Pénfigo benigno familiar de presentación atípica en paciente sin antecedente familiar / Atypical presentation of familial benign pemphigus in patient without familiar background

Resumen La enfermedad de Hailey-Hailey, también llamada pénfigo familiar benigno, corresponde a una genodermatosis debilitante que se transmite mediante un patrón autosómico dominante, con una prevalencia de alrededor de 1 en 50.000 casos. El reporte de antecedentes familiares está presente hasta en 60 % de los pacientes. Se caracteriza por la presencia de vesículas crónicas y recurrentes, erosiones y exulceraciones en zonas de flexura. El tratamiento puede representar un reto, porque a pesar del manejo con terapias tópicas, corticosteroides sistémicos, inmunomoduladores sistémicos y el empleo de láser, ninguna terapia ha logrado una remisión a largo plazo. Se presenta el caso de un paciente masculino, adulto medio, sin antecedente familiar alguno, con historia de placas de superficie descamativa y hematocostras recurrentes crónicas y presentación clínica atípica, dada la localización de lesiones predominantes en miembros superiores, con sospecha inicial de psoriasis vulgar, con posterior toma de biopsia y reporte de patología que evidencia histológia típica de PBF. Por lo cual se indica manejo con corticosteroides sistémicos, sin evidencia de reacciones adversas y con remisión a largo plazo. MÉD.UIS.2020;34(1):101-6

Abstract Hailey-Hailey disease, also called benign familial pemphigus, corresponds to a debilitating genodermatosis that is transmitted through an autosomal dominant pattern, with a prevalence of around 1 in 50,000 cases. The family history report is present in up to 60% of patients. It is characterized by the presence of chronic and recurrent vesicles, erosions and exulcerations in flexural areas. Treatment can be challenging, because despite management with topical therapies, systemic corticosteroids, systemic immunomodulators, and the use of lasers, no therapy has achieved long-term remission.We present the case of a male patient, middle adult, without any family history, with a history of scaly surface plaques and chronic recurrent hematocostras and atypical clinical presentation given the location of predominant lesions in the upper limbs, with initial suspicion of vulgar psoriasis, with subsequent biopsy and pathology report showing typical PBF histology. Therefore, management with systemic corticosteroids without evidence of adverse reactions and with long-term remission is indicated. MÉD.UIS.2020;34(1):101-6

Case for diagnosis. Atypical Grover's disease

Abstract A 55-year-old male presented with an eight-month history of erythematous papules and plaques with demarcated areas of spared skin on his trunk, upper extremities, neck, and face. Grover's disease is a rare, acquired disorder of unknown origin, which is classically characterized by the appearance of erythematous papules on the upper trunk that are usually transient. As in the present case, there are reports of atypical disease, with facial involvement, pityriasis rubra pilaris-like lesions, and a more chronic course.

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.

A Case of Persistent Acantholytic Dermatosis Presenting as a Chronic Single Patch / 대한피부과학회지

Transient acantholytic dermatosis, or Grover's disease, usually appears as pruritic erythematous papules and vesicles on the trunk in middle-aged men. The pathogenesis remains unclear, though sun exposure, heat, and sweating may be aggravating factors. A 58-year-old male visited our clinic for evaluation of an asymptomatic erythematous patch on the left temple that developed 40 years ago. Here, we report the rare case of Grover's disease with atypical features presenting as one large patch on the face.

Enfermedades acantolíticas: caracterización de pacientes con diagnóstico de enfermedad de Hailey-Hailey, enfermedad de Darier y enfermedad de Grover, entre los años 2007 y 2017 en el Hospital Clínico San Borja Arriaran y revisión de la literatura / Characterization of patients diagnosed with Hailey-Hailey disease: Darier's disease and Grover's disease, between 2007 and 2017 at the San Borja Arriaran Clinical Hospital and review of the literature

