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Elevated CPK and isotretinoin
Volume 12 Number 3 March, 1985
Correspondence
T a b l e I. Distribution of lesions in ninetyo n e patients with pityriasis versicolor Site
Number ( %)
Chest Neck Upper portion of back Shoulders Scalp Abdomen Lower portion of back Upper arm Face Axillae Buttocks Groin Perineum Forearms Thighs
87 (95.6) 85 (93.4) 83 (91.2) 80 (88.0) 74 (81.3) 74 (81.3) 74 (81.3) 56 (61.5) 52 (57.1) 50 (55.0) 47 (51.6) 45 (49.4) 32 (35.1) 30 (33.0) 25 (27.5)
tions of 1% econazole foaming solution during bath for either three or six consecutive days. All patients were advised to refrain from using petrolatum or oil lotions during the 4-week period of follow-up. They were seen at 2 and 4 weeks after completion of therapy and were subjected to thorough clinical and laboratory investigations. The absence of fluorescence of skin lesions under Wood's light and also the absence of filamentous forms in 20% KOH and methylene blue/KOH smears at the end of 4 weeks were considered tests of cure. Results. The chest, neck, upper portion of the back, shoulders, and scalp (80%) were the sites most frequently affected (Table I). Although all the patients showed positive results on microscopy, all but three showed yellow fluorescence under Wood's light. Fiftyone patients received a 3-day regimen, and of fortythree followed for 4 weeks, four (9.3%) failed to get mycologic cure; however, clinical improvement was marked in two, slight in one, and none in the remaining failure. Among sixty-five patients given the 6-day regimen, forty-eight were followed for 4 weeks and two (4.2%) failed to be cured. Of these failures, one showed slight improvement and the other, no clinical improvement. The cure rate at the end of 4 weeks was 90.7% with a 3-day regimen and 95.8% with a 6-day regimen. Thirty-seven (40%) showed no trace of the disease while 54 (60%) still showed residual hypopigmented macules. The clinical tolerability was excellent in all but one patient (on a 3-day regimen), in whom it was rated moderate and did not warrant discontinuation of therapy. Comment. Various authorities in the recent past have
581
treated this disease in numerous ways, both topically and systemically3"4 An ideal drug should be one that is 990% effective, easy to apply all over the body including the scalp, requires therapy of short duration, is free from adverse effects, and, of course, is inexpensive. Although selenium disulfide shampoo, miconazole,* and clotrimazole are certainly effective,~,3,5they do not fulfill all the criteria. Selenium disulfide requires 2 weeks' therapy and has an unpleasant odor. Miconazole and clotrimazole are generally available as creams, which, unlike shampoos and foaming solutions, are difficult to apply on all parts of the body, especially the scalp. In view of this, 1% econazole foaming solution is recommended for treatment, Although the.re was no statistically significant difference in the cure rates obtained with the two regimens, the 6-day regimen is recommended, keeping in view the tropical climate of Zambia. Since the patients were not followed for more than 4 weeks, we are unable to comment on once-amonth maintenance therapy, and further studies are indicated.
Subhash K. Hira, M.D. Shahida N. Din, M,B.B,S,, and Jagdish S. Patel, M.B., Ch.B. Dermato-Venereology Division University Teaching Hospital P.O. Box 50001, Lusaka, Zambia, Africa *FredrikssonT: Treatmentof dermatomycosiswith topicalmieonazole (Daktar). OpuseutaMedico21:80-84, 1977. REFERENCES 1. AjeUo L, Padhya A: Dermatophytes and the agents of superficial mycoses, in Lennette EH, Barlow A, Housler JP, editors: Manual of clinical microbiology. Washington, DC, 1980, American Society for Microbiology. 2. Albright SD, Hitch JM: Rapid treatment of tinea versicolor with seleniumsulphide. Arch Dermato193:460-465, 1966. 3. Gip L: The topical therapy of pityriasis versicolor with clotrimazoIe. Postgrad Med J 50:59-63, 1974. 4. Faergemann J, Fredriksson T: An open trial of the effect of a zinc pydthione shampoo in tinea versicolor. Cutis 25:667-671, 1980. 5. FaergemannJ, Fredriksson T: Tinea versicolor: Some new aspects of etiology,pathogenesis, and treatment. Int J Dermatol 21:8-13, 1982.
