ABSTRACT
Background: The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy or with a suspected allergic reaction after the first dose remains to be defined. Methods: In this real-life study, we defined two cohorts of individuals: one pre-vaccination including 187 individuals with high-risk profiles for developing anaphylaxis and a second post-vaccination including 87 individuals with suspected allergic reactions after the COVID-19 mRNA vaccine. Upon negative skin test with an mRNA vaccine, a two-step (10-90%) vaccination protocol was performed. Positive skin tests were confirmed with the basophil activation test (BAT). Results: Among 604,267 doses of vaccine, 87 suspected allergic reactions (5 after the booster) were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% of the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced isolated asthmatic reactions during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism. Conclusion: Sensitization to SARS-CoV-2 mRNA vaccines can be detected with intradermal testing. Significantly more individuals were sensitized to mRNA vaccines in the post-vaccination cohort. A two-step 10-90%-vaccination protocol can be safely administered upon negative skin testing.
ABSTRACT
Intravenous iron infusions rarely result in severe hypersensitivity reactions. The primary suspected hypersensitivity mechanism is an abnormal complement activation by non-IgE antibodies to the carbohydrate moieties stabilizing iron formulations. A major risk factor for hypersensitivity reactions is related to the infusion speed. Fishbane-like reactions usually resolve after pausing the infusion, which can be resumed under medical surveillance and at a lower infusion rate. Yet, anaphylactic reactions require emergency first aid and subsequent strict avoidance of intravenous iron. Desensitization protocols can be implemented in selected cases and under strict medical surveillance to reduce the risks of severe reactions upon re-exposure.
L'administration de fer intraveineux (IV) peut rarement se compliquer de réactions d'hypersensibilités sévères, parfois fatales. Le mécanisme supposé est celui d'une activation anormale du complément, possiblement liée à des anticorps non-IgE (immunoglobuline E) dirigés contre les groupements carbohydrates qui stabilisent la formulation de fer. Un débit de perfusion trop rapide est un facteur important de réaction d'hypersensibilité. En effet, les réactions légères se résolvent généralement après mise en pause de la perfusion, qui peut ensuite être reprise à un débit réduit. Les réactions anaphylactiques nécessitent en revanche un traitement d'urgence et une éviction stricte. Le recours à un protocole de désensibilisation sous surveillance médicale étroite permet, dans certaines situations, de limiter le risque de réaction lors d'une réadministration de fer IV.
Subject(s)
Anaphylaxis , Anemia, Iron-Deficiency , Drug Hypersensitivity , Administration, Intravenous , Allergists , Anaphylaxis/chemically induced , Anemia, Iron-Deficiency/drug therapy , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/etiology , Drug Hypersensitivity/therapy , Humans , Infusions, Intravenous , Iron/adverse effectsABSTRACT
Hereditary angioedema type 1 and 2 are due to a deficiency in C1--esterase inhibitor. This molecule inhibits the generation of bradykinin, a potent inflammatory mediator that increases vascular permeability. Upon accumulation of bradykinin, patients affected develop painful subcutaneous or submucosal edemas that last for several days. In case the upper airways are affected, there is risk of suffocation. This type of angioedema does not respond to antihistamines, cortico-steroids or epinephrine. Management of angioedema attacks consists in injecting C1-esterase inhibitor concentrate or icatibant, a bradykinin receptor B2 antagonist. Preventive measures aim at reducing the frequency and the severity of angioedema attacks. Inhibition of -plasma kallikrein by lanadelumab, a monoclonal antibody adminis-tered subcutaneously, is effective and well tolerated.
Les angiÅdèmes (AE) héréditaires de types I et II sont dus à un déficit en inhibiteur de la C1 estérase ou C1-inhibiteur (C1-INH). Cette molécule régule la formation de bradykinine, un puissant médiateur vasoactif. En cas d'accumulation de bradykinine, les patients développent des Ådèmes sous-cutanés ou sous-muqueux douloureux qui persistent plusieurs jours. L'atteinte des voies aériennes comporte un risque de suffocation. Ce type d'angiÅdème ne répond pas aux antihistaminiques, aux corticoïdes ni à l'adrénaline. Le traitement de la crise comprend l'injection de concentré de C1-INH ou d'icatibant, un antagoniste du récepteur B2 de la bradykinine. Le traitement préventif vise à diminuer la fréquence et la sévérité des crises. L'inhibition de la kallicréine plasmatique par lanadélumab, un anticorps monoclonal administré en sous-cutané, constitue une approche efficace et bien tolérée.
