COVID-19 Immunologic Antiviral Therapy With Omalizumab (CIAO)-a Randomized Controlled Clinical Trial.

Background: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties. Objective: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. Methods: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization. Results: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events. Conclusions: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.

Safety of COVID-19 mRNA vaccination and effects of SARS-CoV-2 infection in children and adults with mast cell disorders.

Mastocytosis is characterized by abnormal clonal mast cell proliferation. Given the paucity of data in patients with mastocytosis, it is crucial to assess the safety of COVID-19 vaccines in this population. We aimed to assess the risk of allergic reactions and the effect of COVID-19 infection among patients with mastocytosis. Participants were recruited from Canada and Israel between December 2021 and May 2022. Consenting participants were administered standardized questionnaires querying whether they were infected with COVID-19, if they received the first and second dose vaccines, and post-vaccination side effects including allergic reactions (urticaria/angioedema, current rash flaring, need for updosing medications, or respiratory symptoms) and common side effects including injection site reaction (ISR) and flu-like symptoms. Forty participants with mastocytosis were administered a standardized questionnaire (median age = 9, 59% male). Amongst all participants, 16 (39%) reported COVID-19 infection and most (75%) reported flu-like symptoms, 3 (19%) were asymptomatic, 1 suffered from shortness of breath/chest pain and 1 from facial flushing. Of the 25 participants who were eligible for vaccination (≥ 5 years old), 80% received a first-dose vaccine and 68% received a second-dose vaccine. Of those who received the first-dose vaccine, most (60%) remained asymptomatic, 20% developed flu-like symptoms, 20% had an ISR, and 1 patient had an allergic reaction (urticaria and swelling). Of those who received the second-dose vaccine, most (53%) were asymptomatic, and 1 had an allergic reaction. No significant difference was found between side effects of both vaccine doses. No reactions fulfilled the criteria for anaphylaxis in either dose. This study reveals that among patients with mastocytosis, COVID-19 vaccine and infection were well-tolerated in the majority of cases.

Food Allergy Education and Management in Early Learning and Childcare Centres: A Scoping Review on Current Practices and Gaps.

Anaphylaxis has occurred in preschools/schools yet there are no consistent food allergy (FA) management practices in early learning and childcare centres (ELCC) across jurisdictions. Presently, there are no reviews that have synthesized FA-related knowledge and management practices within ELCC. We aimed to perform a scoping review of FA management in ELCC, and report on perceived gaps or barriers. A PRISMA-ScR-guided search was conducted for North American, European and Australian articles in English/French in the OVID-MedLine, Scopus, and PsycInfo databases. Two independent reviewers screened the titles/abstracts of 2010 articles and full-text screened 77 articles; 15 of which were specifically related to ELCC. If the two reviewers could not agree to the relevance of a given study, a third reviewer provided guidance. This third reviewer also screened French articles. Thematic and descriptive reports of the studies were presented. We reported solely on pre-Coronavirus Disease pandemic ELCC studies. We included ten articles in this review, which provide evidence that ELCC staff have variable baseline knowledge, comprehension, experience, and practices in place to manage FA. ELCC staff also have limited FA-related training and experience regarding administration of epinephrine auto-injectors (EAI). Emergency Anaphylaxis Plans (EAP) were described in four studies. One study reported the parental influence on the site's food purchasing and FA management. Three studies provided educational interventions, which demonstrated increased and sustained FA-related knowledge and confidence post-intervention. Participants deemed the training beneficial and desired annual training and more FA resources to be available. Across jurisdictions, ELCC staff have provided care and administered EAI in emergencies, but training remained variable. Communication and care planning amongst ELCC staff, and parents, is crucial. Annual education, available EAI and EAPs are tools necessary for effectively managing emergencies.

Bridging Knowledge Gaps in Anaphylaxis Management Through a Video-Based Educational Tool.

