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Plexogenic Pulmonary Hypertension in Systemic Lupus Erythematosus: Report of Two Cases and Review of the Literature Juliet G o l d m a n , BA,* and, William D. Edwards, MD * • University of South Florida, School of Medicine, Tampa, Florida, and the "Division of Anatomic Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

q--lFrom the autopsy records of the Mayo Clinic, two patients with systemic lupus erythematosus were identified in whom plexogenic pulmonary hypertension also developed. Both were women (23 and 30 years old). Their pulmonary artery pressures were 96/30 and 115/ 45 mm Hg, respectively, and their survival after the diagnosis of pulmonary hypertension was only 21 and 19 months, respectively. To our knowledge, only two other cases have been reported. Thus, plexogenic pulmonary hypertension among patients with lupus is rare but is associated with a poor prognosis.

Among patients with autoimmune connective tissue disorders pulmonary hypertension may develop, with or without underlying pulmonary fibrosis. This most commonly occurs with scleroderma (progressive systemic sclerosis) and in patient's with Raynaud's phenomenon (1,2). Hypertensive pulmonary vascular disease may also develop in patients with systemic lupus erythematosus (SLE). In this setting, the obstructive arterial lesions tend to be thrombotic or fibrotic (3). Only rarely has plexogenic disease been described in subjects with SLE and pulmonary hypertension (4,5). Two such cases from our autopsy files are described.

Case 1

Clinical Findings. A previously healthy 17-year-old Caucasian woman developed fatigue, conjunctivitis, and arthralgias in the spring of 1987. Pertinent laboratory findings included positive ANA, anti-DNA, antiFM, and anti-RNP. A diagnosis of SLE was made, and prednisone therapy was begun. There was no evidence Manuscript received August 25, 1993; accepted August 26, 1993. Address for reprints: Dr. W.D. Edwards, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, telephone: (507) 284-9342, fax: (507) 284-1599.

©1994 by Elxevier Science Inc.

of lupus anticoagulant, and studies of coagulation and platelet function were normal. By June 1991, she had also developed mucositis, pericarditis, and Raynaud's phenomenon. At that time, severe pulmonary hypertension was diagnosed echocardiographically, with an estimated right ventricular systolic pressure of 78 mm Hg. By November 1992, the estimated pulmonary artery pressure was 96/30 mm Hg and the patient was short of breath. In February 1993, symptoms had progressed and included dyspnea, orthopnea, chest pain, weight loss, and edema of the lower extremities. Right ventricular failure and ischemia developed and led to the patient's death in March 1993, at the age of 23 years. An echocardiogram taken six days before death revealed a peak systolic pulmonary artery pressure of 102 mm Hg. Autopsy Findings. The right and left lungs weighed 440 g and 480 g, respectively. Dilatation was a prominent feature in the elastic pulmonary arteries, both mediastinal and intrapulmonary. Microscopically, the muscular pulmonary arteries were involved by extensive plexiform lesions (Fig. 1). Several large muscular arteries exhibited necrotizing arteritis, and a few small muscular arteries were the site of concentric laminar intimal proliferation and fibrosis. Medial hypertrophy of muscular pulmonary arteries was diffuse. There was 1054-81';07/94/$7.00

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Figure 1. Photomicrographs of muscular pulmonary arteries (case 1). A. Medial hypertrophy. B. Concentric laminar intimal proliferation. C. Necrotizing arteritis with secondary intimal proliferation. D. Plexiform lesion. (A and C, elastic-van Gieson stain, ×270 and ×135; B and D, hematoxylin-eosin stain, ×360 and ×180.) no evidence of thromboemboli, although aggregates of platelets were commonly observed within capillarysized vessels in plexiform lesions. The heart weighed 540 g (expected mean 310 g and range 210-450 g) (6). Hypertrophy of the right ventricle was severe, as was dilatation of the right ventricle, right atrium, and tricuspid and pulmonary annuli (Fig. 2). Mural thrombus was not present in any cardiac chamber. The liver showed severe congestion microscopically. Abdominal distension was the result of 1,000 mL of ascitic fluid, and the spleen exhibited diffuse capsular

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fibrosis. Microscopially, the kidneys were involved by mild lupus glomerulonephritis.

