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Objetivos: Describir las afecciones dermatológicas más frecuentes en los pacientes con la COVID-19 y precisar si su presencia puede ser utilizada para establecer un diagnóstico temprano o para predecir la evolución de la infección. Métodos: Se realizó una revisión en PubMed/MEDLINE y EMBASE de todos los artículos publicados entre enero 1 y noviembre 1 de 2020, con los términos de la búsqueda centrados en “SARS-CoV-2”, “COVID-19” y “Enfermedades cutáneas”. Resultados: Cumplieron los criterios de inclusión 83 estudios. Lesiones de la piel han sido reportadas en 0.2 % de los pacientes. Las erupciones maculopapulares/morbiliformes, la urticaria y el angioedema, el patrón acral parecido a sabañones y las lesiones vesiculares fueron las dermatosis más frecuentemente informadas. Existen diferencias de opinión entre los investigadores, acerca de un posible valor diagnóstico o pronóstico de las afecciones cutáneas asociadas con la infección. Conclusiones: Es recomendable considerar el diagnóstico de la infección por SARS-CoV-2 en pacientes que consultan por presentar lesiones cutáneas, urticaria o angioedema con o sin otros síntomas de la infección y en especial si existe algún antecedente de exposición reciente a otros sujetos infectados.

"Antecedentes : la urticaria crónica espontánea es una enfermedad común en los adultos, sobre todo entre las mujeres; esta entidad con frecuencia está relacionada con padecimientos autoinmunitarios. Objetivo : evaluar, mediante estudios de laboratorio, si los pacientes con urticaria crónica espontánea tuvieron signos de autoinmunidad. Material y método : estudio transversal de 35 pacientes del área de Alergia e Inmunología del Hospital Juárez de México, diagnosticados con urticaria crónica espontánea. Se les realizó biometría hemática completa, anticuerpos antitiroideos (antiperoxidasa y tiroglobulina), anticuerpos antinucleares, factor reumatoide, anticoagulante lúpico, células LE, prueba cutánea de suero autólogo ( Autologus Serum Skin Test , ASST), complemento (C3 y C4); como estudios adicionales se les realizó prueba de Helicobacter pylori , perfil tiroideo (T3,T4, TSH) y dímero D. Resultados : evaluamos 35 pacientes adultos, 27 eran mujeres. La prueba ASST fue positiva en cuatro pacientes, los anticuerpos antinucleares fueron negativos en todos los casos, pero los anticuerpos antitiroideos resultaron positivos en cuatro pacientes. Las células LE, anticoagulante lúpico, complemento, dímero D, perfil tiroideo y Helicobacter pylori fueron normales o negativos y el factor reumatoide fue positivo en un paciente. Todos los pacientes antitiroideos positivos eran mujeres y de ellas, 26 tuvieron ASST negativa. La correlación entre ASST y AAT no fue significativa. Conclusiones : en nuestro estudio, la mayoría de los pacientes con urticaria crónica espontánea eran mujeres y sólo cuatro tuvieron la prueba ASST positiva, pero esto no se correlaciona con existencia de anticuerpos antitiroideos. La mayor parte de los estudios realizados resultaron normales, por lo que sugerimos no hacer estudios de labo - ratorio innecesarios en esta afección."

This article reviews biologic treatments that are currently applied for the treatment of severe chronic urticaria. Monoclonal anti-immunoglobulin E (omalizumab) is effective and safe in many patients, but accessibility and cost constitute barriers to its wider use. Questions on the optimal duration of the treatment and possible symptom recurrences after discontinuing the drug are still raised. A discussion is presented about several other biologics currently under investigation with potential to be incorporated in the near future in patients with severe chronic urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GALEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast-cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic urticaria, i.e. chronic spontaneous urticaria and chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This article is protected by copyright. All rights reserved.