INTRODUCCIÓN: Las enfermedades acatólicas son un grupo heterogéneo de enfermedades que presentan como característica central histopatológica la acantosis. Generalmente presentan un curso de evolución crónica y recidivante, con variadas manifestaciones clínicas. OBJETIVO: caracterizar los pacientes con diagnóstico de enfermedad acantolítica, bajo 5 criterios clínicos y realizar una revisión de la literatura. MÉTODOS: Se realizó una revisión de la base de datos del Servicio Anatomía Patológica del Hospital San Borja Arriaran (HSBA) entre los años 2007 y 2017 y se complementaron con los antecedentes clínicos extraídos de las fichas clínicas.RESULTADOS: Se obtuvo un total de 13 casos. el 53,8% correspondieron a enfermedad de Darier, 20,6% a enfermedad de Hailey-Hailey y un 20,6% a enfermedad de Grover, obteniendo un promedio de edad al momento del diagnóstico de 22,5 años, 44,3 años y 47,6 años respectivamente. Los antecedentes familiares estuvieron presentes en el 53,8% del total de pacientes, ninguno de ellos presentaba estudio genético. El 61,5% de la muestra correspondió a pacientes de sexo femenino y el promedio de años de evolución previo al diagnóstico fue de 7,4 años para Darier, 8,6 para Hailey-Hailey y para Grover. El 100% de los pacientes con enfermedad de Darier y Grover estaban con terapia sistémica y el 66,6% de enfermedad de Hailey-Hailey con terapia tópica, todos con adecuada respuesta clínica. DISCUSIÓN y conclusiones: las enfermedades acantolíticas corresponden a genodermatosis poco frecuente cuyo diagnóstico y tratamiento constitu-yen un desafío para el dermatólogo

INTRODUCTION: Atytolic diseases are a heterogeneous group of diseases that present acanthosis as a histopathological central characteristic. They usually present a course of chronic and recurrent evolution, with varied clinical manifestations. OBJECTIVE: to characterize the patients diagnosed with acantholytic disease, with 5 clinical criteria and to carry out a review of the literature. METHODS: A review of the database of the Pathological Anatomy Service of the San Bor-ja Arriaran Hospital (HSBA) between 2007 and 2017 was carried out and complemented with the clinical records extracted from the clinical files. RESULTS: A total of 13 cases were obtained. 53.8% corresponded to Darier's disease, 20.6% to Hailey-Hailey's disease and 20.6% to Grover's disease, obtaining an average age at diagnosis of 22.5 years, 44.3 years and 47.6 years respectively. Family history was present in 53.8% of the to-tal patients, none of them had a genetic study. 61.5% of the sample corresponded to female patients and the average of years of evolution prior to diagnosis was 7.4 years for Darier, 8.6 for Hailey-Hailey and for Grover. 100% of the pa-tients with Darier and Grover's disease were on systemic therapy and 66.6% of Hailey-Hailey's disease with topical therapy, all with adequate clinical response. DISCUSSION AND CONCLUSIONS: acantholytic diseases correspond to rare genodermatosis whose diagnosis and treatment constitute a challenge for the dermatologist.

Enfermedad de Grover, una patología ampollar poco frecuente: a propósito de 2 casos / Grover's disease, a pathology blistering unusual: About 2 cases

Grover's disease (GD) or transient acantholytic dermatosis, is a papulovesicular pruritic disease of unknown etiology. It´s most important histopathological finding is the presence of focal acantholysis. The incidence has not been firmly established. Case report: We report two cases of papulovesicular rashes, the first one in a 79 year old man with good response to second line treatment and the second one, in a 30 year old woman. Both with different suspected triggering factors. Comment: GD predominates in white men with an average age of presentation of 61. Clinically, it presents as erythematous papules, crusted-papule and is usually pruritic. The etiopathology is still unknown, but it is associated with triggers such as: ultraviolet radiation (UVR), ionizing radiation, heat, sweat, friction and chemotherapy. Acantholysis is the classic histological finding. Management includes general measures, topical corticosteroids, calcineurin inhibitors, tretinoin, calcipotriene and antihistamines. In refractory cases, second-line treatment is used: oral isotretinoin, systemic corticosteroids and phototherapy. Paradoxically, phototherapy can also trigger GD. Conclusions: Due to the low prevalence of GD in Chile, 2 new cases are provided to the literature. In both cases, the diagnostic presumption was based on an exhaustive clinical history, confirmed by histopathological findings. (AU)

