Scleroderma Presenting with
Pulmonary Hypertension
Cara Fininzio, D.O.
Research Symposium June 9, 2010
Background
• Scleroderma (systemic sclerosis) is rare
multisystem disease, causing fibrosis of
multiple organ systems
• Skin, kidneys, lungs, GI tract, heart, and
blood vessels can be affected
• Two forms are identified but there can be
some overlap
Background
• Diffuse cutaneous
– Rapid development of symmetric skin
thickening
– Greater risk for other visceral disease early in
course
• Limited cutaneous
– Symmetric thickening of skin on distal
extremities/ face
– Can have features of CREST
Background
• Diffuse:
– Distal and proximal extremities, trunk, and
face skin involvement
– Raynaud’s phenomenon at onset or within 1
year of skin changes
– Pulmonary involvement (fibrosis), renal, GI,
cardiac
– Antitopoisomerase I AB
Background
• Limited:
– Distal extremity/ face skin involvement
– Raynaud’s may precede by years
– GI, PAH after 10-15 years of disease, biliary
cirrhosis
– Anticentromere AB
Case Report
History
• A 69 year old Caucasian Female presented
with worsening SOB and DOE for the past
couple weeks
• ROS: + orthopnea, SOB, DOE
Past History
• PMH- CHF/ Cardiomyopathy, HTN,
Osteoporosis, Raynaud’s phenomenon,
Pulmonary HTN, GERD, SAR, Lower
Extremity Edema, Pruritis, Pneumonia
September 2008
• PSH - Tonsillectomy as child
• Allergies – None, NKDA
Past History
Medications:
Lisinopril 5mg po daily
Furosemide 20mg po daily
Carvedilol 3.125mg po daily
KCl 10meq po daily
Omeprazole 20mg po daily
Loratadine 10mg po daily
Fosamax 70mg po q week
Calcium + Vitamin D po daily
FeSo4 325mg po BID
Past History
• Social- Married, retired, G4P3013, ~5 pack year
tobacco history (quit 38 years ago), recovered
alcoholic since 9/2008 (admits to a couple beers
up to 2 pints of whiskey/ day in past)
• Preventive – Colonoscopy 2007, Pap 2005,
Mammogram 1/2009 all negative, Pneumonia
Vaccine 2008, Influenza Vaccine, Measles and
Varicella diseases ad child
Past History
• FxHx – Mother deceased in 80s (Breast
CA at age 35), Father deceased age 67 with
DM
Previous Testing
• Chest CT – Mild mediastinal
lymphadenopathy 5-15mm nonpathologic,
no hilar lympadenopathy, mild
cardiomegaly
• 2D echo – LVEF 30% (1/2009), pulmonary
artery pressure of 40mmHg
Previous Testing
• PFT – FVC 2.87L 116% predicted, FEV1
2.08L 105% predicted, FEV1/FVC 73%,
no bronchodilator response, Diffusion
Capacity 49% predicted
• CXR – Bilateral prominent interstitial
markings chronic from 4/20/06
comparison, normal heart size
Physical Exam
• BP 131/74, P 69, RR 18, SaO2 100% on 2L NC,
Afebrile
• Gen: A& O x 3, well developed, NAD
• HEENT: NC/AT, PERRLA, EOMI, MMM,
trachea midline, no thyromegaly or
lymphadenopathy
• Neck: +JVD, no carotid bruits
• Heart: Regular S1S2, no murmur, rubs, or
gallops, soft heart sounds
Physical Exam
• Lungs: bibasilar crackles, no wheezing or
rhonchi
• Abdomen: soft, NT/ND, + bowel sounds, no
organomegaly, no rebound or guarding
• Ext: trace pitting edema BL lower extremities,
+2/4 distal pulses, no clubbing or cyanosis
• Skin: tightening/shiny skin of lower extremities
and hands with mild erythema
• Neuro: CN II-XII intact, strength 5/5 BL,
cerebellar function intact
Workup
• Admitted with decompensated CHF
– BNP 3360, mild bilateral pleural effusions and
cardiomegaly on CXR, TnI 0.040.080.05
• Pulmonology consult- pHTN unclear etiology
consider primary, ANA, RF, Lupus anticoagulant,
complete PFT with DLCO, consider right heart
catheterization and possible Revatio or Bosantan
Workup
