Evaluation the Effect of Ginseng Plant Root Extract on Complications of Azathioprine on Ovarian Follicles and TSH, LH and Progesterone Hormones in Rats

Background: The search for herbal remedies has gained significant attention due to chemical drugs’ potentially harmful side effects. Finding plants that can mitigate these adverse effects is crucial for enhancing the well-being of individuals undergoing chemical drug treatments. Aim: Numerous studies have demonstrated the potent antioxidant properties of ginseng. Azathioprine, a widely used drug, has been shown to induce detrimental side effects on various body tissues. Thus, this study aimed to assess the efficacy of ginseng in reducing the harmful effects of azathioprine on ovarian tissue. Materials and Methods: In this study, mice were divided into groups and injected with ginseng root extract and azathioprine. Ovarian weight and histological analysis were conducted to evaluate the number of ovarian follicles and corpus luteum. Furthermore, the levels of FSH, LH, and progesterone in the blood of the study groups were assessed using ELISA. Results: In treatment group 4 (ginseng extract and azathioprine), compared to treatment group 2 (azathioprine only), a significant increase in the weight of both left and right ovaries was observed. Treatment group 4 also exhibited a notable increase (P<0.05) in the number of primordial, primary, and atretic follicles. The concentration of progesterone significantly increased in treatment group 4 compared to treatment group 2 (p<0.01). Conclusion: The findings of this study indicate that azathioprine can have destructive effects on ovarian tissues, while ginseng extract demonstrates the potential to reduce these detrimental side effects. Furthermore, ginseng extract appears to positively regulate FSH and progesterone hormones.

Evolución clínica en neuromielitis óptica comparando el manejo con azatioprina o rituximab / Clinical evolution in neuromyelitis optica when comparing management with azathioprine and rituximab

RESUMEN INTRODUCCIÓN: El espectro de trastornos de neuromielitis óptica (NMOSD) es un grupo de enfermedades desmielinizantes, inflamatorias y autoinmunes, caracterizadas por episodios recurrentes de neuritis óptica y mielitis transversa longitudinal extensa, entre otras manifestaciones clínicas. Su tratamiento crónico se basa en el uso de terapias inmunosupresoras como azatioprina (AZA), micofenolato mofetilo (MFM) o rituximab (RTX). El objetivo del presente estudio es realizar un análisis comparativo de la respuesta al tratamiento con AZA o RTX. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, analítico, retrospectivo, en el cual se incluyeron inicialmente 69 pacientes con diagnóstico confirmado de NMOSD. Tras aplicar los criterios de inclusión y exclusión 59 pacientes fueron incluidos en el análisis final. RESULTADOS: En el grupo de RTX se evidenció una mejoría importante en el estado funcional en comparación con el grupo de AZA, en el que se vio un empeoramiento de este al año de seguimiento. El perfil de seguridad fue similar entre ambos grupos, con una adherencia significativamente superior en el grupo de RTX. DISCUSIÓN: Los hallazgos del presente estudio respecto a las ventajas del uso de RTX sobre AZA se encuentran en concordancia con resultados de estudios previos reportados en la literatura. CONCLUSIONES: Los resultados respaldan el uso de RTX sobre AZA como terapia de mantenimiento para pacientes con NMOSD, al estar asociado principalmente con una mejoría notable en la funcionalidad de los pacientes, al igual que una mayor adherencia al tratamiento.

ABSTRACT INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a group of inflammatory, autoimmune, and demyelinating disorders. Its hallmark behavior is characterized by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis, among other clinical manifestations. Chronic therapy is based primarily in immunosuppressive therapies such as azathioprine (AZA), mycophenolate mofetil (MMF), or rituximab (RTX). The goal of this study is to perform a comparative analysis of response rates to chronic treatment with either AZA or RTX. MATERIALS AND METHODS: A retrospective observational analytic study was designed with an initial cohort of 69 patients with a diagnosis of NMOSD. After application of the inclusion and exclusion criteria a total of 59 patients were finally included in the analysis. RESULTS: The RTX group had an improved functional status when compared to the AZA group; in the latter this feature worsened after a one-year follow-up. There was also a comparable safety profile between the two groups with a significantly greater adherence to RTX regimes. DISCUSSION: The findings of the current study as to the benefits of RTX in comparison to AZA are similar to the results of previous studies. CONCLUSION: These results favor the use of RTX as maintenance treatment of NMOSD, because of its greater benefit mainly in the improvement in functional status of patients, as well as a greater adherence to treatment.

