A CASE OF IMMUNE RECONSTITUTION SYNDROME IN DISSEMINATED HISTOPLASMOSIS

Abstract

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Immune reconstitution syndrome (IRS) was first described in tuberculosis patients started on therapy but is most often associated with HIV patients with opportunistic infections (OIs) started on antiretroviral therapy. There is now growing recognition of IRS in other immunosuppressed populations with OIs. We present a case of disseminated histoplasmosis in a renal transplant patient who developed worsening respiratory failure after antifungal treatment was initiated. CASE PRESENTATION: A 42-year-old female status post renal transplant on mycophenolate mofetil, tacrolimus, and prednisone, was admitted to the ICU with 1 month of fevers, night sweats, weight loss, dry cough, and dyspnea on exertion. On exam, she had fever, hypoxia requiring 6 liters via nasal cannula, increased work of breathing and diffuse fine crackles. Labs were remarkable for pancytopenia, lactate dehydrogenase of 653 unit/L and ferritin over 30,000 ng/ml. Computerized tomography of the chest showed diffuse ground glass opacities. Empiric antibiotics were initiated including treatment for pneumocystis pneumonia (trimethoprim/sulfamethoxazole and higher dose prednisone) and disseminated fungal infection. Mycophenolate was held. Peripheral blood smear showed encapsulated organisms in neutrophils and blood and sputum cultures were positive for Histoplasma capsulatum. Treatment was consolidated to liposomal amphotericin and prednisone was again reduced to home dose. On day 6, she decompensated requiring 45 liters at 100% and vasopressor support. Prednisone was increased to 40 mg twice daily with subsequent rapid improvement. DISCUSSION: Our patient had a paradoxical response to therapy with worsening hypoxemia and cardiovascular collapse suggestive of IRS after initiation of therapy and reduction in immunosuppression. After re-starting high dose prednisone, she had rapid and sustained improvement. There is growing recognition of IRS in post-transplant patients with OIs coupled with iatrogenic withdrawal of immunosuppressive therapy. The exact pathophysiology of IRS is unknown, but it is thought to be an increase in the inflammatory state, particularly cell mediated immune response. Diagnosis of IRS is challenging as it may not represent one single syndrome, rather a spectrum of syndromes and there are no definitive diagnostic criteria for IRS in the post-transplant population. While there is no standardized treatment for IRS, corticosteroids are often used. CONCLUSIONS: Our case represents IRS associated with disseminated histoplasmosis in a renal transplant patient. IRS is increasingly described in this patient population and it is important that clinicians are aware of this complication and are aware of the potential consequences of reducing immunosuppression. Reference #1: Delliere S et al. Understanding pathogenesis and care challenges of immune reconstitution inflammatory syndrome in fungal infections. J Fungi 2018; 4(4): 139. Reference #2: Jazwinski A et al. Immune reconstitution syndrome in a patient with disseminated histoplasmosis and steroid taper: maintaining the perfect balance. Mycoses 2009; 54: 270-272. Reference #3: Sun H et al. Opportunistic infection associated immune reconstitution syndrome in transplant recipients. CID 2011; 53: 168-176. DISCLOSURES: No relevant relationships by Ankita Agarwal, source=Web Response No relevant relationships by Wendy Armstrong, source=Web Response No relevant relationships by Jonathan Sevransky, source=Web Response