NLRP3 Regulates IL-4 Expression in TOX+ CD4+ T Cells of Cutaneous T Cell Lymphoma to Potentially Promote Disease Progression.

In cutaneous T cell lymphoma (CTCL), a dominant Th2 profile associated with disease progression has been proposed. Moreover, although the production and regulation of IL-4 expression during the early stages of the disease may have important implications in later stages, these processes are poorly understood. Here, we demonstrate the presence of TOX+ CD4+ T cells that produce IL-4+ in early-stage skin lesions of CTCL patients and reveal a complex mechanism by which the NLRP3 receptor promotes a Th2 response by controlling IL-4 production. Unassembled NLRP3 is able to translocate to the nucleus of malignant CD4+ T cells, where it binds to the human il-4 promoter. Accordingly, IL-4 expression is decreased by knocking down and increased by promoting the nuclear localization of NLRP3. We describe a positive feedback loop in which IL-4 inhibits NLRP3 inflammasome assembly, thereby further increasing its production. IL-4 induced a potentially malignant phenotype measured based on TOX expression and proliferation. This mechanism of IL-4 regulation mediated by NLRP3 is amplified in late-stage CTCL associated with disease progression. These results indicate that NLRP3 might be a key regulator of IL-4 expression in TOX+ CD4+ T cells of CTCL patients and that this mechanism might have important implications in the progression of the disease.

Clinical variants of mycosis fungoides in a cohort.

INTRODUCTION: Mycosis fungoides (MF) is the most common primary skin T-cell lymphoma, which is characterized for a heterogeneous clinical expressivity. OBJECTIVE: To report clinical variants and sociodemographic characteristics in patients with MF under the care of a dermatological hospital. METHODS: 290 patients with MF clinical and histopathological diagnosis attended to over the course of 11 years were included. Sociodemographic description of patients was made, who were classified according to clinical and histopathological variants. RESULTS: MF was recorded in 57.9 % of women and 42 % of men. The most common clinical variant was the classic type in 46.2 %; dyschromic variants accounted for 35.2 %, out of which hypopigmented MF was the most representative (17.6 %); poikilodermatous MF accounted for 4.1 %, and folliculotropic, for 3.1%. The papular variant occurred in six patients (2.1 %), the single-plaque variety in three (1%), and the ichthyosiform, syringotropic and granulomatous slack skin varieties occurred in one patient each. The granulomatous variant was found in 0.7 %, and 1.4 % had erythroderma. CONCLUSIONS: The most common MF clinical variant was classic plaque stage, followed by dyschromic variants. Other clinical variants accounted for 18.6 %.

INTRODUCCIÓN: La micosis fungoide es el linfoma primario de células T en piel más frecuente, con expresividad clínica heterogénea. OBJETIVO: Reportar las variedades clínicas y las características sociodemográficas en pacientes con micosis fungoide tratados en un hospital dermatológico. MÉTODOS: Se incluyeron 290 pacientes con diagnóstico clínico e histopatológico de micosis fungoide atendidos en el transcurso de 11 años. Se realizó descripción sociodemográfica de los pacientes, quienes se clasificaron conforme las variantes clínicas e histopatológicas. RESULTADOS: La micosis fungoide se presentó en 57.9 % mujeres y 42 % hombres. La variedad clínica más común fue la clásica en 46.2 %; la discrómica representó 35.2 %, del cual la hipopigmentada fue la más representativa (7.6 %); la poiquilodérmica constituyó 4.1 % y la foliculotrópica, 3.1 %. La variedad papular se presentó en seis pacientes (2.1 %), la de placa única en tres (1 %) y la ictiosiforme, siringotrópica y la piel laxa granulomatosa, en un paciente cada una. La variedad granulomatosa se encontró en 0.7 % y 1.4 % presentó eritrodermia. CONCLUSIONES: La variedad clínica más frecuente de micosis fungoide fue la clásica en fase de placa, seguida de las variedades discrómicas. Otras variedades clínicas representaron 18.6 %.

