Differential gene expression in drug hypersensitivity reactions: induction of alarmins in severe bullous diseases.

BACKGROUND: Delayed hypersensitivity reactions to drugs can be life-threatening and constitute a growing problem in clinical practice. Although drug-specific T cells seem to be involved, the cellular and molecular bases of their aetiopathology are not fully understood. OBJECTIVES: To study the molecular mechanisms underlying the pathogenesis and the clinical heterogeneity of cutaneous delayed hypersensitivity reactions to drugs. MATERIALS AND METHODS: We characterized the gene expression profiles of peripheral blood mononuclear cells (PBMCs) isolated from patients during the acute phase of the reaction and upon resolution of clinical symptoms using a cDNA array technology. Low-density arrays were used to confirm differential expression of selected genes during the acute disease in patients and to compare gene expression in patients and exposed control donors by quantitative real-time polymerase chain reaction. RESULTS: Eighty-five genes were found to be differentially expressed during the acute phase of cutaneous drug-induced delayed hypersensitivity reactions. Furthermore, 92 genes with distinct expression patterns in severe and benign diseases during the acute phase were identified. PBMCs from patients with severe bullous diseases showed a characteristic gene expression pattern with lower expression of genes encoding T cell-specific proteins and high expression of cell cycle-related genes and genes coding for inflammatory-related mediators among which several endogenous damage-associated molecular patterns (DAMPs) or alarmins were found. CONCLUSIONS: Distinct gene expression profiles in PMBCs define benign and severe clinical entities. Overexpression of endogenous DAMPs in Stevens-Johnson syndrome and toxic epidermal necrolysis suggest that drugs can trigger the alarmin system in sensitized patients leading to life-threatening diseases.

Arrugamiento acuagénico palmar en unniño con fibrosis quística / Aquagenic wrinkling of the palmas in a young boy with cystic fibrosis

El arrugamiento acuagénico es una afección cutánea descrita en la última década. Se considera poco frecuente, característico de mujeres jóvenes eidiopático; aunque en al menos tres enfermos se ha relacionado con la toma de antiinflamatorios inhibidores selectivos de la ciclooxigenasa-2. Recientementese ha recuperado su vinculación, realizada hace más de 30 años, con la fibrosis quística, y se ha referido en tres pacientes con dicha enfermedad.Describimos un nuevo caso en un niño de 5 años con fibrosis quística, documentada con estudio genético. Discutimos su eventual consideracióncomo marcador cutáneo de la fibrosis quística (AU)

Aquagenic wrinkling is a cutaneous condition described in the last decade. It is considered to be uncommon, typical in young females and idiopathic;although it has been related with selective inhibitor of cyclooxygenasa-2 anti-inflammatory medication intake in at least three patients. Recently itsrelationship with cystic fibrosis, recognised more than 30 years earlier, has been recovered and three patients have been reported in with that disease.A new genetically documented cystic fibrosis case in a 5 year old boy is described. The eventual consideration of this condition as a cystic fibrosis cutaneousmarker is discussed (AU)

Up-regulation of CCL17, CCL22 and CCR4 in drug-induced maculopapular exanthema.

BACKGROUND: Maculopapular exanthema has been reported to be the most frequently drug-induced cutaneous reaction. Although T lymphocytes are involved in the pathomechanism of this disease, little is know about the recruitment of these cells to the skin. OBJECTIVE: The aim of this work is to study the role of the chemokines TARC/CCL17 and MDC/CCL22 in the lymphocyte trafficking to affected skin in drug-induced exanthemas. METHODS: Real-time PCR was performed to quantify gene expression levels of CCL17, CCL22 and their receptor CCR4 in lesional skin biopsies and in peripheral blood mononuclear cells from patients. CCL27 and CCL22 proteins were detected in the skin by immunochemistry. Protein expression of CCR4 was determined by flow cytometry in peripheral blood lymphocytes. Functional migration assays to CCL17 and CCL22 were assessed to compare the migratory responses of peripheral blood lymphocytes from patients and healthy subjects. RESULTS: CCL17 and CCL22 were up-regulated in maculopapular exanthema-affected skin. CCR4 mRNA levels and protein expression were increased in peripheral blood mononuclear cells during the acute phase of the disease. The increased expression of the receptor was consistent with a higher response of peripheral blood lymphocytes to CCL17 and CCL22 compared with the migratory response in healthy donors. CONCLUSION: TARC/CCL17 and MDC/CCL22 might cooperate in attracting T lymphocytes to skin in drug-induced maculopapular exanthemas.

