Drug-induced Allergic Reactions Research Articles

Drug-induced allergy

Drug-induced allergy

Erythema Multiforme and Hypersensivity Myocarditis Caused by Ampicillin

To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.

Lymphocyte stimulation test with tetrazolium-based colorimetric assay for diagnosis of drug-induced allergic hepatitis.

The lymphocyte stimulation test (LST) is useful for diagnosing drug-induced allergy and identifying the causative drug. In this study, we examined the usefulness of 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as a marker for LST in diagnosing drug allergy. In a basic study using normal peripheral blood mononuclear cells, the normal range of stimulation index (SI) was 0.92-1.38, and the mean SI for all drugs tested was 1.134 +/- 0.111 (mean +/- S.D.). The cut-off value of SI for diagnosis of drug allergy was thus set at over mean + 2S.D. for possibly positive, and at over mean + 3S.D. as a definitely positive reaction. Forty-six cases of suspected drug-induced allergic hepatitis involving 85 drugs were diagnosed by this assay, and the possibly positive and definitely positive rates were 54.3% (SI > or = 1.4) and 41.3% (SI > or = 1.5), respectively. A clinical study was made of 113 patients with diagnosed drug-induced allergic hepatitis. Forty-nine (43%) of the patients were male and 64 (57%) were female. In 85% of cases the allergic reaction occurred within one month of taking medication, but there were a number of cases in whom onset occurred after long-term incubation. The main clinical symptoms were jaundice, itching, eruption, fever, and general malaise. In about 75% of cases glutamic oxaloacetic transaminase (GOT) or glutamic pyruvic transaminase (GPT) returned to normal range within one month after medication was halted.(ABSTRACT TRUNCATED AT 250 WORDS)

Perioperative nonspecific histamine release : a new classification by aetiological mechanisms and evaluation of their clinical relevance

As a consequence of the performance of a randomized controlled clinical trial on perioperative histamine release and cardiovascular and respiratory disturbances, several types of increases in plasma histamine had to be distinguished instead of only two which existed at the beginning of the study : drug-induced allergic and pseudoallergic reactions. First of all, the new classification by aetiology (clinical epidemiology) was derived from a metaanalysis (secondary analysis) of the most recent literature. According to that histamine release in the perioperative period has several, different causes and is involved in several, different disease manifestations. A clear distinction (classification), however, is necessary if histamine release as an unwanted (adverse) effect has to be recognized, value judged according to its clinical relevance and therefore also prevented by histamine antagonists. Histamine release by neuro-endocrine and neuro-inflammatory mechanisms, cytotoxic histamine release and local, cytokine induced histamine release have been distinguished from pseudoallergic histamine release, but its functions are not yet clear. It has been analysed in prospective trials which used special clinical situations as models : patients on a normal ward or before and during upper GI endoscopy without premedication, but also in specific phases of laparoscopic cholecystectomy (trocar phase and dissection phase). Their existence in the clinical reality is now very likely, but new trials must investigate the pathophysiological effects such as in metabolism, coagulation, pulmonary haemodynamics (shunt volume) and gastric acid secretion. Histamine release by pseudoallergic mechanisms, however, was identified in the very vulnerable post-induction phase of anaesthesia up to skin incision. Its incidence was much higher than ever expected and its clinical relevance was demonstrated by the severity of reactions and the intervention strategies of the anaesthetists who were blinded concerning the type of the plasma substitute given and the prophylaxis with antihistamines. Pseudoallergic histamine release was clearly unwanted (adverse). Its occurence in the other phases of anaesthesia has to be further evaluated in the tedious procedure of data analysis of the Mainz-Marburg-trial. The overall incidence of histamine release in the trial was so incredibly high (72 % of all patients, some of them with up to 4 episodes of histamine release) that a distinction between pseudoallergic (unwanted) and other types of histamine release (possibly less unwanted or even beneficial) is urgently needed. In the phase of steady state (maintenance) of anaesthesia the H 1- + H 2-prophylaxis was highly effective. Further analysis must show whether this is also the case during the phases of induction of anaesthesia. Many of the pseudoallergic histamine release reactions (72 %) occur without cutaneous signs — even with plasma histamine levels of 12 ng · ml −1, i.e. in the range of usually life-threatening reactions. The clinical picture of these reactions has to be revised. Since in the case of haemodynamic instability alone the anaesthetist cannot distinguish between histamine-induced reactions and cardiovascular reactions based on other mechanisms, a considerable underreporting of the reactions is fully understandable. Plasma histamine assays are necessary under strict quality control to create awareness of this considerable clinical problem. If that is understood the questions of antihistamines : yes or no ? to whom ? at which time ? and which drugs and dose ? will be asked in a different way than hitherto.

