Dupilumabe e upadacitinibe comparados a medicamentos imunossupressores para o tratamento de dermatite atópica moderada a grave refratária a terapia tópica: revisão rápida de evidências / Dupilumab and upadacitinib compared to immunosuppressive drugs for the treatment of moderate to severe atopic dermatitis refractory to topical therapy: rapid review of evidence

Tecnologia: Dupilumabe e upadacitinibe. Comparadores: Azatioprina, metotrexato, ciclosporina, micofenolato de mofetila. Indicação: Tratamento de dermatite atópica severa em pacientes adultos. Pergunta: Dupilumabe e upadacitinibe são mais eficazes e tão seguros quanto ciclosporina ou outros agentes imunossupressores para obter os desfechos de saúde no tratamento sistêmico de dermatite atópica moderada a grave refratária à terapia atópica? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED e Cochrane Library, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionados três estudos que atenderam aos critérios de inclusão. Conclusão: Dupilumabe, upadacitinibe, ciclosporina e azatioprina são mais eficazes que placebo nos desfechos de eficácia (reduzir sinais clínicos em escalas, reduzir sintomas em escalas) para tratamento da dermatite atópica moderada a grave refratária à terapia tópica, mas esses medicamentos não diferem entre si. Dupilumabe, upadacitinibe, ciclosporina e azatioprina são bem tolerados e seguros

Technology: Dupilumab, upadacitinibe. Comparators: Azathioprine, methotrexate, cyclosporine, mycophenolate mofetil. Indication: Treatment of severe atopic dermatitis in adult patients. Question: Are dupilumab and upadacitinib more effective and as safe as cyclosporine or other immunosuppressive agents for achieving health outcomes in the systemic treatment of moderate to severe atopic dermatitis refractory to atopic therapy? Methods: A bibliographic survey was done in the PUBMED e Cochrane Library databases, following predefined search strategies. The methodological quality of systematic reviews was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: Three studies that met the inclusion criteria were selected. Conclusion: Dupilumab, upadacitinib, cyclosporine, and azathioprine are more effective than placebo on efficacy endpoints (reduce clinical signs on scales, reduce symptoms on scales) for treating moderate to severe atopic dermatitis refractory to topical therapy, but these drugs do not differ from each other. Dupilumab, upadacitinib, cyclosporine, and azathioprine are well tolerated and safe

Pharmacogenetic testing improves treatment responses in patients with PLA2R-related membranous nephropathy / 南方医科大学学报

OBJECTIVE@#To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients.@*METHODS@#A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment.@*RESULTS@#Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05).@*CONCLUSION@#Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.

Effect of Eltrombopag on Response to Immunosuppressive Therapy in Patients with Transfusion-Dependent Non-Severe Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To compare the efficacy of eltrombopag combined with cyclosporine A (CsA) and CsA alone in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA).@*METHODS@#The clinical data of 76 patients with treatment-naive TD-NSAA in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from December 2017 to June 2021 were retrospectively analyzed. Among them, 45 cases were treated with eltrombopag combined with CsA, and 31 patients with compatible baseline characters were treated with CsA alone. The efficacy of patients between the two groups was compared, and the factors affecting the curative effects were also analyzed.@*RESULTS@#There were significant differences in hematological response (HR) and complete response(CR) rates between the two groups at 3, 6, 12 months, and follow-up endpoint of treatment (P<0.05). With the prolongation of eltrombopag treatment time, the curative effect increased gradually, and the patients achieved more CR and HR rates by the end of the follow-up period. Simultaneously, with the increase in the maximum stable dose of eltrombopag, the HR rate increased gradually. The megakaryocyte count in eltrombopag group was higher than that in control at 6 and 12 months (P<0.05). Compared with the control group, the median time of platelet transfusion independence in eltrombopag group was more shorter (P=0.018), and the median platelets transfusion volume was lower (P=0.009). At 3, 6, 12 months after eltrombopag, the change of platelet in eltrombopag group was higher than that in the control group (P<0.05). Analysis of related factors affecting the efficacy showed that sex, age, iron overload, platelet count before treatment had no effect on the efficacy, and the median maximum stable dosage and the administration period for eltrombopag were related to the curative effect. The patients of eltrombopag group experienced adverse events of varying degrees, but the reactions were mild and mostly tolerated.@*CONCLUSION@#Eltrombopag can effectively improve the hematopoietic response and promote platelet recovery for TD-NSAA patients with relatively more residual hematopoietic cells, and it is safe and well tolerated.

