Expert Recommendations on the Evaluation of Sunscreen Efficacy and the Beneficial Role of Non-filtering Ingredients.

A variety of non-filtering agents have been introduced to enhance sunscreen photoprotection. Most of those agents have only weak erythema protective properties but may be valuable and beneficial in supporting protection against other effects of UV radiation, such as photoimmunosuppression, skin aging, and carcinogenesis, as well as photodermatoses. The question arises how to measure and evaluate this efficacy since standard SPF testing is not appropriate. In this perspective, we aim to provide a position statement regarding the actual value of SPF and UVA-PF to measure photoprotection. We argue whether new or additional parameters and scales can be used to better indicate the protection conferred by these products against the detrimental effects of natural/artificial, UV/visible light beyond sunburn, including DNA damage, photoimmunosuppression and pigmentation, and the potential benefits of the addition of other ingredients beyond traditional inorganic and organic filters to existing sunscreens. Also, we debate the overall usefulness of adding novel parameters that measure photoprotection to reach two tiers of users, that is, the general public and the medical community; and how this can be communicated to convey the presence of additional beneficial effects deriving from non-filtering agents, e.g., biological extracts. Finally, we provide a perspective on new challenges stemming from environmental factors, focusing on the role of the skin microbiome and the role of air pollutants and resulting needs for photoprotection.

Ulceración esofágica por ingestión de doxiciclina / Doxycycline induced esophageal ulceration

La ulceración esofágica por ingestión de doxiciclina es una de las causas más frecuentes de lesión esofágica. Ha sido subdiagnosticada y escasamente reconocida en dermatología. El dolor retroesternal, la odinofagia de aparición brusca y el antecedente de ingesta de doxiciclina u otros fármacos son características que facilitan su diagnóstico. Puede presentar complicaciones serias, como hemorragias, estenosis y mediastinitis.

Esophageal ulceration due to ingestion of doxycycline is one of the most frequent causes of esophageal injury. It has been underdiagnosed and scarcely recognized in dermatology. Retrosternal pain, sudden odynophagia and a history of doxycycline or other drugs intake are some of the characteristics that lead to diagnosis. It may cause severe complications such as bleeding, stenosis and mediastinitis.

Frontal Fibrosing Alopecia Associated with Lichen Planus Pigmentosus: Not Only in Dark Phototypes.

The association between frontal fibrosing alopecia and lichen planus pigmetosus was first described in African women. Later, most reports about this association involved dark-skinned patients. Here, we describe 5 cases of frontal fibrosing alopecia associated with lichen planus pigmentosus in light-skinned women from Argentina. Our communication highlights the strength of both entities' association also in lower Fitzpatrick phototypes.

Nevoid Basal Cell Carcinoma Syndrome: PTCH1 Mutation Profile and Expression of Genes Involved in the Hedgehog Pathway in Argentinian Patients.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCC), mainly caused by PTCH1 gene mutations. Our current study aimed to establish (1) PTCH1 germinal and somatic mutational status, (2) component and Hedgehog (HH) pathway targets gene expression patterns, and (3) profile variations according to the genetic background in BCC and normal surrounding skin (NSS). We collected 23 blood and 20 BCC patient samples and analyzed the PTCH1 gene using bidirectional sequencing and multiplex ligation-dependent probe amplification. Quantitative PCR was used to determine the mRNA expression levels of PTCH1, SMO, GLI3, and CCND1 in paired samples of BCC and NSS from 20 patients and four non-NBCCS skin controls (C). Our analyses identified 12 germline and five somatic sequence variants in PTCH1. mRNA levels of PTCH1, SMO, and GLI3 were higher in NSS compared to C samples, reaching maximum values in BCC samples (p < 0.05). NSS with PTCH1 germline mutations had modified SMO,PTCH1, and GLI3 mRNA levels compared to samples without mutation (p < 0.01). Two PTCH1 mutations in BCC led to an increase in PTCH1, SMO, and GLI3, and a decrease in CCND1 mRNA levels (p < 0.01 vs. BCC with germline mutation only). These results indicate that besides PTCH1, other genes are responsible for NBCCS and BCC development in a population exposed to high UV radiation. Additionally, the mutational events caused increased expression of HH-related genes, even in phenotypically normal skin.

Homeostasis in Topical Photoprotection: Getting the Spectral Balance Right.

