Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

ABSTRACT Visceral Leishmaniasis (VL) is a potentially fatal disease and may be associated with primary or acquired immunodeficiencies. There are few reports, in the literature, of inborn errors of immunity. Here, we report two cases of VL as a marker of inborn errors of immunity, namely, GATA2 and RAB27A deficiency. Our data suggest that VL patients should be screened for primary immunodeficiency, particularly in cases of VL relapse. (VL immunodeficiencies reports literature immunity Here namely GATA RABA RAB A deficiency immunodeficiency relapse

Abstract We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient’s susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient.

OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.

Abstract Myeloperoxidase (MOP) is present in monocyte and neutrophil lysosomes, catalyzing hydrogen peroxide and chloride ion conversion to hypochlorous acid. MOP seems to destroy pathogens during phagocytosis by neutrophils and is considered an important defense against innumerous bacteria. We present a patient who had MOP deficiency, who presented with a subacute form of paracoccidioidomycosis and later with peritoneal tuberculosis. MOP deficiency leads to the diminished destruction of phagocytized pathogens. This case gives important evidence of an association between MOP deficiency and increased susceptibility to infection by Paracoccidioides brasiliensis and Mycobacterium tuberculosis.

RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do paciente, apresentações disponíveis e forma de obtenção deste recurso terapêutico em nosso meio.

ABSTRACT In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil.

Abstract: Here, we describe a case of hepatosplenic schistosomiasis that progressed to widespread persistent dermatophytosis. Significant T and B lymphocytopenia was confirmed. T-cell deficit is associated with increased susceptibility to fungal infections of skin and mucous membranes. The accumulation of a large amount of blood cells in the spleen could have played a crucial role in the development of lymphocytopenia in the present case. Alternatively, the schistosomiasis-induced increase in prostaglandin E2 levels could have inhibited the production of interferon-γ, a cytokine fundamental to fungal resistance. This case shows the potential of hepatosplenic schistosomiasis to impair the immune response.

Abstract Cryptococcosis is a fungal infection caused by Cryptococcus neoformans that tends to affect immunocompromised individuals. The fungi are mostly acquired by inhalation, which leads to an initial pulmonary infection. Later, other organs - such as the central nervous system and the skin - can be affected by hematogenous spread. In addition, cutaneous contamination can occur by primary inoculation after injuries (primary cutaneous cryptococcosis), whose diagnosis is defined based on the absence of systemic involvement. The clinical presentation of cutaneous forms typically vary according to the infection mode. We report an unusual case of disseminated cryptococcosis in an immunocompetent patient with cutaneous lesions similar to those caused by primary inoculation. This clinical picture leads us to question the definition of primary cutaneous cryptococcosis established in the literature.

OBJETIVO: Estudar e comparar o aspecto dos cabelos de portadores das síndromes de Chédiak-Higashi e Griscelli-Prunieras, tanto na microscopia óptica convencional quanto com luz polarizada. MÉTODO: Cabelos de dois doentes portadores da síndrome de Chédiak-Higashi e de dois portadores da síndrome de Griscelli-Prunieras foram obtidos e estudados tanto à microscopia convencional quanto com luz polarizada. RESULTADOS: Na microscopia óptica convencional, os cabelos dos doentes portadores da síndrome de Chédiak-Higashi mostraram grânulos de melanina regulares, com distribuição homogênea e de maior tamanho em comparação aos presentes no cabelo normal. À microscopia de luz polarizada notou-se aspecto brilhante e refringência policromática. Diferentemente, os cabelos dos doentes portadores da síndrome de Griscelli-Prunieras apresentaram à microscopia convencional, grânulos de melanina irregulares e maiores do que os presentes no cabelo normal e os presentes nos cabelos dos doentes portadores da síndrome de Chédiak-Higashi, preferencialmente próximos à medula das hastes pilosas. À microscopia de luz polarizada apresentaram aspecto monotonamente esbranquiçado. CONCLUSÃO: O exame dos cabelos pela microscopia convencional nas síndromes de Chédiak-Higashi e Griscelli-Prunieras revela diferenças sutis no reconhecimento dessas doenças. No presente trabalho apresentamos evidência de que o exame das hastes pilosas com microscopia de luz polarizada - não descrito previamente - contribui na diferenciação de ambas doenças sugerindo que esse seja um método diagnóstico útil na distinção entre as síndromes de Chédiak-Higashi e Griscelli Prunieras, especialmente nos casos em que estudos moleculares mais sofisticados não estejam disponíveis.

