RESUMO
INTRODUCTION: There has been substantial increase in food allergies in recent decades. The management of severe food allergy often includes strict avoidance and medical therapies. However, oral immunotherapy (OIT) is a promising treatment option for these patients, which is still being investigated. METHODS: The study recruited children from 2 years onward with a history of wheat anaphylaxis who had been referred to the Mofid Children Hospital. Wheat allergy was confirmed by a double-blind placebo-controlled food challenge. OIT was started to reach 5.28 g of wheat protein supplied in 60 g of bread. Besides immunologic measurements, a second and third oral food challenge (OFC) was performed after 3 months and 1 year of maintenance therapy to evaluate the long-term efficacy of wheat OIT (WOIT). RESULTS: Seventeen patients completed the 3-month maintenance phase; 8 of them demonstrated negative OFCs. All of the 9 with positive OFCs were asked to continue the daily consumption of 60 g of bread for another year. Three patients with positive OFCs were followed for 1 more year and were asked to continue eating 60 g of bread every other day. The serum level of wheat sIgE was significantly increased at the end of the buildup phase (p = 0.026) and dramatically dropped at the end of the maintenance phase (p = 0.022). CONCLUSION: To conclude, WOIT is an effective and safe modality of treatment if it is administered under strict supervision.
Assuntos
Anafilaxia , Dessensibilização Imunológica , Hipersensibilidade a Trigo , Administração Oral , Alérgenos , Anafilaxia/etiologia , Anafilaxia/terapia , Criança , Método Duplo-Cego , Seguimentos , Humanos , Fatores Imunológicos , Imunoterapia , Triticum/efeitos adversos , Hipersensibilidade a Trigo/terapiaRESUMO
BACKGROUND: Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. OBJECTIVES: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. METHODS: Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. RESULTS: The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs. CONCLUSIONS: This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.
Assuntos
Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Adolescente , Criança , Pré-Escolar , Consanguinidade , Feminino , Genes Recessivos/genética , Genes Recessivos/imunologia , Predisposição Genética para Doença/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Síndromes de Imunodeficiência/mortalidade , Lactente , Irã (Geográfico) , Síndrome de Job/genética , Síndrome de Job/imunologia , Síndrome de Job/mortalidade , Masculino , Mutação/genética , Mutação/imunologia , Fenótipo , Estudos Retrospectivos , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Análise de Sequência de DNA/métodos , Taxa de SobrevidaRESUMO
BACKGROUND: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. METHOD: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. RESULTS: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. CONCLUSIONS: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.
Assuntos
Síndromes de Imunodeficiência/epidemiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Suscetibilidade a Doenças , Feminino , Seguimentos , Predisposição Genética para Doença , Testes Genéticos , Geografia Médica , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/etiologia , Lactente , Recém-Nascido , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Vigilância da População , Prevalência , Sistema de Registros , Adulto JovemRESUMO
In the last decade, autosomal recessive interleukin-12 receptor ß1 (IL-12Rß1) deficiency, the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD), has been diagnosed in a few children and adults with severe tuberculosis in Iran. Here, we report three cases referred to the Immunology, Asthma and Allergy ward at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD) at Masih Daneshvari Hospital from 2012 to 2017 with Mycobacterium tuberculosis and non-tuberculous mycobacteria infections due to defects in IL-12Rß1 but with different clinical manifestations. All three were homozygous for either an IL-12Rß1 missense or nonsense mutation that caused the IL-12Rß1 protein not to be expressed on the cell membrane and completely abolished the cellular response to recombinant IL-12. Our findings suggest that the presence of IL-12Rß1 deficiency should be determined in children with mycobacterial infections at least in countries with a high prevalence of parental consanguinity and in areas endemic for TB like Iran.
