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Minocycline in Acne Is Still an Issue

Minocycline in Acne Is Still an Issue Minocycline and lupuslike syndrome in acne patientsSturkenboom MC, Meier CR, Jick H, Stricker BHArch Intern Med. 1999;159:493-497 The objective of this case-control study was to compare the risk of developing a lupuslike syndrome in patients with acne following exposure to minocycline or other tetracyclines with that in nonexposed subjects. The study population consisted of a cohort of 27,688 patients with acne aged 15 to 29 years, identified in the General Practice Research Database, currently owned by the UK Department of Health, London. This database includes medical records of more than 4 million people in the United Kingdom, provided anonymously by a selected group of general practitioners trained to record medical medical information in a standardized way. For this study, 319 practices contributed information between January 1991 to February 1996. From this cohort the authors, blinded to any tetracycline exposure, identified all patients with a first-time diagnosis of systemic lupus erythematosus or polyarthralgia/polyarthritis and obtained from general practitioners all medical records and laboratory reports for review. Cases were included if they had negative findings in a rheumatoid arthritis test or latex agglutination test, positive or unmeasured antinuclear antibodies, elevated or unmeasured erythrocyte sedimentation rate, or absent or unmeasured anti-DNA antibodies. Eight controls were matched with each patient by practice, age, and sex. Exposure to minocycline, tetracycline, oxytetracycline, doxycycline, and other drugs known to cause drug-induced lupus was assessed from the computer records. Drug use was classified as current or past (stopped more than 2 weeks before the index date). The cumulative exposure was calculated by summing up the total defined daily doses (defined according to the World Health Organization Collaborating Centre for Drug Statistics Methodology, Oslo, Norway) and categorized as 100 or lower, or higher than 100. If more than 1 type of tetracycline was used, the doses were summed as well, but the subject was classified as a multiple user. After manual review of the computerized patient profiles, 29 patients who presented with a lupuslike syndrome and 152 controls were included in this analysis. The risks and 95% confidence intervals (CIs) of lupuslike syndrome associated with current use of any tetracyclines were 32.7 (14.9-62.1) per 100,000 prescriptions among female patients and 2.3 (1.0-13.0) among male patients. The risks for specific tetracyclines among women were 17.2 (2.1-62.1) cases per 100,000 prescriptions among oxytetracycline users, and 52.8 (19.4-115.0) cases per 100,000 prescriptions among minocycline users. The analysis findings of the case-control data showed that the odds ratio (OR) of lupuslike syndrome for current use of any tetracyclines compared with nonuse was 3.5 (95% CI, 1.3-7.0). Past use of any tetracyclines presented an OR of 1.3 (95% CI, 0.5-3.3). Of individual tetracyclines, the OR for current single use of minocycline was 8.5 (95% CI, 2.1-35.0) compared with nonuse or past use of all tetracyclines combined. Current use of doxycycline, oxytetracycline, or tetracycline combined was associated with an OR of 1.7 (95% CI, 0.4-8.1). In the stratified results for the number of cumulative defined daily doses, the OR associated with current use of minocycline with more than 100 defined daily doses was 16.0 (95% CI, 1.5-175.0), whereas that associated with less than 100 defined daily doses was 6.1 (95% CI 1.1-33.0). Including in the logistic model the use of other drugs that have been associated with drug-induced lupus, such as ibuprofen, oral contraceptives, and penicillins, did not change the estimates. No association was found with cigarette smoking. The authors conclude that the risk of lupuslike syndrome was increased 8.5 fold in young women currently using minocycline for acne compared with nonusers or past users, and that this effect is strongest for longer-term use. They also state that since lupuslike syndrome is uncommon and reversible after stopping minocycline treatment, the increased risk associated with minocycline use only moderately affects the risk/benefit balance associated with the treatment of acne with this widely used drug. Editor's Comment A case of minocycline-related lupus was first described in 1992 in a 22-year-old Japanese