Iatrogenic Kaposi Sarcoma Precipitated by Anti-Tumor Necrosis Factor-Alpha (Anti-TNF-α) Therapy

Abstract

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.

Kaposi's sarcoma in an Ankylosing Spondylitis patient treated with Anti-Tumor Necrosis Factor-Alpha (Anti-TNF-α) Therapy

“…7,8 Iatrogenic CS due to TNF-α inhibitor therapy is rare. 9 Although some meta-analyses of clinical trial data found an increased risk of cancer using TNF-α inhibitor, observational data, especially from registries, generally did not confirm these findings. 10 Overall, there is evidence that TNF-α inhibitors do not increase the risk of most solid tumors, except for some skin cancers.…”

“…16 To our knowledge, five KS cases were identified with the use of infliximab, three cases with adalimumab, one with golimumab, and one with certolizumab pegol. 9,[17][18][19][20][21][22][23][24][25][26] unclear and should be addressed by appropriate studies. In most of the cases, KS was notably localized to the skin.…”

“…A close relationship between adalimumab and KS has been emphasized in previous studies. 9,22,23 These patients consisted of rheumatoid arthritis patients. No patients with AS were reported.…”

Current issues in the management of patients with HIV infection and rheumatic diseases

“…Mariappan и соавт. [28] сообщили о случае гистологически подтвержденной ятрогенной СК, развившейся у 66-летней женщины с серопозитивным РА без ВИЧ-инфекции через 2 мес после начала терапии АДА. Ранее пациентка без эффекта получала лечение МТ, ГКХ и ЭТЦ.…”

Tofacitinib Kullanımı Sonrası Gelişen İyatrojenik Kaposi Sarkomu Olgusu

“…Sunduğumuz olgu steroid, metotreksat ve tofacitinib kullanımı sonucu gelişen ancak steroid ve metotreksat kesilmesine rağmen gerilemeyen, sadece tofacitinib kullanımı sonucu iatrojenik Kaposi sarkomu gelişen yurtiçinden bildirilen ilk olgudur. İnfliksimab kullanımı sonrası beş olgu, adalimumab üç, golimumab bir, vedolizumab iki, sertolizumaba bağlı bir adet olgu bildirilmiştir [6][7][8] . Ayrıca diabetes mellitus, immunsupresyon ve steroid kullanımı sonucu dermatofit enfeksiyonlarının daha yaygın ve şiddetli seyretmesine neden olmaktadır 9 .…”