Assuntos
Mutação , Infecções por Mycobacterium/genética , Receptores de Interleucina-12/genética , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Irã (Geográfico) , Masculino , Mycobacterium/isolamento & purificação , Infecções por Mycobacterium/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Linhagem , Receptores de Interleucina-12/imunologia , Tuberculose/genética , Tuberculose/microbiologiaRESUMO
Food allergy is a common health problem worldwide, with increasing prevalence during recent decades. The only approved treatments for food allergy are food avoidance and administration of emergency medications in case of accidental exposure, which negatively affects patients' quality of life, so new treatments are highly desirable. Different food immunotherapy modalities have recently been used, with variable success rates in the induction of desensitization and tolerance, and different numbers and types of adverse reactions. Adverse reactions, especially intolerable gastrointestinal symptoms, are the most important causes of immunotherapy withdrawal. Eosinophilic esophagitis has been reported as a complication of milk, egg, and peanut oral immunotherapies and sublingual immunotherapy for respiratory allergies, but not for food allergies. Eosinophilic gastritis and eosinophilic colitis also rarely happened following egg and milk oral immunotherapies. The patients undergoing oral and sublingual immunotherapies should be closely followed up for a long time, and those with gastrointestinal symptoms should be evaluated by endoscopy of the gastrointestinal tract. These complications are usually reversible after early diagnosis and stopping the immunotherapy protocol.
Assuntos
Dessensibilização Imunológica/efeitos adversos , Hipersensibilidade Alimentar/terapia , Gastroenteropatias/prevenção & controle , Administração Oral , Administração Sublingual , Alérgenos/imunologia , Animais , Endoscopia , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Humanos , Suspensão de TratamentoRESUMO
BACKGROUND/AIM: Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. METHODS: Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. RESULTS: Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT were 58.4, 95.8, 93.3 and 69.9%, respectively. CONCLUSIONS: Considering the significant difference in LTT results between the case and control groups in patients receiving carbamazepine and phenytoin, and not observing such a difference in patients receiving phenobarbital and lamotrigine, LTT results are more valuable for the diagnosis of hypersensitivity reactions following the administration of carbamazepine and phenytoin. The LTT has good specificity but low sensitivity for the diagnosis of drug hypersensitivity reactions.
Assuntos
Anticonvulsivantes/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/imunologia , Ativação Linfocitária/imunologia , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Estudos de Casos e Controles , Criança , Síndrome de Hipersensibilidade a Medicamentos , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Síndrome de Stevens-Johnson , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Common variable immune deficiency (CVID) is a heterogeneous syndrome with a wide variety of signs and symptoms. This study describes the phenotyping and survival of the CVID patients in the allergy and clinical immunology department of Rasol-E-Akram Hospital of Iran University of Medical Sciences in Tehran. METHOD: We retrospectively reviewed hospital files of CVID patients in our department until January 2014. All patients were diagnosed with standard diagnostic criteria of CVID, treated and visited monthly, during the follow-up period. We divided the patients into four phenotypes; infection only, cytopenia, polyclonal lymphocytic infiltration and unexplained enteropathy. The immunologic, demographic and clinical findings in different phenotypes were analysed. RESULTS: The study included 47 CVID patients with mean age at onset of symptoms and diagnosis of 11.2 and 20.2 years, respectively. Phenotyping of our patients was: only infection (62%), cytopenia (26%) and PLI (19%) and 94% of cases had only one phenotype. We did not find a significant relation between the clinical phenotypes and immunologic or demographic data. Rate of parental consanguinity in our cases was 47%. Parental consanguinity was related to lower age at onset, lower age at diagnosis and higher baseline IgG levels. Patients with malignancy and autoimmunity had significantly higher age at onset. Our patients were followed-up for 6.9 years and the mortality rate during this time was 6%. CONCLUSIONS: Parental consanguinity and age at onset of CVID symptoms may have important roles in CVID manifestations.