Pemphigus foliaceus as a differential diagnosis in vesicobullous lesions / Pênfigo foliáceo como diagnóstico diferencial em lesões vesicobolhosas

ABSTRACT Given the challenge of clinical diagnosis of bullous skin lesions, this report aimed to discuss the histological changes, the presentation and clinical reasoning for diagnosis of these lesions. At the same time, the importance of the pathology was reviewed to identify these clinical scenarios. In this case report, we highlighted the clinical progression of a case of pemphigus foliaceus.

RESUMO Considerando o desafio do diagnóstico clínico de lesões cutâneas de apresentação bolhosa, o presente trabalho procurou discutir as alterações histológicas, a apresentação e o raciocínio clínico para o diagnóstico de tais lesões. Paralelamente, a importância da patologia foi revisada na identificação destes quadros. Neste relato de caso, destaca-se a evolução clínica de um quadro de pênfigo foliáceo.

A Case of Papular Acantholytic Dyskeratosis Treated with Carbon Dioxide Laser / 대한피부과학회지

Papular acantholytic dyskeratosis is a collection of papular skin lesions that occur in the intertriginous and genital area. They show a characteristic histology of focal suprabasal acantholysis that distinguishes it from Hailey-Hailey disease or Darier disease. We describe a 50-year-old man with an asymptomatic papular eruption on the perianal area for several years. Histologically, a biopsy specimen showed diffuse hyperkeratosis and irregular acantholysis throughout the epidermis. We used carbon dioxide laser therapy as a therapeutic option. Despite causing a long and painful healing process, a considerable reduction of the symptoms was achieved. Although we do not know the precise nature or the incidence of this disease, papular acantholytic dyskeratosis should be included in the differential diagnosis of verrucous papules in perineal or perianal areas and carbon dioxide laser may represent a good therapeutic option.

Detection of apoptosis in pemphigus vulgaris by TUNEL technique

Abstract: Background: Pemphigus is part of a group of blistering diseases that affect the skin and mucous membranes. Based on its autoimmune origin, autoantibodies develop in pemphigus that are directed toward cell surface components of keratinocytes. However, some data cannot be explained, such as the lack of a relationship between autoantibody levels and the severity of clinical manifestations, treatment resistance, the presence of inflammatory infiltrates and the potential occurrence of apoptosis as determinants of vesicle formation. Objective: To examine the presence of apoptosis in pemphigus vulgaris by TUNEL technique. Methods: In this cross-sectional study, we selected 15 paraffin-embedded tissues from subjects who were diagnosed with pemphigus vulgaris by hematoxylin and eosin staining. The samples were subjected to TUNEL assay and examined under an Olympus BX61 fluorescence microscope. Positivity was categorized dichotomously, and the statistical analysis was performed using the X2 test. Results: Positivity was observed in basal layer cells in 14 (93.3%) cases. In 13 (86.7%) of the positive cases, we noted espinosum and granular layers that formed the blister roof, and in 12 cases (80%), positive acantholytic cells were observed. Conclusions: TUNEL positivity was observed in pemphigus vulgaris, implicating apoptosis in the pathophysiology of this condition, which can help guide the development of apoptotic blockers as therapeutics.

Grover Disease Showing Features of Nonspecific Eczematous Dermatosis / 대한피부과학회지

Grover disease (GD), also referred to as transient or persistent acantholytic dermatosis, is an acquired pruritic papular or papulovesicular eruption characterized histopathologically by focal acantholysis and dyskeratosis. Because GD resembles several generalized papular diseases, the diagnosis of GD is a clinical challenge, particularly when dermatologists meet patients without papular eruptions. We experienced two elderly men showing eczematoid plaques with severe pruritus on their backs. Histopathological examinations revealed a focal acantholysis, spongiosis, and dyskeratosis, a pattern consistent with GD. We report two cases of GD with clinical features of nonspecific eczematous dermatosis.

