pyrazolone and Drug-Hypersensitivity

The aim of this study is to critically review the relevant literature published on basophil activation test, presenting the current knowledge and future perspectives.. Basophil activation test (BAT) results varied accordingly to the class of the drug studied, and have promising results in immediate hypersensitivity reactions to pyrazolone (selective reactors), neuromuscular blockers, beta-lactams, and platinum compounds, all examples of classical IgE-mediated hypersensitivity drug reactions. Currently, BAT is applied in research settings, but based in the results of our review, the test can be considered as a diagnostic tool for daily practice for selected patients and selected drugs, when the test is available, particularly for patients who experienced severe reactions and when diagnosis cannot be stablished by serum-specific IgE and skin testing, in order to avoid unnecessary drug provocations tests.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Basophil Degranulation Test; Basophils; beta-Lactams; Drug Hypersensitivity; Humans; Hypersensitivity, Immediate; Neuromuscular Agents; Pyrazolones

Topics: Agranulocytosis; Anaphylaxis; Anti-Inflammatory Agents, Non-Steroidal; Drug Eruptions; Drug Hypersensitivity; Humans; Pyrazoles; Pyrazolones

Based on the radioallergosorbent test (RAST), the authors have developed a series of assays to detect IgE and IgG antibodies against a number of frequently used drugs. In this system drugs bound covalently to cellulose paper are incubated with serum and washed; the hapten-specific IgE and IgG antibodies are then qualified and quantified by means of 125I-labelled anti-human IgE and IgG respectively. Thus far the sera of 1,228 patients have been analyzed following therapy with betalactam antibiotics, co-trimoxazole, salicylates, pyrazolones, flavonoids and tetrahydroisoquinoline. The induction of IgG antibodies is a frequent occurrence and that of IgE rare. Isolated high titers of IgE are associated mainly with anaphylactic reactions; in the presence of simultaneously raised IgG titers such side reactions are often absent. Highest IgG titers were found in patients with immune hemolysis after betalactam antibiotics, flavonoids and tetrahydroisoquinoline. In the other types of side reaction specific IgG titers were not significantly higher than in patients without side reactions. The estimation of circulating antibodies against drugs cannot yet be utilized diagnostically except in the rare cases of anaphylactic side reactions. However, the method described permits specific and sensitive detection of sensitization and is suited for scientific purposes.

Topics: Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Drug Hypersensitivity; Flavonoids; Humans; Immunoglobulin E; Immunoglobulin G; Penicillins; Pyrazoles; Pyrazolones; Radioimmunosorbent Test; Salicylates; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

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

The diagnosis of a drug allergy is mainly based upon a very detailed history and the clinical findings. In addition, several in vitro or in vivo tests can be performed to demonstrate a sensitization to a certain drug. One of the in vitro tests is the lymphocyte transformation test (LTT), which can reveal a sensitization of T-cells by an enhanced proliferative response of peripheral blood mononuclear cells to a certain drug.. To evaluate the sensitivity and specificity of the LTT, 923 case histories of patients with suspected drug allergy in whom a LTT was performed were retrospectively analysed.. Based on the history and provocation tests, the probability (P) of a drug allergy was estimated to be > 0.9, 0.5-0.9, 0.1-0.5 or < 0.1, and was put in relation to a positive or negative LTT.. Seventy-eight of 100 patients with a very likely drug allergy (P > 0.9) had a positive LTT, which indicates a sensitivity of 78%. If allergies to betalactam-antibiotics were analysed separately, the sensitivity was 74.4%. Fifteen of 102 patients where a classical drug allergy could be excluded (P < 0.1), had nevertheless a positive LTT (specificity thus 85%). The majority of these cases were classified as so-called pseudo-allergic reaction to NSAIDs. Patients with a clear history and clinical findings for a cotrimoxazole-related allergy, all had a positive LTT (6/6), and in patients who reacted to drugs containing proteins, sensitization could be demonstrated as well (i.e. hen's egg lysozyme, 7/7). In 632 of the 923 cases, skin tests were also performed (scratch and/or epicutaneous), for which we found a lower sensitivity than for the LTT (64%), while the specificity was the same (85%).. Although our data are somewhat biased by the high number of penicillin allergies and cannot be generalized to drug allergies caused by other compounds, we conclude that the LTT is a useful diagnostic test in drug allergies, able to support the diagnosis of a drug allergy and to pinpoint the relevant drug.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity; Humans; Lymphocyte Activation; Penicillins; Predictive Value of Tests; Pyrazoles; Pyrazolones; Sensitivity and Specificity; Skin Tests; T-Lymphocytes; Trimethoprim, Sulfamethoxazole Drug Combination

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 relationships 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.

Topics: Animals; Antibodies; Cross Reactions; Drug Hypersensitivity; Guinea Pigs; Haptens; Immunization; Indicators and Reagents; Passive Cutaneous Anaphylaxis; Pyrazoles; Pyrazolones; Skin Tests; Structure-Activity Relationship

On the basis of animal experiments and clinical findings, pyrazolones are found to have adverse renal effects. However, the latter are minor, very rare, and of practically no clinical relevance. In animals, pyrazolones induce proteinuria, oliguria, retention of substances excreted via the urine, and probably, in rare cases, papillary necrosis. Oliguria is rare in humans. A contribution of pyrazolone drugs in a specific case of papillary necrosis and in rare cases of acute interstitial nephritis is not proven, yet possible. Pyrazolone drugs induce renal injury less frequently than do the other classical analgesics.

Topics: Acute Kidney Injury; Aged; Aminopyrine; Analgesics; Animals; Antipyrine; Cats; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Hematuria; Humans; Kidney Diseases; Kidney Papillary Necrosis; Male; Middle Aged; Nephritis, Interstitial; Phenacetin; Proteinuria; Pyrazoles; Pyrazolones; Rabbits; Rats

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

In a retrospective investigation 469 pseudoallergic reactions (analgesics asthma reactions) that emerged in 197 patients with analgesics intolerance have been analysed. Besides mostly severe asthma-attacks 26.5% of the reactions were sneeze-attacks and in 37.5% nasal secretion was found. 86% of the reactions emerged within a maximum of 45 minutes after oral application of the analgesic. About a third of the analgesics-asthma reactions occurs together with reactions of the nose mucous membrane. So the connection of analgesics-asthma and chronic hyperplastical changes of the mucous membrane of the upper respiratory tract is also reflected in the course of the pseudoallergic intolerance reaction.

Topics: Analgesics; Aspirin; Asthma; Drug Hypersensitivity; Humans; Hypersensitivity, Immediate; Nasal Mucosa; Pyrazoles; Pyrazolones; Retrospective Studies; Time Factors

About one third of patients with anaphylactic reactions to pyrazolones showed contact urticaria induced by to at least one pyrazolone after 30-60 min in patch test. This reaction was never observed in patients with various exanthemas or allergic contact dermatitis to these medicaments. Contact urticaria in patch test was mostly caused by propyphenazone, aminophenazone, and metamizole. The suspicious pyrazolone provoked positive results in only about 70%. No correlation could be found between contact urticaria in patch test and severity of allergic history, short interval before skin test and atopic constitution.

Topics: Adolescent; Adult; Aged; Anaphylaxis; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Patch Tests; Pyrazoles; Pyrazolones; Skin Tests; Urticaria

Topics: Aminopyrine; Asthma; Drug Hypersensitivity; Hypersensitivity; Pyrazoles; Pyrazolones; Toxicology