Nefrite tubulointersticial e uveíte com granulomas não caseosos na biópsia óssea

Copyright © Ordem dos Médicos 2014The Tubulointerstitial Nephritis and Uveitis syndrome is a very rare condition, probably under-diagnosed in clinical practice. It is characterized by the combination of an interstitial nephritis and uveitis, and is an exclusion diagnosis. Tissue non caseating granuloma can be rarely present, with only 6 cases reported on bone marrow. We present a case of a 55 year old female with a 3-month history of asthenia and weight loss. Blood tests showed anemia and renal insufficiency. Renal biopsy revealed interstitial nephritis and the bone marrow biopsy showed caseating granuloma. One month later anterior uveitis of the left eye appeared. An extensive exclusion of all possible causes allowed a diagnosis of Tubulointerstitial Nephritis and Uveitis syndrome with caseating granuloma in bone marrow. As ocular and renal manifestations may not occur simultaneously, Tubulointerstitial Nephritis and Uveitis Syndrome should be systematically considered in cases of interstitial nephritis and/or uveitis, and tissue granulomas can be part of this rare syndrome.info:eu-repo/semantics/publishedVersio

Hypercalcemia and Extensive Chest Metastasis of Vulvar Squamous Cell Carcinoma

A 73-year-old woman with a diagnosis of vulvar carcinoma submitted to curative surgery 5 years previously, presented to the emergency department with prostration and vulvar haemorrhage. Although the gynaecological examination was unremarkable, she had a mass in the left chest wall and hypercalcemia. A CT scan of the thorax revealed a voluminous left hemithorax mass invading the mediastinum, lung, pleura and chest wall. Ultrasound-guided biopsy of the mass showed infiltration by a well-differentiated keratinizing squamous cell carcinoma (SCC). This case report describes an extremely rare metastatic pattern in vulvar SCC concomitant with paraneoplastic hypercalcemia

Methimazole associated eosinophilic pleural effusion: a case report

© The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Adverse reactions associated to anti-thyroid drugs include fever, rash, arthralgia, agranulocytosis and hepatitis that are thought to be hypersensitivity reactions. Five cases of pleural effusion associated to thionamides have also been reported, two with propylthiouracil and three with carbimazole. Case presentation: We report here a case of a 75-year-old man admitted because of unilateral pleural effusion. The patient had a recent diagnosis of hyperthyroidism and 6 days after starting methimazole complained of pleuritic chest pain. He had elevated C-reactive protein and erythrocyte sedimentation rate and normal white blood cell count and liver enzymes. Chest radiography showed a moderate right pleural effusion and the ultrasound revealed a loculated effusion that was shown to be an eosinophilic exudate. Conclusions: The temporal relationship between methimazole intake and the development of pleural effusion combined with the extensive exclusion of alternative causes, namely infectious, neoplastic and primary auto-immune diseases, led to the diagnosis of hypersensitivity reaction to methimazole. The thionamide was stopped and corticosteroid was started with complete resolution of the pleural effusion in 3 months. Awareness of this rare adverse reaction of anti-thyroid drugs is important and methimazole can be added to the list of possible etiologies of drug-induced eosinophilic pleural effusion.info:eu-repo/semantics/publishedVersio

Major CD4 T-Cell Depletion and Immune Senescence in a Patient with Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) results from primary defects in phagocytic reactive oxygen species (ROS) production. T-cell evaluation is usually neglected during patients’ follow-up, although T-cell depletion has been reported in CGD through unknown mechanisms. We describe here a 36-year-old patient with X-linked CGD with severe CD4 T-cell depletion <200 CD4 T-cells/μl, providing insights into the mechanisms that underlie T-cell loss in the context of oxidative burst defects. In addition to the typical infections, the patient featured a progressive T-cell loss associated with persistent lymphocyte activation, expansion of interleukin (IL)-17-producing CD4 T-cells, and impaired thymic activity, leading to a reduced replenishment of the T-cell pool. A relative CD4 depletion was also found at the gut mucosal level, although no bias to IL-17-production was documented. This immunological pattern of exhaustion of immune resources favors prompt, potentially curative, therapeutic interventions in CGD patients, namely, stem-cell transplantation or gene therapy. Moreover, this clinical case raises new research questions on the interplay of ROS production and T-cell homeostasis and immune senescence

Human FOXN1-Deficiency Is Associated with αβ Double-Negative and FoxP3+ T-Cell Expansions That Are Distinctly Modulated upon Thymic Transplantation

Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the αβDN subset persisted 5 years post-transplantation. Involution of thymus allograft likely occurred 3 years post-transplantation based on sj/βTREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings

Analysis of the Seroprevalence of HIV and HIV 2 infection in women living in an area of the city of Lisbon