woman by Matsuura et al1 in a letter to the Lancet. A direct relationship between minocycline use and drug-related lupus was then proposed in 1994 by Byrne et al,2 who reported 5 cases of lupuslike syndrome in young female patients who had been taking minocycline for several years. Since then, several cases of minocycline-related autoimmune diseases have been reported.3-20 An article by Gough et al6 published in January 1996 in the British Medical Journal, reported that as of April 1994, 11 cases of minocycline-induced lupus erythematosus and 16 cases of autoimmune hepatitis had been reported in England to the Committee on Safety of Medicines. Among them, 2 patients died while taking the drug for acne, and another patient needed a liver transplant. Following this publication, a marked drop in minocycline prescription occurred in the United Kingdom, as documented in a letter by Ferguson et al21 from the Prescription Pricing Authority of Newcastle upon Tyne, United Kingdom, published in the British Medical Journal in 1998. In a recent review of 82 published cases of minocycline-related autoimmune diseases,22 4 syndromes have been identified: drug-induced lupus, autoimmune hepatitis, serum sickness, and vasculitis, all of which occurred in patients treated for acne. Antinuclear antibodies and antineutrophil cytoplasmic antibodies were present in over 90% of serum samples. Most recently, in a report of 14 British cases,23 HLA class II typing demonstrated that all of the 13 patients tested were either DR4+ or DR2+, supporting the hypothesis of a genetic susceptibility to minocycline-induced autoimmune diseases. The article by Sturkenboom and colleagues summarized above is the only analytical study that provides an estimate of the relative risk of lupuslike syndrome occurrence in young women exposed to long-term use of minocycline for treatment of acne, and substantiates the warnings coming from case series reports. Despite its limitations, mainly the rather unspecific case definition and lack of information on antinuclear antibody test results in most of the cases, the finding of an 8.5-fold increased risk of lupuslike syndrome for single use of minocycline confirms the unusual propensity of this drug for causing potentially serious adverse reactions. Although these reactions are relatively rare (but likely underreported), and seem to occur in genetically predisposed individuals, they raise concerns about the safety of minocycline for treating young people for an essentially benign condition such as acne. Because there is no way to preventively identify subjects at risk for drug-related lupus (with the exception of those with a family history of systemic lupus erythematosus), it is advisable that dermatologists use caution when prescribing a long-term minocycline treatment for acne and consider safer alternative drugs. A cooperative effort of the Clinical Epidemiology Unit of the Istituto Dermopatico dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico (IDI-IRCCS) and the Archives of Dermatology References 1. Matsuura TShimizu YFujimoto HMiyazaki TKano S Minocycline-related lupus [letter]. Lancet. 1992;3401553Google ScholarCrossref 2. Byrne PAWilliams BDPritchard MH Minocycline-related lupus. Br J Rheumatol. 1994;33674- 676Google ScholarCrossref 3. Inoue CNKondo YSuwabe NIgarashi YTada K Minocycline-related lupus in childhood [letter]. Eur J Pediatr. 1994;153540Google ScholarCrossref 4. Quilty BMcHugh N Lupus-like syndrome associated with the use of minocycline. Br J Rheumatol. 1994;331197- 1198Google ScholarCrossref 5. Gordon PMWhite MIHerriot RMartin JCReid DM Minocycline-associated lupus erythematosus. Br J Dermatol. 1995;132120- 121Google ScholarCrossref 6. Gough AChapman SWagstaff KEmery PElias E Minocycline-induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome. BMJ. 1996;312169- 172Google ScholarCrossref 7. Knowles SRShapiro LShear NH Serious adverse reactions induced by minocycline: report of 13 patients and review of the literature. Arch Dermatol. 1996;132934- 939Google ScholarCrossref 8. Masson CChevailter APascaretti CLegrand EBregeon CAudran M Minocycline related lupus. J Rheumatol. 1996;232160- 2161Google Scholar 9. Golstein PEDeviere JCremer M Acute hepatitis and drug-related lupus induced by minocycline treatment. Am J Gastroenterol. 1997;92143- 146Google Scholar 10. Singer SJPiazza-Hepp TDGirardi LSMoledina NR Lupuslike reaction associated with minocycline. JAMA. 1997;277295- 296Google ScholarCrossref 11. Crosson JStillman MT Minocycline-related lupus erythematosus with associated liver disease. J Am Acad Dermatol. 