The accuracy of the diagnosis of suspected paracetamol (acetaminophen) hypersensitivity: results of a single-blinded trial.

BACKGROUND: Hypersensitivity to paracetamol (acetaminophen) is rare and very few clinical data are available in the literature. MATERIALS AND METHODS: Eighty-four patients (28 males and 56 females, 5-70 years old) with a suspicion of paracetamol hypersensitivity were referred to our drug allergy clinic between May 1996 and May 2000. The reaction had occurred 1-96 months prior to the consultation. Single-blinded placebo-controlled oral challenges were carried out in 82 patients, under strict hospital surveillance. RESULTS: Most of the patients experienced skin eruptions 82/84 (97.6%), with 10 cases of anaphylactic shock (11.9%). Twenty-six (30.9%) reactions were immediate (occurring within the first hour after drug intake), 53 (63.1%) non-immediate and five could not remember. Oral provocation tests (OPT) demonstrated drug hypersensitivity in 11 patients only. The two patients not tested (due to a history of life-threatening reaction) were included in the positive group. Thus, 13 (15.5%) patients had paracetamol hypersensitivity and 71 (84.5%) had not. All the 13 positive patients had skin eruptions, five with anaphylactic shock. 9/13 had immediate reactions. Using OPT, 10 out of 11 had the same clinical reaction but more delayed. In both groups, whether hypersensitive to paracetamol or not: atopy was similar (7/13-53.8% and 31/71-43.7%), sex ratio was not different (M/F 0.3 and 0.5), 3/13 (23.1%) and 0/71 (0%) had aspirin/ibuprofen hypersensitivity. CONCLUSION: The clinical history of paracetamol (acetaminophen) hypersensitivity is rarely sufficient to set a firm diagnosis and only OPT can confirm this. Careful OPT reproduces the same symptoms (not more severe in our hands) with the same or slightly more delayed chronology. Atopy and sex are not risk factors.

Long-term safety and efficacy of nevirapine tolerance induction.

BACKGROUND: The most frequent side-effects due to nevirapine (Viramune), the first non-nucleoside HIV reverse transcriptase inhibitor introduced for clinical use, are cutaneous hypersensitivity reactions. In non-serious cases, tolerance induction can be proposed. OBJECTIVE: Describe the long-term safety and efficacy of tolerance induction to nevirapine. METHODS: Six HIV-infected patients started a tolerance 1 to 2 months after an episode of nevirapine hypersensitivity. Increasing doses of nevirapine (2.5, 10, 25, 100, 250 and 750 microg and 2.5, 5, 10, 25, 50 and 100 mg) were given orally at half-hour intervals under strict medical surveillance and patients were followed up regularly. RESULTS: All but two of the patients tolerated this induction well. One had a mild and transient reaction on day 1; nevirapine was not stopped. One had a moderate to severe reaction one month later; nevirapine was stopped and he recovered fully. All other patients have been taking nevirapine for more than 3 months without any adverse reaction. CONCLUSION: Therefore, when no alternatives are available in severely ill and hypersensitive HIV-infected patients, tolerance induction is a possible therapeutic option.

Cysteinyl-leukotriene release test (CAST) in the diagnosis of immediate drug reactions.

BACKGROUND: The diagnosis of allergic reactions to drugs is difficult. Most skin tests are not standardized, and in vitro tests are needed to avoid provocation tests. Cross-linking of IgE on basophils is known to cause the release of both cysteinyl leukotriene (Cys-LT) and histamine. We aimed to evaluate the diagnostic utility (sensitivity, specificity, and efficiency) of measurement of sulfidoleukotrienes in drug allergy. METHODS: We performed a prospective study in 55 patients with proven immediate adverse reactions to drugs (30 to beta-lactams, six to acetaminophen, and 19 to aspirin) and 64 drug-exposed nonallergic controls. Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Cys-LT release was determined after drug-allergen stimulation by the cellular antigen stimulation test (CAST(R)) technique. Histamine release was also assessed on the same samples by enzyme immunoassay. Spontaneous and anti-FcepsilonRIalpha-induced mediator release was also studied in all subjects. Sensitivity, specificity, and efficiency were calculated. RESULTS: Net Cys-LT release was over the maximal threshold given by the manufacturer in 19/55 patients and in 9/64 controls. Net histamine release was over 5% of total histamine content in 28/55 patients and 34/64 controls. The efficiency of both tests was low. CONCLUSION: Thus, in most cases, the in vitro Cys-LT test has little or no diagnostic utility and is not superior to histamine release.

[Immunoallergic reactions of drug origin: epidemiologic and clinical data]. / Les réactions immuno-allergiques d'origine médicamenteuse: données épidémiologiques et cliniques.

