Stein H B, Patterson A C, Offer R C, Atkins C J, Teufel A, Robinson H S
Ann Intern Med. 1980 Jan;92(1):24-9. doi: 10.7326/0003-4819-92-1-24.
Adverse effects to D-penicillamine were studied prospectively over 3 years in 259 patients with rheumatoid arthritis. Ninety-five percent had had gold therapy previously, yet 70% benefited from D-penicillamine therapy. Of the 275 courses given, 160 (58%) were complicated by at least one reaction, including rashes (44%), dysgeusia (20%), gastrointestinal upset (18%), stomatitis (10%), proteinuria (7%), thrombocytopenia (3%), and leukopenia (2%). Their occurrences peaked in the first 6 months of treatment, except for proteinuria and thrombocytopenia, which peaked in the second 6 months. Reactions were commoner at daily doses above 250 mg; mean daily doses for proteinuria, thrombocytopenia, and leukopenia were higher (approximately 600 mg/d) than for the others (approximately 500 mg/d). Of 114 discontinued courses, 73 (27%) were due to adverse reactions. The remaining reactions were controlled by altering dosages and symptomatic treatment. Only obliterative bronchiolitis (two cases) was irreversible; it resulted in the only death in our series, possibly attributable to penicillamine.
对259例类风湿性关节炎患者进行了为期3年的青霉胺不良反应前瞻性研究。95%的患者以前接受过金制剂治疗，但70%的患者从青霉胺治疗中获益。在给予的275个疗程中，160个（58%）至少出现一种不良反应，包括皮疹（44%）、味觉障碍（20%）、胃肠道不适（18%）、口腔炎（10%）、蛋白尿（7%）、血小板减少症（3%）和白细胞减少症（2%）。除蛋白尿和血小板减少症在治疗的第二个6个月达到高峰外，其他不良反应在治疗的前6个月达到高峰。每日剂量超过250mg时不良反应更常见；蛋白尿、血小板减少症和白细胞减少症的平均每日剂量（约600mg/d）高于其他不良反应（约500mg/d）。在114个停止的疗程中，73个（27%）是由于不良反应。其余的不良反应通过调整剂量和对症治疗得到控制。只有闭塞性细支气管炎（2例）是不可逆的；这是我们系列中唯一的死亡原因，可能归因于青霉胺。