1997;36 ((5 pt 2)) 867- 868Google ScholarCrossref 12. Farver DK Minocycline-induced lupus. Ann Pharmacother. 1997;311160- 1163Google Scholar 13. Shapiro LEKnowles SRShear NH Comparative safety of tetracycline, minocycline, and doxycycline. Arch Dermatol. 1997;1331224- 1230Google ScholarCrossref 14. Akin EMiller LCTucker LB Minocycline-induced lupus in adolescents. Pediatrics. 1998;101926- 928Google ScholarCrossref 15. Knights SELeandro MJKhamashta MAHughes GR Minocycline-induced arthritis. Clin Exp Rheumatol. 1998;16587- 590Google Scholar 16. Christodoulou CSEmmanuel PRay RAGood RASchnapf BMCawkwell GD Respiratory distress due to minocycline-induced pulmonary lupus. Chest. 1999;1151471- 1473Google ScholarCrossref 17. Schrodt BJKulp-Shorten CLCallen JP Necrotizing vasculitis of the skin and uterine cervix associated with minocycline therapy for acne vulgaris. South Med J. 1999;92502- 504Google ScholarCrossref 18. Piette AMRamanoelina JGepner PLarroche CBletry O Systemic reaction induced my minocycline treatment: a report of four patients and a review of the literature. Rev Med Interne. 1999;20869- 874Google ScholarCrossref 19. Dadamessi ILeduc IDuche A et al. Autoimmune hepatitis and lupus syndrome associated with minocycline. Rev Med Interne. 1999;20930- 933Google ScholarCrossref 20. Tournigand CGenereau TPrudent MDiemert MCHerson SChosidow O Minocycline-induced clinical and biological lupuslike disease. Lupus. 1999;8773- 774Google ScholarCrossref 21. Ferguson JJJenkins MGVField J Paper in BMJ influenced prescribing of minocycline. BMJ. 1998;31672- 73Google ScholarCrossref 22. Elkayam OYaron MCaspi D Minocycline-induced autoimmune syndromes: an overview. Semin Arthritis Rheum 1999;28392- 397Google ScholarCrossref 23. Dunphy JOliver MRands ALLovell CRMcHugh NJ Antineutrophil cytoplasmic antibodies and HI-A class II alleles in minocycline-induced lupuslike syndrome. Br J Dermatol. 2000;142461- 467Google ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Minocycline in Acne Is Still an Issue

Archives of Dermatology , Volume 136 (9) – Sep 1, 2000

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References (26)

Publisher
American Medical Association
Copyright
Copyright © 2000 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.136.9.1143
Publisher site
See Article on Publisher Site

Abstract

Minocycline and lupuslike syndrome in acne patientsSturkenboom MC, Meier CR, Jick H, Stricker BHArch Intern Med. 1999;159:493-497 The objective of this case-control study was to compare the risk of developing a lupuslike syndrome in patients with acne following exposure to minocycline or other tetracyclines with that in nonexposed subjects. The study population consisted of a cohort of 27,688 patients with acne aged 15 to 29 years, identified in the General Practice Research Database, currently owned by the UK Department of Health, London. This database includes medical records of more than 4 million people in the United Kingdom, provided anonymously by a selected group of general practitioners trained to record medical medical information in a standardized way. For this study, 319 practices contributed information between January 1991 to February 1996. From this cohort the authors, blinded to any tetracycline exposure, identified all patients with a first-time diagnosis of systemic lupus erythematosus or polyarthralgia/polyarthritis and obtained from general practitioners all medical records and laboratory reports for review. Cases were included if they had negative findings in a rheumatoid arthritis test or latex agglutination test, positive or unmeasured antinuclear antibodies, elevated or unmeasured erythrocyte sedimentation rate, or absent or unmeasured anti-DNA antibodies. Eight controls were matched with each patient by practice, age, and sex. Exposure to minocycline, tetracycline, oxytetracycline, doxycycline, and other drugs known to cause drug-induced lupus was assessed from the computer records. Drug use was classified as current or past (stopped more than 2 weeks before the index date). The cumulative exposure was calculated by summing up the total defined daily doses (defined according to the World Health Organization Collaborating Centre for Drug Statistics Methodology, Oslo, Norway) and categorized as 100 or lower, or higher than 100. If more than 1 type of tetracycline was used, the doses were summed as well, but the