Elkayam O, Levartovsky D, Brautbar C, Yaron M, Burke M, Vardinon N, Caspi D
Department of Rheumatology, Tel Aviv Medical Center, Israel.
Am J Med. 1998 Dec;105(6):484-7. doi: 10.1016/s0002-9343(98)00325-8.
Prolonged treatment with minocycline for acne vulgaris has been associated with the development of arthralgia, arthritis, and other autoimmune phenomena. We characterized the clinical, laboratory, and immunological profiles of seven patients with this syndrome.
Clinically the patients were studied with special emphasis on prior minocycline treatment, presenting symptoms, physical findings, course, and outcome. Laboratory tests included fluorescent antinuclear and antineutrophil cytoplasmic (ANCA) antibodies, as well as antibodies to myeloperoxidase, bactericidal permeability increasing protein, elastase, cathepsin G, lactoferrin, cardiolipin, and histone.
All 7 patients presented with polyarthritis or arthralgia, morning stiffness, and fever after 6 to 36 months of minocycline treatment. The skin was involved in five patients (three with livedo reticularis and two with subcutaneous nodules). Two patients had chronic active hepatitis. Increased titers of perinuclear ANCA (p-ANCA) were detected in all seven patients; five patients had fluorescent antinuclear antibodies, two had antihistone autoantibodies and one had anticardiolipin antibodies. Antigenic characterization of p-ANCA disclosed antibodies to bactericidal permeability increasing protein in one patient, to elastase in three patients, and to cathepsin G in five patients. Symptoms resolved in five patients upon discontinuation of minocycline; the other two patients were treated with corticosteroids and also achieved remissions.
Minocycline-induced autoimmune syndrome is characterized by reversible polyarthralgia or arthritis, morning stiffness, fever, frequent skin involvement, occasional chronic active hepatitis, and increased titers of p-ANCA with various minor p-ANCA-related antigens.
长期使用米诺环素治疗寻常痤疮与关节痛、关节炎及其他自身免疫现象的发生有关。我们对7例患有该综合征患者的临床、实验室及免疫学特征进行了描述。
对患者进行临床研究，特别关注既往米诺环素治疗情况、出现的症状、体格检查结果、病程及转归。实验室检查包括荧光抗核抗体和抗中性粒细胞胞浆抗体（ANCA），以及抗髓过氧化物酶、杀菌通透性增加蛋白、弹性蛋白酶、组织蛋白酶G、乳铁蛋白、心磷脂和组蛋白的抗体。
所有7例患者在米诺环素治疗6至36个月后均出现多关节炎或关节痛、晨僵及发热。5例患者皮肤受累（3例有网状青斑，2例有皮下结节）。2例患者有慢性活动性肝炎。所有7例患者均检测到核周ANCA（p-ANCA）滴度升高；5例患者有荧光抗核抗体，2例有抗组蛋白自身抗体，1例有抗心磷脂抗体。p-ANCA的抗原特性分析显示，1例患者有抗杀菌通透性增加蛋白抗体，3例患者有抗弹性蛋白酶抗体，5例患者有抗组织蛋白酶G抗体。5例患者停用米诺环素后症状缓解；另外2例患者接受皮质类固醇治疗后也实现了病情缓解。
米诺环素诱导的自身免疫综合征的特征为可逆性多关节痛或关节炎、晨僵、发热、皮肤常受累、偶尔出现慢性活动性肝炎，以及p-ANCA滴度升高且伴有各种与p-ANCA相关的次要抗原。
