Minimal Antigenic Evolution after a Decade of Norovirus GII.4 Sydney_2012 Circulation in Humans.

Norovirus is a major human pathogen that can cause severe gastroenteritis in vulnerable populations. The extensive viral diversity presented by human noroviruses constitutes a major roadblock for the development of effective vaccines. In addition to the large number of genotypes, antigenically distinct variants of GII.4 noroviruses have chronologically emerged over the last 3 decades. The last variant to emerge, Sydney_2012, has been circulating at high incidence worldwide for over a decade. We analyzed 1449 capsid sequences from GII.4 Sydney_2012 viruses to determine genetic changes indicative of antigenic diversification. Phylogenetic analyses show that Sydney_2012 viruses scattered within the tree topology with no single cluster dominating during a given year or geographical location. Fourteen residues presented high variability, 7 of which mapped to 4 antigenic sites. Notably, ~52% of viruses presented mutations at 2 or more antigenic sites. Mutational patterns showed that residues 297 and 372, which map to antigenic site A, changed over time. Virus-like particles (VLPs) developed from wild-type Sydney_2012 viruses and engineered to display all mutations detected at antigenic sites were tested against polyclonal sera and monoclonal antibodies raised against Sydney_2012 and Farmington_Hills_2002 VLPs. Minimal changes in reactivity were detected with polyclonal sera and only 4 MAbs lost binding, with all mapping to antigenic site A. Notably, reversion of residues from Sydney_2012 reconstituted epitopes from ancestral GII.4 variants. Overall, this study demonstrates that, despite circulating for over a decade, Sydney_2012 viruses present minimal antigenic diversification and provides novel insights on the diversification of GII.4 noroviruses that could inform vaccine design. IMPORTANCE GII.4 noroviruses are the major cause of acute gastroenteritis in all age groups. This predominance has been attributed to the continued emergence of phylogenetically discrete variants that escape immune responses to previous infections. The last GII.4 variant to emerge, Sydney_2012, has been circulating at high incidence for over a decade, raising the question of whether this variant is undergoing antigenic diversification without presenting a major distinction at the phylogenetic level. Sequence analyses that include >1400 capsid sequences from GII.4 Sydney_2012 showed changes in 4 out of the 6 major antigenic sites. Notably, while changes were detected in one of the most immunodominant sites over time, these resulted in minimal changes in the antigenic profile of these viruses. This study provides new insights on the mechanism governing the antigenic diversification of GII.4 norovirus that could help in the development of cross-protective vaccines to human noroviruses.

Tratamiento de linfomas cutáneos de células T con bexaroteno / Treatment of cutaneous T-cell lymphomas with bexarotene

Introducción. La elección del tratamiento en los linfomas cutáneos de células T (LCCT) depende del estadio clínico de la enfermedad y del estado general del paciente. Hasta hoy no existe ningún tratamiento curativo para esta enfermedad y el objetivo es controlar los síntomas y prevenir la progresión de la enfermedad. El bexaroteno es un retinoide agonista específico de los receptores X de los retinoides con actividad antitumoral. Su uso fue aprobado por la Food and Drug Administration (FDA) como tratamiento de LCCT refractarios a al menos una terapia sistémica previa. Pacientes y métodos. Realizamos un estudio descriptivo de 9 pacientes que han sido tratados con bexaroteno en la Unidad de Linfomas de nuestro servicio. Analizamos las características clínicas de los pacientes y eficacia del tratamiento y recogemos los efectos secundarios presentados. Resultados. La respuesta global al tratamiento fue del 44,4 % (4/9). Un total de 2 pacientes presentaron una remisión completa y los otros dos, una remisión parcial. La tolencia al tratamiento fue buena y los efectos secundarios más frecuentes fueron la hipertrigliceridemia, la hipercolesterolemia y el hipotiroidismo central. Conclusiones. Aunque se trata de una serie de únicamente 9 pacientes los resultados que obtuvimos son similares a los descritos previamente. El bexaroteno es una opción terapéutica eficaz en este grupo heterogéneo de enfermedades

Introduction. The choice of treatment in cutaneous T-cell lymphomas (CTCLs) depends on the clinical stage of the disease and the patient's general condition. To date, there is no curative treatment for this disease, and the objective is to control the symptoms and prevent the disease from progressing. Bexarotene is an X receptor-specific retinoid with anti-tumor activity. Its use as treatment for CTCLs refractory to at least one prior systemic therapy has been approved by the FDA. Patients and methods. We carried out a descriptive study of 9 patients treated with bexarotene in the Lymphoma Unit of our department. We analyzed the clinical characteristics of the patients and the efficacy of the treatment, and we collected data on the side effects that appeared. Results. The overall response to the treatment was 44.4 % (4/9). 2 patients had full remission and 2 had partial remission. Tolerance to the treatment was good, and the most frequent side effects were hypertriglyceridemia, hypercholesterolemia and central hypothyroidism. Conclusions. Even though this is a series of only 9 patients, the results that we obtained are similar to ones previously described. Bexarotene is an effective therapeutic option in this heterogeneous group of diseases