Introduction: We aimed to develop and test the effectiveness of an education tool to help pediatric patients and their families better understand anaphylaxis and its management, and to improve current knowledge and treatment guidelines adherence. Methods: From June 2019 to May 2022, 128 pediatric patients with history of food-triggered anaphylaxis who presented to the allergy outpatient clinics at the study institution were recruited. Consenting families were asked to complete 6 questions related to the triggers, recognition, and management of anaphylaxis at the time of presentation to the clinic. Participants were shown a 5-min animated video on the causes, presentation, and management of anaphylaxis. At the end of the video, the participants were redirected to the same 6 questions to respond again. The scores were recorded in proportion of correct answers (minimum 0.0; maximum 1.0). Results: The mean age of the patients was 5.8 ± 4.5 years (range: 0.5-18.8 years). The majority were males (70 patients; 54.7%). The mean baseline prevideo education questionnaire score was 0.76 ± 0.2 (range: 0.3-1.0), whereas the mean follow-up score was 0.82 ± 0.2 (range: 0.3-1.0). This score difference of 0.06 was statistically significant (P < 0.001). There were no significant associations between change in scores and age or gender of the participants. Conclusion: Our video teaching method was successful in educating patients and their families to better understand anaphylaxis and its management at the moment of the clinical encounter. Retention of knowledge at long-term follow-up should be assessed.

Urticaria and angioedema in children and adolescents: diagnostic challenge.

Urticaria diagnosis may be challenging in children since it can be triggered or related to numerous conditions. In this paper, we reviewed the main aspects regarding the diagnosis of urticaria in the pediatric population. Acute urticaria is often due to viral infections. However, other culprits, including foods, insect stings, drugs, contrast media, vaccination, latex, and medical diseases, may account for acute patterns. Laboratory tests and confirmatory allergy tests should be individualized and guided by history. Chronic urticaria (CU) is defined when hives and/or angioedema last for more than 6 weeks. The most common type of chronic urticaria in children is chronic spontaneous urticaria (CSU). Chronic inducible urticaria (CindU) is less common but is important to diagnose in order to manage appropriately and reduce the risk of severe reactions. Inducible forms in children are often diagnosed with specific provocation tests similar to the tests used in adults. Given that chronic urticaria could rarely be a presentation of vasculitis, systemic-onset juvenile idiopathic arthritis, or auto-inflammatory syndromes, it is important to rule out these conditions. It is crucial to differentiate cases of chronic urticaria from mastocytosis and Bradykinin-mediated angioedema, given that treatment may differ. The management of chronic urticaria in children has improved over the last decade because of the development of both clear management guidelines and new effective drugs. It is crucial to increase awareness for appropriate diagnosis and new available treatment to improve the management of chronic urticaria in children.

Omalizumab for the Treatment of Bullous Pemphigoid: A Systematic Review of Efficacy and Safety.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease. Current treatment strategies are limited by their efficacy and/or side effect profile and the need for safer and effective alternatives is undeniable. We aimed to conduct a systematic review focusing on the efficacy and safety of omalizumab in BP patients. Embase, PubMed, Cochrane, and clinicaltrials.gov were searched for English and French articles published from inception to July 1, 2021, using search terms "omalizumab" OR "Xolair" OR "IGE025" OR "olizumab" AND "bullous pemphigoid." Screening and data extraction was performed by two raters independently. The primary outcome was complete response (CR), and secondary outcomes were partial response (PR), flare-ups, adverse events/vital status. In total, 22 articles were included, with a total of 56 patients. All patients had a refractory BP with mean disease duration of 13.5 ± 20.2 months (Standard Deviation (SD)) and failed 3.1 ± 1.6 therapies and many remained corticosteroids dependent. Overall, 87.5% of patients responded to treatment (55.4% CR and 32.1% PR), 7.1% discontinued the protocol and only 5.4% were non responders. A third of patients were able to discontinue all other therapies and most others were able to discontinue or taper systemic corticosteroids to <10 mg daily. Flare-ups occurred in 57.7% of patients upon discontinuation of omalizumab and/or steroid tapering, most patients recaptured response thereafter. Omalizumab was well tolerated by most patients. Omalizumab appears to be a promising treatment for BP with a good response rate and safety profile. However, several limitations were identified in current literature, and highlight the need for randomized controlled trials of omalizumab in BP.

Plerixafor on a WHIM - Promise or Fantasy of a New CXCR4 Inhibitor for This Rare, but Important Syndrome?

Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) is a primary immunodeficiency syndrome. Patients with WHIM syndrome are more susceptible to human papillomavirus (HPV) infections and commonly present to a dermatologist with recalcitrant to treatment warts. Other cardinal features of WHIM syndrome include recurrent sinopulmonary bacterial infections, neutropenia/lymphopenia, low levels of immunoglobulins (IgG, IgA, IgM) and myelokathexis. Research demonstrated that truncating gain-of-function mutations of the C-X-C chemokine receptor type 4 gene (CXCR4) are responsible for this disease. Plerixafor, a specific small molecule antagonist of CXCR4, is currently used for peripheral blood hematopoietic stem cell (HSC) mobilization in stem cell transplant recipients. It has recently shown promise for the treatment of WHIM syndrome in phase I/II clinical trials. In this paper we review the emerging patient clinical data for this medication and highlight the role of CXCR4 in other important skin diseases including keratinocyte carcinomas, psoriasis and cutaneous T-cell lymphoma.

Food Allergy Education and Management in Schools: A Scoping Review on Current Practices and Gaps.

Currently, no synthesis of in-school policies, practices and teachers and school staff's food allergy-related knowledge exists. We aimed to conduct a scoping review on in-school food allergy management, and perceived gaps or barriers in these systems. We conducted a PRISMA-ScR-guided search for eligible English or French language articles from North America, Europe, or Australia published in OVID-MedLine, Scopus, and PsycINFO databases. Two reviewers screened 2010 articles' titles/abstracts, with 77 full-text screened. Reviewers differed by language. Results were reported descriptively and thematically. We included 12 studies. Among teachers and school staff, food allergy experiences, training, and knowledge varied widely. Food allergy experience was reported in 10/12 studies (83.4%); 20.0-88.0% had received previous training (4/10 studies; 40.0%) and 43.0-72.2% never had training (2/10 studies; 20.0%). In-school policies including epinephrine auto-injector (EAI) and emergency anaphylaxis plans (EAP) were described in 5/12 studies (41.7%). Educational interventions (8/12 studies; 66.7%) increased participants' knowledge, attitudes, beliefs, and confidence to manage food allergy and anaphylaxis vs. baseline. Teachers and school staff have more food allergy-related experiences than training and knowledge to manage emergencies. Mandatory, standardized training including EAI use and evaluation, and the provision of available EAI and EAPs may increase school staff emergency preparedness.

Prominent Role of Type 2 Immunity in Skin Diseases: Beyond Atopic Dermatitis.

Type 2 immunity, illustrated by T helper 2 lymphocytes (Th2) and downstream cytokines (IL-4, IL-13, IL-31) as well as group 2 innate lymphoid cells (ILC2), is important in host defense and wound healing.1 The hallmark of type 2 inflammation is eosinophilia and/or high IgE counts and is best recognized in atopic diathesis. Persistent eosinophilia, such as seen in hypereosinophilic syndromes, leads to fibrosis and hence therapeutic Type 2 inhibition in fibrotic diseases is of high interest. Furthermore, as demonstrated in cutaneous T cell lymphoma, advanced disease is characterized by Th1 to Th2 switch allowing cancer progression and immunosuppression. Development of targeted monoclonal antibodies against IL-4Rα (eg, dupilumab) led to a paradigm shift for the treatment of atopic dermatitis (AD) and stimulated research to better understand the role of Type 2 inflammation in other skin conditions. In this review, we summarize up to date knowledge on the role of Type 2 inflammation in skin diseases other than AD and highlight whether the use of Type 2 targeted therapies has been documented or is being investigated in clinical trials. This manuscript reviews the role of Type 2 inflammation in dermatitis, neurodermatitis, IgE-mediated dermatoses (eg, bullous pemphigoid, chronic spontaneous urticaria), sclerodermoid conditions and skin neoplasms.

Successful Milk Oral Immunotherapy Promotes Generation of Casein-Specific CD137+ FOXP3+ Regulatory T Cells Detectable in Peripheral Blood.

