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Other Fungal Diseases of the Lung. Ömrüm Uzun. DISCLOSURES. Consultant and speaker for, or grants from:. Basilea Erkim Gilead Janssen Cilag Merck Pfizer Schering Plough. Diagnostic Problems in Invasive Pulmonary Aspergillosis. Clinical symptoms are not characteristic.
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Other Fungal Diseases of the Lung Ömrüm Uzun
DISCLOSURES Consultant and speaker for, or grants from: • Basilea • Erkim • Gilead • Janssen Cilag • Merck • Pfizer • Schering Plough
Diagnostic Problems in Invasive Pulmonary Aspergillosis Clinical symptoms are not characteristic. Clinical signs are rarely specific. Aspergilli could be the pathogen or colonizer, therefore: Superficial cultures Antigen tests, PCR surveys, methods for detection of antibody and/or metabolites should be carefully interpreted.
GM Testing in Allo-HSCT Maertens et al. JID 2002;186:1297. Temporal association of antigenemia & other diagnostic tests + culture CT Chest X-ray GM 6 days 2 days 1 day
GM Testing: “Cut-off Point“Maertens et al. JCM 1999, 37: 3223; Blood 2001, 97: 1604; Br J Haem 2004, 126: 852 ELISA Sensitivity: 60%-100% Specificity: 81%-98% Producing company 1.5 Static index 0.8 Dynamic index FDA Europe 0.5
Systematic CT in Diagnosis of IPACaillot et al. J Clin Oncol 1997;15:139. SURVIVAL Systematic CT CT when indicated RETROSPECTIVE ANALYSIS n = 37 0 50 100 150 200 gün SYSTEMATIC BT BEFORE AFTER Days until diagnosis Since admission Since the first suspicion Halo sign before dx 31 ± 9 7 ± 5 1 / 8 21 ± 5 2 ± 1 23 / 25
Course of CT Findings Caillot et al. J Clin Oncol 2001,19:253. Day0 24 100% - - 0 Day7 18 22% 50% 28% 900 Day14 16 19% 18% 63% 2,900 Day3 13 68% 31% 8% 0 CT(n) Typicalhalo Non-specific Typical“air-crescent” PMN/mm3 (median)
0 10 20 30 40 50 60 70 80 90 Day VRC vs. AmB-d in IA: SurvivalHerbrecht et al. NEJM 2002;347:408. 1.0 0.8 0.6 Probability of survival HR = 0.60 (95% CI 0.40 to 0.89), p=0.012 0.4 Amphotericin B -> OLATVoriconazole -> OLAT 0.2 0.0 Ben De Pauw’
Risk Factors for Zygomycosis • Diabetic ketoacidosis • Iron overload • Desferrioxamine therapy • Neutropenia • GVHD • Corticosteroid therapy • IV drug use • Advanced AIDS • Disruption of skin integrity
Problems in Diagnosis • Ubiquity in nature • Difficulty in obtaining tissue sample • Difficulty in microscopic differentiation • Delayed growth in culture • No serological surrogate marker • Difficulty in differentiating from other mould infections clinically
Reversed Halo Sign Wahba H, et al. CID 2008;46:1733
Causative Pathogens in Zygomycosis Roden MM, et al. CID 2005, 41: 634
Zygomycosis: Review of Reported Cases Roden MM, et al. CID 2005, 41: 634
The Impact of Underlying Disease on the Involvement Site Roden MM, et al. CID 2005, 41: 634
Mortality in Zygomycosis Roden MM, et al. CID 2005, 41: 634
Mortality in Zygomycosis Roden MM, et al. CID 2005, 41: 634
PSC “Salvage” in Zygomycosis Greenberg RN et al, AAC 2006;50:126. 24 pts CR/PR 21% intolerant %80 (4/5) 79% refractory %79 (15/19) Hematological malignancy %63 Allo-BMT / PBSCT %46 Organ transplant recipient %17 DM %21
21 y.o. Relapsed ALL On chemo (Cortikosteroid+) Rapidly progressing dyspnea Hypoxia
1910 Antonio Carinii described in rat lung tissue • Protozoon (trophozoid & cyst forms, response to pentamidine) • 1988 Classified as fungus after sequencing of ribosomal RNA subunit • 2002 Pneumocystis infecting humans: Pathologist Jirovec
494 pts. • Age • Subsequent attacks of PCP • Hb ↓ • Pulmonary Kaposi sarcoma 547 episodes 10.1% (1985-1989) mortality 16.9% (1990-1996) (1996-2006) 9.7%
Treatment of PCP D’Avignon DC, et al. Semin Respir Crit Care 2008;29:132.
“Salvage” Treatment of HIV-Related PCP Benfield T, et la. J Acquir Immune Defic Syndr 2008:48:63.
Corticosteroids in the Treatment of PCP in HIV (+) Patients Briel M, et al. Cochrane, 2009
Colonisation by Pneumocystis jiroveci Morris A et al. JID 2008;197:10.
Pneumocystis jiroveci Kolonizasyonu: Morris A et al. JID 2008;197:10.
Pneumocystis jiroveci Kolonizasyonu: Morris A et al. JID 2008;197:10.
Pneumocystis jiroveci Kolonizasyonu: Morris A et al. JID 2008;197:10.