Exposure to Azathioprine Metabolites and Clinical Outcome in Indian Patients with Crohn’s Disease

Aim: To determine the concentration of 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP), the interpatient variability, and the relationship with disease activity in patients with Chron’s disease on long-term stable doses of azathioprine (AZA). Methods: This is a prospective, tertiary care single-center hospital study in adult Chron’s disease patients treated with AZA. The quantification of phenotypic thiopurine methyltransferase enzyme activity in red blood cells and the estimation of the concentration of 6-TGN and 6-MMP in whole blood was performed using the HPLC-UV detector method. A clinical response was categorized as remission (Harvey-Bradshaw Index [HBI] < 5) or improvement (drop from baseline of at least three points of HBI) based on HBI. Exposure to metabolite concentrations and the clinical response to AZA treatment was observed. Results: Study analysis included 30 patients who were initiated on AZA, and they were followed up with an estimation of metabolite concentrations to determine their clinical outcome. At six months, 93% of (n = 28) patients continued to be on AZA and had clinical improvement. All the patients achieved remission of Chron’s disease. Only two patients developed adverse effects such as joint pain and thrombocytopenia. Conclusion: AZA is a safe and effective therapy in managing Chron’s disease when administered after determining thiopurine methyltransferase phenotype and with dose optimization performed using therapeutic drug monitoring of 6-TGN and 6-MMP.

C-reactive protein levels and prevalence of leukopenia in patients with inflammatory bowel disease treated with azathioprine and/or mesalazine: a real-life study

ABSTRACT Objective To examine serum C-reactive protein levels and the prevalence of leukopenia in patients with Crohn's disease or ulcerative colitis undergoing treatment with azathioprine and/or mesalazine. Methods Retrospective observational study based on clinical and laboratory data collected from medical records of 76 adult patients with inflammatory bowel disease treated with azathioprine, mesalazine or both. Sex, age, diagnosis, number of blood samples and elevated serum C-reactive protein levels during the follow-up period were recorded. The following variables were analyzed in terms of C-reactive protein levels and leukopenia episodes: sex, age, diagnosis of inflammatory bowel disease and type of drug. Statistical analyses included multiple logistic regression and the Fisher's exact test for qualitative variables. Results Leukopenia was observed in 18.4% of patients and was associated with older age and higher doses of medication. In 44% of patients, C-reactive protein levels were high. However, symptoms were not associated with abnormal levels of this marker. Conclusion Regardless of symptoms, serum C-reactive protein levels were not a reliable indicator of controlled inflammatory bowel disease. Leukopenia was independently associated with older age and higher doses of medication and is a common side effect, which should be routinely monitored.

Effect of “shilajit+golden rosa” or vitos preparation on immune response cells (CD4, CD8, IGG, CD64) by azathioprine induced immunosuppression in mice / Монголын эм зүй, эм судлал

Introduction@#During many decides, compounds derived from natural raw materials have demonstrated their effectiveness as therapeutic agents in different areas, such as metabolic disorder, immune system diseases and its regulations. Natural based products, like herbal medicines and minerals are implicated in the regulation of immune function. They control the immune system in a pleiotropic manner and participate in various processes of the adaptive/innate immunity. Therefore, natural raw material has great potential for targeted immune modulators, in the treatment of certain types of immunologic and inflammatory diseases, like rheumatoid arthritis, plaque psoriasis, ankylosing spondylitis and immune deficiency. The purpose of this survey was to study influence of “Shilajit +Golden Rosa” combined shot preparation named by Vitos on immune system in the experimental and preclinical circumstances.@*Goal@#The purpose of this survey was to study influence of “Shilajit +Golden Rosa” Vitos shot preparation on immune system in the experimental and preclinical circumstances.@*Material and Methods@#The immune deficiency was to created by Azathioprine through 5 days in the Balb/c mice after that control group, preparation of “Shilajit +Golden Rosa” Vitos shot were administrated appropriate doses by oral during 10 days. Then we collected blood and quantified amount of CD4+, CD8+, IgG and CD64 (Mouse Elisa Kit Assay: Catalog.No:WAM-568, Elisa Reader, 450 <b>нм</b>, Melsin Medical Co.LTD, www. melsin.com) on the 5^th, 10^th days.@*Results@#All statistical analyses were conducted with SPSS version 20.0 software (IBM, Armonk, NY). Oneway ANOVA was used to assess statistical significance between “Shilajit +Golden Rosa” Vitos shot group and days of observation. Mean values of CD4+, CD8+, CD4/CD8 ratio, IgG, CD64 levels determined in the control and sample group. CD4+, CD8+, CD4/CD8 ratio, IgG and CD64 levels were significantly increased in the “Shilajit +Golden Rosa” Vitos shot group compared with control group by 20.8-67.8 per cent (p<0.05, p<0.01).@*Conclusion@#It’s concluded that, “Shilajit +Golden Rosa” Vitos shot preparation shows immune-stimulator activity not only in the level of cellular (T cells:CD4+, CD8+) but also humoral immunity (B cells: IgG, CD64) in the previously using Azathioprine (75mg/kg) to provoke pathological model of immunosuppression

Recurrent idiopathic granulomatous hypophysitis: learnings through case studies / 中华内分泌代谢杂志

In this article, we summarize clinical features and management of 3 cases with pathology confirmed granulomatous hypophysitis, to improve knowledge and provide treatment guidance in this regards. Patients presented with headache, blurred vision and central diabetes insipidus, respectively. The imaging manifestations were sellar area or pituitary stalk occupying lesions, and the nature was undetermined. The symptoms were not completely relieved after subtotal resection or biopsy. The symptoms could be controlled by high dose glucocorticoid, but relapsed after reduction. Two patients were treated with glucocorticoid combined with azathioprine. One case had no recurrence after withdrawal of the drug and 1 patient was still in treatment. Therefore, for the patients whose symptoms are still not relieved after operation and recurred after glucocorticoid reduction, the scheme of high-dose glucocorticoid combined with immunosuppressant azathioprine can be considered, which may achieve satisfactory curative effect and prognosis.

