Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions. Proposed by the Working Party of the ESCD

University of Amsterdam, Amsterdamo, North Holland, Netherlands
Contact Dermatitis (Impact Factor: 3.75). 12/2001; 45(6). DOI: 10.1034/j.1600-0536.2001.450601.x


Skin testing with a suspected drug has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (CADR). Many isolated reports of positive drug skin tests are published, but without detailed information concerning the clinical features of the CADR and the method used in performing drug skin tests, such data are not very informative. A working party of the European Society of Contact Dermatitis (ESCD) for the study of skin testing in investigating cutaneous adverse drug reactions, has proposed the herein-reported guidelines for performing skin testing in CADR in order to standardize these procedures. In each reported case, the imputability of each drug taken at the onset of the CADR and a highly detailed description and characterization of the dermatitis need to be given. Drug skin tests are performed 6 weeks to 6 months after complete healing of the CADR. Drug patch tests are performed according to the methods used in patch testing in studying contact dermatitis. The commercialized form of the drug used by the patient is tested diluted at 30% pet. (pet.) and/or water (aq.). The pure drug is tested diluted at 10% in pet. or aq. In severe CADR, drug patch tests are performed at lower concentrations. It is also of value to test on the most affected site of the initial CADR. Drug prick tests are performed on the volar forearm skin with the commercialized form of the drug, but with sequential dilutions in cases of urticaria. Intradermal tests (IDT) are performed with sterile sequential dilutions (10–4, 10–3, 10–2, 10–1) of a pure sterile or an injectable form of the suspected drug with a small volume of 0.04 ml. Drug skin tests need to be read at 20 min and also later at D2 and D4 for patch tests, at D1 for prick tests and IDT. All these tests also need to be read at 1 week. The success of skin tests varies with the drug tested, with a high % of positive results, for example, with betalactam antibiotics, pristinamycin, carbamazepine and tetrazepam on patch testing, or with betalactam antibiotics and heparins on delayed readings of IDT. The results of drug skin tests also depend on the clinical features of the CADR. The use of appropriate control patients is necessary to avoid false-positive results.

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    • "Lymphocyte transformation tests (LTT) which are often carried out only inhighly specialized research laboratories, are not consistently useful as they are often drug-specific and reaction-specific [13, 14, 15, 16, 17]. Patch test positivity is also dependent on the type of cutaneous drug eruption and putative drug [18, 19]. Positive patch tests have been reported for INH and EMB associated MPE [20] and eczematous eruptions [21]. "
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    ABSTRACT: BackgroundAntituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist.ObjectiveTo describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy.MethodsConsecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug.ResultsThere were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB.ConclusionTailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment.
    Full-text · Article · Jul 2014
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    • "The results are graded from negative reaction to extreme positive reaction with intense erythema and coalescing vesicles [14]. Patch test should be done at the site of previous lesion and need a sufficient time to avoid refractory period [13, 15]. These considerations could decrease false negative results. "
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    ABSTRACT: Fixed drug eruption is an uncommon adverse drug reaction caused by delayed cell-mediated hypersensitivity. Levocetirizine is an active (R)-enatiomer of cetirizine and there have been a few reports of fixed drug eruption related to these antihistamines. We experienced a case of levocetirizine-induced fixed drug eruption and cross-reaction with other piperazine derivatives confirmed by patch test. A 73-year-old female patient presented with recurrent generalized itching, cutaneous bullae formation, rash and multiple pigmentation at fixed sites after taking drugs for common cold. She took bepotastine besilate (Talion®) and levocetirizine (Xyzal®) as antihistamine. She took acetaminophen, pseudoephedrine 60 mg / triprolidine 2.5 mg (Actifed®), dihydrocodeinebitartrate 5 mg / di-methylephedrine hydrochloride 17.5 mg / chlorpheniramine maleate 1.5 mg / guaifenesin 50 mg (Codening®) and aluminium hydroxide 200 mg / magnesium carbonate 120 mg (Antad®) at the same time. Patch test was done with suspected drugs and the result was positive with levocetirizine. We additionally performed patch test for other antihistamines such as cetirizine, hydroxyzine, fexofenadine and loratadine. Piperazine derivatives (cetirizine and hydroxyzine) were positive, but piperidine derivatives (fexofenadine and loratadine) were negative to patch test. There was no adverse drug reaction when she was challenged with fexofenadine. We report a case of levocetirizine-induced fixed drug eruption confirmed by patch test. Cross-reactions were only observed in the piperazine derivatives and piperidine antihistamine was tolerant to the patient.
    Full-text · Article · Oct 2013
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    • "Four patients had a history of skin manifestations as the clinical symptoms of adverse reactions after the injection of local anesthetics, six had circulatory symptoms, three had respiratory symptoms, eight had central nervous symptoms, and three had other symptoms. According to the guidelines proposed by Barbaud, et al. [11], patients who have histories of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, or leucocytoclastic vasculitis on histological examination caused by local anesthetics should be excluded from allergy tests. However, none of our patients showed such conditions. "
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    ABSTRACT: Some dental patients have histories of adverse reactions to local anesthesia. The aim of the present study was to investigate the frequency of allergy to local anesthetics of dental patients who had histories of adverse reactions to local anesthesia based on the results of allergy tests in our institute over a period of 5 years. We investigated the past medical records of dental patients retrospectively, and twenty patients were studied. Three of the 20 showed a positive or false-positive reaction in the intracutaneous test, and one patient showed a false-positive reaction in the challenge test. Our results suggest that the frequency of allergy to local anesthetics is low even if patients have histories of adverse reactions to local anesthesia. However, allergy tests of local anesthetics should be performed in patients in whom it is uncertain whether they are allergic.
    Full-text · Article · Aug 2011 · The Open Dentistry Journal
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