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 Hodgkin's disease s/p allogenic
matched sibling stem cell transplant 4/16/2007 complicated by
cutaneous GVHD who is now 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
demonstrated 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 swelling.
No unusual activity or exposure
Sick contacts – father with a “cold” several
weeks prior. No TB contacts.
PMH

Hodgkin's 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 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 Klebsiella 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 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
R>L
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 1716
LDH 3117
Alb 2.9


BCx pending
Ucx pending
Imaging
Imaging
CT read

Numerous nodular 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 negative)
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 negative

PCR on BAL






HSV ½ neg
CMV neg
Diagnosis

BAL viral culture positive for


Parainfluenza virus type 3
Transbronchial biopsy results suggestive of DAD with
type II pneumocyte, 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 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 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 years
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
cause 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 Hutchinson 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. Parainfluenza 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 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 risk 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 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
Mortality

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 patients 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
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
Associated 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 seen 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 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