1、A stem cell transplant patient with cough and SOB.,ID Case Conference Wednesday September 26th, 2007 David Fitzgerald, MD,History of Present Illness,23 year old white male with h/o Hodgkins disease s/p allogenic matched sibling stem cell transplant 4/16/2007 complicated by cutaneous GVHD who is now
2、admitted for acute SOB and hypoxia. He was at his baseline state until a few days PTA when he developed a non-productive cough and rhinitis. He became progressivly more SOB and was having increasing difficulty with ADLs due to DOE, Was referred by oncology for PFT evaluation on 9/3/07 this demonstra
3、ted markedly reduced FEV1, FVC and DLCO with a pulse oximetry reading in the mid 80s on RA. Patient was admitted to BM transplant unit for further evaluation.,HPI,Cough is non-productive with no hemoptysis. Increasing fatigue over last 2 weeks. He denies any fever, chills, NS, chest pain, leg swelli
4、ng. No unusual activity or exposure Sick contacts father with a “cold” several weeks prior. No TB contacts.,PMH,Hodgkins disease - diagnosed in 2000 treated with combined chemotherapy and XRT with prolonged remission relapse in 2004. Relapsed and treated with salvage gemcitabine and vinorelbine and
5、then autologous SCT.Relapse again in 10/06 with mediastinal and neck disease treated with etoposide and Ara-C + steroids. Allogenic matched sibling SCT in 4/07 campath conditioning and fludarabine, busulfan History of glucose intolerance/diabetes mellitus due to steroids Skin GVHD History of Klebsie
6、lla pneumoniae bacteremia/sepsis,Social History No tobacco, no EtOH, no drugs. Lives with father. No recent travel. No pets. Not sexually active,Family History Mother died of an accident. Father and sister are well.,Meds,Voriconazole 200 mg po BID Septra DS once daily Cellcept 1000 mg bid Prednisone
7、 50 mg qd Prograf 1 mg BID Synthroid 100 mcg qd,Physical,Tm 36.5 P 117 BP 108/81 R 18 Sat 100% ON 40 FiO2 Chronically ill appearing with mild respiratory distress HEENT Perrla, eomi, anicteric, OP without exudate or lesions Neck supple No LAN,CV tachy, but reg with no murmur Lungs bibasilar crackles
8、 RL Abd soft, NT, ND, no HSM Skin diffuse scaly eruption on forearms c/w GVHD Neuro A+O x 3, grossly non-focal,Data,WBC 5.1 ANC 4.9 Hgb 9.7 Plt 33 Basic panel WNL Bun/Cr 30/1.3 T bili 0.6 AST 74 ALT 108 Alk phos 342 GGT 1716LDH 3117 Alb 2.9,BCx pending Ucx pending,Imaging,Imaging,CT read,Numerous no
9、dular groundglass opacities scattered throughout all segments of the lungs. There are scattered foci of confluent ground glass consolidation. There are no pleural effusions.,Further testing,Urine histo ag negative Serum crypto negative Aspergillus Ag negative Serum PCR CMV 500 copies (repeat negativ
10、e) EBV neg Adeno neg HHV6 neg Parvo neg,Bronch,Quant cx - 10,000 organism PCP DFA neg Bacterial Culture neg AFB cx negative Fungal cx negativePCR on BAL HSV neg CMV neg,Diagnosis,BAL viral culture positive for Parainfluenza virus type 3Transbronchial biopsy results suggestive of DAD with type II pne
11、umocyte, hyperplasia, fibrin, hemorrhage, sparse acute inflammation and focal edema. - Bronchial wall shows essentially no inflammation, making graft versus host disease unlikely. - No fungal or AFB organisms seen by fungus or AFB stains.,Diagnosis,Parainfluenza virus type 2 pneumonia,Parainfluenza
12、virus,RNA virus Family of Paramyxoviridae 5 types 1, 2, 3, 4a, 4b Initially described 1950s as cause of croup layrngotracheobronchitis in children,Parainfluenza virus,Virus has a tropism for the respiratory tract, replicating only in cells of the respiratory epithelial layer Causes acute respiratory
13、 tract infections Repeated infections occur thoughout life Reinfection usually involves only the upper respiratory tract in immunocompetent adults LRI more common with type 3 infection Immunity wanes quickly,Parainfluenza virus,Types 1 and 2 cause seasonal fall epidemics that often will alternate ye
