212
CORRESPONDENCK
Oral contraceptives and antibiotics in acne SIR. The efficacy of the oral contraceptive pill in patients taking antibiotics' unfortunately remains unresolved. We have recently reported a possible case of contraceptive pill failure due to oral minocycline.- and have reviewed the literature on this controversial issue. We concluded that the risk of pregnancy attributable to the concomitant use of antibiotics appears to be very small, and suggested that these drugs can be safely prescribed. The patients should be made aware of the possibility, alheit remote, of a drug interaction. In another recent review the same conclusion was reached.' The study of I)rs Hughes and Cunliffe' certainly has obvious flaws. It is retrospective, involves only a small number of patients, and the results of questioning patients on past u.sage of antibiotics are not reliable unless they have a perfect memory. There were two pregnancies in an estimated 1 (i 3 woman years of continued pill-antibiotic combination. This represented a sixfold risk of pregnancy when compared to a normal failure rate, which was said to be 2 per 1 ()(){) woman years {/; test: Perience it is advisable to estimate the relative risk with an incidence density ratio rather than using /} statistics. With these data we came to a relative risk of 6-1 (9S%CI: ]-l-J4-()). Apparently, the effect is statistically only of borderline significance. Secondly, the authors did not interview a control group of women on contraceptive pills who had not used antibiotics concomitantly. The upper limit of the normal failure rate as quoted by the niEinufacturers of oral contraceptives is not necessarily the failure rate under everyday circumstances. The rate of unintended pregnancy has also been reported to be approximately 1%.* If this figure were to be used as normal failure rate, there would be no increased risk. As Ihey conclude that their results require further study, we feel that the advice against the use of oral antibiotics in acne subjects who are on oral contraceptives is premature. We fear that their advice may shift prescribing habits and result in the increased use of the teratogenic rctinoids in women of childbearing age. Lawyers in the U.S.A.. where 'suing your doctor' appears to have become a national sport.^ may well be grateful for this letter, but dermatologists most likely will not. Department of Dermatolaifij. Carohis Hospiliil. P.O.
Box
nOL
A.C.DK GKOOT H.RsHiiis B.H.C.STRI(KF.R
5200 BD 's-Hertogenhosch. The Ncthi'riands
References 1 Hught-'s liR, Ciinlifl'c VV], IiittTiictions between the oral contraceplivt' pill ami anlibiotk-s. Br I Denmitol 1990; 122: 717. 2 de Grool AC. F.shuis 11, Strieker BHC. Inefficacy oforai contraception during use of minocycline, ^cd T Ciciwi-skd 1990: 154: 1227-9. i fleischcr Ail |r. Resnifk SD. The efTect of antibiotics on the eflicLiey of oral contraceptives. A controversy rt-visiled. Arch IX-rwiitoI 1989: 12S: 1562-4.
4 Holiabaush KS. VVagni-r RF \T. Weeden VVV. Smith F,B. Patient personal injury liligation againsi dermaiology residency programs in the tJnited States. 19M-1988, Arch Ik'niuiwl 1990: 126: 618-622. ADONIS (H)O7O96391OOO5H
Successful treatment of alopecia areata using the contact allergen diphencyprone SIR. Diphencyprone (diphenylcyclopropenone-1) has been used successfully in Leeds for the treatment of alopecia areata |AA) and alopecia totaiis (AT) for J years. Currently we have 78 adult patients (1 7 male. f>l female) who have been treated with diphencyprone (Ul'C) for 8 months or longer. All patients recruited have had alopecia for a minimum of 6 months: the average duration of alopecia was 7 years (range ()• 5- i S years). Forty-live of the patients presented with AT and 3 i with AA. After 8 months of weekly therapy. 29 patients i22 AT. seven AA) showed no growth, but 49 (2 5 AT. 2f) AA) showed regrowth of hair. Twenty-five of these 49 achieved complete regrowth of scalp hair (18 AA. seven AT). Righteen of the 49 have good regrowth of scalp hair which is continuing to progress, and six have some regrowth ranging from sparse terminal hairs to patchy regrowth. Therefore, after a minimum of 8 months treatment with DPC 52% of patients showed regrowth: i2% had complete regrowth. 2 i% had good progressing regrowth and 8% had some regrowth. It would seem therefore, that in our hands DPC is a useful treatment for AA and AT. It continues to surprise us that our results are not mirrored in tjthcr centres.' A possible explanation for the differences in response to Di'C between various centres is patient selection: however, there was no signilicant difference in the duration of alopecia for those that regrew (mean 8 years) and those that did not (mean 10 years), upholding the observations made on our original cohort.Diphencyprone is obtainable commercially as a pure substance. However, each batch of the compound is analysed for impurities, in particular for the presence of the mutagenic precursor 7.aidibromodibenzylketone. Djphencyprone is stable and when in solution with acetone has a shelf-life of i months. provided that Jt is protected from UV-light by storage in amber glass bottles. All patients must be instructed to keep their heads covered for a minimum of 6 h post-therapy and advised not to wash their heads for 48 h after the application of DPC. Sensitization is achieved by applying a 2% solution to a small area on the scalp (4-cm diameter), and if this does not result in adequate sensitization the process is repeated beneath plastic occlusion. Thereafter, weaker concentrations of DPC are applied (O-Ol. ()-()25. 0-05-2%) and gradually increased in order to elicit erythema and pruritus in the area of treatment for Bf) h post-therapy. Only one side of the scalp is treated until the optimum concentration is found, to avoid the possibility of a widespread adverse reaction. Treatment is weekly. Signed informed consent is given by all patients. The need for adequate contraception is stressed and treatment does not start until a negative pregnancy test is received for patients of childbearing age. flaematologicai. hepatic and renal function
