Secondary Logo

Journal Logo

Pulmonary Capillary Hemangiomatosis Associated with Primary Pulmonary Hypertension

Report of 2 New Cases and Review of 35 Cases from the Literature

ALMAGRO, PEDRO M.D.; JULIÀ, JOAQUIM M.D.; SANJAUME, MARIA M.D.; GONZÁLEZ, GUADALUPE M.D.; CASALOTS, JAUME M.D.; HEREDIA, JOSÉ LUIS M.D., PH.D.; MARTÍNEZ, JESÚS M.D., PH.D.; GARAU, JAVIER M.D.

Article
Free

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of primary pulmonary hypertension characterized by thin-walled microvessels infiltrating the peribronchial and perivascular interstitium, the lung parenchyma, and the pleura. These proliferating microvessels are prone to bleeding, resulting in accumulation of hemosiderin-laden macrophages in alveolar spaces. Here we report 2 cases of PCH with pulmonary hypertension, 1 of them associated with mechanical intravascular hemolysis, a feature previously reported in other hemangiomatous diseases, but not in PCH. Case 2 was diagnosed by pulmonary biopsy; to our knowledge the patient is the second adult to be treated with interferon α-2a.

Review of the literature identified 35 patients with PCH and pulmonary hypertension. The prognosis is poor and median survival was 3 years from the first clinical manifestation. Dyspnea and right heart failure are the most common findings of the disease. Hemoptysis, pleural effusion, acropachy, and signs of pulmonary capillary hypertension are less common. Chest X-ray or computed tomography scan usually shows evidence of interstitial infiltrates, pulmonary nodules, or pleural effusion. Hemodynamic features include normal wedge pressures. Radiologic and hemodynamic findings are undifferentiated from those of pulmonary veno-occlusive disease but differ from other causes of primary pulmonary hypertension.

Epoprostenol therapy, considered the treatment of choice in patients with primary pulmonary hypertension, may produce pulmonary edema and is contraindicated in patients with PCH. Regression of lesions was reported in 1 patient treated with interferon therapy and 2 other patients stabilized, including our second patient. PCH was treated successfully by lung transplantation in 5 cases. Early recognition of PCH in patients with suspected primary pulmonary hypertension is possible based on clinical and radiologic characteristics. Diagnosis by pulmonary biopsy is essential for allowing appropriate treatment.

From Services of Internal Medicine (PA, JJ, MS, JG), Pathology (GG, JC), Pneumology (JLH), and Intensive Care (JM), Hospital Mútua de Terrassa, University of Barcelona, Terrassa, Catalonia, Spain.

Address reprint requests to: Dr. Pedro Almagro, Hospital Mútua de Terrassa, Pl. Dr. Robert, 5, 08221 Terrassa (Barcelona), Catalonia, Spain. Fax: 34937365059; e-mail: 19908pam@comb.es.

Accessible online at “http://www.md-journal.com”. To search for Medicine articles in PubMed, use the journal name “Medicine Baltimore”.

Back to Top | Article Outline

Introduction

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of primary pulmonary hypertension. First described in 1978 by Wagenvoort et al (42), PCH is caused by an uncontrolled proliferation of pulmonary capillaries infiltrating vascular, bronchial, and interstitial pulmonary structures. Dyspnea is the most common manifestation and the presence of hemoptysis, pleural effusion, an interstitial radiologic pattern, or signs of postcapillary hypertension are all signs that, if present in the setting of primary pulmonary hypertension, should suggest the disease. The prognosis is poor and median survival is approximately 3 years from the initial clinical manifestation. Symptomatic treatment with diuretics, oxygen, and warfarin has been used widely, and interferon α-2a has been proposed as specific therapy (45,46,47), while prostaglandins, which are considered the treatment of choice in primary pulmonary hypertension of other causes, are contraindicated (4,14,18). The possibility of using several treatment options should encourage physicians to maintain a high degree of clinical suspicion and perform pulmonary biopsy in patients with primary pulmonary hypertension when any of the signs mentioned above is present.

In this article we present 2 new cases of PCH and assess the clinical, radiographic, functional, and pathologic characteristics, after a review of all cases reported in the English-language literature. Finally, therapeutic options are analyzed.

