Mariappan Aathi Lakshmi, Desai Shreya, Locante Alberto, Desai Palak, Quraishi Javairia
Internal Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, USA.
Pathology, AMITA Health Saints Mary and Elizabeth Medical Center, Chicago, USA.
Cureus. 2021 Feb 16;13(2):e13384. doi: 10.7759/cureus.13384.
Kaposi sarcoma (KS) is a vascular neoplasm caused by human gammaherpesvirus 8 (HHV-8). Four subtypes of KS are described: classic (Mediterranean), epidemic (acquired immunodeficiency syndrome (AIDS)-associated), endemic (sub-Saharan Africa), and iatrogenic. Iatrogenic KS due to tumor necrosis factor-alpha (TNF-α) inhibitor therapy is particularly rare. A 66-year-old female with a history of seropositive rheumatoid arthritis (RA) presented with a skin lesion on her right second toe. Diagnosed with RA four years prior, she failed to respond to methotrexate, hydroxychloroquine, and etanercept. As a result, she was started on adalimumab. Approximately two months into therapy, she presented to the emergency room with a dark brown skin lesion on her right second toe. She underwent excisional biopsy of the mass, which demonstrated a tumor composed of spindle cells forming slit-like spaces with extravasated red blood cells. The tumor was positive for cluster of differentiation 31 (CD31), CD34, and HHV-8 immunostains and negative for smooth muscle antibody (SMA) and desmin immunostains, consistent with Kaposi sarcoma. Human immunodeficiency virus (HIV) serology was negative. The patient was diagnosed with iatrogenic KS. Adalimumab was discontinued. The patient was started on alitretinoin and underwent adjuvant radiation therapy to minimize recurrence. TNF-α is a pro-inflammatory cytokine that has been implicated in many inflammatory diseases and in cell apoptosis. While anti-TNF-α agents have improved outcomes in many immune-mediated diseases, higher rates of infections and malignancy have also been reported. The incidence of KS with anti-TNF-α therapy remains a rare entity. Therefore, it is extremely important for patients receiving biologic agents, including TNF-α inhibitors, to have a close follow-up and receive routine skin evaluation for malignancy. Clinicians should have a high index of suspicion for KS in such non-HIV patients started on immunosuppressive agents.
卡波西肉瘤（KS）是一种由人类γ疱疹病毒8型（HHV-8）引起的血管肿瘤。KS有四种亚型：经典型（地中海型）、流行型（与获得性免疫缺陷综合征（AIDS）相关）、地方型（撒哈拉以南非洲）和医源性。因肿瘤坏死因子-α（TNF-α）抑制剂治疗导致的医源性KS极为罕见。一名66岁血清阳性类风湿关节炎（RA）女性患者，右第二趾出现皮肤病变。她四年前被诊断为RA，对甲氨蝶呤、羟氯喹和依那西普治疗无效。因此，开始使用阿达木单抗治疗。治疗约两个月后，她因右第二趾出现深褐色皮肤病变到急诊室就诊。她接受了肿物切除活检，结果显示肿瘤由梭形细胞组成，形成裂隙样间隙并伴有红细胞外渗。肿瘤分化簇31（CD31）、CD34和HHV-8免疫染色呈阳性，平滑肌抗体（SMA）和结蛋白免疫染色呈阴性，符合卡波西肉瘤。人类免疫缺陷病毒（HIV）血清学检查为阴性。该患者被诊断为医源性KS。停用阿达木单抗。患者开始使用阿利维A酸并接受辅助放疗以降低复发风险。TNF-α是一种促炎细胞因子，与许多炎症性疾病和细胞凋亡有关。虽然抗TNF-α药物在许多免疫介导疾病中改善了治疗效果，但也有报道称感染和恶性肿瘤发生率更高。抗TNF-α治疗导致KS的发生率仍然很低。因此，对于接受生物制剂（包括TNF-α抑制剂）治疗的患者，密切随访并接受常规皮肤恶性肿瘤评估极为重要。对于开始使用免疫抑制剂的此类非HIV患者，临床医生对KS应保持高度怀疑。
