Should patients with a large local reaction be offered VIT? A Pro-Con debate.

Insect stings can cause large local reactions (LLRs) that are IgE-mediated and associated with considerable morbidity. A risk for systemic reactions including anaphylaxis to subsequent stings has been reported and is often noted by patients and health care providers. Guidelines do not recommend venom immunotherapy (VIT) for LLR based on the relatively low risk of anaphylaxis, but this is debated in this review. On the Pro side: the risk of anaphylaxis may be higher than reported in the limited literature, especially in patients who had only 1 LLR; new species with more potent stings are spreading into new areas; the quality of life can be markedly impaired by LLR; VIT is generally safe and highly effective. On the Con side: LLR are benign; stings occur infrequently; VIT has significant cost; systemic reactions occur more often to VIT than to stings in patients with LLR; FDA approval and published guidelines do not recommend VIT for LLR. In practice, shared decision-making is appropriate to incorporate knowledge of the natural history and known high-risk factors in the context of the patient's personal values and preferences.

Mosquito hypersensitivity may be associated with atopic background in children.

BACKGROUND: Many children encounter unusual or "exaggerated" reactions such as large local, atypical or systemic reactions after mosquito bites. OBJECTIVE: The aim of this study was to document the clinical features of children with mosquito allergy and investigate the possible associations between demographic features and type of reactions in this population. METHODS: Children with large local or unusual reactions after mosquito bites who attended to our outpatient pediatric allergy department were enrolled in the study along with control subjects. RESULTS: A total of 180 children (94 with mosquito allergy and 86 age and sex-matched control subjects) with a median age of 6.8 years (IQR 5.5-9.3) were enrolled. Atopy (35.1% vs. 11.6%, p < 0.001) and grass pollen sensitization (28.7% vs. 8.1%, p < 0.001) were significantly more frequent in children with mosquito allergy. Skin prick test with mosquito allergen was positive in only 6 children (6,4%). Grass pollen sensitization was most common in children (28.7%) followed by sensitization to house dust mite (9.6%). 30 children (31.9%) had an accompanying atopic disease such as allergic rhinitis, asthma or atopic dermatitis. Bullae were significantly more frequent in children with asthma (41.7% vs.15.9, p = 0.034). The median duration of symptoms after onset were significantly longer in patients with ecchymosis, with immediate wheals and in children whose symptoms start in 20 min to 4 hours after mosquito bites. CONCLUSION: There is an association between unusual, large local or exaggerated reactions after mosquito bites and allergic diseases in children. The severity of reactions increases with age and particularly in children with atopic background.

Mosquito hypersensitivity may be associated with atopic background in children

Background Many children encounter unusual or “exaggerated” reactions such as large local, atypical or systemic reactions after mosquito bites. Objective The aim of this study was to document the clinical features of children with mosquito allergy and investigate the possible associations between demographic features and type of reactions in this population. Methods Children with large local or unusual reactions after mosquito bites who attended to our outpatient pediatric allergy department were enrolled in the study along with control subjects. Results A total of 180 children (94 with mosquito allergy and 86 age and sex-matched control subjects) with a median age of 6.8 years (IQR 5.5–9.3) were enrolled. Atopy (35.1% vs. 11.6%, p < 0.001) and grass pollen sensitization (28.7% vs. 8.1%, p < 0.001) were significantly more frequent in children with mosquito allergy. Skin prick test with mosquito allergen was positive in only 6 children (6,4%). Grass pollen sensitization was most common in children (28.7%) followed by sensitization to house dust mite (9.6%). 30 children (31.9%) had an accompanying atopic disease such as allergic rhinitis, asthma or atopic dermatitis. Bullae were significantly more frequent in children with asthma (41.7% vs.15.9, p = 0.034). The median duration of symptoms after onset were significantly longer in patients with ecchymosis, with immediate wheals and in children whose symptoms start in 20 min to 4 hours after mosquito bites. Conclusion There is an association between unusual, large local or exaggerated reactions after mosquito bites and allergic diseases in children. The severity of reactions increases with age and particularly in children with atopic background (AU)

Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases.

