JEADV
LETTER TO THE EDITOR
Doxepin-induced bullous pemphigoid-like drug eruption Editor Doxepin is an FDA-approved tricyclic anti-depressant which is useful in the treatment of anxiety disorders, insomnia and depression. Doxepin is effective in the treatment of chronic urticaria and pruritus because of its H1 and H2 anti-histaminic effect. Topical forms of doxepin are also effective in the treatment of atopic dermatitis, eczemas and lichen simplex chronicus. There are many case reports in the literature regarding doxepin-associated contact dermatitis.1,2 However, data regarding bullous pemphigoid-like drug eruption following doxepin administration are very limited. Here, we report a case of doxepin-associated bullous pemphigoid-like eruption. Ninety-year-old female patient was hospitalized in our department because of bullous skin eruption. Prior to skin eruption she suffered from generalized pruritus for 1 year. She used different anti-histaminic drugs which were not effective so, 20 days prior to skin eruption she received doxepin. She avoided the use of antibiotics and nonsteroidal anti-inflammatory drugs prior to eruption. Dermatological evaluation revealed bullous skin lesions on urticarial ground all over the body (Fig. 1). Oral mucosa and palmoplantar surfaces were also involved. Four skin
samples were obtained from both, bullous lesions and perilesional intact skin of the back and palmar region. Microscopic evaluation of skin samples taken from bullous lesions showed subepidermal splitting, sparse keratinocytes necrosis and dermal perivascular and interstitial polymorph nuclear leucocytes infiltration (Fig. 1). Direct immunofluorescence examination was negative. Laboratory investigation showed highly elevated IgE (2281 IU/mL) and specific IgE (69.1 5(+) kUA/l Rast Mtd). Radioallergosorbent test detected allergy to the house dust mite. The routine blood test was in normal range. The administration of doxepin was stopped and skin lesions gradually started to fade. Administration of systemic immunosuppressive drugs was avoided. There are some reports in the literature regarding bullous pemphigoid-like skin eruption following the administration of drugs like ibuprofen, nafcillin and nicotinamide.3–5 However, reports in the literature regarding doxepin-induced bullous eruptions are limited. There is a case of bullous pemphigoid (BP) induced by penicillin which demonstrates subepidermal splitting in the microscopic evaluation and linear depositions in DIF examination.6 In our case, the skin lesions were similar to BP and pruritus was considered as a prodromal symptom of BP. However, four skin samples taken from different skin lesions were not positive for BP, because DIF positivity is an obligatory diagnostic criterion for BP.7 DIF negativity, improvement after doxepin cessation, allergy positivity for dust ruled out BP and
(a)
(b)
(c)
(d)
Figure 1 Bullous lesions on erythematous urticarial base on abdomen and extremities (a, b). Subepidermal splitting and slightly mixed inflammatory cell infiltration in the dermis of palmar skin (H&E 940) (c). Subepidermal splitting (H&E 9200) (d).
JEADV 2015
© 2015 European Academy of Dermatology and Venereology
Letter to the Editor
2
made us to think about drug eruption. So, doxepin was considered as a possible triggering factor of bullous eruption. Furthermore, oral and palmoplantar involvement of skin lesions demonstrated distribution of erythema multiforme major without targetoid lesions. As an underlying cause of pruritus, allergy to dust was suspected. There were no other pathologies. Malignancy screening also was negative. So, we concluded that highly elevated IgE level and pruritus are not related to BP, but the signs of atopy. In conclusion, doxepin is an often prescribed drug for the treatment of pruritus. Since, pruritus is the prodromal sign of BP, following the administration of doxepin, bullous lesions may evolve either due to BP or the use of doxepin . After the exclusion of BP, doxepin should be considered as a triggering factor of bullous lesions. M. Iskandarli,1,* B. Yaman,2 B. Gerceker Turk,1 G. Ozturk1 1
Departments of Dermatology and Venereology, 2Pathology, Ege University Faculty of Medicine, Izmir, Bornova 35100, Turkey *Correspondence: M. Iskandarli. E-mail: [email protected]
JEADV 2015
References
1 Buckley DA. Contact allergy to doxepin. Contact Dermatitis 2000; 43: 231–232. 2 Bonnel RA1, La Grenade L, Karwoski CB, Beitz JG. Allergic contact dermatitis from topical doxepin: Food and Drug Administration’s postmarketing surveillance experience. J Am Acad Dermatol 2003; 48: 294–296. 3 Laing VB, Sheretz EF, Flowers FP. Pemphigoid-like bullous eruption related to ibuprofen. J Am Acad Dermatol 1988; 19: 91–94. 4 Ho SA, Aw DC. Bullous drug eruption secondary to nicotinic acid/laropiprant. Ann Acad Med Singapore 2012; 41: 134–135. 5 Chang MO, Koh ES, Kim MJ et al. Nafcillin-induced bullous skin eruption with granulocytopenia in a patient with end-stage renal disease. Intern Med 2012; 51: 287–289. 6 Brown MD, Dubin HV. Penicillamine-induced bullous pemphigoid-like eruption. Arch Dermatol 1987; 123: 1119–1120. 7 Kershenovich R, Hodak E, Mimouni D. Diagnosis and classification of pemphigus and bullous pemphigoid. Autoimmun Rev 2014; 13: 477–481. DOI: 10.1111/jdv.13012
© 2015 European Academy of Dermatology and Venereology