Background: Oral immunotherapy (OIT) is an emerging treatment for cow's milk protein (CMP) allergy in children. The mechanisms driving tolerance following OIT are not well understood. Regulatory T cells (TREG) cells are key inhibitors of allergic responses and promoters of allergen-specific tolerance. In an exploratory study, we sought to detect induction of allergen-specific TREG in a cohort of subjects undergoing OIT. Methods: Pediatric patients with a history of allergic reaction to cow's milk and a positive Skin Pick Test (SPT) and/or CMP-specific IgE >0.35 kU, as well as a positive oral challenge to CMP underwent OIT with escalating doses of milk and were followed for up to 6 months. At specific milestones during the dose escalation and maintenance phases, casein-specific CD4+ T cells were expanded from patient blood by culturing unfractionated PBMCs with casein in vitro. The CD4+ T cell phenotypes were quantified by flow cytometry. Results: Our culture system induced activated casein-specific FOXP3+Helios+ TREG cells and FOXP3- TEFF cells, discriminated by expression of CD137 (4-1BB) and CD154 (CD40L) respectively. The frequency of casein-specific TREG cells increased significantly with escalating doses of milk during OIT while casein-specific TEFF cell frequencies remained constant. Moreover, expanded casein-specific TREG cells expressed higher levels of FOXP3 compared to polyclonal TREG cells, suggesting a more robust TREG phenotype. The induction of casein-specific TREG cells increased with successful CMP desensitization and correlated with increased frequencies of casein-specific Th1 cells among OIT subjects. The level of casein-specific TREG cells negatively correlated with the time required to reach the maintenance phase of desensitization. Conclusions: Overall, effective CMP-OIT successfully promoted the expansion of casein-specific, functionally-stable FOXP3+ TREG cells while mitigating Th2 responses in children receiving OIT. Our exploratory study proposes that an in vitro TREG response to casein may correlate with the time to reach maintenance in CMP-OIT.

The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Anaphylaxis to patent blue dye in a 17-year-old boy.

Patent blue V dye (PBV) is frequently used as a perioperative drug for lymphangiography, as well as a food additive. Hypersensitivity to PBV is poorly documented in adults and had not been previously described in children. The diagnosis of PBV allergy depends on corroboration of history consistent with an IgE-mediated reaction and confirmatory skin tests. We present in this paper a paediatric case of PBV anaphylaxis and of biphasic reaction that exemplifies the challenges involved in diagnosing and managing this rare but potentially life-threatening allergic reaction.

De-labeling of ß-lactam allergy reduces intraoperative time and optimizes choice in antibiotic prophylaxis.

BACKGROUND: Suspected penicillin allergic individuals receive suboptimal non-ß-lactams for intraoperative prophylaxis which may prolong operations and have negative clinical outcomes. We therefore studied if ß-lactam de-labeling optimized choice of prophylactic antibiotics and improved intraoperative time efficiency. METHODS: A multistep approach was used. It included a risk assessment tool by an allergist, ß-lactam skin testing and oral provocation. To determine the value of de-labeling, we appraised intraoperative antibiotic choices and correlated them with time to first incision. RESULTS: A total of 194 patients were evaluated preoperatively. Four patients were diagnosed ß-lactam allergic on skin testing. Of the remaining 190 skin test negative patients, 146 were ß-lactam challenged. Only 5% reacted and were considered ß-lactam allergic. Cefazolin became the perioperative antibiotic of choice for 77% of patients requiring antibiotic prophylaxis. Only 5 confirmed ß-lactam allergic patients received intraoperative vancomycin. Patients avoiding use of vancomycin saved an average of 22 minutes in operative time. Of the 44 patients not having a ß-lactam challenge, 36 received antibiotics and 18 (50%) of these were prescribed intraoperative cefazolin. CONCLUSION: Using this three step process, almost all of those claiming penicillin allergy were de-labeled. In most patients that were drug challenged, ß-lactam antibiotics became the perioperative drug of choice. In cases where oral challenge was not used in the assessment only 50% were given a ß-lactam. The reduced use of vancomycin minimized delays in initiation of incision time, thus improving operative efficiency. Ultimately, randomized controlled studies are required to objectively determine the effectiveness of this approach.

Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy.

BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. OBJECTIVE: We sought to investigate genetic susceptibility to PA. METHODS: Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations. RESULTS: An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA (P = 1.80 × 10-8), whereas SNPs associated with Src kinase-associated phosphoprotein 1 (SKAP1), matrix metallopeptidase 12 (MMP12)/MMP13, catenin α3 (CTNNA3), rho GTPase-activating protein 24 (ARHGAP24), angiopoietin 4 (ANGPT4), chromosome 11 open reading frame (C11orf30/EMSY), and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association (P ≤ 1.49 × 10-6). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, C11orf30, and EXOC4 were significant (P ≤ 1.49 × 10-6). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance (P = 7.50 × 10-11), whereas SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, and EXOC4 and additional C11orf30 SNPs were suggestive (P ≤ 1.49 × 10-6). Functional annotation indicated that SKAP1 regulates expression of CBX1, which colocalizes with the EMSY protein coded by C11orf30. CONCLUSION: This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.

