Computed tomography as a diagnostic tool for disseminated histoplasmosis

Transcription

1 Computed tomography as a diagnostic tool for disseminated histoplasmosis Poster No.: B-0973 Congress: ECR 2015 Type: Scientific Paper Authors: V. V. Maller, M. O. afzal, S. Shankar; Memphis, TN/US Keywords: Abdomen, Lymph nodes, Spleen, CT, Laboratory tests, Outcomes analysis, Infection, Outcomes DOI: /ecr2015/B-0973 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 16

2 Purpose Introduction Histoplasmosis is a common systemic fungal infection in the Southwestern United States of America (1). Histoplasmosis is caused by Histoplasma Capsulatum, which is endemic in Mississippi and Ohio River valleys. While in immunocompetent individuals histoplasmosis is asymptomatic and self-limiting, in immunocompromised individuals it can cause an entire spectrum of infection including localized pulmonary to disseminated life threatening infection (2,3,4). Disseminated histoplasmosis is a progressive systemic fungal infection, which affects almost all systems including the reticuloendothelial system, lungs, gastrointestinal tract, renal tract, central nervous system, bone marrow and adrenal glands (5,6). Early diagnosis and treatment is imperative. Most patients are started on empiric antifungal therapy based on high index of clinical suspicion of infection until the laboratory tests confirm the diagnosis. Diagnosis is based on the detection of Histoplasma antigen in Urine or serum. The gold standard is blood culture (7). However, treatment is both toxic and expensive. Various imaging features have been associated with disseminated histoplasmosis. Pulmonary findings include diffuse reticulonodular infiltrates, lobar consolidations, ground glass consolidation and mediastinal lymphadenopathy. Common extrapulomary findings include hepatomegaly, splenomegaly, splenic hypodensities, bilateral adrenal enlargement with nodularity and enlarged lymph nodes (5). These imaging features are not specific to disseminated histoplasmosis and can be seen in various other conditions including tuberculosis, sarcoidosis and other granulomatous infections. Purpose The purpose of our study was to see the possibility of reliably determining which category of patients with clinically suspected disseminated histoplasmosis should receive the therapy and which category should await confirmatory blood tests based on CT scan alone. Additionally, we wanted to evaluate a CT scoring system based on the foregoing to increase the diagnostic probability for initiation of treatment with a higher degree of confidence than currently. Page 2 of 16

3 Methods and materials In our retrospective study, we enrolled 20 patients who had confirmed disseminated histoplasmosis based on positive blood tests and 20 patients who were suspected of having the disease but with negative blood tests. Both groups were matched with age group of years and median age of 35. Both the groups had patients with underlying disease like HIV and other causes of immunosuppression. Charts, pertinent laboratory data and CT chest, abdomen pelvis images of these patients were reviewed and compared. Two radiologists who were blinded to the blood test results reviewed all CT scans independently. All CT scans were performed on a Toshiba Aquilion 64 slice scanner. For the purpose of the study, reticulonodular pulmonary infiltrates, patchy or lobar consolidation, ground glass infiltrates were considered markers of pulmonary involvement. Hepatomegaly, splenomegaly, splenic hypodensities, adrenal nodularity, and lymph node calcification were used as markers of intra-abdominal disease. Spleen and liver were measured on coronal images with a cut-off value of 13 and 18 cm respectively. For each category a score of 0 was assigned for normal findings and 1 for abnormal findings. Lymphadenopathy was scored using a 0-3 scale, 0 being normal, 1 being prominent lymph nodes less than 1 cm, 2 being enlarged lymph nodes less than 2 cm and 3 being large necrotic nodes. Page 3 of 16

4 Table 1: CT scoring for disseminated histoplamosis. References: Department of Radiology, University of Tennessee Health Science Center, Memphis/USA Page 4 of 16

5 Table 2: Lymph node CT scoring system for disseminated histoplamosis References: Department of Radiology, University of Tennessee Health Science Center, Memphis/USA Images for this section: Page 5 of 16

6 Table 1: CT scoring for disseminated histoplamosis. Table 2: Lymph node CT scoring system for disseminated histoplamosis Page 6 of 16

7 Results Fig. 1: 33 year old patient with positive blood tests for disseminated histoplasmosis. Axial CT chest images (A & B)demonstrate diffuse reticulonodular infiltrates and lobar consolidation. Axial CT abdomen images (C, D, E & F) show splenic hypodensity (white arrow), adrenal enlargement with nodularity (red arrow) and multiple enlarged lymph nodes (yellow arrows). References: Department of Radiology, University of Tennessee Health Science Center, Memphis/USA Page 7 of 16

8 Fig. 2: 29 year old patient with positive blood tests for disseminated histoplasmosis. Axial CT chest image (A) demonstrates reticulonodular infiltrates with tree in bud, axial and coronal CT abdomen images(b & C)show multiple enlarged lymph nodes (yellow arrows) and splenomegaly. References: Department of Radiology, University of Tennessee Health Science Center, Memphis/USA Table 3: Group 1 consisting of patients with positive blood tests for histoplasmosis. References: Department of Radiology, University of Tennessee Health Science Center, Memphis/USA Page 8 of 16

9 Table 4: Control group consisting of patients with negative blood tests for histoplasmosis. References: Department of Radiology, University of Tennessee Health Science Center, Memphis/USA Table 5: 2x2 contingency table Page 9 of 16

