Penicillin is the most common cause of drug-induced allergic reactions, ranging from simple cutaneous reactions such as urticaria and maculopapular exanthema to anaphylactic reactions.
Mechanisms of penicillin allergy
Penicillins are small molecules that bind to plasma proteins and form hapten-carrier complexes. Binding of the beta-lactam ring to lysine residues leads to the formation of the major antigen determinants, penicilloyl-polylysine, binding to carboxyl and thiol groups leads to the formation of various minor antigen determinants. In IgE-mediated reactions, the dendritic cells bind and internalize the proteins that have bound the penicillin and present them with the MHC II receptor to the native CD4-positive T cells (type 0 helper T cells). In the presence of interleukin 4, the naive T cells differentiate into penicillin-specific type 2 helper cells that produce interleukin 4 and interleukin 13. This in turn promotes the differentiation of B cells into plasma cells that secrete IgE specific for penicillin. Penicillin-specific IgE is bound by the Fc receptors of basophils and mast cells. When penicillin is administered again, the crosslinking of the IgE molecules by the penicillin-hapten carrier complex triggers the degranulation of the mast cells and the allergic symptoms occur.
Consequences of the penicillin allergy label
Approximately 10-20% of the population is labeled penicillin allergic by adulthood, either because of an actual allergic reaction or because of a symptom that occurred independently of penicillin administration but has been interpreted as allergic. Approximately 10% of people who have actually suffered IgE-mediated reactions lose the positive skin test each year. Therefore, less than five percent of patients with the label penicillin allergy actually have such an allergy. As a penicillin allergy is rarely questioned, these patients are often given more toxic alternatives and broad-spectrum antibiotics instead of penicillin, which work less well, have more side effects, are more expensive and lead to more antibiotic resistance. Cross-reactions with higher-generation cephalosporins are often not present, so that these drugs could be used in the case of an actual penicillin allergy.
Clarification of a penicillin allergy
Skin testing is the clarification of choice. Intradermal tests are usually carried out. Caution is advised in case of previous severe reactions.
The sensitivity of 70% for the soft type reactions is not particularly good, but the specificity is high. The ideal time for clarification is between 1-6 months after the event.
The in vitro tests have a lower sensitivity, but can be used as a supplement or if skin tests are not possible. We offer you testing for specific IgE for the following beta-lactam antibiotics:
- c1 – Penicilloyl G
- c2 – Penicilloyl V
- c5 – Ampicilloyl
- c6 – Amoxicilloyl
- c7 – Cefaclor
All of them are serum, although EDTA or heparin blood can also be used as an alternative.