Xantogranuloma múltiple del adulto / Multiple adult xanthogranuloma

El xantogranuloma juvenil es una histiocitosis decélulas no Langerhans (HCNL) poco frecuente, de carácter benigno y que afecta predominantemente a niños pequeños. Clínicamente se caracteriza por la aparición de una o varias lesiones papulonodulares amarillo-parduzcas localizadas en zona superior del cuerpo, sobre todo en cabeza y cuello. Los xantogranulomas en adultos son menos frecuentes y generalmente se presentan como lesiones solitarias. El diagnóstico de xantogranulomas múltiples en adultos es excepcional. Se describe el caso de una paciente diagnosticada de esta rara enfermedad

Juvenile xanthogranuloma is an infrequent, benign,normolipemic, non-Langerhans cell histiocytosis, which primarily affects young children. Clinically, it is characterized by the appearance of one or several brownish-yellow papulonodular lesions on the upper body, especially on the head andn eck. Xanthogranulomas are less frequent in adults, and generally present as solitary lesions. The diagnosis of multiple xanthogranulomasin adults is exceptional. We describe the case of a female patient diagnosed with this rare disease

Placas amarillentas en tronco y flexuras axilares / Yellowish plaques on the trunk and the axillary folds

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Urticaria solar. Estudio de 20 casos / Solar urticaria. Study of 20 cases

Introducción. La urticaria solar es una enfermedad poco frecuente, pero probablemente infradiagnosticada. Se caracteriza por la aparición de forma súbita de habones en zonas habitualmente no fotoexpuestas tras irradiación solar o con otras fuentes artificiales de luz visible o ultravioleta. Los casos publicados en la literatura médica son pocos, por lo que la información que tenemos acerca de la enfermedad y su evolución natural es limitada. Material y métodos. Se han recopilado los datos de los 20 pacientes que han sido diagnosticados de urticaria solar en nuestro servicio en los últimos 12 años (1990-2002), para intentar obtener información acerca de las características de esta enfermedad. Resultados. Como características más relevantes de nuestra serie cabe destacar que el 60 % de los pacientes eran mujeres; la duración media de la enfermedad antes de acudir a un dermatólogo era de alrededor de 3 años. En el 55 % de los pacientes se respetaban zonas habitualmente fotoexpuestas como cara y manos (fenómeno de habituación o hardening). Los espectros responsables de la urticaria solar eran luz visible, UVA y UVB, por ese orden. Respecto a los tratamientos, con antihistamínicos y fotoprotectores se obtuvo una respuesta parcial y buenos resultados mediante desensibilizaciones progresivas con UVA/sol. Conclusión. La urticaria solar es probablemente una enfermedad infradiagnosticada en nuestro medio. Hay pocas series publicadas que nos permitan conocer las características más importantes de la enfermedad. Se han recopilado los datos más interesantes de nuestros pacientes y se han comparado con el resto de las series publicadas en el intento de conocer mejor esta fotodermatosis

Introduction. Solar urticaria is an infrequent disorder, but is probably underdiagnosed. It is characterized by the sudden appearance of weals in areas that are not usually photoexposed after exposure to the sun or to artificial sources of visible or ultraviolet light. Few cases have been published in literature, so the information available about this disorder and its natural evolution is limited. Material and methods. We have compiled data from 20 patients diagnosed with solar urticaria in our department in the last 12 years (1990-2002) in order to try to obtain information about the characteristics of this condition. Results. As the most relevant characteristics of our series, we can mention the fact that 60 % of the patients were women, and the average duration of the condition before consulting a dermatologist was 3 years. In 55 % of the patients, areas that are usually photoexposed, such as the face and hands, were less severely affected (due to acclimatization or hardening). The spectra responsible for the SU were visible light, UVA and UVB, in that order. With regard to treatment, we obtained a partial response with antihistamines and photoprotectors, and good results using progressive desensitization with UVA/sunlight. Conclusion. Solar urticaria is probably an underdiagnosed condition in our milieu. There are few series in literature that provide any information about the most significant characteristics of this disorder. We have compiled the most relevant data from our patients and we have compared it with the other published series in an attempt to learn more about this photodermatosis

[Treatment of cutaneous T-cell lymphomas with bexarotene]. / Tratamiento de linfomas cutáneos de células T con bexaroteno.