Effect of Tacrolimus and Cyclosporine Immunosuppressants on Peripheral Nerve Regeneration: Systematic Review and Meta-analysis / Efeito dos imunossupressores tacrolimus e ciclosporina na regeneração de nervos periféricos: Revisão sistemática e metanálises

Abstract Peripheral nerve damage is an important cause of seeking medical attention. It occurs when the continuity of structures is interrupted and the propagation of nervous impulses is blocked, affecting the functional capacity of individuals. To assess the effects of the immunosuppressants tacrolimus and cyclosporine on the regeneration of peripheral nerves, a systematic review of the literature was carried out. The articles included were published until September 2018 and proposed to evaluate the effects of the immunosuppressants tacrolimus and cyclosporine on nerve regeneration and neuroprotection, available in the MEDLINE, EMBASE, Cochrane Library, Web of Science, Oxford Pain Relief Database, and LILACS databases. The research analysed a total of 56 articles, of which 22 were included in the meta-analysis. Statistical analysis suggests the protective effect of tacrolimus in the regeneration of the number of myelinated axons (95% confidence interval [CI]: 0.93-2.39; p< 0.01); however, such effect was not observed in relation to cyclosporine (95%CI: - 0.38-1.18; p» 0.08) It also suggests that there is a significant relationship between the use of tacrolimus and myelin thickness (95%CI» 2.00-5.71; p< 0. 01). The use of immunosuppressants in the regeneration of peripheral nerve damage promotes an increase in the number of myelinated axons in general, regardless of the administered dose. In addition, it ensures greater myelin thickness, muscle weight and recovery of the sciatic functional index. However, heterogeneity was high in most analyses performed.

Resumo As lesões nervosas periféricas são uma causa importante de busca por atendimento médico. Elas ocorrem quando há a interrupção da continuidade das estruturas e do bloqueio da propagação dos impulsos nervosos, afetando a capacidade funcional dos indivíduos. Para avaliar os efeitos dos imunossupressores tacrolimus e ciclosporina na regeneração de nervos periféricos, foi realizada uma revisão sistemática da literatura. Foram incluídos artigos publicados até setembro de 2018, que se propunham avaliar os efeitos dos imunossupressores tacrolimus e ciclosporina na regeneração nervosa e neuroproteção, disponíveis nas bases de dados MEDLINE, EMBASE, Cochrane Library, Web of Science, Oxford Pain Relief Database e LILACS. A pesquisa analisou um total de 56 artigos, dos quais 22 foram para metanálise. A análise estatística sugere o efeito protetor do tacrolimus na regeneração do número de axônios mielinizados (intervalo de confiança [IC] 95%: 0,93-2,39; p< 0,01); todavia tal efeito não foi observado em relação à ciclosporina (IC95%: - 0,38-1,18; p» 0,08). Ela também sugere haver uma relação significativa entre o uso do tacrolimus e a espessura da mielina (IC95%: 2,00-5,71; p< 0,01). O uso de imunossupressores na regeneração de lesão nervosa periférica promove um aumento no número de axônios mielinizados de forma geral, independentemente da dose administrada. Além disso, garante uma maior espessura da mielina, um maior peso muscular e restabelecimento do índice da função do nervo ciático. Todavia, a heterogeneidade foi alta na maioria das análises realizadas.

