Oral thrush (eg, white buccal and palatal plaques) and bilateral tender lymphadenopathy in a patient with a history of intravenous drug use are highly suggestive of HIV infection.  HIV is further supported by the presence of Kaposi sarcoma (KS), a vascular tumor common in HIV-positive individuals and an AIDS-defining malignancy.

KS is strongly associated with human herpesvirus type 8 (HHV-8), as well as an impaired T-cell response (eg, HIV infection).  HHV-8 infects vascular and lymphatic endothelial cells, causing their differentiation into a mixed phenotype thought to increase oncogenic potential.  The viral genome also contains several oncogenes that cause endothelial proliferation (eg, inhibit cell cycle regulation and apoptosis), thus promoting tumorigenesis.  In addition, HHV-8 induces production of angiogenic and inflammatory cytokines, creating a favorable environment for cell growth.

AIDS-related KS most commonly involves the skin, presenting as multiple red, purple, or brown papules or plaques that appear on the lower extremities.  Lesions can also develop on the mucosal membranes of the face and genitals, and frequently spread internally to involve the lungs and gastrointestinal tract (eg, bleeding/hemoptysis).  Histopathology typically shows a proliferation of spindle-shaped endothelial cells with slit-like vascular spaces, red blood cell extravasation, and inflammation.

(Choice A)  Epstein-Barr virus is associated with Burkitt lymphoma, particularly in patients who are HIV positive.  Burkitt lymphoma can involve the lymph nodes and may present with lymphadenopathy and constitutional symptoms (eg, weight loss).  However, red-purple, papular skin lesions would not be expected.

(Choice B)  Hepatitis C virus can cause cryoglobulinemia, which often presents with palpable purpura (eg, nonblanching, hemorrhagic papules) on the lower extremities due to the deposition of immune complexes in small vessels.  These lesions are typically associated with arthralgia and weakness.

(Choice C)  Herpes simplex virus type 1 can cause herpetic whitlow, a cutaneous finger infection characterized by clusters of vesicles (not red-purple papules) that may ulcerate and crust, often accompanied by burning and tingling.

(Choice E)  Treponema pallidum, which causes syphilis, can have variable cutaneous manifestations, depending on the stage of infection.  Common skin lesions include chancres (eg, painless anogenital ulcers with indurated borders), diffuse erythematous macules, condylomata lata (eg, gray, wart-like growths), and gummata (eg, ulcerated nodules).

Educational objective:
Kaposi sarcoma is a vascular tumor strongly associated with human herpesvirus type 8.  It typically presents as red, purple, or brown papules and plaques on the extremities of patients who are HIV positive.