Dermatite atópica grave: guia prático de tratamento da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria / Severe atopic dermatitis: a practical treatment guide from the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

A dermatite atópica (DA) é uma doença cutânea inflamatória, crônica, comum, complexa e de etiologia multifatorial, que se manifesta clinicamente com prurido muitas vezes incapacitante, lesões recorrentes do tipo eczema, xerose e que pode evoluir para liquenificação. Embora o conhecimento sobre a sua fisiopatologia venham crescendo nos últimos anos, ainda as formas graves são frequentes e representam um desafio para o clínico. Para o presente guia realizou-se revisão não sistemática da literatura relacionada à DA grave refratária aos tratamentos habituais com o objetivo de elaborar um documento prático e que auxilie na compreensão dos mecanismos envolvidos na DA, assim como dos possíveis fatores de risco associados à sua apresentação. A integridade da barreira cutânea é um dos pontos fundamentais para a manutenção da homeostase da pele. Além dos cuidados gerais: evitação dos agentes desencadeantes e/ou irritantes, o uso de hidratantes, suporte emocional, entre outros, o uso de agentes anti-inflamatórios/imunossupressores de uso tópico e/ou sistêmico também foi revisado. A aquisição de novos agentes, os imunobiológicos e as pequenas moléculas, melhorou a terapêutica para os pacientes com formas graves de DA, sobretudo as refratárias aos tratamentos convencionais.

Atopic dermatitis is a chronic, common, and complex inflammatory skin disease with a multifactorial etiology. It manifests clinically with often disabling pruritus, recurrent eczema-like lesions, and xerosis, and can progress to lichenification. Although understanding of the disease's pathophysiology has been growing in recent years, severe forms are still frequent and represent a challenge for clinicians. A non-systematic review of the literature on severe atopic dermatitis refractory to conventional treatment was conducted to develop the present guide, whose purpose is to help clarify the mechanisms involved in the disease and possible risk factors. The integrity of the skin barrier is fundamental for maintaining skin homeostasis. In addition to general care, patients should avoid triggering and/or irritating agents and moisturizers and seek emotional support, etc.; the use of topical and/or systemic anti-inflammatory/immunosuppressive agents was also reviewed. New agents, immunobiologicals, and small molecules have led to a broader range of therapies for patients with severe forms of the disease, especially cases refractory to conventional treatment.

Conversion to Mycophenolate Mofetil Monotherapy in Liver Recipients: Calcineurin Inhibitor Levels are Key

Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

Enfermedad renal crónica en pacientes trasplantados de hígado en el Hospital Pablo Tobón Uribe 2005-2013 / Chronic Kidney Disease in Liver Transplant Patients in the Hospital Pablo Tobón Uribe 2005-2013

Avances en la terapia inmunosupresora han revolucionado los resultados a largo plazo del trasplante de hígado, sin embargo esto ha incrementado la prevalencia de enfermedad renal crónica (ERC); existen algunos factores de riesgo asociados como el uso de inhibidores de calcineurínicos, la presencia de diabetes e hipertensión. El objetivo de este estudio es determinar la incidencia de ERC en los pacientes trasplantados de hígado del hospital Pablo Tobón Uribe durante los años 2005-2013 y evaluar las complicaciones asociadas. Metodología: cohorte retrospectiva. Resultados: se evaluaron 215 pacientes trasplantados de hígado, la edad mediana fue de 50,37 años (DE ± 12,6), el 42,8% mujeres; 3,3% de los pacientes necesitaron terapia de reemplazo renal al primer mes del trasplante; la terapia inmunosupresora más utilizada fue ciclosporina en el 90,7%. Durante el seguimiento la tasa de filtración disminuye con el tiempo, con una mediana de 86,2 mL/min/1,73 (DE ± 25,9) al momento del trasplante y llegando a 74,2 mL/min/1,73 (DE ± 24,5) a 3 años de seguimiento. La velocidad de deterioro de la función renal por medio del modelo de ecuaciones generalizadas estimadas fue de 3,5 mL/año (IC: 95% 2,44-4,74, p= 0,000). Al momento del trasplante de hígado el 16,3% de los pacientes presentaban una TFG menor a 60 mL/min; a tres años de seguimiento fue de 29,6%; al agrupar las complicaciones encontradas, según presencia o no de disfunción renal al final del seguimiento, encontramos que a excepción de la muerte, la presencia de enfermedad cerebrovascular y enfermedad coronaria fue similar en ambos grupos. Conclusión: la ERC es una complicación frecuente en los pacientes trasplantados de hígado, nuestra recomendación es el control frecuente de los marcadores de daño renal.