Grover Disease Showing Features of Nonspecific Eczematous Dermatosis / 대한피부과학회지

Grover disease (GD), also referred to as transient or persistent acantholytic dermatosis, is an acquired pruritic papular or papulovesicular eruption characterized histopathologically by focal acantholysis and dyskeratosis. Because GD resembles several generalized papular diseases, the diagnosis of GD is a clinical challenge, particularly when dermatologists meet patients without papular eruptions. We experienced two elderly men showing eczematoid plaques with severe pruritus on their backs. Histopathological examinations revealed a focal acantholysis, spongiosis, and dyskeratosis, a pattern consistent with GD. We report two cases of GD with clinical features of nonspecific eczematous dermatosis.

A Case of Linear Grover Disease Distributed along the Blaschko Line / 대한피부과학회지

Grover disease (also known as transient or persistent acantholytic dermatosis) is a pruritic polymorphic papulovesicular eruption that is histologically characterized by the presence of epidermal acantholysis. It primarily occurs in middle-aged individuals and manifests as scattered erythematous or brown papules as well as papulovesicles on the sun-exposed skin of the trunk. A 52-year-old man had erythematous papules and patches linearly arranged on the left thigh and leg with mild pruritus. The skin lesions were successfully treated with a topical corticosteroid. However, 2 months later, the lesions recurred. The histological examination of a punch biopsy revealed focal acantholytic clefts with dyskeratotic cells, hyperkeratosis, and the infiltration of perivascular lymphocytes and eosinophils. Taken together with the late onset and lack of family history, we diagnosed this condition as Grover disease distributed along the Blaschko line, a condition presented here for the first time.

Pénfigo vulgar, reporte de un caso clínico / Pemphigus vulgaris: report on a clinical case

Introducción: el pénfigo vulgar es una enfermedad ampollosa, mucocutánea, poco frecuente, de base autoinmunitaria y de carácter grave, curso agresivo y evolución crónica, que requiere tratamiento continuo y sistemático para evitar su evolución letal. Se caracteriza por la aparición de ampollas intraepiteliales acantolíticas y costras con predilección por el cuero cabelludo, áreas de presión, axilas, ingle y mucosas. Caso: en el presente artículo se describe el caso de un paciente con lesiones localizadas en el rostro y cuero cabelludo. Clínica e histológicamente fue diagnosticado como pénfigo vulgar. El tratamiento consistió en corticoides orales e inmunosupresores obteniéndose notable mejoría clínica en el paciente.

Introduction: pemphigus vulgaris is a rare autoimmune blistering disease, characterized by an aggressive and chronic course, requiring continuous and systematic treatment to prevent lethal evolution. It is characterized by the appearance of intraepithelial acantholytic blisters and scabs with a predilection for the scalp, pressure areas, armpits, groin and mucous membranes. Case study: in this article we present the case of a patient with localized lesions on the face and scalp, clinically and histologically was diagnosed as pemphigus vulgaris. Treatment consisted of oral corticosteroids and immunosuppressive treatment.

Presentación simultánea de pénfigos vulgar y foliáceo / Simultaneous presentation of pemphigus vulgaris and foliaceus / Apresentação simultânea de pênfigo vulgar e foliáceo

El pénfigo foliáceo y el pénfigo vulgar son enfermedades autoinmunes caracterizadas por vesículas y ampollas que se rompen fácilmente dejando erosiones superficiales. Las ampollas están localizadas en diferentes sitios de la epidermis dependiendo del perfil inmunológico con el que cursen. Se reporta el caso de una paciente con presentación simultánea de pénfigo vulgar y pénfigo foliáceo, una asociación de baja incidencia con pocos casos informados en la literatura.