Meta-analysis of the effectiveness of rituximab and cyclophosphamide combined with azathioprine in the treatment of anti-neutrophil cytoplasmic antibodies-related vasculitis / 中华风湿病学杂志

Objective:To evaluate the effectiveness and safety of rituximab (RTX) and cyclophosphamide/azathioprine (CYC/AZA) in the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis (AAV).Methods:After setting up the search strategy, the inclusion and screening criteria of the literature were determined, the Pubmed, Cochrane Library, Embase, China Biomedical Literature Database, CNKI, Wanfang Database, Weipu Database were searched for RTX and CYC/AZA treatment for AAV. For randomized controlled studies, in which the experimental group was RTX for AAV, and the control group was CYC/AZA for AAV were included. The retrieval time span was from January 2000 to June 2021, and the data obtained were analyzed using Revman 5.3 software.Results:A total of 9 articles and 4 studies were included, with a total of 384 patients, including 203 cases in the experimental group and 181 cases in the control group. In the treatment of AAV, the difference in the remission rate of RTX and CYC/AZA treatment of AAV was statistically significant, and the remission rate of the RTX group was higher [ OR(95% CI)=1.58(1.03, 2.40), P=0.03]. For the remission rates of different types of AAV, RTX and CYC/AZA were benefit for the treatment of granulomatous vasculitis, microscopic polyangiitis, eosinophilic granulomatous vasculitis, there was no statistically significant difference in the remission rate of patients with protease 3-related vasculitis and myeloperoxidase-related vasculitis. The incidence of granulocytopenia in the RTX group was significantly lower than that in the CYC/AZA group, and RTX treatment could reduce the incidence of other serious adverse reactions. Conclusion:For the remission induction therapy, RTX is not inferior to CYC for all subtypes of AAV. In the maintenance treatment phase, RTX has a higher remission rate and a lower recurrence rate. During the entire treatment process, patients who were treated with RTX had a higher long-term remission rate than patients who were not treated with RTX. RTX can effectively reduce the occurrence of adverse reactions such as neutropenia.

Efficacy of infliximab in the treatment of small intestinal Crohn's disease and its effects on simple endoscopic score for Crohn's disease, routine blood test and nutritional indexes / 中国基层医药

Objective:To investigate the efficacy of infliximab in the treatment of small intestinal Crohn's disease and its effects on simple endoscopic score for Crohn's disease (SES-CD), routine blood test and nutritional indexes.Methods:Eighty-four patients with small intestinal Crohn's disease who received treatment in Zhejiang Xin'an International Hospital between November 2019 and March 2021 were included in this study. They were randomly divided into control and observation groups with 42 patients each. The control group was treated with azathioprine. The observation group was treated with azathioprine and infliximab. Clinical efficacy, SES-CD score, hemoglobin (Hb) level, white blood cell (WBC) count, platelet (PLT), albumin (ALB), pre-albumin (PA) and total protein (TP) levels pre- and post-treatment were compared between the two groups.Results:Response rate in the observation group was significantly higher than that in the control group [92.8% (39/42) vs. 73.8% (31/42), χ2 = 5.48, P < 0.05]. There was no significant difference in SES-CD score pre-treatment between the control and observation groups [(7.24 ± 1.30) points vs. (7.33 ± 1.27) points, t = -0.34, P > 0.05]. After treatment, SES-CD scores in the control and observation groups were (5.12 ± 1.17) points and (4.22 ± 0.98) points, respectively, which were significantly decreased compared with those before treatment ( t = 11.01, 14.66, both P < 0.001). After treatment, SES-CD score in the observation group was significantly lower than that in the control group ( t = 4.19, P < 0.001). Before treatment, there were no significant differences in Hb level [(110.23 ± 16.19) g/L vs. (112.27 ± 15.98) g/L], WBC count [(7.61 ± 2.54) × 10 9 g/L vs. (7.47 ± 2.61) × 10 9 g/L] and PLT level [(420.14 ± 130.27) × 10 9 g/L vs. (419.23 ± 131.15) × 10 9 g/L] between the control and observation groups ( t = -0.58, 0.25, 0.03, all P > 0.05). After treatment, Hb level [(120.25 ± 14.36) g/L and (130.17 ± 12.24) g/L ], WBC count [(6.01 ± 1.88)× 10 9 g/L, (5.13 ± 1.96) × 10 9 g/L) and PLT level [(321.79 ± 110.21) × 10 9 g/L, (267.25 ± 100.23) × 10 9 g/L] in the control and observation groups were significantly decreased compared with those before treatment ( tcontrol group = -4.70, 6.60, 8.02, tobservaton group = -7.91, 3.50, 4.99, all P < 0.05). Hb level post-treatment in the observation group was significantly higher than that in control group ( t = -3.41, P < 0.05) . WBC count and PLT level in the observation group were significantly lower than those in the control group ( t = 2.10, 2.37, both P < 0.05). Before treatment, there were no significant differences in ALB level [(33.14 ± 5.66) g/L vs. (32.98 ± 5.73) g/L], PA level [(220.17 ± 71.14) mg/L vs. (219.89 ± 70.26) mg/L], TP level [(61.23 ± 8.21) g/L vs. (60.95 ± 8.17) g/L] between control and observation groups ( t = 0.12, 0.01, 0.15, all P > 0.05). After treatment, ALB level [(38.29 ± 6.13) g/L, (44.23 ± 6.07) g/L], PA level [(281.14 ± 85.23) mg/L, (320.27 ± 82.01) mg/L], TP level [(67.23 ± 7.22) g/L, (73.28 ± 6.97) g/L] in the control and observation groups were significantly increased compared with those before treatment ( tcontrol group = -7.90, -4.30, -5.08, tobservation group = -13.76, -7.52, -11.45, all P < 0.05). After treatment, ALB, PA and TP levels in the observation group were significantly higher than those in the control group ( t = -4.46, -2.14, -3.89, all P < 0.05). Conclusion:Infliximab is highly effective on small intestinal Crohn's disease. It can effectively decrease SES-CD score, improve routine blood parameters and nutritional indexes, alleviate azathioprine-induced myelosuppression, and reduce gastrointestinal reactions.

