The Burden of Hereditary Angioedema in a Large Family in Brazil.

INTRODUCTION: Hereditary angioedema (HAE) is a rare genetic disease characterized by submucosal and subcutaneous edema with high morbidity and possibility of mortality. This study presents the sociodemographic characteristics of a large Brazilian family with HAE. METHODS: Descriptive cross-sectional study with patients from two family branches coming from the same city and HAE diagnosis was carried out. Clinical, laboratory, and treatment data of patients have been collected. Genetic testing was performed on some individuals. Correlation tests and comparisons between variables were applied using IBM SPSS Statistics® 2.0 program. RESULTS: We provide a detailed characterization of two families affected by HAE due to C1-INH deficiency, residing in a small town in southern Brazil. These families harbor an identified mutation in the SERPING1 gene (c.1104del, p.Asp369ThrfsTer2). The mean age at HAE diagnosis was 16.7 (±14.0) years, with the mean onset of symptoms at 6.0 (±6.1) years of age. A correlation was observed between patients' current age and age at HAE diagnosis, with older patients being diagnosed later than younger individuals (p < 0.0001). On average, there were 16.8 emergency visits in the past year (±24.8), and 53.5% of patients reported at least one lifetime hospitalization. Notably, treatment modalities often diverged from consensus recommendations regarding optimal prophylaxis and management of HAE attacks. CONCLUSIONS: This study describes one of the largest known families with HAE in Brazil and highlights the significant impact of unfavorable social conditions on disease control.

Impact of asthma control on quality of life in an outpatient setting in Brazil.

INTRODUCTION: The goal of asthma therapy is asthma control. As a chronic disease, asthma may cause considerable physical, emotional and social restrictions impacting quality of life. The aim of this study was to analyze control of asthma symptoms in an outpatient setting in Brazil and its impact on quality of life. METHODS: A pilot cross-sectional study was performed in two public centers in the metropolitan region of São Paulo, Brazil. Control of asthma symptoms was assessed according to GINA guidelines, and quality of life was analyzed by the Mini Quality of Life Questionnaire (mini-AQLQ). RESULTS: A total of 47 adult patients with asthma were analyzed. Asthma was controlled in 8 patients (17.0%), partially controlled in 26 patients (55.3%) and uncontrolled in 13 patients (27.7%). Patients with controlled asthma showed better mini-AQLQ scores (4.99 ± 1.10) as compared to those with partly controlled (3.66 ± 1.10) and uncontrolled asthma (2.59 ± 0.64; p < 0.001 for both). Most patients (85.1%) were taking inhaled corticosteroids (ICS) and long-acting bronchodilators (LABA) as controller treatment. CONCLUSIONS: Better asthma control had a positive impact on Health-Related Quality of Life (HRQoL) contributing to a better disease management. Few patients reached full asthma control in our specialty ambulatory center, suggesting further initiatives are required to improve the quality of asthma care in Brazil.

In-vitro NLRP3 functional test assists the diagnosis of cryopyrin-associated periodic syndrome (CAPS) patients: A Brazilian cooperation.

OBJECTIVE: To report our five-years experience on the use of NLRP3 inflammasome functional assays in the differential diagnosis of Brazilian patients with a clinical suspicion of CAPS. PATIENTS AND METHODS: The study included 9 patients belonging to 2 families (I, II) and 7 unrelated patients with a clinical suspicion of AID according to Eurofever/PRINTO classification, recruited between 2017 and 2022. The control group for the NLRP3 functional assay consisted of 10 healthy donors and for the CBA cytokines measurement of 19 healthy controls. Patients underwent clinical evaluation, genetic and functional analysis. RESULTS: All members of the family I received the diagnosis of Muckle-Wells Syndrome (MWS), carried the NLRP3 Thr348Met variant and resulted positive for the functional assay. The 2 patients of the family II resulted negative for the mutational screening but positive for the functional assay compatible with a MWS clinical phenotype. In 2 unrelated patients with NLRP3 mutations, including a novel mutation (Gly309Val, Asp303His), a positive functional test confirmed the clinical diagnosis of NOMID. 3 unrelated MWS and 1 FCAS patients resulted negative to the genetic screening and positive for the functional test. One patient with a FCAS-like phenotype harbored the NLRP12 His304Tyr variant confirming the diagnosis of FCAS2. CONCLUSION: The NLRP3 inflammasome functional assay can assist the clinical diagnosis of CAPS even in patients with unknown genetic defects.

