Role of delayed cellular hypersensitivity and adhesion molecules in amoxicillin-induced morbilliform rashes

Background: Morbilliform rashes induced by amoxicillin are thought to be caused by a delayed cell-mediated immune reaction. The importance of amoxicillin skin tests is not well defined. A better understanding of the mechanisms of amoxicillin-induced morbilliform rashes can be obtained by performing cutaneous immunohistological studies on specimens from amoxicillin-induced morbilliform rashes and positive amoxicillin skin test results. Observations: Skin biopsy specimens were obtained from 5 patients who had developed an amoxicillin-induced morbilliform rash. All patients underwent amoxicillin prick, patch, and intradermal tests. Similar immunohistological investigations were performed on amoxicillin-induced morbilliform rashes and positive skin test biopsy specimens, with a special focus on the expression of adhesion molecules. Three of the 5 patients developed delayed positive results to intradermal and patch tests and 2 patients developed delayed positive results to prick tests. Amoxicillin-induced morbilliform rashes were well reproduced by skin tests, with similar immunohistological results in amoxicillin-induced morbilliform rashes and skin test biopsy specimens. Keratinocytes were activated and expressed CD54 (intercellular adhesion molecule 1), perivascular lymphocytes were mostly CD2(+), CD3(+), and CD4(+) and exhibited CD11a through CD18 (leukocyte function-associated antigen 1) and often HLA-DR and/or CD62L (leukocyte endothelial cell adhesion molecule 1); and endothelial cells were activated with a strong expression of CD54 (intercellular adhesion molecule 1), CD62E (endothelial leukocyte adhesion molecule 1), and CD31 (platelet endothelial tell adhesion molecule 1) in lesser amounts. Conclusions: Findings of this clinical and immunohistochemical study support the theory of a T-cell-mediated immune reaction in patients with amoxicillin-induced morbilliform rashes, with a strong involvement of adhesion molecules both on endothelial and infiltrating cells. Our findings emphasize the importance of delayed readings of amoxicillin prick, intradermal, and patch tests.