Assuntos
Imunodeficiência de Variável Comum/epidemiologia , Imunodeficiência de Variável Comum/genética , Consanguinidade , Adolescente , Adulto , Idade de Início , Autoimunidade , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/mortalidade , Feminino , Seguimentos , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Adulto JovemRESUMO
Background: The vaccination is one of the acceptable and recomended solution to prevent and control of COVID-19. The aim of this study was to determine the efficacy of sinopharm vaccination in children aged 12-17 in Tehran. Methods: The case population study was performed from October 2021 to March 2022 among 1,500 children with positive PCR test reffered in Mofid Children's Hospital in Tehran. 64 children aged 12-17 years were included. The data were collected by the hospital information system (HIS), vaccination information registration systems and questionnaire with their families. The coverage and efficacy of vaccination determined with equels commented by WHO. Results: Out of 64 children, 52 children were 12 to 15 years old (13.35±1.08), 12 children were 16 to 17 years old (16.55±0.52). 48.4% had received two doses of vaccine. The highest rate of positive PCR was observed in February 2022. Sinopharm vaccine coverage in this age group was 93.6% for the first dose and 81.1% for the second dose. Based on this information, 48.4% children in this study have received two complete doses of the COVID-19 vaccine. The efficacy of the vaccine was estimated as 94.4% (95% CI 90.2 to 97.7). Conclusion: It seems the coverage of Sinopharm vaccination in the age group of 12-17 years in Tehran is favorable and has high efficacy in this age group. In order to obtain more accurate and comprehensive estimation, it is recommended to take a sample on a wider level of the community.
RESUMO
Background: Primary ciliary dyskinesia (PCD), also known as the immotile-cilia syndrome, is a clinically and genetically heterogeneous syndrome. Improper function of the cilia causes impaired mucociliary clearance. Neonatal respiratory distress, rhinosinusitis, recurrent chest infections, wet cough, and otitis media are respiratory presentations of this disease. It could also manifest as infertility in males as well as laterality defects in both sexes, such as situs abnormalities (Kartagener syndrome). During the past decade, numerous pathogenic variants in 40 genes have been identified as the causatives of primary ciliary dyskinesia. DNAH11 (dynein axonemal heavy chain 11) is a gene that is responsible for the production of cilia's protein and encodes the outer dynein arm. Dynein heavy chains are motor proteins of the outer dynein arms and play an essential role in ciliary motility. Case Presentation. A 3-year-old boy, the offspring of consanguineous parents, was referred to the pediatric clinical immunology outpatient department with a history of recurrent respiratory tract infections and periodic fever. Furthermore, on medical examination, situs inversus was recognized. His lab results revealed elevated levels of erythrocyte sedimentation rate (ESR) and C reactive protein (CRP). Serum IgG, IgM, and IgA levels were normal, while IgE levels were elevated. Whole exome sequencing (WES) was performed for the patient. WES demonstrated a novel homozygous nonsense variant in DNAH11 (c.5247G > A; p. Trp1749Ter). Conclusion: We reported a novel homozygous nonsense variant in DNAH11 in a 3-year-old boy with primary ciliary dyskinesia. Biallelic pathogenic variants in one of the many coding genes involved in the process of ciliogenesis lead to PCD.
RESUMO
Primary immunodeficiencies are a diverse group of rare genetic disorders, among which phagocytic dysfunction impairs neutrophil function in a wide range of inherited disorders. Due to the heterogeneity of the disorders a multidisciplinary approach is often required for early diagnosis and initiation of appropriate treatments. The aim of this study was to evaluate the imaging findings in children admitted with phagocytic primary immunodeficiencies. Thirty-five children who fulfilled the inclusion criteria for phagocytic dysfunction were enrolled in this study. The patients were under close observation and monitoring from January 2011 until data locking in December 2017. The diagnosis of phagocytic immunodeficiency was confirmed by the patient's clinical course, presentation features, and laboratory data. Among the 35 patients studied, the most frequent condition was chronic granulomatous disease (CGD) (23 patients), followed by different types of neutropenia (8 patients) and Job's syndrome (4 patients). Mediastinal and hilar lymphadenopathies and consolidation were the most frequent presentations. There was a significant relationship between mediastinal/hilar lymphadenopathies and fungal infections. A meaningful relationship was also found between pulmonary nodules without halo signs in patients with concomitant tuberculosis and fungal infections. A significant correlation was found between CGD, pulmonary fibrotic changes, and mediastinal lymphadenopathies. The most frequent radiological manifestations in children included mediastinal and hilar consolidations. Physicians' awareness of the radiological and clinical manifestations of these inherited diseases may be helpful in the early diagnosis and timely initiation of specific prophylaxis measures to prevent infections and also to initiate hematopoietic stem cell transplantation as the curative management modality.
