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Concept: Anaphylaxis

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Mast cell activation syndrome (MCAS) is a condition with signs and symptoms involving the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems. It can be classified into primary, secondary, and idiopathic. Earlier proposed criteria for the diagnosis of MCAS included episodic symptoms consistent with mast cell mediator release affecting two or more organ systems with urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope or near syncope, tachycardia, wheezing, conjunctival injection, pruritus, and nasal stuffiness. Other criteria included a decrease in the frequency, severity, or resolution of symptoms with anti-mediator therapy including H(1) and H(2)histamine receptor antagonists, anti-leukotrienes, or mast cell stabilizers. Laboratory data that support the diagnosis include an increase of a validated urinary or serum marker of mast cell activation (MCA), namely the documentation of an increase of the marker above the patient’s baseline value during symptomatic periods on more than two occasions, or baseline serum tryptase levels that are persistently above 15 ng/ml, or documentation of an increase of the tryptase level above baseline value on one occasion. Less specific assays are 24-h urine histamine metabolites, PGD(2) (Prostaglandin D(2)) or its metabolite, 11-β-prostaglandin F(2) alpha. A recent global definition, criteria, and classification include typical clinical symptoms, a substantial transient increase in serum total tryptase level or an increase in other mast cell derived mediators, such as histamine or PGD2 or their urinary metabolites, and a response of clinical symptoms to agents that attenuate the production or activities of mast cell mediators.

Concepts: Immune system, Allergy, Mast cell, Symptom, Histamine, Receptor antagonist, Anaphylaxis, Tryptase

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Intramuscular epinephrine is the gold standard treatment for anaphylaxis. Intramuscular injection provides more rapid and higher plasma concentrations than subcutaneous routes. Given the increasing epidemic of obesity patients are at increased risk of subcutaneous delivery, we therefore assessed the depth of subcutaneous tissue in a population of patients with anaphlaxis. Patients already prescribed epinephrine autoinjectors (EAIs) for anaphylaxis were examined with ultrasound and measurements of skin-to-muscle depth (STMD) at anterolateral thigh and anterior thigh were performed. 28 patients (23 female, 5 male) with an age range of 18-75 took part in the study and in 68% the STMD was greater than EAI needle length (15.02mm) using the anterolateral thigh, the recommended administration site. The key predictors for increased STMD were female gender (p 0.0003) and a BMI > 30 (p 0.04). EAIs require longer needles to ensure intramuscular administration and ultrasound at point of prescription would aid needle length selection. This article is protected by copyright. All rights reserved.

Concepts: Male, Gender, Epinephrine, Route of administration, All rights reserved, Anaphylaxis, Copyright, Hypodermic needle

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Mast cells have gained notoriety based on their detrimental contributions to IgE-mediated allergic disorders. Although mast cells express the vitamin D receptor (VDR), it is not clear to what extent 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) or its predominant inactive precursor metabolite in the circulation, 25-hydroxyvitamin D3 (25OHD3), can influence IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA) in vivo.

Concepts: Immune system, Vitamin D, Asthma, Cell biology, Allergy, Mast cell, Anaphylaxis, Allergic conjunctivitis

