- Email: [email protected]
MINOXIDIL FOR MALE-PATTERN BALDNESS
1436
change in infusion frequency, dose (0-2 g/kg of Scottish National Blood Transfusion Service IgG), or preinfusion serum concentrations of IgG (38-5-5 gjl).2 Roifman and colleagues’ article illustrates the importance of the early diagnosis of hypogammaglobulinaemia. Paediatricians, earnose-and-throat surgeons, chest and general physicians-to whom such patients with chronic and recurrent acute bacterial infection present-should seek to measure immunoglobulin concentrations early in their management, given the safety3,4 and efficacy of replacement therapy in this condition, especially when started soon after the onset of infections. Blood Transfusion
Centre,
Royal Infirmary,
Edinburgh EH3 9HB
P. E. WILLIAMS P. L. YAP D. B. L. MCCLELLAND
1. Hill SL, Morrison HM, Burnett D, Stockley RA. Short term response of patients with bronchiectasis to treatment with amoxyrillin given in standard or high doses orally or by inhalation. Thorax 1986; 41: 559-65. 2. Leen CLS, Yap PL, McClelland DBL. Increase of serum immunoglobulin level into the normal range m primary hypogammaglobulinaemia by dosage individualisation of intravenous immunoglobulin. Vox Sang 1986; 51: 278-86. 3. Leen CLS, Yap PL, Williams PE, McClelland DBL. Tolerance of SNBTS intravenous immunoglobulin in patients with primary hypogammaglobulinaemia: Report of 1235 infusions. Scott Med J (in press). 4. Leen CLS, Yap PL, Neill G, McClelland DBL, Westwood A. Serum ALT levels in patients with primary hypogammaglobulinaemia receiving replacement therapy with intravenous immunoglobulin or fresh frozen plasma. Vox Sang 1986; 50: 26-32.
ALOPECIA AFTER IMMUNOGLOBULIN INFUSION
SIR,-Intravenous immunoglobulin is a recognised treatment for thrombocytopenic purpura (ITP).l Adverse effects are uncommon and immunoglobulin is generally regarded to be safe. We report three cases of alopecia developing after infusion of immunoglobulin. Three women (aged 19,42, and 61) with ITP were treated with intravenous immunoglobulin prepared by the Scottish National Blood Transfusion Service (pH4/pepsin treated).2 All achieved a autoimmune
temporary rise to normal platelet counts. Within 1-4 weeks of treatment, the patients complained of diffuse alopecia. Two of them were examined by a dermatologist, who noted telogen hair fall. In the two cases scalp biopsy was done 6 weeks to 2 months after immunoglobulin infusion, and histology revealed no abnormality. Immunoglobulin deposition around the follicles was not seen by immunofluorescent technique (university department of dermatology, Glasgow). The alopecia resolved within 4 months. These patients were taking 5-20 mg prednisolone at the time of immunoglobulin infusion. The combination may have been responsible but prednisolone is not a known cause of alopecia. The Committee on Safety of Medicines has been notified of one case of alopecia after ’Kabiglobulin’ and the manufacturers of ’Sandoglobulin’ have also had one report of alopecia. An immunological basis for the alopecia remains possible despite the negative immunofluorescent studies; perhaps these would have been more informative if they had been done immediately after the infusion. Departments of Haematology and Dermatology, Monklands District General Hospital, Airdrie ML6 0JS
D. CHAN-LAM E. J. FITZSIMONS W. S. DOUGLAS
1. Imbach P, Miller B, Imholz B, Wagner HP. Intravenous immunoglobulin therapy in immune thrombocytopenic purpura and other immune related haemorrhagic disorders in childhood. In: Morrell A, Nydegger UE, eds. Clinical use of intravenous immunoglobulin. London: Academic Press, 1986: 177-85. 2. Cuthbertson B, Perry RJ, Foster PR, Reid KG, Crawford RJ, Yap PL. Factors influencing the viral safety of intravenous immunoglobulin. J Infect (in press). 3. Joint Formulary Committee. Corticosteroids. In: British National Formulary no 13. London: British Medical Association/Pharmaceutical Society of Great Britain, 1987: 236-42.
