Understanding drug allergies

doi:10.1067/mai.2000.106156

Journal of Allergy and Clinical Immunology

Volume 105, Issue 6, Part 2, June 2000, Pages S637-S644

https://doi.org/10.1067/mai.2000.106156 Get rights and content

Abstract

At this time, the incidence of adverse drug reactions can only be estimated because the intensive monitoring and documenting that is required to make this determination does not exist at most hospitals and clinics. Despite these limitations, a meta-analysis of prospective studies has estimated the incidence of serious adverse drug reactions in hospitalized patients to be 6.7% and the incidence of fatal adverse drug reactions to be 0.32%. When evaluating and managing the condition of a patient who has experienced an adverse drug reaction, the physician first obtains an accurate history and performs a careful physical examination to determine whether the reaction was immunologic in nature. Drug reactions that are immunologically mediated (1) require a period of sensitization, (2) occur in a small proportion of the population, (3) are elicited at drug doses far below the therapeutic range, and (4) subside after drug discontinuation in most instances. All possible culprit drugs should be identified, with dosages and dates of administration and discontinuation, and the patient should be asked about any previous drug exposure history. Although immunodiagnostic tests for allergic drug reactions are limited, several tests do exist and may be useful in the identification of drug-specific antibodies, drug-specific T lymphocytes, or mediators from activated cells. If the reaction was not consistent with an IgE-mediated event and if it did not involve serious organ damage, cautious rechallenge may be considered. For those reactions that appear to be IgE-mediated and for which there is no reliable skin test reagent, drug desensitization may be performed by allergists who are trained in this procedure. (J Allergy Clin Immunol 2000;105:S637-44.)

Section snippets

Overall incidence and clinical significance

Although most studies of ADR incidence that are currently available in the literature have been performed in Europe, a number of US studies also exist. In 1998, Lazarou et al¹ performed a meta-analysis of 39 prospective studies from US hospitals and estimated the overall incidence of ADRs in hospitalized patients to be 6.7%, with a 0.32% incidence of fatal ADRs. When both serious and nonserious ADRs were considered together, the percentage more than doubled, to 15.1% of hospitalized patients.

Definition of terms

To clearly understand the terms used to describe allergic drug reactions, it is important to recognize how they are grouped under the much larger ″umbrella” category of ADRs. ADRs are divided into predictable and unpredictable reactions. Predictable reactions are dose dependent, are usually related to the known pharmacologic actions of the drug, and are observed to occur in otherwise normal patients. Examples of predictable reactions include toxicity, side effects, secondary drug effects, and

Initial evaluation

When evaluating and managing the condition of a patient who has experienced an ADR, the physician must first obtain an accurate medical history and perform a careful physical examination. The determination must be made regardless of whether the reaction was immunologic in nature. Obtaining an accurate medical history is a critically important step in making this determination. All possible culprit drugs should be identified and recorded, along with their dates of administration and

Drug desensitization: when should it be performed

Desensitization is defined as the conversion of a patient with a drug allergy from a highly sensitive state to a state in which the drug is tolerated. The procedure is performed by the cautious administration of incremental doses of the drug to the patient over a period of hours to days. It is implemented in patients with known or presumed IgE antibodies to a particular drug for whom no alternative drug is available.

In the past, acute drug desensitization was considered an approach to the

CONCLUSION

Information critical to the successful management of the patient with drug allergy includes accurate historic data, a carefully performed physical examination, and selected general and/or specific diagnostic tests. It is not unusual for an allergist to spend one hour or more gathering relevant medical history information. Questions about drug dosage, previous drug exposure, temporal relationship between drug administration and reaction onset, and clinical manifestations of the reaction should

