VOL.

3

No.

124,

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PULMONARY PROGRESSIVE RICHARD

By

ARTERIAL HYPERTENSION SYSTEMIC SCLEROSIS* J. STECKEL, and PETER

M.D.,t MARSHALL M. KELLY, M.D.

LOS ANGELES,

VER the past 2 years, the authors have encountered several cases of roentgenologically evident pulmonary arterial hypertension (PAH), occurring in conjunction with progressive systemic sclerosis (P55; scleroderma). Although a review of the medical literature revealed earlier reports of this association,’5’7” no report devoted to the occurrence of pulmonary arterial hypertension in PSS was encountered in the English language radiological literature. Having been impressed by what seemed a relatively frequent occurrence of chest roentgenographic changes reflecting pulmonary hypertension in PSS, we have reviewed all of the cases of clinically and/or pathologically established PSS seen over the past io years at this institution on which complete medical records and chest roentgenograms were available. A total of cases

of

standards which will

systemic

sclerosis

for this review, be presented here. CRITERIA

AND

met

the

clinical,

variants; analysis.

these For

having

for

*

Presented

the

Seventy-fifth

Annual

of the

Only and

sound, heart

medical

records

evidence

of PAH

those lateral

component

of

were

Departments

of Radiological

Sciencest

and

or cases

chest

evidence etc.).

surveyed

(i.e., increased the second heart

a widely split or fixed sound, right ventricular

trocardiographic ular hypertrophy,

Meeting

pathologic

split second heave, elec-

of right

ventric-

RESULTS

Of the 41 cases of established P55 meeting the standards set forth for this review ( see above), 3 showed unequivocal evidence of PAH on all chest roentgenograms that were available, and an additional i cases had chest roentgenographic findings which were highly indicative of PAH. In this series, therefore, chest roentgenograms on approximately ii per cent ( of 4!) of the cases reviewed showed definite or probable roentgenographic evidence of PAH

the

American

Roentgen

Ray

Society,

San

Francisco,

California,

1974.

From the t Associate

§

at

the

clinical

pulmonic

the frequency of occurrence of roentgenographic pulmonary arterial hypertension, cases were also excluded if there were any

24-27,

embolism). posteroanterior

Finally,

of

from estimating

or

roentgenograms of good quality following the establishment of the diagnosis of PSS were included in the review, and in most instances multiple chest studies were available. The primary roentgenographic criteria employed for the diagnosis of PAH included enlargement of the main pulmonary artery segment or pulmonary outflow tract, and unequivocal enlargement of both right and left main pulmonary arteries; secondary criteria included rapid peripheral tapering of pulmonary arterial branches and signs of right ventricular enlargement.

METHODS

were excluded purposes of

roentgenographic,

pulmonary

Only cases with a pathologic (biopsy and/or autopsy) diagnosis or unequivocal clinical findings of P55 were included in this review. Several cases of apparent systemic sclerosis presented a symptom complex which was nonspecific, suggesting the possibility of another collagen disorder such as rheumatoid or systemic lupus erythematosus final

M.D.,

evidence of another pulmonary parenchymal or vascular disease (i.e., emphysema

the

results

BEIN,

CALIFORNIA

O

4!

E.

IN

UCLA School

Medicine,

Professor

of Radiological Sciences. Chief Resident in Radiological Sciences. Assistant Clinical Professor of Medicine.

46!

of Medicine,

Los

Angeles,

California.

September

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J.

R.

462

Steckel,

M.

E.

following a diagnosis of progressive systemic sclerosis. Although minimal-to-moderate interstitial fibrosis was evident in the “positive” cases, the apparent severity of pulmonary arterial hypertension noted roentgenographically

and/or

pathologically

was out of proportion to the degree and extent of the interstitial lung disease. Unfortunately, in this retrospective series of 4! patients, pressure measurements by cardiac catheterization and pulmonary function studies were performed infrequently; therefore, an effective correlation of these parameters with the roentgenologic findings is not

possible

with

In an additional clinical findings monic

second

the

available

8 patients (usually an sound)

data.

in this review, increased pul-

were

consistent

with

PAH; pulmonary vascular changes at autopsy suggested the presence of pulmonary arterial hypertension in another patients. Therefore, of the 4! cases reviewed, i 5 cases (7 per cent) might be inferred to have had PAH by roentgenologic, clinical, and/or patholDgic criteria (Table i). More sophisticated studies, including cardiac and pulmonary artery catheterization in “subclinical” cases, might conceivably

have

revealed

early PAH,

had

further

the

studies

instances

been

of

performed.

Bein

and

P.

pulmonary

sented

Kelly

M.

arterial

briefly

CASE

first

I.

5975

JULY,

hypertension

are

pre-

here.