Back to Top | Article Outline

Patients and Methods

We report here 2 new cases and the results of a literature review of primary pulmonary hypertension and PCH. We searched the MEDLINE database (National Library of Medicine, Bethesda, MD) for PCH in humans, using the key words pulmonary capillary hemangiomatosis, pulmonary hemangiomatosis, lung hemangiomatosis, hemangiomatosis, primary pulmonary hypertension and interferon therapeutic use. Additional case reports were identified from the references of selected articles. The search period was 1960 to October 2001. We found 37 cases of PCH with primary pulmonary hypertension. All but 2 (29,34), written in Japanese and Polish, respectively, could be reviewed. Two cases (45,47) reported in a review of interferon treatment were not included because of lack of pertinent clinical information. Finally, we did not include cases with pathologic findings of PCH found in the context of other clinical situations without primary pulmonary hypertension (1,8,15,37).

Back to Top | Article Outline

Case Reports

Case 1

A 58-year-old man was admitted to hospital in July 1992 with progressive dyspnea. He was an active 30-pack-year smoker and had a 6-year history of dyspnea. He was an obese man with central cyanosis and clubbing. Cardiovascular examination disclosed a sternal systolic murmur compatible with tricuspid insufficiency and bibasal rales, jugular vein distention, hepatojugular reflux, and bilateral ankle edema. Blood chemistries showed hemoglobin 17.9 g/L; leukocyte count 5,320/mm3; platelets 150,000/mm3; total bilirubin 27.7 μmol/L; direct bilirubin 7.33 μmol/L; AST 28 IU/L; ALT 58 IU/L; γGT 58 IU/L; phosphatase alkaline 172 IU/L, and normal renal function. An extensive battery of autoantibody tests was negative. Basal arterial blood gases revealed severe hypoxemia (pO2 47 mmHg, pCO2 30 mmHg, pH 7.46). Chest X-rays showed an interstitial bibasal pattern, Kerley B lines, and prominent pulmonary arteries (Figure 1), confirmed with computed tomography (CT) scan. Electrocardiographic findings were a 90° axis and right ventricular strain. Diuretics and oxygen therapy were started with clinical improvement. Spirometric parameters performed after patient stabilization disclosed a forced vital capacity (FVC) of 4.81 L (115%), a forced expiratory value in the first second (FEV1) of 3.65 L (118%), and a total lung capacity of 6.36 L (105%). The diffusing capacity of the lung for CO (DLco) corrected with alveolar volume was severely diminished (25%). Pulmonary scintigraphy showed hypoperfusion of apical segments matching with ventilatory defects, not suggestive of pulmonary embolism. Pulmonary arteriography showed signs of pulmonary hypertension without perfusion defects. The echocardiographic appearance of left heart valves and cavities was normal. Isotopic left ventriculography showed an ejection fraction of 51%. While bronchoscopic macroscopic examination was normal, numerous hemosiderin-laden macrophages were found in the transbronchial biopsies.

Fig. 1

Fig. 1

With the suspicion of primary pulmonary hypertension due to pulmonary veno-occlusive disease, right heart catheterization was performed. High right ventricular and pulmonary pressures were found: 48/11 mmHg (normal <25/<5 mmHg) and 77/28 mmHg (normal <25/<12 mmHg), respectively, with a pulmonary artery wedge pressure of 2 mmHg (normal <12 mmHg) and a cardiac output of 4.4 L/min. The patient refused pulmonary biopsy and was considered a poor candidate for transplantation because of obesity and age. Warfarin and chronic oxygen therapy were prescribed after discharge. He was admitted in the ensuing months several times for exacerbation of his right heart failure. Intravascular mechanic hemolysis was present (hemoglobin 16.4 g/L; reticulocytes 36 per thousand; haptoglobin 10.2 mg/dL; LDH 586 IU/L; total bilirubin 87.21 μmol/L; direct bilirubin 18 μmol/L; anisocytosis and schistocytes were seen in the peripheral smear examination). His last admission in 1996 was prompted by severe heart failure with supraventricular tachycardia and hypotension. The patient died shortly thereafter.

