Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from Postgraduate Medical Journal (August 1978) 54, 516-527.

Dermatomyositis: observations on the use of immunosuppressive therapy and review of literature Cairo-Glasgow Study Group AHMED EL- GHOBAREY GEZA BALINT M.R.C.P. M.D. (Budapest) KAREL DE CEULAER W. CARSON DICK M.D. (Leuven) M.D., M.R.C.P.

W. W. BUCHANAN M.D., F.R.C.P. TAHSIN HADIDI* T. A. HASSAN* F.R.C.P. M.R.C.P.

The Centre for Rheumatic Diseases, University Department ofMedicine, Royal Infirmary, Protected by copyright. Glasgow, Scotland, and *Maadi Armed Forces Hospital, and Azhar University, Cairo, Egypt

Summary The response to therapy and the subsequent Seven young adults, six of whom were male, all clinical course are briefly described as follows. suffering from dermatomyositis unassociated with Patient N.D. was treated with . The malignancy are described. These patients were not course of therapy, clinical response and changes in adequately controlled with high doses of corti- serum muscle are summarized in Fig. 1. costeroids but all responded when immunosuppressive Intravenous dexamethasone was discontinued at the therapy was also given. nineteenth week and by the end of the twenty-first week the dose of was reduced to 10 mg/ day.

Introduction http://pmj.bmj.com/ Dermatomyositis (as the name suggests) is a The patient was discharged at the end of the syndrome consisting of associ- twenty-fourth week. clinical One year later, the patient had a relapse, the ated with skin lesions (Pearson, 1966a; Currie and subsequent course and response to treatment are Walton, 1971). The disease is predominantly found summarized in Fig. 2. was discon- in females and is of unknown aetiology, although tinued after 14 weeks and the daily dose of predniso- disordered immunological mechanisms have been lone gradually reduced to 2 5 mg/day at the end of suggested (Dawkins and Mastalgia, 1973). A clear the seventeenth week. At this time the was

patient on September 28, 2021 by guest. association with malignancy has been documented clinically very much improved. in patients aged 40 years or more (Vanderploeg, Patient M.B. had a cervical sympathectomy for 1977; Curtis, Blaylock and Harrell, 1952; Bat- severe Raynaud's phenomenon of the hands but schwarov and Minkov, 1968). showed no improvement. One month after surgery, The effects of therapy in the characteristic skin and progressive general- a group of patients with dermatomyositis whose ized of dermatomyositis developed. disease had proved resistant to corticosteroids are The diagnosis was confirmed by laboratory tests as now described and the literature is reviewed. outlined in Table 2. The course of the disease and the response to treatment are illustrated in Fig. 3. Patients Two years later, the patient had muscle aches, The clinical and laboratory data on the seven tired easily and had a recurrence of facial dis- patients are summarized in Tables 1 and 2. coloration and fever. Muscle levels were 0032-5473/78/0800-0516 $02.00 © 1978 The Fellowship of Postgraduate Medicine Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from Dermatomyositis: use of immunosuppre-ssive therapy 517

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I 0- 0, l0:;I-4 Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from 518 Ahmed El-Ghobarey et al. TABLE 2. Laboratory data for seven patients with dermatomyositis Muscle Muscle enzymes ESR Pulmonary Electro- Skin Creatine Lactate Aspartate (mm/ function Patient Biopsy myography biopsy kinase dehydrogenase transaminase WBC first test (jm/ml) (gm/ml) (pm/ml) (cells/i) hour) N.D. Positive Positive Positive 182 255 67-2 114 x 1021 30 M.B. Positive Positive Positive 390 380 96 12-6 56 A.M.H. Positive Positive Not done 1 15-7 255 18-3 12-0 37 M.N.S. Positive Positive ,, , 120 240 19-2 5-3 20 E.H. Positive Positive , 9, 2000 420 76-8 12-4 64 M.A.I. Positive Positive 97 5 120 48-0 11-6 22 M.M. Pos:tive Positive 655 72 5 75 10-2 24 Restrictive defect