Elevated C P K and isotretinoin
To the Editor: McBumey and Rosen (J AM ACAD DERMATOL 10:528-529, 1984) reported one case of elevated ereatine phosphokinase (CPK) in a patient under treatment
Journal of the American Academy of Dermatology
Correspondence
582
T a b l e I. Summary o f cases o f elevated creatine phosphokinase Sex
Pretreatment CPK (normal, 0-224)
CPK elevation/wk noted
Comment
27 20 22 17
M M M M
134 50 75 95
864/wk 5 1,950/wk 1 3,520/wk 4* 360/wk 22
5 6 7~"
19 21 22
F M M
102 88 80
584/wk 12 438/wk 13 318/wk 17
7~:
22
M
77
327/wk 17
Isotretinoin discontinued at wk 6 Returned to normal level at wk 3 CPK normal at wk 8 Remained elevated at 368 4 wk posttreatment CPK 104 at wk 13 Repeat levels pending CPK elevated to 366 at 19 wk CPK 77 at 4 w k posttreatment Repeat level pending
Case No.
Age
1 2 3 4
J
*Accompaniedby elevationsof lactic,dehydrogenase(LDH),aspartate transaminase (AST;SGOT), alanine transaminase (ALl'; SGPT). Patient gives historyof liftingweights. No hepatomegalynoted. tFirst 20-week course. ~:Second20-weekcourse. with isotretinoin. We have found similar elevations in seven patients.~ The cases are summarized in Table I. There were four patients with significant CPK elevations, and three had moderate elevation. All the patients were undergoing treatment for severe n o d u l o cystic ache and were on standard doses (1.0-1.2 mg/ kg) of isotretinoin, None o f the patients had myalgias or muscle weakness. The elevation of the CPK in seven of ninety-eight patients treated with isotretinoin indicates a need for inclusion of the CPK as part of the routine monitoring of patients on isotretinoin.
Judith T. Lipinski, M.D., and Benjamin Schwimmer, M.D. Wayne State University School of Medicine Department of Dermatology, Detroit, MI 48201 REFERENCE
1. Windhorst DB, Nigra T: General clinical toxicology of oral retinoids. J AM ACADDE~ATOL 6:675-682, 1982.
Reply
To the Editor: The cases reported by Drs. Lipinski and Schwinner with regard to elevated creatine phosphokinase (CPK) levels in patients using isotretinoin (Accutane) bring to nine the total number of cases reported in the last 6 months in the "Correspondence" section of this JOURr,rAL.~'2 In addition, since the first published report of a patient on isotretinoin with debilitating myalgia and high CPK level, which we reported in March 1984, we have now treated a total of thirty-one patients with ache with isotretinoin (all white, 14 male, 17 female, ages
14-58). Of these thirty-one patients, ten (7 male, 3 female, ages 15-26) have had elevated CPK activity during the course of therapy. Two male patients of these ten patients reported associated muscle pain, and their levels of CPK at that time were significantly elevated: 4,21.0 U/liter and 1,225 U/liter. One of the patients was participating in spring footbaU'practice. The other eight patients had lower ranges of CPK: from 168 to 947 U/ liter. Of these eight, only one reported an involvement in vigorous physical activity, namely, jogging, but she had been jogging regularly for about 2 years. CPK is found primarily in skeletal muscle and myocardium, although appreciable amounts are present in the brain. Little or no CPK activity is present in liver, kidney, pancreas, or red blood cells. CPK is composed of three isoenzymes identified by electrophoresis, namely, BB or CK, in brain tissue; MB or CK2 found i n myocardium and skeletal muscle; MM or CK3 in skeletal muscle and comprising 60% of myocardial CPK activity. Normal serum CK (1-140 U/liter) is virtually 100% MM isoenzyme. The presence of elevated MB isoenzyme usually indicates damage to the myocardium, but this is not absolutely specific. 3 It is well recognized in the literature that serum CPK greater than twenty-fold of normal is common in healthy runners tested 24 hours after a marathon event.* A fairly well-confirmed hypothesis is that the elevation of CPK in marathon runners is due to skeletal muscle injury. This is substantiated, in marathon runners under intense training, by muscle biopsies that showed m y o -
*DressendorferRH, Wade CE: The muscular overuse syndrome in long-distance runners. Physicianand SportsmedieineU: 116-130, 1983.