CORRESPONDENCK
Oral contraceptives and antibiotics in acne SIR. The efficacy of the oral contraceptive pill in patients taking antibiotics' unfortunately remains unresolved. We have recently reported a possible case of contraceptive pill failure due to oral minocycline.- and have reviewed the literature on this controversial issue. We concluded that the risk of pregnancy attributable to the concomitant use of antibiotics appears to be very small, and suggested that these drugs can be safely prescribed. The patients should be made aware of the possibility, alheit remote, of a drug interaction. In another recent review the same conclusion was reached.' The study of I)rs Hughes and Cunliffe' certainly has obvious flaws. It is retrospective, involves only a small number of patients, and the results of questioning patients on past u.sage of antibiotics are not reliable unless they have a perfect memory. There were two pregnancies in an estimated 1 (i 3 woman years of continued pill-antibiotic combination. This represented a sixfold risk of pregnancy when compared to a normal failure rate, which was said to be 2 per 1 ()(){) woman years {/; test: Perience it is advisable to estimate the relative risk with an incidence density ratio rather than using /} statistics. With these data we came to a relative risk of 6-1 (9S%CI: ]-l-J4-()). Apparently, the effect is statistically only of borderline significance. Secondly, the authors did not interview a control group of women on contraceptive pills who had not used antibiotics concomitantly. The upper limit of the normal failure rate as quoted by the niEinufacturers of oral contraceptives is not necessarily the failure rate under everyday circumstances. The rate of unintended pregnancy has also been reported to be approximately 1%.* If this figure were to be used as normal failure rate, there would be no increased risk. As Ihey conclude that their results require further study, we feel that the advice against the use of oral antibiotics in acne subjects who are on oral contraceptives is premature. We fear that their advice may shift prescribing habits and result in the increased use of the teratogenic rctinoids in women of childbearing age. Lawyers in the U.S.A.. where 'suing your doctor' appears to have become a national sport.^ may well be grateful for this letter, but dermatologists most likely will not. Department of Dermatolaifij. Carohis Hospiliil. P.O.
Box
nOL
A.C.DK GKOOT H.RsHiiis B.H.C.STRI(KF.R
5200 BD 's-Hertogenhosch. The Ncthi'riands
References 1 Hught-'s liR, Ciinlifl'c VV], IiittTiictions between the oral contraceplivt' pill ami anlibiotk-s. Br I Denmitol 1990; 122: 717. 2 de Grool AC. F.shuis 11, Strieker BHC. Inefficacy oforai contraception during use of minocycline, ^cd T Ciciwi-skd 1990: 154: 1227-9. i fleischcr Ail |r. Resnifk SD. The efTect of antibiotics on the eflicLiey of oral contraceptives. A controversy rt-visiled. Arch IX-rwiitoI 1989: 12S: 1562-4.
4 Holiabaush KS. VVagni-r RF \T. Weeden VVV. Smith F,B. Patient personal injury liligation againsi dermaiology residency programs in the tJnited States. 19M-1988, Arch Ik'niuiwl 1990: 126: 618-622. ADONIS (H)O7O96391OOO5H
Successful treatment of alopecia areata using the contact allergen diphencyprone SIR. Diphencyprone (diphenylcyclopropenone-1) has been used successfully in Leeds for the treatment of alopecia areata |AA) and alopecia totaiis (AT) for J years. Currently we have 78 adult patients (1 7 male. f>l female) who have been treated with diphencyprone (Ul'C) for 8 months or longer. All patients recruited have had alopecia for a minimum of 6 months: the average duration of alopecia was 7 years (range ()• 5- i S years). Forty-live of the patients presented with AT and 3 i with AA. After 8 months of weekly therapy. 29 patients i22 AT. seven AA) showed no growth, but 49 (2 5 AT. 2f) AA) showed regrowth of hair. Twenty-five of these 49 achieved complete regrowth of scalp hair (18 AA. seven AT). Righteen of the 49 have good regrowth of scalp hair which is continuing to progress, and six have some regrowth ranging from sparse terminal hairs to patchy regrowth. Therefore, after a minimum of 8 months treatment with DPC 52% of patients showed regrowth: i2% had complete regrowth. 2 i% had good progressing regrowth and 8% had some regrowth. It would seem therefore, that in our hands DPC is a useful treatment for AA and AT. It continues to surprise us that our results are not mirrored in tjthcr centres.' A possible explanation for the differences in response to Di'C between various centres is patient selection: however, there was no signilicant difference in the duration of alopecia for those that regrew (mean 8 years) and those that did not (mean 10 years), upholding the observations made on our original cohort.Diphencyprone is obtainable commercially as a pure substance. However, each batch of the compound is analysed for impurities, in particular for the presence of the mutagenic precursor 7.aidibromodibenzylketone. Djphencyprone is stable and when in solution with acetone has a shelf-life of i months. provided that Jt is protected from UV-light by storage in amber glass bottles. All patients must be instructed to keep their heads covered for a minimum of 6 h post-therapy and advised not to wash their heads for 48 h after the application of DPC. Sensitization is achieved by applying a 2% solution to a small area on the scalp (4-cm diameter), and if this does not result in adequate sensitization the process is repeated beneath plastic occlusion. Thereafter, weaker concentrations of DPC are applied (O-Ol. ()-()25. 0-05-2%) and gradually increased in order to elicit erythema and pruritus in the area of treatment for Bf) h post-therapy. Only one side of the scalp is treated until the optimum concentration is found, to avoid the possibility of a widespread adverse reaction. Treatment is weekly. Signed informed consent is given by all patients. The need for adequate contraception is stressed and treatment does not start until a negative pregnancy test is received for patients of childbearing age. flaematologicai. hepatic and renal function