Pulse/minm 5C

250k Protected by copyright. 200 Serum muscle enzymes (j.m/ml) ..0*

50

Muscle power 6-

Dexamethosone 40- (mg 20v0 150 http://pmj.bmj.com/ Prednisolone 100 (mg) 50

0 2 4 6 8 10 12 14 16 18 20 22 24 Weeks FIG. 1. (Patient N.D.) Changes in the muscle power, on September 28, 2021 by guest. pulse rate and serum muscle enzymes during the first course of treatment with oral prednisolone and intra- venous dexamethasone. ----; - ; SGOT -. normal. Prednisolone was increased to 60 mg/day. returned to normal in three weeks and the tem- The patient developed back pain and an X-ray perature settled after 5 weeks. Despite high doses of showed collapsed lumbar vertebrae. Prednisolone prednisolone over a period of eight weeks, muscle was stopped and in daily doses of power showed only slight improvement. Because of 100 mg produced symptomatic relief. this, intravenous injections of 50 mg methotrexate Patient A.M.H. was begun on daily oral doses of were given every 5 days for 12 weeks and subsequent 60 mg prednisolone. Serum muscle enzyme had improvement of muscle power enabled the patient Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from Dermatomyositis: use of immunosuppressive therapy 519

150 Pulse/mi 00 50_ 0 275 250 225 - 200 Serum muscle 175 enzymes (,mr/ml) 150 - 125 100 _ 75 - 50 25

Muscle power 4

Methotrexate 40 (mg v) 208

Prednisolone 100

(mg) 50' Protected by copyright.

0 2 4 6 8 10 12 14 16 18 20 22 Weeks FIG. 2. (Patient N.D.) Changes in the muscle power, pulse rate and serum muscle enzymes during the second course of treatment with intravenous methotrexate, after relapse. Creatine kinase ---- ; Lactate dehydrogenase SGOT aspartate transaminase .....

100__ Pulse/min 50

400 http://pmj.bmj.com/ 300 Serum muscle enzymes (Mm/ml) 200 \" 200 100 , \

50 -... C on September 28, 2021 by guest. Muscle power 4 (grade) 2 -, 7 77 Methotrexote 40 (mg i.v.) 20 75 Prednisolone 50 (mg) 25

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Weeks FIG. 3. (Patient M.B.) Changes in the muscle power, pulse rate and serum muscle enzymes during the course of treatment with prednisolone and intravenous methotrexate. Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from 520 Ahmed El-Ghobarey et al. cardiomegaly and early heart failure in addition to other features of dermatomyositis. After 8 weeks, there was no significant improvement with 80 mg prednisolone, and cyclophosphamide 400 mg/day was begun. Four weeks later, muscle power had improved and had disappeared. The heart size had returned to normal and there were no signs of heart failure. Four months later the patient's condition relapsed. At that time, the patient was receiving 10 mg of prednisolone and 100 mg cyclophosphamide/day. Increasing the dose of the latter to 300 mg/day brought about an immediate improvement. Two years after admission the patient's condition was satisfactory and he continued to take 10 mg pred- nisolone alone. Patient M.A.I. was initially thought to have myasthenia gravis until he developed skin lesions typical of dermatomyositis. Laboratory tests con- firmed the diagnosis (Table 2). When the patient failed to respond to 80 mg prednisolone daily after 10 weeks, intravenous injection of methotrexate was begun, beginning with Protected by copyright.

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FIG. 4. Extensive skin ulceration due to intravenous methotrexate. to walk. During this time, the patient also received prednisolone which was continued, after metho- trexate was stopped, in a maintenance dose of 10 mg/day. http://pmj.bmj.com/ Patient M.N.S. started oral therapy in a daily dose of 80 mg prednisolone. Since there was only slight improvement in the patient's clinical condition, methotrexate was begun after 2 months in gradually increasing doses of 5 to 50 mg/week by intravenous injection. Five weeks after beginning