SCID and Other Inborn Errors of Immunity with Low TRECs - the Brazilian Experience.

Severe combined immunodeficiency, SCID, is a pediatric emergency that represents the most critical group of inborn errors of immunity (IEI). Affected infants present with early onset life-threatening infections due to absent or non-functional T cells. Without early diagnosis and curative treatment, most die in early infancy. As most affected infants appear healthy at birth, newborn screening (NBS) is essential to identify and treat patients before the onset of symptoms. Here, we report 47 Brazilian patients investigated between 2009 and 2020 for SCID due to either a positive family history and/or clinical impression and low TRECs. Based on clinical presentation, laboratory finding, and genetic information, 24 patients were diagnosed as typical SCID, 14 as leaky SCID, and 6 as Omenn syndrome; 2 patients had non-SCID IEI, and 1 remained undefined. Disease onset median age was 2 months, but at the time of diagnosis and treatment, median ages were 6.5 and 11.5 months, respectively, revealing considerable delay which affected negatively treatment success. While overall survival was 51.1%, only 66.7% (30/45) lived long enough to undergo hematopoietic stem-cell transplantation, which was successful in 70% of cases. Forty-three of 47 (91.5%) patients underwent genetic testing, with a 65.1% success rate. Even though our patients did not come from the NBS programs, the diagnosis of SCID improved in Brazil during the pilot programs, likely due to improved medical education. However, we estimate that at least 80% of SCID cases are still missed. NBS-SCID started to be universally implemented in the city of São Paulo in May 2021, and it is our hope that other cities will follow, leading to early diagnosis and higher survival of SCID patients in Brazil.

Acquired Angioedema due to C1-Inhibitor Deficiency: A Challenging Condition.

BACKGROUND: Acquired deficiency of C1 inhibitor (AAE-C1-INH) is a very rare cause of recurrent angioedema, with few cases reported in the literature. We aimed to describe a series of patients with AAE-C1-INH who were diagnosed and received care at angioedema reference centers in Brazil, affiliated to the Brazilian Group of Studies on Hereditary Angioedema. METHODS: Fourteen patients from 8 Brazilian Angioedema Reference Centers, diagnosed with AAE-C1-INH, were included in this study. Clinical data collected included sex, date of birth, date of onset of symptoms, date of diagnosis, plasma levels of antigenic and/or functional C1-INH, levels of C4 and C1q, location and treatment of angioedema attacks, long-term prophylaxis, associated diseases, and definitive treatment. RESULTS: Fourteen patients were identified with AAE-C1-INH. Most patients (10/14; 71.4%) were female. The median age at onset of symptoms was 56.5 years (range, 14-74 years; interquartile range [IQR], 32-64 years), and median age at diagnosis was 58.0 years (range, 20-76 years; IQR, 38-65 years), with a median time until diagnosis of 2 years (range, 0-6 years; IQR, 1-3 years). The most common manifestations were cutaneous (face, eyelids, lips, trunk, hands, feet, and genitals). Most patient had low levels of C4 (13/14; 92.8%) and of antigenic C1-INH (8/14; 57.1%). Four had decreased functional activity of C1-INH (4/7; 57.1%) and C1q levels were low in 5 patients (5/12; 41.6%). Underlying diseases were identified in all 14 patients, with lymphoma of the splenic marginal zone and monoclonal gammopathy of undetermined significance being the most frequent. Nine patients (64.2%) needed long-term prophylactic treatment for recurrent angioedema and 5 patients (46.7%) required treatment for angioedema attacks. Most of them (12/14; 85.7%) had resolution of angioedema. CONCLUSION: Therapy of AAE-C1-INH aims to control symptoms; however, diagnosis and treatment of the underlying disease, when present, should be an important target and may lead to the resolution of angioedema in patients with AAE-C1-INH.

Immunity and inflammatory biomarkers in COVID-19: A systematic review.

