Hailey-Hailey disease: clinical, diagnostic and therapeutic update.

Hailey-Hailey disease is a rare genodermatosis described in 1939, with an autosomal dominant inheritance pattern, characterized by compromised adhesion between epidermal keratinocytes. It has an estimated prevalence of 1/50,000, with no gender or race predilection. It results from a heterozygous mutation in the ATP2C1 gene, which encodes the transmembrane protein hSPA1C, present in all tissues, with preferential expression in keratinocytes. Mutations in the ATP2C1 gene cause changes in the synthesis of junctional proteins, leading to acantholysis. It usually begins in adulthood, with isolated cases at the extremes of life. It manifests as vesico-bullous lesions mainly in the flexural areas, which develop into erosions and crusts. Chronic lesions may form vegetative or verrucous plaques. Pruritus, a burning feeling and pain are common. It evolves with periods of remission and exacerbation, generally triggered by humidity, friction, heat, trauma and secondary infections. The diagnosis is based on clinical and histopathological criteria: marked suprabasal acantholysis, loosely joined keratinocytes, giving the appearance of a "dilapidated brick wall", with a few dyskeratotic cells. The acantholysis affects the epidermis and spares the adnexal epithelia, which helps in the differential diagnosis with pemphigus vulgaris. Direct immunofluorescence is negative. The main differential diagnoses are Darier disease, pemphigus vegetans, intertrigo, contact dermatitis, and inverse psoriasis. There is no cure and the treatment is challenging, including measures to control heat, sweat and friction, topical medications (corticosteroids, calcineurin inhibitors, antibiotics), systemic medications (antibiotics, corticosteroids, immunosuppressants, retinoids and immunobiologicals) and procedures such as botulinum toxin, laser and surgery. There is a lack of controlled clinical trials to support the choice of the best treatment.

Familial "benign" pemphigus? Erythroderma and fatal outcome

Abstract Hailey-Hailey disease, or familial benign pemphigus, is a rare bullous genodermatosis that usually presents with flaccid blisters, erosions, and maceration limited to flexural areas, resulting in increased morbidity and reduced quality of life for affected patients. The authors report an unusual case of generalized Hailey-Hailey disease with erythroderma and fatal outcome.

Familial "benign" pemphigus? Erythroderma and fatal outcome.

Hailey-Hailey disease, or familial benign pemphigus, is a rare bullous genodermatosis that usually presents with flaccid blisters, erosions, and maceration limited to flexural areas, resulting in increased morbidity and reduced quality of life for affected patients. The authors report an unusual case of generalized Hailey-Hailey disease with erythroderma and fatal outcome.

Pênfigo crônico familiar benigno / Familial benign chronic pemphigus

O objetivo deste trabalho é relatar o caso de mulher, 44 anos, branca (fototipo 3), apresentando placas eritemato-violáceas com vesículas rompidas, maceração e odor intenso e desagradável em ambas as axilas e região inguinal, com início há dez anos. Foi diagnosticado Pênfigo Crônico Familiar Benigno ou doença de Hailey-Hailey, uma genodermatose autossômica dominante rara desencadeada por mutação no cromossomo 3q21-24 (AU)

The aim of this study is to report the case of a 44-year-old white (skin type 3) woman presenting with erythematous-violaceous plaques with ruptured vesicles, maceration, and intense and unpleasant odor in both armpits and groin, starting ten years ago. Benign familial chronic pemphigus, or Hailey-Hailey disease, a rare autosomal dominant genodermatosis triggered by a mutation on chromosome 3q21-24, was diagnosed (AU)

Mononeuritis multiplex: association with infectious condition and familial background in a tropical environment: a case report.

Mononeuritis multiplex is characterized by an asymmetric pattern with affection of the peripheral nervous system; this form of polyneuropathy is often seen in non-systemic vasculitis. We present a case of multiplex neuropathy in a patient with histologicaly verified Hailey-Hailey disease. With the exception of this comorbidity--in its characteristic form presenting additionally with a superinfected subdermal node--we did not find any other possible etiologic factor possibly causative of multiplex neuritis. The diagnosis was confirmed by electrophysiological testing. To our knowledge, this is the first case report indicating a possible relationship between Hailey-Hailey disease and multiplex neuritis. There exists only one related study in the literature, which was conducted in Columbia--our patient's home country. This study delineates a clinically similar dermal disease (pemphigus foliaceus) in patients from rural Colombia (El Bagre). The authors detected anti-neuronal antibodies which were interpreted to be responsible for the pathognomonic burning sensations.

