LETTRE
À LA
Thérapie DOI: 10.2515/therapie/2014025
RÉDACTION
© 2014 Société Française de Pharmacologie et de Thérapeutique
Lichen Associated with Metformin Ahmed Zaïem1,2, Rym Sahnoun1,2, Talel Badri2,3, Ghozlane Lakhoua1,2, Wafa Koubaa4, Sarrah Kastalli1,2, Riadh Daghfous1,2, Mohamed Lakhal1,2 and Sihem El Aidli1,2 1 National Center of Pharmacovigilance, Tunis, Tunisia 2 Tunis El Manar University, Medicine Faculty, Tunis, Tunisia 3 Dermatology Department, Habib Thameur Hospital, Tunis, Tunisia 4 Pathological Anatomy Laboratory, Habib Thameur Hospital, Tunis, Tunisia Fig. 1. The small papules presented by the patient.
Text received September 30th, 2013; accepted January 20th, 2014 The case was reported to the Tunisian National Pharmacovigilance Centre on April 8th, 2010 Abstract – We report an exceptional case of bullous lichen induced by metformin in a patient with diabetes mellitus. Keywords: metformin; bullous lichen; adverse effect Résumé – Lichen associé à la metformine. Nous rapportons un cas exceptionnel de lichen bulleux induit par la metformine chez une patiente diabétique. Mots clés : metformine ; lichen bulleux ; effet indésirable Abbreviations: see end of article.
1. Introduction Lichen is a chronic itching dermatosis characterized by shiny flat purplish blue polygonal papules affecting any part of the body but it is most likely to appear on the extension part of the limbs.[1] It can be induced by drugs such as antimalarial drugs, angiotensinconverting enzyme inhibitors and oral hypoglycemic drugs mainly with sulfonylureas.[2] There is only one case of lichen planus associated with metformin.[3] We report the first case of bullous lichen induced by metformin in a patient with diabetes mellitus.
later, the patient developed a general cutaneous eruption. The lesions consisted of small, shiny and polygonal papules associated with pinkish purplish blue papules in the limbs. Metformin was stopped and insulin therapy started. The eruption resolved spontaneously within 3 months after discontinuation of metformin. In February 2010, metformin was prescribed again at 1 700 mg/ day to reduce insulin resistance. One month after starting metformin therapy, the patient presented a general cutaneous eruption, similar to the one presented in 2007. The lesions consisted of small, shiny and polygonal papules associated with pinkish purplish blue papules in the limbs (figure 1). The patient developed also mucous lesions at the mouth and at the nose. A skin biopsy showed bullous lichen: focal lesions of hypertrophic acanthosis in the epidermis with lesions of junctional dermatitis represented by vacuolated keratinocytes and apoptotic bodies, sometimes responsible for a dermo-epidermal detachment (figures 2, 3). A lymphocytic infiltrate in band under epithelium was observed in the superficial dermis. The patient was treated by ultraviolet light B (UVB) therapy and the lesions healed one month after metformin withdrawal. Serological tests for infections (hepatitis B virus [HVB], hepatitis C virus [HVC], syphilis) were all negative. The case was reported to the Tunisian National Pharmacovigilance Centre and analyzed according to the French method of imputation.[4] The causality of metformin was retained with an imputation score of I2 (possible).
3. Discussion 2. Case report In 2007, a 58-year-old woman was treated for non-insulindependent diabetes mellitus by metformin 2 550 mg/day. One month
Lichenoïd eruption is an exceptional adverse drug reaction. The main implicated drugs are usually angiotensin-converting enzyme inhibitors (captopril), beta-blockers (practolol), anti-infectives (ethambutol, ketoconazole), non steroidal anti-inflammatory drugs
Article publié par EDP Sciences
2
Zaïem et al.
Fig. 2. Lesions of junctional dermatitis with vacuolated keratinocytes and a dermo-epidermal detachment.
(indomethacin), anti-malarial drugs (quinine) and heavy metals (gold).[5,6] Only one case of lichenoïd drug eruption induced by metformin was found in literature.[3] In this case, the patient was treated for diabetes since 5 years with glibenclamide. Two weeks after starting metformin at the dose of 1 700 mg/day, he presented purplish blue papules and small plaques with adherent scales and prominent skin markings lesions. The skin biopsy was consistent with lichen planus. Our case reported the occurrence of lichen after one month of metformin therapy. This delay was consistent with the literature data for lichenoïd eruption induced by other drugs: it usually varies between 1 week to 3 years.[1,5] In our case, the lesions consisted of bullous lichen. In literature, lichen is always planus which is a moderate form of this cutaneous affection.[2] Lichen planus was also the form found in the case published by Azzam et al.[3] The mechanism of drug-induced lichen remains unknown. Lichen may be initiated by a cell-mediated immunologic response to an induced antigenic change in skin or mucosa. Lichen may have an immunopathological etiology since it is frequently associated with other autoimmune disease, including primary biliary cirrhosis, sicca syndrome (most known as Gougerot-Sjögren syndrome), diabetes mellitus, and hepatic disorders.[5,7]
Fig. 3. Dermo-epidermal detachment.
