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BACKGROUND: Egg is the third most common food allergy in children; however, data on pediatric egg-induced anaphylaxis are sparse. OBJECTIVE: To describe the clinical characteristics, management, and outcomes of pediatric egg-induced anaphylaxis. METHODS: Children presenting with anaphylaxis were recruited from 13 emergency departments as part of the Cross-Canada Anaphylaxis Registry, from which data on anaphylaxis triggered by egg were extracted. Multivariate logistic regression was used to determine factors associated with prehospital epinephrine autoinjector (EAI) use and to compare anaphylaxis triggered by egg with other triggers of food-induced anaphylaxis (FIA). RESULTS: We recruited 302 children with egg-induced anaphylaxis. The mean age was 2.6 years (SD = 3.6), and 55.3% were male. Only 39.4% had previously been diagnosed with an egg allergy. Prehospital EAI use was 32.1%, but this was not significantly lower than in other triggers of FIA (P = .26). Only 1.4% of patients required hospital admission. Relative to other triggers of FIA, patients with egg-induced anaphylaxis were significantly younger (P < .001) and exhibited more vomiting (P = .0053) and less throat tightness (P = .0015) and angioedema (P < .001). CONCLUSION: To the best of our knowledge, this is the largest published cohort of pediatric egg-induced anaphylaxis. In this cohort, prehospital EAI use was very low. In addition, we identified certain symptoms that distinguish egg-induced from other triggers of FIA. Taken together, high suspicion is crucial in identifying egg-induced anaphylaxis, given the younger patient demographic and frequent lack of FIA history.
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Anafilaxia , Hipersensibilidad al Huevo , Epinefrina , Humanos , Anafilaxia/tratamiento farmacológico , Anafilaxia/etiología , Anafilaxia/diagnóstico , Anafilaxia/terapia , Masculino , Femenino , Estudios Transversales , Hipersensibilidad al Huevo/terapia , Hipersensibilidad al Huevo/diagnóstico , Hipersensibilidad al Huevo/inmunología , Hipersensibilidad al Huevo/complicaciones , Preescolar , Niño , Epinefrina/uso terapéutico , Epinefrina/administración & dosificación , Lactante , Canadá/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Sistema de RegistrosRESUMEN
BACKGROUND: Cow's milk is one of the most common and burdensome allergens in pediatrics, and it can induce severe anaphylactic reactions in children. However, data on cow's milk-induced anaphylaxis are sparse. OBJECTIVE: To describe the epidemiology of pediatric cow's milk-induced anaphylaxis and to determine risk factors for repeat emergency department (ED) epinephrine administration. METHODS: Between April 2011 and May 2023, data were collected on children with anaphylaxis presenting to 10 Canadian EDs. A standardized form documenting symptoms, triggers, treatment, and outcome was used. Multivariate logistic regression was used. RESULTS: Of 3118 anaphylactic reactions, 319 milk-induced anaphylaxis cases were identified (10%). In the prehospital setting, 54% of patients with milk-induced anaphylaxis received intramuscular epinephrine. In those with milk-induced anaphylaxis, receiving epinephrine before presenting to the ED was associated with a reduced risk of requiring 2 or more epinephrine doses in the ED (adjusted odds ratio, 0.95 [95% CI, 0.90-0.99]). Children younger than 5 years of age were more likely to experience a mild reaction compared with that in older children, who experienced a moderate reaction more often (P < .0001). Compared with other forms of food-induced anaphylaxis, children presenting with milk-induced anaphylaxis were younger; a greater proportion experienced wheezing and vomiting, and less experienced angioedema. CONCLUSION: Prehospital epinephrine in pediatric milk-induced anaphylaxis is underused; however, it may decrease risk of requiring 2 ED epinephrine doses. Milk-induced anaphylaxis in children younger than 5 years of age may be less severe than in older children. Wheezing and vomiting are more prevalent in milk-induced anaphylaxis compared with that of other foods.