INTRODUCTION: The choice of treatment in cutaneous T-cell lymphomas (CTCLs) depends on the clinical stage of the disease and the patient's general condition. To date, there is no curative treatment for this disease, and the objective is to control the symptoms and prevent the disease from progressing. Bexarotene is an X receptor-specific retinoid with anti-tumor activity. Its use as treatment for CTCLs refractory to at least one prior systemic therapy has been approved by the FDA. PATIENTS AND METHODS: We carried out a descriptive study of 9 patients treated with bexarotene in the Lymphoma Unit of our department. We analyzed the clinical characteristics of the patients and the efficacy of the treatment, and we collected data on the side effects that appeared. RESULTS: The overall response to the treatment was 44.4% (4/9). 2 patients had full remission and 2 had partial remission. Tolerance to the treatment was good, and the most frequent side effects were hypertriglyceridemia, hypercholesterolemia and central hypothyroidism. CONCLUSIONS: Even though this is a series of only 9 patients, the results that we obtained are similar to ones previously described. Bexarotene is an effective therapeutic option in this heterogeneous group of diseases.

[Solar urticaria. Study of 20 cases]. / Urticaria solar. Estudio de 20 casos.

INTRODUCTION: Solar urticaria is an infrequent disorder, but is probably underdiagnosed. It is characterized by the sudden appearance of weals in areas that are not usually photoexposed after exposure to the sun or to artificial sources of visible or ultraviolet light. Few cases have been published in literature, so the information available about this disorder and its natural evolution is limited. MATERIAL AND METHODS: We have compiled data from 20 patients diagnosed with solar urticaria in our department in the last 12 years (1990-2002) in order to try to obtain information about the characteristics of this condition. RESULTS: As the most relevant characteristics of our series, we can mention the fact that 60 % of the patients were women, and the average duration of the condition before consulting a dermatologist was 3 years. In 55 % of the patients, areas that are usually photoexposed, such as the face and hands, were less severely affected (due to acclimatization or hardening). The spectra responsible for the SU were visible light, UVA and UVB, in that order. With regard to treatment, we obtained a partial response with antihistamines and photoprotectors, and good results using progressive desensitization with UVA/sunlight. CONCLUSION: Solar urticaria is probably an underdiagnosed condition in our milieu. There are few series in literature that provide any information about the most significant characteristics of this disorder. We have compiled the most relevant data from our patients and we have compared it with the other published series in an attempt to learn more about this photodermatosis.

[Multiple adult xanthogranuloma]. / Xantogranuloma múltiple del adulto.

Juvenile xanthogranuloma is an infrequent, benign, normolipemic, non-Langerhans cell histiocytosis, which primarily affects young children. Clinically, it is characterized by the appearance of one or several brownish-yellow papulonodular lesions on the upper body, especially on the head and neck. Xanthogranulomas are less frequent in adults, and generally present as solitary lesions. The diagnosis of multiple xanthogranulomas in adults is exceptional. We describe the case of a female patient diagnosed with this rare disease.

Eritema anular eosinofílico / Eosinophilic annular erythema

Introducción. El eritema anular eosinofílico, inicialmente descrito en la infancia, es una rara enfermedad benigna y autolimitada que se caracteriza por la presencia de lesiones anulares eritematosas recurrentes, que normalmente se localizan en el tronco y las extremidades. El curso es recidivante con intervalos libres de enfermedad. El estudio histológico muestra en la dermis un infiltrado perivascular con linfocitos y eosinófilos. No suele detectarse eosinofilia en sangre periférica. Su etiología es desconocida. El tratamiento con antipalúdicos de síntesis ha demostrado ser eficaz en los 2 casos publicados. Un varón de 59 años consultó por presentar pápulas urticariales y lesiones anulares recurrentes, no pruriginosas, en el tronco, desde hacía 3 meses. La biopsia mostró un infiltrado linfocítico de predominio perivascular con eosinófilos en la dermis. La enfermedad remitió espontáneamente en 10 meses (AU)

Tuberculosis cutánea en cicatriz quirúrgica / Skin tuberculosis in a surgical scar

La afectación cutánea por M. tuberculosis supone el 1 % de todas las formas extrapulmonares. Se presenta el caso de un varón de 55 años con antecedente de probable tuberculosis pulmonar en la juventud que refería que le habían extirpado unas adenopatías cervicales 20 años antes. Consultó por la aparición de una placa eritematosa, lineal, de años de evolución, sobre la cicatriz quirúrgica del cuello. A la exploración física no presentaba adenopatías palpables, ni otras lesiones cutáneas. La biopsia cutánea mostró una inflamación granulomatosa de tipo tuberculoide y las tinciones de ácido peryódico de Schiff y Ziehl-Neelsen fueron negativas. En el cultivo del tejido creció M. tuberculosis y el resto de estudios analíticos y radiológicos fueron normales o negativos. Con el diagnóstico de lupus vulgar sobre cicatriz quirúrgica se realizó tratamiento tuberculostático, que condujo a la curación de la lesión. Nuestro paciente presentó un lupus vulgar limitado a la zona de la cicatriz de linfadenectomía que sugerimos ocurrió por diseminación durante el acto quirúrgico de extirpación de adenopatías tuberculosas, que no fueron diagnosticadas en su momento (AU)

Lesiones verrucosas subcutáneas en una paciente con trasplante renal / Subcutaneeous verruca lesions in a female renal transplant recipient

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