Immunosuppressed Patient Presenting With Fever, Interstitial Pneumonia, and Brain Lesions

Clinical Infectious Diseases, Nov 2015

Anthony Amoroso, Catherine M. Stefaniuk, Michelle Stehura, Linda M. Sandhaus, Elie Saade, Scott A. Fulton, Michael R. Jacobs

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Immunosuppressed Patient Presenting With Fever, Interstitial Pneumonia, and Brain Lesions

Clinical Infectious Diseases® Immunosuppressed Patient Presenting With Fever, Interstitial Pneumonia, and Brain Lesions 0 University and University Hospitals Case Medical Center , 11100 Euclid Ave, Cleveland, OH 44106 1 Division of Infectious Diseases, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center , Cleveland, Ohio 2 Department of Pathology 3 Catherine M. Stefaniuk Figure 1. Composite picture of cytospin preparation of cerebrospinal fluid showing intracellular organisms within polymorphonuclear cells and monocytes and 1 extracellular organism (Wright stain). Arrows indicate organisms. Original magnification ×1000. ANSWER TO THE PHOTO QUIZ - Diagnosis: Disseminated toxoplasmosis in a hematopoietic stem cell transplant recipient. The organisms that are seen in the cerebrospinal fluid (CSF), both within and outside the neutrophils and monocytes, are small, oval-shaped protozoa, showing blue cytoplasm and single red nuclei with Wright stain (Figure 1). Few organisms were present in the cytospin CSF preparation, and initial review was negative. These findings are consistent with tachyzoites (trophozoites) of Toxoplasma gondii, although other sporozoa have similar morphologic features [1]. The diagnosis of toxoplasmosis was confirmed by positive Toxoplasma B1 gene polymerase chain reaction (PCR) in bronchoalveolar lavage fluid (4 300 000 copies/mL) as well as CSF (34 600 copies/mL). The patient was Toxoplasma seropositive prior to his stem cell transplant, and presented with overwhelming disseminated toxoplasmosis following chemotherapy and multiple hematopoietic stem cell transplants (HSCTs). He died from respiratory failure associated with Toxoplasma pneumonia. Disseminated toxoplasmosis involving the lungs, central nervous system (cerebral hemispheres, dural membrane, spinal cord and pituitary gland), heart, gastrointestinal tract, liver, kidneys, and bone marrow was found at autopsy. Patients with disseminated toxoplasmosis are noted to have a worse prognosis if they present with myocarditis, encephalitis, pneumonia, or hepatitis [2]. High mortality is associated with hematological malignancies, allogeneic HSCT with cord blood and delayed or poor engraftment, high Simplified Acute Physiology Score II, high Sequential Organ Failure Assessment score, elevated lactate levels, systolic cardiac dysfunction, and invasive mechanical ventilation. Diagnosis of Toxoplasma reactivation is best evaluated by demonstration of tachyzoites in blood, bone marrow, bronchoalveolar lavage, CSF, or tissue biopsy. Toxoplasma B1 gene PCR to demonstrate the presence of Toxoplasma DNA in blood, tissues, and other specimens is also available. Toxoplasma serology can also be used, but HSCT patients frequently demonstrate stable antibody titers posttransplant or a rise of immunoglobulin G but not immunoglobulin M or immunoglobulin A titers, thus limiting the value of this test [1]. Toxoplasmosis can be diagnosed by direct microscopy, Toxoplasma B1 PCR, and changes in serology. Direct examination of stained fluid, tissue sections, or smears is highly specific, but lacks sensitivity [1]. Suitable stains include Giemsa, Wright, hematoxylin-eosin, and immunohistochemical staining using Toxoplasma-specific labeled antibodies [3]. The B1 gene in T. gondii is a sensitive and specific target used for detection by PCR, with approximately 35 copies of this gene per organism [4]. Correia et al reported sensitivity of 1.5%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 36.5% in blood, and sensitivity of 35.3%, specificity of 100%, PPV of 100%, and NPV of 44.7% in CSF by PCR in AIDS patients with cerebral toxoplasmosis [5]. This case illustrates the need to monitor Toxoplasmaseropositive HSCT recipients for the development of reactivation toxoplasmosis, the necessity for consideration of toxoplasmosis in the differential diagnosis of infection in an immunocompromised host, the diagnosis of toxoplasmosis by the presence of intracellular tachyzoites in CSF, and confirmation of this diagnosis by positive T. gondii PCR on bronchoalveolar lavage fluid and CSF specimens. Acknowledgments. Toxoplasma B1 polymerase chain reaction was performed by Viracor-IBT Laboratories, Lee’s Summit, Missouri. Potential conflicts of interest. All authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 1. Robert-Gangneux F , Darde ML . Epidemiology of and diagnostic strategies for toxoplasmosis . Clin Microbiol Rev 2012 ; 25 : 264 - 96 . 2. Schmidt M , Sonneville R , Schnell D , et al. Clinical features and outcomes in patients with disseminated toxoplasmosis admitted to intensive care: a multicenter study . Clin Infect Dis 2013 ; 57 : 1535 - 41 . 3. Held TK , Kruger D , Switala AR , et al. Diagnosis of toxoplasmosis in bone marrow transplant recipients: comparison of PCR-based results and immunohistochemistry . Bone Marrow Transplant 2000 ; 25 : 1257 - 62 . 4. Joseph P , Calderon MM , Gilman RH , et al. Optimization and evaluation of a PCR assay for detecting toxoplasmic encephalitis in patients with AIDS . J Clin Microbiol 2002 ; 40 : 4499 - 503 . 5. Correia CC , Melo HR , Costa VM . Influence of neurotoxoplasmosis characteristics on real-time PCR sensitivity among AIDS patients in Brazil . Trans R Soc Trop Med Hyg 2010 ; 104 : 24 - 8 .

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Anthony Amoroso, Catherine M. Stefaniuk, Michelle Stehura, Linda M. Sandhaus, Elie Saade, Scott A. Fulton, Michael R. Jacobs. Immunosuppressed Patient Presenting With Fever, Interstitial Pneumonia, and Brain Lesions, Clinical Infectious Diseases, 2015, 1888-1889, DOI: 10.1093/cid/civ701