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Anafilaxia , Femenino , Animales , Bovinos , Niño , Humanos , Anafilaxia/tratamiento farmacológico , Anafilaxia/epidemiología , Anafilaxia/etiología , Leche/efectos adversos , Ruidos Respiratorios , Canadá/epidemiología , Epinefrina/uso terapéutico , Servicio de Urgencia en Hospital , Alérgenos , Vómitos/tratamiento farmacológicoRESUMEN
BACKGROUND: Epinephrine is the first-line treatment for anaphylaxis but is often replaced with antihistamines or corticosteroids. Delayed epinephrine administration is a risk factor for fatal anaphylaxis. Convincing data on the role of antihistamines and corticosteroids in anaphylaxis management are sparse. OBJECTIVE: To establish the impact of prehospital treatment with epinephrine, antihistamines, and/or corticosteroids on anaphylaxis management. METHODS: Patients presenting with anaphylaxis were recruited prospectively and retrospectively in 10 Canadian and 1 Israeli emergency departments (EDs) between April 2011 and August 2022, as part of the Cross-Canada Anaphylaxis REgistry. Data on anaphylaxis cases were collected using a standardized form. Primary outcomes were uncontrolled reactions (>2 doses of epinephrine in ED), no prehospital epinephrine use, use of intravenous fluids in ED, and hospital admission. Multivariate regression was used to identify factors associated with primary outcomes. RESULTS: Among 5364 reactions recorded, median age was 8.8 years (IQR, 3.78-16.9); 54.9% of the patients were males, and 52.5% had a known food allergy. In the prehospital setting, 37.9% received epinephrine; 44.3% received antihistamines, and 3.15% received corticosteroids. Uncontrolled reactions happened in 250 reactions. Patients treated with prehospital epinephrine were less likely to have uncontrolled reactions (adjusted odds ratio [aOR], 0.955 [95% CI, 0.943-0.967]), receive intravenous fluids in ED (aOR, 0.976 [95% CI, 0.959-0.992]), and to be admitted after the reaction (aOR, 0.964 [95% CI, 0.949-0.980]). Patients treated with prehospital antihistamines were less likely to have uncontrolled reactions (aOR, 0.978 [95% CI, 0.967-0.989]) and to be admitted after the reaction (aOR, 0.963 [95% CI, 0.949-0.977]). Patients who received prehospital corticosteroids were more likely to require intravenous fluids in ED (aOR, 1.059 [95% CI, 1.013-1.107]) and be admitted (aOR, 1.232 [95% CI, 1.181-1.286]). CONCLUSION: Our findings in this predominantly pediatric population support the early use of epinephrine and suggest a beneficial effect of antihistamines. Corticosteroid use in anaphylaxis should be revisited.
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Anafilaxia , Servicios Médicos de Urgencia , Masculino , Humanos , Niño , Femenino , Anafilaxia/tratamiento farmacológico , Anafilaxia/epidemiología , Anafilaxia/etiología , Estudios Retrospectivos , Datos de Salud Recolectados Rutinariamente , Canadá/epidemiología , Epinefrina/uso terapéutico , Servicio de Urgencia en Hospital , Antagonistas de los Receptores Histamínicos/uso terapéutico , Corticoesteroides/uso terapéuticoRESUMEN
BACKGROUND: There is a lack of patient educational resources about chronic urticaria (CU). AIMS: To develop and test the effectiveness of an education tool to help paediatric patients and their families better understand CU and its management. METHODS: From July 2020 to May 2022, paediatric patients with a history of CU who presented to the allergy outpatient clinics at our institution were recruited. Consenting families and patients were asked to complete five questions related to the definition, causes and management of CU at the time of presentation to the clinic. Participants were shown a 5-min animated video addressing the main knowledge gaps about CU. At the end of the video, participants were redirected to the same five questions to respond again. The scores were recorded as a proportion of correct answers (range 0·0-1·0). RESULTS: In total, 53 patients [30 girls (56·6%), 23 boys (43·4%); mean age 9·7 ± 5·1 years, range 1·4-18·5 years] were recruited. The mean baseline pre-video education questionnaire score was 0·67 ± 0·2 (range 0·2-1·0), while the mean post-video score was 0·94 ± 0·1 (range 0·4-1·0), a mean score difference of 0·27, which was statistically significant (P < 0·001). At the 1-year follow-up, 14 (26·4%) patients answered the questionnaire again to assess retention of knowledge; the mean score was 0·83 ± 0·2 (range 0·2-1·0). CONCLUSIONS: Our educational video was successful in educating patients and their families to better understand urticaria. Future studies should aim to optimize patient education through nontraditional tools such as videos, and compare knowledge gain using different methods of education.