[Leishmania braziliensis: report of a pediatric imported case with response to liposomal amphotericin B]. / Leishmania braziliensis: descripción de un caso pediátrico importado con respuesta a anfotericina B liposomal.

Leishmania braziliensis is the main etiologic agent of leishmaniasis in South America. A 9-year-old boy consulted for the presence of round, ulcerative lesions with raised borders that were painful and have appeared after a travel to Bolivia and Brazil. The culture for parasites showed leishmanias and the PCR was positive for L. braziliensis. The patient underwent treatment with itraconazol but due to the persistence of lesions he received liposomal amphotericin B with complete resolution of the lesions. In all lesions by L. braziliensis the treatment must be systemic due to the risk of mucosal dissemination. Liposomal amphotericin B is a convenient alternative to pentavalent antimonials given its efficacy and good tolerance.

Leishmania braziliensis: descripción de un caso pediátrico importado con respuesta a anfotericina B liposomal / Leishmania braziliensis: report of a pediatricimported case with response to liposomalamphotericin B

Leishmania braziliensis es el principal agente etiológico de leishmaniasis cutánea en América del Sur. Un varón de 9 años consultó por lesiones redondeadas ulceradas de bordes sobreelevados, que eran dolorosas y habían aparecido después de un viaje por Bolivia y Brasil. En el cultivo de parásitos se objetivaron Leishmanias y la reacción en cadena de la polimerasa (PCR) para L. braziliensis fue positiva. El paciente realizó tratamiento con itraconazol, y por persistencia de las lesiones inició anfotericina B liposomal con resolución completa de las mismas. En toda lesión por L. braziliensis el tratamiento debe ser sistémico por el riesgo de diseminación mucosa. La anfotericina B liposomal es una buena alternativa a los antimoniales pentavalentes por su eficacia y buena tolerancia

Leishmania braziliensis is the main etiologic agent of leishmaniasis in South America. A 9-year-old boy consulted for the presence of round, ulcerative lesions with raised borders that were painful and have appeared after a travel to Bolivia and Brazil. The culture for parasites showed leishmanias and the PCR was positive for L. braziliensis. The patient underwent treatment with itraconazol but due to the persistence of lesions he received liposomal amphotericin B with complete resolution of the lesions. In all lesions by L. braziliensis the treatment must be systemic due to the risk of mucosal dissemination. Liposomal amphotericin B is a convenient alternative to pentavalent antimonials given its efficacy and good tolerance

[Acrocyanosis as a form of presentation of progressive systemic sclerosis]. / Acrocianosis como forma de debut de una esclerosis sistémica progresiva.

Acrocyanosis is an infrequent entity characterized by persistent and symmetrical erythrocyanotic discoloration of the hands, feet and face, which is not preceded by episodes of previous paleness. Acrocyanosis can be secondary to a variety of underlying causes, but is uncommon as a form of presentation of systemic sclerosis. We present a new clinical case of this disease and discuss its etiopathogenic, clinical, diagnostic and therapeutic characteristics; in addition to, we seek to distinguish this term from others that might be confused in the literature.

Acrocianosis como forma de debut de una esclerosis sistémica progresiva / Acrocyanosis as a form of presentation of systemic sclerosis

La acrocianosis es un cuadro clínico caracterizado por una coloración azul violácea persistente y simétrica de zonas acras, principalmente manos y pies, que no está precedida por episodios de palidez previos. Es una entidad que puede asociarse a diversas causas subyacentes, pero es infrecuente que lo haga como forma de debút de una esclerosis sistémica progresiva. Se presenta a continuación un nuevo caso de esta patología y se comentan sus características etiopatogénicas, clínicas y diagnósticas más relevantes además de un intento de diferenciar este término de otros con los que existe confusión en la literatura

Acrocyanosis is an infrequent entity characterized by persistent and symmetrical erythrocyanotic discoloration of the hands, feet and face, which is not preceded by episodes of previous paleness. Acrocyanosis can be secondary to a variety of underlying causes, but is uncommon as a form of presentation of systemic sclerosis. We present a new clinical case of this disease and discuss its etiopathogenic, clinical, diagnostic and therapeutic characteristics; in addition to, we seek to distinguish this term from others that might be confused in the literature

Tinea manuum inflamatoria / Inflammatory tinea manuum

No disponible