References 1.
Levy A, Le Cleach L. Lichen plan et dermatoses lichénoïdes. EMC Dermatologie Cosmetologie 2005; 2:132-46 Doi: 10.1016/S0246-0319(05)41211-X
2.
Ellgehausen P, Elsner P, Burg G. Drug-induced lichen planus. Clin Dermatol 1998; 16: 325-32
3.
Azzam H, Bergman R, Friedman-Birnbaum R. Lichen planus associated with metformin therapy. Dermatology 1997; 194: 376
4.
Bégaud B, Evreux JC, Jouglard J, et al. Unexpected or toxic drug assessment (imputation). Actualization of the method used in France. Therapie 1985; 40: 111-8
5.
Halevy S, Shai A. Lichenoid drug eruptions. J Am Acad Dermatol 1993; 29: 249-55
6.
Ben Salem C, Chenguel L, Ghariani N, et al. Captopril-induced lichen planus pemphigoides. Pharmacoepidemiol Drug Saf 2008; 17: 722-4
7.
Hsiao L, Yoshinaga A, Ono T. Drug-induced bullous lichen planus in a patient with diabetes mellitus and liver disease. J Am Acad Dermatol 1986; 15: 103-5
Conflicts of interests. None. Abbreviations. VHB: hepatitis B virus; VHC: hepatitis C virus; UVB therapy: ultraviolet light B therapy.
© Société Française de Pharmacologie et de Thérapeutique
Correspondence and offprints: Ahmed Zaiem, National Center of Pharmacovigilance, 9 avenue Dr Zouhaier Essafi, 1006 Tunis, Tunisia. E-mail: [email protected]
Thérapie
À LA
Thérapie DOI: 10.2515/therapie/2014025
RÉDACTION
© 2014 Société Française de Pharmacologie et de Thérapeutique
Lichen Associated with Metformin Ahmed Zaïem1,2, Rym Sahnoun1,2, Talel Badri2,3, Ghozlane Lakhoua1,2, Wafa Koubaa4, Sarrah Kastalli1,2, Riadh Daghfous1,2, Mohamed Lakhal1,2 and Sihem El Aidli1,2 1 National Center of Pharmacovigilance, Tunis, Tunisia 2 Tunis El Manar University, Medicine Faculty, Tunis, Tunisia 3 Dermatology Department, Habib Thameur Hospital, Tunis, Tunisia 4 Pathological Anatomy Laboratory, Habib Thameur Hospital, Tunis, Tunisia Fig. 1. The small papules presented by the patient.
Text received September 30th, 2013; accepted January 20th, 2014 The case was reported to the Tunisian National Pharmacovigilance Centre on April 8th, 2010 Abstract – We report an exceptional case of bullous lichen induced by metformin in a patient with diabetes mellitus. Keywords: metformin; bullous lichen; adverse effect Résumé – Lichen associé à la metformine. Nous rapportons un cas exceptionnel de lichen bulleux induit par la metformine chez une patiente diabétique. Mots clés : metformine ; lichen bulleux ; effet indésirable Abbreviations: see end of article.
1. Introduction Lichen is a chronic itching dermatosis characterized by shiny flat purplish blue polygonal papules affecting any part of the body but it is most likely to appear on the extension part of the limbs.[1] It can be induced by drugs such as antimalarial drugs, angiotensinconverting enzyme inhibitors and oral hypoglycemic drugs mainly with sulfonylureas.[2] There is only one case of lichen planus associated with metformin.[3] We report the first case of bullous lichen induced by metformin in a patient with diabetes mellitus.