RESUMO
AIM: Herein, we present five children and adolescents with a final diagnosis of non-celiac gluten sensitivity (NCGS). BACKGROUND: Non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extra-intestinal symptoms triggered by ingestion of gluten-containing compounds, e.g., wheat, rye, and barley, in subjects without celiac disease or wheat allergy. METHODS: Demographic characteristics, clinical manifestations, serum biomarkers and skin prick test were evaluated. Patient data was also recorded after they followed a gluten-free diet (GFD). Height and weight were measured, and all patients were examined 6 months after following the suggested GFD. RESULTS: All patients had failure to thrive and abdominal pain. Clinical symptoms were reduced, and significant weight and height gains were detected after 1 month of following a gluten-free diet. CONCLUSION: The relationship between failure to thrive (FTT) and NCGS is still unknown; hence, NCGS may be one of the main causes of FTT which can be prevented by gluten-free diets.
RESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) can be present in the form of multisystem inflammatory disease in children. Case Presentation. A 25-month-old boy presented with fever, malaise, diffuse maculopapular rashes, and mucosal involvement during the COVID-19 pandemic. He was first diagnosed with Stevens-Johnson syndrome (SJS). Further evaluation revealed lymphopenia, thrombocytopenia, and elevated levels of C-reactive protein (CRP), ferritin, and fibrinogen. This was followed by a positive polymerase chain reaction (PCR) test for COVID-19. In addition to receiving initial care for SJS, he was treated for MIS-C, which led to his recovery after four days. CONCLUSION: COVID-19 infection should be considered in children with fever and dermatological features during the pandemic because it may cause different features of the multisystem inflammatory syndrome in children (MIS-C), suggestive of delayed hyperimmune response.
RESUMO
Respiratory diseases are considered as significant causes of morbidity and mortality in primary immunodeficiencies. This study aimed to reveal the radiologic patterns of thoracic involvement in these disorders. A total of 58 patients, including 38 cases with combined cellular-humoral and 20 cases with humoral immunodeficiencies, were enrolled in this study. The "combined" group consisted of 12 cases with severe combined immunodeficiency (SCID) and 26 cases with combined immunodeficiency. The "humoral" group included seven patients with Hyper IgM syndrome (HIGMs), seven cases with common variable immunodeficiency (CVID), three patients with X-linked agammaglobulinemia, and three patients with other types of humoral primary immunodeficiencies (PIDs). The mean age of patients at the time of evaluation was 3.3±3.8 and 5.3±3.9 years in combined and humoral groups, respectively. The findings of chest X-rays and CT scans were interpreted and compared. There was a significant difference for alveolar opacification between combined and humoral immunodeficiencies (58% vs. 30%). The bronchopneumonia-like pattern was detected as a significant finding in patients with SCID (42%) and HIGMs (43%). Atrophy of the thymus was detected significantly often in cases of SCID (67%). Two patients with CVID and lipopolysaccharide-responsive and beige-like anchor protein deficiency showed parenchymal changes of granulomatous lymphocytic interstitial lung disease. No significant difference was detected for bronchiectasis, bronchitis/bronchiolitis patterns, pleural effusion, and thoracic lymphadenopathy. Distinct subtypes of primary immunodeficiency may provoke differing and comparable radiological patterns of thoracic involvement; which can clue the clinician and radiologist to the diagnosis of the disease.