PURPOSE: To study and compare the appearance of hairs from patients with Chédiak-Higashi and Griscelli-Prunieras syndromes under light and polarized light microscopy. METHOD: Hairs from 2 Chédiak-Higashi and 2 Griscelli-Prunieras patients were obtained and examined under normal and polarized light microscopy. RESULTS: Under light microscopy, hairs from Chédiak-Higashi patients presented evenly distributed, regular melanin granules, larger than those seen in normal hairs. Under polarized light microscopy, shafts exhibited a bright and polychromatic refringence appearance. In contrast, hair from Griscelli-Prunieras patients, under light microscopy, exhibited bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, shafts appeared monotonously white. CONCLUSION: Light microscopic examination of hair shafts of patients with Chédiak-Higashi or Griscelli-Prunieras syndrome reveals subtle differences that are useful in identifying both disorders, but not in distinguishing between them. We provide evidence that polarized light microscopy of hair shafts, an approach that has not been previously described, aids in differentiating between these syndromes. We propose hair study by polarized light microscopy as a helpful complementary diagnostic method for differential diagnosis between CHS and GPS, especially when the more sophisticated molecular studies are not available.

OBJETIVOS: A primeira descrição clínica completa do angioedema hereditário (HAE) foi relatada por William Osler, em 1888. As formas de angioedema com deficiência de C1-INH são divididas em hereditárias e adquiridas. A terapêutica pode ser direcionada aos ataques agudos ou profilaxia de novos episódios. O tratamento de escolha é feito através de hormônios masculinizantes, podendo também ser indicado os inibidores da ativação do cininogênio e do plasminogênio como o ácido tranexâmico ou o ácido e-aminocapróico e a reposição de concentrado de C1-INH. O presente estudo relata a evolução de 10 pacientes (quatro famílias) acometidos por HAE e as peculiaridades do tratamento utilizado em cada caso. MÉTODOS: Dez pacientes (1-38 anos) com HAE foram diagnosticados através de história clínica e exames laboratoriais. Os testes realizados para avaliação do sistema complemento foram: dosagem sérica de C1-INH, C4 e C3 e ensaio hemolítico (CH50 e APH50) para as vias clássica e alternativa. O tratamento foi indicado de acordo com a gravidade dos sintomas, idade, sexo e resposta terapêutica. RESULTADOS: A avaliação clínica evidenciou 4/10 pacientes com edema subcutâneo recorrente; 3/10 pacientes com edema de laringe prévio e 3/10 pacientes com sintomas esporádicos. Sintomas de gravidade diferentes foram evidenciados na mesma família. A avaliação laboratorial (dosagem sérica) demonstrou: níveis de C1-INH diminuídos em 10/10; níveis diminuídos de C4 8/10; níveis indetectáveis de CH50 em 3/10 e diminuídos em 6/10; níveis diminuídos de APH50 em 2/10. 6/10 pacientes não receberam tratamento específico, sendo que dois deles apresentam alto risco para asfixia; uma adolescente tem sido controlada com ácido e-aminocapróico, uma criança que fazia uso de danazol passou a receber ácido tranexâmico, uma paciente de 30 anos recebe oxandrolona e um homem de 38 anos está em tratamento com danazol. CONCLUSÃO: Apesar do HAE ser causado pelo mesmo defeito e acometer membros da mesma família, diferentes critérios têm sido estabelecidos para o tratamento desses pacientes. Foram indicados diferentes esquemas terapêuticos para HAE e alguns dos pacientes puderam ser seguidos sem terapia medicamentosa.

PURPOSE: Hereditary Angioedema was first described by William Osler in 1888 and it is caused by a hereditary or acquired deficiency of C1 esterase inhibitor (C1-INH). Treatment is indicated for acute attacks or prophylaxis of angioedema which occur in the subcutaneous tissue respiratory or gastrointestinal tracts. Treatment includes attenuated androgens, inhibitors of kininogen or plasminogen, like tranexamic acid or e-aminocaproic acid and the administration of C1-INH concentrate. We describe the peculiarities of the treatment chosen for 10 patients (4 families) with HAE and their evolution. METHODS: Ten patients (1-38 years old) with HAE were diagnosed by clinical history and laboratory evaluation. The following tests were performed for the complement system: C1-INH, C4 and C3 levels and hemolytic assay (CH50 and APH50) for the classic and alternative pathways. Treatment was initiated considering severity of symptoms, age, gender and therapeutic response of the patient. RESULTS: Clinical evaluation showed: 4/10 patients with recurrent subcutaneous edema; 3/10 with previous laryngeal edema and 3/10 with sporadic symptoms. Different severity of symptoms was verified in the same family. The laboratory evaluation detected: low C1-INH levels (10/10); low serum C4 level (8/10); undetectable CH50 (3/10) and low CH50 levels (6/10); low APH50 levels (2/10). Six out of ten patients did not receive any specific treatment and 2 of them had high risk of asphyxia. One adolescent had been controlled with e-aminocaproic acid, one child had been changed from danazol to tranexamic acid, a 30 year old female patient had received oxandrolone and a 38 year old man had been treated with danazol. CONCLUSIONS: Although HAE is caused by the same defect and affects members of the same family, various approaches have been taken to treat these patients. We observed different alternatives of prophylactic therapy for HAE, of which some did not require drug therapy.