• Renal consult for Stage IV renal failure
• Recommended discontinue ACE inhibitor,
lasix, avoid IV contrast and NSAIDS,
testing ordered for autoimmune cause,
consider mediastinal LN biopsy to rule out
lymphoma/ sarcoidosis
Workup
• Normal Esophogram and Upper GI with
small bowel follow through
• Renal US unremarkable
• Renal flow scan showed mild-moderate
chronic parenchymal dysfunction
bilaterally
Workup
• 2D Echo 2/21/2009 - LVEF 60%, moderate
to severe PAH with RVSP 64mmHg, LVH,
diastolic dysfunction
• 2D Echo on 3/25/09 - LVEF 55%, severe
PAH with RVSP 60-80mmHg, severely
enlarged right atrium/ ventricle, impaired
diastolic function
Workup
• Cardiology consult
• Unable to normalize shortness of breath
with diuretics, no obvious heart pathology,
pulmonary HTN not generally associated
with ETOH toxicity
• Rheumatologic workup in process
Workup
• ANA Positive, SCL- 70 Ab 154, Negative
cold agglutinins, ESR 1, C3 105, C4 11
(low), RF <20, Centromere Ab 12, Histone
Abs 19, IgG <1, SSA Ro Ab 15, SSB La
Ab 11, Smith Ab 7, Jo-1 Ab 27, DS DNA
Ab 69
Summary
Our patient:
• Positive ANA and SCL-70 Ab
• PAH with RVSP of 60-80mmHg on Echo
• Raynaud’s phenomenon and thickened
mildly erythematous skin changes
Summary
• Our patient was treated with
supplemental oxygen and was referred
to Hospice care due to rapid
progression of her symptoms and
decline in physical function
• She died three months after the
diagnosis of scleroderma was made
Discussion
Scleroderma
• Mortality rate for systemic sclerosis has
been a constant increasing trend for the past
several decades [1]
• Increased knowledge and understanding of
scleroderma may be contributing to the
increasing prevalence [1]
• Apparent increased mortality of the disease
seen from 1999-2002 [1]
Scleroderma
• A study by Mendoza showed age-adjusted
mortality of systemic sclerosis was 3.2 times
greater in women than men [1]
• Mortality of this disease continues to trend
upward due to the lack of a specifically targeted
cure, but improvements in survival have been
noted [1]
• Most likely explained by decreased morbidity
from better management of pulmonary
hypertension and renal crisis than in the past [1]
Pulmonary Hypertension
• Commonly seen pathologic process and often
the cause of death in multiple connective
tissue disorders, including systemic sclerosis
[2]
• Up to 40% of patients with scleroderma have
been reported to have pulmonary
hypertension [2]
• Those with the limited form seem to have an
increased risk compared to those with diffuse
skin disease [2]
Pulmonary Hypertension
• PAH is important in determining the
prognosis in patients with systemic sclerosis
[2]
• Increased risk of developing pulmonary
hypertension with positive U3RNP/ fibrillation
and anticentromere antibodies [2]
• Decrease with antitopoisomerase (Scl-70)
antibodies [2]
Raynaud’s and Scleroderma
• Diffuse intimal proliferation causes occlusion
of the lumen in blood vessels [3]
• Leads to the narrowing and vasculopathy seen
in pulmonary vascular disease as well as
digital vessel pathology (i.e. Raynaud's) [3]
• Raynaud's disease has been shown to be an
associated risk factor for pulmonary
hypertension in patients with systemic
sclerosis [3]
Raynaud’s and Scleroderma
• Showed that patients with pulmonary
hypertension had a longer duration of
Raynaud's at the time of diagnosis compared
to those without pulmonary hypertension and
scleroderma [3]
• In the patients with pulmonary hypertension
the DLCO was very low at the time of
diagnosis [3]
• The pulmonary artery systolic pressures were
