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Notes: To determine the influence of the acyl side chain on the IgE antibody specificity of the two most common penicillins inducing allergic reactions in our community, benzyl-penicillin (BP) and amoxicillin (AX), IgE positive sera from a group of 24 patients allergic to penicillin were studied. RAST was determined in parallel to benzyl penicilloyl-polylysine (BPO-PLL) and amoxicilloyl-polylysine (AX-PLL) in each serum, and values greater than an established coefficient of variation of 15% were considered as different for either of the haptens used (BP and AX). 16 sera proved to be more positive to BP (Group A), six to AX (Group B) and in two IgE was positive to both haptens with a similar value (Group C). RAST titration concentration effect curves and RAST inhibition studies with a pool of sera from each group (A, B, C) and individual sera showed that most of them were more specific for either BPO or AX, a minority being of similar value to both. These findings indicate that the side chain structure of penicillins is relevant in the constitution of the antigenic determinant, although in some instances the common chemical structure of betalactam is recognised mainly by the IgE antibodies. The clinical relevance of these data needs to be established.

Notes: Background and Objective Ainpicillin (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.Objective To study tbe specificity of tbe IgE response in a group of subjects who had an immediate allergic reaction after the administration of AMP.Methods Subjects developing an immediate response (anapbylaxis or urticaria) after the administration of AMP or an aminopenicillin derivative witb 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-polyllsine (AX-PLL) and ampicilloyl-polylisine (AMPPLL). The specificity of the IgE antibody response was studied by RAST and RAST inbibition. Subjects were classified in three categories: group A: those who were skin test and/or RAST positive to determinants derived from benzylpenicllin, group B: those who were negative to determinants derived from benzylpenicillin but were skin lest and/or RAST positive to determinants derived from AX and AMP and group C: those who were exclusively positive to determinants derived from AMP.Results 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 tbree cases. RAST inhibition studies showed that in some instances tbe side chain of AMP could induce specific responses with a variable degree of crossreactivity between BP and AX.Conclusions Atbough AMP can induce an immediate IgE response in subjects allergic to betalactams and tbe structure of the side chain may contribute to the specificity of the response, our results indicate tbat in most instances crossreactivity with the other penicillins exists and that in the groups studied selective reactions to just AMP derived determinants were uncommon.

Notes: Background  Atopic dermatitis (AD) is an inflammatory skin disease whose lesions can have two stages: acute and chronic. In skin biopsies a biphasic pattern of cytokine expression has been shown, Th2 in acute lesions and Th1 in chronic AD lesions.Objective  We investigated the expression of an activation marker and a homing receptor, as well as cytokine production, in different peripheral blood T cell subpopulations from AD patients with chronic (Group A) and acute lesions (Group B) and controls.Methods  We evaluated 26 adult AD patients (12 Group A, 14 Group B) and 14 non-atopic controls. IgE was measured by immunoassay. CD4, CD8, cutaneous-lymphocyte-associated antigen (CLA) and human leucocyte antigen (HLA)-DR expression, and cytokine production (IL-2, IL-13, IFN-γ, TNF-α, IL-10, IL-4) were analysed in mononuclear cells by flow cytometry.Results  In Group B there was a significant increase in eosinophil levels and a non-significant increase in IgE. In Group A we found an increase in CLA+CD4+ cells (8.19±1.84) compared with controls (4.83±0.53) (P〈0.05) and CD4+HLA-DR+ cells in the CLA+ subpopulation (45.54±15.40) compared with controls (30.49±6.07) (P〈0.05). In the CLA+CD4+ subpopulation, there was a significant increase in IL-4, IL-13 and TNF-α production in Group B (12.46±7.7, 11.26±5.97, 43.92±15.55) compared with controls (5.34±3.50, 4.54±1.78, 19.29±9.97) with no differences in Group A.Conclusion  Greater immunological differences were detected in peripheral blood from patients with acute compared with chronic lesions, especially in the circulating T cell-subset with skin tropism that preferentially responded to cutaneous allergens. This is the first demonstration of phenotypic changes in circulating CLA+ T cells between AD patients with acute and chronic lesions.

Notes: Background There are instances where individuals may come into contact with penicillins without being aware of it. This non-therapeutic exposure from different sources may cause sensitization and even clinical manifestations in subjects allergic to penicillins.Objective To determine the capacity that inadvertent contact with penicillins may have in inducing resensitization and symptoms in patients diagnosed as allergic to penicillins who were followed over a long period of time after their initial evaluation. Methods A follow-up study of penicillin-allergic subjects who agreed to be regularly tested for in vitro and in vivo control of their sensitivity. Skin tests were carried out with major and minor determinants of benzylpenicillin (BPO and MDM), amoxicillin (AX), and ampicillin (AMP), and specific IgE antibodies were determined by radioallergosorbent test (RAST). A questionnaire was sent to and answered by the subjects in order to see if they experienced symptoms at any time during the follow-up period. In addition, if any unexplained symptoms occurred, a bleeper system was used to contact the allergy centre.Results Seven subjects experienced anaphylactic reactions with no obvious cause. At the time of their initial allergic reaction, which was caused by exposure to prescribed penicillin, the subjects had one or more positive skin tests and/or RAST results to penicillin related reagents. However, over the following 2–4 years all their tests became negative. After reporting their unexplained reaction all seven had one or more positive skin tests and/or RAST results again and when retested 1 week later RAST measure ments showed that levels of penicillin-specific IgE were maintained or increased. None of the subjects had knowingly received penicillin but the questionnaire showed that six had been exposed to it and in the seventh case exposure was likely. In two cases contact was by sexual intercourse with a partner who was receiving penicillin, three subjects had handled penicillin formulations and one had drunk from a glass previously used for giving penicillin. In the seventh case exposure could have occurred whilst in hospital for surgery, although this was not proven.Conclusions these results show that non-therapeutic exposure to penicillin can cause severe symptoms and that in vitro and in vivo testing can help in the diagnosis of such cases.

