Dermatomyositis of childhood is an uncommon disorder affecting many organs of which skin and muscle are the most prominent. It was first described in 1887 simultaneously in several countries, with Unverricht in particular giving an account of its salient clinical features. Although there were scattered case reports throughout the earlier part of this century, it was in the 1950s and 1960s that large series of cases were accumulated. These served to emphasize the unique clinical and pathologic nature of this inflammatory disorder in children.
In 1966 Banker and Victor described eight fully autopsied cases. Their pathologic reports emphasized the essential lesion in this illness - namely, the diffuse angiitis with thrombosis and secondary infarction. These infarctions, in turn, give rise to the symptom complex defining childhood dermatomyositis.
Various corticosteroids have been used in the treatment of dermatomyositis since 1953. Although there is still some controversy over dosage regimens and ultimate efficacy, most experts agree that prognosis in children has improved since the advent of vigorous steroid treatment. Other immunosuppressants have been tried more recently; however, results of comparative studies between these drugs and steroids are not available.
CLINICAL PRESENTATION (TABLE 1)
As mentioned previously, dermatomyositis of childhood is a systemic disease affecting numerous organs, including skeletal muscle, skin, gastrointestinal tract, adipose tissue, and portions of the peripheral nervous system. It has a rather characteristic clinical presentation, which varies from child to child only in severity and rapidity of onset.
The onset is usually insidious and rarely acute, occurring over several weeks to several months. The earliest symptoms are of a vague nature, with constitutional symptoms including malaise, fatigue, "general misery" (Dubowitz) and a low-grade fever. Usually concurrent with these complaints is the appearance of the characteristic skin rash described below. Muscle weakness is the other major clinical symptom in the disease and frequently appears slightly after the onset of the constitutional complaints. Dermatomyositis is remarkable among neuromuscular disorders in its association of muscle weakness with definite systemic complaints. This association has given rise to a useful rule of thumb in clinical pediatric practice, according to Dubowitz and Brooke, that " 'misery' plus muscle weakness equals dermatomyositis" until proven otherwise.
Statistics. Dermatomyositis is a relatively rare disorder with one or two new cases per year seen in large urban referral centers. In most large series there is a preponderance of girls over boys of roughly 3:2. It can occur from infancy to late teenage, with average onset occurring in the middle of the first decade of life. The onset is usually insidious over several months but may be acute and fulminant. The duration of the disease is quite variable, with the active phase lasting several years.
General signs and symptoms. The children often have nonspecific constitutional symptoms that precede the onset of muscular weakness or the rash. The most common of these are anorexia, malaise, listlessness, excessive fatigue, and low-grade fever. Occasionally, the patients appear acutely ill and may be misdiagnosed as having a variety of infectious processes.
Skin manifestations. It is the remarkable skin rash of dermatomyositis, along with the muscle weakness, that defines the characteristic clinical appearance of the childhood form of the illness. Skin changes occur early in virtually all cases. The most common skin changes in childhood dermatomyositis include the appearance of a rash around the eyes and upper face that has a characteristic dull erythematous or violaceous hue. There may be associated periorbital edema as well. A similar rash occurs over the extensor surfaces of the rest of the body, particularly the knees, elbows, knuckles, and interphalangeal region. Capillary dilatations may be very prominent, especially over the nail beds. Later skin lesions become scaly or atrophic, frequently with telangiectasis, and the skin becomes paper-thin in the involved areas (Figure 1). With resolution, previously involved regions may become hypo- or hyperpigmen ted. Less commonly, the skin involvement may be manifested by a faint scaling eruption, sometimes accompanied by increased pigmentation or ulceration.
Figure 1. Closeup of 1 2-year-old child with dermatomyositis, showing red lesions on the fingers and knees.
Muscular involvement. Muscle weakness is a constant feature of the disease but may be quite variable in severity. Some cases may be very mild, and the weakness may be missed unless specifically sought in the history and with functional tests. Although theoretically all skeletal muscles may be involved in the disease, there is a marked propensity for involvement of proximal limbs, trunk, and pharyngeal muscles. Respiratory muscles may also be involved; in rare instances, the disease may present with fulminant ventilatory failure. Facial muscles are occasionally mildly weak. Extraocular muscles are almost never affected. Sphincters are generally spared as well.