BACKGROUND: Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. OBJECTIVE: To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. METHODS: A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. RESULTS: From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. LIMITATIONS: Registry analysis does not measure incidence. Morphologic misclassification is possible. CONCLUSIONS: We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination.

Characterization of the sensitization profile of bee venom allergic patients ­ Association with the severity of reaction? / Caracterização do perfil de sensibilização molecular de doentes alérgicos à picada de abelha - Associação com a gravidade da reação?

Introduction: Bee venom (BV) allergy, a common cause of anaphylaxis in adults, is often associated with severe reactions. The use of component-resolved diagnostics (CRD) increases diagnostic accuracy. Objectives: To characterize the sensitization profile of BV allergic patients and a possible correlation with the severity of reaction. Materials and methods: We selected patients with a clinical history of BV allergy, positive skin tests, and specific IgE (sIgE) for BV. The allergenic profile was analyzed by both CRD and Western blot using a well-defined and properly characterized BV extract. Results: Forty-four patients were included, 30 (68.2%) were men. Mean age was 48.9 (SD 17.9) years. Eleven (25%) had large local reactions (LLRs) and 33 (75%) had systemic sting reactions (SSRs). One patient with negative sIgE for BV had positive sIgE for Api m 1, Api m 5, and Api m 10. The sensitization frequency for BV, Api m 1, Api m 2, Api m 3, Api m 5, and Api m 10 was 97.7%, 75%, 47.7%, 20.5%, 40.9%, and 61.4%, respectively. Five patients (11.4%) were sensitized to all BV components. CRD association showed that 5 patients (11.4%) were sensitized only to Api m 1, 8 (18.2%) to Api m 1/Api m 3/Api m 10, and 16 (36.6%) to Api m 1/ Api m 10. Twenty-eight patients (84.8%) with SSRs were sensitized to Api m 1, and concomitant sensitization to Api m 1/Api m 10 was detected in 20 (60.6%). There was a significant difference in Api m 1 between patients with LLRs and SSRs (p = 0.0104). Similar profiles were identified by Western blot analysis, with relevance for the detection of Api m 6 in 28 (64%) and Api m 4 in 16 (36%) patients. Conclusion: The analysis of the sensitization profile using CRD and the association of several of these components can increase diagnostic accuracy in BV allergy. Our data showed that concomitant sensitization to Api m 1 and Api m 10, detected by both CRD and electrophoretic profile, may be associated with SSRs. We emphasize the identification of sensitization to Api m 6 in > 50% of patients, which may be considered a major allergen, and to Api m 4, which may be related to reactions during BV immunotherapy.

Introdução: A alergia ao veneno de abelha (VA) é uma causa frequente de anafilaxia em adultos e está muitas vezes associada a reações graves. O diagnóstico por componentes moleculares (CRD) contribui para uma melhor caracterização desta alergia. Objetivos: Caracterização do perfil de sensibilização molecular de doentes alérgicos ao veneno de abelha e possível correlação com a gravidade da reação. Material e métodos: Selecionaram-se doentes com história de alergia a VA, testes cutâneos e IgE específica (sIgE) positivos para VA. Avaliou-se o perfil alergênico por CRD e por Western Blot, utilizando extrato de VA bem caracterizado. Resultados: 44 doentes, 30 (68,2%) sexo masculino. Média de idades 48,9 ± 17,9 anos, 11 (25%) com reacções locais exuberantes e 33 (75%) com reações sistêmicas à picada (SSR). Um doente tinha sIgE negativa para VA, mas Api m 1, Api m 5 e Api m 10 positivas. A frequência de sensibilização para VA, Api m 1, Api m 2, Api m 3, Api m 5 e Api m 10 foi 97,7%; 75%; 47,7%; 20,5%; 40,9% e 61,4%, respectivamente. Cinco (11,4%) doentes estavam sensibilizados a todos os componentes. Por associação de CRD, detectaram-se 5 (11,4%) doentes sensibilizados apenas a Api m 1, 8 (18,2%) a Api m 1/Api m 3/Api m 10, e 16 (36,6%) a Api m 1/Api m 10. Vinte e oito (84,8%) doentes com SSR tinham Api m 1 positiva e 20 (60,6%) tinham Api m 1/Api m 10 simultaneamente positivas. Observou-se uma diferença estatisticamente significativa para a Api m 1 entre doentes com reações locais exuberantes e sistêmicas (p = 0,0104). Os perfis detectados por Western Blot foram semelhantes, de referir, à detecção de Api m 6 em 28 (64%) e Api m 4 em 16 (36%) dos doentes. Conclusão: A análise do perfil de sensibilização através de CRD e a sua associação aumentam a precisão do diagnóstico de alergia a VA. Sensibilização simultânea a Api m 1 e Api m 10 identificados tanto por CRD como por perfil eletroforético, pode estar associada à ocorrência de SSR. Destaca-se a sensibilização a Api m 6 em > 50% dos doentes, podendo ser considerado um alergênio major, e a Api m 4, possivelmente associado a reações durante a imunoterapia com VA.

