Case Presentation:  A 41 year-old male with HIV/AIDS (diagnosed three years ago), cutaneous Kaposi Sarcoma (KS), started on combination antiretroviral treatment (cART) three months ago (CD4 270, Viral load (VL) >2000 at the time of initiation of cART), recent VL of 39, who presented with worsening shortness of breath, cough, abdominal pain, abdominal distention and weakness for the past 1-2 weeks. He also reported enlarging KS lesions on the skin (right thigh) and worsening peripheral edema for the past two months. Vital signs on admission were remarkable for tachycardia to 110bpm, tachypnea and desaturation to 88-90% on room air. On physical exam, patient was breathing rapidly with decreased breath sounds on right base. Bilateral axillary lymph nodes were palpable. Extensive KS plaques with nodular tumors and ulcerations were noted on the right leg. Also, KS lesion was seen on the hard palate. Abdomen was distended with positive fluid wave. CT chest revealed large encapsulated right pleural effusion and a small pleural effusion with multiple irregular opacities in the left lung apex. CT abdomen/pelvis showed large ascites with extensive metastatic disease to liver, spleen, spine, adrenals and retroperitoneal lymph nodes. Axillary lymph node biopsy showed KS with tumor cells positive for HHV-8 and CD31. Pleural and ascitic fluid analyses were consistent with PEL, cells positive for HHV-8, EBV, BOB1 and CD45. Patient was started on dose adjusted EPOCH chemotherapy. However, on day 9, developed acute respiratory failure and was intubated. Later, developed multifactorial multi organ failure requiring vasopressor support and hemodialysis. Upon clinical improvement and successful extubation, patient decided not to pursue further treatment and opted for hospice care. 

Discussion: Immune reconstitution inflammatory syndrome (IRIS) can cause significant morbidity and mortality if not promptly recognized and treated. It is usually characterized by paradoxical worsening of previously treated disease or unmasking of previously subclinical disease. IRIS is more commonly observed to occur in patients with low CD4 count and high viral load at the time of initiation on cART. IRIS associated flare of KS, most common AIDS-defining malignancy, or development of PEL (rare type of non-Hodgkin’s Lymphoma) are rare and have only been described in a few case reports. Our patient developed extensive worsening of KS and new PEL after initiation of cART with significant reduction in viral load.

Conclusions:

With the rapid expansion and development of more potent new HIV/AIDS treatment regimens, IRIS may occur more frequently. Thus, better understanding of the risk factors and development of predictors for IRIS are warranted.