Besides exhibiting weakness, the muscles may be painful or tender and may have a brawny, indurated feel to palpation. Common complaints include clumsiness, difficulty climbing and running, frequent falls, and problems with walking upstairs or getting out of chairs. If the muscles of respiration or swallowing are involved, there may be a variety of problems, including change in voice, dysphagia, nasal regurgitation, aspiration, and sometimes frank respiratory insufficiency. Significant involvement of the palatorespiratory muscles indicates a more severe prognosis.
Gastrointestinal tract. There may be involvement of the gastrointestinal tract throughout its entire length, manifested as hemorrhage, ulceration, perforation, and infarction. Patients may develop episodes of severe abdominal pain, hematemesis, melena, or peritonitis. In some series, significant gastrointestinal tract involvement accounts for most deaths due to childhood dermatomyositis and represents a distinct difference between the childhood and adult forms of the disease. The intestinal signs and symptoms are secondary to the occlusive vasculitis which is the probable pathogenetic basis of the disease.
Calcinosis. Subcutaneous deposits of calcium, usually localized, occur in 20 to 40 per cent of children at a later stage in the disease. These may ulcerate and extrude and, rarely, become infected. The calcifications may be generalized, and they may give a striking armorlike appearance on x-ray.
Cardiac disease. Rare patients may manifest evidence of myocardial involvement with congestive failure. However, the review by Bitnum et al. describes electrocardiographic abnormalities in eight of 13 cases. Six of these had changes suggestive of myocardial ischemia with ST-T wave changes. Arrhythmia may (rarely) occur as well.
Miscellaneous. Hepatosplenomegaly, as well as some nonspecific lymphadenopathy, may occur in 10 to 20 per cent of cases. Some patients develop joint contractures, sometimes surprisingly early in the course of the disease. Muscle atrophy may be found, usually in a later stage. Deep tendon reflexes are usually hypoactive.
LABORATORY AIDS IN THE DIAGNOSIS OF CHILDHOOD DERMATOMYOSITIS
The diagnosis of dermatomyositis of childhood is essentially a clinical one, based on the history and the constellation of signs and symptoms described previously. The laboratory is helpful only insofar as it confirms the clinician's impression. There is no single laboratory test diagnostic of the disease, and all the tests mentioned below may be relatively normal or nonspecific in a patient with active disease. There are, nevertheless, some very useful studies that should be obtained in suspected cases of dermatomyositis.
Serum enzymes. The "muscle" enzymes are very useful, and the ones usually determined are creatine Phosphokinase and aldolase. They are usually elevated in the active stage of the disease and help in the therapeutic management.
Sedimentation rate. This may or may not be elevated during the active phase. It is sometimes useful in following patients, since an unexpected rise may herald a recrudescence of activity.
Electromyography. There is a very characteristic set of electromyographic findings in these patients. These include spontaneous fibrillations and positive waves suggestive of denervation in the presence of complex polyphasics, with small amplitude and brief duration suggestive of myopathy. This combination of "neuropathic" and "myopathic" features is very important in the appropriate clinical setting. Nerve conduction velocities are normal.
Muscle and skin biopsies. These are usually done to confirm the clinical impression. The changes on muscle biopsy may vary from virtually normal to a very florid picture. In the typical case the muscle biopsy shows a diagnostic combination of inflammatory cell infiltrates in the endomysial connective tissue and accentuation around blood vessels, with arteritis. There may be frank vascular occlusion. Both degeneration and regeneration occur (Figure 2). There is also a very characteristic pattern of muscle fiber atrophy on cross-section with a perifascicular distribution. This tendency for the fiber atrophy to occur on the borders of fascicles is not seen in other disorders and, in some cases, may be the only abnormality in the muscle biopsy. Skin biopsy may show inflammatory infiltrates with capillary dilatation and areas of arteritis.