The solar radiation range has harmful and beneficial effects. Sunscreens, which selectively block specific spectral regions, may potentially interfere with skin homeostasis. For instance, the ultraviolet (UV) B waveband produces erythema and DNA damage; simultaneously, it induces pre-vitamin D3 synthesis. UVA1 and visible light can both induce pigmentation in skin phototypes IV-VI, and act in synergy to induce erythema and persistent pigment darkening. In contrast, UVA may contribute to blood pressure control and cardioprotection by inducing release of nitric oxide from intracutaneous photolabile nitric oxide derivatives. Finally, infrared A radiation alters the collagen equilibrium of the dermal extracellular matrix but is involved in the regulation of body temperature and in nitric oxide release, with a potential beneficial impact on blood pressure regulation. Ideally, photoprotection should thus be performed with a neutral density filter, mitigating all radiation ranges homogeneously, to maintain solar spectrum homeostasis. Natural compounds such as mycosporine-like amino acids are promising natural UV radiation-filtering compounds for an improved homeostasis with our environment. Lastly, we should not forget individual characteristics and behavior, as homeostasis differs according to individual phototypes and skin exposure behaviors.

[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.

Current challenges in photoprotection.

Electromagnetic radiation in the ultraviolet, visible, and infrared ranges all produce biologic effects. Ultraviolet filters are the most well-studied photoprotective measure for the adverse effects of ultraviolet radiation. Because of the reported endocrinologic effects of oxybenzone in animal studies, its effects on coral reefs, and its photocontact allergy potential, its use has been minimized in many countries worldwide. New developments in topical antioxidants and oral and subcutaneous agents (eg, Polypodium leucotomos extract, afamelanotide, nicotinamide) with photoprotective and antiphotocarcinogenic properties could potentially provide addition modalities for protection against the effects of visible light and infrared radiation.

Alopecia fibrosante frontal / Frontal fibrosing alopecia

La alopecia fibrosante frontal (AFF) pertenece al grupo de las alopecias cicatrizales linfocitarias primarias y presenta un patrón clínico distintivo de retroceso progresivo de lalínea de implantación capilar frontotemporal. Se realizó una revisión retrospectiva de 18 mujeres adultas con diagnóstico de AFF entre el 1 de junio de 2008 y el 1 de junio de 2014 en el CEMIC, el Hospital Cosme Argerich, Buenos Aires Skin y la práctica privada. La edad promedio fue de 69 años, todas las pacientes eran posmenopáusicas y presentaban retroceso de la línea de implantación frontotemporal por alopecia cicatrizal. El cuadro se asoció a pérdida completa o parcial de las cejas en dieciséis de las pacientes y sólo una presentó alopecia en otro sitio anatómico. Una paciente presentó pápulas no inflamatorias color piel en cara, otra de ellas liquen plano oral y dos liquen vulvar. Los tratamientos indicados incluyeron esteroides tópicos, acetónido de triamcinolona intralesional, doxiciclina, inhibidores de 5 alfa reductasa y metotrexate...

[Nevoid basal cell carcinoma syndrome with corpus callosum agenesis, PTCH1 mutation and absence of basal cell carcinoma]. / Síndrome de carcinoma basocelular nevoide con agenesia de cuerpo calloso, mutación en PTCH1 y ausencia de carcinoma basocelular.

Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or Gorlin-Goltz syndrome is a rare autosomal dominant disorder, mainly due to PTCH1 gene mutations, that comprises a broad spectrum of clinical manifestations. The presence of multiple basal cell carcinomas (BCCs) is a cardinal sign in NBCCS, therefore cases in which BCCs are absent entails a delay in the diagnosis.We present a 14 years old boy with a clinical diagnosis of NBCCS by the presence of odontogenic cysts, hypertelorism, macrocephaly, and corpus callosum agenesia, but with absence of skin lesions. His 43 years old mother has NBCCS diagnosis and no history of BCCs. For a deeper study, PTCH1 mutation screening from peripheral blood samples were performed by both bidirectional sequencing and multiplex ligation dependent probe amplification (MLPA) techniques. The proband and his mother carry 25 pb duplication in exon 10 (c.1375dupl25bp) that causes a reading frameshift with a premature stop codon. Bioinformatics analysis predicted that this mutation results in a truncated protein shorter than normal. Our results suggest that complete clinical and genealogical studies accompanied by genetic analysis are essential in the early detection of the NBCCS cases such the one presented here.