Correspondence
T a b l e I. Distribution of lesions in ninetyo n e patients with pityriasis versicolor Site
Number ( %)
Chest Neck Upper portion of back Shoulders Scalp Abdomen Lower portion of back Upper arm Face Axillae Buttocks Groin Perineum Forearms Thighs
87 (95.6) 85 (93.4) 83 (91.2) 80 (88.0) 74 (81.3) 74 (81.3) 74 (81.3) 56 (61.5) 52 (57.1) 50 (55.0) 47 (51.6) 45 (49.4) 32 (35.1) 30 (33.0) 25 (27.5)
tions of 1% econazole foaming solution during bath for either three or six consecutive days. All patients were advised to refrain from using petrolatum or oil lotions during the 4-week period of follow-up. They were seen at 2 and 4 weeks after completion of therapy and were subjected to thorough clinical and laboratory investigations. The absence of fluorescence of skin lesions under Wood's light and also the absence of filamentous forms in 20% KOH and methylene blue/KOH smears at the end of 4 weeks were considered tests of cure. Results. The chest, neck, upper portion of the back, shoulders, and scalp (80%) were the sites most frequently affected (Table I). Although all the patients showed positive results on microscopy, all but three showed yellow fluorescence under Wood's light. Fiftyone patients received a 3-day regimen, and of fortythree followed for 4 weeks, four (9.3%) failed to get mycologic cure; however, clinical improvement was marked in two, slight in one, and none in the remaining failure. Among sixty-five patients given the 6-day regimen, forty-eight were followed for 4 weeks and two (4.2%) failed to be cured. Of these failures, one showed slight improvement and the other, no clinical improvement. The cure rate at the end of 4 weeks was 90.7% with a 3-day regimen and 95.8% with a 6-day regimen. Thirty-seven (40%) showed no trace of the disease while 54 (60%) still showed residual hypopigmented macules. The clinical tolerability was excellent in all but one patient (on a 3-day regimen), in whom it was rated moderate and did not warrant discontinuation of therapy. Comment. Various authorities in the recent past have
581
treated this disease in numerous ways, both topically and systemically3"4 An ideal drug should be one that is 990% effective, easy to apply all over the body including the scalp, requires therapy of short duration, is free from adverse effects, and, of course, is inexpensive. Although selenium disulfide shampoo, miconazole,* and clotrimazole are certainly effective,~,3,5they do not fulfill all the criteria. Selenium disulfide requires 2 weeks' therapy and has an unpleasant odor. Miconazole and clotrimazole are generally available as creams, which, unlike shampoos and foaming solutions, are difficult to apply on all parts of the body, especially the scalp. In view of this, 1% econazole foaming solution is recommended for treatment, Although the.re was no statistically significant difference in the cure rates obtained with the two regimens, the 6-day regimen is recommended, keeping in view the tropical climate of Zambia. Since the patients were not followed for more than 4 weeks, we are unable to comment on once-amonth maintenance therapy, and further studies are indicated.
Subhash K. Hira, M.D. Shahida N. Din, M,B.B,S,, and Jagdish S. Patel, M.B., Ch.B. Dermato-Venereology Division University Teaching Hospital P.O. Box 50001, Lusaka, Zambia, Africa *FredrikssonT: Treatmentof dermatomycosiswith topicalmieonazole (Daktar). OpuseutaMedico21:80-84, 1977. REFERENCES 1. AjeUo L, Padhya A: Dermatophytes and the agents of superficial mycoses, in Lennette EH, Barlow A, Housler JP, editors: Manual of clinical microbiology. Washington, DC, 1980, American Society for Microbiology. 2. Albright SD, Hitch JM: Rapid treatment of tinea versicolor with seleniumsulphide. Arch Dermato193:460-465, 1966. 3. Gip L: The topical therapy of pityriasis versicolor with clotrimazoIe. Postgrad Med J 50:59-63, 1974. 4. Faergemann J, Fredriksson T: An open trial of the effect of a zinc pydthione shampoo in tinea versicolor. Cutis 25:667-671, 1980. 5. FaergemannJ, Fredriksson T: Tinea versicolor: Some new aspects of etiology,pathogenesis, and treatment. Int J Dermatol 21:8-13, 1982.
