Mattos K P H, Cintra M L, Gouvêa I R, Ferreira L Á, Velho P E N F, Moriel P
Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil.
J Clin Pharm Ther. 2017 Oct;42(5):573-578. doi: 10.1111/jcpt.12543. Epub 2017 May 11.
What is known and objective Polymyxins were widely used until the 1960s; however, they fell into disfavour owing to their toxicity. The subsequent growth of infections caused by multidrug-resistant Gram-negative bacteria has led to renewed use of this class of antimicrobials in clinical practice. Acquired skin hyperpigmentation (SH) following intravenous polymyxin B treatment has been previously reported, but little is known about its pathogenesis, clinical course and treatment. To improve understanding of these issues, we conducted a prospective study of adult patients receiving intravenous polymyxin B treatment. Methods Patients receiving intravenous polymyxin B treatment were followed throughout the course of treatment. Clinical, dermatoscopic, histologic and immunohistochemical skin properties of patients who presented with SH were studied. Results and discussion Skin hyperpigmentation was noted in 8% of patients (n=20/249); however, clinical, dermatoscopic, histologic and immunohistochemical examinations were performed only in three patients for whom the consent of relatives was obtained. Histologic and immunohistochemical findings showed an abundant melanocyte-pigmented dendritic network. Langerhans cells' hyperplasia and dermal IL-6 overexpression were also found, presumably for an inflammatory process due to polymyxin B use. As polymyxin B causes the release of histamine, which is known for its melanogenic effect, it is possible that skin darkening is associated with this inflammatory mediator. What is new These clinical and dermatoscopic findings contribute to a better understanding of how the pigmentary reaction manifests following intravenous polymyxin B treatment. Conclusion We concluded that hyperpigmentation due to intravenous polymyxin B treatment is associated with an inflammatory process and subsequent melanocyte activation. Although the pigmentary disorder neither influences the outcome of the therapy nor warrants discontinuation of treatment, it nevertheless considerably affects the patient's quality of life.
多黏菌素在20世纪60年代前被广泛使用；然而，因其毒性而不再受青睐。随后，耐多药革兰氏阴性菌引起的感染增加，导致这类抗菌药物在临床实践中重新被使用。此前已有静脉注射多黏菌素B治疗后出现获得性皮肤色素沉着（SH）的报道，但对其发病机制、临床过程及治疗了解甚少。为更好地理解这些问题，我们对接受静脉注射多黏菌素B治疗的成年患者进行了一项前瞻性研究。
对接受静脉注射多黏菌素B治疗的患者在整个治疗过程中进行随访。对出现SH的患者的临床、皮肤镜、组织学和免疫组化皮肤特性进行研究。
8%的患者（n = 20/249）出现皮肤色素沉着；然而，仅对3名获得亲属同意的患者进行了临床、皮肤镜、组织学和免疫组化检查。组织学和免疫组化结果显示有丰富的黑素细胞色素沉着树突状网络。还发现朗格汉斯细胞增生和真皮白细胞介素-6过表达，推测是由于使用多黏菌素B引起的炎症过程。由于多黏菌素B会导致组胺释放，而组胺具有致黑素生成作用，皮肤变黑可能与这种炎症介质有关。
这些临床和皮肤镜检查结果有助于更好地理解静脉注射多黏菌素B治疗后色素反应的表现。
我们得出结论，静脉注射多黏菌素B治疗引起的色素沉着与炎症过程及随后的黑素细胞激活有关。尽管色素紊乱既不影响治疗结果，也无需停药，但它仍会严重影响患者的生活质量。