Síndrome de carcinoma basocelular nevoide con agenesia de cuerpo calloso, mutación en PTCH1 y ausencia de carcinoma basocelular

El síndrome del carcinoma basocelular nevoide (SCBCN) o de Gorlin-Goltz es un raro desorden autosómico dominante con un amplio espectro de manifestaciones clínicas. El signo cardinal es la presencia de múltiples carcinomas basocelulares (CBCs) y su ausencia demora el diagnóstico. Presentamos un adolescente de 14 años con diagnóstico de SCBCN por la presencia de queratoquistes odontogénicos, hiper­telorismo, macrocefalia y agenesia del cuerpo calloso pero sin lesiones cutáneas. La madre, de 43 años, tiene diagnóstico de SCBCN y no presenta CBCs. Para completar el estudio se realizó secuenciación bidireccional y Multiplex Ligation dependent Probe Amplification (MLPA) en sangre periférica para buscar mutaciones en PTCH1, principal gen responsable del síndrome. Se encontró una mutación germinal novel en el paciente y la madre: una duplicación de 25 pb en el exón 10 (c.1375dupl25bp). El análisis bioinformático predijo un corrimiento del marco de lectura y un codón stop prematuro, que produciría una proteína trunca más corta que lo normal. Nuestros resultados sugieren que el estudio clínico y genealógico completo con análisis genético es fundamental para la detección temprana de casos como el presente.

Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or Gorlin-Goltz syndrome is a rare autosomal dominant disorder, mainly due to PTCH1 gene mutations, that comprises a broad spectrum of clinical manifestations. The presence of multiple basal cell carcinomas (BCCs) is a cardinal sign in NBCCS, therefore cases in which BCCs are absent entails a delay in the diagnosis.We present a 14 years old boy with a clinical diagnosis of NBCCS by the presence of odontogenic cysts, hypertelorism, macrocephaly, and corpus callosum agenesia, but with absence of skin lesions. His 43 years old mother has NBCCS diagnosis and no history of BCCs. For a deeper study, PTCH1 mutation screening from peripheral blood samples were performed by both bidirectional sequencing and multiplex ligation dependent probe amplification (MLPA) techniques. The proband and his mother carry 25 pb duplication in exon 10 (c.1375dupl25bp) that causes a reading frameshift with a premature stop codon. Bioinformatics analysis predicted that this mutation results in a truncated protein shorter than normal. Our results suggest that complete clinical and genealogical studies accompanied by genetic analysis are essential in the early detection of the NBCCS cases such the one presented here.

Inhibidores de 5 α reductasa / 5 α reductase inhibitors. Safety profile

El finasteride es un fármaco desarrollado inicialmente para tratar la hiperplasia prostática benigna (HPB). Desde 1997 es también utilizado para el tratamiento de la alopecia androgenética (AG) masculina. El dutasteride se introdujo en el año 2003 para el tratamiento de la HPB. Posteriormente, recibió la aprobación para el tratamiento de la alopecia AG masculina en Corea. Los ensayos que evaluaron la utilización de estos dos fármacos como agentes quimio-preventivos para el desarrollo del cáncer de próstata arrojaron resultados controversiales. Recientemente la Food and Drug Administration de EEUU (FDA) modificó el prospecto de los inhibidores de la 5α reductasa, alertando sobre el incremento en el riesgo de desarrollar cáncer de próstata más agresivo asociado a su uso. Los dermatólogos que prescriben estos fármacos deben conocer los efectos secundarios de estas drogas y reconocer en términos generales, la problemática actual del cáncer de próstata.

Finasteride is a drug originally developed to treat benign prostatic hyperplasia (BPH). Since 1997 is also used for the treatmentof male androgenetic alopecia. Dutasteride was introduced in 2003 for the treatment of BPH. Subsequently received approvalfor the treatment of male androgenetic alopecia in Korea. Trials evaluating the use of these drugs as preventive chemotherapyagents for the development of prostate cancer yielded conflicting results. Recently the Food and Drug Administration (FDA)amended the prospectus of the 5α-reductase inhibitors, warning about the increased risk of developing aggressive prostatecancer associated with its use. Dermatologists who prescribe these drugs should know their side effects and recognize thecurrent issue of prostate cancer.

