Pulmonary Vasculitis in Behçet Disease

reviews Pulmonary Vasculitis in Behc¸et Disease* A Cumulative Analysis Og˘uz Uzun, MD; Tekin Akpolat, MD; and Levent Erkan, MD

Study objectives: The aims of this study were to investigate the frequency of pulmonary problems in Behc¸et disease (BD), and to discuss lesser-known features of pulmonary BD such as clinical characteristics, analysis of prognosis, and evaluation of treatment options with respect to the previously published cases. Design: We conducted a comprehensive review of the literature to analyze cumulated data about pulmonary involvement in BD. Setting: We found 159 articles regarding pulmonary disease associated with BD in May 2003. Patients: The evaluation of these articles demonstrated 598 pulmonary problems in 585 cases. Results: Pulmonary artery aneurysms (PAAs) are the most common pulmonary lesion in BD, and these are almost always associated with hemoptysis. Seventy-eight percent of patients with aneurysms have concomitant extrapulmonary venous thrombi or thrombophlebitis. Other pulmonary problems are reported in BD, and these are principally related to vascular lesions and radiologic abnormalities. Conclusions: Pulmonary vascular problems, either PAA or involvement of small-sized vessels, are the main pulmonary disorders in BD. Immunopathologic findings indicate that the underlying pathogenesis is pulmonary vasculitis, which may result in thrombosis, infarction, hemorrhage, and PAA formation. Patients with small nonspecific radiologic abnormalities should be followed up closely since early diagnosis of vascular lesions may be life-saving. Immunosuppression is the main therapy for the treatment of a vasculitis. It is important that pulmonary angiitis is not mistaken for pulmonary thromboembolic disease since fatalities have occurred in BD shortly after initiation of anticoagulation/thrombolytic treatment. (CHEST 2005; 127:2243–2253) Key words: anticoagulation; Behc¸et disease; immunosuppression; pulmonary artery aneurysm; pulmonary thromboembolic disease; vasculitis Abbreviations: BD ⫽ Behc¸et disease; ISG ⫽ International Study Group; PAA ⫽ pulmonary artery aneurysm; PTE ⫽ pulmonary thromboembolic

¸ et disease (BD) is a multisystem disorder B ehc characterized by vasculitis first described by Hulusi Behc¸et in 1937,1 and consists of a triad of recurrent ulcers of the oral and genital mucosa with relapsing uveitis. Since its first description, involve*From Departments of Pulmonary Medicine (Drs. Uzun and Erkan) and Internal Medicine (Dr. Akpolat), Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey. Manuscript received April 6, 2004; revision accepted December 1, 2004. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Og˘uz Uzun, MD, 19 Mayıs Universitesi, Tıp Fak, Go¨g˘u¨s Hst. ABD 55139, Kurupelit-Samsun, Turkey; e-mail: [email protected] www.chestjournal.org

ment of other organs has been described. Skin, CNS, GI, and pulmonary involvements are among those reported. Subcutaneous thrombophlebitis, deep vein thrombosis, epididymitis, arterial occlusion, and/or aneurysms, arthralgia, arthritis, family history, and renal problems are other features of BD.2–10 Several types of pulmonary problems associated with BD have been defined, and these problems can be classified into three groups (1) pulmonary artery aneurysm (PAA), (2) pulmonary parenchymal changes, and (3) a miscellany including pulmonary artery occlusion, pleural effusion, and pulmonary obstructive airway disease, et al (Table 1).11–131 Almost all the articles describing pulmonary complications of BD are presented as “case reports.” There CHEST / 127 / 6 / JUNE, 2005