Case 2 Clinical Findings. A 12-year-old Caucasian female presented in 1972 with arthritis, was diagnosed to have SLE, and started on steroid therapy. From 1984 to 1985, she developed episodes of bronchitis and sinusitis. By July 1988, syncopal spells had occurred. Cardiac catheterization revealed severe pulmonary hypertension with a pulmonary artery pressure of 115/45 mm Hg (mean 75), and Doppler echocardiographic studies were confirmatory. There was no evidence of lupus anticoagulant. Coumadin therapy was begun in 1989. In February 1990, at the age of 30, she was admitted with a two-week history of anorexia, diarrhea, and rectal bleeding. However, the patient rapidly lost con-

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sciousness and died. Blood drawn in the emergency room was ANA positive. Autopsy Findings. The right and left lungs weighed 410 g and 350 g, respectively. Branches of the pulmonary arteries were focally involved by shallow atheromatous plaques. Multiple sections of the small muscular arteries revealed numerous plexiform lesions, some of which contained focal fibrin deposition (Fig. 3). Additional lesions included medial hypertrophy, concentric laminar intimal fibrosis, and focal arteritis. There was no evidence of pulmonary emboli. The heart weighed 410 g (expected mean 282 g and range 193-413 g) (6) and was involved by marked right ventricular hypertrophy and mild biventricular dilatation. As a result of straightening of the septum, both ventricles were D-shaped in cross section (Fig. 2). There was also a serous pericardial effusion (135 mL). Microscopically, the liver was congested and the kidneys showed mild segmental proliferative mesangiopathy.

Discussion Although patients with SLE may develop pulmonary hypertension, this is an uncommon occurrence. When present, pulmonary arterial obstruction is generally thrombotic or fibrotic in nature and is associated with the presence of ribonucleic protein antibody, rheumatoid factor, and lupus anticoagulant (4). The development of plexogenic pulmonary arteriopathy is distinctly uncommon. In fact, to our knowledge, only 2 cases have previously been reported in the English literature (4,5). To these, another 2 cases from our institution are added. Although Wakaki et al. (7) listed 3 published cases of SLE with plexogenic pul-

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• "igure 2. Gross cardiac specimens, in short-axis view. A. Right ventricular (RV) hypertrophy and dilatation, with straightened ventricular septum and dilated tricuspid annulus (case 1). B. Right ventricular hypertrophy, with straightened ventricular septum and bilateral D-shaped ventricular chambers (case 2). LV = left ventricle. monary hypertension, the patients' age, gender, pulmonary artery pressure, and survival time were not provided. Hence, clinical information is available for only 4 patients (Table 1). Of the 4 cases, all were women, and their ages ranged from 23 to 45 years (mean 34). This is in keeping with the fact that patients with the plexogenic form of primary pulmonary hypertension usually succumb between the ages of 17 and 41 years (mean 29) (8). Raynaud's phenomenon was described in 3 of the 4 and preceded the development of pulmonary hypertension in each. An association between Raynaud's phenomenon and pulmonary hypertension has been recognized for many years, and intense pulmonary vasoconstriction is thought to result in vascular injury, with fibrinoid degeneration, necrotizing arteritis, and the development of plexiform lesions (2,5). Of the 4 patients with SLE and plexogenic disease, 3 had systolic or mean pulmonary artery pressures that approached systemic levels. In this regard, it is of interest to note that plexogenic disease is generally the only form of pulmonary hypertension in which systemic levels of blood pressure are commonly achieved. Only uncommonly are such pressures recorded in patients with thromboembolic pulmonary hypertension or chronic pulmonary venous hypertension. For the plexogenic form of primary pulmonary hypertension in general, survival at 6 months and at 1 and

