Delayed skin reactions to metamizol
Authors: J.M. Borja, P.A. Galindo, E. Gomez, F. Feo
Journal: Allergy (2003)

Pyrazolone derivatives, especially metamizol, are some of the most prescribed analgesics throughout the world. Three cases of delayed drug allergy.They are frequently implicated in severe and unpredictable reactions. According to the etiologic mechanism, the following classification is proposed (1, 2): Allergic reactions, usually anaphylaxis and urticaria/angioedema, probably due to an IgE-mediated mechanism. In these cases, patients tolerate different nonsteroidal antiinflammatory drugs (NSAIDs). Nonallergic NSAID hypersensitivity (3) (NSAID intolerance), probably via cyclooxygenase inhibition, leading to an overproduction of leukotrienes. NSAIDs can precipitate asthma attacks and/or urticaria or angioedema. Severe skin and/or mucosal reactions, such as Stevens–Johnson syndrome, toxic epidermal necrolysis, fixed drug eruption, and contact dermatitis. Probably a cell-mediated mechanism is implicated. Other clinical syndromes, such as agranulocytosis, thrombocytopenia, and vasculitis whose mechanism is unknown. Here we present three cases of adverse skin reactions to systemic administration of metamizol (Nolotil). Patient 1: An 18-year-old man began treatment for pharyngoamygdalitis with amoxicillin (500 mg/8 h), metamizol (500 mg/8 h) and acetaminophen (650 mg/8 h) orally. After 48 h he developed a generalized maculopapular exanthema without pruritus. The clinical picture was spontaneously resolved in 15 days with mild desquamation. Patient 2: A 61-year-old woman who received metamizol 2 g and clarithromycin 500 mg intravenously. After 12 h she developed a maculopapular exanthema with pruritus. This reaction was resolved in 15 days after antihistamine treatment. Patient 3: An 80-year-old woman received metamizol 500 mg/8 h orally for 4 days. Two days after withdrawal, she developed a generalized exanthema with progressive vesiculation and exudation. The diagnosis was eczematous dermatitis. Allergic tests: We performed skin prick tests (SPT) with metamizol at 400 mg/ml, intradermal tests (ID) with dilutions from 1 : 1000 to 1 : 10 and patch tests (PT) with Leukotest on each patient's back with metamizol 10% in water. Readings of SPT and ID were done at 20 min, 6 h, 12 h, 24 h and 48 h. Patch tests were read at 48 h and 96 h. SPT, ID and PT were also performed in 10 control patients. In patients 1 and 2, we also carried out skin tests and single-blind placebo-controlled challenge tests (SBPCCT) with the other implicated drugs. Challenge with acetylsalicylic acid was performed in order to confirm (or not confirm) nonallergic NSAID hypersensitivity. Challenges with metamizol were not carried out for ethical reasons and skin tests results. The results of the study are shown in Table 1. Most allergic reactions to pyrazolone derivatives are those whose suspected mechanism is IgE-mediated (e.g. anaphylaxis or urticaria) or cell mediated (contact dermatitis and fixed drug eruption) (4–6). In our country (probably due to high a prescription rate, usually of metamizol) pyrazolones cause approximately 47% of all adverse reactions to NSAIDs and 10% of adverse reactions to all drugs (7). SPT and ID tests, read at 12, 24 and 48 h, and patch tests prove useful in the diagnosis of delayed allergy to metamizol, and they avoid the need to perform challenges. Considering these skin and patch tests results, these adverse reactions to metamizol are probably due to an immunological mechanism that is cell mediated. Accepted for publication 10 September 2002 Allergy 2003: 58:84–85 Copyright © Blackwell Munksgaard 2003 ISSN 0105-4538