ABSTRACT
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.
ABSTRACT
BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are lymphoid proliferations associated with post-transplant immunosuppression. Most originate from B cells and are associated with Epstein-Barr virus (EBV) infection. Although extranodal involvement is common, cutaneous presentation is rare. OBJECTIVE: To report and characterize cutaneous manifestations of PTLD from clinical, histopathologic, and immunohistochemistry standpoints. METHODS: Patients' information was obtained retrospectively by reviewing medical records. Skin biopsies were submitted to histological and immunohistochemistry analysis, and EBV detection was performed by in situ hybridization and polymerase chain reaction (PCR) analysis. Staging examinations were included. A literature review of reported cutaneous PTLD cases was performed. RESULTS: We describe two cases of primary cutaneous and 2 cases of systemic PTLD with secondary cutaneous manifestations. All had late onset disease, which presented at least 6 years after transplantation. Histopathologic findings were compatible with monomorphic PTLD in three cases and plasmacytic hyperplasia in one case. EBV was detected in two patients. Both patients with systemic disease had fatal outcome, and those with primary cutaneous involvement responded to treatment. LIMITATIONS: Due to the rare incidence of cutaneous manifestation of PTLD, the analysis of a large number of cases was not possible. CONCLUSION: Although rare, PTLD should be considered in the differential diagnosis of late onset cutaneous complications post-renal transplant.
