Leprosy detection rate in patients under immunosuppression for the treatment of dermatological, rheumatological, and gastroenterological diseases: a systematic review of the literature and meta-analysis.

BACKGROUND: Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases. METHODS: We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression. RESULTS: The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000-0.00266; I2 = 0%, p = 0.55). CONCLUSION: Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions. TRIAL REGISTRATION: This review is registered in PROSPERO with the registry number CRD42018116275 .

Unexpected better outcome in a liver transplant recipient with COVID-19: a beneficial effect of tacrolimus? / Evolución clínica en un receptor de trasplante de hígado con la COVID-19: ¿Un efecto benéfico del tacrolimus?

Coronavirus disease 2019 (COVID-19) is a serious respiratory illness caused by SARS-CoV-2. There is controversy about whether their immunosuppressive status is a risk factor or a protective factor for developing severe disease. We report herein the clinical outcome of three family members that had COVID-19 infection, presenting with and without different risk factors that have been described in more severe disease. Paradoxically, the patient with more risks of developing a severe disease, a 64-year-old woman, 2-years liver transplant recipient under treatment with tacrolimus, presented a similar outcome compared to the two other members of the family. She showed shorter hospitalization time, similar clinical outcome with fewer oxygen needs. The present clinical observation raises the question about the possible beneficial effect of tacrolimus in patients with COVID-19. Indeed, tacrolimus (FK-506) have an inhibitory effect on human coronaviruses by: 1) an antiviral effect by binding to the FK-506-binding proteins (FKBP) with a subsequent inhibition of their peptidyl-prolyl cis/trans isomerase (PPIase) activity, which seems to be important for the coronavirus life cycle; and 2) regulating the immune response by the inhibition of the activity of the nuclear factor of activated T-cells (NFAT) required for immunosuppression. The present observation states that liver recipients' patients with COVID-19 may not have worse outcomes when compared with other patients that have COVID-19 risk factors and puts in evidence the two mechanisms related to tacrolimus.

Cuidados del paciente reumático frente al coronavirus (COVID-19). Recomendaciones de la Sociedad Chilena de Reumatología / Care of the rheumatic patient against the coronavirus (COVID-19). Recommendations of the Chilean Society of Rheumatology

Resumen: En nuestra permanente preocupación por el bienestar de nuestros pacientes, especialmente en rela ción con el riesgo de Infección por COVID 19; la Sociedad Chilena de Reumatología ha elaborado una serie de recomendaciones sobre el tratamiento farmacológico de nuestros pacientes y la preven ción de infección COVID-19. Sugerimos que, ante cualquier sospecha de infección, se comuniquen con su médico para establecer los pasos a seguir, que busquen y cumplan con los consejos ofrecidos por el Ministerio de Salud, Servicios de Salud o sus respectivos Hospitales y Centros de Salud, ya que contarán con la información más actualizada y adaptada a las circunstancias locales. Y para finalizar, reiteramos las medidas preventivas que el Minsal ha difundido sobre el distanciamiento social, lavado de manos, uso de mascarilla y protección facial.

Abstract: In our permanent concern for the well-being of our patients, especially in relation to the risk of COVID 19 infection, the Chilean Society of Rheumatology has developed a series of recommenda tions on the pharmacological treatment of our patients and the prevention of COVID 19 infection. We suggest that, in case of any suspicion of infection, you contact your doctor to establish the steps to follow, and that you seek and comply with the advice offered by the Ministry of Health, Health Servi ces or their respective Hospitals and Health Centres, as they will have the most updated information adapted to local circumstances. And finally, we reiterate the preventive measures that the Ministry has disseminated regarding social distancing, hand washing, use of masks and facial protection.

Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?

BACKGROUND: Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient. CASE PRESENTATION: A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression. CONCLUSIONS: Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R.

Qualitative and quantitative tear film abnormalities in dogs: [review] / Anormalidades quali-quantitativas do filme lacrimal de cães

Tear film disorders in dogs can be classified into quantitative or qualitative abnormalities, or both, and are commonly observed in daily clinical practice. Inadequate production of one or more tear film components can lead to variable degrees of ocular disorders, called keratoconjunctivitis sicca. Keratoconjunctivitis sicca in dogs has several causes, but in most cases the disease is idiopathic, with T lymphocytes playing a role. In veterinary medicine, the diagnosis is made based on the results of the Schirmer tear test. In this article, we review aspects related to the etiopathogenesis and diagnosis of keratoconjunctivitis sicca in dogs and discuss new therapeutic modalities for this disease.(AU)

Anormalidades do filme lacrimal de cães podem ser classificadas quanto ao seu aspecto quantitativo, qualitativo ou ambos, sendo comumente observada na prática cotidiana. Intercorrências na produção de um ou mais componentes do filme lacrimal ensejam distúrbios oculares em graus variados, denominados ceratoconjuntivite seca. Diversas são as causas da ceratoconjuntivite seca em cães, mas a maioria dos casos é de caráter idiopático, estando associada à participação de linfócitos T. O diagnóstico em medicina veterinária é firmado com base nos valores obtidos pelo teste da lacrimal de Schirmer. O presente artigo objetiva revisar os aspectos relacionados à etiopatogenia e ao diagnóstico da ceratoconjuntivite seca em cães, assim como discutir novas modalidades terapêuticas para a doença.(AU)

