunction with physical therapy seems to be the most effective treatment at this time. Except for the presence of cutaneous lesions, there is little to distinguish dermatomyositis from polymyositis. The incidence of other collagen diseases and malignant lesions among these patients is high. REFERENCES 1. Adams, R. D., Denny-Brown, D. and Pearson, C. M.: Diseases of Muscle: A Study in Pathology. New York, P. B. Hoeber, 1953,556 pp. 2. Christianson, H. B., Brunsting, L. A. ond Perry, H. 0.: Dermatomyositis: Unusual Features, Complications, and Treatment. A.M.A. Arch. Dermal,. 74: 581-589 (Dec.) 1956. 3. Christianson, H. B., O'Leary, P. A. and Power, M. H.: Urinary Excretion or Creatine and Creatininc in Dermatomyositis. J. Invest. Dermat. 27: 431441 (Dec.) 1956. 4. Dubois, E. L.: Evaluation of Steroids in Systemic Lupus Erythematoms with Particular Emphasis on Triamcinolone and Methylprednisolone. Metaholism 7: 509-525, 1958. 5. Eaton, L. M.: The Perspective of Neurology in Regard to Polymyositis: A Study of 41 Cases. Neurology 4: 245-263 (April) 1954. 6. MacLean, Kenneth and Schurr, P. H.: Reversible Amyotrophy Complicating Treatment with Fludrocortisonc. Lancet 1: 701-703 (April 4) 1959. 7. Muller, S. A., Winkelmann, R. K. and Brunsting, L. A.: Calcinosis in Dermatomyositis: Observations on Course of Disease in Children and Adults. A.M.A. Arch. Dermat. 79: 669-673 (June) 1959. 8. Unverricht, H. T. V.: Polymyositis acuta progressiva. Ztschr. klin. Med. 12: 533-549, 1887. 9. Wagner, E.: Fall einer seltnen Muskelkrankheit. Arch. Heilk. 4: 282, 1863. 10. Walton, J. N. and Adams, R. D.: Polymyositis. Baltimore, Williams & Wilkins Company, 1958, 270 pp.