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Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis
Journal of the American Academy of Dermatology Volume 34, Number 5, Part 1
Pearls of wisdom
817
Abstracts from the literature Randomised controlled trial assessing effectiveness of health education leaflets in reducing incidence of sunburn D e y P, Collins S, Will S, et al. Br M e d J 1995; 311:1062-3. Now here's a novel study. These investigators randomized airplane flights from Manchester, England, to North America or Europe with regard to placing a leaflet entitled "If you worship the sun, don't sacrifice your skin" in the seat pocket (intervention flights) or not (control flights). Then, on return flights to Manchester, they distributed questionnaires about sunburn, skin type, and length of vacation. There were 12,385 evaluable questionnaires, representing a 69% response rate. Unfommately, presence of the questionnaires did not correlate with reduced incidence of severe sunburn while people were on holiday. The authors conclude that perhaps this method of primary prevention isn't such a good idea.
Elizabeth F. Sherertz, MD
Outpatient management of acute urticaria: the role of prednisone Pollack CV, R o m a n o TJ. Ann Emerg M e d 1995; 26:547-51. The standard emergency department treatment of acute generalized urticaria without respiratory distress or angioedema is use of H1 antihistamines such as diphenhydramine (50 mg) or hydroxyzine (25 mg) every 4 to 6 hours. In a randomized, placebo-controlled, double-blind study, the efficacy of a short course of prednisone, 20 mg every 12 hours for 4 days, was evaluated in addition to standard treatment. Forty-three patients were entered into the study, of whom 24 received prednisone and 14 received placebo. All of the prednisone-treated patients had an improved symptomatic and clinical response to antihistamine treatment by days 2 and 5. The authors conclude that, although most patients improve to some degree with antihistamines alone, the addition of a 4-day prednisone burst improves the efficacy and pace of resolution.
Elizabeth A. Abel, MD
Medication use and the risk of StevensJohnson syndrome or toxic epidermal necrolysis Breastfeeding as prophylaxis against atopic disease: prospective follow-up study until 17 years old Saafinen UM. Lancet 1995;346:1065-9. Prolonged breast-feeding for 6 months or longer was previously shown to be prophylactic against atopic disease in infants up to 3 years of age. A prospective long-term follow-up study was completed for 150 of the 236 infants enrolled in the initial study. Subjects were placed into three groups: those who had received breastfeeding that was prolonged (>6 months), intermediate (1 to 6 months), or short (<1 month). Follow-up history and examinations including laboratory tests for allergy were conducted at 1, 3, 5, 10, and 17 years of age. In this study, prolonged breast-feeding was found to be prophylactic against atopic disease, including atopic eczema, food allergy, and respiratory allergy throughout childhood and adolescence.
Elizabeth A. Abel, MD
Roujean J-C, Kelly JP, Naldi L, et al. N Engl J M e d 1995;333:1600-7. These authors surveyed networks in France, Germany, Italy, and Portugal and compared drag use between 245 persons with toxic epidermal necrolysis (TEN) or StevensJohnson Syndrome (SJS) and 1147 control subjects. They identified certain drags that have excessive risks for TEN/SJS development. Sulfonamides, particularly trimethoprim-sulfamethoxazole, aminopenicillins, quinolones, and cephalosporins carried the highest relative risk for agents used for short-term therapy. Acetaminophen carfled a high relative risk in countries other than France. Among drags intended for long-term therapy, the greatest risks were for anticonvulsants including phenytoin, carbamazepine, phenobarbital; valproic acid; oxicam nonsteroidal antiinflammatory agents; allopurinol; and corticosteroids. The risk was greatest within the first severn months of therapy. In addition, the authors did not find an increased risk associated with thiazides or oral hypoglycemic agents.
818
Journal of the American Academy of Dermatology May 1996
Pearls of wisdom
COMMZNT: This list is what might be expected, with the exception that corticosteroids were included among potential causative agents. The authors suggest that even among drags with the highest risk, the number of cases per 1,000,000 exposures is extremely low; thus, when indicated, these therapeutic agents should be utilized unless a safer, equally effective alternative is available.
COMMErCr: Periodic interruption of methotrexate therapy may be an option for those patients taking low maintenance doses.
Jeffrey P. Callen, MD
Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir
Elizabeth F. Sherertz, MD
Wald A, Zeh J, Barnum G, et al. Ann Intern M e d 1996;!24:8-15.
Melatonin madness Reppert SM, W e a v e r DR. Cell 1995;83:1059-62. The pineal gland secretes melatonin with striking circadian rhythm driven by daily light-dark cycles. Books and articles claim (probably without much if any scientific validity) that melatonin can reverse aging, treat AIDS and Alzheimer's disease, and prevent pregnancy. It can induce sleep and abort jet lag, but timing of the administration with regard to a person's current circadian rhythm is critical. COMMENT: I learned that much of melatonin's miracle is hype. Unfortunately, the article gives no clue as to when I should take the drug on my next trip overseas.