Comparison of the clinical effects of two different doses (0. 05% and 0. 1%) of topical cyclosporine A in dry eyes with meibomian gland dysfunction / Comparação de efeitos clínicos de duas doses diferentes (0, 05% e 0, 1%) de ciclosporina A tópica em olhos secos com disfunção da glândula tarsal

ABSTRACT Objective: To compare the clinical efficacy of two different doses of topical cyclosporine A used in addition to artificial tears in the treatment of patients with meibomian dysfunction and secondary dry eye. Methods: Fifty patients aged 18 to 40 years, who presented to our clinic between June 2020 and June 2021 were included in our study. Patients were divided into two groups as Group A (topical cyclosporine A 0.05%) and Group B (topical cyclosporine A 0.1%). All the patients underwent a detailed ophthalmological examination, basal Ocular Surface Disease Index measurement, and Schirmer 1 and tear break-up time tests at all visits. Results: The mean age was 32±7.1 years in Group A and 30.7±8.5 years in Group B. In Group A, there were 15 women and ten men, and Group B consisted of 14 women and 11 men. There was no difference between the groups in terms of age and gender distribution (p>0.05). Schirmer 1 and tear break-up time results and Ocular Surface Disease Index score also did not significantly differ between the groups (p>0.05). Conclusion: Cyclosporine A 0.05% and 0.1% eye drops were both seen to be effective in managing dry eye disease in patients with meibomian gland dysfunction.

RESUMO Objetivo: Comparar a eficácia clínica de duas doses diferentes de ciclosporina A tópica utilizada além da lágrima artificial no tratamento de pacientes com disfunção da glândula tarsal e olho seco secundário. Métodos: No estudo, foram incluídos 50 pacientes com idades entre 18 e 40 anos, que se apresentaram em nossa clínica entre junho de 2020 e junho de 2021. Os pacientes foram divididos em dois grupos: Grupo A (ciclosporina A 0,05% tópica) e Grupo B (ciclosporina A 0,1% tópica). Todos os pacientes foram submetidos a um exame oftalmológico detalhado, medição basal do Índice de Doença da Superfície Ocular, e testes de Schirmer 1 e de tempo de ruptura em todas as visitas. Resultados: A idade média foi de 32±7,1 anos no Grupo A e 30,7±8,5 anos no Grupo B. No Grupo A, havia 15 mulheres e dez homens, e o Grupo B consistia de 14 mulheres e 11 homens. Não havia diferença significativa entre os grupos em termos de distribuição por idade e gênero (p>0,05). Os resultados do Schirmer 1 e do tempo de ruptura e do Índice de Doenças da Superfície Ocular também não apresentaram diferença significativa entre os grupos (p>0,05). Conclusão: Observou-se que os colírios de ciclosporina A 0,05% e 0,1% são eficazes no tratamento da síndrome do olho seco em pacientes com disfunção da glândula tarsal.

Pharmacokinetic study of anti-human T-cell porcine immunoglobulin combined with cyclosporine A immunosuppressive therapy in patients with severe aplastic anemia / 中华血液学杂志

Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.

Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy / 中华血液学杂志

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).

Correlation between Serum G-CSF Level and Immune Function in Children with Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To observe the occurrence of immune dysfunction in children with aplastic anemia (AA) and the factors that may lead to immune dysfunction, analyze the relationship between the expression of granulocyte colony stimulating factor (G-CSF) and immune dysfunction.@*METHODS@#A total of 34 children with AA treated in our hospital from December 2016 to September 2018 were selected. All the children received immunosuppressive therapy (IST) for 6 months. According to whether the children had immune dysfunction after 6 months of treatment, they were divided into occurrence group and non occurrence group. General information and laboratory indices were compared between the two groups, and serum G-CSF level was tested, the relationship between serum G-CSF level and immune dysfunction in AA children after treatment with IST was observed and analyzed.@*RESULTS@#After treatment with IST for 6 months, 12 cases developed immune dysfunction (35.29%). Serum interferon (IFN)-γ level of the occurrence group was higher but G-CSF level was lower than those of the non occurrence group (P<0.05), while the difference of other baseline data was not statistically significant (P>0.05). Multiple regression analysis showed that overexpression of serum IFN-γ and low expression of G-CSF were both the influencing factors of immune dysfunction in AA children after IST treatment (OR>1, P<0.05). ROC curve was drawn, and the result showed that the area under the curve (AUC) of serum G-CSF level predicted the risk of immune dysfunction after IST was 0.843>0.80, when the index cut-off value was set at 6.614 pg/ml, the predictive value was ideal.@*CONCLUSION@#AA children have a higher risk of immune dysfunction after IST, which may be related to the low expression of serum G-CSF. The detection of serum G-CSF expression can be considered to predict the risk of immune dysfunction in AA children after IST, so as to guide early clinical intervention.

