Drug provocation test

Aberer W. Bircher A, Romano A, et al Drug provocation testing in the diagnosis of drug hypersensitivity reactions general considerations. Allergy 2003 58 854-863. 

Messaad D, Sahla H, Benahmed S, Godard P, et al. Drug provocation tests in patietns with a history suggesting an imeediate drug hypersensitivity reaction. Ann Intern Med 2004 140 1001-1006. 

Hein UR, Chantraine-Hess S, Worm M, Zuberbier T, Henz BM Evaluation of systemic provocation tests in patients with suspected allergic and pseudo-allergic drug reactions. Acta Derm Venereol 1999 79 139-142. 

In a case of fixed drug eruption, a provocation test showed cross-reactivity with tinidazole but not with sec-nidazole (24). 

Kanwar AJ, Bharija SC, Singh M, Belhaj MS. Ninety-eight fixed drug eruptions with provocation tests. Dermatologica 1988 177(5) 274-9. 

A 10-year-old-boy developed an extensive fixed drug eruption when he took co-trimoxazole (trimethoprim 200 mg, sulfamethoxazole 40 mg bd) 8 weeks after having had a fixed drug eruption due to nimesuhde. An oral provocation test with co-trimoxazole 1 month later showed reactivation within 12 hours in the form of severe itching and erythema at the sites of the lesions with one-quarter of the dose. 

Attempts to establish the cause should as far as possible be carried out in vitro. Trial exposure to drugs on which the patient s history casts suspicion may lead to serious hemorrhages. If a provocation test is essential, the amount of drug administered should be very small, far below the normal dose. 

Deliberate provocation of the pathological manifestations by exposure to a small dose of the drug must still be regarded as the most reliable evidence of a drug allergy. However, it must always be remembered that each fresh exposure carries a by no means negligible risk. The decision to carry out a provocation test must never be taken without careful consideration. If such a test is performed, the patient must be kept under close observation, preferably in hospital, for an adequate time. In the first instance, the dose should not exceed one-tenth of the normal single dose. 

Fawcett and Pepys (1976) reported the case of a patient who developed immediate bronchospasm and an urticarial reaction after ingestion of a commercial combination of three tetracyclines no reactions could be elicited by oral challenge with the different tetracyclines, tartrazine, or the blue coating of the drug, whereas a provocation test with the commercial preparation was positive. Other clinical patterns, such as fixed drug eruptions (Kandil 1969 Delaney 1970 Csonka et al. 1971 Brown 1974 Shimizu and Shimao 1977 Pasricha and Shukla 1979), vascular purpura (Schoenfeld 1964) and a picture similar to systemic lupus erythematosus (SLE) (Sulkowski and Haserick 1964) have also been described. Contact dermatitis seems to be a very rare complication it was, however, observed after contact with oxytetracycline (Dohn 1962 Bojs and Moller 1974) and minocycline. In the latter case subsequent oral therapy with the same drug was followed by a systemic reaction and the sensitivity was confirmed by epicutaneous tests (Shelley and Heaton 1973). 

On suspicion of a drug allergy, the first step is discontinuation of the responsible agent a subsequent rapid regression can be taken as proof that the drug was indeed responsible. In serious hypersensitivity reactions, for example Lyelfs syndrome, anaphylactic shock, thrombocytopenic purpura, periarteritis nodosa, and lupus erythematosus medicamentosus, functional tests in the sense of a provocation test are extremely dangerous and are to be avoided. In epicutaneous tests too we have to proceed with extreme care. 

Table 4.3 Doses of some commonly used drugs employed in provocation testing...

NSAlDs—nonsteroidal anti-inflammatory drugs For aspirin provocation testing see Sect. 9.5.2.1.3.1 Administered subcutaneously using solution 20 mg/ml... 

Aberer W, Kranke B. Provocation tests in drug hypersensitivity. Immunol Allergy Clin North Am. 2009 29 567-84. 

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