Approach to Patients with Stinging Insect Allergy.

Stinging insect allergy is uncommon but can be life threatening. Diagnosis requires clinical history and confirmative skin or blood testing by an allergist. Baseline serum tryptase level can be used to stratify risk. Treatment is supportive for all reactions except for anaphylaxis, which is treated with intramuscular epinephrine, recumbent posture, and adjunct measures such as IV fluids, and oxygen. Venom immunotherapy is most effective for long-term management in patients with a history of anaphylaxis. Venom immunotherapy rapidly reduces the risk of sting anaphylaxis by up to 98% and maintenance treatment can be stopped after 5 years in most cases.

Large local reactions to Hymenoptera stings: Outcome of re-stings in real life.

BACKGROUND: Large local reaction to Hymenoptera stings is usually defined as a swelling >10 cm which lasts longer than 24 hours, sometimes associated with erythema, pruritus and blisters. Currently, the risk of subsequent systemic reactions after re-stings is considered low (2%-15%). Therefore, a diagnostic workup in case of large local reaction is often judged unnecessary, as well as adrenaline auto-injector and venom immunotherapy prescription. The aim of this study was to prospectively evaluate the outcome of re-stings in a real-world setting, in patients with a history of one previous large local reaction. METHODS: We consecutively enrolled patients who experienced their first large local reaction (as per EAACI definition), treated with antihistamine and steroids. They were followed for field re-stings and assessed for risk of subsequent systemic reactions. RESULTS: We enrolled 662 patients. Out of the 225 re-stung subjects, 24% did not experience reactions, 52% reported a second large local reaction and 24% had systemic reactions. The risk of subsequent systemic reactions was higher in case of skin test reactivity to Apis mellifera or Vespula species (OR 2.1 and 3.8, respectively), in particular if positive at 0.001 µg/mL concentration (OR 13.4 and 16.5, respectively). CONCLUSIONS: Systemic reactions, after a previous large local reaction, occur more frequently than that reported by literature. After analysing the predictive role of large local reactions for systemic reactions, we demonstrated that an accurate diagnostic workup may be considered, particularly skin tests. Further studies in different countries are needed to confirm these results and large local reaction management.

Stinging insect hypersensitivity: Evaluation and management in children and youth.

There are two types of IgE-mediated reactions to stinging insects: large local reactions and systemic reactions. Acute management of large local reactions is symptomatic and a patient history of a large local reaction does not indicate need for an epinephrine auto-injector or venom immunotherapy. By contrast, acute management of systemic reactions requires intramuscular epinephrine. Long-term management includes prescribing an epinephrine auto-injector and consideration for venom immunotherapy by a paediatric allergist.

A Very Big Hand Is a Very Big Problem: Soft-Tissue Infection, Venous Thrombosis, or Just an Insect Sting?