Oral mucosa transplantation may improve tear film osmolarity in dogs with keratoconjunctivitis sicca - a preliminary study / [Transplante da mucosa oral na melhoria da osmolaridade do filme lacrimal em cães com ceratoconjuntivite seca - estudo preliminar]

The objective of this study was to evaluate the use of cyclosporine 1% alone or associated with oral mucosa transplantation (OMT) in dogs with dry keratoconjunctivitis (KCS). Schirmer Tear Test (STT-1) and Tear Film Osmolarity (TFO) were measured in both eyes of 30 adult dogs (before and 45 days after treatment. The animals were divided into three groups (10 dogs for group): control (normal dogs), group I (GI, treated with 1% cyclosporine alone), and group II (GII, treated with 1% cyclosporine and OMT). All STT-1 and TFO values were subjected to the Shapiro-Wilk normality test, and all were normally distributed. STT-1 and TFO values before and after treatment were subjected to the T-Student Test. The STT­1 and TFO values of the right eye were subjected to Repeated Measures ANOVA followed by a Tukey Test for comparison between groups I and II. Means with a value of p≤0.05 were considered significant. There was a decreased osmolarity in both groups after treatment. Mean osmolarity in GII (322.60±16.56 mOsm/L) was significantly lower than GI (336.40±5.66 mOsm/L). The OMT associated with cyclosporine 1% improved the osmolarity of the tear film in dogs with KCS with a seeming synergism between the clinical and surgical treatments.(AU)

Avaliou-se o uso de ciclosporina 1% isolada ou associada ao transplante de mucosa oral (TMO) em cães com ceratoconjuntivite seca (CCS). O teste lacrimal de Schirmer (TLS-1) e a osmolaridade do filme lacrimal (OFL) foram medidos em ambos os olhos, em 30 cães adultos, antes e 45 dias após o tratamento. Os animais foram divididos em três grupos (10 cães por grupo): controle (cães saudáveis), grupo I (GI, tratados apenas com ciclosporina 1%) e grupo II (GII, tratados com 1% de ciclosporina associada ao TMO). Todos os valores do TLS-1 e da OFL foram submetidos ao teste de normalidade Shapiro-Wilk, e todos foram distribuídos normalmente. Os valores de TLS-1 e OFT antes e depois do tratamento foram submetidos ao teste T-Student. Os valores TLS-1 e OFT do olho direito foram submetidos à ANOVA de medidas repetidas, seguida por um teste de Tukey para comparação entre os grupos I e II. Valor de P≤0,05 foi considerado significativo. Houve uma diminuição da osmolaridade em ambos os grupos após o tratamento. A osmolaridade média no GII (322,60±16,56 mOsm/L) foi significativamente inferior à no GI (336,40±5,66 mOsm/L). O TMO associado à ciclosporina 1% melhorou a osmolaridade do filme lacrimal em cães com CCS, com uma sinergia aparente entre os tratamentos clínicos e cirúrgicos.(AU)

Síndrome de reacción a drogas con eosinofilia y síntomas sistémicos asociado a herpesvirus humano 6. Caso pediátrico tratado con ciclosporina y corticoides / Drug reaction with eosinophilia and systemic symptoms syndrome associated with human herpesvirus 6. A pediatric case treated with cyclosporine and corticosteroids

La reacción a drogas con eosinofilia y síntomas sistémicos es una reacción adversa cutánea rara, potencialmente grave. Puede presentar fiebre, erupción cutánea polimorfa, edema facial y/o linfoadenopatías. La reactivación del virus herpes humano tipo 6 se asocia a un curso más grave y/o prolongado.Un lactante de 22 meses en tratamiento con fenobarbital presentó lesiones eritematopapulares, fiebre, leucocitosis, proteína C reactiva elevada y alteración de pruebas hepáticas. Se realizó biopsia de piel compatible con reacción adversa a drogas. Se trató con corticoides sistémicos e inmunoglobulina intravenosa sin respuesta. La reacción en cadena de la polimerasa para virus herpes humano tipo 6 resultó positiva. Se inició ciclosporina más prednisona, con buena respuesta. Existe poca evidencia del uso de ciclosporina en adultos, cuando los corticoides sistémicos son inefectivos. Este es el primer reporte pediátrico Podría ser una alternativa efectiva o un complemento de los corticosteroides sistémicos cuando no responde a tratamientos convencionales.