Elevated C P K and isotretinoin
To the Editor: McBumey and Rosen (J AM ACAD DERMATOL 10:528-529, 1984) reported one case of elevated ereatine phosphokinase (CPK) in a patient under treatment
Journal of the American Academy of Dermatology
Correspondence
582
T a b l e I. Summary o f cases o f elevated creatine phosphokinase Sex
Pretreatment CPK (normal, 0-224)
CPK elevation/wk noted
Comment
27 20 22 17
M M M M
134 50 75 95
864/wk 5 1,950/wk 1 3,520/wk 4* 360/wk 22
5 6 7~"
19 21 22
F M M
102 88 80
584/wk 12 438/wk 13 318/wk 17
7~:
22
M
77
327/wk 17
Isotretinoin discontinued at wk 6 Returned to normal level at wk 3 CPK normal at wk 8 Remained elevated at 368 4 wk posttreatment CPK 104 at wk 13 Repeat levels pending CPK elevated to 366 at 19 wk CPK 77 at 4 w k posttreatment Repeat level pending
Case No.
Age
1 2 3 4
J
*Accompaniedby elevationsof lactic,dehydrogenase(LDH),aspartate transaminase (AST;SGOT), alanine transaminase (ALl'; SGPT). Patient gives historyof liftingweights. No hepatomegalynoted. tFirst 20-week course. ~:Second20-weekcourse. with isotretinoin. We have found similar elevations in seven patients.~ The cases are summarized in Table I. There were four patients with significant CPK elevations, and three had moderate elevation. All the patients were undergoing treatment for severe n o d u l o cystic ache and were on standard doses (1.0-1.2 mg/ kg) of isotretinoin, None o f the patients had myalgias or muscle weakness. The elevation of the CPK in seven of ninety-eight patients treated with isotretinoin indicates a need for inclusion of the CPK as part of the routine monitoring of patients on isotretinoin.
Judith T. Lipinski, M.D., and Benjamin Schwimmer, M.D. Wayne State University School of Medicine Department of Dermatology, Detroit, MI 48201 REFERENCE
1. Windhorst DB, Nigra T: General clinical toxicology of oral retinoids. J AM ACADDE~ATOL 6:675-682, 1982.
Reply
To the Editor: The cases reported by Drs. Lipinski and Schwinner with regard to elevated creatine phosphokinase (CPK) levels in patients using isotretinoin (Accutane) bring to nine the total number of cases reported in the last 6 months in the "Correspondence" section of this JOURr,rAL.~'2 In addition, since the first published report of a patient on isotretinoin with debilitating myalgia and high CPK level, which we reported in March 1984, we have now treated a total of thirty-one patients with ache with isotretinoin (all white, 14 male, 17 female, ages
14-58). Of these thirty-one patients, ten (7 male, 3 female, ages 15-26) have had elevated CPK activity during the course of therapy. Two male patients of these ten patients reported associated muscle pain, and their levels of CPK at that time were significantly elevated: 4,21.0 U/liter and 1,225 U/liter. One of the patients was participating in spring footbaU'practice. The other eight patients had lower ranges of CPK: from 168 to 947 U/ liter. Of these eight, only one reported an involvement in vigorous physical activity, namely, jogging, but she had been jogging regularly for about 2 years. CPK is found primarily in skeletal muscle and myocardium, although appreciable amounts are present in the brain. Little or no CPK activity is present in liver, kidney, pancreas, or red blood cells. CPK is composed of three isoenzymes identified by electrophoresis, namely, BB or CK, in brain tissue; MB or CK2 found i n myocardium and skeletal muscle; MM or CK3 in skeletal muscle and comprising 60% of myocardial CPK activity. Normal serum CK (1-140 U/liter) is virtually 100% MM isoenzyme. The presence of elevated MB isoenzyme usually indicates damage to the myocardium, but this is not absolutely specific. 3 It is well recognized in the literature that serum CPK greater than twenty-fold of normal is common in healthy runners tested 24 hours after a marathon event.* A fairly well-confirmed hypothesis is that the elevation of CPK in marathon runners is due to skeletal muscle injury. This is substantiated, in marathon runners under intense training, by muscle biopsies that showed m y o -
*DressendorferRH, Wade CE: The muscular overuse syndrome in long-distance runners. Physicianand SportsmedieineU: 116-130, 1983.