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Urticaria Crónica , Urticaria , Masculino , Femenino , Humanos , Niño , Lactante , Preescolar , Adolescente , Urticaria/terapia , Instituciones de Atención AmbulatoriaRESUMEN
BACKGROUND: Data on the clinical and demographic features of Canadian patients with hereditary angioedema (HAE) are lacking. OBJECTIVE: To describe the clinical and demographic features in a large Canadian HAE cohort and compare them with patients with HAE in other countries. METHODS: An online questionnaire was distributed to the members of 2 Canadian HAE patient groups to collect information on demographics and HAE clinical characteristics. All participants 18 years of age or older with HAE type I or II were eligible. Frequency, location, prodromes, and triggers of HAE attacks, including types of HAE treatment, were characterized. RESULTS: Among the 90 participants who completed the online survey, 57% self-identified as having HAE type 1 and 26% HAE type II. The average diagnostic delay was 11 years. In the preceding 6 months, 24% of the participants had no attacks and 35% experienced greater than 5 attacks. The most frequently affected regions of the body were the abdomen (83%), arms orlegs (63%), face (41%), and larynx or throat (41%). Approximately 87% of the participants reported having access to C1 inhibitor at home, and 69% reported using it for long-term prophylaxis. CONCLUSION: Canadian patients with HAE share common clinical characteristics with patients with HAE in other countries. They had a delay in HAE diagnosis and a high burden of disease, as indicated by the high frequency of attacks in the preceding 6 months. This study provides a better understanding of the demographic and clinical characteristics of Canadian patients with HAE.
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Angioedemas Hereditarios , Adulto , Angioedemas Hereditarios/diagnóstico , Angioedemas Hereditarios/tratamiento farmacológico , Angioedemas Hereditarios/epidemiología , Canadá/epidemiología , Proteína Inhibidora del Complemento C1 , Diagnóstico Tardío , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Sesame can cause severe allergic reactions and is a priority allergen in Canada. OBJECTIVE: To assess clinical characteristics and management of pediatric sesame-induced anaphylaxis and identify factors associated with epinephrine treatment. METHODS: Between 2011 and 2021, children with sesame-induced anaphylaxis presenting to 7 emergency departments (ED) in 4 Canadian provinces and 1 regional emergency medical service were enrolled in the Cross-Canada Anaphylaxis Registry. Standardized recruitment forms provided data on symptoms, severity, triggers, and management. Multivariate logistic regression evaluated associations with epinephrine treatment pre-ED and multiple epinephrine dosages. RESULTS: Of all food-induced anaphylactic reactions (n = 3279 children), sesame accounted for 4.0% (n = 130 children), of which 61.5% were boys, and the average (SD) age was 5.0 (4.9) years. Hummus containing sesame paste triggered 58.8% of reactions. In the pre-ED setting, 32.3% received epinephrine, and it was more likely to be used in boys (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.08-1.50) and those with a known food allergy (aOR, 1.36; 95% CI, 1.11-1.68]). In the ED, 47.7% of cases received epinephrine, with older children more likely to receive multiple epinephrine doses (aOR, 1.00; 95% CI, 1.00-1.02). CONCLUSION: In Canada, hummus is the major trigger of sesame-induced anaphylaxis. Knowledge translation focused on prompt epinephrine use and product-labeling policies are required to limit sesame reactions in communities.
