Case Presentation: A 49-year-old female with Adult-onset Still’s disease on prednisone 40 mg daily for three months presented to ED with right leg weakness and intractable headache for one week. CT head was unrevealing. LP showed an opening pressure of 29.5cmH2O, 97 WBCs (88% lymphocytes), 36 RBCs, protein of 56mg/dL, and glucose of 46mg/dL. CSF PCR for Cryptococcus neoformans was positive. Initially, amphotericin B and flucytosine were started, but the latter was held for thrombocytopenia after one week. Patient completed a 6-week course of amphotericin B alone for induction. Steroids were tapered over four weeks. Five weeks into treatment, CSF PCR was again positive for cryptococcus, so patient received a second round of induction – this time with amphotericin B, fluconazole, and flucytosine – for six weeks. She was discharged on oral fluconazole for eight weeks. One month after discharge, patient was brought in for declining mental status for a week. She was minimally responsive to verbal stimuli and had new left hemiparesis with persistent right leg weakness. MRI brain showed acute infarcts in the right caudate lobe as well findings consistent with meningoencephalitis. LP showed an opening pressure of 36cmH2O,113 WBCs (70% lymphocytes), protein of 157mg/dL, and glucose of 40 mg/dL. Surprisingly, repeat CSF Cryptococcus PCR and cultures were negative. Given the timeline of patients presentation one month after discontinuation of steroids, and workup consistent with sterile meningitis, immune reconstitution inflammatory syndrome was identified as the likely diagnosis. Patient was started on Prednisone 50 mg daily. Two days later LP showed normalization of opening pressure to 25cmH2O, and improvement of CSF protein to 61mg/dL and glucose to 68mg/dL. Steroids were slowly tapered by 1mg per week. Six weeks after presentation, the patient’s mental status returned to baseline, left hemiparesis resolved, and right lower extremity strength significantly improved.
Discussion: Immune Reconstitution Inflammatory Syndrome (IRIS) is a collection of inflammatory disorders with paradoxical worsening of preexisting infectious processes that is temporally related to recovery of the immune system [1]. First described with initiation of antiretroviral therapy in HIV patients, IRIS has been reported in patients with rheumatologic conditions upon withdrawal of corticosteroids [2] and after reduction in immunosuppressive therapy in organ transplant recipients [3]. We present a case of IRIS in a non-HIV patient with cryptococcal meningitis.
Conclusions: IRIS in the setting of rapid discontinuation of corticosteroids is generally managed by reintroduction of steroids and slow taper over months. The approach to management is adapted from our knowledge of IRIS in HIV patients. Our patient first developed cryptococcal meningitis due to steroid-induced immunosuppression and later developed worsening of her symptoms upon rapid discontinuation of steroids. LP and MRI brain are important diagnostic tools for CNS IRIS as evident from our case. Clinicians should have a high index of suspicion for IRIS in patients presenting with new findings in the setting of rapid discontinuation of steroids due to infection, especially once a persistent or new infectious etiology is ruled out.
