Report Hailey-Hailey disease in Tunisia R. Benmously-Mlika 1 *, MD, M. Bchetnia 2,3 *, MD, S. Deghais 1 , MD, S.A. Ben Brick 2 , PhD, C. Charfeddine 2 , PhD, A. Debbiche 4 , MD, S. Haouet 5 , MD, M. Mokni 3,6 , MD, S. Abdelhak 2 , PhD, M.R. Kamoun 7 , MD, A. Ben Osman 6 , MD, S. Fenniche 1 , MD, and I. Mokhtar 1 , MD 1 Dermatology Department, Habib Thameur Hospital-Tunis, 2 ‘‘Molecular Investigation of Genetic Orphan Diseases’’ Research Unit, Institut Pasteur de Tunis, 3 ‘‘Study of Hereditary Keratinization Disorders’’ Research Unit, La Rabta Hospital, 4 Histopathology Department, Habib Thameur Hospital, 5 Histopathology Department, La Rabta Hospital, 6 Dermatology Department, La Rabta Hospital, and 7 Dermatology Department, Charles Nicolle Hospital, Tunis, Tunisia Correspondence Rym Benmously-Mlika, MD Department of Dermatology Habib Thameur Hospital Ali Ben Ayed Street N°8 – 1008 Montfleury Tunis Tunisia E-mail: rym.benmously@rns.tn *The authors contributed equally to this study. Conflict of interest: None. Summary Background Most of the published reports on Hailey-Hailey disease (HHD) come from European and Asian countries. We report here the clinical and genetic investigation of 20 patients affected with HHD in Tunisia. Methods Affected individuals from three large teaching hospitals in Tunis were recruited for the study over a 25-year period. Nine patients were identified through the active files and examined together with their family members that were visited in their respective regions. We have clinically examined in total 65 individuals and then identified 11 new cases. Patients were included on the basis of evocative skin lesions, biopsy proven HHD and negative immunofluorescence. Investigations to rule out fungal, bacterial and viral infections were done according to clinical symptoms. Results Twenty patients (12 males and 8 females) from 8 families were included in the present study with more than 55% that were undiagnosed before this investigation. Four patients had mild disease, eight had moderate disease and another eight had severe disease, among whom seven were females. Parental consanguinity was found in 7 cases out of 20 cases (35%). The neck region was first affected in half (4/8) of the male patients. Groins were first affected in 42% (5/12) of the female patients. Depression complicated the course of the disease in two female patients with severe HHD. We report an original association of supernumerary nipples with HHD in two sisters from the north of Tunisia. In 10 patients, the disease has become less troublesome with aging. Conclusion HHD is underestimated. Physicians must be aware of this disease in case of resistant intertriginous dermatosis especially with a positive family history as nine out of 20 patients were misdiagnosed. Background Hailey-Hailey disease (HHD) is a rare autosomal domi- nant hereditary disorder of keratinocyte cohesion charac- terized by recurrent eruption of vesicles and bullae, predominantly involving the body folds. It is caused by heterozygous mutations in the ATP2C1 gene, encoding the human secretory pathway Ca 2+ /Mn 2+ ATP-ase protein (hSPCA1). Most of the published reports on HHD come from European 1 and Asian countries. 2 In Tunisia, only isolated patients have been described thus far. 3,4 We report here the clinical and genetic investigation of 20 patients affected with HHD. Patients and methods Affected individuals from three large teaching hospitals in Tunis (Habib Thameur, La Rabta and Charles Nicolle) were recruited for the study. We have retrospectively reviewed the records of nine patients collected through a 25-year period from January 1981 to December 2005. We sent letters of inquiry to the patients and all of them replied. We have re-examined them and their family members who were visited in their respective regions. Sixty-five affected and unaffected individuals were interviewed and clinically examined. The newly identified patients were biopsied for histopathology and direct immunofluorescence. All patients included fulfilled the following criteria: evocative skin lesions with biopsy proven HHD and negative direct immunofluorescence for IgG, IgA, and IgM. Investigations to rule out fungal, bacterial, and viral infections were carried out according to clinical symptoms. On clinical examination, the disease was classified as mild if the number of affected areas was under 2, moderate if the number of affected areas was between 3 and 5 and severe if the number of affected areas equals or was 6 or over. 396 International Journal of Dermatology 2010, 49, 396–401 ª 2010 The International Society of Dermatology