Drug reaction with eosinophilia and systemic symptoms is a rare and potentially serious skin adverse reaction, with fever, polymorphous skin rash, facial edema, and/or lymphadenopathy. Reactivation of human herpes virus type 6 has been associated with a more severe and/or prolonged course. A 22-month-old infant under phenobarbital treatment developed erythematous-papular lesions, fever, leukocytosis, elevated C-reactive protein, and abnormal liver tests. The skin biopsy was compatible with an adverse drug reaction. Treatment with systemic corticosteroids and intravenous immunoglobulin had no response. Polymerase chain reaction for human herpesvirus type 6 was positive, and cyclosporine plus prednisone was started with a good response. There is little evidence for the use of cyclosporine in adults when systemic corticosteroids are ineffective. This is the first report of pediatric drug reaction with eosinophilia and systemic symptoms treated with cyclosporine, which could be an effective alternative or an adjunct to systemic corticosteroid therapy unresponsive to conventional treatments.

Evaluation of the Efficacy of Cyclosporin A Combined with Recombined Human Erythropoietin in the Treatment of Patients with Chronic Aplastic Anemia / 中国医学科学院学报

Objective To compare the efficacy and safety of cyclosporin A(CsA)and CsA combined with recombined human erythropoietin(rhEPO)in the treatment of patients with chronic aplastic anemia(CAA).Methods Data of 79 patients with CAA treated at Department of Hematology,PUMC Hospital between January 2016 and June 2018 were collected for retrospective analysis.Forty-five patients were treated with CsA+rhEPO,and the other 34 patients with CsA alone.All the enrolled patients were treated for at least 1.5-2.0 years and followed for at least 1.0 year.The efficacy,side effects,long-term outcomes were compared between the two groups,and factors that may influence the efficacy were analyzed.Results The patients treated with CsA+rhEPO included 14 males and 31 females,with a median age of 43(19,73)years old.The median treatment duration of CsA and rhEPO was 26(12,38)and 4(3,6)months,respectively,and the median followed-up time was 24(12,42)months.The patients treated with CsA alone included 16 males and 18 females,with a median age of 36(16,85)years old.The median CsA treatment duration was 24(12,40)months and the median follow-up time was 25(12,40)months.There was no statistical difference in baseline characteristics between the two groups(all

Linfohistiocitosis hemofagocítica secundaria a infección crónica activa por virus de Epstein-Barr en un hospital pediátrico en México: series de casos y revisión de la literatura / Hemophagocytic lymphohistiocytosis secondary to chronic active Epstein-Barr virus infection in a pediatric hospital in Mexico: case series and literature review

INTRODUCCIÓN: La linfohistiocitosis hemofagocitica (HLH) secundario está asociada a enfermedades malignas, genéticas o autoinmunes, pero también a infecciones principalmente EBV hasta en un 70%, sin embargo hay poca información. Esta entidad se caracteriza por un curso variable y recurrente que conlleva a una alta morbimortalidad con complicaciones potencialmente mortales. OBJETIVO: Describir las características clínicas y evolución de los pacientes pediátricos con diagnóstico de HLH secundario a CAEBV. RESULTADOS: Se incluyeron 7 pacientes, edad media al diagnóstico fue 52 meses con predilección al sexo masculino. Todos los pacientes fueron tratados con un régimen quimioterapéutico multiagente, que incluye corticosteroide, etopósido y Ciclosporina. Después del tratamiento 6 pacientes presentaron remisión y uno de ellos reactivación. La media de seguimiento fue 19 meses y la supervivencia libre de enfermedad (SLE) 16 meses. CONCLUSIÓN: Podemos observar que el curso clínico es variable en ocasiones fulminantes y con pobre respuesta al tratamiento. Un diagnóstico temprano, así como detectar los factores pronóstico podría ayudar a adaptar estrategias de tratamiento que cambiaría la evolución clínica.