Mark V. Dahl, MD
Interruption of long-term methotrexate treatment in psoriasis: evaluation of clinical course and laboratory parameters after discontinuation and reintroduction of weekly oral methotrexate Van Dooren-Greebe RJ, Kuijpers ALA, Termoshuizen F, et al. Acta D e r m Venereol (Stockh) 1995; 75:393-6. This retrospective study examined parameters after methotrexate had been discontinued in 10 patients with psoriasis who had been receiving long-term (mean, 12.7 years) weekly oral methotrexate (weekly divided dose, up to 15 mg per week). Three of the 10 patients had a relapse within 4 weeks; the remaining seven patients were able to remain methotrexate free for at least 11 weeks. The lower the dose before discontinuation allowed more weeks free of therapy. Laboratory parameters showed a significant decrease in serum transaminase levels in the first 3 weeks without therapy. The authors conclude that interruption of methotrexate treatment leads to reduced cumulative dose and potential for hepatotoxicity. However, overall 7 of the 10 patients preferred continuous methotrexate therapy.
A double-blind, placebo-controlled, crossover study was conducted on 34 women with herpes simplex virus type 2 (HSV-2) antibody only and genital herpes of less than 2 years' duration. Participants were randomly chosen to receive either (1) acyclovir, 400 mg twice daily for 70 days, followed by a "washout period" of 14 days, followed by placebo for 70 days or (2) the placebo first and acyclovir second. The women themselves collected daily genital swabs from their ~alvas, perianal fossa, and cervicovaginal areas, maintained a diary, and were examined at times of recurrences. Fifteen of the 17 women who received placebo had at least 1 day of subclinical shedding compared with 3 of 17 women in the acyclovirtreated group (p <0.001). In the placebo group, asymptomatic shedding occurred on 6.9% of all days compared with 0.03% of days in subjects taking acyclovir. The crossover confirmed the results in paired sample analysis. Haft of the culture-positive episodes occurred without discernible lesions. COMMZIWr: Acyclovir reduces but does not completely stop subclinical shedding of HSV-2. The hope is that failures might have been due to compliance problems or bowel absorption problems. The authors caution all patients with HSV-2 infections "to use condoms at all times and abstain from sexual intercourse during recurrences."
Mark V. Dahl, MD
Ability of primary care physicians to recognize physical findings associated with HIV infection Pauuw DS, Wenrich MD, Curtis JR, et al. J A M A 1995;274:1380-2. One hundred thirty-four general internists or family practitioners examined standardized patients as part of a study. The patients presented histories that were designed to direct physicians to anatomic areas with positive physical findings (oral hairy leukoplakia, Kaposi's sarcoma,
Pearls of wisdom
817
Abstracts from the literature Randomised controlled trial assessing effectiveness of health education leaflets in reducing incidence of sunburn D e y P, Collins S, Will S, et al. Br M e d J 1995; 311:1062-3. Now here's a novel study. These investigators randomized airplane flights from Manchester, England, to North America or Europe with regard to placing a leaflet entitled "If you worship the sun, don't sacrifice your skin" in the seat pocket (intervention flights) or not (control flights). Then, on return flights to Manchester, they distributed questionnaires about sunburn, skin type, and length of vacation. There were 12,385 evaluable questionnaires, representing a 69% response rate. Unfommately, presence of the questionnaires did not correlate with reduced incidence of severe sunburn while people were on holiday. The authors conclude that perhaps this method of primary prevention isn't such a good idea.
Elizabeth F. Sherertz, MD
Outpatient management of acute urticaria: the role of prednisone Pollack CV, R o m a n o TJ. Ann Emerg M e d 1995; 26:547-51. The standard emergency department treatment of acute generalized urticaria without respiratory distress or angioedema is use of H1 antihistamines such as diphenhydramine (50 mg) or hydroxyzine (25 mg) every 4 to 6 hours. In a randomized, placebo-controlled, double-blind study, the efficacy of a short course of prednisone, 20 mg every 12 hours for 4 days, was evaluated in addition to standard treatment. Forty-three patients were entered into the study, of whom 24 received prednisone and 14 received placebo. All of the prednisone-treated patients had an improved symptomatic and clinical response to antihistamine treatment by days 2 and 5. The authors conclude that, although most patients improve to some degree with antihistamines alone, the addition of a 4-day prednisone burst improves the efficacy and pace of resolution.
Elizabeth A. Abel, MD
Medication use and the risk of StevensJohnson syndrome or toxic epidermal necrolysis Breastfeeding as prophylaxis against atopic disease: prospective follow-up study until 17 years old Saafinen UM. Lancet 1995;346:1065-9. Prolonged breast-feeding for 6 months or longer was previously shown to be prophylactic against atopic disease in infants up to 3 years of age. A prospective long-term follow-up study was completed for 150 of the 236 infants enrolled in the initial study. Subjects were placed into three groups: those who had received breastfeeding that was prolonged (>6 months), intermediate (1 to 6 months), or short (<1 month). Follow-up history and examinations including laboratory tests for allergy were conducted at 1, 3, 5, 10, and 17 years of age. In this study, prolonged breast-feeding was found to be prophylactic against atopic disease, including atopic eczema, food allergy, and respiratory allergy throughout childhood and adolescence.