Pemphigus foliaceus and vulgaris are autoimmune diseases characterized by blisters that break easily leaving behind superficial erosions, with different locations in the epidermis depending on the immunologic profile with which they present. We report the case of a patient with simultaneous presentation of pemphigus vulgaris and pemphigus foliaceus, an association of low incidence with few cases reported in the literature.

O pênfigo foliáceo e o pênfigo vulgar são doenças autoimunes caracterizadas por vesicular e bolhas que se quebram facilmente deixando erosões superficiais. As bolhas ficam localizadas em diferentes regiões da epidermes dependendo do perfil imunológico. Reportamos o caso de um paciente com apresentação simultânea de pênfigo vulgar e pênfigo foliáceo, uma associação de baixa incidência com poucos casos informados na literatura.

Localized Darier's Disease Mimicking Lichen Simplex Chronicus on the Back / 대한피부과학회지

Darier's disease is an autosomal dominant acantholytic skin disorder. The disease is characterized by symmetric distribution of hyperkeratotic papules in seborrheic regions of the skin and nail changes with potential for exacerbation by ultraviolet light, heat, occlusion, or stress. It presents as generalized (hypertrophic or vesiculobullous type) or localized (linear or zosteriform type) condition. A 53-year-old male patient presented with hyperkeratotic verrucous papules on the back that had an onset in childhood. Clinically, his condition resembled lichen simplex chronicus. The lesions were exacerbated by sun exposure or sweating. A 3-mm punch biopsy specimen revealed prominent acantholysis with hyperkeratosis and parakeratosis. Numerous corps grains and corps ronds were present near the granular layer. We report a case of localized Darier's disease mimicking lichen simplex chronicus on the back. The skin lesion improved following treatment with a topical corticosteroid. Localized Darier's disease should be considered as one of the differential diagnoses of lichen simplex chronicus on the back.

Paraneoplastic Pemphigus Associated with Hepatocellular Carcinoma / 대한피부과학회지

PNP is a rare autoimmune mucocutaneous blistering disease associated with neoplasms, most frequently of the lymphoproliferative type. As PNP is clinically characterized by polymorphous mucosal lesions and cutaneous eruptions, it is important to differentiate it from erythema multiforme, Stevens-Johnson syndrome, lichen planus, and other bullous diseases. A diagnosis of PNP can be confirmed by immunologic studies such as direct and indirect immunofluorescence, immunoblotting, immunoprecipitation. Rare PNP cases related to nonhematological solid tumors have been reported. A 54-year-old male visited us with generalized pruritic scaly lichenoid lesions on the whole body from 5 weeks prior to his first visit. He also presented with extensive painful ulcers and erosions on the oral mucosa and lips for 2 months. Histopathologic findings showed lichenoid infiltration with vacuolar interface change, lichenoid interface dermatitis, keratinocyte apoptosis, and suprabasal acantholysis with cleft. Indirect immunofluorescence using normal human skin showed IgG deposition at the intercellular space. Immunoblotting using normal epidermal extracts in the serum of patient detected antibody to the 190 kDa (envoplakin), 210 kDa (periplakin) molecules polypeptides. He also had a hepatocellular carcinoma and chemoradiotherapy done before. The diagnosis of paraneoplastic pemphigus (PNP) was made. To our knowledge, there are only two reports of PNP associated with hepatocellular carcinoma worldwide, yet no report in Korean literature. Herein, we report the first case of PNP associated with hepatocellular carcinoma in Korea.

Scanning electron microscopy of acantholysis in pemphigus foliaceus / Microscopia eletrônica de varredura da acantólise no pênfigo foliáceo

We performed scanning electron microscopy of an inverted blister roof in a case of pemphigus foliaceus. The loss of intercellular adherence could be easily seen with low magnification. The acantholytic keratinocytes displayed an irregular and sometimes polygonal contour. Round cells, typically seen in light microscopy, were also observed. The examination of a blister roof allows ultrastructural documentation of the acantholytic changes.