methotrexate, the patient developed necrotic skin on September 28, 2021 by guest. ulceration (Fig. 4) which healed when methotrexate was discontinued over a period of 3 weeks, by which time the muscle power had improved considerably. For maintenance immunosuppressive therapy, cyclo- phosphamide 100 mg orally/day was substituted for intravenous methotrexate which had caused recur- rence of the skin ulceration when it was given again to the patient after the ulcers had healed. One year after admission, the patient was well and continued to take 7-5 mg prednisolone in addition to cyclophosphamide therapy. FIG. 5. Extensive soft tissue calcification in a female Patient E.H. had a severe myocarditis with with dermatomyositis. Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from Dermatomyositis: use of immunosuppressivc therapy 521 a dose of 5 mg and increasing the weekly dose 1953), and tuberculosis was thought to be another gradually to a maximum of 50 mg. Six weeks later, causative factor (Grunke, 1926); associated malig- the patient showed marked improvement, and he nancy was suggested by Sterz (1916) and Kankeleit was discharged from hospital on 15 mg prednisolo- (1916) and was present in 12-9% of cases reviewed by lone/day. The patient has remained well on this dose Shuermann (1951). for 3 years. Patient M.M., female, aged 26 years, had been Aetiology and pathogenesis treated with 20 mg prednisolone for 12 months Evidence is accumulating that cell-mediated im- without effect. On admission to hospital the patient munity plays a central part in the pathogenesis of was confined to bed and had severe bed sores. polymyositis (Haas and Arnason, 1974; Esiri, X-rays of her limbs showed extensive calcification of MacLennan and Hazelman, 1973; Johnson, Fink soft tissues (Fig. 5). Laboratory tests confirmed the and Ziff, 1972). Dawkins and Mastalgia (1973) diagnosis of dermatomyositis (Table 2). suggested that the cellular immune response was Prednisolone was begun in a daily dose of 60 mg specifically directed at muscle cells. There is also and increased by 20 mg after 2 weeks and 1 month. evidence that humoral immune response has an Muscle power improved only slightly from grade 2/5 important role in the pathogenesis of dermatomyo- to 3/5 (British Medical Research Council, 1943). sitis (Wolf, Adelstein and Sharp, 1977; Nishikai Intravenous methotrexate was begun in a weekly and Homma, 1977; Rechlin and Mattioli, 1974). dose of 5 mg gradually increasing to 50 mg/week. Whitaker and Engel (1972) found IgG, IgM and C3 The dose of prednisolone was reduced to 15 mg/day deposition in the vessel walls of all nine patients with and after 6 weeks the patient was able to climb childhood dermatomyositis; Lisk and Zweman stairs. The patient has remained well for 2 years. (1976) reported increased circulating IgG levels in

patients with dermatomyositis. Patients with der- Protected by copyright. Comment matomyositis and agammaglobulinaemia have been The seven patients described all failed to respond described (Gottof, Smith and Sugar, 1972; Guilliano, adequately to high doses of corticosteroids over a 1974). Virus involvement has also been claimed as an period of 2 months. Most authorities consider that aetiological factor (Hashimoto et al., 1971; Sato et high doses of corticosteroid are effective in the al., 1971; Chou and Gutman, 1970; Chou, 1968). majority of patients with dermatomyositis and Kagen, Limball and Christian (1974) noted sero- especially so when the disease is acute (Winkle- logical evidence of toxoplasmosis among patients mann et al., 1968). However, there are a small with polymyositis. Familial incidence of poly- number of patients who do not respond to such -dermatomyositis, has also been described therapy and who improve when immunosuppressive (Lewkonia and Buxton, 1973; Christianson, Brun- drugs are added to a corticosteroid regimen (Currie sting and Perry, 1956). Polymyositis was recently and Walton, 1971). The patients described above reported following penicillamine therapy (Fernan- would appear to fall into this category, but there is dez, Swinson and Hamilton, 1977) and a case of

