Pénfigo paraneoplásico asociado a leucemia linfocítica crónica / PARANEOPLASTIC PENPHIGUS ASSOCIATED TO CHRONIC LYMPHOCYTIC LEUKEMIA

El pénfigo paraneoplásico es una dermatosis ampollar autoimmune asociada a un proceso neoplásico, conocido previamente o no. Se presenta con mayor frecuencia en hombres, entre los 45 y 70 años, pero también puede manifestarse en niños. La clínica es polimorfa. Existen 5 variantes posibles: pénfigo símil, penfigoide ampollar símil, eritema multiforme símil, enfermedad de injerto contra huésped símil y liquen plano símil. Todas ellas comparten una característica en común: la estomatitis severa, dolorosa, progresiva y refractaria a los tratamientos convencionales, que obliga a descartar esta enfermedad. Si bien los antígenos involucrados en su fisiopatogenia son múltiples, la detección de anticuerpos Ig G anti envoplaquina y anti periplaquina constituye el método de diagnóstico más específico. En la actualidad se utilizan los criterios de diagnóstico de Camisa y Helm, que se basan en hallazgos clínicos (erupción mucocutánea polimorfa), histológicos (acantolisis) e inmunohistoquímicos (inmunofluorescencia directa, indirecta e inmunoprecipitación positivas). El abordaje de esta enfermedad debe considerar dos aspectos: el tratamiento del pénfigo en sí y el de la neoplasia asociada, que puede ser benigna (raro) o maligna (con mayor frecuencia). El pronóstico es severo (mortalidad del 75-90%) y en la mayoría de los casos la causa de muerte depende de las complicaciones de la enfermedad, como sepsis y bronquiolitis obliterante. Se presenta un paciente varón de 67 años con PPN asociado a Leucemia Linfocítica Crónica que respondió satisfactoriamente al tratamiento instaurado (meprednisona + quimioterapia con fludarabina, ciclofosfamida y rituximab) y no presentó recidiva a más de 2 años de seguimiento interdisciplinario.

Paraneoplastic pemphigus is an autoimmune blistering disease associated with neoplasms, previously known or not. It occurs most often in men, between 45-70 years, but can also manifest in children. The clinic is polymorphic. There are 5 possible variants: pemphigus-like, bullous pemphigoid-like, erythema multiforme-like, graft versus host disease-like and lichen planus-like. All of them share a common characteristic: a severe, painful, progressive and refractory to conventional treatments stomatitis, which forces us to rule out this disease. Although the antigens involved in its physiopathogenesis are multiple, the detection of anti-envoplakin and anti-periplakin IgG antibodies constitutes the most specific diagnostic method. At present, the diagnostic criteria of Camisa and Helm are used, which are based on clinical (polymorphic mucocutaneous eruption), histological (acantholysis) and immunohistochemical findings (direct and indirect immunofluorescence and immunoprecipitation positive). The approach to this disease must consider two aspects: treatment of the pemphigus as well as the associated neoplasm, which can be benign (rare) or malignant (more frequently). The prognosis is severe (mortality of 75-90%) and in most cases the cause of death depends on the complications of the disease, such as sepsis and bronchiolitis obliterans. We present a 67-year-old male patient with PPN associated with Chronic Lymphocytic Leukemia who responded satisfactorily to the established therapy (meprednisone + chemotherapy with fludarabine, cyclophosphamide and rituximab) and did not present recurrence after more than two years of interdisciplinary follow-up.

Role of autoantibodies against the linker subdomains of envoplakin and periplakin in the pathogenesis of paraneoplastic pemphigus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The presence of autoantibodies against multiple epidermal proteins is an important feature in paraneoplastic pemphigus (PNP). Circulating anti-desmoglein 3 autoantibody, the major pathogenic autoantibody in pemphigus vulgaris (PV), has been proved pathogenic in PNP. Because of many clinical differences between PNP and PV, we speculate about the involvement of other autoantibodies in the pathogenesis of PNP. Envoplakin (EPL) and periplakin (PPL) are recognized by most PNP sera. Their linker subdomains are highly homologous and necessary for the association of intermediate filaments.</p><p><b>METHODS</b>We characterized the autoantibodies against the linker subdomains of EPL and PPL in PNP patients' sera and their associated tumors by enzyme-linked immunosorbent assay (ELISA) and immunofluorence. We also applied the purified autoantibodies against EPL and PPL from PNP sera to cultured human epidermal keratinocytes (HEK), to evaluate the changes of cell-cell adhesion.</p><p><b>RESULTS</b>Autoantibodies against EPL and PPL were detected in most PNP patients by ELISA, and the decrease of these autoantibodies after removal of the tumors was roughly comparable to the improvement of clinical symptoms. Cultured tumor cells from PNP patients secreted these autoantibodies. Specific immunoglobulin receptors for EPL and PPL were found on B lymphocytes in tumors from PNP. Furthermore, purified anti-EPL and anti-PPL autoantibodies from PNP sera were capable of dissociating cultured human epidermal keratinocytes.</p><p><b>CONCLUSION</b>Autoantibodies against EPL and PPL may also be pathogenic in PNP.</p>