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Figure 3. Photomicrographs of muscular pulmonary arteries (case 2). A. Medial hypertrophy. B. Concentric laminar intimal fibrosis. C. Plexiform lesion, with dilated distal vessels. D. Plexiform lesion (glomerulus-like), with fibrin deposition (arrows) in small vascular channels. (A and B, elastic-van Gieson stain, x270 and x360; C and D, hematoxylin-eosin stain, x 180 each). 2 years has b e e n r e p o r t e d to be a b o u t 50%, 35%, and 20%, respectively (8). The presence of plexogenic disease in patients with S L E appears to have a similarly

p o o r prognosis. A m o n g the 4 cases, 1 died 5 m o n t h s after p u l m o n a r y hypertension was diagnosed, and 2 died at 19 and 21 months. O n l y 1 patient survived m o r e than 2 years, In s u m m a r y , the d e v e l o p m e n t of plexogenic pulm o n a r y hypertension in patients with S L E is a rare occurrence. W h e n present, however, it is generally associated with near-systemic p u l m o n a r y artery pressure and with a p o o r prognosis. L u n g transplantation m a y improve survival (9).

Table 1. Reported Cases of Plexogenic Pulmonary Hypertension in SLE Year (ref) 1988 (5) 1992 (4) 1993 (present case) 1993 (present case)

Raynaud's Age, Gender Phenomenon 45, 39, 30, 23,

F F F F

Yes Yes No Yes

Survival (yr)

PA Pressure mm Hg (mean)

SLE to Death

PPH to Death

62/20 (34) -- (71) 115/45 (74) 96/30 (--)

0.4* 17 9 6

0.4 5 1.6 1.8

PA, pulmonary artery, PPH, plexogenic pulmonary hypertension; SLE, systemic lupus erythematosus. *Arthralgias and Raynaud's phenomenon were present for 10 years, but the diagnosis of SLE was not made until the pulmonary hypertension was evaluated.

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GOLDMAN AND EDWARDS PLEXOGENIC PULMONARY HYPERTENSION [N SLE

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2. Kay JM, Heath D. Pathologic study of unexplained pulmonary hypertension. Semin Respir Meal 1985;7:180-192.

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3. Wilson L, Tomita T, Braniecki M. Fatal pulmonary hypertension in identical twins with systemic lupus erythematosus. Hum Pathol 1991:22:295-297.

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4. Roncoroni A J, Alvarez C, Molinas F. Plexogenic arteriopathy associated with pulmonary vasculitis in systemic lupus erythematosus. Respiration 1992;59:52-56. 5. Kanemoto N, Sato M, Morinchi J, lchikawa Y~ Gioto Y, Sasadaira H. An autopsied case of systemic lupus erythematosus with

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pulmonary hypertension: a case report. Angiology 1988;39:187192. Kitzman DW, Scholz DG, Hagen PT, Ilstrup DM, Edwards WD. Age-related changes in normal human hearts during the first 10 decades of life: part II (maturity). A quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clin Proc 1988;63: 137-146. Wakaki K, Koizumi F, Fukage M. Vascular lesions in systemic lupus erythematosus with pulmonary hypertension. Acta Pathol Jpn 1984;34:593-604. Pietra GG, Edwards WD, Kay JM, et al. Histopathology of primary pulmonary hypertension: a qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung and Blood Institute, primary pulmonary hypertension registry. Circulation 1989;80:1198-1206. Randhawa P, Yousem S. The pathology of lung transplantation. Pathol Annu 1992;27:247-279.

Plexogenic pulmonary hypertension in systemic lupus erythematosus: Report of two cases and review of the literature.

From the autopsy records of the Mayo Clinic, two patients with systemic lupus erythematosus were identified in whom plexogenic pulmonary hypertension ...
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