INTRODUCTION: Secondary hemophagocytic lymphohistiocytosis (HLH) is associated with malignant, genetic or autoimmune diseases but also with infections mainly EBV in up to 70%, however there is little information. This entity is characterized by a variable and recurrent course that leads to high morbidty and mortality with life-threatening complications. OBJECTIVE: To describe the clinical characteristics and evolution of pediatric patients with a diagnosis of HLH secondary to CAEBV. RESULTS: 7 patients were included, mean age at diagnosis was 52 months with a predilection for males. All patients were treated with a multiagent chemotherapeutic regimen, including corticosteroid, etoposide, and cyclosporine. After treatment, 6 patients presented remission and one of them had reactivation. The mean follow-up was 19 months and disease-free survival (DFS) 16 months. CONCLUSION: We can observe that the clinical course is variable, sometimes fulminant and with poor response to treatment. An early diagnosis as well as detecting prognostic factors could help to adapt treatment strategies that would change the clinical course.

Informe diário de evidências COVID-19: busca realizada em 3 de junho de 2020 / COVID-19 daily evidence report: search conducted on June 3, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos.

Informe diário de evidências COVID-19: busca referente aos dias 13, 14 e 15 de junho de 2020 / COVID-19 daily evidence report: search for June 13, 14 and 15, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos.

Extensive pyoderma gangrenosum-like lesions revealing a case of hyperzincemia and hypercalprotectinemia: when to suspect it?

Abstract Hyperzincemia and hypercalprotectinemia is a rare inflammatory disease caused by a mutation in the PSTPIP1 gene, with a dysregulation of calprotectin metabolism. Calprotectin is a zinc-binding protein with antimicrobial properties and pro-inflammatory action. The authors report the case of a 20 year-old girl with cutaneous ulcers comparable with pyoderma gangrenosum, growth failure and chronic anemia, who was given the diagnosis of hyperzincemia and hypercalprotectinemia. Measurement of serum zinc and calprotectin concentrations are indicated in these cases.

Brimonidine-induced unilateral ocular lichen planus: a case report / Líquen plano ocular unilateral induzido por brimonidina: relato de caso

ABSTRACT This report was written to describe a case of unilateral brimonidine-induced conjunctival lichen planus. Because the ophthalmic examination indicated chronic conjunctivitis or drug-induced pseudopemphigoid, the patient underwent thorough ophthalmic and systemic examinations, as well as conjunctival biopsy and direct immunofluorescence studies. A 71-year-old woman with unilateral left eye findings of chronic conjunctivitis was referred to our Ophthalmology Department. The patient reported that chronic conjunctivitis began shortly after she initiated use of topical brimonidine. Ophthalmic examination revealed foreshortening of the inferior fornix and symblepharon. Conjunctival biopsy revealed submucous lymphocytes and shaggy distribution of fibrinogen on direct immunofluorescence; this was suggestive of ocular lichen planus. No other systemic lesions were found that were consistent with the presentation of lichen planus. A good response was observed to topical cyclosporine treatment. To our knowledge, this may be the first report of unilateral ocular lichen planus without systemic findings. The correlation with the initiation of topical brimonidine suggests that this might be the first case of biopsy-confirmed brimonidine-induced ocular lichen planus.

RESUMO Este relato é para descrever um caso de líquen plano conjuntival unilateral induzido por brimonidina. Como o exame oftalmológico indicava conjuntivite crônica ou pseudopenfigóide induzido por medicamento, o paciente foi submetido a exames oftalmológicos e sistémicos completos, além de biópsia conjuntival e estudos de imunofluorescência direta. Uma mulher de 71 anos de idade com achados unilaterais do olho esquerdo de conjuntivite crônica foi encaminhada ao nosso departamento de Oftalmologia. A paciente relatou que a conjuntivite crônica começou logo após o início do uso da brimonidina tópica. O exame oftalmológico revelou encurtamento do fórnice inferior e do symblepharon. A biópsia conjuntival revelou linfócitos submucosos e distribuição felpuda de fibrinogênio na imunofluorescência direta; isso era sugestivo de líquen plano ocular. Não foram encontradas outras lesões sistêmicas compatíveis com a apresentação do líquen plano. Uma boa resposta foi observada no tratamento tópico com ciclosporina. Pelo nosso conhecimento, este pode ser o primeiro relato de líquen plano ocular unilateral sem achados sistêmicos. A correlação com o início da brimonidina tópica sugere que este pode ser o primeiro caso de líquen plano ocular induzido por brimonidina confirmado por biópsia.