Other laboratory tests. These are mentioned only because they are usually normal. Complete blood count, other routine blood chemistries, and routine x-rays are not helpful in general. LE preparations, ANA tests, and rheumatoid factors are almost always negative.
Associated diseases. Childhood dermatomyositis, unlike the adult variety, is not associated with an increased inddence of malignancy. It is therefore not necessary to put these children through a workup in search of a carcinoma.
CLINICAL COURSE AND PROGNOSIS
Although the clinical presentation of dermatomyositis in children is characteristic, the course may be quite variable with regard to both severity of disease and duration of symptoms. The ultimate outcome does not seem to depend on age at onset, the patient's sex, or whether symptoms presented in an acute or insidious fashion; nor is there any correlation with the severity of weakness, except when respiratory or palatal dysfunction is present. Spontaneous exacerbations and remissions in the acute phase of the disease are not uncommon. This has made the comparison of various treatment regimens difficult and has hampered the clinician in prognosticating for his patient.
Series published before the widespread use of corticosteroids, and reviewed by Wedgewood and Cohen in 1953, suggested a significant mortality and morbidity. Death occurred in one-third of the patients, usually within the first two years of the acute illness. The two most common causes of death are (1) perforation of the bowel wall or gastrointestinal bleeding secondary to ulceration and (2) respiratory infection secondary to aspiration or respiratory insufficiency when palatal or respiratory muscles were involved. Significant morbidity was reported in an additional one-third of the patients in whom the disease remained active or, after remission of the acute phase, there were contractures and severe wasting and atrophy of muscles, leaving the patient functionally incapacitated. These statistics were supported by additional series reviewed by Bitnum et al. in 1964.
Figure 2. Cross-section of muscle biopsy of patient with childhood dermatomyositis. showing inflammatory lesion around a blood vessel and small fibers in the periphery of a muscle bundle (pe rifase icular atrophy).
Another late complication adding to the morbidity is the calcinosis described previously; although not unique to the childhood forms, this occurs with much greater frequency in children. It consists of ectopic deposition of calcium in soft tissue. In contrast to the 5 per cent incidence reported in adults, it has been reported in 30 to 60 per cent of treated or untreated cases in children. It typically occurs later, two to five years after the onset of symptoms.
Although it is believed to be secondary to inflammation of muscle, the origin of this phenomenon remains unknown. The subcutaneous deposits frequently cause ulceration of the skin, with chronic sinus formation and extrusion and drainage of calcified material. In addition to being cosmetically disfiguring, deposition of this material, when it occurs in tendons or periarticular tissues, can cause severe limitation of motion. Treatment with chelating agents has been of some help in management of this condition and will be discussed in a later section concerned with therapy. Initially, the presence of calcinosis was thought to be a good prognostic sign. However, as noted, it is unusual to see this before the second year and most reported deaths have occurred within this two-year period. Therefore, it would seem a better marker of the duration of the disease than a prognostic indicator. It is worth emphasizing that its occurrence late in the course of the illness in a patient without other signs of exacerbation does not suggest a disease relapse.
SIGNIFICANT CLINICAL COMPLICATIONS
In children with dermatomyositis, there does not appear to be any associated incidence of malignancy. Only two cases, believed to be atypical, have been reported with associated lymphoma or lymphosarcoma. This association has been reported to be as high as 20 per cent in the adult form.
A complete list of significant clinical complications of childhood dermatomyositis is given in Table 2.
THERAPY (TABLE 3)
Since the exact cause of this disorder remains undetermined, treatment must be aimed at supportive measures to decrease the mortality and morbidity of the disease. Initial reports in the 1950s and 1960s suggested improvement following the use of corticosteroids, but the dosage and duration of treatment varied. Currently a more vigorous approach, using initial high-dose therapy with prednisone, is being advocated by most authors for the acute phase of the illness. This represents a dosage of 40-60 mg. per day or 1.5-2 mg. per kilogram per day. This is continued for a minimum of six weeks or until there is clinical improvement both subjectively, with decrease in malaise, and objectively, with remission of fever, regression of rash and skin manifestations, and eventual improvement in strength.