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ETHNOPHARMACOLOGICAL RELEVANCE: Xylopia aethiopica has been traditionally used in the form of the dried fruit decoction to treat bronchitis, asthma, arthritis and rheumatism in Ghana, Nigeria and Cameroon. AIM OF THE STUDY: To evaluate the anti-anaphylactic and anti-inflammatory effects of a 70% aqueous ethanol extract of the fruits of Xylopia aethiopica MATERIALS AND METHODS: Systemic anaphylaxis was induced by the injection of either compound 48/80 or lipopolysaccharide, LPS and survival rates of mice monitored for 1h or 7 days respectively while IgE-mediated anaphylaxis in a local allergic reaction was studied in the pinnal inflammation model in mice. Clonidine-induced catalepsy in mice was used to evaluate the indirect antihistamine effect of Xylopia aethiopica, XAE. The effects of XAE assessed on the maximal and total oedema responses in the carrageenan-induced paw oedema in mice was used to evaluate the anti-inflammatory action of the extract. RESULTS: Administered at 30,100,300 and 1000mgkg(-1) p.o., XAE dose dependently suppressed compound 48/80-induced mouse systemic anaphylactic shock and offered 63% protection to mice against LPS-induced endotoxic shock at a dose of 300mgkg(-1). In addition, the extract (30-300mgkg(-1)) in a dose dependent manner significantly inhibited by 23-62% the mouse pinnal inflammation. Clonidine-induced catalepsy in mice was significantly suppressed in a dose and time dependent manner when administered both prophylactically and therapeutically. In the same doses, when administered before the induction of the mouse carrageenan-induced paw oedema, the mean maximal swelling attained during 6h was reduced to 41.02±6.94%, 35.61±4.30%, and 29.09±4.90% of the inflamed control response respectively and total paw swellings induced over the 6h were also dose-dependently and significantly suppressed to 74.84±14.84%, 63.95±9.37%, and 48.13±10.90% of the inflamed control response respectively. Administered after the induction of the carrageenan paw oedema the mean maximal swelling attained during 6h was suppressed to 49.84±3.95%, 43.62±1.01%, and 35.97±1.34% of the inflamed control response respectively while the total paw swellings induced over the 6h were also dose-dependently and significantly suppressed at 100 and 300mgkg(-1) to 72.39±4.38% and 60.81±3.25% of the inflamed control response respectively CONCLUSION: These findings suggest that XAE inhibits mast cell-dependent immediate allergic reactions and exhibit anti-inflammatory actions through the inhibition of histamine release from mast cells via stabilizing the cell membrane. Our results contribute towards validation of the traditional use of Xylopia aethiopica in the treatment of bronchitis, asthma, arthritis and rheumatism.

Concepts: Immune system, Inflammation, Asthma, Allergy, Mast cell, Anaphylaxis, Skin allergy test, Allergen immunotherapy

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HPC infusions have been associated with a variety of adverse events related to either patient or HPC product-related factors. Studies documenting infusion-related AEs in children are limited. We reviewed HPC infusion records in 354 children. Infusion-related adverse events were classified as follows: grade 0-absent, grade I-mild, grade II-moderate, grade III-severe, grade IV-life-threatening, and grade V-death. The percentage of patients with grade 0, I, and II-IV AEs was as follows: 0 = 67%, I = 23.4%, and II-V = 9.6% (one patient had fatal anaphylactic reaction to dimethyl sulfoxide). The incidence of grade II-IV hypertension was 7.1%. There was a higher incidence of AEs with infusion of allogeneic bone marrow versus allogeneic PBSCs (47.4% vs 25.3%, P = .001). Cryopreserved products had a lower incidence of infusion-associated AEs compared with fresh HPC products (24% vs 39.4%, P = .003). Allogeneic HPC infusion volume (>100 mL) was a significant risk factor for infusion-associated AEs (P < .001). Patients >10 years who received autologous HPC infusions had higher risk of AEs when compared to patients <10 years (P = .01). Our study demonstrated that despite a high incidence of infusion-associated hypertension, HPC infusion is relatively safe in children. Investigating strategies to optimize management of hypertension in the setting of HPC infusion is warranted.

Concepts: Epidemiology, Cancer, Patient, Bone marrow, Epinephrine, Hematopoietic stem cell, Anaphylaxis

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There is no standardised method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2x baseline tryptase+2mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS).

Concepts: Cell biology, Mast cell, Anaphylaxis, Tryptase

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Outside clinical trials, data on systemic reactions (SRs) due to allergen immunotherapy (AIT) are scarce.

Concepts: Clinical trial, Asthma, Immunology, ClinicalTrials.gov, Clinical psychology, Anaphylaxis, Allergen immunotherapy

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A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV) has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2-60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged ≥9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target population for vaccination (≥9 years old) for which CYD-TDV has a satisfactory safety profile. Long-term safety will continue to be monitored in the ongoing follow-up of efficacy trials. Safety and effectiveness in real-life settings will be assessed through post-licensure studies.

Concepts: Clinical trial, Malaria, Effectiveness, Clinical research, Placebo, Efficacy, Dengue fever, Anaphylaxis