MINOXIDIL FOR MALE-PATTERN BALDNESS
SiR,—We wish
the survey of selected published androgenetic alopecia by Dr de Groot and colleagues (May 2, p 1019). These workers calculate responses to treatment in a manner we find difficult to interpret. They make three calculations: (1) they divide change in terminal hair count in articles
on
to comment on
minoxidil in
treated with minoxidil by follicle density in non-balding (2) they divide absolute post-treatment terminal hair counts in bald men by follicle density in non-balding men; and (3) they divide both changes and absolute values of non-vellus hair counts by the bald
men
men;
same
denominator
as
above. The denominator chosen is follicle
density in non-balding men, a rounded-up overestimate of a figure to which they refer (485/cnr’). In balding scalps the follicle density is reduced and in one study was reported as 250/cm compared with 400/cm2 in normal controls in the same study.l de Groot et al that one countable terminal hair emanates from each follicle. reality, some follicles will have no visible hairs present and in others there may be more than one hair per follicle. Vellus and indeterminate hairs will also be present. Some of the former will not be visible (ie, countable). We cannot meaningfully interpret the ratios calculated by de Groot and colleagues as measures of response. The counts referred to by de Groot and colleagues show that there is approximately a doubling of the existing terminal hairs on treatment with topical minoxidil (’Regaine’). We suggest that this simple approach is more helpful to the reader. Although de Groot and colleagues are conservative in their approach, they consider topical minoxidil reasonably safe and do offer some constructive suggestions on marketing the product. assume
In
Upjohn Ltd, Crawley, West Sussex RH10 2NJ 1.
A. D. MITCHELL R. DE VILLEZ
Headington JT, Novak E. Clinical and histologic studies of male pattern baldness treated with topical minoxidil. Curr Ther Res 1984; 36: 1098-106.
EXPOSURE TO BENZODIAZEPINES IN UTERO
SIR,-Laegreid et all describe abnormalities in infants exposed to benzodiazepines in utero. As they note, the detection of the "dysmorphic signs" was not population based and was dependent upon clinical observation and subject to referral (centripetal) bias. The article implies a frequency of a syndrome with benzodiazepine use of 7 out of 36 cases (30 in study B and 6 in study A). Benzodiazepine abuse was implied. However, if use of abusive substances was denied, only benzodiazepines were tested for. Some bias resulted since not all patients had blood tested for benzodiazepines. The number of patients using or testing positive for benzodiazepines might have been higher and the occurrence rate of abnormalities lower. Additionally, polydrug abuse is common. Perhaps a "street drug" might have had a higher association with the syndrome suggested in the letter. Perhaps such abuse might also involve abuse of intravenous substances which would increase the chance for viruses such as cytomegalovirus, hepatitis virus, or human immunodeficiency virus. A pharmaceutical company, like a genetic referral centre, suffers from centripetal bias, seeing a predominance of retrospective (outcome already known) reports of congenital abnormalities. Abnormalities are focused on and referred to specialists (as in Laegreid’s letter). By contrast, a drug-exposed mother delivered of a normal child tends to get "lost" in the physician’s files. There is also the concern for congenital abnormalities and withdrawal problems with benzodiazepines.2 Possibly because of this concern, Upjohn has had a surprisingly atypical number of "prospective" reports (received during the pregnancy with outcome undetermined) of exposure in utero to benzodiazepines. Experience with the two short-life benzodiazepines we manufacture appears different from Laegreid’s. By the end of 1986, we had received 441 reports of exposure in utero to alprazolam or triazolam tablets through our worldwide voluntary reporting system. Almost all reports are US prospective cases with exposure during the first trimester. Blood testing to verify use of alprazolam, triazolam, or other concurrent drugs was not done. Most of the pregnant women discontinued use during their first trimester when pregnancy was diagnosed. About two dozen patients continued alprazolam use throughout the pregnancy. About one-fifth of all reported cases are still awaiting the outcome of the pregnancy. One-sixth of the cases reported have been lost to follow-up and another one-sixth of the cases have had an elective abortion, for various reasons. There have been 16 reports of