A 67-year-old woman developed severe edema of her right hand and forearm, for which she was treated with antibiotics, without benefit. The echography excluded a venous thrombosis. Subsequently, she referred a wasp sting before the development of the edema. Specific Hymenoptera venom immunoglobulin E (IgE) was found to be positive for paper wasp and yellow jacket. A large local reaction (LLR) was diagnosed due to the hymenoptera sting. Self-injectable epinephrine was prescribed for possible, though unlikely, systemic reactions following hymenoptera stings. LEARNING POINTS: The differential diagnosis of an upper forearm and hand oedema may be challenging.In order to reach the correct diagnosis and to prescribe proper treatment, careful examination and history taking is essential.All possible causes should be taken into proper consideration.Large local reaction (LLR) is characterized by hot, flushed and thick edema after a hymenoptera sting. As the risk of a systemic reaction, upon the first sting following a consistent index LLR, it is important to recognize an LLR in order to prescribe self-injectable epinephrine to prevent the occurrence of anaphylaxis.

Risk of anaphylaxis in patients with large local reactions to hymenoptera stings: a retrospective and prospective study.

BACKGROUND: In the few studies available, the risk of developing systemic reactions (SR) to hymenoptera stings in patients with previous large local reactions (LLRs) to stings ranges from 0 to 7 %. We evaluated both retrospectively and prospectively the risk of SRs in patients with LLRs to stings. METHODS: An overall number of 477 patients, 396 with an SR as the first manifestation of allergy and 81 with a history of only LLRs after hymenoptera stings, were included in the study. All patients had clinical history and allergy testing (skin tests and/or specific IgE) indicative of allergy to venom of only one kind of Hymenoptera. Of the 81 patient with LLRs, 53 were followed-up for 3 years by annual control visits, while the 396 patients with SR were evaluated retrospectively. RESULTS: Among the 396 patients with an SR, only 17 (4.2 %) had had a previous LLR as debut of allergy, after an history of normal local reactions to Hymenoptera stings. All the 81 patients with a history of only LLRs had previously had at least two LLRs, with an overall number of 238 stings and no SR. Among the 53 patients who were prospectively evaluated we found that 31 of them (58.3 %) were restung by the same type of insect, with an overall number of 59 stings, presenting only LLRs and no SR. CONCLUSIONS: Our findings confirm that patients with repeated LLRs to stings had no risk of SR, while a single LLR does not exclude such risk. This has to be considered in the management of patients with LLRs.

Sensitization to Hymenoptera venoms is common, but systemic sting reactions are rare.

BACKGROUND: Sensitization to Hymenoptera venom without systemic sting reactions (SSRs) is commonly observed in the general population. Clinical relevance for a future sting has not yet been investigated. OBJECTIVE: We aimed to evaluate the effect of these debatable sensitizations with deliberate sting challenges and to monitor serologic changes for up to 2 years. METHODS: One hundred thirty-one challenges with bees and wasps were performed in 94 subjects with a hitherto irrelevant sensitization. The clinical outcome was recorded, and results of specific IgE (sIgE) determinations, skin tests, and basophil activation tests were correlated to the sting reaction. sIgE levels were monitored in reactors and nonreactors after 3 hours, 1 week, 4 weeks, and 1 year. RESULTS: Only 5 (5.3%) patients had SSRs, but 41 (43.6%) had large local reactions (LLRs) after the sting. Compared with the general population, there was a 9.5-fold higher risk for LLRs but not for SSRs. Three hours after the sting, sIgE levels slightly decreased, but none of the 94 subjects' results turned negative. After 1 week, sIgE levels already increased, increasing up to 3.5-fold (range, 0.2- to 34.0-fold) baseline levels after 4 weeks. To assess the clinical relevance of this increase, we randomly selected 18 patients for a re-sting. Again, 50% had an LLR, but none had an SSR. CONCLUSION: Although sensitization to Hymenoptera venoms was common, the risk of SSRs in sensitized subjects was low in our study. The sIgE level increase after the sting was not an indicator for conversion into symptomatic sensitization. Currently available tests were not able to distinguish between asymptomatic sensitization, LLRs, and SSRs.