[Analysis of a case series of adult patients with severe atopic dermatitis treated with dupilumab in Argentina]. / Análisis de una serie de casos de pacientes adultos con dermatitis atópica severa tratados con dupilumab en Argentina.

Introduction: Severe atopic dermatitis (AD) treatment is an unmet need, given the limited efficacy and safety of classical systemic treatments (CSTs). Dupilumab is a monoclonal antibody that blocks the signaling of the interleukins that mediate the inflammatory response involved in AD. Methods: the clinical response of a group of patients from Argentina with severe AD and insufficient response and/or toxicity to CSTs who were treated with dupilumab before commercial availability was analyzed. EASI, SCORAD, DLQI scales and analog visual scales of pruritus and sleep were evaluated, during a median follow-up of 189 days. In addition, the incidence of adverse events was analyzed. Results: 20 patients (13 male) were included; median age: 37.5 years; median AD evolution: 20 years; atopic comorbidity: 70%. 100% had received systemic corticosteroids (serious complications: 20%). Main reasons for discontinuation of CSTs were lack of efficacy and occurrence of adverse events. All scores were significantly and steadily reduced, with identifiable clinical response at the second month of treatment. At the end of the follow-up, only 3 patients required concomitant systemic immunosuppressive treatment. Dupilumab was well tolerated, with mild and controllable adverse events. Discussion: Dupilumab is the only biological agent with high efficacy demonstrated in clinical and observational studies. In this case series, its effectiveness was confirmed in difficult-to-treat patients with severe AD and inadequate response to CSTs. The safety profile was favorable and consistent.

Introducción: El tratamiento de la dermatitis atópica (DA) severa es una necesidad insatisfecha, dada la limitada eficacia y seguridad de los tratamientos sistémicos clásicos (TSC). Dupilumab es un anticuerpo monoclonal que bloquea la señalización de las interleuquinas mediadoras de la respuesta inflamatoria involucrada en la DA. Métodos: se analizó la respuesta clínica de un grupo de pacientes de Argentina con DA severa y respuesta insuficiente y/o toxicidad a los TSC que fueron tratados con dupilumab antes de su disponibilidad comercial. Se evaluaron las escalas EASI, SCORAD, DLQI y escalas visuales analógicas de prurito y sueño, durante una mediana de 189 días de seguimiento, así como la incidencia de eventos adversos. Resultados: Se incluyeron 20 pacientes (13 varones); mediana de edad: 37,5 años; mediana de evolución de la DA: 20 años; comorbilidad atópica: 70%. El 100% habían recibido corticoides sistémicos (complicaciones graves: 20%). Los principales motivos de suspensión de los TSC fueron falta de eficacia y aparición de eventos adversos. Los puntajes de todas las escalas se redujeron significativa y sostenidamente, con respuesta clínica evidente al segundo mes de tratamiento. Al final del seguimiento, solo 3 pacientes requerían tratamiento inmunosupresor sistémico concomitante. Dupilumab fue bien tolerado, con eventos adversos leves y controlables. Dsicusión: el dupilumab constituye el único agente biológico con elevada eficacia demostrada en estudios clínicos y observacionales. En esta casuística, se confirmó su efectividad en pacientes con DA severa de difícil tratamiento y respuesta inadecuada a los TSC. El perfil de seguridad resultó favorable y sostenido a mediano plazo.

Primary cutaneous lymphoma in Argentina: a report of a nationwide study of 416 patients.

BACKGROUND: The aim of this study was to determine the relative frequency of primary cutaneous lymphoma (PCL) in Argentina according to the new World Health Organization (WHO)-European Organization for the Research and Treatment of Cancer (EORTC) classification system. METHODS: A total of 416 patients from 21 dermatology services were included during a 5-year period (2010-2015); these patients were classified using WHO-EORTC criteria. RESULTS: There were 231 (55.2%) males and 185 (44.8%) females; the male-to-female ratio was 1.35. The median age of the patients was 57 years (range, 0-90 years). Most patients were Caucasian (79%), and only 16% of patients were registered as Amerindian. Most patients (387/416, 93%) had cutaneous T-cell lymphoma (CTCL); 28 patients (6.7%) were diagnosed with cutaneous B-cell lymphoma (CBCL). The most frequent CTCL subtypes, in decreasing order of prevalence, were mycosis fungoides (MF), including its variants (75.7%); CD30+ primary cutaneous lymphoproliferative disorders (7.2%); and Sézary syndrome (SS) (3.1%). Cutaneous follicle center lymphoma was the most common CBCL subtype (2.9%). In the subset of patients ≤20 years of age, the most common condition was MF (57%), followed by extranodal NK-T nasal-type lymphoma (14%). CONCLUSIONS: This study revealed relatively higher rates of MF and lower rates of CBCL in Argentinean patients that have been reported in American and European countries.