change in infusion frequency, dose (0-2 g/kg of Scottish National Blood Transfusion Service IgG), or preinfusion serum concentrations of IgG (38-5-5 gjl).2 Roifman and colleagues’ article illustrates the importance of the early diagnosis of hypogammaglobulinaemia. Paediatricians, earnose-and-throat surgeons, chest and general physicians-to whom such patients with chronic and recurrent acute bacterial infection present-should seek to measure immunoglobulin concentrations early in their management, given the safety3,4 and efficacy of replacement therapy in this condition, especially when started soon after the onset of infections. Blood Transfusion
Centre,
Royal Infirmary,
Edinburgh EH3 9HB
P. E. WILLIAMS P. L. YAP D. B. L. MCCLELLAND
1. Hill SL, Morrison HM, Burnett D, Stockley RA. Short term response of patients with bronchiectasis to treatment with amoxyrillin given in standard or high doses orally or by inhalation. Thorax 1986; 41: 559-65. 2. Leen CLS, Yap PL, McClelland DBL. Increase of serum immunoglobulin level into the normal range m primary hypogammaglobulinaemia by dosage individualisation of intravenous immunoglobulin. Vox Sang 1986; 51: 278-86. 3. Leen CLS, Yap PL, Williams PE, McClelland DBL. Tolerance of SNBTS intravenous immunoglobulin in patients with primary hypogammaglobulinaemia: Report of 1235 infusions. Scott Med J (in press). 4. Leen CLS, Yap PL, Neill G, McClelland DBL, Westwood A. Serum ALT levels in patients with primary hypogammaglobulinaemia receiving replacement therapy with intravenous immunoglobulin or fresh frozen plasma. Vox Sang 1986; 50: 26-32.
ALOPECIA AFTER IMMUNOGLOBULIN INFUSION
SIR,-Intravenous immunoglobulin is a recognised treatment for thrombocytopenic purpura (ITP).l Adverse effects are uncommon and immunoglobulin is generally regarded to be safe. We report three cases of alopecia developing after infusion of immunoglobulin. Three women (aged 19,42, and 61) with ITP were treated with intravenous immunoglobulin prepared by the Scottish National Blood Transfusion Service (pH4/pepsin treated).2 All achieved a autoimmune
temporary rise to normal platelet counts. Within 1-4 weeks of treatment, the patients complained of diffuse alopecia. Two of them were examined by a dermatologist, who noted telogen hair fall. In the two cases scalp biopsy was done 6 weeks to 2 months after immunoglobulin infusion, and histology revealed no abnormality. Immunoglobulin deposition around the follicles was not seen by immunofluorescent technique (university department of dermatology, Glasgow). The alopecia resolved within 4 months. These patients were taking 5-20 mg prednisolone at the time of immunoglobulin infusion. The combination may have been responsible but prednisolone is not a known cause of alopecia. The Committee on Safety of Medicines has been notified of one case of alopecia after ’Kabiglobulin’ and the manufacturers of ’Sandoglobulin’ have also had one report of alopecia. An immunological basis for the alopecia remains possible despite the negative immunofluorescent studies; perhaps these would have been more informative if they had been done immediately after the infusion. Departments of Haematology and Dermatology, Monklands District General Hospital, Airdrie ML6 0JS
D. CHAN-LAM E. J. FITZSIMONS W. S. DOUGLAS
1. Imbach P, Miller B, Imholz B, Wagner HP. Intravenous immunoglobulin therapy in immune thrombocytopenic purpura and other immune related haemorrhagic disorders in childhood. In: Morrell A, Nydegger UE, eds. Clinical use of intravenous immunoglobulin. London: Academic Press, 1986: 177-85. 2. Cuthbertson B, Perry RJ, Foster PR, Reid KG, Crawford RJ, Yap PL. Factors influencing the viral safety of intravenous immunoglobulin. J Infect (in press). 3. Joint Formulary Committee. Corticosteroids. In: British National Formulary no 13. London: British Medical Association/Pharmaceutical Society of Great Britain, 1987: 236-42.