subject was classified as a multiple user. After manual review of the computerized patient profiles, 29 patients who presented with a lupuslike syndrome and 152 controls were included in this analysis. The risks and 95% confidence intervals (CIs) of lupuslike syndrome associated with current use of any tetracyclines were 32.7 (14.9-62.1) per 100,000 prescriptions among female patients and 2.3 (1.0-13.0) among male patients. The risks for specific tetracyclines among women were 17.2 (2.1-62.1) cases per 100,000 prescriptions among oxytetracycline users, and 52.8 (19.4-115.0) cases per 100,000 prescriptions among minocycline users. The analysis findings of the case-control data showed that the odds ratio (OR) of lupuslike syndrome for current use of any tetracyclines compared with nonuse was 3.5 (95% CI, 1.3-7.0). Past use of any tetracyclines presented an OR of 1.3 (95% CI, 0.5-3.3). Of individual tetracyclines, the OR for current single use of minocycline was 8.5 (95% CI, 2.1-35.0) compared with nonuse or past use of all tetracyclines combined. Current use of doxycycline, oxytetracycline, or tetracycline combined was associated with an OR of 1.7 (95% CI, 0.4-8.1). In the stratified results for the number of cumulative defined daily doses, the OR associated with current use of minocycline with more than 100 defined daily doses was 16.0 (95% CI, 1.5-175.0), whereas that associated with less than 100 defined daily doses was 6.1 (95% CI 1.1-33.0). Including in the logistic model the use of other drugs that have been associated with drug-induced lupus, such as ibuprofen, oral contraceptives, and penicillins, did not change the estimates. No association was found with cigarette smoking. The authors conclude that the risk of lupuslike syndrome was increased 8.5 fold in young women currently using minocycline for acne compared with nonusers or past users, and that this effect is strongest for longer-term use. They also state that since lupuslike syndrome is uncommon and reversible after stopping minocycline treatment, the increased risk associated with minocycline use only moderately affects the risk/benefit balance associated with the treatment of acne with this widely used drug. Editor's Comment A case of minocycline-related lupus was first described in 1992 in a 22-year-old Japanese woman by Matsuura et al1 in a letter to the Lancet. A direct relationship between minocycline use and drug-related lupus was then proposed in 1994 by Byrne et al,2 who reported 5 cases of lupuslike syndrome in young female patients who had been taking minocycline for several years. Since then, several cases of minocycline-related autoimmune diseases have been reported.3-20 An article by Gough et al6 published in January 1996 in the British Medical Journal, reported that as of April 1994, 11 cases of minocycline-induced lupus erythematosus and 16 cases of autoimmune hepatitis had been reported in England to the Committee on Safety of Medicines. Among them, 2 patients died while taking the drug for acne, and another patient needed a liver transplant. Following this publication, a marked drop in minocycline prescription occurred in the United Kingdom, as documented in a letter by Ferguson et al21 from the Prescription Pricing Authority of Newcastle upon Tyne, United Kingdom, published in the British Medical Journal in 1998. In a recent review of 82 published cases of minocycline-related autoimmune diseases,22 4 syndromes have been identified: drug-induced lupus, autoimmune hepatitis, serum sickness, and vasculitis, all of which occurred in patients treated for acne. Antinuclear antibodies and antineutrophil cytoplasmic antibodies were present in over 90% of serum samples. Most recently, in a report of 14 British cases,23 HLA class II typing demonstrated that all of the 13 patients tested were either DR4+ or DR2+, supporting the hypothesis of a genetic susceptibility to minocycline-induced autoimmune diseases. The article by Sturkenboom and colleagues summarized above is the only analytical study that provides an estimate of the relative risk of lupuslike syndrome occurrence in young women exposed to long-term use of minocycline for treatment of acne, and substantiates the warnings coming from case series reports. Despite its limitations, mainly the rather unspecific case definition and lack of information on antinuclear antibody test results in most of the cases, the finding of an 8.5-fold increased risk of lupuslike syndrome for single use of minocycline confirms