Elizabeth A. Abel, MD
Roujean J-C, Kelly JP, Naldi L, et al. N Engl J M e d 1995;333:1600-7. These authors surveyed networks in France, Germany, Italy, and Portugal and compared drag use between 245 persons with toxic epidermal necrolysis (TEN) or StevensJohnson Syndrome (SJS) and 1147 control subjects. They identified certain drags that have excessive risks for TEN/SJS development. Sulfonamides, particularly trimethoprim-sulfamethoxazole, aminopenicillins, quinolones, and cephalosporins carried the highest relative risk for agents used for short-term therapy. Acetaminophen carfled a high relative risk in countries other than France. Among drags intended for long-term therapy, the greatest risks were for anticonvulsants including phenytoin, carbamazepine, phenobarbital; valproic acid; oxicam nonsteroidal antiinflammatory agents; allopurinol; and corticosteroids. The risk was greatest within the first severn months of therapy. In addition, the authors did not find an increased risk associated with thiazides or oral hypoglycemic agents.
818
Journal of the American Academy of Dermatology May 1996
Pearls of wisdom
COMMZNT: This list is what might be expected, with the exception that corticosteroids were included among potential causative agents. The authors suggest that even among drags with the highest risk, the number of cases per 1,000,000 exposures is extremely low; thus, when indicated, these therapeutic agents should be utilized unless a safer, equally effective alternative is available.
COMMErCr: Periodic interruption of methotrexate therapy may be an option for those patients taking low maintenance doses.
Jeffrey P. Callen, MD
Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir
Elizabeth F. Sherertz, MD
Wald A, Zeh J, Barnum G, et al. Ann Intern M e d 1996;!24:8-15.
Melatonin madness Reppert SM, W e a v e r DR. Cell 1995;83:1059-62. The pineal gland secretes melatonin with striking circadian rhythm driven by daily light-dark cycles. Books and articles claim (probably without much if any scientific validity) that melatonin can reverse aging, treat AIDS and Alzheimer's disease, and prevent pregnancy. It can induce sleep and abort jet lag, but timing of the administration with regard to a person's current circadian rhythm is critical. COMMENT: I learned that much of melatonin's miracle is hype. Unfortunately, the article gives no clue as to when I should take the drug on my next trip overseas.
Mark V. Dahl, MD
Interruption of long-term methotrexate treatment in psoriasis: evaluation of clinical course and laboratory parameters after discontinuation and reintroduction of weekly oral methotrexate Van Dooren-Greebe RJ, Kuijpers ALA, Termoshuizen F, et al. Acta D e r m Venereol (Stockh) 1995; 75:393-6. This retrospective study examined parameters after methotrexate had been discontinued in 10 patients with psoriasis who had been receiving long-term (mean, 12.7 years) weekly oral methotrexate (weekly divided dose, up to 15 mg per week). Three of the 10 patients had a relapse within 4 weeks; the remaining seven patients were able to remain methotrexate free for at least 11 weeks. The lower the dose before discontinuation allowed more weeks free of therapy. Laboratory parameters showed a significant decrease in serum transaminase levels in the first 3 weeks without therapy. The authors conclude that interruption of methotrexate treatment leads to reduced cumulative dose and potential for hepatotoxicity. However, overall 7 of the 10 patients preferred continuous methotrexate therapy.
A double-blind, placebo-controlled, crossover study was conducted on 34 women with herpes simplex virus type 2 (HSV-2) antibody only and genital herpes of less than 2 years' duration. Participants were randomly chosen to receive either (1) acyclovir, 400 mg twice daily for 70 days, followed by a "washout period" of 14 days, followed by placebo for 70 days or (2) the placebo first and acyclovir second. The women themselves collected daily genital swabs from their ~alvas, perianal fossa, and cervicovaginal areas, maintained a diary, and were examined at times of recurrences. Fifteen of the 17 women who received placebo had at least 1 day of subclinical shedding compared with 3 of 17 women in the acyclovirtreated group (p <0.001). In the placebo group, asymptomatic shedding occurred on 6.9% of all days compared with 0.03% of days in subjects taking acyclovir. The crossover confirmed the results in paired sample analysis. Haft of the culture-positive episodes occurred without discernible lesions. COMMZIWr: Acyclovir reduces but does not completely stop subclinical shedding of HSV-2. The hope is that failures might have been due to compliance problems or bowel absorption problems. The authors caution all patients with HSV-2 infections "to use condoms at all times and abstain from sexual intercourse during recurrences."
Mark V. Dahl, MD
Ability of primary care physicians to recognize physical findings associated with HIV infection Pauuw DS, Wenrich MD, Curtis JR, et al. J A M A 1995;274:1380-2. One hundred thirty-four general internists or family practitioners examined standardized patients as part of a study. The patients presented histories that were designed to direct physicians to anatomic areas with positive physical findings (oral hairy leukoplakia, Kaposi's sarcoma,