Kaposi Sarcoma Masquerading as Methicillin-Resistant Staphylococcus aureus Soft Tissue Infection of the Foot in an Immunocompromised Transgender Female

Kaposi sarcoma (KS) is an acquired immunodeficiency syndrome-defining malignancy caused by human herpesvirus-8 (HHV-8), predominantly affecting immunocompromised individuals, particularly those with untreated or advanced human immunodeficiency virus (HIV). Here, we present the case of a 28-year-old homeless transgender female with untreated HIV (CD4 count = 175 cells/μL, HIV RNA = 221,000 copies/mL), latent syphilis, and methamphetamine use disorder, who presented with a five-month history of progressive left foot pain, ulceration, and swelling. Initial examination revealed extensive bilateral lower extremity ulcerative lesions, with a necrotic, violaceous mass on the left hallux and a similar lesion on the right medial ankle, raising suspicion for KS. However, the presence of purulent drainage and surrounding erythema suggested a superimposed bacterial infection. Bedside incision and drainage of the left hallux lesion was performed, followed by formal surgical debridement and excision of infected soft tissue masses. Histopathologic examination confirmed KS, characterized by spindle cell proliferation, slit-like vascular channels, and HHV-8 positivity on immunohistochemical staining. Wound cultures grew methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), indicating a concurrent bacterial infection. The patient was initiated on antiretroviral therapy with Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) and treated with linezolid and amoxicillin-clavulanate for MRSA. Wound care and offloading led to significant improvement, with reduced drainage and progressive healing. This case underscores the diagnostic and therapeutic challenges of KS masquerading as MRSA soft tissue infection in immunocompromised patients. The overlapping clinical features of KS and bacterial infections, particularly in the lower extremities, highlight the importance of early biopsy, histopathologic confirmation, and a multidisciplinary approach to care. Furthermore, this case emphasizes the impact of social determinants of health, such as homelessness and substance use, on disease progression and treatment outcomes. Addressing these barriers is essential for improving care in vulnerable populations with complex, multifactorial conditions.