other fungal diseases of the lung
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
ÖU 04/2009
Other Fungal Diseases of the Lung
Ömrüm Uzun
ÖU 04/2009
Consultant and speaker for, or grants from:
●Basilea●Erkim●Gilead●Janssen Cilag●Merck●Pfizer●Schering Plough
DISCLOSURES
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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.
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GM ChestX-ray
CT + culture
6 days 2 days 1 day
Temporal association of antigenemia & other diagnostic tests
GM Testing in Allo-HSCTMaertens et al. JID 2002;186:1297.
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GM Testing: “Cut-off Point“Maertens et al. JCM 1999, 37: 3223; Blood 2001, 97: 1604; Br J Haem 2004, 126: 852
0.5
0.8
1.5
FDAEurope
Producingcompany
Static index
Dynamic index
ELISASensitivity: 60%-100%Specificity: 81%-98%
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0
20
40
60
80
100
0 50 100 150 200 gün
Systematic CTCT when indicated
RETROSPECTIVEANALYSIS
n = 37
Days until diagnosis Since admission Since the first suspicionHalo sign before dx
SYSTEMATIC BTBEFORE AFTER
31 ± 9 7 ± 51 / 8
21 ± 5 2 ± 1
23 / 25
Systematic CT in Diagnosis of IPACaillot et al. J Clin Oncol 1997;15:139.
SURVIVAL
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CT (n)
Typical halo
Non-specific
Typical “air-crescent”
PMN/mm3 (median)
Day0
24
100%
-
-
0
Day3
13
68%
31%
8%
0
Day7
18
22%
50%
28%
900
Day14
16
19%
18%
63%
2,900
Course of CT FindingsCaillot et al. J Clin Oncol 2001,19:253.
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0.0
0.2
0.4
0.6
0.8
1.0
Pro
bab
ility
of
su
rviv
al
0 10 20 30 40 50 60 70 80 90Day
Amphotericin B -> OLAT
Voriconazole -> OLAT
HR = 0.60 (95% CI 0.40 to 0.89), p=0.012
VRC vs. AmB-d in IA: SurvivalHerbrecht et al. NEJM 2002;347:408.
Ben De Pauw’
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IA Treatment Guidelines of IDSA, 2008
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●Diabetic ketoacidosis●Iron overload●Desferrioxamine therapy●Neutropenia●GVHD●Corticosteroid therapy●IV drug use●Advanced AIDS●Disruption of skin integrity
Risk Factors for Zygomycosis
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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
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Reversed Halo SignWahba H, et al. CID 2008;46:1733
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Causative Pathogens in ZygomycosisRoden MM, et al. CID 2005, 41: 634
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Zygomycosis: Review of Reported Cases
Roden MM, et al. CID 2005, 41: 634
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The Impact of Underlying Disease on the Involvement SiteRoden MM, et al. CID 2005, 41: 634
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0%
20%
40%
60%
80%
100%
46%
76%
31%
79%85%
100%
SinusPulmonaryCutaneousCerebralGIDisseminated
Mortality in ZygomycosisRoden MM, et al. CID 2005, 41: 634
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Mortality in ZygomycosisRoden MM, et al. CID 2005, 41: 634
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Posaconazole
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24 ptsChart Title
79% refractory
21% intolerant
Hematological malignancy %63Allo-BMT / PBSCT %46Organ transplant recipient %17DM %21
PSC “Salvage” in ZygomycosisGreenberg RN et al, AAC 2006;50:126.
CR/PR
%79 (15/19)
%80 (4/5)
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21 y.o. Relapsed ALL On chemo (Cortikosteroid+)Rapidly progressing dyspneaHypoxia
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●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
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Krajicek BJ, et al. Curr Opin Pul Med 2008:14:228.
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494 pts.
547 episodes
16.9%
9.7%
mortality
10.1% (1985-1989)
(1990-1996)
(1996-2006)
●Age●Subsequent attacks of PCP●Hb ↓●Pulmonary Kaposi sarcoma
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Treatment of PCPD’Avignon DC, et al. Semin Respir Crit Care 2008;29:132.
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“Salvage” Treatment of HIV-Related PCP Benfield T, et la. J Acquir Immune Defic Syndr 2008:48:63.
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Corticosteroids in the Treatment of PCP in HIV (+) Patients
Briel M, et al. Cochrane, 2009
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Colonisation by Pneumocystis jiroveci Morris A et al. JID 2008;197:10.
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Pneumocystis jiroveci Kolonizasyonu: Morris A et al. JID 2008;197:10.
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Pneumocystis jiroveci Kolonizasyonu: Morris A et al. JID 2008;197:10.
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Pneumocystis jiroveci Kolonizasyonu: Morris A et al. JID 2008;197:10.
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