no definite proof that the immunosuppressive drugs hereditary complement C2 deficiency and dermato- http://pmj.bmj.com/ were responsible. It is very easy to fall into the myositis was reported by Leddy et al. (1975). post hoc (ergo) propter hoc fallacy, and it cannot be excluded that the patients might have improved Incidence anyway. However, the authors are reasonably con- Pearson (1966a) described a female to male pre- fident that if high doses of corticosteroid drugs do dominance of 2:1, but a male to female predomi- not improve the patient's condition after 6-8 weeks nance of 3:1 if malignancy was associated. The of treatment, immunosuppressive drugs should be disease was commoner in adults than in children, added. In view of the many possible side effects with a peak incidence at the fifth to sixth decade. on September 28, 2021 by guest. including late effects such as neoplasm (Burnet, Pearson saw one patient with polymyositis per 1967; Editorial, 1972), they believe that immuno- million of the population annually. Age-adjusted suppressive drugs should only be used after an incidence rate for hospital-diagnosed polymyositis adequate trial of corticosteroid therapy. was 5 cases/106 of the population annually over a 22-year period. Incidence was highest in Negro Historical review females according to Medsger, Robinson and Masi Dermatomyositis was originally described by (1971), and Barnes and Mawr (1976) emphasized the Wagner (1887) and by Unvericht (1887). Later, it female predominance in dermatomyositis. Poly- was thought to be associated with metabolic defects myositis-dermatomyositis accounted for 22.6%/ in a of infection, endocrine dysfunction and allergy group of 186 patients with muscle disease (Fessel, (Pick, 1935; Turner, 1937; O'Leary and Waisman, 1973). The group with definite dermatomyositis 1940; Holmes, 1948; Wedgwood, Cook and Cohen, described in this article and which has a predomi- Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from 522 5Ahmed El-Ghobarey et al. nance of male over female ratio, does not conform to burg, Nielson and Yurchok, 1971) have been the previously described bi-modal distribution of reported. It has been recorded that ophthalmoplegia female dominance with a peak incidence in the third and retinopathy can occur with dermatomyositis to fourth decade. (Susac, Garcia-Mullen and Glaser, 1973; Harrison, Frenkel and Grossman, 1973; Fruman et al., 1976). Clinical features of the distal nail fold associated with Muscular weakness and characteristic skin rash telangiectasis (Fitzpatrick, Arndt and Clark, 1971). are the classical features. The muscle weakness, pre- Bluish-red plaques around the base of the nails and dominantly proximal and symmetrical with pain and diffuse redness and shininess of the nail folds (Rook, tenderness, progresses during weeks or months. Wilkinson and Ebling, 1968) and peri-ungual Constitutional symptoms may be severe, leading to erythema and linear telangiectasis on the cuticle and death in a few days or weeks (Pearson, 1966b). The the base of the nails (Braverman, 1970) are seen in rash includes lilac discoloration of the upper eyelids, almost all cases. The nail fold changes are related to and peri-orbital oedema; Gottron's sign consists of the serum enzymes in some patients (Samitz, 1974). scale erythema and dusky red patches or linear The association of amyloidosis with dermatomyositis streaks over the knuckles, elbows, medial maleoli, has been reported (Zilko and Dawkins, 1975). neck, face, forehead and upper chest and back, with dermal atrophy (Bohan and Peter, 1975). The rash Classification may appear initially with the muscle disease develop- Group I: Primary idiopathic polymyositis. ing later (Krain, 1975). Dysphagia, with the food remaining at the upper part of the oesophagus Group II: Primary idiopathic dermatomyositis. occurs; there may also be aperistalsis of the whole Group III: Dermatomyositis (or polymyositis) oesophagus. Arthralgia is common. Raynaud's associated with

malignancy. Protected by copyright. phenomenon is present in 30%. (Pearson, 1966a) or less (Winkleman et al., 1968). De Vere and Bradley Group IV: Childhood dermatomyositis (or poly- (1975) noted that dysphagia occurs in 28%, arthral- myositis) associated with . gia in 32% and Raynaud's phenomenon in 55%/ of Group V: Polymyositis or dermatomyositis with cases of polymyositis. The commonest symptoms in associated collagen vascular disease. children are muscular weakness, stiffness, fatiga- bility and characteristic skin rash (Hansen and Diagnostical criteria Farnreich, 1967). Development of in sub- Although there are no generally accepted criteria cutaneous tissue or muscle may indicate a favourable for the diagnosis of dermatomyositis, five criteria prognosis in the childhood type. Calcification is could be used (Bohan and Peter, 1975): more common after a severe episode of acute myositis and in childhood 1. The symmetrical weakness of limb girdle muscles dermatomyositis (Pearson, and anterior neck flexors progressing over weeks or 1971); it developed in 50% of both treated and months with or without dysphagia or respiratory