Ulcerative colitis - treatment with biologicals

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Diagnostic and therapeutic guidelines for plaque psoriasis - Brazilian Society of Dermatology

Abstract: Psoriasis is a chronic inflammatory disease that affects 1.3% of the Brazilian population. The most common clinical manifestations are erythematous, scaling lesions that affect both genders and can occur on any anatomical site, preferentially involving the knees, elbows, scalp and genitals. Besides the impact on the quality of life, the systemic nature of the disease makes psoriasis an independent risk factor for cardiovascular disease, especially in young patients with severe disease. By an initiative of the Brazilian Society of Dermatology, dermatologists with renowned clinical experience in the management of psoriasis were invited to form a work group that, in a partnership with the Brazilian Medical Association, dedicated themselves to create the Plaque Psoriasis Diagnostic and Treatment Guidelines. The relevant issues for the diagnosis (evaluation of severity and comorbidities) and treatment of plaque psoriasis were defined. The issues generated a search strategy in the Medline-PubMed database up to July 2018. Subsequently, the answers to the questions of the recommendations were devised, and each reference selected presented the respective level of recommendation and strength of scientific evidence. The final recommendations for making up the final text were worded by the coordinators.

Pure red cell aplasia and anti-erythropoietin antibodies in patients on hemodialysis: a report of two cases and a literature review / Aplasia pura de células vermelhas e anticorpo antieritropoietina em pacientes de hemodiálise: relato de dois casos e revisão da literatura

ABSTRACT Introduction: Anemia is a frequent multifactorial complication of CKD seen in patients on dialysis derived mainly from impaired erythropoietin (EPO) production. A less common cause of anemia in individuals with CKD is pure red cell aplasia (PRCA) secondary to the production of anti-EPO antibodies. Objective: This paper aimed two describe two cases of PRCA secondary to the production of anti-EPO antibodies including choice of treatment, patient progression, and a literature review. Materials: This study included the cases of two patients with CKD on hemodialysis with severe anemia in need of specific investigation and management. Results: Patient 1 with CKD secondary to hypertension treated with EPO for 7 months showed persistent decreases in hemoglobin (Hb) levels despite the subcutaneous administration of increasing doses of EPO; the patient required recurring blood transfusions. Workup and imaging tests were negative for the main causes of anemia in individuals with CKD on dialysis. Patient 2 with CKD secondary to adult polycystic kidney disease had been taking EPO for 2 years. The patient developed severe abrupt anemia the month he was started on HD, and required recurring transfusions to treat the symptoms of anemia. Workup and imaging findings were inconclusive. Specific laboratory tests confirmed the patients had anti-EPO antibodies. After six months of immunosuppressant therapy (corticosteroids + cyclosporine) the patients were stable with Hb > 9.0 g/dl. Conclusion: PRCA is a rare condition among patients on dialysis treated with rhEPO and should be considered as a possible cause of refractory anemia. Treating patients with PRCA may be challenging, since the specific management and diagnostic procedures needed in this condition are not always readily available.

