1. Atypical Presentation of Scedosporium Pneumonia Gabriel Johnson, DO Leslie Spikes, MD Department of Internal Medicine University of Kansas Medical Center Kansas City, KS

2. Introduction  Provide a brief overview of scedosporium epidemiology  Present an unusual case of a life-threatening Scedosporium infection in a patient without typical risk factors for fungemia  Identify diagnostic and therapeutic challenges

3. Scedosporium Infections in Humans  Localized infections:  Bronchiectatic lungs  Mycetomas  Disseminated infections:  Transplant wards  Up to 10% of cystic fibrosis patients colonized in transplant wards  Near drowning events  Rarely in the immuno-competent Cortez et. Al. Infections Caused by Scedosporium spp. Clin Microbiol Rev. 2008 January; 21(1): 157–197.

4. Complication of organ transplant  Study of 80 cases of scedosporium infection in transplant patients at 5 academic institutions  23 hematopoietic stem cell transplants  57 solid organ transplants  Disseminated infection  2 noncontiguous organs or + blood culture  69% of HSCT with scedosporium  53% of SOT with scedosporium Husein et. al. Infections due to Scedosporium in Transplant Recipients: Clinical Characteristics. Clinical Infectious Disease 2005 Jan 1;40

5. Scedosporium - overview  Ubiquitous white mold  Tolerates aerobic and anaerobic conditions and wide range of temperature and osmolarity  Transmission  Direct inoculation (mycetoma)  Inhalation of airborne particles Williamson et. al. Genetic Epidemiogy of Scedosporium in Patients with Chronic Lung Disease. J Clin Microbiol. 2001 January; 39(1): 47–50.

6. Species  Scedosporium apiospermum  Typically sensitive to multi-agent antifungal therapy  Voriconazole associated with survival improvement over amphotericin  Scedosporium prolificans  Treatment generally requires immunosuppression reversal and surgical intervention. Cortez et. Al. Infections Caused by Scedosporium spp. Clin Microbiol Rev. 2008 January; 21(1): 157–197.

7. American Society for Microbiology: Clinical Microbiology Reviews

8. Infection sites 2000-2007 Cortez et. Al. Infections Caused by Scedosporium spp. Clin Microbiol Rev. 2008 January; 21(1): 157–197. Lungs59% Sinuses36% Bone/joint8% Eyes7% Hands4% Feet4% CNS3% Blood3% Abdomen2%

9. Case Report  A 72 year old woman presented to ER  3 months of progressive hemoptysis  Diffuse pulmonary nodules on recent imaging  5 days of fever, chills, and myalgias

10. Past Medical History  Pulmonary arterial hypertension  Diagnosed 2 years prior  Likely secondary to chronic pulmonary emboli  On continuous infusion intravenous treprostinil  On warfarin for chronic thromboemboli  Breast cancer  Right mastectomy and radiation 8 years prior  No history of atypical or recurrent infections

11. Recent Medical History  CT guided needle biopsy of pulmonary nodule had been performed 3 weeks prior  Histology: necrotic tissue, peribronchial fibrosis and chronic inflammatory changes without granulomas  Gram stain/culture: no bacterial or fungal growth  Cytology: no malignant cells

12. Social History  Independently performs activities of daily living  25 pack years but quit 2 years prior  No occupational or environmental exposures

13. Physical Exam T 36.7 BP 121/70 P 99 R 24 Pulse ox: 95% on room air HEENT – Unremarkable Chest – right sided indwelling Hickman catheter Heart – Unremarkable Lungs Diminished breath sounds bilaterally, no rales, rhonchi, or wheezing Abdomen: Unremarkable Extremities/Skin: Unremarkable

14. Laboratory Data  Fungitell: 257 (41 previously) [Normal < 40]  Blood Culture: Scedosporium elements WBC12.9 Hgb12.3 Plt239 Neut80% INR3.4 Histoplasma AbHIV screen GalactomannanCMV, EBV pcr Aspergillus AbRVP ANAHep A,B,C Scl70Mycoplasma Anti-dsDNAChlamydia The following were negative

15. 3 weeks prior

16. Hospital Course  Sudden hemoptysis of 600 ml frank blood  Resolved with reversal of anticoagulation  Bronchoscopy with lavage performed  Hemorrhagic fluid with negative cultures  Repeat CT guided biopsy of left lobe nodule  Pathologic findings unchanged and unremarkable  Hickman catheter removed  No fungal or bacterial growth on tip culture

17. Hospital Course  Amphotericin and voriconazole initiated  Repeat CT 2 weeks later showed progression  Patient requested to discontinue all IV medications and go home with home health care  Oral voriconazole and terbinafine  Oral sildenafil  New 2 L oxygen requirement

18. Speciation and Sensitivity  Speciation: Scedosporium Apiospermum  Sensitivity testing:  AmphotericinR  Caspofungin R  MicafunginS  VoriconazoleS  ItraconazoleS  PosaconazoleS

19. Resolution  Patient’s hypoxia improved and she was able to titrate off oxygen  No recurrence of fever or hemoptysis  She completed 6 months of antifungal therapy with voriconazole and terbinafine

20. Radiographic regression 4 months later

21. Case Summary  Atypical presentation of a rare fungal pathogen  Diagnostic difficulties  Voriconazole as preferred agent  Questioning her risk factors

22. Acknowledgments Dr. Leslie Spikes Associate Professor of Internal Medicine University of Kansas Medical Center

23. European Society for Imunodeficiencies Unusual infections or unusually severe course of infections T lymphocyte deficiency WAS STAT1 deficiency Hypermorphic mutations in IκBα X–linked lymphoproliferative syndrome DeVries et.al. Clinical & Experimental Immunology vol. 145, iss. 2. pages 204–214, August 2006