14、ars 3 is endemic but has an April May spring peak Most common isolate in children More common to cause pneumonia Types 4a and 4 b are rare,Clinical manifestations,Children PIV causes 60% of croup cases barking cough , hoarseness and stridor Adults causes 15% of URIs Immunocompromised adults common c
15、ause of URIs and also LRIs,Diagnosis,Cell culture grows in cell culture PCR also available,Parainfluenza in immunocompromised hosts,Significant cause of morbidity and mortality among HSCT recipients Limited data available on its presentation and treatment,Clinical Trial Data,Large study from Fred Hu
16、tchinson Cancer center Evaluated data on 3577 HSCT recipients 1990-1999 All pts with URI sxs received Nasopharyngeal swab Also cxs done on all bronch specimens, lung bxps and autopsy Ribavirin was used at discretion of treating physician but was a standardized dose and course Nichols W, et al. Parai
17、nfluenza virus infections after hematopoietic stem cell transplantation: rick factors, response to antiviral therapy and effect on transplant outcome. Blood 2001;98:573-78.,Epidemiology in SCT pts,PIV was isolated from 7.1% of the 3577 patients PIV3 was most common form (90%) Occurred year round but
18、 in clusters,Results,Clinical presentation 81% of PIV 3 infections were URI, 7% with pneumonia and 6% both No real difference in clinical characteristics of the patients who did and did not develop PIV 3,Results,Risk factors for progression to LRI Receipt of corticosteroids was the only dependent ri
19、sk factor,Corticosteroid use and progression to LRI,Association present for both autologous and allogenic transplants Dose dependent,Copathogens,53% of pts with PIV3 LRI had copathogens Aspergillus fumigatus was most common copathogen - 24% Similar to association of Staph aureus with influenza PIV3
20、infection may damage the epithelium and allow other organisms to penetrate or may exert an immunosuppressive effect,Mortality,Overall mortality in PIV3 LRI was 35% at 30 days and 75% at 180 days after dx of pneumonia The majority died with persistent radiographic or clinical evidence of pneumonia,Mo
21、rtality,Risk factors for mortality Presence of co-pathogens on BAL at time of PIV3 diagnosis was associated with increased mortality 48% vs 19% at 30 days 96% vs 50 % at 180 days Need for mechanical ventilation also mortality risk,Treatment,Aerosolized ribavirin +/- IVIG were used in 33 of 55 patien
22、ts with PIV3 pneumonia Characteristics of the two groups were similar but treated group had more intubated patients and more pts requiring O2,Treatment and Viral Shedding,No difference in duration of viral shedding 35% of treated pts continued to shed at 3 weeks compared to 33% of untreated patients
23、 Only 35% of treated patients shed for 10 days compared to 50% of untreated patients,Treatment and Mortality,No difference in 30 day mortality between the treated and untreated groups Even after stratification by presense of copathogen,Conclusions,PIV infections were relatively common after SCT Asso
24、ciated with increased mortality Overall 24.1% of patients with PIV3 infection developed pneumonia Development of LRI was driven by administration of steroids for GVHD Copathogens were commonly isolated from Pts with PIV pneumonia Copathogens were associated with increased mortality,No real benefit s
25、een with ribavirin and IVIG although not a randomized trial,Further course,Initially covered with broad spectrum antibiotics including imipenim, vanco, voriconazole, bactrim, doxy. Received increasing doses of steroids due to concern that may be GVHD When cx + for PIV pt begun on oral ribavirin and
26、IVIG Had a worsened course and received several days of pulse dose steroids 850 mg bid with some improvement Steroids weaned to 125 mg BID Rebronch 12 days later still with viral cx + for PIV3. No other copathogens identified Remains on broad spectrum abx with relatively stable O2 requirement at 4 L Could not obtain aerosolized ribavirin since not used at UNC for 5 years Difficult to use as it is teratogenic and mutagenic and aerosol gets everywhere,Search PubMed,Parainfluenza Virus Type 2 Case Reports Reviews Differential Diagnosis Drug Therapy,