untreated children with polymyositis and dermato- http://pmj.bmj.com/ myositis in the Rose (1974) series. Calcification muscle involvement. occurs with normal levels of inorganic ions of 2. Characteristic . calcium and phosphorus in the extracellular fluids 3. Raised serum sarcoplasmic enzymes. owing to alteration of the tissues or loss of local 4. . inhibition of calcification such as tissue protein- polysaccharides or inorganic pyrophosphate in the 5. Characteristic skin lesion. extracellular fluids (Mills, 1971). Respiratory muscle When the rash is present with three or four criteria weakness may occur and lesser skeletal muscles may the diagnosis is definite, rash with two criteria makes on September 28, 2021 by guest. also become involved including cricopharyngeal, the diagnosis a probable one, and a possibility if the facial, extra-ocular and distal limb muscles rash accompanies one criterion. The degrees of (Porubsky, Murry and Pratt, 1973; Bates, Stevens muscle weakness are classified into six stages (British and Hudgson, 1973; Saunders, Huntley and Sharp, Medical Research Council, 1943): 1973; Sanger and Kirby, 1973). Interstitial pneu- 0 - no contraction, 1 - flickering or trace of contrac- monia (Degos, Civatte and Belaich, 1971), pulmon- tion, 2 - active movement with gravity eliminated, ary fibrosis, asymptomatic or accompanied by acute 3 - active movement against gravity, 4 - active move- febrile pneumonia (Frazier and Miller, 1974; ment against gravity and resistance, 5- normal Schwarz et al., 1976). Pulmonary involvement could power. be fatal (Park and Nyhan, 1975). Myocardial Laboratory findings for the diagnosis of dermato- involvement with cardiac failure (Babka and Pepine, myositis are summarized in Table 3. The differential 1973) or with and heart block (Schaum- diagnosis of dermatomyositis is shown in Table 4. Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from Dermatomyositis: use of immunosuppressive therapy 523

TABLE 3. Abnormal laboratory tests, with their clinical significance in patients with dermatomyositis

Investigation Findings Comment

Serum muscle Raised sarcoplasmic enzymes in the serum of the following: These enzymes could be found enzymes increased also in: - Creatine phosphokinase (the most reliable (Vigos, 1972)) - Motor neurone disease - Aldolase. - Muscle dystrophies - Lactate dehydrogenase. - Endocrine - Transaminases (aspartate, alanine). - Toxins - Infection - They may be normal in severe muscle atrophy

Electromyography Trial of: - Polyphasic short small motor unit potentials. Protected by copyright. - Fibrillation potential. - Bizarre high frequency repetitive discharges (Marinacci, 1965; Lambert et al., 1954)

Muscle biopsy Muscle neurosis, phagocytosis, large vesicular nuclei and - True necrotizing vasculitis prominent nucleoli. may be seen in childhood Type I and II muscle fibre atrophy, especially perivascular form (Thomson, 1968). with internal migration of nuclei. Massive muscle necrosis and Fibre size variation and vacuolization. absence of if Mononuclear inflammatory cell infiltration. there is accompanying malig- Perifascicular atrophy. nancy (Urich and Wilkinson,

- Capillary damage and undulating tubules in muscle, 1970). capillary endothelium in all childhood forms but only in http://pmj.bmj.com/ some patients with adult type dermatomyositis (Carpenter et al., 1976).

Skin biopsy Poikiloderma (epidermal liquefaction of basal cell layer These changes tend to confirm the and vascular dilatation (Janis and Winkelman, 1968). diagnosis in the presence of a com- Changes in the involved skin resemble those observed in patible clinical history.

systemic erythematosus. on September 28, 2021 by guest. Mucin deposits in the form of acid mucopolysaccharides (Alcian blue reaction), in the involved and non-involved skin.

Capillaroscopy Dilated irregular tortuous vessels in the nail folds and cuticular thickening and hyperkeratosis with or without erythema (Samitz, 1974).

99mTc phosphate For evaluation of extent and severity of calcinosis (Sarmiento et al., 1975). Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from 524 Ahmed El-Ghobarev et al. TABLE 4. of a patient with dermato- The association between malignancy and dermato- myositis myositis has been overestimated. Bohan and Peter Lesion Muscle disease (1975) thought that the diagnosis of the one facili- tates the diagnosis of the other, increasing the double Dystrophies - Pseudohypertrophic (Duchenne) diagnosis and discrepancy between in-patients and - Limb girdle (Erbe) the general population. Not one of the present seven Granulomatous - Sarcoidosis cases had associated malignancy. Endocrine - Thyrotoxicosis - Myxoedema Treatment - Hyperparathyroid To date (1977), there is - Cushing's disease no report of a controlled - Diabetes mellitus study carried out in the treatment of dermatomyos- itis particularly in acute life-threatening cases Metabolic - Periodic paralysis (Pearson, 1963) and no differentiation made in the treatment of dermatomyositis and Glycogenosis - McArdle's syndrome (type V) polymyositis. Most investigators feel that corticosteroids are End-plate lesion - Myasthenia gravis highly effective (Maulder et al., 1963) other than those due to unresectable carcinoma (Pearson, 1969; Infection - Influenza Winkelman et al., 1968). The treatment of - Rubella under- - Trichinelliasis lying malignancy is claimed to improve the myo- Trypanosomiasis pathy (Arnudell et al., 1960; Copeman and Alexan- - Schistosomiasis der, 1967). In 1940, O'Leary and Waisman reported a Vaccination - Rubella vaccination 50% Protected by copyright. mortality rate in untreated cases. Rose and Walton Neurone lesion - Motor neurone disease (1966) reported only a 14% mortality rate where - Progressive muscle atrophy of infancy steroids were used; whereas Winkelman et (Werdnig-Hoffman) and early adult al., spinal muscle atrophy (Kukelberg (1968), reviewing the records of 289 patients, found Wellander) equal remission and mortality rate in both steroid- treated and untreated groups. This discrepancy Drugs - Corticosteroids could be due to lack of definite criteria in the treated - Penicillamine cases. It is claimed that steroids are effective in - Clofibrate - Alcohol childhood dermatomyositis (Sullivan et al., 1972). Serious side effects from steroids in polymyositis khab%omyolysis - Strenuous exercise are claimed to be few (Pearson, 1963b). - Heat stroke Age, sex and race as well as duration of disease - Crus injury - Malignant hyperpyrexia did not correlate with steroid resistance (Arnett et - Poisoning by certain sea snakes al., 1973) which was defined by Metzger et al. (1974), http://pmj.bmj.com/ as lack of clinical response after a 2-3 months' daily Unknown - dose of 40-80 mg prednisolone. To date, various immunosuppressive drugs have been used in the treatment of dermatomyositis, in- cluding thioguanine, 6-mercaptopurine, azathio- Malignancy and dermatomyositis prine and oral methotrexate (Demis, Brown and Cases of dermatomyositis complicated by malig- Crosby, 1964; Schirren, 1966; McFarlin and Griggs, nancy tend to be reported more often than un- 1968; Haas, 1973; Benson and Aldo, 1973). Bailin on September 28, 2021 by guest. complicated ones. Malignancy has been reported as et al. (1975) and Hurd (1973) claimed that metho- occurring in 15-52% of all cases (Rose and Walton, trexate is a potent cytotoxic and immunosuppressive 1966; Barwick and Walton, 1963; Arnudell, Wilkin- drug; Hersh, Wong and Freireich (1966) have son and Haserick, 1960) and as much as 71 % in men emphasized its anti-inflammatory action. Malaviya, over the age of 50 years (Shy, 1962). Myositis and Many and Schwartz (1968) successfully treated four malignancy follow within a year of each other; the patients resistant to prednisolone with intravenous most common malignancy being a tumour of the methotrexate. By intermittent intravenous regimen, ovary and stomach; the least common is that of the high portal concentration of methotrexate and hepa- colon or rectum. Dermatomyositis patients with totoxicity are minimized (Metzger et al., 1974a; malignancy tend to be older than those with der- Decker, 1973). Seven patients did not respond to matomyositis alone, and younger than those with , cyclophosphamide and to thoracic cancer alone (Barnes and Mawr, 1976). duct drainage, subsequently four of them responded Postgrad