References

1. Chang, C. C., & Perfect, J. R. (2016). Repeated therapeutic lumbar punctures in cryptococcal meningitis - necessity and/or opportunity?. Current opinion in infectious diseases, 29(6), 539–545. https://doi.org/10.1097/QCO.0000000000000315 2. Henao-Martínez, A. F., Chastain, D. B., & Franco-Paredes, C. (2018). Treatment of cryptococcosis in non-HIV immunocompromised patients. Current opinion in infectious diseases, 31(4), 278–285. https://doi.org/10.1097/QCO.0000000000000458 3. George, I. A., Spec, A., Powderly, W. G., & Santos, C. A. Q. (2018). Comparative Epidemiology and Outcomes of Human Immunodeficiency virus (HIV), Non-HIV Non-transplant, and Solid Organ Transplant Associated Cryptococcosis: A Population-Based Study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 66(4), 608–611. https://doi.org/10.1093/cid/cix867 4. Baddley JW, Forrest GN; AST Infectious Diseases Community of Practice. Cryptococcosis in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13543. doi: 10.1111/ctr.13543. Epub 2019 Apr 14. PMID: 30900315.

Discussion

Cryptococcosis in immunosuppressed hosts has a 20% mortality rate. Treatment usually depends on the organ systems involved, but in cases of cryptococcal meningitis or disseminated disease, it involves induction with amphotericin/flucytosine for 2-6 weeks, consolidation with fluconazole for 8 weeks (may be extended to 6-12 months). Management of intracranial pressure with serial lumbar taps with a goal of less than 20 cmH2O or a 50% reduction is proven to reduce mortality in meningitis patients. Placement of temporary external draining devices is common. Monitoring for response to therapy is important and is done by serial ICP measurements, negativization of cultures/ stains, and resolution of neurologic symptoms. Prophylactic treatment against cryptococcosis has been studied only in HIV-positive patients with a low CD4 count.

Case Presentation

A 71-year-old male presented to our hospital with complaints of fatigue, episodic headaches, and an intermittent, non-productive cough for 2-3 months. His medical history was significant for a renal transplant (one year ago), CAD, type 1 DM, hypertension, and hyperlipidemia, and he was on outpatient suppressive therapy with mycophenolate, tacrolimus, and prednisone. On presentation, he was stable and afebrile. Initial labs showed mild leukocytosis (11.3 x109/L). Chest X-ray showed a new left lower lobe opacity. MRI brain did not show any evidence of an acute intracranial process. He was empirically treated for bacterial pneumonia, however, his clinical status continued to deteriorate. CT chest showed bilateral multifocal areas of nodular consolidation with ground glass opacities. Lumbar puncture (LP) revealed cryptococcal antigen, which was also detected in serum. He underwent bronchoscopy and BAL fungal culture confirmed pulmonary cryptococcosis. Induction therapy with intravenous amphotericin-B/flucytosine was initiated. The patient continued to have waxing and waning mentation concerning for ongoing encephalopathy, along with persistent cough and fevers. Repeat MRI brain was concerning for increased intracranial pressure (ICP), which was confirmed on repeat LP. Subsequently, he underwent 12 LPs to mitigate the increased ICP, and eventually, a lumbar drain was placed. Each LP led to a brief period of improvement in mentation, but was followed closely by lethargy, unresponsiveness, and random myoclonic jerks later. CSF cultures remained positive even after two weeks of induction therapy. Given the slow response, induction treatment was broadened to triple therapy with amphotericin-B, flucytosine, and fluconazole, and the duration was extended to four weeks. CSF culture s subsequently demonstrated clearance and the patient showed symptomatic improvement with decreased cough, return to baseline mentation, and disappearance of new fever spikes. The lumbar drain was removed and he was transitioned to consolidation therapy with eight weeks of intravenous fluconazole.

Introduction

Cryptococcosis, an opportunistic fungal infection, is a source of significant morbidity and mortality in immunocompromised hosts. Even though initially described in HIV-positive patients,it is now known that approximately half of cryptococcosis cases occur in HIV-negative hosts (such as solid organ transplant patients), with a higher mortality rate. If the infection spreads to more than two non-contiguous organ systems, it is called disseminated cryptococcosis. We present a case of an elderly HIV- negative immunocompromised gentleman with disseminated cryptococcosis presenting with pneumonia and meningitis.

Authors

Unnati Bhatia(1), Ioannis Karageorgiou(1), Carmen Demarco(2) 1 Department of Internal Medicine, William Beaumont University Hospital, Royal Oak, MI, USA. 2 Department of Infectious Diseases, William Beaumont University Hospital, Royal Oak, MI, USA.

Title

The true pressure of a disease: Disseminated Cryptococcal infection in a renal transplant patient