Assuntos
Agamaglobulinemia/diagnóstico por imagem , Imunodeficiência de Variável Comum/diagnóstico por imagem , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico por imagem , Síndrome de Imunodeficiência com Hiper-IgM/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Imunodeficiência Combinada Severa/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Criança , Pré-Escolar , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
AIM: Considering the allergic basis of Eosinophilic esophagitis (EoE), this study was conducted to evaluate peripheral blood Tregs in children with EoE. BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of gastrointestinal tract. Regulatory T cells (Tregs) have a confirmed role in allergic disorders. METHODS: Children with EoE, gastroesophageal reflux disease (GERD) and healthy controls (HC) (10 subjects in each group) were recruited after diagnosis by a pediatric gastroenterologist and allergist. After obtaining informed written consent, peripheral blood was obtained. Peripheral blood mononuclear cells were isolated by Ficoll gradient centrifugation. Flowcytometry was used to enumerate peripheral blood Tregs (CD4 +CD25 +FOXP3+ gated lymphocytes were considered as Tregs). RESULTS: CD4+ gated lymphocytes significantly increased in EoE and GERD groups compared to HC group (p= 0.018). Tregs also was significantly increased in EoE in comparison to HC group (p=0.016). There were no statistically significant differences in Tregs of EoE as compared to GERD subjects (p=0.085). CONCLUSION: Peripheral blood Tregs increase in patients with EoE as compared to healthy controls, which may be indicative of a feedback mechanism to regulate inflammatory responses.
RESUMO
Chronic granulomatous disease (CGD) is a rare genetic disorder of neutrophil activity, resulting in increased rate of recurrent infections with catalase-positive bacteria and fungi, as well as various autoimmune diseases such as sarcoidosis, rheumatoid arthritis, and discoid and/or systemic lupus erythematosus. Few reports have reported lupus erythematosus (LE) in patients with X-linked CGD (XL-CGD) and carriers, and very few in autosomal recessive CGD (AR-CGD). Here, we present 5 patients with CGD developing LE at different ages to emphasize on the importance of appropriate follow-up and treatment in patients with CGD with clinical signs and symptoms of autoimmune diseases and even in those with negative serologic results.
Assuntos
Genes Recessivos , Genes Ligados ao Cromossomo X , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/genética , Adolescente , Alelos , Biomarcadores , Biópsia , Criança , Suscetibilidade a Doenças , Feminino , Genótipo , Humanos , Irã (Geográfico) , Masculino , Fenótipo , Adulto JovemRESUMO
Usage of cancer chemotherapeutics drugs can be associated with adverse drug reactions. When IgE-mediated drug reactions are formed following administration of a chemotherapeutics drug that is a drug of choice, drug desensitization protocols can be helpful. HSR can be allergic or nonallergic, but the clinical manifestations are similar. RDD is effective when used appropriately, however it is often over utilized instead of performing a drug challenge. RDD is both an acceptable approach and a high-risk treatment modality in patients, in whom the offending agent is the first choice in chemotherapy. The safety of this modality has been acceptable in large studies. The side effects are often less frequent and less severe by repeating the protocol. We present 4 cases of successful desensitization in cancer patients, who have developed IgE- mediated reactions to their major chemotherapy drug.
RESUMO
BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 µ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with µ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with µ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.
Assuntos
Agamaglobulinemia , Imunodeficiência de Variável Comum , Síndrome de Imunodeficiência com Hiper-IgM , Adolescente , Adulto , Tirosina Quinase da Agamaglobulinemia/genética , Agamaglobulinemia/genética , Agamaglobulinemia/mortalidade , Ligante de CD40/genética , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/mortalidade , Diarreia/genética , Diarreia/mortalidade , Feminino , Estudos de Associação Genética , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/genética , Síndrome de Imunodeficiência com Hiper-IgM/mortalidade , Cadeias mu de Imunoglobulina/genética , Masculino , Meningite/genética , Meningite/mortalidade , Mutação , Poliomielite/genética , Poliomielite/mortalidade , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Atopic dermatitis (AD) is a common, chronic, relapsing and inflammatory skin disease characterized by pruritus and xerosis (dry skin). Its prevalence is on the increase worldwide, particularly in children. As the pathogenesis of AD involves a complex interaction of genetic, environmental and immunological factors, its definitive treatment is difficult. OBJECTIVE: This clinical trial was designed as equivalence study to investigate the effect of aqueous extract of edible dried fig fruit on the severity of AD as measured with scoring atopic dermatitis (SCORAD), in comparison with Hydrocortisone 1.0% as the routine treatment of AD and base cream as a placebo. METHOD: Forty five children aged 4 months to 14 years with mild to moderate AD (SCORAD <50) were randomly assigned, in a double blind manner, to three treatment groups in order to perform a randomised, double blinded, placebo-controlled clinical trial. The patients were instructed to apply their allocated creams twice a day for two weeks. RESULTS: The randomised, placebo-controlled trial indicates that the new treatment had significantly increased efficacy in terms of reducing the SCORAD index, pruritus and intensity scores in comparison with Hydrocortisone 1.0% (p<0.05) and the placebo failed to ameliorate the symptoms. CONCLUSION: Safety, efficacy, tolerability, and symptom relief were considerable in fig fruit extract in comparison with hydrocortisone 1.0%. This clinical trial suggests that fig fruit extract can be used instead of low potent corticosteroid in mild to moderate cases of AD.