Qualitative and quantitative tear film abnormalities in dogs: [review]

Tear film disorders in dogs can be classified into quantitative or qualitative abnormalities, or both, and are commonly observed in daily clinical practice. Inadequate production of one or more tear film components can lead to variable degrees of ocular disorders, called keratoconjunctivitis sicca. Keratoconjunctivitis sicca in dogs has several causes, but in most cases the disease is idiopathic, with T lymphocytes playing a role. In veterinary medicine, the diagnosis is made based on the results of the Schirmer tear test. In this article, we review aspects related to the etiopathogenesis and diagnosis of keratoconjunctivitis sicca in dogs and discuss new therapeutic modalities for this disease.

Anormalidades do filme lacrimal de cães podem ser classificadas quanto ao seu aspecto quantitativo, qualitativo ou ambos, sendo comumente observada na prática cotidiana. Intercorrências na produção de um ou mais componentes do filme lacrimal ensejam distúrbios oculares em graus variados, denominados ceratoconjuntivite seca. Diversas são as causas da ceratoconjuntivite seca em cães, mas a maioria dos casos é de caráter idiopático, estando associada à participação de linfócitos T. O diagnóstico em medicina veterinária é firmado com base nos valores obtidos pelo teste da lacrimal de Schirmer. O presente artigo objetiva revisar os aspectos relacionados à etiopatogenia e ao diagnóstico da ceratoconjuntivite seca em cães, assim como discutir novas modalidades terapêuticas para a doença.

Fatores de risco associados à calcinose na dermatomiosite juvenil / Risk factors associated with calcinosis of juvenile dermatomyositis

OBJETIVO: Identificar fatores de risco associados à calcinose em crianças e adolescentes com dermatomiosite juvenil. MÉTODOS: Prontuários de 54 pacientes com dermatomiosite juvenil foram estudados. Foram avaliados dados demográficos; características clínicas: grau de força muscular (I a V do Medical Research Council), presença de comprometimentos pulmonar (distúrbio ventilatório restritivo com presença ou ausência do anticorpo anti-Jo-1), gastrointestinal (refluxo gastroesofágico) e cardíaco (pericardite e/ou miocardite); exames laboratoriais: elevação de enzimas musculares (creatinoquinase, aspartato aminotransferase, alanina aminotransferase e desidrogenase lática) e terapias utilizadas: corticoterapia isolada ou associada à cloroquina e/ou imunossupressor. Os pacientes foram divididos em dois grupos de acordo com a presença ou ausência de calcinose e foram avaliados através de análise univariada e multivariada. RESULTADOS: Calcinose foi evidenciada em 23 (43 por cento) pacientes, sendo em seis (26 por cento) antes do diagnóstico e em 17 (74 por cento) após. A análise univariada revelou que comprometimentos cardíaco (p = 0,01) e pulmonar (p = 0,02) e necessidade da utilização de um ou mais imunossupressores (metotrexato, ciclosporina A e/ou pulsoterapia com ciclofosfamida endovenosa) no tratamento da dermatomiosite juvenil (p = 0,03) foram associados com uma maior incidência de calcinose. A análise multivariada mostrou que comprometimento cardíaco (OR = 15,56; IC95 por cento 1,59-152,2) e uso de um ou mais imunossupressores (OR = 4,01; IC95 por cento 1,08-14,87) foram as únicas variáveis independentes associadas à presença de calcinose. CONCLUSÕES: O aparecimento da calcinose foi freqüente na dermatomiosite juvenil, habitualmente na evolução da doença. A calcinose foi associada aos casos mais graves, que apresentaram envolvimento cardíaco e necessitaram da utilização de imunossupressores no seu tratamento.

OBJECTIVE: To identify risk factors associated with calcinosis in children and adolescents with juvenile dermatomyositis. METHODS: A review was carried out of the medical records of 54 patients with juvenile dermatomyositis. Data were collected on demographic characteristics, clinical features: muscle strength (stages I to V of the Medical Research Council scale), pulmonary involvement (restrictive pulmonary disease with presence or absence of anti-Jo1 antibodies), gastrointestinal problems (gastroesophageal reflux) and/or heart disease (pericarditis and/or myocarditis); laboratory tests: elevated muscle enzyme levels in serum (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase and/or lactate dehydrogenase); and on the treatments given: corticoid therapy in isolation or associated with hydroxychloroquine and/or immunosuppressants. The patients were divided into two groups, depending on presence or absence of calcinosis and data were evaluated by both univariate and multivariate analyses. RESULTS: Calcinosis was identified in 23 (43 percent) patients, and in six (26 percent) patients it had emerged prior to diagnosis while in 17 (74 percent) it was post diagnosis. The univariate analysis revealed that cardiac (p = 0.01) and pulmonary (p = 0.02) involvement and the need for one or more immunosuppressor (methotrexate, cyclosporine A and/or pulse therapy with intravenous cyclophosphamide) to treat juvenile dermatomyositis (p = 0.03) were all associated with an increased incidence of calcinosis. The multivariate analysis then demonstrated that only cardiac involvement (OR = 15.56; 95 percentCI 1.59-152.2) and the use of one or more immunosuppressor (OR = 4.01; 95 percentCI 1.08-14.87) were independently associated with the presence of calcinosis. CONCLUSIONS: Calcinosis was a frequent development among these juvenile dermatomyositis cases, generally emerging as the disease progressed. Calcinosis was associated with...