Realizamos microscopia eletrônica de varredura do teto invertido de uma bolha de um caso de pênfigo foliáceo. Com pequeno aumento, a perda da adesão intercelular pôde ser vista claramente. Os queratinócitos acantolíticos demostraram um contorno irregular, algumas vezes poligonal. Células arredondadas, como vistas tipicamente na microscopia óptica, também foram observadas. O exame de um teto de bolha permite uma documentação ultraestrutural das alterações acantolíticas.

Inmunopatogenia del pénfigo vulgar y el pénfigo foliáceo / Immunopathogenesis of pemphigus vulgaris and pemphigus foliaceus

El pénfigo vulgar y el pénfigo foliáceo son enfermedades ampollosas autoinmunes mediadas por autoanticuerpos dirigidos contra proteínas de los desmosomas, las desmogleínas 1 y 3. Están asociadas con moléculas del complejo mayor de histocompatibilidad (HLA) que por su estructura tienen la capacidad de presentar péptidos antigénicos de las desmogleínas. En los individuos afectados se han descrito la presencia de linfocitos T y B autorreactivos y alteraciones en la regulación del sistema inmune con desequilibrio de las respuestas Th1/Th2. No se conocen con precisión los mecanismos de daño pero la investigación actual indica que los anticuerpos tienen un papel patogénico, inician diferentes cascadas de señalización que provocan la acantólisis y apoptosis de los queratinocitos. El conocimiento de la inmunopatogenia de las enfermedades ampollosas autoinmunes ha permitido el desarrollo y la puesta en práctica de nuevas alternativas terapéuticas.

Pemphigus vulgaris and pemphigus foliaceus are autoimmune blistering diseases mediated by antibodies against desmosomal proteins. They are strongly associated with major histocompatibility complex alleles with the ability to present antigenic peptides of desmogleins. In the affected individuals the presence of auto-reactive T and B lymphocytes, and alterations in the immune system regulation with imbalance of the Th1/Th2 responses have been described. Damage mechanisms are not yet precisely known but current investigation indicates that antibodies play an important pathogenic role: they start different signaling cascades that lead to acantholysis and apoptosis of keratinocytes. Better knowledge of the pathogenesis of autoimmune blistering diseases has been the basis for the development and implementation of new therapeutic approaches.

Enfermedad de Hailey-Hailey / Hailey-Hailey´s disease

La enfermedad de Hailey-Hailey es una genodermatosis rara, producida por mutaciones en el gen ATP2C1. Se caracteriza por afectar áreas de pliegues, simulando intertrigos de diversas etiologías, lo que genera un retraso en su diagnóstico y tratamiento. Debido a su carácter crónico y a los síntomas que ocasiona, como dolor y fetidez, suele afectar la calidad de vida de los pacientes. Se han propuesto numerosos tratamientos tópicos, físicos y sistémicos. Hasta la fecha no existen modalidades terapéuticas que sean totalmente efectivas, si bien el láser de dióxido de carbono (CO2) ha logrado remisiones prolongadas.

Hailey-Hailey’s disease is a rare hereditary disease caused by ATP2C1-gene mutations. Itaffect the folds, simulating intertrigo of various etiologies, leading to a delay in diagnosisand treatment. Its chronic nature, and symptoms such as pain and bad odour, affects thequality of life of patients.Numerous topical, physical an systemic treatments have been proposed. To date there are nofully effective treatment modalities, although CO2 LASER has achieved prolonged remissions.

Acantholytic Acanthoma with an Atypical Presentation / 대한피부과학회지

Acantholytic acanthoma is a rare benign neoplasm of epidermal keratinocytes and this commonly displays as a solitary, asymptomatic keratotic papule on the trunk. The histologic features are hyperkeratosis, acanthosis, papillomatosis and prominent acantholysis. Dyskeratotic cells are occasionally present, but prominent dyskeratosis is not a characteristic feature of acantholytic acanthoma. Herein, we report on a case of acantholytic acanthoma with several dyskeratoses, and this occurred in a 54-year-old woman who presented with a keratotic plaque that repeatedly pealed on the umbilicus.