Enfermedad de Hailey-Hailey en varias generaciones de una familia / Hailey - Hailey disease in several generations of a family

Se describen 2 casos clínicos de hermanos adultos que presentaban pénfigo benigno familiar o enfermedad de Hailey-Hailey, tipo de genodermatosis por alteración en la cohesión epidérmica, atendidos en el Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba. Los pacientes fueron tratados con esteroides en dosis antiinflamatorias, antibióticos y, de forma tópica, linimento vegetal y crema de aloe, además de recibir terapia floral. De manera general, ambos mejoraron su cuadro clínico durante la estadía en dicha institución hospitalaria

Two case reports of adult siblings are described, who presented with benign familial pemphigus or Hailey-Hailey disease --type of genodermatosis by altered epidermal cohesion-- attended in Dr Juan Bruno Zayas Alfonso Teaching General Hospital of Santiago de Cuba. Patients were treated with steroids at anti-inflammatory doses, antibiotics, and topical plant liniment and aloe cream, besides receiving flower therapy. In general, both of them improved the clinical picture during their stay in this institution

Familial benign chronic pemphigus (Hailey-Hailey Disease): use of topical immunomodulators as a modern treatment option.

Benign chronic familial pemphigus (Hailey-Hailey disease) is a rare autosomal dominant blistering skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. The Hailey brothers first described it in 1939. Hailey-Hailey disease usually appears in the third or fourth decade, although it can occur at any age. Heat, sweating and friction often exacerbates the disease, and most patients have worse symptoms during summer. It is characterized clinically by a recurrent eruption of vesicles and bullae at the sites of friction and intertriginous areas. We report a 51-year-old male presenting with grey-brown hyperkeratosis with partial papillomatosis and lichenification in the axillary and inguinal areas and infiltrated erythematous lesions in the infraorbitary region, on the side of the face. Biopsies obtained from inguinal and axillar areas revealed parakeratotic crusts overlying an acantholytic epidermis. A biopsy from one of the lesions from the infraorbital area showed a Jessner-Kanof lymphocytic infiltration. The patient was treated with antimicrobials and four days later, topical Pimecrolimus was started, leading to an improvement of the clinical picture. The efficacy of Pimecrolimus in our case suggests that cellular immunity could play a role in the pathogenesis of Hailey-Hailey disease.

Familial benign chronic pemphigus (Hailey-Hailey Disease): use of topical immunomodulators as a modern treatment option / Pénfigo familiar crónico benigno: Informe de un caso

Benign chronic familial pemphigus (Hailey-Hailey disease) is a rare autosomal dominant blistering skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. The Hailey brothers first described it in 1939. Hailey-Hailey disease usually appears in the third or fourth decade, although it can occur at any age. Heat, sweating and friction often exacerbates the disease, and most patients have worse symptoms during summer. It is characterized clinically by a recurrent eruption of vesicles and bullae at the sites of friction and intertriginous areas. We report a 51-year-old male presenting with grey-brown hyperkeratosis with partial papillomatosis and lichenification in the axillary and inguinal areas and infiltrated erythematous lesions in the infraorbitary region, on the side of the face. Biopsies obtained from inguinal and axillar areas revealed parakeratotic crusts overlying an acantholytic epidermis. A biopsy from one of the lesions from the infraorbital area showed a Jessner-Kanof lymphocytic infiltration. The patient was treated with antimicrobials and four days later, topical Pimecrolimus was started, leading to an improvement of the clinical picture. The efficacy of Pimecrolimus in our case suggests that cellular immunity couldplay a role in thepathogenesis of Hailey-Hailey disease.

Hailey-Hailey disease treatment with Botulinum toxin type A.

