Desensitization for the prevention of drug hypersensitivity reactions

Abstract

Drug desensitization is the temporary induction of tolerance to a sensitized drug by administering slow increments of the drug, starting from a very small amount to a full therapeutic dose. It can be used as a therapeutic strategy for patients with drug hypersensitivity when no comparable alternatives are available. Desensitization has been recommended for immunoglobulin E (IgE)-mediated immediate hypersensitivity; however, its indications have recently been expanded to include non-IgE-mediated, non-immunological, or delayed T cell-mediated reactions. Currently, the mechanism of desensitization is not fully understood. However, the attenuation of various intracellular signals in target cells is an area of active research, such as high-affinity IgE receptor (FcεRI) internalization, anti-drug IgG4 blocking antibody, altered signaling pathways in mast cells and basophils, and reduced Ca 2+ influx. Agents commonly requiring desensitization include antineoplastic agents, antibiotics, antituberculous agents, and aspirin/nonsteroidal antiinflammatory drugs. Various desensitization protocols (rapid or slow, multi-bag or one-bag, with different target doses) have been proposed for each drug. An appropriate protocol should be selected with the appropriate concentration, dosage, dosing interval, and route of administration. In addition, the protocol should be adjusted with consideration of the severity of the initial reaction, the characteristics of the drug itself, as well as the frequency, pattern, and degree of breakthrough reactions.

Desensitization in children allergic to drugs: Indications, protocols, and limits

“…26 DDS should be carefully considered in patients with significant risk factors for fatal breakthrough reactions, such as those with a history of severe HSR as anaphylaxis, those with cardiovascular or respiratory diseases, or mast cell activation syndromes, and those using beta-blockers. 31 Reactions can be classified as mild when only skin symptoms are present, moderate when besides the skin, respiratory and gastrointestinal systems are involved, and severe when there is also hypoxemia, hypotension, syncope, seizures, and cardiac or respiratory arrest. 32 The measurement of serum tryptase at the time of the reaction and its comparison with the basal levels helps to detect mast cell degranulation, as well as IL-6 for CRS.…”

Management of adverse reactions induced by chemotherapy drugs

“…In recent years, different drug desensitization protocols have been developed, not only for immunoglobulin E (IgE)-mediated immediate hypersensitivity but also including non-IgE-mediated, nonimmunological, or delayed T-cell-mediated reactions [7,8,9 && ]. Two categories of desensitization protocols are currently available: rapid drug desensitization (RDD), commonly used, in which full therapeutic doses can be reached in relatively short time, typically 4-12 h [5 & ], and slow drug desensitization (SDD), recommended for some restricted reactions of type IV delayed hypersensitivity reactions with Tcell involvement [7,8].…”

“…In recent years, different drug desensitization protocols have been developed, not only for immunoglobulin E (IgE)-mediated immediate hypersensitivity but also including non-IgE-mediated, nonimmunological, or delayed T-cell-mediated reactions [7,8,9 ▪▪ ].…”

Thyroid diseases and new approaches for their treatment

“…Подход, в основе которого лежит восстановление иммунной толерантности к рецептору ТТГ, основан на повторном введении нарастающих количеств антигена. Этот подход активно применяется в аллергологии [29,30], но до сих пор практически не использовался для лечения аутоиммунных заболеваний, так как введение антигенов может спровоцировать рецидив основного заболевания. Для снижения риска усиления аутоиммунного гипертиреоза в качестве эпитопов выбирали те участки рецептора ТТГ, которые не приводили к генерации аутоантител со стимулирующей активностью [26].…”