later, the patient developed a general cutaneous eruption. The lesions consisted of small, shiny and polygonal papules associated with pinkish purplish blue papules in the limbs. Metformin was stopped and insulin therapy started. The eruption resolved spontaneously within 3 months after discontinuation of metformin. In February 2010, metformin was prescribed again at 1 700 mg/ day to reduce insulin resistance. One month after starting metformin therapy, the patient presented a general cutaneous eruption, similar to the one presented in 2007. The lesions consisted of small, shiny and polygonal papules associated with pinkish purplish blue papules in the limbs (figure 1). The patient developed also mucous lesions at the mouth and at the nose. A skin biopsy showed bullous lichen: focal lesions of hypertrophic acanthosis in the epidermis with lesions of junctional dermatitis represented by vacuolated keratinocytes and apoptotic bodies, sometimes responsible for a dermo-epidermal detachment (figures 2, 3). A lymphocytic infiltrate in band under epithelium was observed in the superficial dermis. The patient was treated by ultraviolet light B (UVB) therapy and the lesions healed one month after metformin withdrawal. Serological tests for infections (hepatitis B virus [HVB], hepatitis C virus [HVC], syphilis) were all negative. The case was reported to the Tunisian National Pharmacovigilance Centre and analyzed according to the French method of imputation.[4] The causality of metformin was retained with an imputation score of I2 (possible).
3. Discussion 2. Case report In 2007, a 58-year-old woman was treated for non-insulindependent diabetes mellitus by metformin 2 550 mg/day. One month
Lichenoïd eruption is an exceptional adverse drug reaction. The main implicated drugs are usually angiotensin-converting enzyme inhibitors (captopril), beta-blockers (practolol), anti-infectives (ethambutol, ketoconazole), non steroidal anti-inflammatory drugs
Article publié par EDP Sciences
2
Zaïem et al.
Fig. 2. Lesions of junctional dermatitis with vacuolated keratinocytes and a dermo-epidermal detachment.
(indomethacin), anti-malarial drugs (quinine) and heavy metals (gold).[5,6] Only one case of lichenoïd drug eruption induced by metformin was found in literature.[3] In this case, the patient was treated for diabetes since 5 years with glibenclamide. Two weeks after starting metformin at the dose of 1 700 mg/day, he presented purplish blue papules and small plaques with adherent scales and prominent skin markings lesions. The skin biopsy was consistent with lichen planus. Our case reported the occurrence of lichen after one month of metformin therapy. This delay was consistent with the literature data for lichenoïd eruption induced by other drugs: it usually varies between 1 week to 3 years.[1,5] In our case, the lesions consisted of bullous lichen. In literature, lichen is always planus which is a moderate form of this cutaneous affection.[2] Lichen planus was also the form found in the case published by Azzam et al.[3] The mechanism of drug-induced lichen remains unknown. Lichen may be initiated by a cell-mediated immunologic response to an induced antigenic change in skin or mucosa. Lichen may have an immunopathological etiology since it is frequently associated with other autoimmune disease, including primary biliary cirrhosis, sicca syndrome (most known as Gougerot-Sjögren syndrome), diabetes mellitus, and hepatic disorders.[5,7]
Fig. 3. Dermo-epidermal detachment.
References 1.
Levy A, Le Cleach L. Lichen plan et dermatoses lichénoïdes. EMC Dermatologie Cosmetologie 2005; 2:132-46 Doi: 10.1016/S0246-0319(05)41211-X
2.
Ellgehausen P, Elsner P, Burg G. Drug-induced lichen planus. Clin Dermatol 1998; 16: 325-32
3.
Azzam H, Bergman R, Friedman-Birnbaum R. Lichen planus associated with metformin therapy. Dermatology 1997; 194: 376
4.
Bégaud B, Evreux JC, Jouglard J, et al. Unexpected or toxic drug assessment (imputation). Actualization of the method used in France. Therapie 1985; 40: 111-8
5.
Halevy S, Shai A. Lichenoid drug eruptions. J Am Acad Dermatol 1993; 29: 249-55
6.
Ben Salem C, Chenguel L, Ghariani N, et al. Captopril-induced lichen planus pemphigoides. Pharmacoepidemiol Drug Saf 2008; 17: 722-4
7.
Hsiao L, Yoshinaga A, Ono T. Drug-induced bullous lichen planus in a patient with diabetes mellitus and liver disease. J Am Acad Dermatol 1986; 15: 103-5
Conflicts of interests. None. Abbreviations. VHB: hepatitis B virus; VHC: hepatitis C virus; UVB therapy: ultraviolet light B therapy.
© Société Française de Pharmacologie et de Thérapeutique
Correspondence and offprints: Ahmed Zaiem, National Center of Pharmacovigilance, 9 avenue Dr Zouhaier Essafi, 1006 Tunis, Tunisia. E-mail: [email protected]
Thérapie