Postmortem examination showed congestive and mildly edematous lungs. No condensation, hemorrhages or emboli were found. A right serous pleural effusion was present. Microscopic examination showed a panlobar and patchy heterogeneous lesion. Interalveolar septae were thickened and infiltrated by numerous thin-walled vessels with their lumen dilated and filled with red blood cells. These capillaries were lined by endothelial cells without atypia and with no mitotic features. There was a variable grade of fibrosis of the septae accompanying the capillary proliferation (Figure 2). Infiltration by capillaries was also observed in the walls of pulmonary vessels and bronchi (Figure 3). Hemosiderin-laden macrophages were found at the alveolar spaces of the affected areas. Some pulmonary arteries showed intimal fibrous thickening and mild luminal reduction. No venous alterations were found.

Fig. 2

Fig. 2

Fig. 3

Fig. 3

Back to Top | Article Outline

Case 2

A 62-year-old man was admitted to hospital in August 1998 with dyspnea. He had a 20-year history of diabetes mellitus with retinopathy, nephropathy, neuropathy, and distal arteriopathy. He was a 20-cigarette-day active smoker who reported no symptoms of chronic bronchitis. Physical examination showed cyanosis, with tachycardia (100/min) and splitting of the first sound, jugular vein distention, hepatojugular reflux, and bilateral ankle edema. Blood chemistries showed glucose 175 mg/dL; normal renal and hepatic function; hemoglobin 15 g/L; 8,500 leukocytes/mm3; and 160,000 platelets/mm3. Basal arterial blood gases were pH 7.40, pO2 35 mmHg, and pCO2 42 mmHg. Electrocardiogram was normal, and bibasal interstitial infiltrates with prominent pulmonary arteries were present in the chest film. A CT scan confirmed these features. Pulmonary scintigraphy was of low probability for pulmonary embolism. Pulmonary arteriography showed mild signs of pulmonary hypertension without perfusion defects. No cardiac chamber enlargement or valvular abnormalities were found in the ultrasound study. Isotopic left ventriculography showed an ejection fraction of 48%. Spirometry parameters were a FVC of 3.850 L (94%), FEV1 of 2.350 L (79%). DLco corrected for alveolar volume was diminished (58%). Right ventricle pressures were 45/1 mmHg, pulmonary artery pressures were 45/20 mmHg, wedge pressure was 20 mmHg, and cardiac index was 2.38 L/min. These hemodynamic findings were consistent with postcapillary pulmonary hypertension. A pulmonary biopsy was performed. At low power microscopic view, the lung parenchyma architecture was well preserved with a congestive appearance. At high magnification numerous small capillaries were appreciated in the interalveolar septae, forming at least a double row (Figure 4), surrounding the bronchi and in the visceral pleura. These alterations had a patchy distribution, intermingled with normal parenchyma. Arterial vessels showed intimal fibrosis and medial thickening. No venous abnormalities were found. Some alveolar spaces were occupied with macrophages.

Fig. 4

Fig. 4

Diuretics and oxygen were started. Warfarin therapy was deemed inappropriate because the patient was at high risk of falling; aspirin was given instead. Therapy with interferon α-2a was started on a 3,000,000 U thrice weekly regimen. Several months later, the dose was reduced because of thrombocytopenia. After 36 months of treatment the patient was alive and the pulmonary artery pressure remained about 45/24 mmHg.

Back to Top | Article Outline

Literature Review

Clinical features

Thirty-seven patients with PCH and primary pulmonary hypertension are summarized in Table 1. Twenty-one were men (55%), and the mean age was 28.8 years (range, 2–71 yr). In 69% of patients, dyspnea was the first complaint, and it became almost universal with the progression of the disease (Table 2). Right heart failure secondary to severe pulmonary hypertension was observed in almost half the patients, especially in advanced stages. Hemoptysis was another common sign of the disease, occurring in more than one-third of the patients along the course of the illness. In 3 cases it was the initial complaint (12,40,42). Fever was reported in 10 patients (13,22,23,28,32,39,42). Pleural effusions occurred in 9 patients (11,18,19,23,32,42,48), and in 4 cases were hemorrhagic. Cyanosis (22,23,31,32) and chest pain (13,22,26) also have been reported. Auscultatory crackles may occur in patients with PCH; other nonspecific signs reported are epistaxis (32), syncope (18,23), clubbing (28,38,46), and hematemesis (32).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

