Oral immunotherapy is an emerging experimental treatment for peanut allergy, but its benefits and harms are unclear. We systematically reviewed the efficacy and safety of oral immunotherapy versus ...allergen avoidance or placebo (no oral immunotherapy) for peanut allergy.
In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, we searched MEDLINE, EMBASE, Cochrane Controlled Register of Trials, Latin American & Caribbean Health Sciences Literature, China National Knowledge Infrastructure, WHO's Clinical Trials Registry Platform, US Food and Drug Administration, and European Medicines Agency databases from inception to Dec 6, 2018, for randomised controlled trials comparing oral immunotherapy versus no oral immunotherapy for peanut allergy, without language restrictions. We screened studies, extracted data, and assessed risk of bias independently in duplicate. Main outcomes included anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life, meta-analysed by random effects. We assessed certainty (quality) of evidence by the GRADE approach. This study is registered with PROSPERO, number CRD42019117930.
12 trials (n=1041; median age across trials 8·7 years IQR 5·9–11·2) showed that oral immunotherapy versus no oral immunotherapy increased anaphylaxis risk (risk ratio RR 3·12 95% CI 1·76–5·55, I2=0%, risk difference RD 15·1%, high-certainty), anaphylaxis frequency (incidence rate ratio IRR 2·72 1·57–4·72, I2=0%, RD 12·2%, high-certainty), and epinephrine use (RR 2·21 1·27–3·83, I2=0%, RD 4·5%, high-certainty) similarly during build-up and maintenance (pinteraction=0·92). Oral immunotherapy increased serious adverse events (RR 1·92 1·00–3·66, I2=0%, RD 5·7%, moderate-certainty), and non-anaphylactic reactions (vomiting: RR 1·79 95%CI 1·35–2·38, I2=0%, high-certainty; angioedema: 2·25 1·13–4·47, I2=0%, high-certainty; upper tract respiratory reactions: 1·36 1·02–1·81, I2=0%, moderate-certainty; lower tract respiratory reactions: 1·55 0·96–2·50, I2=28%, moderate-certainty). Passing a supervised challenge, a surrogate for preventing out-of-clinic reactions, was more likely with oral immunotherapy (RR 12·42 95% CI 6·82–22·61, I2=0%, RD 36·5%, high-certainty). Quality of life was not different between groups (combined parents and self report RR 1·21 0·87–1·69, I2=0%, RD 0·03%, low-certainty). Findings were robust to IRR, trial sequential, subgroup, and sensitivity analyses.
In patients with peanut allergy, high-certainty evidence shows that available peanut oral immunotherapy regimens considerably increase allergic and anaphylactic reactions over avoidance or placebo, despite effectively inducing desensitisation. Safer peanut allergy treatment approaches and rigorous randomised controlled trials that evaluate patient-important outcomes are needed.
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Despite the increasing number of cases of secondary antibody deficiency (SAD) and immunoglobulin (Ig) utilization, there is a paucity of data in the literature on clinical and patient-reported ...outcomes in this population. To describe immunoglobulin utilization patterns, clinical and patient-reported outcomes in patients with SAD on immunoglobulin replacement therapy (IgRT). A cross-sectional study of patients with secondary antibody deficiency enrolled in the Ontario Immunoglobulin Treatment (ONIT) Case Registry from June 2020 to September 2022 was completed. Demographics, comorbidities, indications for immunoglobulin treatment, clinical infections at baseline and post IgRT, and patient-reported outcomes were collected and analyzed. There were 140 patients (58 males; 82 females; median age 68) with SAD during the study period; 131 were on subcutaneous Ig (SCIG) and 9 were on intravenous Ig (IVIG). The most common indication was chronic lymphocytic leukemia (CLL) (N = 52). IgRT reduced the average annual number of infections by 82.6%, emergency room (ER) visits by 84.6%, and hospitalizations by 83.3%. Overall, 84.6% of patients reported their health as better compared to before IgRT. Among those patients who switched from IVIG to SCIG (N = 35), 33.3% reported their health as the same, and 62.9% reported their health as better. This study demonstrates that IgRT significantly improved clinical outcomes and patient-reported general health state in patients with SAD. This study also further supports the use of SCIG in patients with SAD.
Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially life-threatening hypersensitivity reaction to medication. While a relatively rare phenomenon, early ...identification and discontinuation of the offending agent is pivotal to patient management. To our knowledge this is the first reported case of probable atorvastatin induced DRESS syndrome without rash. Case presentation An adult female presented with 4 days of persistent fevers, abdominal and flank pain, malaise, and generalized muscle weakness without any cutaneous reaction following 20 days of therapy with atorvastatin. She was febrile (38.5 degreesC), at presentation with a heart rate of 72, and blood pressure of 93/51 mmHg. Her laboratory investigations at their peak demonstrated an Alkaline Phosphatase (ALP) of 792 U/L, Alanine aminotransferase (ALT) of 265 U/L, gamma glutamyl transferase (GGT) of 236 U/L, total bilirubin at 21 mg/dL, eosinophils 3100 cells/microL, leukocytes 20.2 K/microL, hemoglobin of 12.5 gm/dL. During her admission she had normal creatinine and troponin. Her serology for Hepatitis A, B and C were negative. Cytomegalovirus, Epstein-Barr viral serologies were negative. Antinuclear Antibody (ANA), rheumatoid factor, anti-neutrophil cytoplasmic antibody (ANCA), mitochondrial antibody, and smooth muscle antibody were negative. The patient was initially diagnosed as having pyelonephritis due to nonspecific bilateral flank pain but given ongoing fevers and lack of clinical and laboratory improvement with antibiotics, a diagnosis of atorvastatin induced DRESS syndrome was considered probable, and atorvastatin was discontinued. The patients' clinical status improved gradually without any further therapy and her liver enzymes and eosinophils normalized over the course of a month. Conclusion In patients who present with systemic organ involvement and eosinophilia, even without cutaneous manifestations, clinicians should apply the RegiSCAR criteria for DRESS syndrome. This can then help guide treatment with discontinuation of offending agent, or treatment with systemic corticosteroids.
Serum-sickness like reactions (SSLRs) to amoxicillin have been documented in the medical literature. Beta-lactams are important and commonly used medications especially in the pediatric population. ...Often, SSLRs present within days of and during first exposure/ingestion to the offending agent. We described a unique case of a 4-year-old boy who presented with symptoms of amoxicillin SSLR following his second course of amoxicillin with only 2 months and 10 days between his second and first course.
A 4-year-old boy presented to hospital with a pruritic rash on day 7 of a 10-day course of amoxicillin for otitis media accompanied by fever (38.7 degrees Celsius). On day 7 of his second course of amoxicillin, which was separated from his first course by only 2 months and 10 days, his mother noticed erythematous, raised, pruritic lesions with central clearing on his sternum. He presented to the ED with emesis, progression of the rash to his torso, back, legs, and face, hypotension, angioedema, and joint pain. His bloodwork demonstrated a leukocytosis of 18.6 × 10
g/L with neutrophilic predominance and thrombocytosis with a platelet count of 653 × 10
g/L. He was treated with 5 mg oral cetirizine daily and 1 mg/kg oral prednisone which improved his rash and angioedema. He was managed with up to 4 times the usual dose of cetirizine. He was assessed in our outpatient clinic as an outpatient and penicillin skin testing was unremarkable. A diagnosis of a probable SSLR to amoxicillin was made.
We report an unusual presentation of SSLR following re-exposure to amoxicillin. Our case highlights that patients with previous asymptomatic exposure to amoxicillin can develop SSLR with repeat exposure. Although it is not uncommon for children to develop amoxicillin SSLRs after previous exposure to the drug, this case is unique because of its short time course of 2 months and 10 days months between drug courses. Penicillins are commonly used in the pediatric population. Therefore, it is important to correctly characterize adverse drug reactions to broaden our understanding of SSLRs, prevent unnecessary avoidance of the triggering agent, and improve patient management.