LETTER TO THE EDITOR
Doxepin-induced bullous pemphigoid-like drug eruption Editor Doxepin is an FDA-approved tricyclic anti-depressant which is useful in the treatment of anxiety disorders, insomnia and depression. Doxepin is effective in the treatment of chronic urticaria and pruritus because of its H1 and H2 anti-histaminic effect. Topical forms of doxepin are also effective in the treatment of atopic dermatitis, eczemas and lichen simplex chronicus. There are many case reports in the literature regarding doxepin-associated contact dermatitis.1,2 However, data regarding bullous pemphigoid-like drug eruption following doxepin administration are very limited. Here, we report a case of doxepin-associated bullous pemphigoid-like eruption. Ninety-year-old female patient was hospitalized in our department because of bullous skin eruption. Prior to skin eruption she suffered from generalized pruritus for 1 year. She used different anti-histaminic drugs which were not effective so, 20 days prior to skin eruption she received doxepin. She avoided the use of antibiotics and nonsteroidal anti-inflammatory drugs prior to eruption. Dermatological evaluation revealed bullous skin lesions on urticarial ground all over the body (Fig. 1). Oral mucosa and palmoplantar surfaces were also involved. Four skin
samples were obtained from both, bullous lesions and perilesional intact skin of the back and palmar region. Microscopic evaluation of skin samples taken from bullous lesions showed subepidermal splitting, sparse keratinocytes necrosis and dermal perivascular and interstitial polymorph nuclear leucocytes infiltration (Fig. 1). Direct immunofluorescence examination was negative. Laboratory investigation showed highly elevated IgE (2281 IU/mL) and specific IgE (69.1 5(+) kUA/l Rast Mtd). Radioallergosorbent test detected allergy to the house dust mite. The routine blood test was in normal range. The administration of doxepin was stopped and skin lesions gradually started to fade. Administration of systemic immunosuppressive drugs was avoided. There are some reports in the literature regarding bullous pemphigoid-like skin eruption following the administration of drugs like ibuprofen, nafcillin and nicotinamide.3–5 However, reports in the literature regarding doxepin-induced bullous eruptions are limited. There is a case of bullous pemphigoid (BP) induced by penicillin which demonstrates subepidermal splitting in the microscopic evaluation and linear depositions in DIF examination.6 In our case, the skin lesions were similar to BP and pruritus was considered as a prodromal symptom of BP. However, four skin samples taken from different skin lesions were not positive for BP, because DIF positivity is an obligatory diagnostic criterion for BP.7 DIF negativity, improvement after doxepin cessation, allergy positivity for dust ruled out BP and
(a)
(b)
(c)
(d)
Figure 1 Bullous lesions on erythematous urticarial base on abdomen and extremities (a, b). Subepidermal splitting and slightly mixed inflammatory cell infiltration in the dermis of palmar skin (H&E 940) (c). Subepidermal splitting (H&E 9200) (d).
JEADV 2015
© 2015 European Academy of Dermatology and Venereology
Letter to the Editor
2
made us to think about drug eruption. So, doxepin was considered as a possible triggering factor of bullous eruption. Furthermore, oral and palmoplantar involvement of skin lesions demonstrated distribution of erythema multiforme major without targetoid lesions. As an underlying cause of pruritus, allergy to dust was suspected. There were no other pathologies. Malignancy screening also was negative. So, we concluded that highly elevated IgE level and pruritus are not related to BP, but the signs of atopy. In conclusion, doxepin is an often prescribed drug for the treatment of pruritus. Since, pruritus is the prodromal sign of BP, following the administration of doxepin, bullous lesions may evolve either due to BP or the use of doxepin . After the exclusion of BP, doxepin should be considered as a triggering factor of bullous lesions. M. Iskandarli,1,* B. Yaman,2 B. Gerceker Turk,1 G. Ozturk1 1
Departments of Dermatology and Venereology, 2Pathology, Ege University Faculty of Medicine, Izmir, Bornova 35100, Turkey *Correspondence: M. Iskandarli. E-mail: [email protected]
JEADV 2015
References
1 Buckley DA. Contact allergy to doxepin. Contact Dermatitis 2000; 43: 231–232. 2 Bonnel RA1, La Grenade L, Karwoski CB, Beitz JG. Allergic contact dermatitis from topical doxepin: Food and Drug Administration’s postmarketing surveillance experience. J Am Acad Dermatol 2003; 48: 294–296. 3 Laing VB, Sheretz EF, Flowers FP. Pemphigoid-like bullous eruption related to ibuprofen. J Am Acad Dermatol 1988; 19: 91–94. 4 Ho SA, Aw DC. Bullous drug eruption secondary to nicotinic acid/laropiprant. Ann Acad Med Singapore 2012; 41: 134–135. 5 Chang MO, Koh ES, Kim MJ et al. Nafcillin-induced bullous skin eruption with granulocytopenia in a patient with end-stage renal disease. Intern Med 2012; 51: 287–289. 6 Brown MD, Dubin HV. Penicillamine-induced bullous pemphigoid-like eruption. Arch Dermatol 1987; 123: 1119–1120. 7 Kershenovich R, Hodak E, Mimouni D. Diagnosis and classification of pemphigus and bullous pemphigoid. Autoimmun Rev 2014; 13: 477–481. DOI: 10.1111/jdv.13012
© 2015 European Academy of Dermatology and Venereology