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Patients can be asymptomatic or present respiratory and gastrointestinal symptoms, and even multiple-organ failure which can lead to death. The balance between an effective antiviral response and dysregulated immune response is the key factor determining the severity of COVID-19 progression. A systematic review was performed using the NCBI-PubMed database to find the articles related to COVID-19 immunity and inflammatory response published from 1 December 2019 to 15 April 2020. Haematological, immunological and biochemical parameters were extracted and correlated with disease severity, age and presence of comorbidities. Twelve articles were analysed comprising a total of 1042 hospitalized patients infected with SARS-CoV-2 and 95 different parameters. Total lymphocyte count and levels of CD3+ and CD4+ T cells were decreased in severe and critical cases. Neutrophilia was found in patients who progressed to acute respiratory distress syndrome (ARDS). Interleukin-six (IL-6) was high in mild and severe patients regardless of comorbidities. Erythrocyte sedimentation rate (ESR) and count and C-reactive protein (CRP) levels were increased regardless of disease severity or presence of comorbidities. High levels of D-dimer and lactate dehydrogenase were present in diabetic patients and patients who developed ARDS. Procalcitonin levels were elevated to varying degrees in severe and critical patients. We conclude that the total lymphocyte count, CD3+ and CD4+ T cells are low, especially in severe and critical COVID-19 patients; ESR, CRP and IL-6 were elevated, independent of the severity of disease. Understanding the inflammatory response of COVID-19 patients is essential for the development of better therapeutic and management strategies.

Hereditary angioedema in children and adolescents.

Hereditary angioedema is a genetic disease with autosomal dominant inheritance and, in most cases, caused by C1 inhibitor deficiency. Patients present with recurrent edema affecting sub-cutaneous and mucus membranes with variable onset and severity. More than 50% of patients may become symptomatic before 10 years of age. Family history can help with the diagnosis; however, approximately 25% of the cases are de novo mutations. Biochemical diagnosis should be delayed until after 1 year of age. Children were often excluded from advances in therapy for hereditary angioedema since most of the new medicines were tested in adults and thus excluded by the Food and Drug Administration (FDA) and other agencies for approval to be used in children. Treatment of attacks is available for the pediatric patient; however, barriers still exist for the use of long-term prophylaxis in young children. © 2022 Codon Publications. Published by Codon Publications.

Outcome of SARS-CoV-2 Infection in 121 Patients with Inborn Errors of Immunity: A Cross-Sectional Study.

PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection. METHODS: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. RESULTS: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. CONCLUSION: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

The Challenges in the Follow-Up and Treatment of Brazilian Children with Hereditary Angioedema.

INTRODUCTION: Hereditary angioedema (HAE) with C1 inhibitor (C1-INH) deficiency is a rare autosomal dominant disease. Although the first symptoms can appear in childhood, the diagnosis's delay has a strong impact on the patient's quality of life. We analyzed clinical and laboratory characteristics and the drug therapy of pediatric patients with HAE in Brazil. METHODS: Medical records from 18 reference centers of HAE patients under 18 years of age were evaluated after confirmed diagnosis was performed by quantitative and/or functional C1-INH. RESULTS: A total of 95 participants (51 M:44 F; mean age: 7 years old) out of 17 centers were included; 15 asymptomatic cases were identified through family history and genetic screening. Angioedema attacks affected the extremities (73.5%), gastrointestinal tract (57%), face (50%), lips (42.5%), eyelids (23.7%), genitals (23.7%), upper airways (10%), and tongue (6.3%). Family history was present in 84% of patients, and the mean delay in the diagnosis was 3.9 years. Long-term prophylaxis (51/80) was performed with tranexamic acid (39/80) and androgens (13/80); and short-term prophylaxis (9/80) was performed with tranexamic acid (6/80) and danazol (3/80). On-demand therapy (35/80) was prescribed: icatibant in 7/35, fresh frozen plasma in 16/35, C1-INH plasma-derived in 11/35, and tranexamic acid in 12/35 patients. CONCLUSIONS: This is the first study on HAE pediatric patients in Latin America. Clinical manifestations were similar to adults. Drugs such as androgens and tranexamic acid were indicated off-label, probably due to restricted access to specific drugs. Educational programs should address pediatricians to reduce late diagnosis and tailored child therapy.