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Anafilaxia , Hipersensibilidad a los Alimentos , Sesamum , Adolescente , Alérgenos/uso terapéutico , Anafilaxia/tratamiento farmacológico , Anafilaxia/epidemiología , Anafilaxia/etiología , Canadá/epidemiología , Niño , Preescolar , Servicio de Urgencia en Hospital , Epinefrina/uso terapéutico , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/tratamiento farmacológico , Hipersensibilidad a los Alimentos/epidemiología , Humanos , Masculino , Sistema de Registros , Sesamum/efectos adversosRESUMEN
BACKGROUND: Data are sparse regarding tree nut-induced anaphylaxis (TNA). OBJECTIVE: To characterize rate, clinical characteristics, and management of TNA in children (0-17 years old) across Canada and evaluate factors associated with severe reactions and epinephrine use. METHODS: Between April 2011 and May 2020, data were collected on children presenting to 5 emergency departments in Canada. Multivariate logistic analysis was used to evaluate factors associated with severe reactions (stridor, cyanosis, circulatory collapse, or hypoxia) and epinephrine use. RESULTS: Among 3096 cases of anaphylaxis, 540 (17%) were induced by tree nut. The median age was 5.2 (interquartile range, 2.5-9.5) years and 65.4% were of male sex. Among all reactions, 7.0% were severe. The major tree nuts accounting for anaphylaxis were cashew (32.8%), hazelnut (20.0%), and walnut (11.5%). Cashew-induced anaphylaxis was more common in British Columbia (14.0% difference [95% confidence interval (CI), 1.6-27.6]) vs Ontario and Quebec, whereas pistachio-induced anaphylaxis was more common in Ontario and Quebec (6.3% difference [95% CI, 0.5-12.2]). Prehospital and emergency department intramuscular epinephrine administration was documented in only 35.2% and 52.4% of cases, respectively. Severe reactions were more likely among of male sex (adjusted odds ratio [aOR], 1.05 [95% CI, 1.01-1.10]), older children (aOR, 1.00 [95% CI, 1.00-1.01]), and in reactions triggered by macadamia (aOR, 1.27 [95% CI, 1.03-1.57]). CONCLUSION: Different TNA patterns in Canada may be because of differences in lifestyle (higher prevalence of Asian ethnicity in British Columbia vs Arabic ethnicity in Ontario and Quebec). Intramuscular epinephrine underutilization urges for epinephrine autoinjector stocking in schools and restaurants, patient education, and consistent policies across Canada.
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Anafilaxia , Adolescente , Alérgenos , Anafilaxia/tratamiento farmacológico , Anafilaxia/epidemiología , Anafilaxia/etiología , Niño , Preescolar , Servicio de Urgencia en Hospital , Epinefrina/uso terapéutico , Humanos , Lactante , Recién Nacido , Nueces , OntarioRESUMEN
BACKGROUND: There is a lack of data on seafood-induced anaphylaxis in children in Canada. OBJECTIVE: To evaluate the rate, clinical features, and management of seafood-induced anaphylaxis in children presenting to emergency departments across Canada. METHODS: Children with anaphylaxis were recruited at 6 emergency departments between 2011 and 2020 as part of the Cross-Canada Anaphylaxis REgistry. A standardized form documenting symptoms, triggers, comorbidities, and management was used to collect data. RESULTS: There were 75 fish-induced and 71 shellfish-induced cases of suspected anaphylaxis, most of which were caused by salmon and shrimp, respectively. Mucocutaneous symptoms were most common, whereas respiratory symptoms were associated with patients with fish-induced reactions who have comorbid asthma (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.02-1.36). Prehospital epinephrine was underused (<35%), whereas in-hospital epinephrine was given to less than 60% of the patients. Among those with a known fish or shellfish allergy, prehospital epinephrine use was associated with known asthma (aOR 1.39 [95% CI, 1.05-1.84] and aOR 1.25 [95% CI, 1.02-1.54], respectively). Among children who were assessed by either skin test or specific immunoglobulin E, 36 patients (76.6%) with suspected fish-induced anaphylaxis and 19 patients (51.4%) with suspected shellfish-induced anaphylaxis tested positive. CONCLUSION: Prehospital epinephrine is underused in the management of seafood-induced anaphylaxis. Among children with known seafood allergy, prehospital epinephrine use is more likely if there is a known asthma comorbidity.