Os autores apresentam os resultados de um estudo de seroprevalência da infecção pelo HIV1 (Vírus da Imunodeficiência Humana Tipo 1) e pelo HIV2 (tipo II) em mulheres em idade fértil frequentando uma consulta de Planeamento Familiar e uma consulta de Cuidados Pré-Natais que serve uma população urbana de duas freguesias da cidade de Lisboa em que cerca de 7% é de origem Africana. Foi adoptado um protocolo de trabalho com características de estudo anónimo mas em que se previa a possibilidade da colheita de segunda amostra para confirmação de resultados (modelo non linked). Foram registados através de inquérito os elementos de ordem social e epidemiológica sendo realizado exame clínico a todas as participantes no estudo (1390). Esta fase foi seguida de colheita de amostras de sangue para estudos seroepidemiológicos relacionados com várias infecções virais incluindo o HIV e o HIV2. Foi comparada a população que compareceu (75%) com a que não compareceu á realização de análises verificando-se não haver em geral diferenças significativas entre os dois grupos no que refere a um conjunto de características epidemiológicas, sociais e clínicas. Foram considerados seropositivos para o HIV, os casos com anticorpos anti-HIV detectados por ELISA e confirmados por Western Blot revelando anticorpos contra as três proteínas (env, core e gag) e com resultados igualmente positivos pelos dois métodos em segunda amostra de sangue recolhida subsequentemente. As prevalências de infecção foram quer para o HIV quer para o 111V2 de 0.29% (total 0.58%) na população estudada, sendo a prevalência de HIV 2 de 1 .45% na população de origem Africana. Os seis casos seropositivos detectados incluíam um caso de toxicodependência, um caso de prostituição, um caso de origem Africana, não havendo nos três restantes factores de risco para além da existência de parceiros sexuais múltiplos em duas mulheres. As características clínicas, epidemiológicas e imunológicas dos casos seropositivos são descritas e discute-se a importância da prevalência encontrada. Finalmente salienta-se a relevância da análise e discussão detalhadas, antes do início de qualquer programa de rastreio da infecção pelo HIV, das vantagens, inconvenientes e limitações dos protocolos a usar no contexto da situação concreta do Centro e Comunidade em questão.A seroprevalence study of HIV 1 and HIV 2 infection in women attending a Family Planning and an Antenatal Clinic was done in an area of the City of Lisbon where 7% of the population is of African origin. The protocol of study was of non linked type although with the possibility of colecting a second sample of blood for confirmation of results. Epidemiological, social and clinical data were collected from 1390 women and this was followed by the collection of a blood sample for the seroepidemiological study of HIV 1 and HIV 2 in the population that was submited to blood tests (75%) was compared to the one that missed the test and it was found that no important differences were present between the two. The criteria for HIV1 or HIV 2 positive results were the presence of a positive ELISA test confirmed by an Western Blot revealing antibodies against the three proteins env, core and gag. For a test to be considered positive results by both methods had to be found in a second sample collected later. The prevalences of infection were of 0.29% for HIV 1 and 0.29% for HIV 2 although the prevalence of HIV 2 in the population of African origin was higher (1.45%). The six seropositive cases detected included a drug addict, one prostitute, one case of African origin and two cases with multiple sexual partners. The clinical, epidemiological and immunological features of the seropositive cases are presented and the prevalence found is discussed in the context of other portuguese data. The importance of discussing in detail the advantages and disadvantages of the different protocols of seroprevalence studies in the context of a given Center and Community before starting the screening programmes is stressed.info:eu-repo/semantics/publishedVersio

Insuficiência hepática aguda como apresentação de linfoma não-Hodgkin

Acute hepatic failure (AHF) consists of a sudden appearance of coagulopathy and hepatic encephalopathy in a patient with no previous hepatic disease.  Although the liver is the most affected organ in cancer dissemination, AHF is rare and appears essentially in cancer terminal stages. Even rarer is AHF as an initial finding of cancer. We present a case of a 39 year-old HIV positive patient in whom AHF was the initial manifestation of a non-Hodgkin lymphoma.A Insuficiência Hepática Aguda (IHA) consiste no aparecimento súbito de coagulopatia e encefalopatia hepática em doente sem doença hepática prévia. Embora o fígado seja afectado por metastização, a IHA costuma ser incomum e surgir apenas nos estadios terminais da doença. Apesar de a IHA ser uma forma rara de apresentação de neoplasias, tem sido observada em neoplasias hematológicas, nomeadamente na doença de Hodgkin e linfoma não-Hodgkin difuso de grandes células, B especialmente em doentes imunossuprimidos. É relatado um caso de um doente de 39 anos, vírus da imunodeficiência humana (VIH) 1 postivo, cuja manifestação inaugural de um linfoma não-Hodgkin foi IHA

Human naïve regulatory T-cells feature high steady-state turnover and are maintained by IL-7