Neutrophilic dermatosis: a new skin manifestation and novel pathogenic variant in a rare autoinflammatory disease.

Sideroblastic anaemia, B-cell immunodeficiency, periodic fever and developmental delay (SIFD) is caused by mutations of TRNT1, an enzyme essential for mitochondrial protein synthesis, and has been reported in 23 cases. A 6-month-old girl was evaluated with recurrent fever, failure to thrive, skin lesions and anaemia. She received blood transfusions and empirical antibiotics. Skin lesions, previously interpreted as insect bites, consisted of numerous firm asymptomatic erythematous papules and nodules, distributed over trunk and limbs. Skin histopathology revealed an intense dermal neutrophilic infiltrate extending to the subcutaneous, with numerous atypical myeloid cells, requiring the diagnosis of leukaemia cutis, to be ruled out. Over the follow-up, she developed herpetic stomatitis, tonsillitis, lobar pneumonia and Metapneumovirus tracheitis, and also deeper skin lesions, resembling panniculitis. Hypogammaglobulinaemia was diagnosed. An autoinflammatory disease was confirmed by whole exome sequencing: heterozygous mutations for TRNT1 NM_182916 c.495_498del, p.F167Tfs * 9 and TRNT1 NM_182916 c.1246A>G, p.K416E. The patient has been treated with subcutaneous immunoglobulin and etanercept. She presented with developmental delay and short stature for age. The fever, anaemia, skin neutrophilic infiltration and the inflammatory parameters improved. We describe a novel mutation in SIFD and the first to present skin manifestations, namely neutrophilic dermal and hypodermal infiltration.

Assessment on hereditary angioedema burden of illness in Brazil: A patient perspective.

Background: Hereditary angioedema (HAE) is an autosomal dominant disorder that affects ∼1 in 50,000 individuals. The disorder is characterized by spontaneous and gradual episodes of edema in subcutaneous tissues or mucosal membrane that may endanger the patient's life. Previous studies that concern HAE treatment and burden of illness in the United States and Europe suggest an improvement in the control of HAE. However, no similar data are available in South American patients. The purpose of the present study was to evaluate the burden of disease and compliance to therapy of patients with HAE in Brazil. Methods: We developed a structured questionnaire to assess the variables that influence the diagnosis and treatment of Brazilian patients with HAE. The questionnaire was evaluated by allergists with expertise in HAE and was reformatted before applying it. The consent form was included before survey access; approval from the ethic committee of Faculdade de Medicina do ABC (Santo André, São Paulo, Brazil) was ensured. The Brazilian association of patients with HAE distributed the survey by e-mail to associated patients all over the country, and responses were accepted within a period of 3 months after signing a consent form. Results: Ninety patients (67 women, 23 men; average age, 36.5 years) responded; the main findings were the following: 53 of 90 (64%) had no need of visiting emergency departments in the past 6 months; 71 of 90 (79%) reported life-threatening fear due to their diagnosis; 73 of 90 (83%) had other family members affected, but 54 of 73 of these affected relatives did not look for specific HAE treatment; and 26 of 90 (29%) reported death due to asphyxia or throat swelling in family members. Conclusion: Patients with HAE report understanding how severe their diagnosis represent, but they did not ponder how important their commitment to treatment may decrease the constant fear brought by the disease in its possible swelling crisis. Family data supported this conclusion.

An ABC of the Warning Signs of Hereditary Angioedema.

Hereditary angioedema (HAE) with C1 inhibitor deficiency is a genetic disorder that clinically manifests with attacks of angioedema in the subcutaneous and submucosal tissues, mainly in the extremities, abdomen, and upper airway. During attacks, vascular permeability is increased due to increased bradykinin (BK). This means that special therapies are needed for attacks that do not respond to traditional antiallergic therapies involving antihistamines, corticosteroids, and epinephrine. The recurring attacks may disable patients and lead to frequent visits to emergency rooms where misdiagnoses are common. HAE attacks may be fatal when upper-airway edema occurs, if proper treatment with a C1 inhibitor concentrate or BK receptor antagonist is not administered or an emergency tracheostomy is not performed. We propose a mnemonic method for the warning signs of HAE for the use as a diagnostic tool, i.e., the so-called "ABC" of the warning signs of HAE. The letters represent the following: A = Angioedema, B = Bradykinin, C = C1 inhibitor, D = Distress factors, E = Epinephrine nonresponsive, F = Family history, and G = Glottis/Gastrointestinal edema. To avoid fatalities, medical staff and patients, including family members, must be aware of HAE. An alphabetical mnemonic method has been developed and we hope it may benefit patients.

