Impact of Treatment with Ustekinumab on Severe Infections in a Patient with Uncontrolled Psoriasis and Late-Onset Combined Primary Immunodeficiency: Case Report.

A 35-year-old man with a late-onset combined immunodeficiency (LOCID) variant of common variable immunodeficiency, severe plaque psoriasis, psoriatic arthritis, and Crohn's disease was attended in the Regional Hospital of Presidente Prudente and HC-FMUSP, São Paulo, Brazil. Anti-IL-12/IL-23 (ustekinumab) monoclonal antibody was prescribed due to the failure of other treatments (phototherapy, oral acitretin) for psoriasis and a Psoriasis Area Severity Index >10. We evaluated the impact of treatment with ustekinumab on severe infectious diseases in a patient with uncontrolled psoriasis and LOCID followed for 8 years. Four quarterly doses of ustekinumab 90 mg and human immunoglobulin replacement (10,000 mg at 28-day intervals) were administered. Immunophenotyping, cultures of lymphocytes, genetic sequencing, and whole exome sequencing were performed to investigate the primary immunodeficiency. Normal lymphocyte proliferation; pathogenic variants in genetic sequencing, and clinically significant variants in the whole exome for primary immunodeficiencies were not detected. The main infections before and after treatment with ustekinumab were chronic sinusitis and gastroenteritis. The patient was infected with COVID-19, dengue (twice) and influenza and was hospitalized three times for intravenous antibiotic therapy. Ustekinumab did not influence the susceptibility of the patient with LOCID to severe infections and significantly improved psoriasis, psoriatic arthritis, and Crohn's disease.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2).

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).

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

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).

A rare association between factor H deficiency and lupus: Case report and experimental treatment with curcumin.

Factor H (FH) is one of the most important regulatory proteins of the alternative pathway of the complement system. FH deficiency is a rare condition that causes unregulated C3 consumption, leading to an increased susceptibility to infections and glomerulopathies. Our previous studies have demonstrated a FH deficient patient carrying a c.452G > A, p.R127H FH mutation which leads to a misfolded protein and its retention in the endoplasmic reticulum. In his cultured fibroblasts, FH-delayed secretion was partially rescued when treated with curcumin, and once secreted, exhibited normal regulatory function. Here, we report a childhood-onset systemic lupus erythematosus (cSLE) in this FH deficient patient and the results of experimental treatment with curcumin aiming to rescue FH secretion and regulatory activity.

Evaluation of IFN-γ secretion after stimulation with C. neoformans and C. gattii antigens in individuals with frequent exposure to the fungus.

In this study we produced antigenic extracts from prototypical strains of C. neoformans (VNI-VNIV) and C. gattii (VGI-VGIV) and tested IFN-γ secretion by Elispot. Antigens from the eight Cryptococcus molecular types (VNI -VNIV and VGI - VGIV) were obtained after capsule reduction. IFN-γ secretion by Elispot method were stimulated with C. neoformans and C. gattii antigens. Peripheral blood mononuclear cells of fourteen healthy control subjects, being: five ecotourists, two mycologists, three poultry keepers, and four individuals without reports of exposure to the fungus. We observed a significant increase in IFN-γ secretion in the group of ecotourists, mycologists and bird keepers in relation to the group of individuals without reports of occupational exposures to these agents. Our results suggest the significant increase in IFN-γ secretion may be related to the continuous exposure of these groups of individuals to the fungus, as well as to the specific antigen memory immune response developed during exposure to Cryptococcus.

Disseminated cryptococcosis manifested as a single tumor in an immunocompetent patient, similar to the cutaneous primary forms

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.

Disseminated cryptococcosis manifested as a single tumor in an immunocompetent patient, similar to the cutaneous primary forms.

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.

Leprosy and multiple endocrine neoplasia type i: a case report and review of literature

Context: Leprosy is an infectious disease in which progress to disease and clinical expressions are influenced by environmental factors and by the genetics of the host. The multiple endocrine neoplasia type 1 syndrome (MEN-1) is an inherited disorder that predisposes to endocrine and non-endocrine tumors...

Leprosy and multiple endocrine neoplasia type I: a case report and review of literature / Hanseníase e neoplasia endócrina múltipla tipo 1: relato de caso e revisão de literatura

Context: Leprosy is an infectious disease in which progress to disease and clinical expressions are influenced by environmental factors and by the genetics of the host. The multiple endocrine neoplasia type 1 syndrome (MEN-1) is an inherited disorder that predisposes to endocrine and non-endocrine tumors. Case report: A case of multi-bacillary leprosy in the 18-year-old female patient with MEN- 1, this association was probably an incidental case of an endemic disease in a susceptible individual with a rare syndrome. The investigation of comorbities, especially neglected or emergency disease, is very importance, because the lack of early diagnosis may result in serious complications as development of disabilities especially when there is a leprosy late diagnosis.

Contexto: A hanseníase é uma doença infecciosa cuja evolução e expressões clínicas são influenciadas por fatores ambientais e pela genética do hospedeiro. A síndrome neoplasia endócrina múltipla tipo 1 (NEM-1)é uma desordem hereditária que predispõe a tumores endócrinos e não-endócrinos . Relato de caso: Relata-se um caso de hanseníase multibacilar em paciente de 18 anos de idade com NEM- 1. Esta associação foi, provavelmente, um caso incidental de uma doença endêmica em um indivíduo suscetível com uma síndrome rara. A pesquisa de comorbidades, especialmente entre as doenças negligenciadas ou emergentes é muito importante, porque a falta de diagnóstico precoce pode resultar em complicações graves como o desenvolvimento de deficiências especialmente quando há um diagnóstico de hanseníase tardio.

Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes.

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.

Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes

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.