N.P.

admitted

This to

33

UCLA

old

year

female

in August

was with

1970

a history of Raynaud’s phenomenon and progressive acrosclerosis for 3 years. In December 1969 she had undergone a bilateral cervical sympathectomy for ulceration of the “right knuckles.” Since then she had noted the insidious onset of dyspnea on exertion, mild dysphagia, and arthralgias of the knees and ankles. Physical examin ation revealed indurated, shiny, hyperpigmented skin over the hands and both forearms, and superficial ulcerations were noted dorsally over several of the proximal interphalangeal joints of all joints

bilaterally. of the hands

Limitation and wrists

of motion was also

described. The examination was otherwise remarkable. She was normotensive and electrocardiogrr.m was normal. An upper trointestinal

series

and

small

bowel

unher gas-

follow-

through revealed lack of normal penistalsis in the esophagus, consistent with scleroderma. The patient was seen in the clinic on June 1971 with a continuing complaint of moderate shortness of breath on exertion, which has continued until the present time. Physical examination revealed a widely split second heart sound with the pulmonic component greater than the aortic, and few bibasilar rales. Pulmonary function tests in June 1973 indicated combined mild-to--moderate restrictive and obstructive

defects

with

normal

airway

resistance

and markedly

REPORT

Case

reports

OF

on

roentgenographic

CASES

2 patients with findings diagnostic

chest of

al’norm;tl diffusing capacity. The patient is currntly being followed in the UCLA clinics. A recent chest roentgenogram is shown ii Figure I, A and B. CASE

I

TABLE INCIDENCE

OF

PAH

IN CASES

SYSTEMIC (41

Cases

without

evidence

Roentgenographic

Clinical Autopsy

(see text)

OF PROGRESSIVE

SCLEROSIS CASES)

of

arterial hypertension (PAH): Cases with evidence of PAH: Roentgenographic

first

(definite)

(probable)

II.

N.B.

admitted

This

45 year old in September

to UCLA

a 9 month history exertion. She gave naud’s phenomenon,

female 1968

was with

of increasing a

i

and

dyspnea on history of Rayphysical examination

year

revealed thickened skin over the fingers, hands, toes, and feet. There were multiple telangiec-

pulmonary 26 (63%) 3 2

8 2

‘5(37%)

tases pressure normal patient

over

the

was except to take

face I 10/70

and mm.

upper trunk. Blood Hg. The lungs were

for an apparent inability a very deep breath. The

by the second

heart sound was widely split, with accentuation of the pulmonic component. The examination was otherwise unremarkable. Electrocardiogram showed right ventiicular hypertrophy. cine-esoph agogram and upper gastrointestinal

A

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VOL.

FIG.

No.

524,

I

. Case

B) Posteroanterior for Ravnaud’s phenomenon.

did

arteries, The

not

genograms

of

are enlarged, outflow

tract

Arterial

and lateral In addition,

i. (A and

thectomy pulmonary hypertension.

series

Pulmonary

3

chest roentgenograms the main pulmonary

reveal any abnornaiity. Roentthe hands showed calcinosis with

Resting

showed pH Pulmonary severe

arterial

blood

gas

PO2 66 mm. Hg function tests indicated 7.51,

obstructive

ventilatory

analysis

and

pCO 27. moderately insufficiency. A ill-defined per-

lung scan demonstrated multiple fusion defects bilaterally. Pulnion ary arteriography was performed and ievealed a main pulnionary artery pressure of 140- i6o #{244}o mm. Hg, RV pressure of i6o/io, and RA pressure of 10/3. A left upper branch pulmonary artery injection failed to demonstrate any emboli. Finally, an open lingular lung biopsy showed diffuse pulmonary fibrosis and acute vasculitis consistent with scieroderma. A rept esentative chest roentgenogram is shown in Figure 2, A arid

B.

The patient nosis of ‘‘CRST naud’s,

roderi sion.

was

discharged svndronie

sclerodactvlv,

and

with (calcinosis, telangiectasia

the

diagRay) , scieh vpertendischarge diuretics,

disease asd pu I nn arv seen in clinic following where medications included digitalis, steroids, and anticoagulants. In May was admitted with increasing orthopnea wheezing, and shortly thereafter she enced

a lung She was

a ca

Lliac

arrest.

give evidence ofpnior right artery, as well as the right

with rapid tapering of branch vessels, consistent of right ventricle is also prominent on the lateral

slight resorption of several of the distal phalanges of the left hand. A punch biopsy of the skin of the left hand was consistent with scleroderma.

463

Hypertension

i

she

and experi-

with

pulmonary

sympaand left arterial

view.

Post mortem exam i n ation revealed severe sclerosis of both the pulmonary arteries and the veins, as well as right ventricular hypertrophy and dilatation. \licroscopically, there was dense hyalinized fibrous tissue in the derI_nis ail throughout the submucosa of the gastrointestinal

tract,

In addition, stitial tibrous alveolar ening

was as

occlusion

as

of

in large

and

in the

veins,

vessels

smaller

scieroderma.

scattered interthe pulmonary intimal thick-

\Iild-to-moderate

present well of

with

nild,

was

thickening

septa.

arteries

consistent

there

small

l)V

pulmonary

with

occasional

intiiial

prolifer-

ation. DISCUSSION

In with

a retrospective established

genograms

review PSS,

and

complete

available, 3 definite cases of pulmonary were observed roen

degree

of PAH

and

was

of with

41

cilest

clinical

patients roent-

records

and 2 ilighlV probable arterial hypertension tgenographi cally. The out

of proportion

to the

severity of tile interstitial pulmonary disease attributable to systemic sclerosis. Similarly, review of the non-radiologic literature revealed reported cases with pulmonary hypertension

arteriolar changes at autopsy that

ated

minimal-to-absent

with

of pulmonary

were associfibrotic in-

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464

R.

