Disseminated histoplasmosis after liver transplantation

Infectious Diseases Case Presentation #4 Daniel Caplivski, M.D. Clinical Presentation     CC: fever and diarrhea HPI: 61 year old man s/p liver transplant 11/02 for hepatitis c cirrhosis with hepatocellular carcinoma was admitted to an outside hospital with fever and watery, non-bloody diarrhea. The onset of symptoms began around two weeks prior to his admission to the first hospital. One week after the onset of diarrhea and fever, the patient noted a dry cough, night sweats, chills, weakness, and weight-loss of 26 pounds over several weeks Clinical Presentation Continued ROS: denied headache, visual changes, dysuria, rashes, abdominal pain, but did have mild nausea and one episode of vomiting  PMH: DM, Hepatitis C infection with hepatocellular carcinoma  PSH: Cadaveric liver transplant November 2002  MEDS: tacrolimus, aspirin, insulin, and calcium supplementation  Clinical Presentation Continued     SH: former 1ppd smoker, denied recent alcohol, denied any h/o ivdu no pets or sick contacts He was a former custodial worker in a hospital. He was sexually only with his wife in the recent years Travel History: The patient was originally from the Dominican Republic. He arrived in the United States 38 years ago. He returned for a 2 week visit to Santo Domingo 1 year prior to his transplant. Physical Exam T 39.8 BP 120/78 HR 114 R21 SAT 95% on room air Gen—no acute distress HEENT—anicteric, perrl, eomi, no thrush, no oral lesions Neck—supple, no lan Cor—rrr s1/s2, no murmurs Lungs—clear to auscultation bilaterally Abd—soft nt/nd, nl bs, no palpable hepatosplenomegaly Ex—no edema, no evidence of peripheral emboli Skin—diffuse hypopigmented macules on back on arms Neurologic—nonfocal  Laboratory Values Na K Cl Co2 Bun Cr Aph Alt Ast Ggt Tb db 134 3.6 99 25 17 1.7 102 24 42 74 1.2 0.3 Wbc Hb 2.5 9.1 Hbct Plt 26 96 esr 81 Mcv Neut Lym Pt 88.5 71 23 15.3 Inr 1.3 Ptt 39.9 Ldh 231 Previous Hospitalization    At the outside hospital a diagnostic evaluation was pursued that included abdominal and pelvis CT scan and colonoscopy for the evaluation of diarrhea. Blood and stool cultures were reportedly negative for bacteria, and no ova or parasites were seen in stool samples The patient also underwent chest x-ray, gallium scan, and bronchoscopy because of the patients cough. None of these tests led to establishment of a diagnosis. Previous Hospitalization (continued)      Chest x ray showed no infiltrates or effusions Gallium scan reportedly revealed mildly bilateral pulmonary uptake Bronchoscopy showed no evidence of AFB, and PCP dfa was found to be negative. Serum cryptococcal antigen was negative. Lung biopsy from the right upper lobe: no evidence of tumor, granuloma, or parasites. Silver Methenamine stains for pneumocystis were negative. A legionella antigen from the urine was negative. Previous Hospitalization (continued)      Serologies for CMV and EBV were pending at time of transfer stool was negative for c. difficile toxin Stool was ordered for ova, parasites (including cryptosporidia species) but was not received by the lab Biopsies of the colon reportedly showed no viral inclusion bodies, no evidence of CMV. CT abd/pelvis: splenomegaly (17cm), tiny hypodense hepatic lesion, normal adrenals, no unremarkable loops of bowel. Radiologic Studies Chest X-ray from admission 9/26  Diffuse interstitial lung disease with fine nodularity suggestive of pcp pneumonia versus miliary tuberculosis. Calcified nodule anterior to the heart on the lateral view is most likely a granuloma.  Differential Diagnosis Mycobacterial  Fungal  Bacterial  Parasitic  Viral  Non-infectious  Pathologic Findings     Liver biopsy: multiple noncaseating epithelioid cell granulomas with intracellular microorganims…no acid fast mycobacteria are identified. There are mild lymphocytic portal inflammation and mild lobular necroinflammatory activity with ceroid macrophages. Trichrome stain reveals mild portal fibrosis, mild microvesicular steatosis is noted. No evidence of rejection. Urine Histoplasma was negative Fungal and Parasitic Infections of the GI Tract Candida species  Cryptococcus neoformans  Histoplasma capsulatum  Pneumocystis carinii  Mucoraceae  Aspergillus  Leishmania species  Disseminated Histoplasmosis       Dimorphic fungus endemic to more than 50 countries Primary infection results from inhalation of spores. Can present radiographically as a miliary pattern on chest x-ray. Defects in cellular immunity can result in reactivation and dissemination of the organism. Dissemination can lead to splenomegaly and pancytopenia as organisms invade the reticuloendothelial system and bone marrow. Weight loss and Fever are common presenting signsAdrenal involvement often seen in autopsy studies, though clinical hypoadrenalism is less common. Diagnosis of Histoplasmosis     Urine Histoplasma Antigen: in AIDS patients sensitivity 95%. In immunosuppressed non-AIDS patients sensitivity=82% Bone Marrow biopsy (75% sensitivity), blood cultures (50-70%), BAL (87%)and biopsies of skin lesions were found to have high diagnostic yield in a study of AIDS patients in Argentina Liver or lymph node biopsy have been diagnostic in 25% of cases CSF antigen can also reveal the diagnosis Treatment Recommendations Patients should receive amphotericin B lipid formulation for 3-14 days  Lifelong suppression with oral itraconazole 200mg orally twice a day is recommended.  Unacceptable relapse rates and induction of resistance are associated with fluconazole  Clinical Course    The patient was started on amphotericin B lipid complex. He fever persisted for 42 days while on amphotericin B lipid complex, and then liposomal complex The cough resolved soon after initiating treatment, but the diarrhea persisted for weeks. Because of persistent fevers and pancytopenia he underwent bronchoscopy, colonoscopy and bone marrow biopsy to evaluate for other infectious etiologies. References        Bottone, E., Huprikar, S et al. Textbook-atlas of intestinal infections in AIDS, Vella, S., editor Springer, Milan 2003 Olofinlade, et al. Treatment of the wrong disease with the Right Medication: A Case of Generalized Leishmaniasis Involving the Liver and the Gastrointestinal Tract.. AJG May 2000, 1377 Corti, et al. Disseminated Histoplasmosis and AIDS: Clinical Aspects and Diagnostic Methods for Early Detection. AIDS Patient Care and STDs 14, 3 2000 pp149-153 Wheat, J. Diagnosis and treatment of disseminated hisoplasmosis. Uptodate. 2002 Limaye, et al. Transmission of Histoplasma capsulatum by organ stransplantation. NEJM 343;16: 1163-1166. Lamps et al. The Pathologic Spectrum of Gastrointestinal and Hepatic Histoplasmosis. Am J Clin Pathol 2000; 113: 64-72 Wheat, J. Practice Guidelines for the Management of Patients with Histoplasmosis. Clinical Infectious Diseases 2000; 30: 688-95