[Biosimilars: Expert consensus of the Latin American Society of Psoriasis (SOLAPSO) in Argentina]. / Biosimilares: Consenso de expertos de la Sociedad Latinoamericana de Psoriasis (SOLAPSO) en Argentina.

With the appearance of biological treatments, therapeutics has changed in many rheumatological, dermatological and oncological diseases. Due to the high cost of these biological medicaments and the expiration of patents, the pharmacological industry develops biosimilars, drugs that are a version (copy) of the substance of the original biological medicine, with the aim of facilitating access to these treatments. These biosimilars are prepared according to the specific requirements of regulatory bodies in terms of quality, efficacy and safety, and must be shown they are comparable to the reference product. This paper reviews the international and national regulatory framework, the controversies surrounding biosimilars, and presents the position of a group of experts regarding the use of biosimilars.

Biosimilares: consenso de expertos de la Sociedad Latinoamericana de Psoriasis (SOLAPSO) en Argentina / Biosimilars: Expert consensus of the Latin American Society of Psoriasis (SOLAPSO) in Argentina

Con la aparición de los tratamientos biológicos, se ha modificado la terapéutica de muchas enfermedades, en especial las reumatológicas, dermatológicas y oncológicas. Debido al alto costo de estos productos y el vencimiento de las patentes, la industria farmacológica desarrolla los biosimilares, fármacos que son una versión (copia) de la sustancia de un medicamento biológico original, y que pueden facilitar el acceso a estos tratamientos. Son elaborados de acuerdo a exigencias específicas de organismos reguladores en cuanto a calidad, eficacia y seguridad, y debe demostrarse que son comparables al medicamento de referencia. Este trabajo revisa las normativas regulatorias internacionales y nacionales, las controversias que rodean a los biosimilares y presenta la posición de un grupo de expertos con respecto al uso de biosimilares.

With the appearance of biological treatments, therapeutics has changed in many rheumatological, dermatological and oncological diseases. Due to the high cost of these biological medicaments and the expiration of patents, the pharmacological industry develops biosimilars, drugs that are a version (copy) of the substance of the original biological medicine, with the aim of facilitating access to these treatments. These biosimilars are prepared according to the specific requirements of regulatory bodies in terms of quality, efficacy and safety, and must be shown they are comparable to the reference product. This paper reviews the international and national regulatory framework, the controversies surrounding biosimilars, and presents the position of a group of experts regarding the use of biosimilars.

Biosimilars in psoriasis: Clinical practice and regulatory perspectives in Latin America.

Latin American countries view biosimilar agents as an effective approach to curtail health-care expenditures while maintaining the safety and efficacy profile of their branded innovator comparators. To understand the complexities of the regulatory landscape and key therapeutic issues for use of biosimilars to treat moderate to severe psoriasis in Latin America, the International Psoriasis Council convened dermatology experts from Argentina, Brazil, Chile, Colombia and Mexico in October 2015 to review the definition, approval, marketing and future of biosimilars in each country and develop a consensus statement. The regulatory framework for marketing approval of biosimilars in Latin America is currently a mosaic of disparate, country-specific, regulatory review processes, rules and standards, with considerable heterogeneity in clarity and specificity. Regulations in Argentina, Brazil, Chile and Mexico have undergone multiple refinements whereas Colombia is finalizing draft guidelines. Verification of the similarity in quality, safety and efficacy of biosimilars to the innovator biologic remains a key challenge for policy makers and regulatory authorities. Other key regulatory challenges include: naming of agents and traceability, pharmacovigilance, extrapolation of indications, and interchangeability and substitution. An urgent need exists for more Latin American countries to establish national psoriasis registries and to integrate their common components into a multinational psoriasis network, thereby enhancing their interpretative power and impact. A Latin American psoriasis network similar to PSONET in Europe would assist health-care providers, pharmaceutical companies, regulators and patients to fully comprehend specific products being prescribed and dispensed and to identify potential regional trends or differences in safety or outcomes.

Unusual variants of mycosis fungoides.