The diagnosis of PCH was made premortem in 9 patients: 3 on pulmonary biopsy (2,35,46), 5 in native lung after pulmonary transplantation (7,11,12), and 1 after pneumonectomy (40). The rest were wrongly classified and definitive diagnosis was only reached after necropsy. Primary pulmonary hypertension was the initial diagnosis in 15 patients, 3 were diagnosed with pulmonary fibrosis (9,38,39), another 2 patients were cataloged with pulmonary veno-occlusive disease (12,38), 2 more with pulmonary embolism; other diagnoses were pulmonary hemosiderosis (42), arteriovenous malformation (6), lymphangiectasia, and hemangioendotheliomatosis (32). Pulmonary biopsy was performed in 12 patients.

Twenty-eight patients had died at the time of publication. The median survival in these patients was 3 years from the first clinical manifestation. The immediate cause reported was right heart failure in 11, progressive deterioration of general status in 4 patients, respiratory insufficiency in 4, hemoptysis in 2 cases (32), and “sudden death” in 2 patients (22,23). The ultimate cause of death is not reported in 5 patients.

Back to Top | Article Outline

Complementary studies

Chest X-ray findings were nonspecific; they usually showed a pattern of bilateral interstitial infiltrates (21 cases), in 1 case (6) showed bilateral pulmonary nodules, and were normal in 2 patients (18,23). Cardiomegaly was present in 8 cases and pulmonary artery enlargement in 13. Electrocardiograms were available for 15 patients. They disclosed signs of right ventricular hypertrophy in 13 cases and were normal in 2. Ultrasound heart examination was performed in 20 patients. The most commonly reported alteration was right ventricular dilatation (13 patients), and indirect signs of pulmonary hypertension were present in 6 patients. Finally, 1 patient had a pericardial effusion (39).

CT scan of the thorax was performed in 9 patients: 4 patients showed interstitial infiltrates (10), 2 patients had pulmonary artery enlargement, 2 were found to have mediastinal widening, and 1 case showed bilateral pulmonary nodules (6). Two patients had pleural involvement (2,18), and 1 patient with normal chest X-ray had a normal CT scan.

Pulmonary function tests were reported in 12 patients. They showed obstruction in 2 patients, restriction in 7 patients, and a mixed pattern in 3 patients. The DLCO was diminished in 6 patients (Table 3). Blood gas analysis usually showed hypoxemia. Bronchoscopic examination, even when transbronchial biopsy was performed, was not diagnostic in the 8 patients who had the procedure.

TABLE 3

TABLE 3

Pulmonary angiography was performed in 10 patients. Signs of pulmonary hypertension were present in 1 patient, and pulmonary embolism was suspected in another. Nonspecific vascular abnormalities were present in another patient and the angiography was strictly normal in the remaining patients. Pulmonary scintigraphy was done in 22 patients: 10 had nonspecific perfusion defects; 2 others had moderate to high probability of pulmonary embolism, while the other 10 patients had normal results.

The hemodynamic findings of 20 patients are summarized in Table 4; 2 patients had “normal” pressure and cardiac output (data not shown). They were subjected to heart catheterization before overt disease developed but signs of pulmonary hypertension were later found at autopsy (2,6). Wedge pressures were reported in 16 cases: they were normal in 14 cases and high in 2.

TABLE 4

TABLE 4

Back to Top | Article Outline

Treatment

Different modalities of treatment were used for PCH. The majority of patients were treated with anticoagulants, diuretics, ACE inhibitors, and oxygen. Calcium channel blockers and prostaglandins were used in 6 patients to treat pulmonary hypertension. In all cases prostaglandins had to be withdrawn because of hemodynamic intolerance (7,13,24) and were directly incriminated as the cause of death in 3 patients (14,18). Glucocorticoids were given to 4 patients with no improvement. Pneumonectomy was successfully performed in 1 patient because of massive hemoptysis (40). Interferon α-2a was used in 4 patients with clinical improvement in 3, and in 1 was also followed by improved exercise tolerance and hemodynamic parameters (45–47). Pulmonary transplantation was done in 5 patients (5,9,10) without reproduction of the disease.