2243

Table 1—Cumulative Analysis of Patients With BD and Pulmonary Problems* Type of Pulmonary Involvement PAA Pulmonary parenchymal changes and other pulmonary problems Vascular-related problems Perfusion defect on lung scintigraphy Pulmonary hemorrhage and/or infarction Pulmonary vasculitis Hemorrhagic fibrous tissue Pulmonary artery occlusion Pulmonary embolism Arteriovenous shunt in the right lung Aneurysmal fistula from left main coronary artery to the pulmonary artery Radiologic abnormalities Infiltration on chest radiographic or chest CT (including nodular, reticulonodular lesions) Wedge-shaped, linear, or rounded opacity on chest radiography, CT or angiography Cavitary lesion Unilateral hyperlucent lung Pulmonary mass lesion Hilar enlargement Diaphragmatic elevation Apical tuberculoma-like opacification Infection, immunosuppressive related Pneumonia Pulmonary tuberculosis Pulmonary fungal infection P carinii pneumonia Other/possible unrelated Pleural effusion or adhesion Abnormal pulmonary function finding or chronic obstructive airway disease Bronchial stenosis Lung cancer Pulmonary fibrosis or alveolitis Eosinophilic pneumonia Fibrous mediastinitis Amyloidosis Bronchiolitis obliterans organised pneumonia Pulmonary involvement not specified Total

Cases, No. 201

References 2, 4, 11–82, 87, 100, 122, 128, 131

34 11 5 1 10 33 1 1

22, 50, 85 39, 65, 83, 89, 92, 101, 122, 128 65, 83, 90, 94, 98 91 2, 20, 81 38, 46, 53, 55, 59, 65, 88, 89, 105, 118, 130 84 119

15

22, 50, 59, 84, 96, 97, 99, 103, 107, 108, 127

9

22, 50, 107

5 1 1 4 1 1

22, 45, 86, 108 39 83 50, 108 107 108

1 5 4 1

95 17, 34, 47, 98, 122 55, 86, 93 114

31 18 1 1 5 1 1 1 1 193 598

4, 22, 43, 46, 50, 59, 70, 89, 106–108, 110, 111, 129, 130 107, 112–117 120 121 101, 104, 108, 109 89 130 102 24 87, 123–126, 128, 129

*Table 1 excludes reference 8 (Japanese Autopsy Registry data). When there is a histologic diagnosis, it is used to describe to the present abnormality.

are a few articles100,132–134 reporting case series, but the number of cases in these articles are small and pulmonary problems associated with BD have been reviewed rarely. In a review8 of 170 Japanese BD cases at autopsy, 127 patients (75%) had pulmonary lesions, and pneumonia (n ⫽ 66) and pulmonary edema (n ⫽ 29) were the most common lesions. Other pathologically defined pulmonary lesions were pleuritis/pleural effusion (n ⫽ 9), lung abscess (n ⫽ 6), pulmonary tuberculosis, empyema, bronchitis, fibrosis, hemorrhage, emphysema, alveolitis, thrombosis, and infarction. One patient had carcinoma of the lung. 2244

There was no information about the clinical characteristics of the patients with pulmonary problems, and detailed descriptions of histopathologic examination findings have not been reported. Although the frequency of pulmonary lesions is high in this study, the specificities of these lesions are questionable, as mentioned by the authors.8 Current data regarding the frequency of pulmonary problems and their specificity need further investigation. The frequency of pulmonary problems shows a wide variation, from ⬍ 1 to 18%.123,126,135,136 A cumulative analysis of published cases/reports/ studies to evaluate the clinical characteristics, progReviews

