1. R2. 최태웅 / Pf. 이미숙 The American Journal of Medicine, Vol 127, No 12, December 2014

2. BACKGROUND Pneumocystis jiroveci pneumonia in HIV-negative immunocompromised patients → poor prognosis(high mortality rates 50%) Trimethoprim-sulfamethoxazole(TMP-SMX) prophylaxis → decrease the burden of pneumocystosis in non-HIV- immunocompromised patients

3. BACKGROUND Trimethoprim-sulfamethoxazole ① HIV-infected patients CD4 count in peripheral blood (<200 cells/uL) simple and accurate method to demtermine the risk of pneumocystosis ② HIV-negative patients accuracy of this biomarker is poorly characterized impairment in immunity related to the underlying disease immunosuppressive effect of drugs used to control diseasese (corticosteroids)

4. BACKGROUND Aim  to provide original data on the spectrum of diseases associated with pneumocystosis in non-HIV-infected patients  to estimate the incidence of pneumocystosis in these conditions to better inform the targeted use of TMP-SMX prophylaxis in HIV-negative patients at higher risk

5. Material and Method Pneumocystosis case definition  Retrospective analysis of all patients with pnemocystosis admitted from Jan 1990 to June 2010 to Rennes University Hospital  Case defined by a positive direct examination on BAL  Pneumocystosis documented only by PCR were not included  HIV-negative were included

6. Material and Method Incidence rates of Pneumocystosis according to underlying conditions  non-Hodgkin lymphoma  chronic lymphocytic leukemia  acute leukemia  hematopoietic stem cell transplant  multiple myeloma Hodgkin lymphoma  Waldenström macroglobulinemia  central nervous system cancer /breast cancer / lung cancer  rheumatoid arthritis, polymyalgia rheumatica  Sjögren syndrome  polymyositis, dermatomyositis

7. Material and Method Incidence rates of Pneumocystosis according to underlying conditions  Granulomatosis with polyangiitis  Polyarteritis nodosa  Giant cell arteritis  Sarcoidosis

8. Material and Method Data Analysis  ranked according to the estimated incidence rates of pneumocystosis  Categorical variables - expressed as proportion  chi-squared test or Fisher’s exact test (P value <.05)

9. Results Pneumocystosis Cases in Non-HIV-infected Patients  1990.01 ~ 2010.06 293 cases of pneumocystosis Non-HIV patients(n=154) > HIV infected patients(n=139) 1990-1999 HIV 46% v.s non-HIV 54% 2000-2010 HIV 46% v.s non-HIV 54% ICU admission and ICU mortality rates : higher in non-HIV patients (51.9% vs 28.1% 52.9% vs 15.4%)

10. Results  Pneumocystosis Cases in Non-HIV-infected Patients

12. Result  Prevalence of Underlying Conditions at Risk in the Area, and Estimated Incidence Rates of Pneumocystosis in These Conditions Lung cancer 2.6 case/100,000 Polyarteritis 93.2 case/100,000 Transplant recipients - 13.7 for heart transplant - 44.6 for kidney transplant Hematological malignancy - non- Hodgkin lymphoma, - chronic lymphocytic leukemia - acute leukemia

13. Discussion Prevalence of Underlying Conditions at Risk in the Area, and Estimated Incidence Rates of Pneumocystosis in These Conditions

14. Discussion Main findings on the incidence rates of and risk factors for pneumocystosis 1) pneumocystosis remains a significant problem in both HIV-positive and HIVnegative immunocompromised populations 2) pneumocystosis : more severe in HIV-negative patients higher rates of ICU admission, and in-ICU mortality 3) hematological malignancies : main group at risk among non-HIV-infected patients 4) estimated incidence rates of pneumocystosis in non-HIV-infected immunocompromised patients : vary broadly, from 2 to >90 cases per 100,000 patient-year

15. Discussion Hierarchical classification of groups at risk 1) High risk group (>45 cases per100,000 patient-year) - 3 inflammatory diseases/vasculitis (polyarteritis nodosa, granulomatosis with polyangiitis, and polymyositis/dermatopolymyositis - 3 hematological malignancies (acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma) ⇒ more systematic use of TMP-SMX prophylaxis in these patients : beneficial

16. Discussion Hierarchical classification of groups at risk 2) Intermediate risk group( 25 to 45 cases per 100,000 patient-year) - Waldenström macroglobulinemia - multiple myeloma - central nervous system cancer → threshold to initiate pneumocystosis prophylaxis be low (ie, any additional risk factor, such as prolonged use of corticosteroids, - should prompt TMP-SMX initiation).

17. Discussion Hierarchical classification of groups at risk 3) Low risk group(<25 cases per 100,000 patient-year) - solid tumors - Inflammatory diseases - Hodgkin lymphoma → pneumocystosis prophylaxis : not be routinely recommended

18. Conclusion  These comparative estimates may be used as a guide ⇒ better target pneumocystosis prophylaxis according to the level of risk ① L ow risk group : most solid tumors and inflammatory diseases Hodgkin lymphoma ② Intermediate risk group : Waldenström’s macroglobulinemia multiple myeloma patients on corticosteroids for brain tumors ③ H igh risk group : polyarteritis nodosa, polymyositis/dermatopolymyositis granulomatosis with polyangiitis, : acute leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma