- Email: [email protected]
Treatment of dermatomyositis with methotrexate
Treatment of dermatomyositis with methotrexate Mary E. Zieglschmid-Adams,MD,a Amit G. Pandya,MD: Stanley B. Cohen,MD,b and Richard D. Sontheimer,MDa>c Dallas, Texas Background: No published data exist on the incidence of liver fibrosis in patients with dermatomyositis treated with methotrexate. O@&C Our purpose was to examine the efficacy, steroid-sparing potential, and side effects of methotrexate in patients with dermatomyositis and to report liver biopsy results in four patients. Methods: A retrospective review of all casesof dermatomyositis treated with methotrexate in a dermatology and rheumatology referral practice was conducted. Results: Of the 10 cases reviewed, seven were of dermatomyositis whereas three were of amyopathic dermatomyositis (ADM). Nine patients received oral methotrexate. One patient received intravenous methotrexate. Improvement of cutaneous disease occurred in seven (100%) of the patients with dermatomyositis and in two (66%) of those with ADM; myositis improved in four (57%) of the patients with dermatomyositis. The initial prednisone dose was halved after an average of 18 weeks of methotrexate therapy in the patients with dermatomyositis and 13 weeks in thepatients with ADM. Methotrexate-related side effects occurred in six (86%) of the patients with dermatomyositis and in one (33%) of the patients with ADM. Of the four patients who had liver biopsies, two (50%) showed mild hepatic fibrosis, resulting in discontinuation of the drug. Both patients in whom fibrosis developed had preexisting ste roid-induced diabetes mellitus. Conchsion.- Although methotrexate is an effective treatment for dermatomyositis, side effects are common. Patients with diabetes mellitus should be closely monitored for toxic effects on the liver. (J AM ACAD DERMATOLl995;32:754-7.)
In dermatomyositis,high-doseoral corticosteroidsis consideredthe mainstay of treatment.However,somepatientsareunableto toleratethis treatment or haveprogressionof diseasedespitetherapy. In thesepatients azathioprine,lchlorambuciJ2cyclosporine,3and methotrexatemay be used either aloneor in combinationwith steroids.Intravenous y-globulin has also recentlybeen used.4V6 We describe 10 patientswith dermatomyositisor amyopathic dermatomyositis(ADM) treatedwith methotrexateand examinethe efficacy,steroid-sparing potential,and sideeffectsof this drug. Liver biopsy was performedin four patients.This is the first reportedseriesto includetheseresultsin patientswith dermatomyositistreatedwith methotrexate. From the Departments of Dermatologya and Internal Medicine) University of Texas Southwestern Medical Center, and Rheumatology Division, St. Paul Medical Center? Reprint requests: R. D. Sontheimer, MD, Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9069. Copyright 0190-9622/95
754
&? 1995 by the American $3.00 + 0
16/l/62417
Academy
of Dermatology,
Inc.
PATIENTS
AND METHODS
All 10 patients with dermatomyositis treated with methotrexate from 1975 to 1993 in a university-based private dermatology practice and a community-based private rheumatology practice in Dallas, Tex., were included. Seven patients had a diagnosis of classic dermatomyositis on the basis of typical clinical and histopathologic skin findings and evidence of myositis by physical examination, electromyography, enzyme determination, and/or muscle biopsy.7 Three patients had ADM. The criteria for diagnosis included typical cutaneous manifestations of dermatomyositis persisting for 2 years without clinical evidence of myositis by examination of muscle strength or by measurement of creatine kinase and aldolase.s One of the three patients without myositis met the criteria for confirmed ADM. Two patients who had typical skin findings for less than 2 years without evidence of muscle diseasehad the provisional diagnosis of ADM? None of our patients had malignancy-associated dermatomyositis, All patients had active skin disease at the time of initiation of treatment with methotrexate. Liver biopsy specimens were graded by the method of Roenigk et allo Grade I represents normal to mild fatty changes and mild portal inflammation; grade II includes more severe fatty infiltration and portal tract expansion,
Journal of the American Academy of Dermatology Volume 32, Number 5, Part 1
inflammation, and necrosis; grade IIIA represents mild portal fibrosis; grade IIIB includesmoderate to severefibrosis; and grade IV represents cirrhosis with regenerating nodulesand bridgingof portaltracts.No pretreat-
mentliverbiopsyspecimens wereobtainedfrom ourpatients. RESULTS
Age, sex, race, and presence of muscle disease
Patientsrangedin agefrom 27 to 79 yearsat the time of diagnosis.Only oneof the 10patientswas a man. Six were white, two were Hispanic, and two were black. Sevenpatients (70%) had evidenceof activemyositis. Methotrexate
dose
All patientsweretreatedwith oral methotrexate weekly exceptfor one patient with classicdermatomyositis, who receivedintravenousmethotrexate weekly.The averageinitial dosageof methotrexate was 7.5 mg/wk for the patientswith dermatomyositisand 9.2mg/wk for the patientswith ADM. The averagemaximal weekly methotrexate dose was 14.2mg for the patientswith dermatomyositisand 20 mg for the patientswith ADM. The total cumulativedoseof methotrexatein the patientswith dermatomyositisrangedfrom 52.5to 3042.5mgin 7 to 274weeks(mean,1097mg in 98.3 weeks).In the patientswith ADM the total cumulative methotrexatedoserangedfrom 132.5to 1050 mg in 15to 9 1weeks(mean,6 17.5mg in 50 weeks). All patientswith dermatomyositisand two of the threepatientswith ADM had improvementin their skin diseaseduring methotrexatetherapy.Most patients receivedoral corticosteroidsconcomitantly, but other systemic medications such as hydroxychloroquinewere not used,Sunscreensand topical corticosteroidswere used by most patients before and during methotrexatetherapy. Fifty-sevenpercent(4/7) of the patientswith dermatomyositishad improvementof their myositis during methotrexate treatment. Prednisone
dose
All the patientswith dermatomyositistook prednisonebeforetreatmentwith methotrexate.The averageduration of steroidtherapybeforemethotrexate was 11.3 months, which excludedone patient whohad takenprednisonefor 16years.The average steroiddosageat initiation of methotrexatewas32.5 w/hJ.
Zieglschmid-Adams
et al.
75
Of the patients with ADM, 33% receivedprednisone before methotrexatetherapy. One patient was nevertreatedwith corticosteroids,whereasanother patient beganprednisoneconcurrently with methotrexate.The averageprednisonedosageat initiation of methotrexatewas 60 mg/day. The initial prednisonedosewashalvedin the patients with dermatomyositisafter 4 to 41 weeks (mean, 18 weeks).In the patientswith ADM who took prednisonefor more than 13 weeks(2/3), the initial prednisonedosewashalvedafter an average of 13 weeks. Adverse reactions
Eighty-six percent(6/7) of the patientswith dermatomyositis and 33% (l/3) of thosewith ADM had someform of adversereaction.Stomatitis was reportedin threepatients;gastrointestinaldistressin two; abnormal liver biopsy specimensin two; and lung disease,leukopenia,and alopeciain onepatient each.Some patientshad more than oneadversereaction.Fifty-sevenpercent(4/7) of thepatientswith dermatomyositisand 33%( I /3) of thosewith ADM stoppedmethotrexatebecauseof the severityof the sideeffects. Liver biopsy results
Forty percent(4/10) of the patientshad undergone liver biopsies.Two patients had grade IIIA changesof mild hepatic fibrosis and subsequently had methotrexatediscontinued.One of thesepatients had dermatomyositis, and the other had ADM. Cumulativemethotrexatedoseat thetime of biopsywas385mg for the patient with dermatomyositisand 1050mg for the patientwith ADM. Their weekly doseat the time of biopsy was 12.5and 15 mg/wk, respectively.Both patients had diabetes mellitus from prolongedsteroiduse,and the patient with ADM was also obese. The patient with dermatomyositishad persistentlyelevatedAST levelsanda normal serumalbumin levelbeforebiopsy. The patient with ADM had intermittently elevated AST values before and during the first year of methotrexatetreatment. DISCUSSION
Methotrexatehas beenusedsince 1968to treat steroid-refractorydermatomyositisand polymyositis. A reviewof the literature yieldedreportsof 57 adultswith dermatomyositisor polymyositistreated with methotrexate.11-23 Seventy-fivepercent (43/
Journal
of the American
756 Zieglschmid-Adams et al. 57) had improvementin their disease.Twenty-five percent(3/ 12) of the nonresponders improvedwith a combinationof steroids,methotrexate,and chlorambucil. Of the nonresponders, onereceivedonly onedoseof methotrexate. Adversereactionswere seenin 54% (31/57) of previously reported patients. Stomatitis was the most frequentreactionand occurredin 25% of patients (14/57). Leukopeniaoccurredin 7% of patients (4/57). The three reportedpulmonary complicationsincludeda deathfrom methotrexatepneumonitis, transient bilateral pulmonary infiltrates, and a worseningdiffusioncapacity of carbonmonoxideon pulmonaryfunction tests.Onepatient had diffuse hepatomegalyand an elevatedserum alkaline phosphatase level,andanotherhad a transiently elevatedserumalkaline phosphataselevel.No liver biopsieswere reported in any of the 57 patients treated with methotrexate.In one patient with a history of uterine adenocarcinomaanddermatomyositis a breast adenocarcinomadeveloped2 years after methotrexatetherapy. The largestsingleseriesof patientswith dermatomyositisand polymyositistreatedwith methotrexatewasreportedby Metzger et al.15in 1974.Twenty-two patientswere given intravenousmethotrexate. Seventy-sevenpercent had improvement of muscle strength and/or skin disease.Muscle enzymesnormalizedaftera meanof 10weeks,whereas muscle strength improvement was noted at 13 weeks.In patients with dermatomyositisthe skin diseasebeganto improve as muscle enzymesnormalized.A steroid-sparingeffectwasseen.Half the patientshad minor reversibletoxic effects. In our seriesof patients,all but oneof whom receivedweeklyoral methotrexate,90%had improvement of their skin diseaseand 57Y0(4/7) of the patients with dermatomyositisalsohad improvement in their muscledisease.Only onepatientwith ADM stoppedmethotrexatebecauseof lack of efficacy. The overall diseaseimprovement rate with methotrexatefrom previouslyreportedcasesof dermatomyositis and polymyositis is 75% (43/57). This suggeststhat methotrexateis an effectiveagent in the treatmentof dermatomyositis,especiallyfor the cutaneousmanifestations. Seventypercentof our patients (7/ 10) had side effectswith methotrexatetreatment, and 50% (5/ 10) stoppedmethotrexatebecauseof adversereactions.Side effectsoccurredin 54%(3 l/57) of cases with dermatomyositisand polymyositis previously
Academy
of Dermatology May 1995
reported.Sideeffectsarereportedlessfrequentlyin patientswith rheumatoid arthritis receivingmethotrexate,with onethird of patientsdiscontinuingthis drug becauseof adversereactions.24 A steroid-sparingeffectwasseenwith methotrexate in our patients;the initial prednisonedosecould be halved after an averageof 18 and 13 weeksfor patientswith dermatomyositisand ADM, respectively. Our seriesreportsthe first liver biopsyresultsin patientswith dermatomyositistreated with methotrexate.None of our patientshad pretreatmentbiopsies.Of the four patientswho underwentbiopsy, methotrexatewas stoppedin two becauseof early hepatic fibrosis (grade IIIA), although this is not consideredan absolutecontraindicationto continuedmethotrexatetherapy.25Both our patientswith liver abnormalitieshad diabetesmellitus from steroid use, and one patient was obese.Obesity with diabetesis consideredto be possiblyassociatedwith increasedtoxic effectson the liver from methotrexate.26Both patients with abnormal liver biopsy specimenshad abnormal serum levelsof liver enzymes at some point during the courseof methotrexate therapy. However, elevatedserum transaminaselevels in a patient with dermatomyositis couldreflectactivemyositisaswell asmethotrexateinducedhepatotoxicity. REFERENCES 1. McFarlin DE, Griggs RC. Treatment of inflammatory myopathies with azathioprine. Tram Am Neurol Assoc 1968;93:244-6. 2. Sinoway PA, Callen JP. Chlorambucik an effective corticosteroid-sparing agent for patients with recalcitrant dermatomyositis. Arthritis Rheum 1993;36:319-24. 3. Grau JM, Herrero C, Casademont J, et al. Cyclosporine A as first choice therapy for dermatomyositis. J Rheumatol 199+21:381-2. 4. Dalakas MC, Illa I, Dambrosia JM, et al. A controlled trial of high dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993; 329:1993-2000. 5. Cherin P, Piette JC, Wechsler B, et al. Intravenous gamma globulin as first line therapy in polymyositis and dermatomyositk an open study in 1 I adult patients. J Rheumatol 1994;21:1092-7. 6. Reimold AM, Weinblatt ME. Tachyphylaxis of intravenous immunoglobulin in refractory inflammatory myopathy. J Rheumatol 199+21:1144-6. 7. Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med 1975;292344-7. 8. Euwer RL, Sontheimer RD. Amyopathic dermatomyositis (dermatomyositis sin& myositis). J AM ACAD DERMATOL 1991;24:959-66.
9. Euwer RL, Sontheimer RD. Amyopathic dermatomyositis: a review. J Invest Dermatol 1993;100(supp1):124S-7s.
Journal of the American Academy of Dermatology Volume 32, Number 5, Part 1
10. Roenigk HH Jr, Auerbach R, Maibach HI, et al. Methotrexate guidelines-revised. J AM ACAD DERMATOL 1982;6:145-55. 1I. Malaviya AN, Goldbergh S, PearsonCM. Treatment of dermatomyositiswith methotrexate. Lancet 196&2:485-g. 12. Sokoloff MC, Goldberg LS, PearsonCM, Treatment of corticosteroid-resistantpolymyositis with methotrexate. Lancet 1971;1:14-6. 13. Currie S, Walton JN. Immunosuppressivetherapy in polymyositis.J Neural Neurosurg Psych 1971;34:477-82. 14. Arnett FC, Whelton JC, Zizic TM, et al. Methotrexate therapy in polymyositis.Ann Rheum Dis 1973;32:536-46. 15. Metzger AL, Bohan A, Goldberg LS, et al. Polymyositis and dermatomyositis:combined methotrexate and corticosteroid treatment. Ann Intern Med 1974;81:182-9. 16. Tierney LM Jr. Dermatomyositis-medical staff conference. West J Med 1976;124316-22. 17. Sarova-PinhasI, SiegalT, Turgman J, et al. Methotrexate treatment in dermatomyositis.Eur Neural 1977;16:149-54. 18. El-Ghobarey A, Balint G, DeCeulaer K, et al. Dermatomyositis: observationson the use of immunosuppressive therapy and review of literature. Postgrad Med J 1978; 545 16-27. 19. Giannini M, Callen JP.Treatment of dermatomyositiswith
Zieglschmid-Adams et al. 757 methotrexate and prednisone.Arch Dermatol 1979;115: 1251-2. 20. Callen JP. Dermatomyositisand multiple malignanciesin a patient treated with methotrexate. J Surg Oncol 1983; 24:113-6. 21. Wallace DJ, Metzger AL, White KK. Combination immunosuppressivetreatment of steroid-resistantdermatomyositis/polymyositis.Arthritis Rheum 1985;28:590-2. 22. Ramirez G, AshersonRA, Khamashta MA, et al. Adult onset polymyositis-dermatomyositis:description of 25 patients with emphasison treatment. Semin Arthritis Rheum 199@201114-20. 23. Cagnoli M, Marcheson A, Tosi S. Combined steroid, methotrexate, and chlorambucil therapy for steroid-resistant dermatomyositis.Clin Exp Rheumatol 1991;9:658-9. 24. Tugwell P, Bennett K, Gent M. Methotrexate in rheumatoid arthritis. Ann Intern Med 1987;107:418-9. 25. Roenigk HH Jr, Auerbach R, Maibach HI, et al. Methotrexate in psoriasis:revisedguidelines.J AM ACAD DERMATOL 1988;19:145-56. 26. Lewis JH, Schiff E. Methotrexate-induced chronicliver injury: guidelinesfor detectionand prevention.Am J Gastroenter011988;88:1337-45.
In dermatomyositis,high-doseoral corticosteroidsis consideredthe mainstay of treatment.However,somepatientsareunableto toleratethis treatment or haveprogressionof diseasedespitetherapy. In thesepatients azathioprine,lchlorambuciJ2cyclosporine,3and methotrexatemay be used either aloneor in combinationwith steroids.Intravenous y-globulin has also recentlybeen used.4V6 We describe 10 patientswith dermatomyositisor amyopathic dermatomyositis(ADM) treatedwith methotrexateand examinethe efficacy,steroid-sparing potential,and sideeffectsof this drug. Liver biopsy was performedin four patients.This is the first reportedseriesto includetheseresultsin patientswith dermatomyositistreatedwith methotrexate. From the Departments of Dermatologya and Internal Medicine) University of Texas Southwestern Medical Center, and Rheumatology Division, St. Paul Medical Center? Reprint requests: R. D. Sontheimer, MD, Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9069. Copyright 0190-9622/95
754
&? 1995 by the American $3.00 + 0
16/l/62417
Academy
of Dermatology,
Inc.
PATIENTS
AND METHODS
All 10 patients with dermatomyositis treated with methotrexate from 1975 to 1993 in a university-based private dermatology practice and a community-based private rheumatology practice in Dallas, Tex., were included. Seven patients had a diagnosis of classic dermatomyositis on the basis of typical clinical and histopathologic skin findings and evidence of myositis by physical examination, electromyography, enzyme determination, and/or muscle biopsy.7 Three patients had ADM. The criteria for diagnosis included typical cutaneous manifestations of dermatomyositis persisting for 2 years without clinical evidence of myositis by examination of muscle strength or by measurement of creatine kinase and aldolase.s One of the three patients without myositis met the criteria for confirmed ADM. Two patients who had typical skin findings for less than 2 years without evidence of muscle diseasehad the provisional diagnosis of ADM? None of our patients had malignancy-associated dermatomyositis, All patients had active skin disease at the time of initiation of treatment with methotrexate. Liver biopsy specimens were graded by the method of Roenigk et allo Grade I represents normal to mild fatty changes and mild portal inflammation; grade II includes more severe fatty infiltration and portal tract expansion,
Journal of the American Academy of Dermatology Volume 32, Number 5, Part 1
inflammation, and necrosis; grade IIIA represents mild portal fibrosis; grade IIIB includesmoderate to severefibrosis; and grade IV represents cirrhosis with regenerating nodulesand bridgingof portaltracts.No pretreat-
mentliverbiopsyspecimens wereobtainedfrom ourpatients. RESULTS
Age, sex, race, and presence of muscle disease
Patientsrangedin agefrom 27 to 79 yearsat the time of diagnosis.Only oneof the 10patientswas a man. Six were white, two were Hispanic, and two were black. Sevenpatients (70%) had evidenceof activemyositis. Methotrexate
dose
All patientsweretreatedwith oral methotrexate weekly exceptfor one patient with classicdermatomyositis, who receivedintravenousmethotrexate weekly.The averageinitial dosageof methotrexate was 7.5 mg/wk for the patientswith dermatomyositisand 9.2mg/wk for the patientswith ADM. The averagemaximal weekly methotrexate dose was 14.2mg for the patientswith dermatomyositisand 20 mg for the patientswith ADM. The total cumulativedoseof methotrexatein the patientswith dermatomyositisrangedfrom 52.5to 3042.5mgin 7 to 274weeks(mean,1097mg in 98.3 weeks).In the patientswith ADM the total cumulative methotrexatedoserangedfrom 132.5to 1050 mg in 15to 9 1weeks(mean,6 17.5mg in 50 weeks). All patientswith dermatomyositisand two of the threepatientswith ADM had improvementin their skin diseaseduring methotrexatetherapy.Most patients receivedoral corticosteroidsconcomitantly, but other systemic medications such as hydroxychloroquinewere not used,Sunscreensand topical corticosteroidswere used by most patients before and during methotrexatetherapy. Fifty-sevenpercent(4/7) of the patientswith dermatomyositishad improvementof their myositis during methotrexate treatment. Prednisone
dose
All the patientswith dermatomyositistook prednisonebeforetreatmentwith methotrexate.The averageduration of steroidtherapybeforemethotrexate was 11.3 months, which excludedone patient whohad takenprednisonefor 16years.The average steroiddosageat initiation of methotrexatewas32.5 w/hJ.
Zieglschmid-Adams
et al.
75
Of the patients with ADM, 33% receivedprednisone before methotrexatetherapy. One patient was nevertreatedwith corticosteroids,whereasanother patient beganprednisoneconcurrently with methotrexate.The averageprednisonedosageat initiation of methotrexatewas 60 mg/day. The initial prednisonedosewashalvedin the patients with dermatomyositisafter 4 to 41 weeks (mean, 18 weeks).In the patientswith ADM who took prednisonefor more than 13 weeks(2/3), the initial prednisonedosewashalvedafter an average of 13 weeks. Adverse reactions
Eighty-six percent(6/7) of the patientswith dermatomyositis and 33% (l/3) of thosewith ADM had someform of adversereaction.Stomatitis was reportedin threepatients;gastrointestinaldistressin two; abnormal liver biopsy specimensin two; and lung disease,leukopenia,and alopeciain onepatient each.Some patientshad more than oneadversereaction.Fifty-sevenpercent(4/7) of thepatientswith dermatomyositisand 33%( I /3) of thosewith ADM stoppedmethotrexatebecauseof the severityof the sideeffects. Liver biopsy results
Forty percent(4/10) of the patientshad undergone liver biopsies.Two patients had grade IIIA changesof mild hepatic fibrosis and subsequently had methotrexatediscontinued.One of thesepatients had dermatomyositis, and the other had ADM. Cumulativemethotrexatedoseat thetime of biopsywas385mg for the patient with dermatomyositisand 1050mg for the patientwith ADM. Their weekly doseat the time of biopsy was 12.5and 15 mg/wk, respectively.Both patients had diabetes mellitus from prolongedsteroiduse,and the patient with ADM was also obese. The patient with dermatomyositishad persistentlyelevatedAST levelsanda normal serumalbumin levelbeforebiopsy. The patient with ADM had intermittently elevated AST values before and during the first year of methotrexatetreatment. DISCUSSION
Methotrexatehas beenusedsince 1968to treat steroid-refractorydermatomyositisand polymyositis. A reviewof the literature yieldedreportsof 57 adultswith dermatomyositisor polymyositistreated with methotrexate.11-23 Seventy-fivepercent (43/
Journal
of the American
756 Zieglschmid-Adams et al. 57) had improvementin their disease.Twenty-five percent(3/ 12) of the nonresponders improvedwith a combinationof steroids,methotrexate,and chlorambucil. Of the nonresponders, onereceivedonly onedoseof methotrexate. Adversereactionswere seenin 54% (31/57) of previously reported patients. Stomatitis was the most frequentreactionand occurredin 25% of patients (14/57). Leukopeniaoccurredin 7% of patients (4/57). The three reportedpulmonary complicationsincludeda deathfrom methotrexatepneumonitis, transient bilateral pulmonary infiltrates, and a worseningdiffusioncapacity of carbonmonoxideon pulmonaryfunction tests.Onepatient had diffuse hepatomegalyand an elevatedserum alkaline phosphatase level,andanotherhad a transiently elevatedserumalkaline phosphataselevel.No liver biopsieswere reported in any of the 57 patients treated with methotrexate.In one patient with a history of uterine adenocarcinomaanddermatomyositis a breast adenocarcinomadeveloped2 years after methotrexatetherapy. The largestsingleseriesof patientswith dermatomyositisand polymyositistreatedwith methotrexatewasreportedby Metzger et al.15in 1974.Twenty-two patientswere given intravenousmethotrexate. Seventy-sevenpercent had improvement of muscle strength and/or skin disease.Muscle enzymesnormalizedaftera meanof 10weeks,whereas muscle strength improvement was noted at 13 weeks.In patients with dermatomyositisthe skin diseasebeganto improve as muscle enzymesnormalized.A steroid-sparingeffectwasseen.Half the patientshad minor reversibletoxic effects. In our seriesof patients,all but oneof whom receivedweeklyoral methotrexate,90%had improvement of their skin diseaseand 57Y0(4/7) of the patients with dermatomyositisalsohad improvement in their muscledisease.Only onepatientwith ADM stoppedmethotrexatebecauseof lack of efficacy. The overall diseaseimprovement rate with methotrexatefrom previouslyreportedcasesof dermatomyositis and polymyositis is 75% (43/57). This suggeststhat methotrexateis an effectiveagent in the treatmentof dermatomyositis,especiallyfor the cutaneousmanifestations. Seventypercentof our patients (7/ 10) had side effectswith methotrexatetreatment, and 50% (5/ 10) stoppedmethotrexatebecauseof adversereactions.Side effectsoccurredin 54%(3 l/57) of cases with dermatomyositisand polymyositis previously
Academy
of Dermatology May 1995
reported.Sideeffectsarereportedlessfrequentlyin patientswith rheumatoid arthritis receivingmethotrexate,with onethird of patientsdiscontinuingthis drug becauseof adversereactions.24 A steroid-sparingeffectwasseenwith methotrexate in our patients;the initial prednisonedosecould be halved after an averageof 18 and 13 weeksfor patientswith dermatomyositisand ADM, respectively. Our seriesreportsthe first liver biopsyresultsin patientswith dermatomyositistreated with methotrexate.None of our patientshad pretreatmentbiopsies.Of the four patientswho underwentbiopsy, methotrexatewas stoppedin two becauseof early hepatic fibrosis (grade IIIA), although this is not consideredan absolutecontraindicationto continuedmethotrexatetherapy.25Both our patientswith liver abnormalitieshad diabetesmellitus from steroid use, and one patient was obese.Obesity with diabetesis consideredto be possiblyassociatedwith increasedtoxic effectson the liver from methotrexate.26Both patients with abnormal liver biopsy specimenshad abnormal serum levelsof liver enzymes at some point during the courseof methotrexate therapy. However, elevatedserum transaminaselevels in a patient with dermatomyositis couldreflectactivemyositisaswell asmethotrexateinducedhepatotoxicity. REFERENCES 1. McFarlin DE, Griggs RC. Treatment of inflammatory myopathies with azathioprine. Tram Am Neurol Assoc 1968;93:244-6. 2. Sinoway PA, Callen JP. Chlorambucik an effective corticosteroid-sparing agent for patients with recalcitrant dermatomyositis. Arthritis Rheum 1993;36:319-24. 3. Grau JM, Herrero C, Casademont J, et al. Cyclosporine A as first choice therapy for dermatomyositis. J Rheumatol 199+21:381-2. 4. Dalakas MC, Illa I, Dambrosia JM, et al. A controlled trial of high dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993; 329:1993-2000. 5. Cherin P, Piette JC, Wechsler B, et al. Intravenous gamma globulin as first line therapy in polymyositis and dermatomyositk an open study in 1 I adult patients. J Rheumatol 1994;21:1092-7. 6. Reimold AM, Weinblatt ME. Tachyphylaxis of intravenous immunoglobulin in refractory inflammatory myopathy. J Rheumatol 199+21:1144-6. 7. Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med 1975;292344-7. 8. Euwer RL, Sontheimer RD. Amyopathic dermatomyositis (dermatomyositis sin& myositis). J AM ACAD DERMATOL 1991;24:959-66.
9. Euwer RL, Sontheimer RD. Amyopathic dermatomyositis: a review. J Invest Dermatol 1993;100(supp1):124S-7s.
Journal of the American Academy of Dermatology Volume 32, Number 5, Part 1
10. Roenigk HH Jr, Auerbach R, Maibach HI, et al. Methotrexate guidelines-revised. J AM ACAD DERMATOL 1982;6:145-55. 1I. Malaviya AN, Goldbergh S, PearsonCM. Treatment of dermatomyositiswith methotrexate. Lancet 196&2:485-g. 12. Sokoloff MC, Goldberg LS, PearsonCM, Treatment of corticosteroid-resistantpolymyositis with methotrexate. Lancet 1971;1:14-6. 13. Currie S, Walton JN. Immunosuppressivetherapy in polymyositis.J Neural Neurosurg Psych 1971;34:477-82. 14. Arnett FC, Whelton JC, Zizic TM, et al. Methotrexate therapy in polymyositis.Ann Rheum Dis 1973;32:536-46. 15. Metzger AL, Bohan A, Goldberg LS, et al. Polymyositis and dermatomyositis:combined methotrexate and corticosteroid treatment. Ann Intern Med 1974;81:182-9. 16. Tierney LM Jr. Dermatomyositis-medical staff conference. West J Med 1976;124316-22. 17. Sarova-PinhasI, SiegalT, Turgman J, et al. Methotrexate treatment in dermatomyositis.Eur Neural 1977;16:149-54. 18. El-Ghobarey A, Balint G, DeCeulaer K, et al. Dermatomyositis: observationson the use of immunosuppressive therapy and review of literature. Postgrad Med J 1978; 545 16-27. 19. Giannini M, Callen JP.Treatment of dermatomyositiswith
Zieglschmid-Adams et al. 757 methotrexate and prednisone.Arch Dermatol 1979;115: 1251-2. 20. Callen JP. Dermatomyositisand multiple malignanciesin a patient treated with methotrexate. J Surg Oncol 1983; 24:113-6. 21. Wallace DJ, Metzger AL, White KK. Combination immunosuppressivetreatment of steroid-resistantdermatomyositis/polymyositis.Arthritis Rheum 1985;28:590-2. 22. Ramirez G, AshersonRA, Khamashta MA, et al. Adult onset polymyositis-dermatomyositis:description of 25 patients with emphasison treatment. Semin Arthritis Rheum 199@201114-20. 23. Cagnoli M, Marcheson A, Tosi S. Combined steroid, methotrexate, and chlorambucil therapy for steroid-resistant dermatomyositis.Clin Exp Rheumatol 1991;9:658-9. 24. Tugwell P, Bennett K, Gent M. Methotrexate in rheumatoid arthritis. Ann Intern Med 1987;107:418-9. 25. Roenigk HH Jr, Auerbach R, Maibach HI, et al. Methotrexate in psoriasis:revisedguidelines.J AM ACAD DERMATOL 1988;19:145-56. 26. Lewis JH, Schiff E. Methotrexate-induced chronicliver injury: guidelinesfor detectionand prevention.Am J Gastroenter011988;88:1337-45.