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Anafilaxia , Asma , Hipersensibilidad a los Alimentos , Anafilaxia/diagnóstico , Anafilaxia/tratamiento farmacológico , Anafilaxia/epidemiología , Animales , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/epidemiología , Canadá/epidemiología , Servicio de Urgencia en Hospital , Epinefrina/uso terapéutico , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/epidemiología , Humanos , Alimentos Marinos/efectos adversosRESUMEN
BACKGROUND: Hereditary angioedema (HAE) is associated with decreased quality of life (QoL), which has typically been measured using a generic non-disease-specific questionnaire. OBJECTIVE: We aimed to assess the QoL in patients with HAE type I and II in Canada using a previously validated HAE-specific questionnaire. METHODS: An online questionnaire was sent to the members of two Canadian HAE patient groups to collect data on demographics, HAE clinical course, and QoL scores. All patients 18 years of age or older with HAE type I or II were eligible. The impact of the available clinical factors on the QoL scores was evaluated. Multiple linear regression was performed using clinically relevant factors to predict HAE QoL outcome. RESULTS: Among the 72 patients in the study, the mean total HAE QoL score was 102 (±23) (SD) on a scale of 25 to 135, with higher scores indicating better QoL. Although the total QoL scores correlated positively with patients' level of satisfaction and perceived control (P < .001 for both), it correlated negatively with the number of acute attacks (P = .03). Yet, the types of treatment did not have an impact on the QoL. Predictors, including sex, comorbidities, and the number of attacks, only explained 12% of the variance in the total QoL scores. CONCLUSION: HAE continues to impair QoL in Canadian patients despite receiving recommended treatment. Although the frequency of attacks affects QoL, patients' experience with their HAE care also affects QoL substantially. The study highlights the importance of considering patients' experience with their HAE care as physicians develop an appropriate management plan.
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Angioedemas Hereditarios/fisiopatología , Adulto , Canadá , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y CuestionariosRESUMEN
Bacterial urinary tract infections (UTIs) are one of the most common reasons for children to be admitted to hospital. Bacteria infect and invade the bladder (the lower urinary tract) and if the infection disseminates to the upper urinary tract, significant inflammation in the kidneys may arise. Inflammation is a double-edged sword: it is needed to clear bacteria, but if excessive, kidney tissue is injured. During injury, nephrons are destroyed and replaced with deposition of extracellular matrix and a renal scar. In this review, we explore the pathogenesis of UTIs and discuss the risk factors that result in dissemination of bladder infection to the kidneys. Three major risk factors predispose to kidney infections: the presence of vesicoureteric reflux, the presence of bladder and bowel dysfunction, and defects in the ability of the host immune response to clear bacteria. In this review, we will discuss these factors, their relationship to renal scarring, and potential treatments that might be beneficial to prevent renal scar formation in children.
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Cicatriz/inmunología , Riñón/patología , Pielonefritis/inmunología , Reflujo Vesicoureteral/complicaciones , Inmunidad Adaptativa , Animales , Antibacterianos/uso terapéutico , Niño , Cicatriz/epidemiología , Cicatriz/patología , Cicatriz/prevención & control , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Modelos Animales de Enfermedad , Quimioterapia Combinada/métodos , Glucocorticoides/uso terapéutico , Humanos , Riñón/inmunología , Riñón/microbiología , Inhibidores de la Metaloproteinasa de la Matriz/uso terapéutico , Pielonefritis/tratamiento farmacológico , Pielonefritis/epidemiología , Pielonefritis/microbiología , Factores de Riesgo , Vejiga Urinaria/inmunología , Vejiga Urinaria/microbiología , Reflujo Vesicoureteral/inmunologíaRESUMEN
Kiwifruit is rich in bioactive components including dietary fibers, carbohydrates, natural sugars, vitamins, minerals, omega-3 fatty acids, and antioxidants. These components are beneficial to boost the human immune system and prevent cancer and heart diseases. However, kiwifruit is emerging as one of the most common elicitors of food allergies worldwide. Kiwifruit allergy results from an abnormal immune response to kiwifruit proteins and occur after consuming this fruit. Symptoms range from the oral allergy syndrome (OAS) to the life-threatening anaphylaxis. Thirteen different allergens have been identified in green kiwifruit and, among these allergens, Act d 1, Act d 2, Act d 8, Act d 11, and Act d 12 are defined as the "major allergens." Act d 1 and Act d 2 are ripening-related allergens and are found in abundance in fully ripe kiwifruit. Structures of several kiwifruit allergens may be altered under high temperatures or strong acidic conditions. This review discusses the pathogenesis, clinical features, and diagnosis of kiwifruit allergy and evaluates food processing methods including thermal, ultrasound, and chemical processing which may be used to reduce the allergenicity of kiwifruit. Management and medical treatments for kiwifruit allergy are also summarized.
