Clinical usefulness of patch and challenge tests in the diagnosis of cell-mediated allergy to betalactams

Background: Literature reports dealing with cell-mediated allergy to betala ctams have appeared with increasing frequency in the last years. Objective: To evaluate patients with such reactions and to identify cross-r eactivities among betalactams in order to provide safe guidelines for their further clinical management. Methods: Thirty consecutive subjects with cell-mediated allergy to betalact ams (history of adverse reactions to these antibiotics; serum total IgE wit hin the normal range; absence of serum specific IgE antibodies to penicilli n G and V, amoxicillin, and ampicillin; negative skin tests with a wide pat tern of betalactam preparations; and positive patch-test to at least one be talactam antigenic determinant) were investigated. The subjects admitted to the study were patch tested with a wide variety of betalactam preparations in order to identify alternative molecules tolerat ed by the patient. To better evaluate the cross-reactivity pattern, toleran ce challenges with patch-negative betalactams were also performed in each s ubject. Results: Both specific IgE and skin tests were negative in all patients. Th e skin biopsies performed on the positive patch-tested area in four patient s showed a clear T-lymphocyte, CD4+-type infiltrate, thus definitely provin g the occurrence of a cell-mediated response. A total of 44 adverse reactions (mean: 1.47 episodes for each patient) were reported in history, with a mean interval of 15 hours after betalactam adm inistration. The reported symptoms were mainly cutaneous (maculo-papular ra sh and urticaria) and the responsible drugs were chiefly aminopenicillins ( 86.4% of cases) and penicillin G (9.1%). We were able to identify three separate groups of patients on the basis of clinical history, patch-test, and tolerance challenge pattern: allergy to the side chain of aminopenicillins in 16 patients (53.3%); allergy to the thiazolidine ring in 3 patients (10.0%); undetermined specificity in the remainder 11 patients (36.7%). Cross-reactivity among different betalactam molecules (revealed by positive tolerance tests performed with patch-negative betalactams) was found in 4. 8% of cases only (23.3% of all investigated patients). This fact demonstrat es a very high (95.2%) predictive value of a negative patch-test in excludi ng the occurrence of a cross-reactivity. The mis-match between patch and to lerance tests was observed in 3 out of 178 cases only (1.7% of cases, 10.5% of patients) in groups A and B, and in as much as 12.2% of cases (45.5% of subjects) in group C (P <.05). Conclusions: Delayed allergy to betalactams (mainly to aminopenicillins) ma y be exerted by a cell-mediated response. Patch tests and tolerance challen ges are extremely useful and safe for diagnosis and further clinical treatm ent of these patients, helping to identify safe alternative betalactam mole cules that could be successfully tolerated by the allergic subjects.