Sarcoma mieloide: presentación cutánea de novo / Myeloid sarcoma: de novo cutaneous presentation. Case report and literature review

El sarcoma mieloide (SM), también llamado leucemia mieloide aguda extramedular, tumor extramedular mieloide, sarcomagranulocítico o cloroma, es una neoplasia poco frecuente de células mieloides inmaduras. Compromete con mayor frecuencia piel, tejidos blandos, hueso, periostio y ganglios linfáticos. Puede ser la primera manifestación de la leucemia mieloide aguda(LMA), presentarse simultáneamente o constituir una forma de recaída. El diagnóstico se basa en los hallazgos histopatológicos,en la inmunohistoquímica y el inmunofenotipo, que permiten clasificar diferentes tipos de sarcomas mieloides con diferentes pronósticos. Por lo general el tratamiento y el pronóstico no difieren de la LMA.

Melanoma cutáneo: mortalidad y características de los tumores incidentes en los dos extremos de la vida en la Argentina / Cutaneous melanoma in argentina: mortality and primary tumor

Objetivos. Conocer y comparar en la Argentina, en los jóvenes y adultos, la mortalidad por melanoma cutáneo (MC) y las características de casos incidentes para aportar información útil en el diseño y evaluación de acciones de prevención. Diseño. descriptivo y retrospectivo. Métodos. Se consideraron para el estudio: los jóvenes < 30 años (J) y adultos > 74 años (AM). Los datos de las defunciones para el cálculo de tasas de mortalidad en los períodos 1981-89, 90-98 y 99-07 fueron proporcionados por la Dirección de Estadísticas e Información de Salud del Ministerio de Salud. La información sobre los casos incidentes se obtuvieron del Registro Argentino de Melanoma Cutáneo (RAMC) para el período enero 2002- diciembre 2009. De ellos se estudió la localización, el espesor de Breslow y el tipo histológico.Resultados. En los sucesivos períodos las muertes por MC en J de ambos sexos fue 97, 93 y 123, y en AM 416, 654 y 1.307, respectivamente. En los AM las tasas de mortalidad aumentaron en el tiempo, y fueron siempre menores para las mujeres que para losvarones (varones: 6,3 muertes por MC promedio por cada 100.000 individuos por año en 81-89 a 13,4/100.000 99-07; mujeres: 4,4/100.000 81-89 a 7,5/100.000 en 99-07). El RAMC registró 4.100 casos, 258 fueron en J y 665 en AM. Fueron mujeres el 63% en J y el 47% en AM (p< 0,05). En las mujeres, el 56% de los MC en J y el 36% en AM tuvieron Breslow ≤ 1,00 mm (p< 0,004). En las mujeres predominaron las lesiones en piernas (el 43,4% en J y el 42,2% en AM), mientras que en los hombres fueron el 19,8% y el 12,4% respectivamente (p< 0,005). Conclusión. En las mujeres jóvenes, el menor espesor de Breslow al momento del diagnóstico y las menores tasas de mortalidad por MC con menor incremento temporal de las mismas podrían ser reflejo de una mayor influencia de las acciones de prevención y una mayor atención del propio cuerpo y de la salud por parte del género femenino. Cabe esperar que la continuidad de las actividades del ...

Objectives. To compare mortality rates and main features of cutaneous malignant melanoma(CMM) between two age groups in Argentina (young and elderly patients), in order to increaseknowledge as well as improve planning and preventive actions for this disease.Study design. descriptive and retrospective.Methods. Group J was defined as patients younger than 30 years of age and Group AM patientsover 74 years old. Death reports for periods 1981-89 / 90-98 / 99-07 were provided by theDepartment of Statistics of the Health Ministry and incident cases between 2002 and December2009 by the Argentine Registry of Cutaneous Malignant Melanoma (RAMC). Tumor location,Breslow thickness index and histopathology characteristics were analyzed for all cases.Results. For successive periods, the total number of CMM-associated deaths for both gendersin Group J was 97, 93 and 123 respectively; while these figures were for Group AM 416, 654 and1,307 respectively. On older patients an increase in mortality rates was observed over elapsedtime, being always lower for women than for men (mortality rates for men were 6.3 /100,000population per year during the period of 1981-1989 and 13.4/100,000 between the years1999-2007. Mortality rates for women were: 4.4/100,000 during 1981-1989 and 7.5/100,000and in 1999-2007). RAMC registered 4,100 new cases, of which 258 belonged to Group J and665 to Group AM. Women comprised 63% on group J and 47% on group AM (p<0, 05). Womencomprised 56% of CMM in Group J and 36% on Group AM, having a Breslow tumor thickness≤ 1.00mm (p<0,004). Primary tumors located on lower limbs were more frequently observedamong women (43.4% and 42.2% for Group J and AM respectively), whereas on men this was19.8% and 12.4%, respectively (p<0,005)...