Genetic analysis of hereditary angioedema in a Brazilian family by targeted next generation sequencing.

Hereditary angioedema (HAE) is accompanied by an overproduction of bradykinin (BK) as the primary mediator of swelling. Although many proteins may be involved in regulating the wide spectrum of HAE symptoms, most studies have only focused on C1-INH and FXII. For the first time, a next generation sequencing (NGS) method was applied to develop a robust, time- and cost-effective diagnostic and research tool to analyze selected genes related to HAE. The entire coding region and the exon-intron boundaries of 15 genes from 23 subjects of a Brazilian family, nine of whom were symptomatic, were analyzed by NGS. One new mutation found uniquely in the nine symptomatic patients, p.Ala457Pro in the SERPING1 gene, was estimated as likely to be pathogenic (PolyPhen-2 software analysis) and is the main candidate to be responsible for HAE in these patients. Alterations identified in a few asymptomatic individuals but also found in almost all symptomatic patients, such as p.Ile197Met (HMWK), p.Glu298Asp (NOS3) and p.Gly354Glu (B2R), may also be involved in modulating patient-specific symptoms. This NGS gene panel has proven to be a valuable tool for a quick and accurate molecular diagnosis of HAE and efficient to indicate modulators of HAE symptoms.

Clinical and Genotypic Spectrum of Chronic Granulomatous Disease in 71 Latin American Patients: First Report from the LASID Registry.

AIM: We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database. RESULTS: Latin American CGD patients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9 months, and the mean age at CGD diagnosis was 52.7 months. Recurrent pneumonia was the most frequent clinical condition (76.8%), followed by lymphadenopathy (59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Guérin (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations: p.W361G, p.C282X, p.W483R, p.R226X, and p.Q93X), 16 patients with the common deletion c.75_76 del.GT in exon 2 of NCF1 gene, and two patients with mutations in the CYBA gene. CONCLUSION: The majority of Latin American CGD patients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGD patients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients.

BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies.

BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. OBJECTIVES: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. METHODS: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. RESULTS: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/µL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/µL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). CONCLUSIONS: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

Attending to warning signs of primary immunodeficiency diseases across the range of clinical practice.

PURPOSE: Patients with primary immunodeficiency diseases (PIDD) may present with recurrent infections affecting different organs, organ-specific inflammation/autoimmunity, and also increased cancer risk, particularly hematopoietic malignancies. The diversity of PIDD and the wide age range over which these clinical occurrences become apparent often make the identification of patients difficult for physicians other than immunologists. The aim of this report is to develop a tool for educative programs targeted to specialists and applied by clinical immunologists. METHODS: Considering the data from national surveys and clinical reports of experiences with specific PIDD patients, an evidence-based list of symptoms, signs, and corresponding laboratory tests were elaborated to help physicians other than immunologists look for PIDD. RESULTS: Tables including main clinical manifestations, restricted immunological evaluation, and possible related diagnosis were organized for general practitioners and 5 specialties. Tables include information on specific warning signs of PIDD for pulmonologists, gastroenterologists, dermatologists, hematologists, and infectious disease specialists. CONCLUSIONS: This report provides clinical immunologists with an instrument they can use to introduce specialists in other areas of medicine to the warning signs of PIDD and increase early diagnosis. Educational programs should be developed attending the needs of each specialty.

Serum Levels of Ficolin-3 and Mannose-Binding Lectin in Patients with Leprosy and Their Family Contacts in a Hyperendemic Region in Northeastern Brazil.