Long-term safety of azathioprine for treatment of neuromyelitis optica spectrum disorders / Segurança a longo prazo da azatioprina no tratamento dos transtornos do espectro da neuromielite óptica

ABSTRACT Background: Azathioprine is a common first-line therapy for neuromyelitis optica spectrum disorder (NMOSD). Objective: The aim of this study was to determine whether long-term treatment (>10 years) with azathioprine is safe in NMOSD. Methods: We conducted a retrospective medical record review of all patients at the School of Medicine of the University of São Paulo (São Paulo, Brazil) who fulfilled the 2015 international consensus diagnostic criteria for NMOSD and were treated with azathioprine for at least 10 years. Results: Out of 375 patients assessed for eligibility, 19 were included in this analysis. These patients' median age was 44 years (range=28-61); they were mostly female (17/19) and AQP4-IgG seropositive (18/19). The median disease duration was 15 years (range=10-39) and most patients presented a relapsing clinical course (84.2%). The median duration of treatment was 11.9 years (range=10.0-23.8). The median annualized relapse rates (ARR) pre- and post-treatment with azathioprine were 1 (range=0.1-2) and 0.1 (range=0-0.35); p=0.09. Three patients (15.7%) had records of adverse events during the follow-up, which consisted of chronic B12 vitamin deficiency, pulmonary tuberculosis and breast cancer. Conclusion: Azathioprine may be considered a safe agent for long-term treatment (>10 years) of NMOSD, but continuous vigilance for infections and malignancies is required.

RESUMO Introdução: A azatioprina é um tratamento comum de primeira linha para os transtornos do espectro neuromielite óptica (NMOSD). Objetivo: Este estudo visou determinar a segurança do tratamento a longo prazo (>10 anos) da NMOSD com a azatioprina. Métodos: Foi realizada revisão retrospectiva de todos os prontuários de pacientes que preenchiam critérios de NMOSD de acordo com o "International Consensus Diagnostic Criteria for NMOSD" de 2015 em uso de azatioprina por ao menos 10 anos matriculados no ambulatório de Doenças Desmielinizantes do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Resultados: De 375 pacientes avaliados, 19 preencheram critérios de inclusão para análise. A mediana de idade foi de 44 anos (variância=28-61); os pacientes eram predominantemente do sexo feminino (17/19) e AQP4-IgG soropositivos (18/19). A mediana do tempo de duração de doença foi 11,9 anos (variância=10,0-23,8), a mediana da taxa anualizada de surtos pré e pós-tratamento foi de 1 (variância=0,1-2) e 0,1 (variância=0-0,35), p=0,09. Três pacientes (15,7%) apresentaram registro de eventos adversos durante o seguimento: deficiência crônica de vitamina B12, tuberculose pulmonar e câncer de mama. Conclusão: A azatioprina provavelmente pode ser considerada segura para o tratamento a longo prazo (>10 anos) da NMOSD, porém vigilância contínua de neoplasias e infecções é necessária.

Effectiveness of Echinacea purpurea extract on immune deficiency induced by azathioprine in male albino rats

This study was performed to evaluate the effectiveness of Echinacea purpurea (E.P.) on azathioprine (AZA)-induced immune deficiency in albino rats. Thirty six male albino rats were divided into six equal groups. The first group served as normal control, the second and third groups were treated with two doses of AZA (3 and 5mg/kg/b.w/day IP), respectively for six weeks. The fourth group was treated with 50 mg kg/b.wt/day of Echinacea. The fifth and sixth groups were treated with3 and 5 mg AZAm respectively followed by50 mg E.P. administration. At the end of the experimental period, both doses of AZA revealed a significant reduction in total body and spleen weights, increase in tissue total protein with a significant increase in serum total protein and albumin, a marked decrease in the number of WBCS associated with a decrease in the number of lymphocytes, a significant decrease in serum total anti-oxidant capacity. Also,concentration of immunoglobulins (IgG and IgM) and interleukins (IL4 &IL6) showed a significant increase, while the level of IL10 decreased significantly in splenic tissue. The dose of AZA (5 mg /kg b.wt.) only resulted in a highly significant increase in serum level of T3 and T4. However, treatment with Echinacea purpurea extract had a significant influence on immune deficiency induced by azathioprine. These findings demonstrated that E.P. extract is a promising immunomodulatory agent with a potent therapeutic value in stimulating the immune response.

