Yawalkar N, Reimers A, Hari Y, Hunziker T, Gerber H, Müller U, Pichler W
Institute of Immunology and Allergology, Inselspital Bern, Switzerland.
Dermatology. 1999;199(1):25-30. doi: 10.1159/000018173.
Previous reports indicate that various drugs may induce linear IgA bullous dermatosis (LABD). The role of T cells and T-cell-derived cytokines in the pathomechanism of such skin lesions, however, has remained unclear.
To describe a case of LABD induced by ceftriaxone and metronidazole in an 80-year-old female suffering from cholelithiasis with concomitant cholecystitis and provide evidence that drug-specific T cells and their cytokines may contribute to the development of LABD lesions.
We performed flow cytometry analysis of peripheral blood T cells during LABD, epicutaneous testing (scratch-patch) and lymphocyte proliferation analysis (LTT) with the suspected drugs, routine histological and immunohistochemical examination of the acute skin lesions during LABD as well as of the positive epicutaneous test reactions and measurement of cytokines (IL-4, IL-5, IL-10, TNF-alpha, IFN-gamma) in the supernatant of the LTT cultures.
An increased number mainly of activated CD8+ cells was detected in the peripheral blood during LABD. T cell sensitization to ceftriaxone and metronidazole was confirmed by epicutaneous testing and LTT, indicating that these methods may be useful in identifying the causative drugs. Enhanced cytokine levels, particularly of IL-5, were found in the supernatant of the LTT stimulated with ceftriaxone and metronidazole. Furthermore, in situ expression of IL-5 was confirmed in the patient's skin lesions by immunohistochemistry.
Our findings suggest that in addition to IgA antibodies drug-specific T cells and their subsequent release of cytokines may play an important role in the pathogenesis of drug-induced LABD.
既往报道表明,多种药物可诱发线状IgA大疱性皮肤病(LABD)。然而,T细胞及T细胞衍生细胞因子在这类皮肤病变发病机制中的作用仍不明确。
描述1例80岁患胆结石伴胆囊炎的女性患者由头孢曲松和甲硝唑诱发LABD的病例,并提供证据证明药物特异性T细胞及其细胞因子可能促使LABD皮损的发生。
我们在LABD期间对外周血T细胞进行了流式细胞术分析,用可疑药物进行了表皮试验(划痕斑贴试验)和淋巴细胞增殖分析(LTT),对LABD期间的急性皮肤病变以及阳性表皮试验反应进行了常规组织学和免疫组化检查,并对LTT培养上清液中的细胞因子(IL-4、IL-5、IL-10、TNF-α、IFN-γ)进行了检测。
LABD期间外周血中主要检测到活化CD8+细胞数量增加。表皮试验和LTT证实T细胞对头孢曲松和甲硝唑致敏,表明这些方法可能有助于识别致病药物。在用头孢曲松和甲硝唑刺激的LTT上清液中发现细胞因子水平升高,尤其是IL-5。此外,通过免疫组化证实患者皮肤病变中有IL-5的原位表达。
我们的研究结果表明,除IgA抗体外,药物特异性T细胞及其随后释放的细胞因子可能在药物诱发LABD的发病机制中起重要作用。