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PURPOSE: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and clinical manifestations such as infections, autoimmunity, and malignancy. We sought to determine if responsiveness to interleukin-21 (IL-21), a key cytokine for B cell differentiation, correlates with distinct clinical phenotypes in CVID. METHODS: CVID subjects were recruited through the Canadian Primary Immunodeficiency Evaluative Survey registry. Peripheral blood mononuclear cells were cultured with anti-CD40 ± interferon-gamma, interleukin-4 (IL-4), IL-21, and/or IL-4+IL-21. B cell subpopulations and IgG production were determined at baseline and day 7 by flow cytometry and ELISA. Clinical complications were compared using contingency tables. RESULTS: CVID subjects exhibited decreased CD27+ B cells and IgG production after 7 days of stimulation with anti-CD40+IL-21 (p < 0.05). In a subset of subjects [CVID responders (R)], the addition of IL-4 led to significant increases in CD27+ B cells and IgG (p < 0.05). In CVID non-responders (NR), CD27+ B cells and IgG remained lower despite the addition of IL-4. CVID NR experienced significantly more non-infectious clinical complications of CVID than R [OR 8.8, 95% confidence interval (CI) 1.6 to 48.13]. Previous studies reported that CVID subjects with ≤ 2% class-switched memory B cells were more at risk of these complications, but no significant association was found among this cohort of subjects [OR 3.5, CI 0.9 to 13.3]. In fact, 34.6% of CVID NR had > 2% class-switched memory B cells at baseline. CONCLUSIONS: The IL-4 and IL-21 in vitro assays distinguish two groups of CVID subjects and can be used with baseline B cell subpopulation phenotyping to better identify patients experiencing more vs. fewer clinical non-infectious complications and potentially to modulate therapy.
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Subgrupos de Linfocitos B/inmunología , Linfocitos B/inmunología , Inmunodeficiencia Variable Común/diagnóstico , Interleucina-4/metabolismo , Interleucinas/metabolismo , Adulto , Células Cultivadas , Inmunodeficiencia Variable Común/inmunología , Diagnóstico Diferencial , Femenino , Humanos , Inmunoglobulina G/metabolismo , Memoria Inmunológica , Inmunofenotipificación , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Transducción de Señal , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismoRESUMEN
PURPOSE: Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. The latter is often characterized by the susceptibility to recurrent Candida infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF STAT1 mutations in a large international cohort of CMC patients. METHODS: STAT1 was sequenced in genomic DNA from 57 CMC patients and 35 healthy family members. The functional relevance of nine different STAT1 variants was shown by flow cytometric analysis of STAT1 phosphorylation in patients' peripheral blood cells (PBMC) after stimulation with interferon (IFN)-α, IFN-γ or interleukin-27 respectively. Extended clinical data sets were collected and summarized for 26 patients. RESULTS: Heterozygous mutations within STAT1 were identified in 35 of 57 CMC patients (61%). Out of 39 familial cases from 11 families, 26 patients (67%) from 9 families and out of 18 sporadic cases, 9 patients (50%) were shown to have heterozygous mutations within STAT1. Thirteen distinct STAT1 mutations are reported in this paper. Eight of these mutations are known to cause CMC (p.M202V, p.A267V, p.R274W, p.R274Q, p.T385M, p.K388E, p.N397D, and p.F404Y). However, five STAT1 variants (p.F172L, p.Y287D, p.P293S, p.T385K and p.S466R) have not been reported before in CMC patients. CONCLUSION: STAT1 mutations are frequently observed in patients suffering from CMC. Thus, sequence analysis of STAT1 in CMC patients is advised. Measurement of IFN- or IL-induced STAT1 phosphorylation in PBMC provides a fast and reliable diagnostic tool and should be carried out in addition to genetic testing.