Back to Top | Article Outline

Discussion

Pulmonary capillary hemangiomatosis is a rare disease and an uncommon cause of primary pulmonary hypertension (30,33,41). To our knowledge, only 37 cases with primary pulmonary hypertension have been reported in the world literature. The diagnosis is difficult and requires a high degree of clinical suspicion and accurate pathologic study. Multiple sampling in pulmonary biopsy is essential given the patchy nature of the disease (19). Diagnosis was made with pulmonary biopsy in only 3 cases (2,35,45). The rest were wrongly classified as pulmonary fibrosis, pulmonary veno-occlusive disease, hemosiderosis, and other entities, and definitive diagnosis was reached only after pulmonary transplantation or necropsy.

Similar pathologic findings have been described in necropsies of patients without evidence of primary pulmonary hypertension. The significance of these findings is uncertain. We agree with Havlik et al (15) that PCH occurring in the absence of primary pulmonary hypertension should be considered as a nondiagnostic and incidental finding (1,15). However, patients with these findings should be followed closely since the natural history of the disease is not known. While long survival (up to 12 years) has been reported occasionally (11,37,39), most patients rapidly progress to death over several months of clinical disease (6,35).

Although most cases appear to be sporadic, 3 cases in a family have been described (23). Associations with other entities, including Takayasu arteritis (22), systemic lupus erythematosus (13), Kartagener syndrome (34), and hypertrophic myocardiopathy (20), have been described.

Signs of postcapillary pulmonary hypertension (Kerley B lines, transudative pleural effusion, or a high pulmonary artery wedge pressure) are absent in primary pulmonary hypertension. When hemoptysis or hemorrhagic pulmonary effusion, interstitial lung infiltrates, or signs of postcapillary pulmonary hypertension are present in the setting of primary pulmonary hypertension, both PCH and pulmonary veno-occlusive disease should be strongly considered. Exceptionally, all these signs can be absent (26,35). These findings are reminiscent of those described in pulmonary veno-occlusive disease (3,17,27), which is clinically indistinguishable from PCH. Occasionally, as in our first case, hemosiderin-laden macrophages may be seen in bronchoalveolar lavage and can be a helpful clue to diagnosis. The diagnosis of PCH is established by pulmonary biopsy. It has been stated that transbronchial biopsy should never be performed in this setting because of the high risk of bleeding. Nevertheless, in the 4 cases in whom it was done, included our first patient, no complications were reported (9,28,42).

As in pulmonary veno-occlusive disease, a normal pulmonary artery wedge pressure does not exclude PCH. This can occur because in the wedged position the catheter produces a static column of blood that extends beyond the pulmonary venules to the central pulmonary veins and left atrium. Because central pulmonary vein pressure is measured in this position, it may be normal in PCH (5,44,49).

Several hypotheses have been advanced to explain the presence of pulmonary hypertension in PCH. The most accepted is that proliferating vessels produce “in situ” thrombosis or vascular obliteration with pulmonary hypertension (12,16,38). Other hypotheses focus on local production of vasoconstrictor substances or changes due to pulmonary bleeding and scarring (11,19,26).

In our first patient PCH was associated with mechanical intravascular hemolysis. Rupture of erythrocytes is thought to be produced by their transit through the hemangiomatous vessels. This feature has been reported previously in other hemangiomatous diseases (45,47) but only exceptionally in primary pulmonary hypertension or pulmonary veno-occlusive disease (21,43). This is the first report in relation to PCH, to our knowledge.

There is no etiologic treatment for PCH. Supportive and symptomatic treatment with ACE inhibitors, diuretics, oxygen, and warfarin have been widely used without any measurable impact on the natural course of the disease, but may be considered in those patients with right heart failure. Corticosteroids have not been shown to be useful. Pneumonectomy was successfully performed in 1 patient with massive hemoptysis with no recurrence reported (40). Epoprostenol and other prostaglandins enhance hemodynamic parameters, quality of life, and survival in primary pulmonary hypertension (4), but in the setting of PCH, no benefit has been reported (7,13,24). In fact, worsening of hypoxemia, pulmonary edema, and 3 cases of death have been described in relation to epoprostenol administration (14,18). These data indicate that the use of prostaglandins should be avoided in PCH.