Nodular anterior scleritis associated with Berger's disease / Esclerite anterior nodular associada à doença de Berger

ABSTRACT A 45-year-old female patient presented with a complaint of right eye redness and pain for 7 days. She was under investigation for urinary abnormalities and reported a previous history of recurrent oral ulcers and ocular hyperemia in both eyes. Best-corrected visual acuity was 20/30 and 20/20 in the right and left eyes, respectively. Slit-lamp biomicroscopy of the ocular surface of the right eye revealed nasal scleral hyperemia that persisted after instillation of topical phenylephrine 10%, reinforcing the diagnosis of anterior scleritis. Renal biopsy showed immunoglobulin A immune complexes and confirmed the suspected diagnosis of Berger's disease. Maintenance immunosuppressive therapy with azathioprine following a 6-month induction of remission with cyclophosphamide was necessary after pulse therapy with methylprednisolone. Scleritis is usually related to systemic autoimmune diseases, such as rheumatoid arthritis, and polyangiitis. Herein, we describe a rare case of unilateral anterior scleritis associated with Berger's disease.

RESUMO Paciente de 45 anos, sexo feminino queixava-se de hiperemia e dor no olho direito há sete dias. Encontrava-se sob investigação de alterações urinárias e relatou história pregressa de úlceras orais e hiperemia ocular bilateral recorrentes. A acuidade visual corrigida era de 20/30 no olho direito e 20/20 no esquerdo. A biomicroscopia da superfície ocular do olho direito revelou intensa hiperemia escleral em região nasal que persistiu após a instilação de fenilefrina tópica a 10%, reforçando o diagnóstico clínico de esclerite anterior unilateral. A biópsia renal revelou a presença de imunocomplexos de IgA e confirmou a hipótese de doença de Berger. Uma terapia imunossupressora de manutenção com azatioprina após 6 meses de indução de remissão com ciclofosfamida foi necessária após pulsoterapia com metilprednisolona. A esclerite geralmente está relacionada a doenças autoimunes sistêmicas, como artrite reumatoide e poliangeite. Descrevemos aqui um caso raro de esclerite anterior unilateral associada à doença de Berger.

Efficacy and safety of dupilumab in two adolescents with severe atopic dermatitis / Eficácia e segurança do uso de dupilumabe em dois adolescentes com dermatite atópica grave

ABSTRACT We report the cases of two adolescent siblings with severe atopic dermatitis, who, despite weighing approximately 40kg, presented a good response to dupilumab with the off-label dose for individuals aged 12 years and weighing 60kg. Both had already used cyclosporine, azathioprine, methotrexate and oral corticosteroids for long periods, plus topical treatments with no adequate disease control. Skin lesions were constant and widespread, with frequent skin infections and very poor quality of life, with numerous physical and psychosocial consequences, such as dropping out of school activities due to severe itching, appearance and bullying. They also showed delayed growth and development. In 2018, dupilumab, an immunobiological agent, was approved for treatment of moderate to severe atopic dermatitis in adults and, in 2019, extended to the 12-17-year age group. Although it had already been approved by the Brazilian Health Surveillance Agency, the 200mg presentation (indicated for the weight of patients) was not available, with no expected arrival date. Therefore, weighing the risks and benefits of the situation of both, we chose to treat them with an adult dose (loading dose of 600mg subcutaneously, and 300mg subcutaneously every 2 weeks) despite the low weight. So far, they have received eight injections, showing significant improvement of disease and quality of life. There were no major adverse effects, only worsening of allergic conjunctivitis in one of them. The patients and their family are very satisfied, and we believe that the therapy has been successful.

RESUMO Relatamos os casos de dois irmãos adolescentes com dermatite atópica grave e que, apesar de pesarem cerca de 40kg, apresentaram boa resposta ao dupilumabe com a dose off-label para indivíduos com 12 anos e peso de 60kg. Ambos já tinham usado ciclosporina, azatioprina, metotrexato e corticoide oral por longos períodos, acrescidos de tratamentos tópicos sem controle adequado da doença. As lesões cutâneas eram constantes e disseminadas, e os irmãos apresentavam infeções de pele frequentes e qualidade de vida muito ruim, com inúmeras consequências físicas e psicossociais, como o abandono da atividade escolar pelo prurido intenso, pela aparência e pelo bullying sofrido. Apresentavam também retardo de crescimento e de desenvolvimento. Em 2018, o dupilumabe, um agente imunobiológico, foi aprovado para o tratamento de dermatite atópica moderada a severa para adultos e, em 2019, ampliado para faixa etária de 12 a 17 anos. Embora já tivesse a aprovação da Agência Nacional de Vigilância Sanitária no Brasil, a apresentação de 200mg (indicada para o peso dos pacientes) não estava disponível, sem previsão de chegada. Assim, pesando os riscos e benefícios da situação de ambos, optamos por tratá-los com dose de adulto (ataque de 600mg por via subcutânea e 300mg por via subcutânea a cada 2 semanas) apesar do baixo peso. Até o momento, eles realizaram oito aplicações, apresentando importante melhora da doença e da qualidade de vida. Não houve efeitos adversos importantes - apenas a piora da conjuntivite alérgica em um deles. Os pacientes e sua família estão muito satisfeitos, e nós avaliamos que a terapia está sendo bem-sucedida.