Advances in immunosuppressive therapy have revolutionized long-term results of liver transplantation, but this has increased the prevalence of chronic kidney disease (CKD). Some risk factors including diabetes and hypertension are associated with the use of calcineurin inhibitors. The objective of this study is to determine the incidence of CKD in liver transplant patients at the Hospital Pablo Tobon Uribe from 2005 to 2013 and then assess associated complications. Methods: This is a retrospective cohort study. Results: This study evaluated 215 patients with liver transplants. Average patient age at transplant was 50.37 years (SD +/- 12.6), and 42.8% of the patients were women. Kidney replacements were required by 3.3% of the patients within the first month after liver transplantation. The most frequently used immunosuppressive therapy was cyclosporine which was used for 90.7% of the patients. During follow-up, the filtration rate decreased over time with a median of 86.2ml/min/1.73 (SD +/- 25.9) at transplant. This reached 74.2ml/min/1.73 (SD +/- 24.5) at 3 years follow-up. The rate of deterioration of renal function determined by generalized estimated equations was 3.5ml/year (95% CI 2.44 to 4.74, p = 0.000). At the time of liver transplantation 16.3% of patients had glomerular filtration rates of less than 60ml/min. After three years of follow-up, 29.6% of patients had glomerular filtration rates of less than 60ml/min. By grouping complications such as the presence or absence of renal dysfunction at follow-up, we found that, except for death, the presence of cerebrovascular disease and coronary heart disease was similar in both groups. Conclusion: CKD is a frequent complication in liver transplant patients. Our recommendation is frequent monitoring of kidney damage markers.

Incidencia de enfermedad renal crónica y factores de riesgo para su desarrollo en pacientes postrasplante hepático en el Hospital Universitario Fundación Santa Fe de Bogotá 2004-2008 / Incidence of chronic kidney disease and risk factors for patients who underwent liver transplantation at Fundación Santa Fe University Hospital from 2004 to 2008