Interferon α-2a has been proposed as an attractive treatment. In 1 child treated with interferon α-2a, clinical improvement and histologic regression were documented after 30 months (45,46). These results were later confirmed by the same author in 2 other cases (47), while in a fourth case no apparent response was obtained (6). In another child with pulmonary cavernous hemangiomatosis, a tumoral variety of PCH, clinical and radiologic improvement was maintained after 2 years (50). The mechanism of action of interferon α-2a is not well understood. In vitro studies have shown both an inhibition of endothelial proliferation and migration, and an inhibition of endothelial growth factors (34,43,45). Although interferon inhibits fibrosis by acting in collagen synthesis of fibroblasts, regression of fibrotic areas surrounding hemangiomatous lesions should not be expected. Interferon is especially effective in inhibiting angiogenesis in those situations where rapid cellular turnover is present (hemangiomas, sarcomas, and others).

Interferon should be considered in the treatment of PCH along with supportive treatment. The potential benefit of α-interferon should encourage physicians to perform lung biopsies to confirm this diagnosis. Surgery should be kept in mind in cases of massive hemoptysis. Pulmonary transplantation was the only possible treatment before the implementation of interferon, and should be reserved for suitable nonresponders.

Back to Top | Article Outline

References

1. Ahmed Q, Chung-Park M, Tomashefski Jr. JF Cardiopulmonary pathology in patients with sleep apnea/obesity hypoventilation syndrome. Hum Pathol 28: 264–9, 1997.
2. Al-Fawaz IM, al-Mobaireek KF, al-Suhaibani M, Ashour M. Pulmonary capillary hemangiomatosis. A case report and review of the literature. Pediatr Pulmonol 19: 243–8, 1995.
3. Almagro P, Alvarez M, Garau J. Lung biopsy in pulmonary veno-occlusive disease. Chest 120: 1421–2, 2001.
4. Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH, Koerner SK, Langleben D, Keller CA, Murali S, Uretsky BF, Clayton LM, Jobsis MM, Blackburn SD, Shortino D, Crow JW. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The primary hypertension study group. N Engl J Med 334: 296–301, 1996.
5. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 21–1986. Recent development of pulmonary hypertension seven years after an aortic valve replacement. N Engl J Med 314: 1335–1445, 1986.
6. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 38–2000. A 45-year-old woman with exertional dyspnea, hemoptysis and pulmonary nodules. N Engl J Med 343: 1788–96, 2000.
7. Castro PF, Bourge RC, McGiffin DC, Benza RL, Fan P, Pinkard NB, McGoon MD. Intrapulmonary shunting in primary pulmonary hypertension: An observation in two patients treated with epopostrenol sodium. Chest 114: 334–6, 1998.
8. Cioffi U, De Simone M, Pavoni G, Poggi L, Pisani D, Ferrero S, Santambrogio L. Pulmonary capillary hemangiomatosis in an asymptomatic elderly patient. Int Surg 84: 168–70, 1999.
9. Domingo C, Encabo B, Roig J, Lopez D, Morera J. Pulmonary capillary hemangiomatosis: Report of a case and review of the literature. Respiration 59: 178–80, 1992.
10. Dufour B, Maitre S, Humbert M, Capron F, Simonneau G, Musset D. High-resolution CT of the chest in four patients with pulmonary capillary hemangiomatosis or pulmonary venooclusive disease. AJR Am J Roentgenol 171: 1321–4, 1998.
11. Eltorky MA, Headley AS, Winer-Muram H, Garrett Jr, HE Griffin JP. Pulmonary capillary hemangiomatosis: A clinicopathologic review. Ann Thorac Surg 57: 772–6, 1994.
