CASOS CLíNiCOS Rev Med Chile 2011; 139: 633-637 Familial benign chronic pemphigus (Hailey-Hailey Disease): use of topical immunomodulators as a modern treatment option GeorGi tcherneV1, José carlos cardoso2 ABSTRACT 1Department of Benign chronic familial pemphigus (Hailey-Hailey disease) is a rare autosomal Dermatology and dominant blistering skin disorder characterized by suprabasal cell separation (acan- Venereology, Medical tholysis) of the epidermis. The Hailey brothers first described it in 1939. Hailey-Hailey Faculty, Trakian University disease usually appears in the third or fourth decade, although it can occur at any of Stara Zagora, Stara age. Heat, sweating and friction often exacerbates the disease, and most patients Zagora, Bulgaria. 2Dermatology and have worse symptoms during summer. It is characterized clinically by a recurrent Venereology Department, eruption of vesicles and bullae at the sites of friction and intertriginous areas. We University Hospital of report a 51-year-old male presenting with grey-brown hyperkeratosis with partial Coimbra, Coimbra, papillomatosis and lichenification in the axillary and inguinal areas and infiltrated Portugal. erythematous lesions in the infraorbitary region, on the side of the face. Biopsies Recibido el 13 de octubre obtained from inguinal and axillar areas revealed parakeratotic crusts overlying de 2010, aceptado el 19 de an acantholytic epidermis. A biopsy from one of the lesions from the infraorbital abril de 2011. area showed a Jessner-Kanof lymphocytic infiltration. The patient was treated with antimicrobials and four days later, topical Pimecrolimus was started, leading to an Correspondencia a: improvement of the clinical picture. The efficacy of Pimecrolimus in our case suggests Associated Prof Dr Georgi Tchernev M.D. P.h.D that cellular immunity could play a role in the pathogenesis of Hailey-Hailey disease. Department of (Rev Med Chile 2010; 139: 633-637). Dermatology and Key words: Acantholysis; Anti inflammatory agents, non-steroideal; Calcineurin. Venereology Trakian University of Stara Zagora, zip code 6000 Medical Faculty, 11 Armeiska Street, Stara Pénfigo familiar crónico benigno. Zagora 6000, Bulgaria. Tel: 00359 885 588 424 informe de un caso E-mail: georgi_tchernev@ yahoo.de El pénfigo familiar crónico benigno (enfermedad de Hailey-Hailey) es una José Carlos Cardoso, MD enfermedad ampollar autosómica poco frecuente de la piel, que se caracteriza por Dermatology Department acantolisis de la epidermis. Presentamos un hombre de 51 años que se presentó con University Hospital of una hiperqueratosis de color gris pardo con papilomatosis y liquenificación en las zonas Coimbra axilares e inguinales y lesiones eritematosas infiltradas en la región infraorbitaria a Praceta Mota Pinto 3000 075 Coimbra un lado de la cara. Las biopsias que se obtuvieron de las zonas inguinales y axilares Portugal. mostraron costras hiperqueratóticas sobre una epidermis acantolítica. La biopsia E-mail: ze_carlos_ de las lesiones infraorbitarias mostró una infiltración linfocítica tipo Jessner-Kanof. [email protected] El paciente se trató con antibióticos y cuatro días más tarde se inició pimecrolimus, mejorando el cuadro clínico. 633 CASOS CLíNiCOS Familial benign chronic pemphigus. Report of one case - G. Tchernev et al enign chronic familial pemphigus (hailey- laboratory findings:d ifferential blood count: hailey disease [HHD]) is a hereditary neutrophils: 40.2%; monocytes: 11%; eosinophils: bblistering skin disease, transmitted in an 9.8%; triglycerides: 2.19 mmol/l, Ca: 2.2 mmol/l; autosomal dominant way with variable genetic pe- blood sugar: 6.0 mmol/l. netrance1. it was described for the first time in 1939 erythrocyte sedimentation rate, hemoglobin, by the two brothers hugh and howard hailey2. it haematocrit, cholesterol with all subfractions, is hypothesized that the main reason for the pa- aminostransferases, GGT, electrolytes and iron thologic changes is an altered protein composition were all normal. Serological test for syphilis and of desmosomes leading to acantholysis, deriving antistreptolysin o titer were negative. from ATP2C1 gene mutation localized on chromo- direct immunofluorescence from lesional skin 2 2+ some 3q . The ATP2C1 gene codes a Ca -pump that and indirect immunofluorescence studies were regulates the transportation of calcium from the both negative. cytosol into the Golgi apparatus2,3. in approxima- histological analysis of biopsies obtained from tely 70% of the cases a positive family history may inguinal and axillar areas revealed parakeratotic be elicited. more frequently, the disease becomes crusts overlying an acantholytic epidermis, with apparent during puberty, and intertriginous acantholytic cells and rare diskeratotic cells. A areas