Case Presentation: A 41-year-old man with recently diagnosed HIV/AIDS and Pneumocystis jirovecii pneumonia (PCP) was admitted with 5-day history of fever, throat pain, headache, and dry cough. Six weeks prior to admission, the workup was notable for CD4 88 cells/µL and CT chest imaging with ground glass opacities consistent with PCP. He was initiated on antiretroviral therapy (ART; specifically emtricitabine, tenofovir alafenamide, and dolutegravir), trimethoprim/sulfamethoxazole, and a prednisone taper. He showed clinical improvement by the end of that hospitalization.
Exam on readmission was notable for fever (102.8 °F), and tachycardia (HR to 120s). Physical exam was relevant for small white palatal lesions (thrush), a healing rash on the lower extremities, no lymphadenopathy, no neurologic deficits, and lungs clear to auscultation in all fields. Lab analysis was notable for CD4 count of 138 cells/µL; no leukocytosis, electrolyte abnormality, or decreased renal function was observed. The patient did present with a mild transaminitis of AST 65 units/L and ALT 97 units/L as well as increased LDH at 444 units/L which resolved during the hospital course. Chest x-ray showed an interval resolution of prior airspace disease and chest CT showed improvement of ground glass opacities from prior imaging (Figure 1) as well as discovery of diffuse lymphadenopathy.
Based on the initial presentation, the patient was started on empiric therapy of antibiotics to cover for HCAP and PCP pneumonia. A broad infectious workup was pursued, including blood, urine, and sputum cultures, brain MRI with contrast and a lumbar puncture with CSF analysis and culture. This workup was negative for any causative organisms. Silver stain for PCP pneumonia ultimately was negative as well.
After consultation with infectious disease specialists, a diagnosis of immune reconstitution inflammatory syndrome (IRIS) secondary to the initiation of ART was reached. He was stabilized and was discharged to home with recommendations to continue his ART regimen and to follow up as an outpatient with a HIV specialist.
Discussion: IRIS is a serious complication of HIV infection. It is caused by the rapid increase in T lymphocytes following initiation of ART, which can lead to a pathogen-specific, delayed hypersensitivity response. The severity of the response depends on two factors: the degree of CD4+ T cell suppression prior to ART, and the extent of immune recovery following the initiation of ART. Generally, the treatment of IRIS is primarily to continue to treat the underlying opportunistic infection while continuing HAART therapy. Ancillary agents for IRIS management include NSAIDs and corticosteroids.
To make a diagnosis of IRIS, the patient must meet most of the following criteria: the presence of AIDS with a pre-treatment CD4 count <100 cell/microL, a positive response to HAART, clinical manifestations consistent with an inflammatory condition, a temporal association between ART initiation and onset of symptoms (a range of 29 to 99 days), and a workup to rule out drug-resistant infection, superinfection, drug allergy, adverse drug allergy reaction, noncompliance, or diminished drug absorption. The true difficulty in the diagnosis of IRIS is to definitively exclude other causes of inflammatory symptoms.
Conclusions: After initiation of ART therapy, hospitalists should consider the risk of IRIS in immunocompromised patients. IRIS may be challenging to recognize as it is a diagnosis of exclusion requiring a broad workup to rule out infectious causes.