the unusual propensity of this drug for causing potentially serious adverse reactions. Although these reactions are relatively rare (but likely underreported), and seem to occur in genetically predisposed individuals, they raise concerns about the safety of minocycline for treating young people for an essentially benign condition such as acne. Because there is no way to preventively identify subjects at risk for drug-related lupus (with the exception of those with a family history of systemic lupus erythematosus), it is advisable that dermatologists use caution when prescribing a long-term minocycline treatment for acne and consider safer alternative drugs. A cooperative effort of the Clinical Epidemiology Unit of the Istituto Dermopatico dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico (IDI-IRCCS) and the Archives of Dermatology References 1. Matsuura TShimizu YFujimoto HMiyazaki TKano S Minocycline-related lupus [letter]. Lancet. 1992;3401553Google ScholarCrossref 2. Byrne PAWilliams BDPritchard MH Minocycline-related lupus. Br J Rheumatol. 1994;33674- 676Google ScholarCrossref 3. Inoue CNKondo YSuwabe NIgarashi YTada K Minocycline-related lupus in childhood [letter]. Eur J Pediatr. 1994;153540Google ScholarCrossref 4. Quilty BMcHugh N Lupus-like syndrome associated with the use of minocycline. Br J Rheumatol. 1994;331197- 1198Google ScholarCrossref 5. Gordon PMWhite MIHerriot RMartin JCReid DM Minocycline-associated lupus erythematosus. Br J Dermatol. 1995;132120- 121Google ScholarCrossref 6. Gough AChapman SWagstaff KEmery PElias E Minocycline-induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome. BMJ. 1996;312169- 172Google ScholarCrossref 7. Knowles SRShapiro LShear NH Serious adverse reactions induced by minocycline: report of 13 patients and review of the literature. Arch Dermatol. 1996;132934- 939Google ScholarCrossref 8. Masson CChevailter APascaretti CLegrand EBregeon CAudran M Minocycline related lupus. J Rheumatol. 1996;232160- 2161Google Scholar 9. Golstein PEDeviere JCremer M Acute hepatitis and drug-related lupus induced by minocycline treatment. Am J Gastroenterol. 1997;92143- 146Google Scholar 10. Singer SJPiazza-Hepp TDGirardi LSMoledina NR Lupuslike reaction associated with minocycline. JAMA. 1997;277295- 296Google ScholarCrossref 11. Crosson JStillman MT Minocycline-related lupus erythematosus with associated liver disease. J Am Acad Dermatol. 1997;36 ((5 pt 2)) 867- 868Google ScholarCrossref 12. Farver DK Minocycline-induced lupus. Ann Pharmacother. 1997;311160- 1163Google Scholar 13. Shapiro LEKnowles SRShear NH Comparative safety of tetracycline, minocycline, and doxycycline. Arch Dermatol. 1997;1331224- 1230Google ScholarCrossref 14. Akin EMiller LCTucker LB Minocycline-induced lupus in adolescents. Pediatrics. 1998;101926- 928Google ScholarCrossref 15. Knights SELeandro MJKhamashta MAHughes GR Minocycline-induced arthritis. Clin Exp Rheumatol. 1998;16587- 590Google Scholar 16. Christodoulou CSEmmanuel PRay RAGood RASchnapf BMCawkwell GD Respiratory distress due to minocycline-induced pulmonary lupus. Chest. 1999;1151471- 1473Google ScholarCrossref 17. Schrodt BJKulp-Shorten CLCallen JP Necrotizing vasculitis of the skin and uterine cervix associated with minocycline therapy for acne vulgaris. South Med J. 1999;92502- 504Google ScholarCrossref 18. Piette AMRamanoelina JGepner PLarroche CBletry O Systemic reaction induced my minocycline treatment: a report of four patients and a review of the literature. Rev Med Interne. 1999;20869- 874Google ScholarCrossref 19. Dadamessi ILeduc IDuche A et al. Autoimmune hepatitis and lupus syndrome associated with minocycline. Rev Med Interne. 1999;20930- 933Google ScholarCrossref 20. Tournigand CGenereau TPrudent MDiemert MCHerson SChosidow O Minocycline-induced clinical and biological lupuslike disease. Lupus. 1999;8773- 774Google ScholarCrossref 21. Ferguson JJJenkins MGVField J Paper in BMJ influenced prescribing of minocycline. BMJ. 1998;31672- 73Google ScholarCrossref 22. Elkayam OYaron MCaspi D Minocycline-induced autoimmune syndromes: an overview. Semin Arthritis Rheum 1999;28392- 397Google ScholarCrossref 23. Dunphy JOliver MRands ALLovell CRMcHugh NJ Antineutrophil cytoplasmic antibodies and HI-A class II alleles in minocycline-induced lupuslike syndrome. Br J Dermatol. 2000;142461- 467Google ScholarCrossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Sep 1, 2000

Keywords: acne vulgaris,minocycline

There are no references for this article.