Assuntos
Dermatite Atópica/tratamento farmacológico , Ficus , Fitoterapia , Preparações de Plantas/uso terapêutico , Prurido/tratamento farmacológico , Administração Tópica , Adolescente , Criança , Pré-Escolar , Dermatite Atópica/complicações , Método Duplo-Cego , Feminino , Frutas , Humanos , Hidrocortisona/uso terapêutico , Lactente , Masculino , Pomadas , Preparações de Plantas/administração & dosagem , Preparações de Plantas/farmacologia , Prurido/etiologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
This study aimed to investigate the efficacy and the underlining mechanism of aspirin desensitization among patients with Aspirin Exacerbated Respiratory Disease (AERD). Thirty-eight patients, who had undergone an aspirin challenge test and were diagnosed as having AERD, were engaged in a double-blind randomized clinical trial. They were divided into two groups-an active group of patients who went through aspirin desensitization, and the control group, receiving placebo. Clinical symptoms and the quality of life of the patients-in addition to the levels of interleukin 4 and 5 (IL4), (IL5)-were documented at the beginning of the study and again after six months of aspirin desensitization. The quality of life of the patients was significantly higher in the active group after six months (P = 0.001). Medication requirements and symptom score were manifested to be significantly lower in the active group after six months than at the beginning of the study (P = 0.005, 0.017 respectively). Forced expiratory volume in the second one (FEV1) was, also, significantly higher in the active group after six months of the study (P = 0.032). IL5 was found to be significantly lower in the active group after six months (P = 0.019). However, no significant difference was observed in the levels of IL4 between the two groups (P = 0.152). The study revealed that aspirin desensitization can improve the quality of life of patients with AERD, lessen their symptoms and medication requirements, lower their levels of IL5, and improve some pulmonary function tests such as FEV1.
RESUMO
Cow's milk allergy (CMA) is the most frequent food allergy in children and oral immunotherapy (OIT) is a promising approach for treatment of patients. The most challenging cases are anaphylactic with coexisting asthma and proposing safe protocols is crucial especially in high risk groups. Considering that CMA varies among patients, an individualized OIT protocol would be beneficial to achieve a safer and more efficient method of desensitization. 18 children more than 3 years of age with IgE-mediated CMA were enrolled. CMA was confirmed by positive skin prick test (SPT) and positive oral food challenge (OFC) and 60% of individuals had a convincing history of persistent asthma. SPT with milk extracts, whole fresh milk and serially diluted milk concentrations were performed. The dilution of milk that induced 3-5 mm of wheal in each individual was selected as the starting dilution for OIT. Desensitization began by 1 drop of the defined dilution and continued increasingly. Overall, 16 out of 18 children (88.8%) achieved the daily intake of 120 mL of milk. Four out of these 16 children accomplished the protocol without any adverse allergic reactions. 12 patients experienced mild to severe reactions. Wheal and erythema in SPT (p≤0.001), and sIgE (p≤0.003) to most milk allergens were significantly decreased following desensitization. We successfully desensitized 16 of 18 children with IgE-mediated CMA by individualized desensitization protocol. Individualizing the OIT protocol would be helpful to save time and perhaps to relieve the allergic symptoms after ingesting cow's milk intake.