FIG.

2.

Case

in Case

I

terstitial

tween

in

searched

the and

M.

E.

for,

presence the

the

corresponding

no

correlation

of Raynaud’s

presence

of

be-

phenom-

clinical

phenomenon

aflecting

has

the

and

the

microcirculation

(including

been

relatively

on chest

P.

M.

Kelly

the

discussed lligh

skin,

presence

of lung,

or

in a recent incidence

roentgenograms

of

many

and

or-

kidney)

review.6 PAH

in this

The

observed

series

should

now

study,

possibly

Ganz

raises

the possibility of an even higher occurrence of subclinical pulmonary vascular i llvolvement in this disease, without roentgenologic or clinical man festations. This possibility

be

arterial changes similar (confirmed at autopsy).

subjected

nary

to

the

to those

As in

of

Swan-

of pulmonary

PSS

including

asymptomatic

vascular

1975

a prospective

use

measurements

pressure,

are

JULY,

with

catheter

wilo

severity oIPAH cannot be excluded in this retrospective study, because neither the severity of Raynaud’s phenomenon nor the level of I)ulmonar arterial hypertension were quantified. The possibility that systemic sclerosis is in fact a disease primarily gans

and

artery

and/or

roentgenological evidence of PAH was observed in our series. However, a possible correlation between the severity of Raynaud’s

Bein

pectus deformity. Nevertheless, of pulmonary arterial hypertension of interstitial pulmonary fibrosis is minimal.

evidence

Cllaliges

Although enon

Steckel,

II. (A and B) There is moderate are present and are diagnostic

I, roentgenologic

Case

J.

for

lung

patients

or

Data

involvement.

pulmoof

prog-

individual patient, as well as of basic pathogenetic significance for the disease process, might be obtained by this means. In view of the unexpectedly high mcidence (12 per cent) ofdefinite or probable nostic

changes

in

in the

significance

of

this

PAH

series

would

also

seem

ologist

to

search

PSS

of

and

systemic nosis

on

of

pathic”

roentgenograms

with

PSS, it the radifor PAH in known cases suggest the possibility of incumbent

to

sclerosis of

chest

patients

41

in

the

upon

differential

diag-

evident

“idio-

roentgenologically pulmonary

hypertension. SUMMARY

Forty-one sclerosis

cases were

of

reviewed

progressive retrospectively

systemic in

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VOL.

No.

124,

Pulmonary

3

Arterial

order to ascertain the frequency of roentgenographic pulmonary arterial hypertension (PAH) in progressive systemic sclerosis (PSS). Chest roentgenograms on 12 per cent (5 of 4! ) of the cases reviewed showed definite or probable roentgenographic evidence of pulmonary arterial hypertension, and a total of 15 (37 per cent) might be inferred to have had pulmonary arterial hypertension by recorded roentgenographic, clinical, and/or patho1ogic criteria. The degree of pulmonary

arterial

hypertension

was

out

ciation

in the

differential

genographically monary arterial

diagnosis

evident hypertension.

Richard J. Steckl, M.D. Department of Radiology The Center for the Health University of California,

Los

Angeles,

California

“idiopathic”

REFERENCES I.

of roent-

Case

records

pital

286, 3.

4.

90024

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of

Massachusetts

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New

England

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and

BASHOUR,

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P.

CONNER,

K.,

pulmonary

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logic

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study.

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F. A. Cardio-

scleroderma:

7.,

Heart

systemic

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autopsy

matched

physio-

6z,

1961,

W. A., FRIES, J. F., L. E. Pathologic

D’ANGELO,

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:

study

of

cases and fifty-eight Am. 7. Med., 1968, 46, 428-

controls.

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NAEYE,

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TUMULTY,

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M. A., AKGUN, N., D. H. Pathophysiology heart and respiratory

gen-

66-68o. P., and

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and LINDSTROM, C. Pulmonary in systemic sclerosis. Ann.

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simulator

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of

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1960,262, 2.

of

proportion to the severity of interstitial pulmonary disease attributable to scleroderma. Moreover, no correlation between the presence or recorded severity of Raynaud’s phe iomenon and the presence of clinical and/: r roentgenographic evidence of pulmonary arterial hypertension was observed. Radiologists should be aware of the possibility of pulmonary arterial hypertension in known cases of progressive systemic sclerosis; in addition, they should be prepared to raise the possibility of this asso-

465

Hypertension

other 122,

synopsis

of scleroderma: Johns

diseases.

Hopkins

236-246.

DIVERTIE,

scleroderma.

M.

B., and Dis.

Chest,

TITUS,

1968,