La pandemia actual de COVID-19 ha representado un reto mayúsculo para la sociedad y la comunidad médica, no solo por su alta contagiosidad sino por la variabilidad de las manifestaciones clínicas y su comportamiento impredecible bajo diferentes contextos sanitarios. Ante ello, las medidas preventivas específicas son relevantes para evitar o disminuir contagios entre pacientes y personal de las unidades de salud, considerando que el periodo presintomático durante el cual el individuo contagiado ya puede transmitir el virus varía entre cinco y seis o hasta 14 días, según datos de la Organización Mundial de la Salud. Además, un paciente infectado puede estar asintomático, incluso, algunas personas después de haber padecido COVID-19 pueden continuar expulsando virus por algunos días más después de recuperarse.

Antecedentes: En México, la inmunoterapia con alérgenos (ITA) y con veneno de himenópteros (VIT) se practica tradicionalmente combinando criterios de las escuelas europea y estadounidense; los dos tipos de extractos están comercialmente disponibles en México. Para una ITA adecuada es crucial un diagnóstico oportuno.Objetivo: Presentar GUIMIT 2019, Guía Mexicana de Inmunoterapia 2019, de base amplia, actualizada, que abarca temas de diagnóstico, indicaciones, dosificación, mecanismos, efectos adversos de la ITA y expectativas con esta modalidad de tratamiento.Método: Con la participación de múltiples grupos mexicanos de alergólogos, que incluían los centros formadores universitarios en alergia e inmunología, se desarrolló el documento de la guía según la metodología ADAPTE. Las guías de inmunoterapia de la European Academy of Allergy and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology, German Society for Allergology and Clinical Immunology y del American College of Allergy, Asthma, and Immunology se seleccionaron como guías fuente, ya que recibieron la puntuación AGREE-II más alta entre las guías internacionales disponibles; su evidencia conforma la base científica de GUIMIT 2019.Resultados: En GUIMIT 2019 se emiten recomendaciones fuertes o débiles (sugerencias) acerca de temas directamente relacionados con el diagnóstico in vivo o in vitro de las enfermedades alérgicas mediadas por IgE, la preparación y aplicación de ITA o VIT y sus efectos adversos; se incluye la revisión de las modalidades de ITA para el futuro. Todos los argumentos que se exponen fueron discutidos y votados con > 80 % de aprobación.Conclusión: Un grupo amplio y diverso de expertos en ITA y VIT emitió recomendaciones transculturizadas basadas en evidencia, que alcanzaron consenso; con ellas se pretende mejorar y homologar la práctica de la inmunoterapia en México.

Introduction In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. Methods Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc). Results For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence. Conclusion Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.

Antecedentes: Existe incremento de reacciones adversas a medicamentos y pocos estudios para el diagnóstico.Objetivo: Determinar la utilidad de pruebas modificadas de degranulación de basófilos (DB) y del factor inhibidor de la migración de leucocitos (LIF, leukocyte migration inhibition factor) para comprobar la hipersensibilidad a medicamentos.Métodos: Se estudiaron 177 pacientes, de uno y otro sexo, con diagnóstico de hipersensibilidad a medicamentos, en quienes se determinó pruebas modificadas de DB, LIF, o ambas entre 2009 y 2014. Se parearon con controles positivos, negativos y población no alérgica. Las solicitudes se emitieron de acuerdo con el tipo de hipersensibilidad, considerando tipo I a DB y tipo IV a LIFResultados: 170 pacientes (96.04%) fueron positivos al menos a un medicamento (RR, 4.71). Se realizaron 561 pruebas modificadas de DB (73.62%) y 201 de LIF (26.37%). El sexo femenino fue más frecuente (64.41%); la edad promedio fue de 38.5 años. La prueba modificada de DB resultó positiva en 70.23% y la de LIF en 67.16%. La sensibilidad de las pruebas se incrementó en forma complementaria y a dos diluciones. La correlación de las pruebas fue altamente significativa.Conclusiones: Las mujeres presentan más reacciones a fármacos. La prueba modificada de DB es útil en cualquier edad. Como los medicamentos pueden activar uno u otro mecanismo de hipersensibilidad es importante solicitar las pruebas simultáneamente.