Med J: first published as 10.1136/pgmj.54.634.516 on 1 August 1978. Downloaded from Dermatomyositis: use of immunosuppressive therapy 525 favourably to methotrexate (Metzger et al., 1974a). References Methotrexate and azathioprine were recently re- ARNETT, F.C., WHELTON, J.C., ZIZIE, T.M. & STEVEN, M.B. ported as being effective in acute childhood dermato- (1973) Methotrexate therapy in polymyositis. Annals of myositis (Jacobs, 1977). Prolonged treatment with Rheumatic Diseases, 32, 536. immunosuppressive drugs may lead to malignancy ARNUDELL, F.D., WILKINSON, R.D. & HASERICK, J.R. (1960) (Walpolf, 1958; Burnet, 1967). Fifty cases of metho- Dermatomyositis and malignant neoplasms in adults. trexate lung disease, including three deaths, have Archives of Dermnatology, 82, 772. BABKA, J.C. & PEPINE, C.J. (1973) Hyperkinetic cardio- been reported (Filip et al., 1971; Goldman and vascular state in polymyositis. Chest, 64, 243. Marchella, 1971). Testicular and ovarian dysfuLnc- BAILIN, P.L., TINDALL, J.P., RAENIGK, H.H., MICHAEL, D. & tion, fetal abnormalities and haemorrhagic cystitis HOGAN, D. (1975) Is methotrexate therapy for psoriasis are caused by cyclophosphamide therapy (Warne, carcinogenic? A modified retrospective analysis. Journal of Fairly and Hobbs, 1973). Folic acid antagonists are the American Medical Association, 232, 359. BARNES, B.E. & MAWR, B. (1976) Dermatomyositis and abortifacient (Thiersch, 1952). There is still a malignancy. A review of the literature. Annals of Internal possibility of liver cirrhosis and fibrosis developing Medicine, 84, 68. in patients on an intermittent schedule of metho- BARWICK, D.D. & WALTON, J.N.C. (1963) Polymyositis. trexate therapy (Schein and Winokur, 1975). How- American Journal of Medicine, 35, 646. ever, promising preliminary results with antilympho- BATES, D., STEVENS, J.C. & HUDGSON, P. (1973) Polymyositis have been reported (Denman with involvement of facial and distal musculature. Journal cyte globulin recently of Neurological Science, 19, 105. - et al., 1976). BATSCHWAROV, B. & MINKOV, D.C. (1968) Dermatomyositis and carcinoma. British Journal of Dermatology, 80, 84. BENSON, M.D. & ALDO, M. (1973) Azathioprine therapy in polymyositis. Archives of Internal Medicine, 132, 547. Prognosis BOHAN, A. & PETER, J.B. (1975) Polymyositis and dermato- myositis. New England Journal of Medicine, 13, 344. Protected by copyright. Although mortality and morbidity rates were BRAVERMAN, I.M. (1970) Skin Signs of Systemic Disease, p. reduced among patients in the acute stages of child- 169. W. B. Saunders Co., Philadelphia. hood dermatomyositis receiving high doses of BRITISH MEDICAL RESEARCH COUNCIL (1943) Aid to the adrenocorticosteroids, late progression appeared to Investigation of Peripheral Nerve Injuries, 2nd edn, p. 1. be independent of initial therapy (Miller, 1973). H.M. Stationery Office, London. BURNET, F.M. (1967) Immunological aspects of malignant However, there is evidence that over-treatment with disease. Lancet, i, 1171. corticosteroids may be a factor in the chronicity of CARPENTER, S., KARPATI, G., ROTHMAN, S. & WATTERS, G. the disease with failure of adequate long-term (1976) The childhood type of dermatomyositis. , response in children (Dubowitz, 1976). With modern 26, 952. management the mortality rate in childhood der- CHOU, S.M. (1968) Myxovirus-like structures and accom- panying nuclear changes in chronic polymyositis. Archives matomyositis has been reduced from 30%/ to a of Path.logy, 86, 649. maximum of 1O% (Jacobs, 1977). Rose (1974) found CHOU, S.M. & GUTMAN, L. (1970) Picorna-like crystals in that in childhood dermatomyositis the patients who subacute polymyositis. Neurology, 20, 205. were treated with corticosteroids within one to six CHRISTIANSON, M.B., BRUNSTING, L.A. & PERRY, H.O. months after the onset of their disease had a short (1956) Dermatomyositis. Unusual features, complications http://pmj.bmj.com/ and treatment. American Medical Association Archives of period of severe disability and that the patients who Dermatology, 74, 581. were not treated had a longer period of severe dis- COPEMAN, P.W.M. & ALEXANDER, S. (1967) Dermatomyositis ability but made a good recovery eventually. Steiner adenocarcinoma of male breast, detection of antibodies to et al. (1974) reported regression of calcinosis follow- the neoplasm in the serum. 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