bacampicillin and Drug-Hypersensitivity

Topics: Ampicillin; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Mouth Mucosa

Antigen-specific cell lines or clones are often used as models of drug-specific allergy. However, cloning procedures are time consuming, and the repeated antigen stimulation cycles as well as the addition of various growth enhancers may affect the in vivo relevance of these systems.. Using bacampicillin-allergic subjects, we wanted to investigate the applicability of primary recall in vitro lymphocyte responses to characterize type I and type IV allergy. The sensitivity and specificity of LTT (Lymphocyte transformation test), when used as an in vitro diagnostic tool, were also assessed.. A total of 39 patients with symptoms of type I (rhinitis) or type IV (allergic contact dermatitis, ACD) allergy following occupational exposure to bacampicillin, were included. Ten individuals without penicillin allergy or occupational exposure to bacampicillin served as controls. All subjects were LTT tested. Four patients with rhinitis and two patients with ACD were available for studying the immunophenotype and the TCR-Vbeta repertoire of bacampicillin induced lymphoblasts as well as the cytokine profiles and expression of the activation markers CD23 and CD134 in primary PBMC cultures.. LTT was positive in 87% and at least one of the skin tests was positive in 85% of the patients with allergic symptoms. 69% of the patients with type I allergies were patch test-positive. Results from LTT and skin test correlated in 87% of the cases. The combined sensitivity of LTT and skin tests was 92%. The specificity of LTT was 90% in healthy controls. Bacampicillin induced lymphoblasts were mainly CD4 + in both ACD and rhinitis patients. The TCR-Vbeta profiles of the predominant CD4 + lymphoblasts were heterogeneous with individual skewing towards Vbeta2, Vbeta3, Vbeta5.1 and/or Vbeta14. An increased expression of IFNgamma was detected in bacampicillin treated PBMC cultures from the ACD but not from rhinitis patients. IL-5 was detected in bacampicillin exposed PBMC cultures from all patients but not from healthy controls. This Th2 environment could also be verified by CD23 and CD134 expression.. LTT and skin tests are equally sensitive in identifying bacampicillin allergic subjects. When the two tests are combined, the sensitivity increases. The patch test is useful not only for detection of type IV but also for the identification of type I allergies. When using primary PBMC cultures, IFNgamma is the most suitable cytokine to discriminate between type I and type IV allergy. IL-5 can possibly be used as a general marker for bacampicillin induced allergy. Thus, primary cell cultures may be considered as an alternative to T-cell lines or clones for the study of drug induced allergy.

Topics: Ampicillin; Dermatitis, Allergic Contact; Drug Hypersensitivity; Humans; Interferon-gamma; Interleukin-4; Interleukin-5; Lymphocyte Activation; Receptors, Antigen, T-Cell, alpha-beta; Rhinitis; Skin Tests

Ampicillin (AMP) is a drug that has been prescribed extensively. Reactions that have been reported include exanthema, desquamative contact eczema, urticaria and anaphylaxis. Experimental evidence indicates that the side chain of AMP is a structure that may induce a selective immune response either at the humoral or lymphocyte T-cell level. With regard to IgE reactions, the selectivity and specificity of the response needs to be studied in humans.. To study the specificity of the IgE response in a group of subjects who had an immediate allergic reaction after the administration of AMP.. Subjects developing an immediate response (anaphylaxis or urticaria) after the administration of AMP or an aminopenicillin derivative with the same side chain as AMP were studied. Skin tests were made to determinants generated from benzyl penicillin (BP): benzyl penicilloyl (BPO) and minor determinant mixture (MDM), as well as amoxicillin (AX) and AMP. Specific IgE antibodies were determined to benzyl penicilloyl polylisine (BPO-PLL), amoxicilloyl-polylisine (AX-PLL) and ampicilloyl-polylisine (AMP-PLL). The specificity of the IgE antibody response was studied by RAST and RAST inhibition. Subjects were classified in three categories: group A: those who were skin test and/or RAST positive to determinants derived from benzylpenicillin, group B: those who were negative to determinants derived from benzylpenicillin but were skin test and/or RAST positive to determinants derived from AX and AMP and group C: those who were exclusively positive to determinants derived from AMP.. A total of 48 subjects was included in the study. In group A there were 35 cases, in group B 10 cases, and in group C three cases. RAST inhibition studies showed that in some instances the side chain of AMP could induce specific responses with a variable degree of crossreactivity between BP and AX.. Although AMP can induce an immediate IgE response in subjects allergic to betalactams and the structure of the side chain may contribute to the specificity of the response, our results indicate that in most instances crossreactivity with the other penicillins exists and that in the groups studied selective reactions to just AMP derived determinants were uncommon.

