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1 Head of Division of Drug Information Department of Pharmacy Chung-Ho
Memorial Hospital Kaohsiung Medical University Tzyou 1st Road Kaohsiung,
Taiwan fax 07-3121101-7198
susucy{at}kmu.edu.tw
2 Drug Information Pharmacist Division of Drug Information Department of
Pharmacy Chung-Ho Memorial Hospital Kaohsiung Medical University
3 Drug Dispensing Pharmacist Division of Drug Dispensing Department of
Pharmacy Chung-Ho Memorial Hospital Kaohsiung Medical University
Published Online, September 13, 2005. www.theannals.com, DOI 10.1345/aph.1E377a
Since adverse effects occurred with esomeprazole 40 mg, but not with lower doses or with other PPIs, we speculate that the adverse events that our patient developed were rather drug-specific and dose-dependent and not triggered by a hypersensitivity-like syndrome. Hypersensitivity reactions, in fact, generally occur after the second or third contact with the allergenic substance....In our case, the patient had already taken esomeprazole 20 mg a few months earlier...without appearance of adverse effects. Moreover, he did not present with the hallmark symptoms that are characteristic of a hypersensitivity reaction.
Since the advent of allergen immunotherapy in 1911 by Dr. Leonard Noon in England, the saying "allergy is independent of dose" has proven not to be true for all cases. Some dermatologic drug reactions may be dependent on dose or cumulative toxicity2; most cutaneous drug reactions occur within 5-10 days (with an outside range of 1-28 days) after initiation, but may not occur until after the drug is stopped.2
The antigenicity of a drug depends on a host of drug- and patient-specific factors including dose, duration, number of exposures, route of administration, and chemical properties as well as the age, gender, atopy, and specific genetic polymorphisms of a patient.3 The lag time between initiation of an offending drug and fever varies considerably from one drug to another. Drug fever usually appears within the first week of antibiotic administration4,5 and may take 30-40 days or longer to develop with cardiovascular drugs.5 The onset of acute hypersensitivity infusion syndrome (eg, fever, chest pain, leg pain, urticaria, flushing) usually begins within 1-3 hours after the first infusion, and a delayed-type hypersensitivity reaction (<1%) typically occurs 5-14 days after an infusion.3
Drug fever is a diverse disorder and, although several mechanisms have been identified, an immunologically mediated hypersensitivity reaction is the most common cause.5,6 Either innate or acquired immunity (humoral, cell-mediated) may attribute to this. Classic signs and symptoms of allergic reactions (eg, eosinophilia, urticaria) are generally not features of allergic drug fever.5 Fever can be the sole manifestation of an allergic drug response in approximately 3-5% of cases,5,6 with the clinical picture varying according to the nature of an individual's immune response to the offending agent.
Hypersensitivity reaction may occur with the use of any drug and may therefore not be definitively excluded from the case of esomeprazole-induced central fever with severe myalgia presented by Grattagliano et al.
References
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