Arias J, Fernández-Rivas M, Moral A, García M A, Senent C J
Allergy Section, Hospital Virgen del Valle, Toledo, Spain.
Ann Allergy Asthma Immunol. 1995 Feb;74(2):160-2.
Diflunisal is a difluorophenyl derivative of salicylic acid. We report two patients who presented immediate adverse reactions to diflunisal (Dolobid) that consisted of generalized urticaria and chest tightness.
Diflunisal was conjugated to human serum albumin in order to perform in vivo and in vitro tests (skin prick and intradermal tests, leukocyte histamine release, and RAST). The patients were challenged following a single-blind, placebo-controlled oral procedure with diflunisal and other nonsteroidal antiinflammatory drugs.
Skin tests with diflunisal were negative as were leukocyte histamine release tests and RAST in both patients. They tolerated therapeutic doses of aspirin, salsalate, salicylamide, lysine acetylsalicylate, acetaminophen, dipyrone, and propyfenazone. The oral provocation with diflunisal elicited an immediate response at the cumulative dose of 400 mg in both patients.
These are two exceptional cases of selective adverse reactions to diflunisal with good tolerance to other salicylates and nonsteroidal antiinflammatory drugs. Thus, the inhibition of cyclooxygenase does not seem to be the mechanism involved. The pathogenic mechanism implicated in the reaction remains unclear, both idiosyncratic and immunologic mechanisms could explain our patients' adverse responses.
双氯芬酸是水杨酸的二氟苯基衍生物。我们报告了两名患者,他们对双氯芬酸(Dolobid)出现了即刻不良反应,包括全身性荨麻疹和胸闷。
将双氯芬酸与人血清白蛋白结合,以进行体内和体外试验(皮肤点刺和皮内试验、白细胞组胺释放试验以及放射变应原吸附试验)。按照单盲、安慰剂对照的口服程序,让患者服用双氯芬酸和其他非甾体抗炎药进行激发试验。
两名患者的双氯芬酸皮肤试验、白细胞组胺释放试验以及放射变应原吸附试验均为阴性。他们耐受治疗剂量的阿司匹林、双水杨酸酯、水杨酰胺、赖氨酸乙酰水杨酸、对乙酰氨基酚、安乃近和丙氧苯宗。两名患者口服双氯芬酸激发试验在累积剂量400毫克时均引发了即刻反应。
这是两例对双氯芬酸选择性不良反应的特殊病例,患者对其他水杨酸盐和非甾体抗炎药耐受性良好。因此,环氧化酶的抑制似乎不是其中涉及的机制。反应中涉及的致病机制仍不清楚,特异反应性和免疫机制都可能解释我们患者的不良反应。