MINOXIDIL FOR MALE-PATTERN BALDNESS
SiR,—We wish
the survey of selected published androgenetic alopecia by Dr de Groot and colleagues (May 2, p 1019). These workers calculate responses to treatment in a manner we find difficult to interpret. They make three calculations: (1) they divide change in terminal hair count in articles
on
to comment on
minoxidil in
treated with minoxidil by follicle density in non-balding (2) they divide absolute post-treatment terminal hair counts in bald men by follicle density in non-balding men; and (3) they divide both changes and absolute values of non-vellus hair counts by the bald
men
men;
same
denominator
as
above. The denominator chosen is follicle
density in non-balding men, a rounded-up overestimate of a figure to which they refer (485/cnr’). In balding scalps the follicle density is reduced and in one study was reported as 250/cm compared with 400/cm2 in normal controls in the same study.l de Groot et al that one countable terminal hair emanates from each follicle. reality, some follicles will have no visible hairs present and in others there may be more than one hair per follicle. Vellus and indeterminate hairs will also be present. Some of the former will not be visible (ie, countable). We cannot meaningfully interpret the ratios calculated by de Groot and colleagues as measures of response. The counts referred to by de Groot and colleagues show that there is approximately a doubling of the existing terminal hairs on treatment with topical minoxidil (’Regaine’). We suggest that this simple approach is more helpful to the reader. Although de Groot and colleagues are conservative in their approach, they consider topical minoxidil reasonably safe and do offer some constructive suggestions on marketing the product. assume
In
Upjohn Ltd, Crawley, West Sussex RH10 2NJ 1.
A. D. MITCHELL R. DE VILLEZ
Headington JT, Novak E. Clinical and histologic studies of male pattern baldness treated with topical minoxidil. Curr Ther Res 1984; 36: 1098-106.
EXPOSURE TO BENZODIAZEPINES IN UTERO
SIR,-Laegreid et all describe abnormalities in infants exposed to benzodiazepines in utero. As they note, the detection of the "dysmorphic signs" was not population based and was dependent upon clinical observation and subject to referral (centripetal) bias. The article implies a frequency of a syndrome with benzodiazepine use of 7 out of 36 cases (30 in study B and 6 in study A). Benzodiazepine abuse was implied. However, if use of abusive substances was denied, only benzodiazepines were tested for. Some bias resulted since not all patients had blood tested for benzodiazepines. The number of patients using or testing positive for benzodiazepines might have been higher and the occurrence rate of abnormalities lower. Additionally, polydrug abuse is common. Perhaps a "street drug" might have had a higher association with the syndrome suggested in the letter. Perhaps such abuse might also involve abuse of intravenous substances which would increase the chance for viruses such as cytomegalovirus, hepatitis virus, or human immunodeficiency virus. A pharmaceutical company, like a genetic referral centre, suffers from centripetal bias, seeing a predominance of retrospective (outcome already known) reports of congenital abnormalities. Abnormalities are focused on and referred to specialists (as in Laegreid’s letter). By contrast, a drug-exposed mother delivered of a normal child tends to get "lost" in the physician’s files. There is also the concern for congenital abnormalities and withdrawal problems with benzodiazepines.2 Possibly because of this concern, Upjohn has had a surprisingly atypical number of "prospective" reports (received during the pregnancy with outcome undetermined) of exposure in utero to benzodiazepines. Experience with the two short-life benzodiazepines we manufacture appears different from Laegreid’s. By the end of 1986, we had received 441 reports of exposure in utero to alprazolam or triazolam tablets through our worldwide voluntary reporting system. Almost all reports are US prospective cases with exposure during the first trimester. Blood testing to verify use of alprazolam, triazolam, or other concurrent drugs was not done. Most of the pregnant women discontinued use during their first trimester when pregnancy was diagnosed. About two dozen patients continued alprazolam use throughout the pregnancy. About one-fifth of all reported cases are still awaiting the outcome of the pregnancy. One-sixth of the cases reported have been lost to follow-up and another one-sixth of the cases have had an elective abortion, for various reasons. There have been 16 reports of