Introducción: El factor de transferencia (FT) es el extracto dializable de leucocitos con propiedades de transferencia de inmunidad celular. Su uso se ha extendido en el tratamiento de una amplia gama de padecimientos inmunológicos, infecciosos y como coadyuvante de padecimientos oncológicos. A pesar de ello, no se conocen completamente aspectos importantes de su perfil proteico, concentraciones de componentes y mecanismos de acción.Objetivos: Analizar los perfiles proteicos de diferentes factores de transferencia comercializados en México.Métodos: Se obtuvieron y analizaron 6 FT comercializados en México. Se realizó la cuantificación de proteínas por el método de Bradford, cromatografía líquida de alta resolución (HPLC) y electroforesis en geles de poliacrilamida (SDS-PAGE). Todas las muestras fueron analizadas por duplicado.Resultados: Las concentraciones de proteínas totales de todos los FT analizados fueron menores de 0.2 mg/mL. Los perfiles cromatográficos mostraron diferencias en algunos FT. La concentración de proteínas resultó de 6 hasta casi mil veces más baja en comparación con lo informado por algunos fabricantes.Conclusión: Casi la totalidad de los factores de transferencia comercializados en México carecen de un etiquetado y registro sanitario que cumpla con las normas oficiales vigentes.

Background: Urticaria is a disease that a fth of the population shall suffer once in a lifetime. Recent clinical guidelines have proposed some fundamental changes in the diagnosis and treatment of urticaria, making the development of a national, multidisciplinary guideline, with wide acceptability among different professional groups –both specialists and primary health care workers–, necessary in Mexico. Material and method: Internationally recognized tools for guideline- development were used. An interdisciplinary group of clinical experts (some of them knowledgeable in methodology of guideline develop - ment) determined the objectives and scope of the Evidence Based Clinical Practice Guideline with SCOPE. It was decided to adapt and transculturize international guidelines on the diagnosis and treatment of urticaria. With AGREE-II three high-quality guidelines (Zuberbier 2014, Sanchez-Borges 2012, Powell 2007) were selected to function as basic guidelines (BG). A set of Clinical Questions was formulated that lead to recommendations/suggestions, based on these BG, taking into account the cultural and economic background of Mexico, according to GRADE recommendation development. Results: By a formal process of discussion and voting during several working-sessions, experts and rst level healthcare physicians deter - mined the wording of the nal guideline, taking particularly care of developing a document, adjusted to the reality, values and preferences of the Mexican patients. The use of oral second generation, non-sedating antihistamines as rst line treatment is emphasized. Conclusion: This document is an Evidence Based Clinical Practice Guideline for the diagnosis and treatment of acute and chronic urticaria, based on three, high quality, international guidelines. It was developed by a multidisciplinary group. Tables and algorithms make the guideline user-friendly for both, rst line health care physicians and specialists

Despite the use of newer immunosuppressors such as sirolimus (SRL) and tacrolimus (TRL) in heart transplantation, the rate of humoral rejection has remained unchanged. The aim of this study was to analyze the immunologic and histologic effects of cyclosporine (CsA), SRL, and TRL in a porcine model of arterial transplantation.Each transplant recipient animal (n = 49) received an autograft and an allograft and was then allocated to one of four treatment groups and a 7- or 30-day follow-up period, as follows: a WOT group (without immunosuppressor treatment), 7 days (n = 6) and 30 days (n = 5); a CsA group, 7 days (n = 5) and 30 days (n = 6); an SRL group, 7 days (n = 7) and 30 days (n = 8); and a TRL group, 7 days (n = 6) and 30 days (n = 6). The presence of donor-specific antibodies (DSA) was tested at the end of the follow-up period. Morphometric parameters and inflammatory infiltration were analyzed in the explanted grafts.At 30-day follow-up, SRL was the only treatment capable of suppressing DSA formation (0 of 7 vs 4 of 5 in the WOT group; p0.05). SRL completely prevented aneurismal dilation and reduced the number of macrophages in the allografts. TRL treatment achieved a greater reduction of T lymphocytes. CsA did not prevent the reduction in total vascular area at 7 days that was achieved with the SRL and TRL groups. Animals treated with CsA had the largest number of T lymphocytes and macrophages in both follow-up periods.SRL prevented DSA formation and reduced the number of macrophages as compared with TRL and CsA.