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Candidiasis Mucocutánea Crónica/diagnóstico , Síndromes de Inmunodeficiencia/diagnóstico , Leucocitos Mononucleares/inmunología , Mutación/genética , Factor de Transcripción STAT1/metabolismo , Adulto , Candidiasis Mucocutánea Crónica/genética , Células Cultivadas , Citocinas/metabolismo , Análisis Mutacional de ADN , Femenino , Humanos , Síndromes de Inmunodeficiencia/genética , Masculino , Linaje , Fenotipo , Estructura Terciaria de Proteína/genética , Factor de Transcripción STAT1/genéticaAsunto(s)
Anafilaxia/inmunología , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/inmunología , Adolescente , Anafilaxia/sangre , Niño , Preescolar , Progresión de la Enfermedad , Servicio de Urgencia en Hospital , Femenino , Hipersensibilidad a los Alimentos/sangre , Humanos , Inmunoglobulina E/sangre , Lactante , Masculino , Pruebas Cutáneas , Triptasas/sangreAsunto(s)
Trastornos Linfoproliferativos/genética , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria/genética , Adolescente , Resultado Fatal , Trasplante de Células Madre Hematopoyéticas , Humanos , Recién Nacido , Trastornos Linfoproliferativos/terapia , Masculino , Mutación , FenotipoRESUMEN
UNLABELLED: IRAK-4 deficiency causes IL-1R and TLR signaling failure, resulting in minimal clinical features despite invasive bacterial infection. We report the course of a 7-year-old IRAK-4-deficient girl presenting in the first year with multiple occult Staphylococcus aureus lymphadenitis. She was managed with antibiotic prophylaxis (sulfa/trimethoprim/PenV, then - due to neutropenia - Cefprozil), pneumococcal vaccination (PCV-7, Pneumovax23, PCV-13) and vigilance. Pneumococcal-specific IgG levels were monitored. No bacterial infections occurred on prophylaxis for 6 years after initial presentation. IgG response to pneumococcal polysaccharide was satisfactory but short-lived, requiring frequent boosting. At age 7, patient developed a morning headache and vomited once. Cefprozil was administered and re-dosed. Over 12 h, she was fatigued without other symptoms. Low fever accompanied another emesis. A few hours later she was confused, and purpuric rash appeared. Emergency physicians diagnosed sepsis/meningitis and started vancomycin-ceftriaxone. Respiratory failure and cerebellar herniation occurred <24 h after first symptoms. Blood and CSF grew Streptococcus pneumoniae type 6C resistant to second-generation cephalosporins. The patient's latest PCV-13 vaccination was 6 weeks before death, which included serotype 6A. Immunoglobulins were normal except IgG4 was increased (3.4 g/L). IgG response to vaccine antigens was satisfactory. IgG to 6A is reported to cross-react with 6C, but this was not the case here. CONCLUSION: Despite antibiotic prophylaxis and repeated vaccination, even older IRAK-4-deficient patients are at high risk of rapidly fatal infection due to emergence of antibiotic resistance. These patients need early assessment at any age, bacterial culturing, alternative empiric antibiotic therapy and close observation when even vaguely unwell. Based on increasingly recognized immunological and/or clinical impairments in B cell function, and possibly other defects, long-term IgG prophylaxis in addition to antibiotics is recommended.
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Profilaxis Antibiótica , Inmunoglobulina G/inmunología , Síndromes de Inmunodeficiencia/inmunología , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/etiología , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Niño , Resultado Fatal , Femenino , Humanos , Quinasas Asociadas a Receptores de Interleucina-1/inmunología , Enfermedades de Inmunodeficiencia PrimariaRESUMEN
BACKGROUND: Cephalosporins, ß-lactam antibiotics, commonly cause allergic reactions. OBJECTIVE: To assess the clinical characteristics and management of pediatric patients with suspected cephalosporin allergy using direct graded oral challenges (GOCs). METHODS: Children referred for suspected cephalosporin allergy at 4 Canadian clinics were recruited over 10 years. Data on demographics, clinical reaction characteristics, and management were collected through a questionnaire. Patients underwent a direct GOC (initially 10% of the treatment dose, then 90% after 20 min), and reactions were monitored 1 week postchallenge. Families were contacted annually for up to 5 years to detect subsequent antibiotic reactions. Logistic regression analysis identified factors associated with positive GOC reactions. RESULTS: Among the 136 patients reporting cephalosporin allergy, 75 (55.1%) were males with a median age of 3.9 years (interquartile range 2.3-8.7). Cefprozil represented the most common cephalosporin linked to the index reaction (67.6% of cases). Of the 136 direct GOCs, 5.1% had an immediate and 4.4% a nonimmediate reaction, respectively. Positive GOCs conducted in children with a history of skin-limited nonsevere rashes were classified as mild, benign skin rashes. Positive GOCs were more likely in children with food allergies (adjusted odds ratio 1.14; 95% confidence interval [95% CI] 1.00-1.29). CONCLUSIONS: Direct GOCs are safe and effective for diagnosing pediatric cases that report nonvesicular skin-limited symptoms while being treated with cephalosporins.
