Paracetamol Hypersensitivity: Clinical Features, Mechanism and Role of Specific IgE

Abstract

Background: Paracetamol is a common antipyretic/analgesic and a component of many prescription and over- the- counter preparations. Hypersensitivity reactions to paracetamol appear to be increasing, but there are few prevalence data. The mechanism is poorly understood. We identified the clinical features of 32 patients with suspected paracetamol allergy, investigated the underlying mechanism and examined co-existing non-steroidal anti-inflammatory drug (NSAID) tolerance. Methods: Aclinical history was taken and skin tests and an oral challenge were performed in 32 patients with suspected paracetamol allergy. Results: Patients presented with a combination of urticaria, angio-oedema (face, hands), erythema (cutaneous features in 94%), dyspnoea (including laryngeal oedema), rhinoconjunctivitis, cough, abdominal pain and anaphylaxis. Two patients had a positive skin prick test (SPT) and unequivocal history of acute urticaria/facial angio-oedema/conjunctivitis/cough after paracetamol with no other triggers. One patient had a positive intradermal test. Oral challenge was positive in 15 of 31 patients (including self-challenge in 4), triggering (a combination of) rhinitis, conjunctivitis, pruritus, erythema, urticaria, angio-oedema, dyspnoea and abdominal pain. Sensitivity was evident in 1 patient on the basis of the patient’s history. Overall, paracetamol hypersensitivity was confirmed in 16 of the 32 patients (50%). Twelve of the 16 paracetamol-allergic patients (75%)tolerated NSAIDs (negative challenge in 6, negative history in 6). Four of these 16 patients (25%) were intolerant of NSAIDs (positive challenge in 1, self-challenge in 3). Conclusions: In past reports on paracetamol hypersensitivity, only single cases of a positive SPT and detectable specific IgE have been described. Our data confirm that specific IgE may be a mechanism underlying paracetamol hypersensitivity, as in this series 18.8% of the patients had specific IgE. In 81.2% of patients, negative skin tests did not exclude paracetamol hypersensitivity, suggesting that it may be mediated by leukotrienes. However, three quarters of our patients tolerated NSAIDs, implicating an alternative mechanism. In patients with suspected paracetamol allergy, skin tests should be performed in addition to clinical history and oral challenge.

Reported Case of Paracetamol and Non-Steroidal Anti- Inflammatory Drug (NSAID)-Induced Seizures in a Patient with HIV Infection

“…In our patient, we did not observe any of such reported reactions as rashes, skin eruption or bronchospam [1][2][3][4][5]. Our patient experienced profuse night sweats followed by generalized jerky movements of the body similar to a tonic-clonic seizure.…”

“…The immediate reaction to paracetamol and diclofenac in our patient may suggest that this may be IgE-mediated but our patient did not exhibit the classic features of paracetamol IgEmediated reaction [1]. It is possible that other mechanisms may be involved in the reaction of this patient.…”

“…While many individuals who show allergic reactions to paracetamol may tolerate NSAIDs, it is not unusual for some patients to show allergies to both paracetamol and NSAIDs [1,2,4]. The immediate reaction to paracetamol and diclofenac in our patient may suggest that this may be IgE-mediated but our patient did not exhibit the classic features of paracetamol IgEmediated reaction [1].…”

“…While the medications have analgesic properties, paracetamol unlike NSAIDs lack antiinflammatory properties. Allergic reactions to paracetamol have been widely reported and studied in various parts of the world [1][2][3][4]. Some of the reported reactions range from urticaria and angioedema to severe skin eruptions like toxic epidermal necrolysis.…”

“…Some of the reported reactions range from urticaria and angioedema to severe skin eruptions like toxic epidermal necrolysis. Other reported reactions to paracetamol include rhinitis, conjunctivitis, abdominal pain and bronchospasm [1,5]. Some of these reactions are thought to be immunoglobulin E (IgE)-mediated [1].…”