Reduction of serum enzymes, such as creatine Phosphokinase, can be helpful indicators of the patient's progress but should not be relied upon solely. When a clinical remission is induced, reduction of the steroid dosage must be slow and tailored to correspond with the patient's course. Any exacerbation should be treated by resumption of steroids at a higher dose; usually, return to the dose level before recurrence of symptoms is sufficient. However, exacerbations requiring higher dosages to regain remission also occur.
Most investigators would agree that after tapering from the initial dose, which may take several months, a maintenance level of 5-15 mg. per day of prednisone or 0.25 mg. per kilogram per day is required to keep the patient asymptomatic. As the active phase of the disease may last two to three years, maintenance therapy is continued for that long to prevent relapses. More rapid tapering and earlier discontinuation of steroids may be possible in individual cases and have been advocated by some authors, but all stress the need for close clinical monitoring of the patient during the reduction of steroids and careful adjustment of the dosage to the patient's response.
With the use of this regimen, significant reduction in mortality and severity, as well as in duration of symptoms, has been reported in comparison with untreated or less vigorously treated patients. Emphasis must be placed on early diagnosis and initiation of treatment to further improve the patient's chances for good recovery and to prevent chronic changes in muscle. With this treatment program, a survival rate with complete recovery or only mild disability has been reported in as high as 60 to 90 per cent of cases. The use of steroids in patients in the late stages of the disease, with fixed contractures and evidence of muscle atrophy, may not be of benefit.
Although steroid therapy is beneficial, the risk inherent in chronic steroid administration must be thoroughly understood by the clinician and complications anticipated, whenever possible, to prevent iatrogenic disease. Virtually all patients will show changes associated with Cushing's syndrome, usually reversible on discontinuation of steroids. Electrolytes and blood sugar should be monitored serially as hypokalemia and hyperglycemia occur. Hypertension is not infrequently seen; it is usually dose related and may respond to reduction of steroids.
An increased incidence of gastrointestinal bleeding has been reported by some authors among children on steroids. Others have not seen this complication, however, and it must be noted that gastrointestinal bleeding secondary to ulceration and infarction of the bowel wall has been reported in as many as 25 per cent of cases, even before the advent of steroids. One must also be alerted to the possibility of infection either from common agents or from more opportunistic organisms. Tuberculin testing should be done before initiation of steroids. Other complications have included growth retardation and osteoporosis, with an increased incidence of compression fractures. Emotional disturbances - including increased lability, depression, and, less commonly, acute psychotic episodes - have been reported.
Alternate-day therapy has been advocated by some and is believed to decrease the incidence of these side effects. Although used in a variety of disorders requiring prolonged steroid therapy, this regimen has not been reported in significant numbers of patients with childhood dermatomyositis to allow comparison with the more commonly used dosage schedule.*
In addition to steroid therapy, emphasis should be placed on a vigorous program of physiotherapy. In the acute phase, if severe weakness is present, a passive range of motion of joints and, if necessary, splinting in a functional position to prevent contractures have been used. With clinical improvement, however, the patient should be encouraged to participate to the level of his ability in a more active program aimed at achieving functional independence and unassisted ambulation.
In patients in whom there is significant palatal or respiratory dysfunction, careful pulmonary toilet, including suctioning and postural drainage, is essential. In a small number of patients, tracheostomy and/or maintenance on a respirator to allow adequate ventilation may be required to tide the patient over the hyperacute phase of the illness.
There have been varying reports concerning the incidence of calcinosis following treatment with a high dosage of steroids. It is believed by some that early treatment with high-dose steroids has decreased the incidence of this disabling late complication of the disease. However, this is not universally accepted. Some authors have even suggested a higher incidence with prolonged steroid therapy. Treatment of calcinosis consists of chronic administration of chelating agents, such as ethanehydroxydiphosphate (10 mg./kg./day); however, results using these types of drugs are frequently poor. In some cases, surgical excision of nodules has been helpful.