found to be >70mm Hg [3]
Raynaud’s and Scleroderma
• Steen found their group of patients with long
duration (greater than 10 years) of
Raynaud's to have severe pulmonary
hypertension with right heart changes
• Determined that patients should be
suspected to have pulmonary hypertension if
they have had longstanding limited disease,
ANA or anticentromere, PASP >40 mm Hg or
DLCO <65% predicted [3]
Testing Modalities
• Echocardiogram, PFTs, exercise testing, and
serum biomarkers are among the most
common and effective screening modalities
for pulmonary hypertension [4]
• In symptomatic patients, echocardiography
has a 90% sensitivity and 75% specificity for
detecting moderate to severe pulmonary
artery pressure elevations [4]
Testing Modalities
• Several studies have examined exercise
echocardiography in patients with
scleroderma and reported elevated
pulmonary artery pressures [4]
– They were not confirmed with right heart
catheterization
• DLCO in pulmonary function testing was
found to show a linear decrease over 15
years in patients with systemic sclerosis who
would eventually develop pulmonary
hypertension [3]
Testing Modalities
• The 6MWD (6 minute walk distance) showed
to be useful in assessment of severity of
pulmonary hypertension [4]
– Has not been used specifically to screen for it in
patients with systemic sclerosis
• BNP has been used as a marker of right
ventricular dysfunction in patients with
pulmonary hypertension due to systemic
sclerosis [4]
– It has not been validated to be a good screening
tool alone
Conclusion
• This report demonstrates the effects of
scleroderma on the lungs demonstrated by
rapidly progressing symptoms from
pulmonary artery hypertension in our patient
• Our patient did complain of pruritis several
months prior to her pulmonary symptoms
– likely were due to skin changes and tightening
secondary to underlying to scleroderma
Conclusion
• During her visits with a previous physician she
was complaining of pruritis and treated
symptomatically with PO antihistamines
• Diagnosis of Raynaud’s phenomenon for
several years before she presented with
pulmonary symptoms
• History of alcohol abuse and cardiomyopathy
may also have contributed to delay in workup
and diagnosis of scleroderma
Conclusion
• Although a small percentage of patients with
Raynaud’s will end up developing
scleroderma, it was an early sign of our
patient’s disease
• Recognition and complete evaluation would
not necessarily have changed the disease
course or outcome of our patient
• Earlier recognition of the signs and symptoms
of scleroderma may have led to an earlier
diagnosis in our patient
References
• 1. Mendoza F, Derk CT. Systemic Sclerosis Mortality in
the United States 1999-2002 Implications for Patient
Care. J Clin Rheumatol. 2007;13(4):187-192.
• 2. Goldberg A. Pulmonary Arterial Hypertension in
Connective Tissue Diseases. Cardiology in Review.
2010;18(2):85-88.
• 3. Steen VD. The Lung in Systemic Sclerosis. J Clin
Rheumatol. 2005;11(1):40-46.
• 4. Bull TM. Screening and therapy of pulmonary
hypertension in systemic sclerosis. Curr Opin
Rheumatol. 2007;19:598-603.
References
• 5. Coghlan JG, Pope J, Denton CP. Assessment
of endpoints in pulmonary arterial hypertension
associated with connective tissue disease. Curr
Opin Pulm Med. 2010;16(suppl 1):S27-S34.
• 6. Farmer RG, Gifford RW, Hines EA.
Prognostic Significance of Raynaud’s
Phenomenon and Other Clinical Characteristics
of Systemic Scleroderma. A Study of 271
Cases. Circulation. 1960;XXI:1088-1095.