Azathioprine: its uses in dermatology

Abstract This is a narrative review of azathioprine. This medication is immunomodulatory and immunosuppressive, and it has been used widely through different medical specialties to modify disease. It has been proven useful for several dermatoses and it has encountered success when used as an off-label indication for other dermatologic diseases. Its mechanism of action is described thoroughly, as well as precautions for monitoring adequate levels in patients using it. Dermatologists should also be aware of the possible adverse events it may present. In dermatology it can be used in bullous and autoimmune diseases, and in other conditions, including intractable pruritus, atopic dermatitis, photodermatoses, psoriasis, and others. Azathioprine offers an alternative as a steroid-sparing agent and this review helps dermatologists prescribe it safely to all patients who require it.

Hepatotoxicidade induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada / Azathioprine-induced hepatotoxicity in a Vogt-Koyanagi-Harada syndrome patient

Este relato teve como objetivo apresentar um caso de hepatotoxicidade colestática induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada. À admissão, apresentava icterícia +3/+4, acolia fecal e colúria, além de aumento de marcadores hepáticos, sendo compatível com síndrome colestática, cuja etiologia foi confirmada após exclusão de outras causas possíveis e retirada da azatioprina. A paciente evoluiu, após 1 semana de retirada do fármaco, com diurese livre de coloração menos escura e evacuação presente, sem acolia. Além disso, houve melhora nos exames que precederam a alta hospitalar

This report aimed at presenting a case of azathioprine-induced cholestatic hepatotoxicity in a patient with Vogt-Koyanagi-Harada syndrome. On admission, she presented with jaundice +3/+4, acholic feces, and choluria, as well as increased hepatic markers, all consistent with cholestatic syndrome, the etiology of which was confirmed after other possible causes were ruled out and azathioprine was discontinued. After 1 week of the drug discontinuation, the patient progressed with free diuresis of lighter color and defecation, with no acholia. In addition, tests performed before discharge were improved.

Treatment of Idiopathic Immune Mediated Hemolytic Anaemia in Dogs

Immune-mediated hemolytic anemia (IMHA) is the most common autoimmune disease in dogs. This study was conducted to evaluate prednisolone and azathioprine therapeutic protocols for the management of idiopathic IMHA in dogs. The anaemic dogs brought with clinical signs such as pale or icteric mucous membranes were screened for IMHA by saline agglutination and spherocyte count and confirmed by flow cytometry. The positive cases were further subjected to haematology, biochemistry, coagulation profile, MAT and polymerase chain reaction (PCR) for the diagnosis of underlying secondary causes like Babesia spp, Ehrlichia canis and Leptospira spp (secondary IMHA). Thirty two cases were positive for IMHA, out of which thirteen cases were primary (Idiopathic) IMHA (17.3 %) and remaining nineteen cases were secondary IMHA (82.7 %) due to underlying causes such as Babesia gibsoni (13), Ehrlichia canis (3) and Leptospira spp. (3) respectively. Immunosuppressive therapy with prednisolone and prednisolone in combination with azathioprine and specific therapy of etiological agent with supportive therapy was used. Significant increase in Hb, PCV, RBC and thrombocyte count, significant decrease in leucocyte, neutrophil, monocyte and total protein and significant increase in ALT activity was recorded after therapy. Prednisolone was found to be effective in the management of canine IMHA than prednisolone combined with azathioprine

Clinical and laboratory data in pediatric autoimmune hepatitis: study from referral center in Iran / Datos clínicos y de laboratorio en hepatitis autoinmune pediátrica: estudio del centro de referencia en Irán