The present study aimed at analyzing the serum levels of mannose-binding lectin (MBL) and ficolin-3 (FCN3) in leprosy patients and their healthy family contacts in a hyperendemic region in northeastern Brazil. A cross-sectional study was carried out with 90 patients who had been diagnosed with leprosy and 79 healthy family contacts. Serum levels of the MBL and FCN3 proteins were measured using the immunofluorometric assay (ELISA). Clinical information was determined from the patients' charts. It was observed that the leprosy patients were more likely to be male (OR = 2.17; p = 0.01) and younger than fifteen years of age (OR = 2.01; p = 0.03) when compared to the family contacts. Those under 15 years of age had higher levels of MBL (4455 ng/mL) than those over 15 years of age (2342 ng/mL; p = 0.018). Higher FCN3 levels were identified in patients with indeterminate leprosy (41.9 µg/mL) compared to those with the lepromatous form (34.3 µg/mL; p = 0.033) and in those with no physical disabilities (38.1 µg/mL) compared to those with some disability (p = 0.031). Higher FCN3 levels were also observed in the group of patients without leprosy reactions (37.4 µg/mL) compared to those with type 1 (33.7 µg/mL) and type 2 (36.1 µg/mL) reactions. The MBL levels were higher in children under 15 years of age than they were in adults. It was evidenced that higher FCN3 serum levels were associated with early and transient clinical forms and lower expression in severe forms of leprosy.

Inborn Errors of Immunity: how to diagnose them?

OBJECTIVES: Inborn Errors of Immunity are characterized by infectious conditions and manifestations of immune dysregulation. The diversity of clinical phenotypes can make it difficult to direct the laboratory investigation. This article aims to update the investigation of immunological competence in the context of primary defects of the immune system. SOURCE OF DATA: Searches were carried out on Pubmed to review articles published in the last five years, in English, French or Spanish, using the terms "diagnosis" OR "investigation" AND "immunodeficiency" or "primary immunodeficiency" or "inborn errors of immunity" NOT "HIV". Recent textbook editions have also been consulted. SUMMARY OF FINDINGS: The immune system competence investigation should be started based on clinical phenotypes. Relevant data are: characterization of infectious conditions (location, recurrence, types of infectious agents, response to treatment), age during symptom onset and associated manifestations (growth impairment, allergy, autoimmunity, malignancies, fever and signs of inflammation without the identification of infection or autoimmunity) and family history. These data contribute to the selection of tests to be performed. CONCLUSIONS: The diagnostic investigation of Inborn Errors of Immunity should be guided by the clinical characterization of patients, aiming to optimize the use of complementary tests. Many diagnoses are attained only through genetic tests, which are not always available. However, the absence of a diagnosis of certainty should never delay the implementation of therapeutic measures that preserve patient life and health.

Inborn errors of immunity associated with characteristic phenotypes.

OBJECTIVES: The aim of the report is to describe the main immunodeficiencies with syndromic characteristics according to the new classification of Inborn Errors of Immunity. DATA SOURCE: The data search was centered on the PubMed platform on review studies, meta-analyses, systematic reviews, case reports and a randomized study published in the last 10 years that allowed the characterization of the several immunological defects included in this group. DATA SYNTHESIS: Immunodeficiencies with syndromic characteristics include 65 immunological defects in 9 subgroups. The diversity of clinical manifestations is observed in each described disease and may appear early or later, with variable severity. Congenital thrombocytopenia, syndromes with DNA repair defect, immuno-osseous dysplasias, thymic defects, Hyper IgE Syndrome, anhidrotic ectodermal dysplasia with immunodeficiency and purine nucleoside phosphorylase deficiency were addressed. CONCLUSIONS: Immunological defects can present with very different characteristics; however, the occurrence of infectious processes, autoimmune disorders and progression to malignancy may suggest diagnostic research. In the case of diseases with gene mutations, family history is of utmost importance.

Triggers of Exacerbation in Chronic Urticaria and Recurrent Angioedema-Prevalence and Relevance.

Patients with urticaria and angioedema often have triggers that cause an outbreak or a swelling episode or worsen their chronic condition. Exploring these factors with each patient may result in better understanding and control of their disease. Patients should be advised to avoid known triggers, if feasible, or prepare to prevent or control an exacerbation with appropriate pretreatment if avoidance is not possible. In this review, we describe and discuss a variety of factors for which there is evidence that they cause or exacerbate chronic spontaneous urticaria and angioedema. These potentially exacerbating factors include drugs, food additives, and naturally occurring pseudoallergens, mental stress, and trauma.