Topics: Adult; Aged; Amoxicillin; Ampicillin; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Italy; Male; Middle Aged; Penicillins; Radioallergosorbent Test; Sensitivity and Specificity; Skin Tests; Spain; Time Factors; Urticaria

Eight workers with clinically diagnosed or suspected occupational allergy caused by penicillins were studied by the lymphocyte transformation test (LTT) and by skin test. The majority of the workers handled bacampicillin, some of them had been in contact with benzylpenicillin and one worked with azidocillin only. Six workers had eczema and 2 workers suffered from rhinitis only. Lymphocytes from workers with bacampicillin-induced symptoms responded to this drug in vitro by an increased 3H-thymidine incorporation and by lymphoblastogenesis. Bacampicillin-specific allergy had been confirmed by positive patch test in 5 workers. Lymphocytes from bacampicillin-allergic workers did not respond to other penicillins such as benzylpenicillin or azidocillin in vitro. However, such penicillins were antigenic in vitro since lymphocytes from an azidocillin patch test positive worker proliferated on exposure to azidocillin in vitro. The findings at the cellular level were further supported by the specificity of the skin test. Thus, bacampicillin patch test positive workers had a negative skin reaction to benzylpenicillin. In conclusion, these data suggest the role of penicillin side chains in the sensitization process underlying occupational allergy to penicillins. LTT can be used as a tool for studying antigenic specificities involved in a sensitization process leading to penicillin allergy.

Topics: Ampicillin; Drug Hypersensitivity; Drug Industry; Eczema; Humans; Lymphocytes; Occupational Diseases; Patch Tests; Penicillin G; Rhinitis, Allergic, Perennial; Structure-Activity Relationship

Twenty-five workers with clinically diagnosed or suspected occupational hypersensitivity caused by contact with bacampicillin, alprenolol, and/or quinidine were studied by the lymphocyte transformation test and by skin tests. Ten healthy exposed workers, 16 job applicants, and seven healthy nonexposed laboratory workers served as control subjects. Lymphocyte transformation was measured by 3H-thymidine uptake into DNA and by counting of lymphoblasts on cell smears. Lymphocytes from workers with contact eczema or with eczema in combination with conjunctivitis and rhinitis responded to offending drugs in vitro as demonstrated by an increased 3H-thymidine incorporation and by the presence of lymphoblasts in the cultures. In vitro proliferative responses were reproduced during a 4-year period. Drug-specific allergy was confirmed by positive patch test in most workers with eczema. In addition, bacampicillin-specific lymphocyte proliferation was also observed in workers with suspected bacampicillin hypersensitivity but with negative skin tests. They suffered mostly from eczema in combination with conjunctivitis and rhinitis or from conjunctivitis/rhinitis only. Lymphocytes from most control subjects did not respond in vitro to bacampicillin, alprenolol, or quinidine. Weak proliferative responses to bacampicillin were observed in two of the 16 job applicants. The exquisite specificity of drug-induced lymphocyte responses is demonstrated. Thus, lymphocytes from a quinidine-sensitive worker did not respond in vitro to the quinidine stereoisomer, quinine. Furthermore, lymphocytes from a bacampicillin-sensitive worker responded to some penicillins, such as pivampicillin and ampicillin, but not to others, such as benzylpenicillin or pivmecillinam. These data suggest the role of N-acylamido side chain in the sensitization of lymphocytes from this particular donor. In conclusion, lymphocyte transformation test can be used for the detection of offending agents in occupationally sensitized workers. Furthermore, lymphocytes from such individuals may serve as a model for study of specificity of cellular reactions underlying drug-induced hypersensitivity.

Topics: Adult; Ampicillin; Dermatitis, Occupational; Drug Hypersensitivity; Female; Humans; Lymphocyte Activation; Male; Middle Aged; Occupational Diseases; Skin Tests

Topics: Alprenolol; Ampicillin; Chlormethiazole; Dermatitis, Occupational; Drug Hypersensitivity; Humans; Lymphocyte Activation; Metoprolol; Occupational Diseases; Quinidine