ABSTARCT Background : Autoimmune hepatitis (AIH) is an auto-inflammatory liver disease of children and adults, affecting patients of any age, sex, race or ethnicity, with more prevalence in females. Objective : The aim of this study was to evaluate clinical manifestation, laboratory findings, and outcome of children with autoimmune hepatitis. Materials and methods : We evaluated 86 patients treated and followed with final diagnosis of AIH between years 2010 to 2018. Physical findings (including jaundice, hepatomegaly, splenomegaly and encephalopathy), liver enzymes, liver histology and autoantibodies (including ANA, Anti LKM-1 and ASMA) were extracted from medical files. Then the patients were followed for their final outcome (including response to medical treatment or successful treatment withdrawal, liver transplantation or death). Results : Among 86 patients with AIH with mean age 9.10±4.36 years old, 66.27% were females. Jaundice (75.6%) and hepatomegaly (46.5%) were the most frequent physical findings, followed by splenomegaly (32.6%) and encephalopathy (17.4%). Aminotransferases including AST and ALT were elevated at least 3 times more than upper limit of normal in most of the patients (61.6% and 55.81%, respectively). Autoantibodies were available in 53 of 86 patients, 24.5% had AIH-1, 3.8% had AIH-II and 67.9% were seronegative. Medical treatment including prednisolone and azathioprine was started for patients, 53 of 86 cases (61.6%) had remission and 11 of 86 (13.7%) tolerated medication withdrawal successfully. Among all cases, 26 (30.2%) patients needed liver transplantation. Mortality rate was 9 among 86 cases (10.5%). Conclusion : Jaundice and hepatomegaly was the most frequent clinical findings. Mortality rate was 10.5%.

RESUMEN Antecedentes : La hepatitis autoinmune (AIH) es una enfermedad hepática autoinflamatoria de niños y adultos, que afecta a pacientes de cualquier edad, sexo, raza u origen étnico, con mayor prevalencia en las mujeres. Objetivo : El objetivo de este estudio fue evaluar la manifestación clínica, los hallazgos de laboratorio y el resultado de los niños con hepatitis autoinmune. Materiales y métodos : Evaluamos 86 pacientes tratados y seguidos con el diagnóstico final de AIH entre los años 2010 a 2018. Los hallazgos físicos (incluyendo ictericia, hepatomegalia, esplenomegalia y encefalopatía), enzimas hepáticas, histología hepática y autoanticuerpos (incluidos ANA, Anti LKM-1 y ASMA) se extrajeron de las historias médicas. Luego, los pacientes fueron seguidos para su resultado final (incluida la respuesta al tratamiento médico o la retirada exitosa del tratamiento, el trasplante de hígado o la muerte). Resultados : Entre 86 pacientes con AIH con una edad media de 9,10 ± 4,36 años, el 66,27% eran mujeres. La ictericia (75,6%) y la hepatomegalia (46,5%) fueron los hallazgos físicos más frecuentes, seguidos de esplenomegalia (32,6%) y encefalopatía (17,4%). Las aminotransferasas que incluyen AST y ALT se elevaron al menos 3 veces más que el límite superior de la normalidad en la mayoría de los pacientes (61,6% y 55,81%, respectivamente). Los autoanticuerpos estaban disponibles en 53 de 86 pacientes, 24,5% tenían AIH-1, 3,8% tenían AIH-II y 67,9% eran seronegativos. Se inició tratamiento médico que incluyó prednisolona y azatioprina, 53 de 86 casos (61,6%) tuvieron remisión y 11 de 86 (13,7%) toleraron el retiro de medicamentos con éxito. Entre todos los casos, 26 (30,2%) pacientes necesitaron un trasplante de hígado. La tasa de mortalidad fue de 9 entre 86 casos (10,5%). Conclusión : la ictericia y la hepatomegalia fueron los hallazgos clínicos más frecuentes. La tasa de mortalidad fue del 10,5%.

Comparación entre dos esquemas de inmunosupresión en pacientes con trasplante hepático en un hospital universitario en Medellín, Colombia / Comparison of two immunosuppressive regimens for liver transplant patients in a university hospital in Medellín, Colombia

Introducción. El desarrollo de terapias inmunosupresoras en trasplante hepático ha sido uno de los aspectos fundamentales que ha permitido disminuir la presencia de rechazos y mejorar la supervivencia del injerto y de los pacientes. El presente estudio se hizo para conocer la efectividad de dos esquemas de tratamiento inmunosupresor en una cohorte de pacientes con trasplante hepático, entre 2006 y 2017, en un hospital universitario en Medellín, Colombia. Metodología. Se realizó un estudio observacional retrospectivo donde se compararon dos esquemas de tratamiento inmunosupresor con ciclosporina (CsA) y azatioprina (AZA) versus tacrolimus (TAC) y micofenolato (MMF). Resultados. Se incluyeron 147 pacientes al estudio, 79 mujeres y 68 hombres, con una mediana de edad de 55 años. La tasa de incidencia de rechazo agudo en el grupo CsA/AZA fue de 7,3 y para el grupo TAC/MMF fue de 13,8, con una razón de tasas de 0,53 (IC95%=0,31-0,89) por cada 100 personas/año, siendo esta diferencia estadísticamente significativa (p=0,02). No hubo diferencias significativas entre los grupos con respecto a la presencia de rechazo crónico, supervivencia del injerto o de los pacientes. Con respecto a los efectos adversos asociados al tratamiento, solo hubo diferencia significativa en una mayor presencia de diarrea en el grupo TAC/MMF. Conclusión. Solo se encontró diferencia significativa en cuanto a un número mayor de rechazos agudos en el grupo tratado con TAC/MMF. Estos hallazgos están en concordancia con la experiencia local, en la que en pacientes seleccionados se puede utilizar este esquema, con buenos resultados clínicos y menores costos para el sistema de salud. Hasta el momento, esta es la primera cohorte retrospectiva de Colombia y Latinoamérica que realiza una comparación, como la expuesta.

