Lesions of pemphigus vulgaris on irradiated skin

Summary Pemphigus vulgaris (PV) is an autoimmune blistering disease produced by IgG autoantibodies against desmoglein (Dsg)3. Lesions on the skin and mucosa can, in rare cases, be induced by radiotherapy. We report a patient with a history of microprolactinoma and PV, who had only oral lesions from the beginning of her illness but 2 months after treatment with radiotherapy for a breast neoplasia, developed skin lesions limited to the irradiated area. Over the following few months, she also developed autoantibodies against Dsg

An imbalance in Akt/mTOR is involved in the apoptotic and acantholytic processes in a mouse model of pemphigus vulgaris

Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by the presence of IgG autoantibodies against Dsg3. Our aim was to investigate the molecular events implicated in the development and localization of apoptosis and acantholysis in PV. We used a passive transfer mouse model together with immunohistochemical (IHC) techniques and the TUNEL assay, with quantification analysis in the basal layer of the epidermis. The activated signalling molecules analysed and apoptotic cells detected showed an identical localization. Herein, we found for the first time in vivo an increased expression of activated HER receptor isoforms in the basal layer in PV lesions. Besides, we observed the almost total lack of activated Akt compared with a higher level of activated mTOR within the basal cells of the epidermis. Our observations strongly support that the restriction of acantholysis to the basal layer may be due, at least in part, to the selective and increased presence of activated HER receptor isoforms in these cells. After phosphorylation of HER receptor isoforms, intracellular signalling pathways are activated in the basal layer. In addition, the imbalance in Akt/mTOR that takes place in the basal cells may provide intracellular signals necessary for the development of apoptosis and acantholysi

Ear, nose and throat manifestations in pemphigus vulgaris

Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein 3. There are two clinical forms: mucosal (MPV) and mucocutaneous (MCPV). The frequency of ear, nose and throat (ENT) involvement in PV is not clearly defined. Only a few isolated individual cases have been reported. OBJECTIVES: The objective of our study was to determine the incidence of ENT involvement in patients with PV. PATIENTS: We studied prospectively all 16 patients diagnosed with PV and treated in the Department of Dermatology of the University Clinic of Navarra between 2001 and 2005. They were 10 cases of MPV and six cases of MCPV. All patients were evaluated for ENT manifestations by endoscopic examination. RESULTS: Of the 16 patients, 13 presented with throat symptoms (81%), 12 pharyngeal (75%) and seven laryngeal symptoms (44%). Fourteen patients (88%) had active PV lesions on endoscopic evaluation (eight patients had active lesions on both pharyngeal and laryngeal mucosa, four had PV lesions only on laryngeal mucosa and two had PV lesions on pharyngeal mucosa). Laryngeal lesions were most commonly present in MPV patients. The frequency of nasal symptoms (38%) was lower than active PV lesions (62%) found on ENT examination. Oral symptoms and oral active PV lesions were the most frequent findings (94%). Only three patients with MCPV showed erosions on the external auditory canal. CONCLUSIONS: As ENT endoscopy allows more extensive areas of mucosa to be examined than simple visual inspection, we recommend that it be included in the examination of all patients with PV. By obtaining more complete information concerning the extent of the disease, a more accurate diagnosis can be made, better choice of drug and dose may be decided and, ultimately, response to treatment may be improved

Papel de las isoformas HER y la mTOR en la acantólisis del pénfigo vulgar en un modelo murino

El pénfigo vulgar (PV) es una enfermedad ampollosa autoinmune que afecta a piel y mucosas, caracterizada por la presencia de autoanticuerpos IgG frente a la desmogleína 3 (Dsg3) que provocan una ruptura intraepitelial de la epidermis llamada acantólisis. El mecanismo por el cual se produce la acantólisis no es del todo conocido. Nuestro objetivo en este trabajo fue investigar los eventos moleculares implicados en el desarrollo y la localización de la apoptosis y la acantólisis en el PV. Parra ello empleamos el modelo murino de tranferencia pasiva con estudios de inmunohistoquímica con un análisis cuantitativo y la técnica TUNEL para el estudio de la apoptosis. Tanto las moléculas de señalización activadas analizadas como las células apoptóticas detectadas mostraron la misma localización. Hemos observado por primera vez in vivo un aumento de la expresión de las isoformas activadas de los receptores HER en la capa basal de la epidermis en las lesiones de PV. La importancia de este hallazgo se ve reforzada por el hecho de que el pretratamiento de los ratones con erlotinib (inhibidor de HER1, HER2 Y HER3) inhibió tanto la enfermedad clínica como histológica. Además, hemos hallado una casi nula expresión de la Akt activada comparada con un nivel más elevado de la mTOR activada dentro de las células basales de la epidermis. Tras el pretratamiento de los animales con rapamicina (inhibidor de mTRO) pudimos observar cómo se anularon las manifestaciones clínicas e histológicas del PV. Nuestras observaciones sugieren que la acntólisis podría estar restringida a la capa basal, al menos en parte, por el aumento selectivo de las isoformas activadas de los receptores HER que ocurre en estas células. Después de la forsforilación de las isoformas de los receptores HER, se activarían vías de señalización intracelular en la capa basal epidérmica. Además, el desequilibrio de Akt/mTOR que tiene lugar en las células de la capa basal podría aportar las señales intracelulares necesarias para el desarrollo de la apoptosis y la acantólisis

Successful topical sirolimus treatment of epidermal nevus in a patient with phacomatosis spilosebacea

Epidermal nevi (EN) are hamartomas of keratinocytic or epidermal appendages which are most frequently seen as isolated birthmarks. EN syndromes (ENS) are a heteroge- neous group of disorders caused by somatic mosaicism and characterized by the presence of an EN with associated in- volvement of other organ systems.1 Phacomatosis spilose- bacea (PSS) is a rare ENS defined by the co-occurrence of papular speckled lentiginous nevus (or nevus spilus) and nevus sebaceus (NS), a common type of EN.2 Postzygotic- activating HRAS mutation in a multipotent progenitor cell has been described as the underlying pathogenetic mecha- nism of both types of nevi in PSS.2,3 Treatment of EN can be challenging. Although full-thickness excision is curative, these lesions may occur in locations where the surgery would result in disfigurement. Other treatments like topical corti- costeroids, retinoic acid and 5-fluorouracil or ablative laser have been used with different and limited results.1,