Unusual variants of mycosis fungoides (MF) differ substantially from the classical presentation, and most of them resemble other dermatologic diseases. The authors reviewed files of patients with MF who consulted our clinic between November 1995 and June 2010 to evaluate the relative frequency and clinical behavior of these variants. Among 98 patients with MF, 32 (32.65%) had unusual variants. The most common types included follicular MF (31.25%), hypopigmented MF (18.75%), poiquilodermic MF (15.6%), and erythrodermic MF (12.5%). Less common variants included unilesional MF, bullosa MF, ichthyosiform MF, granulomatous slack skin, and pigmented purpura-like MF. Progressive disease and MF-related death were most commonly associated with follicular MF, bullosa MF, and erythrodermic MF.

Síndrome linfoproliferativos CD30+. Serie de 26 casos y revisión de la literatura / CD30(+)-lymphoproliferative disorders. Report of a 26-case-series and literature review

Introducción. Los síndromes linfoproliferativos que expresan CD30+ en la piel (SLP CD30+) incluyen las formas cutáneas primarias (SLP-CP) CD30+ (papulosis linfomatoide (LyP), linfoma anaplásico a células grandes primario cutáneo (PC-ALCL) y casos borderline) que tienen un buen pronóstico y las secundarias a otro linfoma (linfoma anaplásico de células grandes (ALCL) secundario a micosis fungoide (MF-T), síndrome de Sézary, LyP, enfermedad de Hodgkin), así como tipos infrecuentes de linfomas primarios que expresan este marcador, cuyo comportamiento es más agresivo (leucemia/ linfoma de células T del adulto o el linfoma angiocéntrico cutáneo de células T de la infancia tipo hidroa). También hay que considerar a las infiltraciones cutáneas secundarias a un ALCL sistémico de origen nodal. Es evidente que basándose sólo en los hallazgos histopatológicos es virtualmente imposible diferenciar estas entidades, y por lo tanto los datos de la presentación clínica e incluso muchas veces de la evolución, son cruciales para establecer un diagnóstico definitivo. Objetivos. Describir las características clínicas, histopatológicas y el pronóstico de los pacientes asistidos en la Unidad de Dermatología del Hospital General de Agudos Dr. Cosme Argerich con diagnóstico de SLP CD30+, y realizar una revisión de la literatura. Materiales y métodos. Estudio retrospectivo de revisión de la base de datos de pacientes con diagnóstico histológico e inmunohistoquímico confirmado de SLP CD30+ desde noviembre de 1995 hasta septiembre de 2010. Se evaluó diagnóstico, edad al inicio de la enfermedad, sexo, estadio, tiempo de evolución, respuesta al tratamiento y sobrevida. Resultados. Fueron evaluados 26 pacientes con diagnóstico confirmado de SLP CD30+. De los 26 casos incluidos, 19 (73%) correspondieron a SLP-CP CD30+, 11 (58%) LyP (de las cuales 4 se asociaron a MF), 3 (16%) borderline, y 5 (26%) PC-ALCL...

CD30(+)-lymphoproliferative disorders (CD30(+)-LPD) constitute a heterogeneous groupof neoplasms with different therapeutic approaches and outcomes. They can be primary cutaneous,including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (PC-ALCL)andborderlinecases. A second group is secondary to another lymphoma, such as anaplastic large celllymphoma (ALCL) occurring after mycosis fungoides (MF-T), Sezary syndrome, LyP, and Hodgkin’s disease.Another different group of disorders showing CD30(+) expression, not belonging to the groups abovementioned, must be kept in mind in order to perform a differential diagnosis, including rare primarylymphomas, such as adult T cell leukemia/lymphoma, or angiocentric cutaneous T-cell lymphomaof childhood (hydroa-like lymphoma), and secondary skin involvement due to a systemic ALCL. Asdifferential diagnosis among them is virtually impossible based on histologic features alone, data on theclinical presentation and evolution are crucial to establish a correct diagnosis.

Estudio prospectivo, descriptivo y multicéntrico acerca de la infección de piel y partes blandas por Staphylococcus aureus meticilino-resistente adquirido en la comunidad (SAMRAC) / Multicentric prospective and descriptive study about community-acquired methicillin-resistant Staphylococcus aureus cutaneous and sof tissue infection (CA-MRSA)