Efalizumab in the Treatment of Scalp, Palmoplantar and Nail Psoriasis: Results of a 24-Week Latin American Study.

INTRODUCTION: Plaque-type psoriasis affecting the nails, scalp, hands or feet can often be difficult to treat; for example, topical treatments and phototherapy may not penetrate the nail plate or scalp. The objective of this large, international, multicentre study was to investigate the efficacy of efalizumab in a Latin American population of adult patients with moderate-to-severe chronic plaque psoriasis who were candidates for systemic therapy or phototherapy. METHODS: Eligible patients were enrolled in a 24-week, open-label, single-arm, Phase IIIb/IV study of continuous treatment with subcutaneous efalizumab, 1.0 mg/kg/wk. Involvement of the nails, scalp, or hands or feet was assessed using the Nail Psoriasis Severity Index (NAPSI), the Psoriasis Scalp Severity Index (PSSI), or the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI), respectively. Missing data were handled using a last observation carried forward or nonresponder imputation approach. RESULTS: Of the 189 patients who received treatment, 112 patients had nail involvement, 172 had scalp involvement, and 19 had palmoplantar disease at baseline. At Week 24, >/=50% improvement on the NAPSI, PSSI and PPPASI was observed in 31%, 71% and 68% of patients, respectively, whereas >/=75% improvement on these scores was observed in 17%, 52% and 63%, respectively. Descriptive statistics showed lower NAPSI-75 and higher PSSI-75 and -50 response rates among patients with higher baseline scores. CONCLUSIONS: This open-label, uncontrolled study provides supportive evidence of the potential of efalizumab as a treatment for nail, scalp and palmoplantar psoriasis.

Control of Moderate-to-Severe Plaque Psoriasis with Efalizumab: 24-Week, Open-Label, Phase IIIb/IV Latin American Study Results.

INTRODUCTION: Psoriasis is a debilitating, chronic inflammatory systemic disease affecting around 2% of the South American population. Biological therapies offer the possibility of long-term therapy with improved safety and efficacy. METHODS: We conducted a multicentre, open-label, single-arm, Phase IIIb/IV study of adult patients (18-75 years) with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. Patients received efalizumab subcutaneously (1.0 mg/kg/wk). The primary endpoint was the proportion of patients achieving a Physician Global Assessment (PGA) rating of "excellent" or "cleared" at Week 24. Safety outcomes were adverse events (AEs), serious AEs (SAEs) and abnormalities on laboratory tests. RESULTS: Of 189 patients included in the intent-to-treat and safety populations, 104 (55.0%) were of Hispanic or Latino ethnicity. At Week 24, 92/189 (48.7%) patients achieved or maintained a PGA rating of "excellent" or "cleared". AEs were reported by 161/189 (85.2%) patients, SAEs by 21/189 (11.1%). One patient died during the study (meningoencephalitis). Laboratory findings were consistent with previous experience. CONCLUSIONS: Efalizumab demonstrated sustained control of psoriasis up to 24 weeks in patients from Latin America, confirming results seen in Phase III studies conducted in North America and Europe.

Tumor de células de merkel: revisión de la literatura / Merkel cell tumor: review of literature

El carcinoma de Merkel es un carcinoma primario cutáneo infrecuente. Es una enfermedad potencialmente fatal, con escasa sobrevida en los casos avanzados. Recientemente Feng y col. (2008) identificaron ADN de un nuevo poliomavirus clonalmente integrado en varios casos de carcinoma de Merkel. Esto apoya la posibilidad que dicho virus se encuentre implicado al menos en algunos casos de esta patología. El carcinoma de Merkel carece de características clínicas distintivas, aunque un dato significativo es su rápido crecimiento. Afecta principalmente áreas fotoexpuestas (la mitad de los tumores se localizan en cabeza y cuello) de pacientes añosos. La gran mayoría de ellos se presentan con enfermedad localizada hasta un 30% tiene compromiso de ganglios linfáticos regionales. A pesar de la resección local, las metástasis linfáticas regionales y a distancia son frecuentes y generalmente ocurren en los primeros 2 años del diagnóstico. El tratamiento óptimo aún es incierto, pero los mejores resultados se alcanzan con un manejo interdisciplinario.