Naïve FoxP3-expressing regulatory T-cells (Tregs) are essential to control immune responses via continuous replenishment of the activated-Treg pool with thymus-committed suppressor cells. The mechanisms underlying naïve-Treg maintenance throughout life in face of the age-associated thymic involution remain unclear. We found that in adults thymectomized early in infancy the naïve-Treg pool is remarkably well preserved, in contrast to conventional naïve CD4 T-cells. Naïve-Tregs featured high levels of cycling and pro-survival markers, even in healthy individuals, and contrasted with other circulating naïve/memory CD4 T-cell subsets in terms of their strong γc-cytokine-dependent signaling, particularly in response to IL-7. Accordingly, ex-vivo stimulation of naïve-Tregs with IL-7 induced robust cytokine-dependent signaling, Bcl-2 expression, and phosphatidylinositol 3-kinase (PI3K)-dependent proliferation, whilst preserving naïve phenotype and suppressive capacity. Altogether, our data strongly implicate IL-7 in the thymus-independent long-term survival of functional naïve-Tregs, and highlight the potential of targeting the IL-7 pathway to modulate Tregs in different clinical settings.This work was supported by Fundação para a Ciência e Tecnologia (FCT; POCI2010/IC/83068/2007 to RMMV; PTDC/SAU-MIC/109786/2009 to AES), and Gulbenkian Foundation (96526/2009 to JF; P132532/2013 to AES). SLS, ASA, RBF, ARP, PM and SMF received FCT scholarships

Monozygotic twins concordant for common variable immunodeficiency : strikingly similar clinical and immune profile associated with a polygenic burden

Copyright © 2019 Silva, Fonseca, Pereira, Silva, Barbosa, Serra-Caetano, Blanco, Rosmaninho, Pérez-Andrés, Sousa, Raposo, Gama-Carvalho, Victorino, Hammarstrom and Sousa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Monozygotic twins provide a unique opportunity to better understand complex genetic diseases and the relative contribution of heritable factors in shaping the immune system throughout life. Common Variable Immunodeficiency Disorders (CVID) are primary antibody defects displaying wide phenotypic and genetic heterogeneity, with monogenic transmission accounting for only a minority of the cases. Here, we report a pair of monozygotic twins concordant for CVID without a family history of primary immunodeficiency. They featured a remarkably similar profile of clinical manifestations and immunological alterations at diagnosis (established at age 37) and along the subsequent 15 years of follow-up. Interestingly, whole-exome sequencing failed to identify a monogenic cause for CVID, but unraveled a combination of heterozygous variants, with a predicted deleterious impact. These variants were found in genes involved in relevant immunological pathways, such as JUN, PTPRC, TLR1, ICAM1, and JAK3. The potential for combinatorial effects translating into the observed disease phenotype is inferred from their roles in immune pathways, namely in T and B cell activation. The combination of these genetic variants is also likely to impose a significant constraint on environmental influences, resulting in a similar immunological phenotype in both twins, despite exposure to different living conditions. Overall, these cases stress the importance of integrating NGS data with clinical and immunological phenotypes at the single-cell level, as provided by multi-dimensional flow-cytometry, in order to understand the complex genetic landscape underlying the vast majority of patients with CVID, as well as those with other immunodeficiencies.This work received funding from PAC - PRECISE - LISBOA-01-0145-FEDER-016394, co-funded by FEDER through POR Lisboa 2020 - Programa Operacional Regional de Lisboa PORTUGAL 2020 and Fundação para a Ciência e a Tecnologia; and UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado. Work in MG-C lab is supported by UID/MULTI/04046/2019 Research Unit grant from FCT, Portugal (to BioISI) and FCT research grant PTDC/BIA-CEL/29257/2017.info:eu-repo/semantics/publishedVersio

Major CD4 T-cell depletion and immune senescence in a patient with chronic granulomatous disease

Copyright © 2017 Albuquerque, Fernandes, Tendeiro, Cheynier, Lucas, Silva, Victorino and Sousa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Chronic granulomatous disease (CGD) results from primary defects in phagocytic reactive oxygen species (ROS) production. T-cell evaluation is usually neglected during patients' follow-up, although T-cell depletion has been reported in CGD through unknown mechanisms. We describe here a 36-year-old patient with X-linked CGD with severe CD4 T-cell depletion <200 CD4 T-cells/μl, providing insights into the mechanisms that underlie T-cell loss in the context of oxidative burst defects. In addition to the typical infections, the patient featured a progressive T-cell loss associated with persistent lymphocyte activation, expansion of interleukin (IL)-17-producing CD4 T-cells, and impaired thymic activity, leading to a reduced replenishment of the T-cell pool. A relative CD4 depletion was also found at the gut mucosal level, although no bias to IL-17-production was documented. This immunological pattern of exhaustion of immune resources favors prompt, potentially curative, therapeutic interventions in CGD patients, namely, stem-cell transplantation or gene therapy. Moreover, this clinical case raises new research questions on the interplay of ROS production and T-cell homeostasis and immune senescence.AA, SF, RT, and SS received scholarships from Fundação para a Ciência e Tecnologia (FCT), Portugal.info:eu-repo/semantics/publishedVersio