Variedades clínicas de micosis fungoide en una cohorte / Clinical variants of mycosis fungoides in a cohort

Resumen Introducción: La micosis fungoide es el linfoma primario de células T en piel más frecuente, con expresividad clínica heterogénea. Objetivo: Reportar las variedades clínicas y las características sociodemográficas de pacientes con micosis fungoide tratados en un hospital dermatológico. Métodos: Se incluyeron 290 pacientes con diagnóstico clínico e histopatológico de micosis fungoide atendidos en el transcurso de 11 años. Se realizó descripción sociodemográfica de los pacientes, quienes se clasificaron conforme las variantes clínicas e histopatológicas. Resultados: 58 % de los casos de micosis fungoide se presentó en mujeres y 42 % en hombres. La variedad clínica más común fue la clásica en 46.2 %; la discrómica representó 35.2 %, del cual la hipopigmentada fue la más representativa (7.6 %); la poiquilodérmica constituyó 4.1 % y la foliculotrópica, 3.1 %. La variedad papular se presentó en seis pacientes (2.1 %), la de placa única en tres (1 %) y la ictiosiforme, siringotrópica y la piel laxa granulomatosa, en un paciente cada una. La variedad granulomatosa se encontró en 0.7 % y 1.4 % presentó eritrodermia. Conclusiones: La variedad clínica más frecuente de micosis fungoide fue la clásica en fase de placa, seguida de las variedades discrómicas. Otras variedades clínicas representaron 18.6 %.

Abstract Introduction: Mycosis fungoides (MF) is the most common primary skin T-cell lymphoma, which is characterized for a heterogeneous clinical expressivity. Objective: To report clinical variants and sociodemographic characteristics in patients with MF under the care of a dermatological hospital. Methods: 290 patients with MF clinical and histopathological diagnosis attended to over the course of 11 years were included. Sociodemographic description of patients was made, who were classified according to clinical and histopathological variants. Results: MF was recorded in 57.9 % of women and 42 % of men. The most common clinical variant was the classic type in 46.2 %; dyschromic variants accounted for 35.2 %, out of which hypopigmented MF was the most representative (17.6 %); poikilodermatous MF accounted for 4.1 %, and folliculotropic, for 3.1%. The papular variant occurred in six patients (2.1 %), the single-plaque variety in three (1%), and the ichthyosiform, syringotropic and granulomatous slack skin varieties occurred in one patient each. The granulomatous variant was found in 0.7 %, and 1.4 % had erythroderma. Conclusions: The most common MF clinical variant was classic plaque stage, followed by dyschromic variants. Other clinical variants accounted for 18.6 %.

[Validation of a questionnaire to quantify the risk for skin cancer]. / Validación de un cuestionario para cuantificar el riesgo de cáncer de piel.

INTRODUCTION: Currently, strategies are needed to identify the population at risk for skin cancer in order to implement prevention and for early diagnosis. There are no validated Spanish language instruments to measure skin cancer risk. OBJECTIVES: To design and validate a self-applied questionnaire to quantify the risk of melanoma and non-melanoma skin cancer in a Mexican population. METHODS: A self-applied questionnaire was designed to measure risk factors for skin cancer. Face and content validity was assessed by five experts in skin cancer. The value of each item was weighted according to the relative risk of the risk factors. The questionnaire was applied to extreme groups in order to measure the construct validity. Reliability was evaluated using test-retest method two weeks after the first application. RESULTS: The questionnaire was applied to patients with (n = 147) and without (n = 249) skin cancer from the Dermatologic Center "Dr. Ladislao de la Pascua". The total score of the questionnaire was different in both groups (U = 2,104.5, p = 0.0001) and ROC curve determined that five points or more equals high risk for skin cancer (area 0.964; 95% CI: 0.946-0.981; p = 0.0001). The reliability of the instrument was 0.971 (95% CI: 0.943-0.986; p = 0.0001). CONCLUSION: This is the first Spanish language questionnaire valid to measure risk of skin cancer, whose application at the population level would be useful to identify high-risk individuals who need preventative interventions.