Adverse Drug Reactions (ADR) and Severe Drug Eruptions in Japan

Abstract

The relief system for sufferers from Adverse Drug Reactions (ADR) started in 1980 in Japan. Herein I review 5,406 ADR cases filed in the past 23 years since its inception, as well as 553 dermatological cases filed in the past five years. ADR cases that actually received financial support comprised 74.7% of all filed cases. The most frequent reactions among all filed cases were dermatological disorders, which included 986 cases or 20.7%. The second most frequent reactions were general systemic disorders such as anaphylactic shock, which amounted to 790 cases ; the third was central nervous system disorders (789 cases), including hypoxic encephalopathy and meningitis, and the fourth, hepatobiliary disorders (631 cases). The above four categories accounted for 80% of all cases. Of the causal drugs, the most frequently reported were drugs that affect the central nervous system, including non-steroidal anti-inflammatory drugs (NSAIDs) and anticonvulsant drugs, reported in 2,223 cases. The second most frequent category was antibiotics, consisting of 1,233 drugs, and the third, hormonal drugs consisting of 513 drugs. Among the dermatological ADR cases, the most common disorder was Steven-Johnson syndrome (SJS), followed by toxic epidermal necrosis (TEN). The third most common cases were drug eruptions presenting with “disseminated” patterns resulting in difficult diagnoses. Fourth came erythema multiforme, followed by drug-induced hypersensitivity syndrome (DIHS) and erythroderma (ED). The four severe types of drug eruptions, SJS, TEN, DIHS and ED, accounted for 63.1% of all dermatological ADR, with mortality rates of 32%, 16.7%, 4.8%, and 1.3%, respectively. The most frequently reported sequelae were mucosal lesions resulting from SJS or TEN, specifically visual disorders including loss of sight. We also call attention to severe respiratory sequelae such as chronic respiratory failure due to obstructive bronchiolitis.