RESUMO Introdução: Anemia é complicação frequente da Doença Renal Crônica (DRC) em pacientes dialíticos. Apresenta caráter multifatorial principalmente pela insuficiente produção de eritropoietina (EPO). Situação rara causadora de anemia na DRC é Aplasia Pura de Células Vermelhas (APCV), em decorrência da produção de anticorpos anti-EPO. Objetivo: Descrever 2 casos de APCV com formação de anticorpos anti-EPO, sua abordagem clínica, evolução e revisão de literatura. Métodos: Dois pacientes em hemodiálise que desenvolveram anemia grave, necessitando investigação e manejo específico. Resultados: Paciente nº 1: feminina, 75 anos, DRC secundária à hipertensão arterial. Após 7 meses com EPO desenvolveu queda persistente em valores de hemoglobina (Hb) mesmo com incremento em doses EPO SC, necessitando transfusões de sangue recorrentes. Extensa investigação laboratorial e de imagem resultou negativa para principais causas de anemia. Paciente nº 2: masculino, 66 anos, DRC secundária à DRPA, há 2 anos em uso de EPO. No mês de entrada em HD desenvolveu anemia severa, também exigindo transfusões recorrentes para tratamento da anemia sintomática. Extensa investigação laboratorial e por imagem, sem chegar a uma conclusão definitiva. Em ambos os casos a presença de anticorpos anti-EPO foi confirmada por exames laboratoriais específicos. Terapia imunossupressora resultou em estabilização do quadro e Hb > 9,0 g/dl em ambos os pacientes, 6 meses após início do tratamento. Conclusão: APCV é condição rara entre pacientes dialíticos que recebem EPOHuR e deve ser lembrada como causa de anemia refratária. Seu manejo específico e diagnóstico laboratorial nem sempre acessível, tornando desafiadora a condução dos casos para o nefrologista.

Agrandamiento gingival generalizado en un paciente con trasplante renal / Generalized gingival enlargement in a patient with renal transplant

Introducción: El agrandamiento gingival es el aumento exagerado y desfigurante del volumen de la encía. Su aparición se asocia a fármacos, entre los que se encuentran los inmunosupresores y los bloqueadores de los canales de calcio como la ciclosporina A y amlodipino. Objetivo: Describir un caso clínico de agrandamiento gingival asociado a ciclosporina A y amlodipino, con periodontitis crónica subyacente, su tratamiento y prevención de recidiva. Presentación del caso: Paciente masculino, de 50 años de edad, antecedentes de hipertensión arterial, asma bronquial y hepatitis C, además de presentar insuficiencia renal crónica para la cual se le realizó un trasplante renal. Recibe tratamiento con ciclosporina A y amlodipino. Al examen clínico se observaron aumento de volumen generalizado en la encía, que cubría completamente la corona de los dientes, bolsas periodontales de 5 a 8 mm, sangramiento gingival y movilidad dentaria. Principales comentarios: El proceso diagnóstico permitió comprobar que además del agrandamiento gingival generalizado existía una periodontitis crónica generalizada. Conclusiones: La ingestión de un inmunosupresor como la ciclosporina A con el uso de un bloqueador de los canales de calcio, el amlodipino, y la influencia de factores de connotación local, parecen ser los responsables de la aparición combinada del agrandamiento gingival generalizado y la periodontitis crónica concomitante. La fase higiénica contribuyó considerablemente a mejorar el estado periodontal, cuya solución definitiva se alcanzó con la cirugía periodontal convencional. Se corrobora la importancia del examen periodontal en pacientes candidatos a trasplantes de órganos(AU)

Introduction: Gingival enlargement is an exaggerated and disfiguring increase in gum volume, associating its appearance with drugs like immunosuppressants and calcium channel's blockers such as cyclosporine A and Amlodipine. Objective: To describe a clinical case of gingival enlargement associated to cyclosporine A and amlodipine, presenting chronic underlying periodontitis, its treatment and prevention in case of recurrence. Case Presentation: Male patient, 50 years old with a history of arterial hypertension, bronchial asthma and hepatitis C, and presenting chronic renal failure leading renal transplant. The patient was treated with cyclosporine A and amlodipine. In the clinical examination was observed an increased volume in the gum, which completely covered the crown of the teeth, also periodontal bags of 5 to 8 mm, gingival bleeding and dental mobility. Main Comments: The diagnostic process allowed to verify that in addition to the generalized gingival enlargement there was a generalized chronic periodontitis. Conclusions: The ingestion of an immunosuppressant such as Cyclosporin A with the use of a calcium channel's blocker, amlodipine, and the influence of local connotation factors seem to be responsible for the combined appearance of generalized gingival enlargement and concomitant chronic periodontitis. The hygienic phase contributed considerably to improve the periodontal state, whose definitive solution was achieved with conventional periodontal surgery. The importance of periodontal examination in patients who are candidates for organ transplants is corroborated(AU)