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This retrospective study aimed to evaluate the characteristics of all reported DHRs over 10 years in a tertiary-care allergy clinic in Lebanon.
We conducted a decade-long (2012-21) retrospective analysis of the archived medical records of patients with a history of DHRs. Demographics, clinical history, diagnostic tools, and characteristics of the DHRs were collected and analyzed.
A total of 758 patients experienced DHRs to therapeutic molecules provided for ambulatory care. Our results identified 72 medications. The most frequently implicated drug classes included β-lactam antibiotics (53.8%), followed closely by nonsteroidal anti-inflammatory drugs (48.9%). Of the 758 patients, 32.6% reported DHRs to multiple molecules, and 11.8% reported concomitant DHRs to 1 or several molecules provided in the perioperative setting. Of those, opioids and neuromuscular blocking agents were the 2 most common therapeutic classes. Furthermore, we evaluated the cross-reactivity between molecules of the same class. In neuromuscular blocking agents, rocuronium and cisatracurium were the most commonly cross-reactive, and for opioids, the most common association we recorded was with morphine and pethidine.
Our findings constitute the first step toward a more comprehensive evaluation of the clinical characteristics of DHRs in Lebanon.
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Evidence is lacking on the association between antibiotic use and risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Asians.
We assessed the risk of SJS/TEN associated with different antibiotic classes in Japanese.
We conducted a case-crossover study using a claims database. Firth conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of SJS/TEN associated with antibiotic use in a 56-day hazard period versus 3 control periods. We created 18 cohorts for each antibiotic class and calculated 56-day cumulative incidence per 100,000 new users. The association between antibiotic class and SJS/TEN was also evaluated in each case using the ALgorithm of Drug causality for Epidermal Necrolysis (ALDEN).
Our case-crossover study included 170 SJS/TEN cases. Increased ORs were observed for lincomycins (OR, 33.00 [95% CI, 3.74-4332.05]), trimethoprim-sulfamethoxazole (21.20 [6.73-105.98]), penicillins (14.39 [6.95-34.21]), glycopeptides (14.37 [3.17-136.10]), cephalosporins (7.06 [4.25-12.21]), aminoglycosides (6.55 [1.97-26.84]), quinolones (5.98 [3.34-11.20]), fosfomycin (5.40 [1.20-30.97]), carbapenems (5.09 [1.85-15.64]), tetracyclines (4.95 [1.78-15.27]), and macrolides (3.78 [2.13-6.83]). Cumulative incidence of SJS/TEN was 67.4 for trimethoprim-sulfamethoxazole, 86.2 for glycopeptides, and below 10.0 for the others. Despite the high incidence, only 2 cases had a probable causal relationship with glycopeptides.
Some antibiotic classes, including lincomycins, glycopeptides, aminoglycosides, fosfomycin, and carbapenems, were newly suggested to be associated with risk of SJS/TEN; considered together with the high incidence for trimethoprim-sulfamethoxazole and glycopeptides, these findings warrant caution in clinical practice.
Pyrazinamide-induced neutropenia: One new case
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Le pyrazinamide est un antituberculeux majeur, généralement bien toléré. Ses effets indésirables sont bien connus, parmi lesquels des effets indésirables hématologiques sévères, rarement rapportés.
Il s’agit d’un patient âgé de 12 ans, sans antécédents particuliers connus, traité pour tuberculose ganglionnaire confirmée histologiquement par rifampicine, isoniazide et pyrazinamide. Le traitement a été pris pendant 15 jours, puis arrêté pour rupture de stock pendant cinq jours. Deux heures après la reprise du traitement, l’enfant a présenté un syndrome pseudo-grippal aigu avec neutropénie à 1080/μL, justifiant l’arrêt des antituberculeux. La reprise du traitement, en commençant par le pyrazinamide à faible dose, a entraîné une récidive et fait suspecter le pyrazinamide. L’arrêt, puis le test de réintroduction de cette molécule confirmant le diagnostic, le pyrazinamide a été arrêté définitivement et l’enfant a été mis sous rifampicine, isoniazide et éthambutol. Par ailleurs, le bilan réalisé a mis en évidence une sérologie VIH positive. À notre connaissance, ce cas est le premier cas de neutropénie induite par le pyrazinamide rapporté dans la littérature.
À travers cette observation, nous insistons sur le caractère exceptionnel de cet effet indésirable lié au pyrazinamide que le clinicien doit connaître, ainsi que sur la fréquence des effets indésirables des antituberculeux chez les sujets VIH positifs.
Pyrazinamide is a major antituberculosis, generally well tolerated. Side effects are well known. Among them, severe haematological side effects have been rarely reported.