Background In liver transplantation, mycophenolate mofetil (MMF) is habitually administered using fixed doses. We assessed whether mycophenolic acid (MPA) monitoring could be advisable in liver transplant patients. Methods In 15 liver transplant patients receiving tacrolimus, daclizumab and MMF (1 g bid, orally), we determined the 12-hour plasma MPA pharmacokinetic profile after one dose of MMF at days 6, 10, and 16, and months 3 and 6. The inhibitory capacity of serum MPA on proliferation of CEM cells, a cell line insensitive to other immunosuppressants, was also determined. Results A large interindividual variability in MPA profiles was observed at any time. Regardless of a gradual increase in individual MPA AUC and C(0) over time following transplantation, a substantial proportion of patients had these parameters below the ranges recommended in other organ transplantations throughout the study. When MPA AUC and C(0) were within the recommended ranges, CEM proliferation was inhibited by almost all serum samples, but when these pharmacokinetic parameters were below the recommended ranges, CEM proliferation was very variable and, therefore, unpredictable. No relationship between MPA pharmacokinetics and the efficacy of MMF could be established (only one patient developed rejection), probably due to the concomitant administration of tacrolimus and daclizumab. Gastrointestinal symptoms were the only adverse events with a significant relationship with MPA levels. Conclusions During the first postoperative months, exposure to MPA is low in a considerable proportion of liver transplant patients receiving MMF at a fixed dose of 1 g bid. MPA monitoring appears necessary in these patients.

Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.

We investigated the relationship between the pharmacokinetics and pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order to define an effective and safe therapeutic range. The area under the curve of the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively). Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing significant reductions (82% and 89.6%, respectively; p0.0005) compared with normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1 pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1% reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537, p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030, r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701) production. In treated patients, the Emax inhibitory sigmoidal model showed that a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF-gamma production. The results demonstrated a significant inhibition of calcineurin activity and IL-2 and IFN-gamma production in patients receiving cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384 ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN-gamma synthesis, and the lack of rejection episodes and relevant toxicity.

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.

Mexico 2009 faced the H1N1VI influenza pandemic, a complex immunologic and clinical host response, whose defense mechanisms have yet to be identified. Lack of information on clinical an immunological features in pediatric population with H1N1VI, delay detection of patients at risk of contracting it. This study aims to identify specific immunologic and/or clinical features of pediatric patients with H1N1VI in a federal Hospital in Mexico City. Methods Single-center, observational, non-experimental, prospective trail from September to October 2009, for pediatric patients arriving to Emergency room of Juarez Hospital, with suspicion of H1N1VI, needing to be younger than 17 years, and agree and sign the consent form by tutor. Samples obtained were peripheral blood, and pharyngeal exudate. From blood LS, Cytokine levels, and routine measurements (CBC, BCH) were investigated; the pharyngeal sample underwent PCR study to viral genetic material. Complementary studies such as arterial blood gases or Torax radiography were realized as needed. Results 32 patients participated. PCR results confirmed 18 cases (56%), 1 patient resulted positive for SII. The average age was 9 years old; 12 (67%) were female, and 6 (33%) were male. The mean amount of days from symptom onset to receiving medical attention was 2.5 days. Main symptoms and signs were fever, malaise, cough, rhinorrhea, and headache. Associated risk factors included malnutrition and tobacco exposure. It was demonstrated an elevation of IL-8, followed by IL-6, IL-12 and IL-10. Blood analysis proved no significant findings, though cases of neutrophilia and leukopenia were detected. Conclusions Limited resources, restricted participation from all the possible H1N1VI patients, thus biasing results due to small sample size; however, the obtained data is consistent with existing reports, nevertheless the information is not enough to establish standardized recommendations. Further collaboration among centers, is needed to identify features that can prompt H1N1VI early identification and prevention in pediatric population.