12. Faber CN, Yousem SA, Dauber JH, Griffith BP, Hardesty RL, Paradis IL. Pulmonary capillary hemangiomatosis. A report of three cases and review of the literature. Am Rev Respir Dis 140: 808–13, 1989.
13. Fernandez-Alonso J, Zulueta T, Reyes-Ramirez JR, Castillo-Palma MJ, Sanchez-Roman J. Pulmonary capillary hemangiomatosis as cause of pulmonary hypertension in a young woman with systemic lupus erythematosus. J Rheumatol 26: 231–3, 1999.
14. Gugnani MK, Pierson C, Vanderheide R, Girgis R. Pulmonary edema complicating prostacyclin therapy in pulmonary hypertension associated with scleroderma. A case of pulmonary capillary hemangiomatosis. Arthritis Rheum 43: 699–703, 2000.
15. Havlik DM, Massie LW, Williams WL, Crooks LA. Pulmonary capillary hemangiomatosis-like foci. An autopsy study of 8 cases. Am J Clin Pathol 113: 655–62, 2000.
16. Heath D, Reid R. Invasive pulmonary haemangiomatosis. Br J Dis Chest 79: 284–94, 1985.
17. Holcomb Jr, BW Loyd JE, Ely EW, Johnson J, Robbins IM. Pulmonary veno-occlusive disease: A case series and new observations. Chest 118: 1671–9, 2000.
18. Humbert M, Maitre S, Capron F, Rain B, Musset D, Simonneau G. Pulmonary edema complicating continuous intravenous prostacyclin in pulmonary capillary hemangiomatosis. Am J Respir Crit Care Med 157: 1681–5, 1998.
19. Ishii H, Iwabuchi K, Kameya T, Koshino H. Pulmonary capillary haemangiomatosis. Histopathology 29: 275–8, 1996.
20. Jing X, Yokoi T, Nakamura Y, Nakamura M, Shan L, Tomimoto S, Hano T, Kakudo K. Pulmonary capillary hemangiomatosis: A unique feature of congestive vasculopathy associated with hypertrophic cardiomyopathy. Arch Pathol Lab Med 122: 94–6, 1998.
21. Jubelirer SJ. Primary pulmonary hypertension. Its association with microangiopathic hemolytic anemia and thrombocytopenia. Arch Intern Med 151: 1221–3, 1991.
22. Kakkar N, Vasishta RK, Banerjee AK, Singh S, Kumar L. Pulmonary capillary haemangiomatosis as a cause of pulmonary hypertension in Takayasu’s aortoarteritis. Respiration 64: 381–3, 1997.
23. Langleben D, Heneghan JM, Batten AP, Wang NS, Fitch N, Schlesinger RD, Guerraty A, Rouleau JL. Familial pulmonary capillary hemangiomatosis resulting in primary pulmonary hypertension. Ann Intern Med 109: 106–9, 1988.
24. Lippert JL, White CS, Cameron EW, Sun CC, Liang X, Rubin LJ. Pulmonary capillary hemangiomatosis: Radiographic appearance. J Thorac Imaging 13: 49–51, 1998.
Lynch DA, Hay T, Newell JD, Divgi VD, Fan LL. Pediatric diffuse lung disease: Diagnosis and classification using high-resolution CT. AJR Am J Roentgenol 173: 713–8, 1999.
    26. Magee FJ, Wright JL, Kay M, Peretz D, Donevan R, Churg A. Pulmonary capillary hemangiomatosis. Am Rev Respir Dis 132: 922–5, 1985.
    27. Mandel J, Mark EJ, Hales CA. Pulmonary veno-occlusive disease. Am J Respir Crit Care Med 162: 1964–73, 2000.
    28. Masur Y, Remberger K, Hoefer M. Pulmonary capillary hemangiomatosis as a rare cause of pulmonary hypertension. Pathol Res Pract 192: 290–5, 1996.
    29. Nakano H, Aizawa H, Inoue H, Takata S, Minami T, Hara N, Watanabe T, Sueishi K. [A case of pulmonary capillary hemangiomatosis. Nihon Kokyuki Gakkai Zasshi 39: 471–5, 2001.
    30. Pietra GG, Edwards WD, Kay JM, Rich S, Kernis J, Schloo B, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Levy PS, Reid LM, Vreim CE, Williams GW. 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 80: 1198–206, 1989.