Notes: Background Basophil activation by allergens, including drugs, has been used to determine sensitivity and to study IgE recognition and cross-reactivity.Objective We sought to determine the sensitivity and specificity of a basophil activation test (Basotest) in patients with immediate allergic reactions to betalactams, with a later comparison between patients who were selective (those recognizing the culprit drug excluding benzylpenicillin (BP)) and cross-reactors (those recognizing several penicillin determinants including BP).Methods Basotest to different haptens was performed in 70 patients with immediate allergic reactions to betalactams, classified into three groups: (A) skin test positive independently of CAP/RAST immunoassay value, (B) skin test negative and CAP/RAST positive, and (C) skin test and CAP/RAST negative but drug provocation test positive. Basotest was carried out by flow cytometry following the manufacturer's instructions using different betalactam determinants and results expressed as a stimulation index.Results Of the 70 patients, 34 (48.6%) were positive to Basotest (sensitivity: 48.6%), 31 (44.3%) to CAP/RAST and 46 (65.7%) to either one or the other. Considering the different groups, Basotest was positive in 50.9% of patients in Group A, 60% in Group B and 14.3% in Group C. The specificity was 91.3%. Positivity to the haptens was 28.6% to amoxicillin (AX), 21.7% to BP, 20% to benzylpenicilloyl-poly-l-lysine, 12.5% to ampicillin and 2.2% to minor determinant mixture. In patients with cephalosporin reactions, Basotest to the culprit cephalosporin was positive in 77.7%. There were differences between the two reactor groups in the sensitivity of Basotest (selective to AX=50%, cross-reactors=28.6%; χ2=10.809, P=0.004) and in the CAP/RAST (selective to AX=28.6%, cross-reactors=61.9%; χ2=8.944, P=0.011).Conclusions The sensitivity of Basotest is similar to immunoassays (CAP/RAST). Sensitivity is improved when used in combination. Although further studies are required, Basotest results for cephalosporin allergy seem very promising. This technique does not help differentiate between selective reactors and cross-reactors.

Notes: Background Subjects with IgE responses to betalactams can develop selective or cross-reactive responses after the administration of penicillin derivatives. After the reaction, however, the hapten induces a boosting phenomenon, which may increase the titre and the affinity of the antibody, with the resulting risk of developing allergic reactions to other penicillins.Objective To determine in subjects with selective responses to amoxicillin (AX) and good tolerance to benzylpenicillin (BP) and penicillin V (PV) whether the administration of these compounds induced any change in specificity, measured by either skin or in vitro testing, which could predict the appearance of cross-reactivity.Methods Ten subjects with a selective response to AX were followed-up for 2 years with the periodic administration of penicillin G and V (Group A) and compared with another group composed of 10 persons with identical clinical characteristics but without repeated penicillin administration (Group B). Periodic in vitro and in vivo measurements of specific IgE antibodies were performed at 6-month intervals. Patients were randomized to Group A or B according to their order of inclusion.Results In both groups, skin test reactivity tended to decrease, and although greater in Group A, the difference was not significant compared with Group B. Median RAST values also decreased over time and showed no differences in the exposed group compared with the controls. One patient in Group A became positive to benzylpenicilloyl (BPO), despite becoming negative to AX.Conclusion Subjects with selective IgE responses to side-chain-specific determinants seem to become negative, with no influence from subsequent administration of a closely related penicillin.

Notes: Background Although subjects with a positive history of immediate allergy to penicillin and negative skin test are traditionally considered to tolerate penicillin, current evidence indicates that they may develop an immediate reaction despite negative skin and serum specific IgE tests. It is thought that these patients require additional tests to confirm the diagnosis.Objective To assess in a large group of patients with a history of immediate allergy to penicillins but with both skin test and CAP-FEIA-negative to classical and side chain penicillin determinants, the role of controlled administration of betalactams as a diagnostic test.Methods A group of 330 patients with a history of immediate allergic reactions to penicillins was studied by two evaluators from the same allergy unit using the following protocol: skin tests with major and minor determinants of benzylpenicillin (benzylpenicilloyl-poly l-lysine and minor determinant mixture), amoxicillin and ampicillin, and determination of specific IgE antibodies to penicillins, by CAP-FEIA, in serum. If both tests proved negative, a controlled administration of the drug was then carried out.Results A total of 89 (27%) patients were skin test and CAP-FEIA-negative and therefore required controlled administration of the drug. Of these, 49 developed an immediate response and were therefore considered allergic, and the remainder had good tolerance after administration of both benzylpenicillin and amoxicillin. The clinical characteristics of this group were similar to the other allergic patients who were skin test or CAP-FEIA-positive, except that they were younger (P 〈 0.01). Twenty-two (45%) developed a response to benzylpenicillin and 27 (55%) had a selective response to amoxicillin. Although all reactions appeared within 1 h, a positive correlation was found between the dose inducing the response and the time elapsed from drug administration, for both benzylpenicillin and amoxicillin (P 〈 0.001).Conclusion These data indicate that an important number of subjects are not correctly identified if only skin tests and/or CAP-FEIA are used and that this is particularly relevant for side chain-specific reactions and younger subjects. This suggests that new diagnostic tests are required so as to limit the use of controlled administration.