Allergies and COVID-19 vaccines: An ENDA/EAACI Position paper.

BACKGROUND: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized. METHOD: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed. RESULTS: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. CONCLUSIONS: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.

International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency.

BACKGROUND: There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). OBJECTIVE: We sought to elaborate guidelines for optimizing the management of gynecologic/obstetric events in female patients with HAE-C1-INH. METHODS: A roundtable discussion took place at the 6th C1 Inhibitor Deficiency Workshop (May 2009, Budapest, Hungary). A review of related literature in English was performed. RESULTS: Contraception: Estrogens should be avoided. Barrier methods, intrauterine devices, and progestins can be used. Pregnancy: Attenuated androgens are contraindicated and should be discontinued before attempting conception. Plasma-derived human C1 inhibitor concentrate (pdhC1INH) is preferred for acute treatment, short-term prophylaxis, or long-term prophylaxis. Tranexamic acid or virally inactivated fresh frozen plasma can be used for long-term prophylaxis if human plasma-derived C1-INH is not available. No safety data are available on icatibant, ecallantide, or recombinant human C1-INH (rhC1INH). Parturition: Complications during vaginal delivery are rare. Prophylaxis before labor and delivery might not be clinically indicated, but pdhC1INH therapeutic doses (20 U/kg) should be available. Nevertheless, each case should be treated based on HAE-C1-INH symptoms during pregnancy and previous labors. pdhC1INH prophylaxis is advised before forceps or vacuum extraction or cesarean section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer: Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female patients, genetic counseling, infertility, abortion, lactation, menopause treatment, and endometrial cancer. CONCLUSIONS: A consensus for the management of female patients with HAE-C1-INH is presented.

Complement membrane attack complex and hemodynamic changes during human orthotopic liver transplantation.

Hemodynamic changes and elevation of intracellular calcium following reperfusion in human liver transplantation occur rapidly and do not match the time course of cytokine expression, therefore, we postulate involvement of other, pre-formed substances, such as complement. We studied 40 adult patients undergoing liver transplantation. Blood was drawn for estimation of C3, C4, C3 degradation product, membrane attack complex, and CH100 levels and elastase (a marker of neutrophil activation) at induction of anesthesia, 5 minutes before reperfusion, 5 minutes and 60 minutes after reperfusion. Cardiac output was measured by thermodilution and systemic vascular resistance was calculated at these same time points. There was a significant rise in C5b-9 membrane attack complex (P =.0012) with a corresponding fall in C3 (P =.0013) and C4 (P =.0002) levels and a rise in C3 degradation product levels (P =.0006). There was no significant change in CH100. These changes very closely followed the hemodynamic changes of a significant fall in systemic vascular resistance index (P =.0024) and increase in cardiac index (P =.0005). Elastase rose from 356 +/- 53 to 557 +/- 40 microg/L (P <.0001). There is complement activation and neutrophil activation at reperfusion in liver transplantation. Dilution alone cannot explain the fall in C3 and C4 levels as there is a corresponding increase in membrane attack complex and C3 degradation product levels with time. As both C3 and C4 are consumed, the classical pathway must be active, though alternative and lectin activated pathways may also be involved. These findings may, at least in part, explain the hemodynamic changes typically seen at reperfusion in liver transplantation.