Modulation of the Interleukin-21 Pathway with Interleukin-4 Distinguishes Common Variable Immunodeficiency Patients with More Non-infectious Clinical Complications.

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.

Evaluating Comorbidities, Natural History, and Predictors of Early Resolution in a Cohort of Children With Chronic Urticaria.

Importance: Chronic urticaria (CU) affects 0.1% to 0.3% of children. Most cases have no identifiable trigger and are classified as chronic spontaneous urticaria (CSU). At least half of patients with CSU may have an autoimmune etiology that can be determined in vitro using the basophil activation test (BAT). While 30% to 55% of CU cases resolve spontaneously within 5 years in adults, the natural history and predictors of resolution in children are not known. Objective: To assess the comorbidities, natural history of CU, and its subtypes in children and identify predictors of resolution. Design, Setting, and Participants: We followed a pediatric cohort with chronic urticaria that presented with hives lasting at least 6 weeks between 2013 and 2015 at a single tertiary care referral center. Exposures: Data were collected on disease activity, comorbidities, physical triggers, BAT results, complete blood cell count, C-reactive protein levels, thyroid-stimulating hormone levels, and thyroid peroxidase antibodies. Main Outcomes and Measures: We assessed the rate of resolution (defined as absence of hives for at least 1 year with no treatment) and the association with clinical and laboratory markers. Results: The cohort comprised 139 children younger than 18 years old. Thirty-one patients (20%) had inducible urticaria, most commonly cold induced. Six children had autoimmune comorbidity, such as thyroiditis and type 1 diabetes. Autoimmune disorders (24 patients [17%]) and CU (17 patients [12%]) were common in family members. Positive BAT results (CD63 levels > 1.8%) were found in 58% of patients. Patients with positive BAT results (CD63 level >1.8%) were twice as likely to resolve after 1 year compared with negative BAT results (hazard ratio [HR], 2.33; 95% CI, 1.08-5.05). In contrast, presence of basophils decreased the likelihood of resolution (HR, 0.40; 95% CI, 0.20-0.99). No correlation with age was found. Chronic urticaria resolved in 43 patients, with a rate of resolution of 10.3% per year. Levels of CD63 higher than 1.8% and absence of basophils were associated with earlier disease resolution. Conclusions and Relevance: Resolution rate in children with CU is low. The presence of certain biomarkers (positive BAT result and basophil count) may help to predict the likelihood of resolution.

Natural history and treatment of cutaneous and systemic mastocytosis.

INTRODUCTION: Mastocytosis, a heterogeneous group of disorders, is characterized by an abnormal increase in the number of mast cells that is limited to the skin (cutaneous mastocytosis), involving extracutaneous tissues (systemic mastocytosis), or presenting as solid tumours (mastocytoma and mast cell sarcoma). Recent studies estimate that 1 in 10,000 people are diagnosed with mastocytosis. Although prompt diagnosis and appropriate management are crucial, little is known about the natural history and currently there are no established management guidelines. We have conducted a systematic review to assess the natural history and management of different mastocytosis subtypes. METHODS: A systematic review and meta-analysis were conducted using the PubMed and Ovid database of studies published in English and French over the last fifteen years, from January 2001 to December 2016. Keywords 'Cutaneous mastocytosis', 'Systemic mastocytosis', 'pathophysiology', 'clinical course', 'prognosis', 'drug therapy', and 'therapy' were searched. Rate of complete resolution was subjected to pooled analysis for different mastocytosis subtypes. Meta-analysis was conducted using Stata version 12.0. RESULTS: We reviewed 634 papers, of which 5 were included in the analysis of resolution, and 138 were included in the assessment of management. Pooled estimate for rate of complete resolution varied depending on the mastocytosis subtype. In cutaneous mastocytosis, the complete resolution rate for mastocytoma was 10% per year (95% CI: 4.8%, 15.1%) while the rate for urticaria pigmentosa was 1.9% per year (95% CI: -0.5%, 4.3%). Diffuse cutaneous mastocytosis and systemic mastocytosis subtypes did not show evidence of complete resolution in the studies reviewed. Treatment of cutaneous and systemic mastocytosis is purely symptomatic with topical corticosteroids, antihistamines, omalizumab and imatinib being common choices. CONCLUSION: Rate of resolution of mastocytosis is only shown in urticaria pigmentosa and mastocytoma. Better management guidelines are required to improve the health of these patients.