Resultados terapéuticos en la púrpura trombocitopénica idiopática crónica / Therapeutic results in the chronic idiopathic thrombocytopenic purpura

La púrpura trombocitopénica idiopática es una enfermedad hemorrágica autoinmune relativamente frecuente. Se realizó un estudio retrospectivo en 141 pacientes atendidos entre los años 1983 y 2003, con el objetivo de evaluar los resultados terapéuticos obtenidos en esta enfermedad. Del total evaluado, el 98,6 % necesitó tratamiento con diferentes esquemas terapéuticos y el 1,4 % restante mostró remisiones espontáneas. La modalidad de primera línea (tratamiento esteroideo) fue aplicada al 97,1 % de los pacientes al momento del diagnóstico inicial; la mayoría respondió favorablemente (65,7 %). La esplenectomía fue la segunda modalidad terapéutica, realizada al 54,6 % de los enfermos, que resultó en largos períodos de remisión (62 %, 59,7 % y 54,5 % de respuesta completa sostenida a los 3, 6 y 12 meses posesplenectomía). El tratamiento de tercera línea fue empleado en el 29,1 % de los casos refractarios a las terapias escogidas, con un índice de respuesta del 61,0 %. La prednisona sola o combinada fue el agente terapéutico más utilizado después del fracaso con los esteroides y/o esplenectomía. Los inmunosupresores y los alcaloides de la vinca fueron los más efectivos en estos casos, con 60 % y 71,4 % de respondedores. Se encontró significación estadística al evaluar la respuesta obtenida por línea de tratamiento al mes y a los 6 meses, y al comparar la respuesta inicial según la edad.

Diopathic thrombocytopenic purpura is a relatively common autoimmune hemorrhagic disease. A retrospective study was conducted among 141 patients that received attention from 1983 to 2003 aimed at evaluating the therapeutic results obtained in this disease. Of the total of evaluated patients, 98.6 % needed treatment with different therapeutic schemes and the other 1.4 % showed spontaneoous remissions. The first-line modality (treatment with steroids) was applied to 97.1 % of the patients at the moment of the initial diagnosis. Most of them had a favorable response (65.7 %). Splenectomy was the second therapeutic modality and it was performed in 54.6 % of the sick. It had long periods of remission (62 %, 59.7 % and 54.5 % of sustained complete response at 3, 6 and 12 months postsplenectomy). The third-line treatment was used in 29.1 % of the cases refractory to the therapies selected, with an index of response of 61.0 %. Prednisone alone or combined was the most used therapeutic agent after the failure with steroids and/or splenectomy. The immunosuppressors and alkaloids from Vinca were the most efficient in these cases, with 60 % and 71.4 % of responders. Statistical significance was found on evaluating the response attained by the treatment line at one month and at six months, and on comparing the initial response according to age.

Avances en inmunosupresión en trasplante hepático / Advances in immunossuppression in liver transplantation

The history of Immunosuppresslon is a long one. From the utilization of steroids and azathloptlne In the 50's to the design of humanized molecules that specifically block cell surface receptors. Liver transplantation is one of the procedures that benefit the most with the development of new immunosuppressors and is also one of the reasons to create a new branch in research and clinical practice: transplant medicine. It also set the standards for research in the "immunologic tolerance" field. The cornerstone in the post-liver transplant stage is the utilization of calcineurin inhibitors combined with new anti-metabolites and monoclonal antibodies. All these settings conforms a promising field in the research of new and better immunosuppressing agents.

Se ha recorrido mucho camino desde el diseño de la inmunosupresión en la década de los 50's. Desde la utilización de los esteroides y la azatioprina hasta el desarrollo de moléculas humanizadas, que bloquean específicamente receptores de superficie celular para inducir tolerancia del injerto, ha transcurrido medio siglo. El trasplante hepático ha sido uno de los procedimientos más beneficiados con el desarrollo de las nuevas drogas inmunosupresoras y ha dado origen a una nueva rama de la medicina: la medicina de trasplantes. También ha sentado las bases de investigación tendiente a lograr la "tolerancia inmunológica" del órgano trasplantado. La piedra angular en la inmunosupresión postrasplante hepático es la utilización de los inhibidores de calcineurina que, en combinación con nuevos antimetabolitos y anticuerpos monoclonales, dibujan un futuro promisorio en la búsqueda de mejores agentes.