El Staphylococus aureus meticilino-resistente adquirido en la comunidad (SAMRAC) es uno de los principales patógenos emergentes de la última década, y en algunos países es la principal causa de infecciones de piel y partes blandas. El objetivo de este estudio es describir las características epidemiológicas, clínicas y microbiológicas de las infecciones de piel y partes blandas producidas por SAMRAC en pacientes ambulatorios. Materiales y métodos. Estudio descriptivo, prospectivo, multicéntrico realizado en seis Servicios de Dermatología de la ciudad de Buenos Aires entre julio de 2008 y junio de 2009. Se incluyeron pacientes con infección de piel y partes blandas por SAMRAC documentada por cultivo. La definición de adquisición en la comunidad se basó en criterios epidemiológicos. Resultados. Se reclutaron 114 pacientes, de los cuáles 49% fueron hombres y 51 % mujeres. La media de la edad fue 27 años. El 74% recibió tratamiento con ß lactámicos previo al diagnóstico. Los forúnculos representaron la forma clínica más frecuente (59%), seguido de los abscesos (20%). El antibiótico más indicado fue trimetoprima-sulfametoxasol (68,4%).Las resistencias más frecuentes fueron eritromicina (21,7%) y clindamicina (16,2%), 6 pacientes requirieron internación, 18 pacientes presentaron recurrencias y no se registró ninguna muerte. Conclusiones. Los datos demográficos y clínicos obtenidos en este estudio son similares a los comunicados previamente. La mayoría de los pacientes recibieron tratamiento antibiótico previo, lo que denota una baja sospecha diagnóstica. El impétigo representó una forma de presentación frecuente en la población pediátrica y la celulitis sólo comprometió a mujeres. La resistencia a clindamicina fue mayor al 15%, por lo que no debería ser considerado un antibiótico de primera línea. Las infecciones de piel y partes blandas por SAMRAC son frecuentes en nuestro medio, por lo que debe considerarse en pacientes con lesiones supurativas o falta de...

Community acquired methicillin-resistant Staphylococcus aureus is oneof the main emergent pathogens of the last decade, being the fi rstcause of skin and soft tissue infections in some countries. The purposeof this study is to describe the epidemiologic, clinical, and microbiologicalcharacteristics of CA-MRSA cutaneous and soft tissue infections inan ambulatory setting.Methods. We conducted a multuicentric, prospective, descriptive studyperformed in 6 dermatology units at Buenos Aires from july 2008 to june2009. Patients with documented CA-MRSA skin and soft tissue infectionswere included. Community acquisition was defi ned based on epidemiologiccriteria.Results. We included 114 patients, of which 49% were male and 51%were female. The median age was 27 years. Seventy four percent of the patientshad received beta-lactamic antibiotic treatment prior to inclusion.The main clinical presentation were furuncules (59%) followed by abscesses( 20%). The most frequently prescribed antibiotic was trimethoprim-sulfametoxazole(68,4%). The most frequently recovered isolates were erithromicin-(21,7%) and clindamycin-resistant (16,2%). Six patients requiredhospital admission, 18 had recurrent diseases, and no death was recorded.Discussion. Demographic and clinical data obtained in this study aresimilar to those previously reported. Most of the patients had received antibiotictreatment before inclusion, which shows the low CA-MRSA clinicalsuspicious. Impetigo was fecuently observed among children, and celulitiswas exclusively observed in females. As clindamycin resistance washigher than 15%, this antibiotic should not be considered a fi rst-line treatmentoption. CA-MRSA infections were frecuently observed in our patients,therefore its diagnosis should be considered on suppurative lesionsand non responding pyodermitis (Dermatol Argent 2010;16(2):110-116).

La vitamina D, el sistema inmune y las enfermedades de la piel / Vitamin D, immune system and skin diseases

El sistema endocrino de la vitamina D tiene un rol esencial en la regulación del metabolismo óseo y la homeostasis del calcio. Sin embargo, los hallazgos de las últimas décadas han revelado un amplio rango de acciones que incluyen la regulación de la diferenciación y proliferación celular y la modulación del sistema inmune y otros sistemas endocrinos. A través de la regulación de la inmunidad innata y adquirida participa en la regulación de la respuesta a diversos antígenos. Estas nuevas acciones sugieren que la vitamina D es un factor ambiental con un rol importante en el desarrollo de enfermedades autoinmunes. El nuevo rol modulador de la vitamina D en el sistema inmune ha dado explicación a muchos fenómenos antes desconocidos y ha abierto nuevas oportunidades en el tratamiento de las enfermedades inflamatorias.

The vitamin D endocrine system plays an essential role in calcium ho-meostasis and bone metabolism. Nevertheless, research during the pastdecades has revealed a diverse range of biological actions that includeinduction of cell diff erentiation, inhibition of cell growth,immunomodulation, and control of other hormonal systems.Through the innate and adaptative immune systems modulation, vitamin D regulates the response to many antigens. These new actions suggest an importantrole for vitamin D as a modifi able environmental factor in autoimmune disease.The new fi ndings on vitamin D actions on immunity have explained its role in the pathogenesis of skin autoimmune diseases, and have offered new possibilities for their treatment.