Two sisters with recurrent lesions, one on axillae and other on the groin, and with limited response to classical treatments were treated with injections botulinum toxin type A. We observed marked improvement in the patient treated in the groin and complete remission in the patient treated in the axillae. It was possible to spare the use of systemic antibiotics and topical corticosteroids. The high cost is a restrictive factor to routine use and large studies are necessary to access efficacy and cost benefit profile.

Enfermedad de Hailey-Hailey verrugosa de localización exclusivamente vulvar. Comunicación de un caso / Verrucous Hailey-Hailey disease localized only on the vulvar area. A case report

Una paciente de 22 años consultó por la presencia de pápulas de color blanquecino, pequeñas, de superficie plana, múltiples y levemente pruriginosas, localizadas en vulva, sin otras manifestaciones dermatológicas. Como antecedente familiar de relevancia refirió que su madre presentaba una dermatosis de similares características en pliegues inframamarios y axilas, recurrentes desde la adolescencia. El estudio histológico de la paciente correspondió a una dermatosis acantolítica con disqueratosis, vinculable a un Pénfigo Crónico Benigno Familiar (PCBF) o enfermedad de Hailey-Hailey. Se presentan las características clínicas e histológicas observadas y se analizan los diagnósticos diferenciales que se plantean ante una dermatosis acantolítica de localización exclusivamente genital.

A 22-year-old woman presented with multiple, small, whitish, domeshaped, itchy papules localized on the vulvar area whitout any other dermatologic lesions. Her family history disclosed that her mother had recurrent bullous lesions since her adolescence. The histopathologic examination demonstrated an acantholytic dermatosis with dyskeratosis, corresponding to familial bening pemphigus or Hailey-Hailey disease. Wepresent the clinical and histological characteristics observed in this case and analize the diff erential diagnosis of acantholytic dermatoses localized only on the vulvar area.

Tratamento da doença de Hailey-Hailey com toxina botulínica tipo A / Hailey-Hailey disease treatment with Botulinum toxin type A

Duas irmãs com doença de Hailey-Hailey, com lesões recorrentes - uma em axilas e outra em região inguinal -, e resposta limitada aos tratamentos clássicos. Elas foram tratadas com aplicação de toxina botulínica tipo A. Observamos que houve importante melhora na paciente tratada na região inguinal e remissão completa na paciente em cujas axilas sofreram tratamento. Além disso, foi possível poupar uso de antibióticos sistêmicos e corticoides tópicos. O alto custo é um fator restritivo para uso rotineiro e estudos maiores são necessários para definir eficácia e relação custo-benefício dessa intervenção.

Two sisters with recurrent lesions, one on axillae and other on the groin, and with limited response to classical treatments were treated with injections botulinum toxin type A. We observed marked improvement in the patient treated in the groin and complete remission in the patient treated in the axillae. It was possible to spare the use of systemic antibiotics and topical corticosteroids. The high cost is a restrictive factor to routine use and large studies are necessary to access efficacy and cost benefit profile.

Pénfigo familiar benigno crónico: causa de rechazo conyugal / Chronic benign familiar pemphigus: a cause for conjugal rejection

Pénfigo crónico familiar benigno (enfermedad de Hailey-Hailey) es un desorden ampollar hereditario autonómico dominante con penetrancia y expresividad variables con lesiones recurrentes que predomina en pliegues. Describimos tres pacientes de sexo femenino.

Pénfigo familiar benigno crónico: causa de rechazo conyugal / Chronic benign familiar pemphigus: a cause for conjugal rejection

Pénfigo crónico familiar benigno (enfermedad de Hailey-Hailey) es un desorden ampollar hereditario autonómico dominante con penetrancia y expresividad variables con lesiones recurrentes que predomina en pliegues. Describimos tres pacientes de sexo femenino. (AU)

Pénfigo familiar benigno crónico: causa de rechazo conyugal / Chronic benign familiar pemphigus: a cause for conjugal rejection

Pénfigo crónico familiar benigno (enfermedad de Hailey-Hailey) es un desorden ampollar hereditario autonómico dominante con penetrancia y expresividad variables con lesiones recurrentes que predomina en pliegues. Describimos tres pacientes de sexo femenino. (AU)