are preferentially affected, namely axillary, biopsy from one of the lesions from the infraor- inguinal and neck folds. mucous membranes are bital area was in keeping with Jessner-Kanof far less affected. longitudinal white lines on the lymphocytic infiltration. nails are frequently noticed. bacterial and fungal Smears for microbiologic analyses from the super infection, maceration and frequent sweating axillary and inguinal areas disclosed Staphylococcus (axillary and inguinal hyperhidrosis) are conside- aureus, E. coli and Pseudomonas aeruginosa. red to be important aggravating factors4. however, some authors consider mechanical irritation to Treatment and outcome be the only provoking factor. Vesicular lesions initially, intravenous antibiotic therapy was covered by crusts, erosions and wart-like papules started with flucloxacillin 2 g three times daily are other possible clinical findings.h istologically, and ampicillin 1 g three times daily, due to the there is acantholysis of large areas of the epidermis, proved superinfection with Gram-positive and giving rise to the appearance that was compared to Gram-negative bacteria, as well as local therapy a “dilapidated brick wall”. dyskeratosis can also be with chlorhexidin 1% aqueous solution. four days noticed5. decomposition of the desmosome-kera- after beginning antibiotic therapy, specific therapy tin filament complex is ultrastructurally proved. with topical pimecrolimus twice a day was started, Clinically, the disease has a fluctuating course, and leading to a significant and fast improvement of both the activity and the affected areas may vary2,5. the clinical picture. Discussion Case report The differential diagnosis of familial benign A 51-year-old patient came to the clinic with chronic pemphigus includes all the most frequent skin lesions localized to the axillary and inguinal skin diseases manifesting at the axillary and in- areas that were present since he was 18 years of age guinal areas. (figures 1-4). Topically applied therapy, including Pemphigus vegetans, Neumann type, is not corticosteroids, antimycotics and antibiotics had frequently considered in the differential diagnosis. been ineffective. he did not have any relatives in this disease direct immunofluorescence proves suffering from similar lesions. deposition of lgG and C3-fraction of the comple- on observation, grey-brown hyperkeratosis ment, and indirect immunofluorescence shows with partial papillomatosis and lichenification the presence of anti-desmoglein 3 antibodies. in were noticed in the axillary and inguinal areas (fi- hailey-hailey disease, alterations of the humoral gures 1-4). Additionally, infiltrated erythematous immunity are not found. lesions were found in the infraorbitary region, on The clinical differentiation from inverse psoria- the side of the face. sis is often very difficult, particularly in macerated 634 Rev Med Chile 2011; 139: 633-637 CASOS CLíNiCOS Familial benign chronic pemphigus. Report of one case - G. Tchernev et al Figures 1-4. Clinical manifestation of Hailey-Hailey disease in the intertriginous areas: brown macerated and hyperpigmented ranges at the axillary and inguinal areas. and superinfected lesions2,6. histological features The histopathological and clinical differen- provide essential clues to the differentiation bet- tiation between hhd and darier’s disease is not ween the two diseases, as the typical acantholysis always easy2,5,7. in these cases the clinical picture and occasional dyskeratosis found in HHD are not is decisive, as is the presence of dyskeratotic cells features of psoriatic lesions. and more focal acantholysis in darier’s disease, The diagnosis of acanthosis nigricans may contrasting with the more diffuse acantholysis and also be evoked, especially in the case of hyperpig- less or inexistent dyskeratosis in hhd. mented lesions of hhd that may elude clinical Candidal superinfection seems to be a frequent diagnosis. concomitant infection in lesions of HHD, the same Rev Med Chile 2011; 139: 633-637 635 CASOS CLíNiCOS Familial benign chronic pemphigus. Report of one case - G. Tchernev et al as in inverse psoriasis and in different forms of initial linkage to the cytosolic receptor fKbP-12, pemphigus vegetans. designated also as macrophillin-122,10. in contrast during the last years, the genetic cause and mo- to them, cyclosporin A binds to another cyto- lecular pathogenesis of hailey-hailey disease have solic receptor from the macrophillin group, the been elucidated. The distribution of intracellular cyclophillin2. The macrophillin-12 – Cl complex Ca2+ plays an important role in the regulation of blocks the calcineurin phosphatase and this cell-cell interactions in the epidermis3. damage leads to activation (through dephosphorylation)