In some patients in whom an initial remission cannot be established with steroids or subsequent exacerbation does not seem to be controlled by increased dosage, use of immunosupressive drugs has been tried. These have included 6-MP, azathioprine, methotrexate, and cyclophosphamide, alone or in combination with steroids. Limited clinical experience with these agents in childhood dermatomyositis has resulted in publication of varied results. In general, it would seem that their use should be reserved for cases failing to show an initial response to steroids or in which subsequent exacerbations appear to be resistant to high doses of corticosteroids.
With increased and prolonged survival - and thus longer follow-up - of patients with childhood dermatomyositis, recent reports have suggested late progression of the disease in some patients. Previously, it had been thought that if the patient survived the first two years after onset of symptoms, the active phase of the disease was essentially past. Miller reviewed a series of patients seen between 1958 and 1972 with a follow-up of more than five years. He found that, in addition to the previously reported late findings of chronic contractures and atrophy, some patients show acute exacerbation of symptoms; in some patients, biopsy material suggests continuation of acute inflammatory changes even without associated weakness. This supports the idea that the underlying disease process, although suppressed, may not "burn itself out" in the two-year period previously cited. The need for extended follow-up and close observation of all patients, even those appearing to show initially good response, is essential.
The disease remains one of the most challenging disorders facing the clinician.
Ansell. B. M.. Hamilton, E., and Bywaters, E. G. L. Course and prognosis in juvenile dermatomyositis. In Kakulas, B. A. (ed.). // International Congress on Muscle Disease. International Congress Series. No. 295, part II. Amsterdam: Excerpta Medica. 1973.
Banker, B. Q. Dermatomyositis of childhood. J. Neuropathol. Exp. Neurol. 34 (1975). 46.
Banker, B. Q.. and Victor, M. Dermatomyositis (systemic angiopathy) of childhood. Medicine 45 (1966), 261.
Bitnum, S., et af. Dermatomyositis. J. Pediatr. 64 (1964), 101.
Boyle, J. A., and Buchanan, W. W. Clinical Rheumatology. Philadelphia: J. B. Lippincott Company, 1971.
Carpenter, S.. et al. The childhood type of dermatomyositis. Neurology 26 (1976), 952
Cook. C. D-, Rosen. F. S.. and Banker. B. Q. Dermatomyositis and focal scleroderma. Pediatr. Clin. Nonti Am. 10 (1963), 979.
Dubowitz, V. Muscle disorders in childhood. Br. J. Hosp. Med. 2 (1969). 1627
Dubowitz, V. Treatment of dermatomyositis in childhood. Arch. Dis. Child. 51 (1976). 494.
Dubowitz. V.. and Brooke, M. Muscle Biopsy: A Modem Approach. Philadelphia: W. B. Saunders Company. 1973.
Everett, M. A., and Curtis, A. C. Dermatomyositis: A review of 19 cases in adolescents and children. Arch. Intern. Med. 100 (1957), 70.
Goel, K. M., and Shanks, R. A. Dermatomyositis in childhood: Review of eight cases. Arch. Dis. Child. 51 (1976), 501.
Haas. D. C. Treatment of polymyositis with immunosuppressive drugs. Neurology 23 (1973). 55.
Hanson, V., and Kornreich, H. Systemic rheumatic disorders ("collagen diseases'") in childhood: Lupus erythematosus, anaphylactoid purpura, dermatomyositis, and scleroderma. Bull. Rheum. Dis. 17 (1967). 441.
Hill, R. H.. and Wood. W. S. Juvenile dermatomyositis. Can. Med. Assoc. J. '103 (1970). 1152.
Miller, J.J. Late progression in dermatomyositis of childhood. J. Pediatr. 83 (1973), 543.
Rose, A. B. Childhood polymyositis. Am. J. Dis. Child. 127 (1974). 518.
Vignos. P. J.. Jr.. and Goldwyn. J. Evaluation of laboratory tests in diagnosis and management of polymyositis. Am. J. Med. Sci. 263 (1972), 291 .
Wedgwood. R. J. P., Cook. C. D., and Cohen, J. Dermatomyositis: Report of 26 cases in children with discussion of endocrine therapy in 13. Pediatrics 12 (1953). 447.
SIGNIFICANT CLINICAL COMPLICATIONS