Antecedentes: La enfermedad renal crónica (ERC) se desarrolla frecuentemente después de someter a pacientes a trasplante de órganos sólidos como hepático, cardíaco, pulmonar, intestino delgado, y se asocia con un aumento en la morbimortalidad, costos y deterioro de la calidad de vida del paciente. El desarrollo de enfermedad renal crónica es una complicación común en pacientes postrasplante hepático. Es definida como una tasa de filtración glomerular entre 60 y 29 ml/min/1,73 m² de área de superficie corporal en el postoperatorio. Múltiples factores contribuyen al riesgo de desarrollar ERC en este grupo de pacientes. Entre los más importantes se encuentran la función renal previa al trasplante, medida por la fórmula MDRD (Modification of Diet in Renal Disease), injuria renal aguda durante el perioperatorio, inmunosupresores como los inhibidores de calcineurina. Durante los primeros seis meses del trasplante es cuando ocurre el deterioro mas rápido de la función renal y en meses posteriores esta declina lentamente. Es importante determinar nuestra incidencia de falla renal crónica, el grado de severidad de esta según la clasificación y los factores de riesgo en pacientes de trasplante hepático. El objetivo de este estudio es determinar la incidencia de enfermedad renal crónica y los factores de riesgo para su desarrollo en pacientes postrasplante hepático en el Hospital Universitario Fundación Santa Fe de Bogotá en el periodo comprendido entre enero del 2004 y noviembre de 2008. Materiales y métodos: Es un estudio descriptivo, retrospectivo. La población, fueron los pacientes llevados a trasplante hepático en el Hospital Universitario Fundación Santa Fe de Bogotá entre enero 1 del 2004 y noviembre 11 del 2008, que tuvieran previo al trasplante una función renal normal, calculada por MDRD, excluyendo insuficiencia renal previa al trasplante y aquellos que requirieron trasplante combinado hígado-riñón. Resultados: De 79 pacientes incluidos en el estudio, 27 (34,2% IC 95% 23,9-45,7) presentaron falla renal al sexto mes de seguimiento con un MDRD de estadio 2. De los 27 pacientes que desarrollaron falla renal crónica postrasplante a los seis meses de seguimiento, 6 (22,2%) tenían diagnóstico de cirrosis por NASH; 5 (18,5%) tenían diagnóstico de hepatitis C. Los 27 pacientes que desarrollaron falla renal crónica al sexto mes de seguimiento, tenían un MDRD pretrasplante en promedio de 89,4 ml/min/m²/SC. La falla renal crónica postrasplante es una complicación que viene en ascenso y que se asocia a factores de riesgo pretrasplante y postrasplante, como son hipertensión arterial, diabetes mellitus, hepatitis C e inmunosupresión. Conclusiones: Podemos decir que existe una tendencia a que los pacientes con diagnóstico pretrasplante de cirrosis por NASH y hepatitis C desarrollen más falla renal crónica. La inmunosupresión en el postrasplante inmediato influye en el desarrollo de falla renal crónica; en nuestro trabajo se observa como ciclosporina A, en un gran porcentaje presente en los pacientes que desarrollaron falla renal crónica. Se necesitarán nuevos estudios para determinar asociación entre estos factores de riesgo y el desarrollo de falla renal crónica.

Background: Chronic Renal Failure (CRF) frequently develops in patients who undergo transplantation of solid organs such as livers, hearts, lungs, and small intestines. CRF increases morbidity and mortality rates, increases costs and results in deterioration in the quality of patients' lives. The development of CRF is a common complication in post-liver transplant patients. It is defined as a glomerular filtration rate between 29 and 60 ml/min/1.73 m² of body surface area during post-surgical procedures. Multiple factors contribute to the risk of developing CRF in this group of patients. The most important among these factors are renal function prior to transplantation as measured by MDRD formula (Modification of Diet in Renal Disease), acute perioperative renal failure, and immune-suppressors such as calcineurin inhibitors. During the first six months after transplantation renal function deteriorates rapidly, but declines slowly thereafter. It is important to determine our incidence of chronic renal failure, the degree of severity according to the classification and the risk factors in patients who underwent liver transplantation. The aim of this study is to determine the incidence of chronic renal disease and the risk factors affecting post-liver transplant patients in the Fundación Santa Fe de Bogota University Hospital from January 2004 to November 2008. Materials and methods: This was a descriptive and retrospective study of a population of patients who had undergone liver transplantation in the Fundación Santa Fe de Bogota University Hospital between January 1, 2004 and November 11, 2008. These patients presented normal renal functions as measured by the MDRD formula. We excluded patients with previous renal insufficiency and combined liver-kidney transplantation patients. Results: 79 patients were included in the study. 27 (34.2% CI 95% 23.9 - 45.7) had developed Stage 2 MDRD renal failure by the 6th month of surveillance. 6 of the 27 patients (22.2%) presented cirrhosis resulting from NASH. 5 of the 27 (18.5%) presented hepatitis C. The 27 patients who developed chronic renal failure by the 6th month of surveillance presented an average MDRD score of 89.4 ml/min/m²/SC prior to transplantation. Chronic renal failure following transplantation is an increasingly common complication, associated with risk factors prior to and following transplantation. These factors include arterial hypertension, diabetes mellitus, hepatitis C and immunosuppression. Conclusions: Patients with pre-transplantation diagnoses of cirrhosis resulting from NASH or of hepatitis have a tendency to develop chronic renal failure. Immunosuppression immediately after transplantation influences the development of chronic renal failure. In our study we observed high percentages of cyclosporine A in patients who developed chronic renal failure. New studies are needed to determine the association between these risk factors and the development of chronic renal failure.