10 References: Department of Radiology, University of Tennessee Health Science Center, Memphis/USA In the first group of 20 patients with positive blood culture for histoplasmosis, 16 patients had CT score of #4 with average score of 4.1 (Table 1). In the second group of 20 patients with negative blood cultures only one patient had CT score of 4 and rest of the 19 patients had CT score of <4 with average score of 2.1. The data was analyzed using 2x2 contingency table. The P value calculated using Fisher's exact test. Using 4 as a cut off criteria, we found that CT scoring system for disseminated histoplasmosis had 70% sensitivity, 95% specificity, 93 % positive predictive value and 76 % negative predictive value. The P value was < suggesting that the study was statistically significant. The most striking finding was Adrenal nodularity with 80% specificity and 65% sensitivity. The most consistent finding in the disease group was pulmonary and abdominal lymphadenopathy. The least reliable finding was hepatomegaly. Images for this section: Fig. 1: 33 year old patient with positive blood tests for disseminated histoplasmosis. Axial CT chest images (A & B)demonstrate diffuse reticulonodular infiltrates and lobar consolidation. Axial CT abdomen images (C, D, E & F) show splenic hypodensity (white Page 10 of 16

11 arrow), adrenal enlargement with nodularity (red arrow) and multiple enlarged lymph nodes (yellow arrows). Fig. 2: 29 year old patient with positive blood tests for disseminated histoplasmosis. Axial CT chest image (A) demonstrates reticulonodular infiltrates with tree in bud, axial and coronal CT abdomen images(b & C)show multiple enlarged lymph nodes (yellow arrows) and splenomegaly. Page 11 of 16

12 Table 3: Group 1 consisting of patients with positive blood tests for histoplasmosis. Page 12 of 16

13 Table 4: Control group consisting of patients with negative blood tests for histoplasmosis. Table 5: 2x2 contingency table Page 13 of 16

14 Conclusion The definitive diagnosis of disseminated histoplasmosis requires a high index of clinical suspicion along with isolation of histoplasma antigen in urine, blood or secretions. The final diagnosis rests on the successful isolation of the fungus in cultures of body fluid or organ biopsy, which usually require 2-4 weeks to accomplish/complete. Although these tests offer high sensitivity and specificity, the delay in getting results and starting treatment can increase the morbidity and mortality (8). Lipid formulation of Amphotericin B, an antifungal medicine is used to treat disseminated histoplasmosis, and is the drug of choice. These drugs however are expensive and are associated with many adverse reactions including death. While early treatment is imperative, toxicity of the drug poses a challenge in selecting patients to start empiric treatment while waiting for confirmatory tests. Based on our study, we propose the following protocol. Patients who are immunocompromised and at high risk for disseminated histoplasmosis should be empirically started on treatment due to aggressive nature of the disease. For intermediate and low risk individuals we propose the use of computed tomography based scoring system to decide whether to start empiric treatment or not. Page 14 of 16

15 Fig. 3: Algorithm for patient triage in disseminated histoplasmosis based on CT scoring. References: Department of Radiology, University of Tennessee Health Science Center, Memphis/USA Using our proposed CT-Scoring system, the clinician can increase the diagnostic probability for initiation of treatment with a high degree of confidence. Images for this section: Fig. 3: Algorithm for patient triage in disseminated histoplasmosis based on CT scoring. Page 15 of 16

16 Personal information References Wheat JL.Histoplasmosis.Infect Dis Clin North Am 1988:2: Wheat LJ, Connolly-Stringfield PA, Baker RL, Curfman MF, Eads ME, Israel KS, Norris SA, Webb DH, Zeckel ML.Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. Medicine (Baltimore) Nov;69(6): Review. Chu JH, Feudtner C, Heydon K, Walsh TJ, Zaoutis TE. Hospitalizations for endemic mycoses: a population-based national study.clin Infect Dis Mar 15;42(6): Epub 2006 Feb 1. Wheat LJ, Chetchotisakd P, Williams B, Connolly P, Shutt K, Hajjeh R. Factors associated with severe manifestations of histoplasmosis in AIDS. Clin Infect Dis Jun;30(6): Epub 2000 Jun 14. Radin DR. Disseminated Histoplasmosis. Abdominal CT findings in 16 patients. AJR Am J Roentgenol Nov;157(5): Grover SB, Midha N, Gupta M, Sharma U, Talib VH. Imaging spectrum in disseminated histoplasmosis: case report and brief review. Australas Radiol Apr;49(2): Baddley JW, Sankara IR, Rodriquez JM, Pappas PG, Many WJ. Histoplasmosis in HIV-infected patients in a southern regional medical center: poor prognosis in the era of highly active antiretroviral therapy. Jr. Diagn Microbiol Infect Dis Oct;62(2): doi: / j.diagmicrobio Epub 2008 Jul 1. Hage CA, Ribes JA, Wengenack NL, Baddour LM, Assi M, McKinsey DS, Hammoud K, Alapat D, Babady NE, Parker M, Fuller D, Noor A, Davis TE, Rodgers M, Connolly PA, El Haddad B, Wheat LJ. A multicenter evaluation of tests for diagnosis of histoplasmosis. Clin Infect Dis Sep;53(5): doi: /cid/cir435. Epub 2011 Aug 2. Erratum in: Clin Infect Dis Feb 1;54(3):454 Page 16 of 16