    31. Pycock CJ, Thomas AJ, Marshall AJ, Scaratt W. Capillary haemangiomatosis: A rare cause of pulmonary hypertension. Respir Med 88: 153–5, 1994.
    32. Rowen M, Thompson JR, Williamson RA, Wood BJ. Diffuse pulmonary hemangiomatosis. Radiology 127: 445–51, 1978.
    33. Rubin LJ. Primary pulmonary hypertension. Chest 104: 236–50, 1993.
    34. Slodkowska J, Slupek A, Burakowski J, Bestry I, Filipecki S, Radomski P. [Kartagener syndrome and hemangiomatous proliferation of lung capillaries: Case report and literature review. Pneumonol Alergol Pol 64: 217–24, 1996.
    35. Slovis BS, Chazova I, Loyd JE, Meyrick BO. Pulmonary capillary haemangiomatosis coexistence with sinus venosus ASD: Morphometric analysis and literature review. Eur Respir J 12: 240–4, 1998.
    Stratte EG, Tope WD, Johnson CL, Swanson NA. Multimodal management of diffuse neonatal hemangiomatosis. J Am Acad Dermatol 34: 337–42, 1996.
      37. Takiguchi Y, Uruma T, Hiroshima K, Motoori K, Watanabe R, Hamaoka T, Okada O, Kimura H, Kuriyama T. Stable pulmonary capillary haemangiomatosis without symptomatic pulmonary hypertension. Thorax 56: 815–7, 2001.
      38. Tron V, Magee F, Wright JL, Colby T, Churg A. Pulmonary capillary hemangiomatosis. Hum Pathol 17: 1144–50, 1986.
      39. Vevaina JR, Mark EJ. Thoracic hemangiomatosis masquerading as interstitial lung disease. Chest 93: 657–9, 1988.
      40. Wagenaar SS, Mulder JJ, Wagenvoort CA, van den Bosch JM. Pulmonary capillary haemangiomatosis diagnosed during life. Histopathology 14: 212–4, 1989.
      41. Wagenvoort CA. Lung biopsy specimens in the evaluation of pulmonary vascular disease. Chest 77: 614–25. 1980.
      42. Wagenvoort CA, Beetstra A, Spijker J. Capillary haemangiomatosis of the lungs. Histopathology 2: 401–6, 1978.
      43. Waldhorn RE, Tsou E, Smith FP, Kerwin DM. Pulmonary venoocclusive disease associated with microangiopathic hemolytic anemia and chemotherapy of gastric adenocarcinoma. Med Pediatr Oncol 12: 394–6, 1984.
      44. Weed HG. Pulmonary “capillary” wedge pressure not the pressure in the pulmonary capillaries. Chest 100: 1138–40, 1991.
      45. White CW. Treatment of hemangiomatosis with recombinant interferon alfa. Semin Hematol 27(Suppl 4): 15–22, 1990.
      46. White CW, Sondheimer HM, Crouch EC, Wilson H, Fan LL. Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med 320: 1197–1200, 1989.
      47. White CW, Wolf SJ, Korones DN, Sondheimer HM, Tosi MF, Yu A. Treatment of childhood angiomatous diseases with recombinant interferon alfa-2a. J Pediatr 118: 59–66, 1991.
      48. Whittaker JS, Pickering CA, Heath D, Smith P. Pulmonary capillary haemangiomatosis. Diagn Histopathol 6: 77–84, 1983.
      49. Wiedemann HP. Wedge pressure in pulmonary veno-occlusive disease. N Engl J Med 315: 1233, 1986.
      50. Wu JM, Lin CS, Wang JN, Luo CY, Yu CY, Yang HB. Pulmonary cavernous hemangiomatosis treated with interferon alfa-2a. Pediatr Cardiol 17: 332–4, 1996.

      Cited By:

      This article has been cited 1 time(s).

      Medicine
      Pulmonary Veno-Occlusive Disease: Clinical, Functional, Radiologic, and Hemodynamic Characteristics and Outcome of 24 Cases Confirmed by Histology
      Montani, D; Achouh, L; Dorfmüller, P; Le Pavec, J; Sztrymf, B; Tchérakian, C; Rabiller, A; Haque, R; Sitbon, O; Jaïs, X; Dartevelle, P; Maître, S; Capron, F; Musset, D; Simonneau, G; Humbert, M
      Medicine, 87(4): 220-233.
      10.1097/MD.0b013e31818193bb
      PDF (2870) | CrossRef
      Back to Top | Article Outline
      © 2002 Lippincott Williams & Wilkins, Inc.