薬剤アレルギーの起因薬検出,臨床解析および発現機構に関する研究

As drug allergies are specific,dose independent,and unpredictable,they are difficult to prevent and manage in the clinical setting.The objectives of this study were to analyze drug allergies and elucidate their pathogenesis from the viewpoints of detection of the causative drug,the allergen (drug),the patient (organism) and the mechanism of manifestation of drug hypersensitivity.As for detection of the causative drug,our findings suggest that the leukocyte migration test (LMT) may be more effective than other tests,i.e.the intradermal test,patch test,sensitized hemagglutination test,enzyme-linked immunosorbent assay and drug-induced lymphocyte stimulation test.In addition,the LMT-chamber method appeared to be more sensitive than the LMT-agarose method <br>From the allergen viewpoint,our findings suggest that β-lactam antibiotics and X-ray contrast media have very high allergenicity,and macrolide antibiotics have the lowest allergenicity among antibacterial drugs.In addition,cross-allergic reactions arising among β-lactam antibiotics may be induced by drugs having similar structures in terms of parent skeleton and side chain.<br>From the organism viewpoint,our findings suggest that skin eruption may be the most common drug-induced hypersensitivity symptom,fever alone may be strongly related to allergic reactions,itching may be closely connected with allergic drug eruptions and concomitant symptoms strongly related to drug-induced allergic hepatic injuries.Also,drug-induced blood disorders with short latent periods may be serious and closely related to allergic reactions and patients with previous medical histories of drug allergy may have a very high risk of drug-induced hypersensitivity.Furthermore,drug allergies in elderly persons have a low incidence and a long latent period,and women a high incidence of drug eruption and a low incidence of drug-induced hepatic injury.<br>As regards the mechanism of manifestation of drug hypersensitivity,our findings suggest that IL-1,IL-2 and TNF-α play a part in drug allergies detected by means of the leukocyte migration activating factor and IL-8 in β-lactam antibioticinduced allergies detected by means of the leukocyte migration inhibitory factor.In addition,Shosaiko-to,a traditional Chinese medicine,may have a phytohemagglutinin-like immunologic activity (pseudoallergic effect).Pseudoallergic effects may also be involved in shock in response to lidocaines,iodinated contrast media and NSAIDs.