Introduction. The development of immunosuppressive therapies in liver transplantation has been one of the major contributing factors that have reduced the presence of rejections and improved graft and patient survival. The present study was conducted to determine the effectiveness of two immunosuppressive schemes in a cohort of liver transplant patients, between 2006 and 2017, at a university hospital in Medellin, Colombia. Methodology. A retrospective observational study was performed to compare two immunosuppressive treatment schemes with cyclosporine (CsA) and azathioprine (AZA) versus tacrolimus (TAC) and mycophenolate (MMF). Results. A total of 147 patients were included in the study, 79 women and 68 men, with a median age of 55 years. The incidence rate of acute rejection in the CsA/AZA group was 7.3 while in the TAC/MMF group was 13.8, with a rate ratio of 0.53 (95%CI=0.31-0.89) for every 100 person-year, this difference being statistically significant (p=0.02). There were no significant differences between the groups regarding the presence of chronic rejection, graft or patient survival. With respect to adverse effects associated with the treatment, there was only a significant difference in the presence of diarrhea in the TAC/MMF group. Conclusion. A significant difference was only found in terms of a higher number of acute rejections in the group treated with TAC/MMF. These findings are in agreement with local experience, in which this scheme can be used in selected patients, with good clinical results and lower costs for the health system. So far, this is the first retrospective study in Colombia and Latin America to make a comparison such as the one presented.

Maternal and perinatal outcome of Evan’s syndrome: a 5 years study in a tertiary care centre

Background: Evans syndrome is a rare autoimmune disorder characterized by simultaneous or sequential presence of a positive antiglobulin test, autoimmune haemolytic anemia (AIHA), and immune thrombocytopenia (ITP). It is characterised by frequent exacerbations and remissions within a chronic course. It was first described by Robert Evans in 1951.  Incidence of AIHA is 1 per 75 - 80,000 and ITP is 5.5 /100000 per general adult population.  Incidence of Evans syndrome is 1.8% to 10% of patients with ITP. Objective was to study the maternal and perinatal outcome of women with Evans syndrome (E).Methods: About 4 antenatal mothers were identified with Evans syndrome at St. Johns medical college and hospital, Bengaluru during the study period of 5 years from July 2013-July 2017. They were followed up during their antenatal, intra natal and postnatal period and outcomes were studied. All patients included in the study fulfilled the criteria for Evans syndrome.Results: There were 4 cases of Evans syndrome, with a total number of deliveries of 11859, during this 5 year study. Incidence was 0.09 per 1000 births. All patients presented with bleeding manifestations ranging from mucosal haemorrhage to subarachnoid haemorrhage (SAH) at the time of diagnosis. All patients were on treatment with either 1st or 2nd line of management with corticosteroids/ azathioprine. None had bleeding during pregnancy after the initiation of treatment. Patients had antenatal complications like preeclampsia 25%, IUGR 25%, oligohydraminos 50%, IUD 25%. 2 patients received platelet transfusions intrapartum. None had intrapartum or postpartum haemorrhage. There were no maternal and neonatal mortality.Conclusions: Evans syndrome in pregnancy is a rare condition and requires multi disciplinary approach involving specialists from obstetrics, neonatology, and hematology. Close maternal and fetal surveillance and management during pregnancy is essential to increase the possibility of a favourable pregnancy outcome in these women.

Early Initiation of Steroid-sparing Drugs in Idiopathic Pulmonary Hemosiderosis

Idiopathic pulmonary hemosiderosis is conventionally treated withsteroids, prolonged usage of which maybe deleterious anddisease often recurs on tapering. We initiated hydroxy-chloroquine and azathioprine early in treatment along withsteroids in seven children with idiopathic pulmonaryhemosiderosis, and observed that early introduction of secondline immunosuppressants helped in reducing disease flare andsteroid toxicity without serious adverse effects.

The profile and clinical outcomes of patients with renal involvement due to IgA vasculitis: is azathioprine a good option for treatment?

Abstract Background: The Henoch-Schonlein Purpura (HSP) or IgA vasculitis is the most common vasculitis of childhood and may occur with renal involvement, with hematuria and / or proteinuria, and may cause severe and non-reversible sequelae. Objectives: To establish the profile of patients with renal involvement due to IgA vasculitisand to describe our experience with the use of azathioprine to treat patients with nephritis. Methods: Clinical data were retrospectively collected from medical records of patients with IgA vasculitiswho attended the pediatric rheumatology unit between 1995 and 2017. Patients were separated into two groups based on whether or notthey weretreated with non-glucocorticoid immunosuppressants. Results: From the178 patients with IgA vasculitis, nephritis was found in67 patients (37.6%), 13 of whom receivedtreatment with non-glucocorticoid immunosuppressants. Ten patients responded well to azathioprine and 1 patient to cyclosporine. Forty patients received oral glucocorticoids, whilst 16received intravenous glucocorticoids. Conclusion: Azathioprine may be beneficial in the treatment of IgA vasculitis with renal involvement.