Food allergy is defined as an adverse immunologic response to a food protein. Food-related reactions are associated with a broad range of signs and symptoms that may involve any body system, ...including the skin, gastrointestinal and respiratory tracts, and cardiovascular system. Immunoglobulin E (IgE)-mediated food allergy is a leading cause of anaphylaxis and, therefore, referral to an allergist for timely and appropriate diagnosis and treatment is imperative. Diagnosis entails a careful history and diagnostic tests, such as skin prick tests, serum-specific IgE and, if indicated, an oral food challenge. Once the diagnosis of food allergy is confirmed, strict elimination of the offending food allergen from the diet is generally necessary; however, in the case of cow's milk and egg allergy, many allergic children are able to eat these foods in their baked form. This article provides an overview of the epidemiology, pathophysiology, diagnosis, and management of IgE-mediated food allergy.
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.
Background Allergen exposure at lung and gut mucosae can lead to aberrant TH 2 immunity and allergic disease. The epithelium-associated cytokines thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 ...are suggested to be important for the initiation of these responses. Objective We sought to investigate the contributions of TSLP, IL-25, and IL-33 in the development of allergic disease to the common allergens house dust mite (HDM) or peanut. Methods Neutralizing antibodies or mice deficient in TSLP, IL-25, or IL-33 signaling were exposed to HDM intranasally or peanut intragastrically, and immune inflammatory and physiologic responses were evaluated. In vitro assays were performed to examine specific dendritic cell (DC) functions. Results We showed that experimental HDM-induced allergic asthma and food allergy and anaphylaxis to peanut were associated with TSLP production but developed independently of TSLP, likely because these allergens functionally mimicked TSLP inhibition of IL-12 production and induction of OX40 ligand (OX40L) on DCs. Blockade of OX40L significantly lessened allergic responses to HDM or peanut. Although IL-25 and IL-33 induced OX40L on DCs in vitro , only IL-33 signaling was necessary for intact allergic immunity, likely because of its superior ability to induce DC OX40L and expand innate lymphoid cells in vivo. Conclusion These data identify a nonredundant, IL-33–driven mechanism initiating TH 2 responses to the clinically relevant allergens HDM and peanut. Our findings, along with those in infectious and transgenic/surrogate allergen systems, favor a paradigm whereby multiple molecular pathways can initiate TH 2 immunity, which has implications for the conceptualization and manipulation of these responses in health and disease.
Prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20-30% in those with an allergic first-degree relative. Intestinal ...microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.
The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy.
We identified the most relevant clinical questions and performed a systematic review of randomized controlled trials of probiotics for the prevention of allergy. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. We searched for and reviewed the evidence about health effects, patient values and preferences, and resource use (up to November 2014). We followed the GRADE evidence-to-decision framework to develop recommendations.
Currently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the WAO guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema. The WAO guideline panel suggests: a) using probiotics in pregnant women at high risk for having an allergic child; b) using probiotics in women who breastfeed infants at high risk of developing allergy; and c) using probiotics in infants at high risk of developing allergy. All recommendations are conditional and supported by very low quality evidence.
WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding, and whether to give them to infants.
This is an update to the 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of hereditary angioedema (HAE) patients worldwide. It is a collaboration of ...Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, using the GRADE system, for the management of patients with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. New to the 2019 version of this guideline are sections covering the diagnosis and recommended therapies for acute treatment in HAE patients with normal C1-INH, as well as sections on pregnant and paediatric patients, patient associations and an HAE registry. Hereditary angioedema results in random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased health-related quality of life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada, as in many countries, continues to be neither optimal nor uniform. It lags behind some other countries where there are more organized models for HAE management, and greater availability of additional licensed therapeutic options. It is anticipated that providing this guideline to caregivers, policy makers, patients, and advocates will not only optimize the management of HAE, but also promote the importance of individualized care. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency and intensive care physicians, primary care physicians, gastroenterologists, dentists, otolaryngologists, paediatricians, and gynaecologists who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.
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