Rezidivierende aseptische Meningitis (Mollaret-Meningitis) - spontanes und medikamentös induziertes Auftreten

Since its initial description by Mollaret in 1944, the etiology of the chronic aseptic meningitis has remained unknown. This rare disease may cause diagnostic problems if bacterial or viral causes are suspected. A different form of aseptic meningitis may be seen following a variety of drug treatments, especially with non-steroidal anti-rheumatic drugs: In many reports since 1978, meningitic attacks following administration of ibuprofen have been reported. We describe two cases of Mollaret-Meningitis with certain specialities: one case shows clear encephalitic involvement with aphasia in all six attacks. In the other case, five meningitic attacks appeared spontaneously, while two were drug-induced: the first attack was seen after a lumbar myelography with lopamidol and one attack appeared two hours after oral administration of 400 mg ibuprofen. It is suggested that Mollaret-Meningitis is a special form of a drug-induced allergic reaction, the provoking agent of which remains unknown.

Drugs as allergens

The combining site specificities of IgE antibodies that react with the oral antibacterial agent trimethoprim and found in the sera of two subjects who experienced anaphylaxis after taking the drug, were investigated. Hapten inhibition studies with some close analogues of trimethoprim and a range of other structurally related compounds showed that the allergenic determinant complementary to the IgE antibodies in the serum of one of the subjects was the 3,4-dimethoxybenzyl group. The complementary allergenic structure recognized by the IgE antibodies in the serum from the second subject comprised both the trimethoxybenzyl and diaminopyrimidine rings of trimethoprim. Thus, as with thiopentone, but unlike the neuromuscular blocking drugs, the trimethoprim molecule has more than one determinant each with the capacity to provoke IgE formation, interact with the antibody combining site and provoke drug-induced allergic reactions. The general approach set out here employing carefully selected structural analogues in hapten inhibition studies should be invaluable for confirming specificity and identifying allergenic determinants in IgE antibody-mediated allergic drug reactions.

Defined test reagents for the diagnosis of drug-induced allergy: Antibody-dependent skin reactions towards pyrazolinone and pyrazolidinedione derivatives in the guinea pig

Chemically defined haptenic reagents and haptenic conjugates were synthesized for use in clinical skin testing. One series of reagents was based on the 1-phenyl-2,3-dimethyl-3-pyrazolin-5-one structure, a second series on 1,2-diphenyl-pyrazolidine-3,5-dione. Haptens were connected via flexible spacer molecules which insert considerable distances between haptenic moieties and carriers. The skin test reagents were hexavalent conjugates prepared from the bis-penta- L-lysine carrier ‘PAL’. The methodological details exemplify the application of N-hydroxysuccinimide activated ester derivatives for the preparation of peptidic conjugates. Rabbit and guinea-pig antisera against the haptens were obtained by immunization with human serum albumin conjugates. Efficacy and cross-reactivity relationshios were assessed by guinea pig PCA and by testing actively immunized guinea pigs. A striking lack of cross-reactivity was found between pyrazolinone and pyrazolidinedione haptenic reagents in all test systems. On the other hand, the elicitation of homologous anaphylaxis was highly effective with the PAL conjugates. The data presented and discussed provide a basis for the evaluation of clinical tests performed in order to define drug-induced allergic reactions. They are relevant for immediate-type skin reactions as well as for serological methods.

Drugs as Allergens: The Molecular Basis of IgE Binding to Thiopentone

Using an immunoassay developed for the detection of thiopentone-reactive IgE antibodies, the combining site specificities of such antibodies found in sera of patients who experienced life-threatening anaphylactic reactions to the drug were studied. The antibody combining sites from one patient were complementary to the region of the thiopentone molecule containing a thio group at position 2 of the barbiturate ring. The allergenic determinant recognized by IgE antibodies from another patient encompassed a secondary pentyl group and an ethyl group attached to position 5 on the other side of the barbiturate ring. Thus, it is already clear that there is more than one allergenic determinant on the thiopentone molecule with the capacity to provoke IgE formation and drug-induced allergic reactions.

Drug-induced allergic reactions

Drug-induced allergic reactions