Allergic and pseudoallergic reactions frequently occur in hospitalized patients and represent up to one-third of adverse drug reactions. Allergic reactions are unpredictable reactions, related to immunologic mechanisms. Pseudoallergic reactions mimic allergic reactions but no drug-specific antibody or T-cell proliferation can be demonstrated. Clinical presentations are numerous and heterogeneous, from a mild urticaria to a dramatic anaphylactic shock and an extensive bullous skin disease. A true diagnosis is rarely set up and the tools for it are lacking. In this review, we will focus on some epidemiological data concerning these reactions, including data on incidence, mortality and cost.

[Allergy to macrolides. 21 cases]. / L'allergie aux macrolides. 21 observations.

OBJECTIVE: Allergic drug reactions to macrolides are extremely rare and there is little information in the literature concerning relevant diagnostic tests. PATIENTS AND METHODS: Twenty-one patients were recently seen for assumed allergies (principally urticaria) to diverse macrolides. Skin tests (prick and intradermal tests) were performed with injectable forms of spiramycin and erythromycin. Seventeen out of 21 patients were provoked under strict hospital surveillance. RESULTS: Only 3 patients had a positive provocation test and were thus truly allergic (to spiromycin). They had positive skin tests to both macrolides tested. CONCLUSION: Most hypersensitivity reactions to macrolides are therefore diagnosed with provocation tests.

[Allergy to macrolide antibiotics. Review of the literature]. / L'allergie aux macrolides. Revue de la littérature.

MACROLIDE CLASSES: Macrolides are characterized by their basic structure made up of a lactonic cycle with 2 osidic chains. They are classified according to the number of carbon atoms in the cycle: 14-membered macrolides (erythromycin, troleandomycin, roxithromycin, dirithromycin, clarithromycin), 15-membered macrolides (azithromycin) and 16-membered macrolides (spiramycin, josamycin, midecamycin). MACROLIDE ALLERGY: Allergy to macrolides is extremely rare (0.4% to 3% of treatments). The little information available in the literature is insufficient to establish the usefulness of diagnostic tests. An immediate IgE-dependent hypersensitivity has been shown with erythromycin in some cases but the mechanism remains unknown and skin tests are quite often negative. Clinical manifestations are the same as those encountered with beta-lactams. It would appear that macrolide allergies are unlikely to be class allergies. This is important as eviction advice could be limited to the single causal macrolide.

Predictive capacity of histamine release for the diagnosis of drug allergy.

BACKGROUND: The diagnosis of immediate allergic reactions to drugs is difficult, requiring in vitro test development. Basophils are likely to be involved in these reactions, and to evaluate the sensitivity, the specificity, and the predictive values of the histamine-release test, we performed a prospective study in 68 patients tested for suspected drug allergy. METHODS: Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Histamine release in the presence of the drug was assessed on heparinized whole blood by enzyme immunoassay (Immunotech, France), and the cutoff value was set at 5% of total histamine content. Spontaneous and anti-IgE-induced histamine release was also studied in all subjects. RESULTS: All patients presented to our clinic with reactions ranging from maculopapular exanthema to anaphylactic shock. Thirty-five patients had proven drug allergy; 33 were not allergic to drugs and served as a control group together with 40 other subjects with no history of drug allergy. Net histamine release was positive in 18/35 allergics and 27/73 nonallergics, giving poor sensitivity (51.4%), specificity (63.0%), and positive predictive value (29.3%), but valuable negative predictive value (81.1%). CONCLUSIONS: The usefulness of the in vitro histamine-release test for the diagnosis of drug allergy appears to be insufficient.

Six-hour trimethoprim-sulfamethoxazole-graded challenge in HIV-infected patients.

BACKGROUND: Hypersensitivity reactions to trimethoprim-sulfamethoxazole (TMP-SMX) are very common in HIV-infected patients, leading to drug discontinuation. However, it is the drug of choice as prophylaxis for Pneumocystis carinii pneumonia. OBJECTIVES: We sought to determine the safety and long-term efficacy of a 6-hour TMP-SMX-graded challenge in a group of hypersensitive HIV-infected patients. METHODS: Forty-four consecutive HIV-infected patients with documented TMP-SMX hypersensitivity were seen in our outpatient allergy department. They ingested 12 doses of increasing amounts of TMP-SMX at half-hour intervals. Thereafter, they took 80/400 mg TMP-SMX daily and were advised to "treat through" every nonbullous cutaneous adverse reaction. RESULTS: All 44 patients tolerated the procedure without any adverse reactions during the day of challenge. Eleven of the 44 patients experienced mild hypersensitivity reactions on days 1 to 2 (8 patients) and 8 to 10 (3 patients), consisting mainly on a 1-day pruritic maculopapular eruption. Two patients stopped TMP-SMX at day 1, and 2 stopped it at days 10 and 15, giving an overall success rate at 1 month of 91% (40 of 44). Two were successfully rechallenged late. After a median follow-up of 10 months, 42 patients were taking TMP-SMX without any adverse reaction, giving an overall success rate of 95%. CONCLUSIONS: A 6-hour graded challenge with cautious "treating through" of mild reactions enables more patients to take TMP-SMX and is safe and effective.