We report the case of a 12-year-old patient, without history of lung diseases, treated for lymph node tuberculosis confirmed histologically by rifampicin, isoniazid, and pyrazinamide for 15 days. Treatment was stopped due to interruption of the drugs stock for 5 days. Two hours after resumption of treatment, the child presented an acute influenza-like illness with neutropenia at 1080/μL, justifying stopping antituberculosis treatment. Pyrazinamide was then reintroduced in low doses, but lead to recurrence of clinical symptoms. The response to eviction and reintroduction of pyrazinamide diagnosed the responsability of this drug, which was stopped. The child was then treated with rifampicin, isoniazid and ethambutol. Moreover, the biological tests showed a positive HIV serology. To our knowledge, this case is the first case of pyrazinamide-induced neutropenia reported in the literature.
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Reply
2011, Journal of Allergy and Clinical Immunology
Hypersensitivity reactions to antituberculous therapy
2010, Revue des Maladies Respiratoires
La survenue d’une manifestation d’hypersensibilité pose un problème diagnostique mais aussi thérapeutique. Le but de ce travail est d’étudier la fréquence des réactions allergiques aux antituberculeux, leurs aspects cliniques et les moyens diagnostiques.
Étude rétrospective portant sur 30 patients hospitalisés dans le service de pneumologie de Ibn Nafiss de l’hôpital Abderrahmen Mami de l’Ariana entre janvier 1990 et juin 2008 et ayant présenté une réaction allergique aux antituberculeux.
Les atteintes cutanées étaient les plus fréquentes (80 % des cas), dominées par l’urticaire. La thrombopénie a été notée dans deux cas, le choc anaphylactique dans trois cas, une toxidermie généralisée dans deux cas et une insuffisance rénale chez un malade. Le pyrazinamide a été incriminé dans la plupart des cas (28 %) quand un seul médicament a été retenue comme responsable de la manifestation d’hypersensibilité. Le recours à l’arrêt d’un médicament ou de tout le traitement était nécessaire pour définir l’imputabilité de chaque médicament. L’évolution des manifestations d’hypersensibilité a été favorable dans tous les cas après l’arrêt définitif du médicament incriminé. La guérison totale de la maladie tuberculeuse a été obtenue dans tous les cas.
Une surveillance étroite des malades sous antituberculeux est nécessaire pour détecter l’apparition de réaction allergique et assurer une bonne observance au traitement.
Hypersensitivity reactions to antituberculous drugs pose both a diagnostic and a therapeutic problem. This work aims to study the frequency of allergic reactions to antituberculous drugs, their clinical presentations and the diagnostic approach required.
This retrospective study covered the period from January 1990 to June 2008 at the Ibn Nafis Pulmonary Department of Abderrahmen Mami Hospital in Ariana. It dealt with 30 in-patients who experienced an allergic reaction to antituberculous drugs.
Cutaneous manifestations were the most frequent (80% of cases), predominantly urticarial. Thrombocytopenia was noted in two cases, anaphylactic shock in three cases, a systemic toxidermia in two cases and renal failure in one patient. Pyrazinamide was implicated in most cases (28%) when only one drug was considered to be responsible for the reaction. Interrupting either one drug or the whole treatment was necessary to define the cause of the reaction. The clinical evolution of hypersensitivity signs was favorable in all cases following definitive withdrawal of the responsible drug. Complete recovery from tuberculosis occurred in all cases.
Close monitoring of patients on antituberculous treatment is required to detect the onset of any allergic reaction and ensure an adequate compliance with treatment.
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Understanding drug allergies

Abstract

Section snippets

Overall incidence and clinical significance

Definition of terms

Initial evaluation

Drug desensitization: when should it be performed

CONCLUSION

J Allergy Clin Immunol

J Allergy Clin Immunol

J Pediatr

Immunol Allergy Clin North Am

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies

JAMA

Allergic reactions to drugs and biologic agents

JAMA

Drug-induced cutaneous reactions: a report from the Boston Collaborative Drug Surveillance Program on 152,438 consecutive inpatients, 1975 to 1982

JAMA

Comprehensive hospital drug monitoring: adverse drug reactions: a 20-year survey

Allergy

Disease management of drug hypersensitivity: a practice parameter

Ann Allergy Asthma Immunol

Classification of allergic reactions responsible for clinical hypersensitivity and disease

Drug allergy

Toxicity of sulfonamide-reactive metabolites in HIV-infected, HTLV-infected, and noninfected cells

J Acquir Immune Defic Syndr Hum Retrovirol

Synthesis and in vitro toxicity of hydroxylamine metabolites of sulfonamides

J Pharmacol Exp Ther