pyrazolone and Angioedema

Adverse reactions to drugs are common in the clinical practice. Many outpatients are frequently referred to allergists in order to determine which drugs they can safely take in the future.. We set up an oral single-dose tolerance test procedure to find out for each patient one or more alternative drugs that can be taken when needed.. 452 outpatients (130 male, 322 female) with well-documented reactions (urticaria/angioedema, respiratory symptoms, laryngeal edema, anaphylaxis, exfoliative skin diseases) underwent the challenge. All tests were preceded by a single-blind placebo: if a reaction occurred, a second placebo was administered. Otherwise, a single dose (1/10 of the therapeutic one) of an alternative drug was given blindly and the patient was then observed for 6 h. The drugs used were different in structure from those suspected of having caused the adverse reaction. The patients were followed up at 4- to 6-month intervals, in order to detect any reaction that may have occurred with the tested drugs.. 98 patients (89 women) had untoward reactions after the first placebo and 34 out of them reacted to the second placebo, too. During challenges the reaction rate ranged between 4.6 and 9.0%; these reactions were easily managed and none of them was severe. We followed up 407 patients: 87.2% of them were able to use one or more of the suggested drugs without reactions, 9.3% did not take the drugs and only 3.5% reported reactions to the previously tested drugs.. The challenge procedure proved to be a simple tool for managing patients with adverse reactions to drugs. Its safety and reliability were validated by a long-term follow-up.

Topics: Administration, Oral; Adolescent; Adult; Aged; Angioedema; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Betamethasone; Chlorpheniramine; Drug Hypersensitivity; Drug Tolerance; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Pyrazoles; Pyrazolones; Severity of Illness Index; Single-Blind Method; Time; Treatment Outcome; Urticaria

In sensitive patients pyrazolone drugs can precipitate adverse reactions ranging from urticaria and angioedema to anaphylactic shock, presumably by immunological, IgE-mediated mechanism. However, up to now no genetic factors influencing the development of allergic reaction have been reported in this type of hypersensitivity.. The aim of our study was the investigation whether the susceptibility to development of pyrazolone drugs hypersensitivity (PDH) reactions was associated with HLA class II antigens.. To test this hypothesis we studied the distribution of HLA-DR and DQ antigens in 26 pyrazolone sensitive patients and control groups including unselected general population and clearly defined atopic and non-atopic groups.. Significantly higher frequencies of DQ 7 and DR11 antigens were found in PDH group as compared with control unselected population (RR= 16.48, P < 0.0001; P(cor)< 0.002 and RR = 4.57, P = 0.0002; Pcor = 0.003 for DQ and DR antigen respectively). Similarly, statistically significant increased frequencies of DQ 7 and DR11 in patients with PDH were observed compared with atopic control group (RR= 18.43, P < 0.0001; Pcor <0.002 and RR= 6.33, P= 0.0007; Pcor =0.01, for DQ and DR antigen respectively). However, in comparison to non-atopic control group only the frequency of DQ 7 antigen was significantly increased (RR = 15.42, P = 0.0001; Pcor = 0.0015). DQ 7 antigen was present in 46.1% of PDH patients compared with 4.9%, 4.4% and 5.3% in the general population, atopic and non-atopic groups respectively, suggesting pyrazolone hypersensitivity as a trait positively correlated with this HLA antigen.. Our data suggest a genetic predisposition to pyrazolone hypersensitivity reactions, linked to HLA-DQ locus.

Topics: Adolescent; Adult; Anaphylaxis; Angioedema; Anti-Inflammatory Agents, Non-Steroidal; Cytotoxicity Tests, Immunologic; Drug Hypersensitivity; Female; HLA-DQ Antigens; HLA-DR Antigens; Humans; Male; Middle Aged; Pyrazoles; Pyrazolones; Urticaria

All analgesics can occasionally induce adverse skin reactions. Especially in the early period of pyrazolone therapy, a large variety of cutaneous manifestations were attributed to the use of these drugs. An updated analysis is attempted.

Topics: Angioedema; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Contact; Drug Hypersensitivity; Erythema Multiforme; Humans; Pyrazoles; Pyrazolones; Skin Diseases; Urticaria; Vasculitis