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Hipersensibilidad a las Drogas , Hipersensibilidad , Masculino , Humanos , Niño , Preescolar , Femenino , Cefalosporinas/efectos adversos , Pruebas Cutáneas/efectos adversos , Canadá/epidemiología , Antibacterianos/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/etiología , Monobactamas , Hipersensibilidad/complicaciones , Penicilinas/efectos adversosRESUMEN
BACKGROUND: Food allergies, particularly peanut, represent the predominant cause of anaphylaxis. Whereas early allergen introduction has emerged as a potential preventive strategy, the precise impact of recent guidelines on peanut-induced anaphylaxis rates in Canada remains unclear. OBJECTIVE: To assess the impact of the 2017 Addendum Guidelines for the Prevention of Peanut Allergy on peanut-induced anaphylaxis rates in Canada. METHODS: Using a comprehensive longitudinal registry capturing pediatric anaphylaxis presentations to the Montreal's Children's Hospital, we compared children with and without known peanut allergy who presented with peanut-induced anaphylaxis between 2011 and 2019 inclusive, excluding data beyond 2019 owing to the Coronavirus disease 2019 (COVID-19) pandemic. We calculated rates of peanut-induced anaphylaxis presentations per 100,000 age-adjusted all-cause emergency department visits using 4-month intervals. Interrupted time series analysis was used to compare anaphylaxis rate trends before and after 2017 for children ages 0 to 2 and 3 to 17 years. RESULTS: We examined 2,011 cases of pediatric anaphylaxis, including 429 (21%) triggered by peanuts. Compared with pre-guideline estimates, the yearly rate of change of peanut anaphylaxis rates decreased by 7.96 (95% confidence interval -14.57 to -1.36; P = .018) after 2017 among patients with new-onset anaphylaxis in children 2 years of age or younger (n = 109). No significant changes were identified for older patients ages 3 to 17, or in patients with known peanut allergy. CONCLUSIONS: Early introduction guidelines in Canada are associated with a reduced risk of new-onset peanut-induced anaphylaxis in young children within a single center in Montreal. Further research is required to assess the impact on a wider population and other food allergens.
RESUMEN
BACKGROUND: Oral immunotherapy (OIT) has emerged as the most popular therapy for food allergy. However, data on the long-term adherence and efficacy of this approach are sparse. OBJECTIVE: We aimed to assess the long-term adherence rates to OIT protocol and the associated risk of allergic reactions. METHODS: Patients who completed milk OIT and reached a maintenance dose of 200 mL of milk were surveyed biannually on their dairy consumption and occurrence of allergic reactions. A survival analysis was performed to evaluate the association between the risk of reaction and the adherence to OIT maintenance protocol. RESULTS: The cohort consisted of 50 patients. Only 56% of the cohort adhered to the protocol, which consisted of ingesting a minimum of 200 mL of milk at least 3 times per week. Adherent patients had a significantly reduced risk of allergic reactions as well as a reduced incidence of anaphylaxis, health care/emergency room visits, and epinephrine/antihistamine administration. CONCLUSIONS: The findings demonstrate the importance of consistent maintenance dose consumption in the management of food allergies, with regular milk consumption contributing to the maintenance of unresponsiveness and decreased risk of allergic symptoms.
RESUMEN
We report a family with autosomal dominant chronic mucocutaneous candidiasis as well as recurrent viral infections that segregate with a novel signal transducer and activator of transcription 1 (STAT1) mutation. Prophylactic treatment with fluconazole and immunoglobulin replacement has been initiated, with good clinical response.