nosis, and treatment of patients with pulmonary BD has not previously been conducted. The aims of this study were to investigate frequency of the pulmonary problems in BD, and to discuss lesser-known features of pulmonary BD, such as clinical characteristics, prognosis, and evaluation of treatment options with respect to the previously published cases. Materials and Methods We conducted a comprehensive review of the literature to analyze cumulated data about pulmonary involvement in BD. The PubMed database was searched for articles using the term BD combined with one of the following terms: pulmonary artery, lung, pulmonary involvement, and pleura. Pertinent articles cited as references in the identified articles also were reviewed. These articles were in English, French, Spanish, Japanese, German, Portuguese, Polish, Italian, Romanian, and Turkish; only articles in English are included. We found 159 articles regarding pulmonary disease associated with BD in May 2003, and we could obtain 141 of these articles in our university library. Some of these articles are not directly related to pulmonary problems. Review of these articles highlighted 598 pulmonary problems in 585 cases, and 392 of these cases had clinical data available for evaluation (Table 1). The cases with available clinical data were investigated for the following: (1) clinical characteristics of extrapulmonary manifestations, and the association between extrapulmonary and pulmonary manifestations; (2) the presence of extrapulmonary manifestations for the diagnosis of BD based on the International Study Group (ISG) criteria137 at the presentation time or thereafter (if reported); (3) pulmonary complaints at the time of presentation or during the disease course; (4) the procedures used for the investigation, diagnosis, or confirmation of pulmonary disease; and (5) the treatment modalities that have been used, the success of these treatments, and the prognosis of BD and pulmonary involvement. Patients not fulfilling the diagnostic criteria of the ISG for BD (oral ulceration plus two of the following: genital ulceration, skin involvement, ocular involvement, or positive pathergy test result),137 but reported as BD by the authors were included in the study. Statistics Mann-Whitney U test and ␹2 test with Yates correction were used for statistical analysis. The Kaplan-Meier technique was used to assess survival rates (cases diagnosed by necropsy were excluded, and the time of the last visit was accepted as the final date for the “lost-to-follow-up” time) of patients with BD and PAA.

PAA Clinical characteristics and symptoms of patients with BD and PAA are shown in Tables 2, 3. The mean age of these patients was 30.1 years (range, 10 to 59 years), and 89% of the patients were male. Twenty-nine patients did not fulfill the ISG criteria for the diagnosis of BD at the time of presentation or thereafter. BD and PAA were diagnosed at the same time in 25 patients, and 9 patients did not have sufficient criteria for the diagnosis of BD. PAA was the only accepted manifestation of BD in two cases. The mean interval between the diagnosis of BD and the manifestation of PAA was 5.5 years (range, 6 months to 26 years) among the patients in whom PAA was not the initial manifestation. This interval was significantly shorter in female than in male patients (3.3 years vs 6.1 years, p ⬍ 0.01). Venous thrombosis or subcutaneous thrombophlebitis were common in these patients (78%). Nearly all the patients with PAA had hemoptysis. The diagnostic procedures used for the diagnosis or confirmation of diagnosis of PAA are shown in Table 4. PAA involved one branch of the pulmonary artery in 21 patients, multiple branches in 87 patients, and was found in both lungs in 61 patients. Figure 1 shows cumulative survival of patients with PAA; 1-year and 5-year survival rates were 57% and 39%, respectively. Discussion The first case with BD-associated pulmonary problems was published in 1959.109 Thereafter, many cases with different pulmonary diseases/problems have been reported. Many of these studies cite case reports published before 1937, the description year of BD. The frequency of pulmonary problems shows a wide variation, from ⬍ 1 to 18% (Table 5).123,126,135,136 Pulmonary disorders in BD are one of the most common direct causes of death.145 Although many patients with BD and pulmonary

Table 2—Clinical Features of Patients With BD and PAA

Results

Clinical Features

%

Our findings are presented in two parts: PAA and pulmonary parenchymal changes/other problems. The distinction between pulmonary parenchymal changes and other problems is difficult in most of the cases. Since the specificity of pulmonary parenchymal changes/other problems is not clear and in order to avoid repetition, the data are presented in the “Discussion.”

Oral ulceration Genital ulceration Skin involvement Ocular involvement Pathergy test Arthritis/arthralgia Vascular involvement Human leukocyte antigen-B(51)5 Cranial involvement

94 90 79 46 82 95 78 53 8

www.chestjournal.org

CHEST / 127 / 6 / JUNE, 2005

2245

Table 3—Symptoms of Patients With BD and PAA Symptoms

%

Hemoptysis Massive hemoptysis Chest pain Dyspnea Fever Cough Weight loss Pleural chest pain Sputum Fatigue

93 26 21 19 19 14 11 6 2 1

problems have been presented in the literature, a cumulative analysis of these cases has not previously been done. This study includes nearly 90% of the published cases. It should be kept in mind that this cumulative analysis includes only the reported cases. In addition, the reported cases could have special or uncommon manifestations. In spite of these limitations and disadvantages, this study analyzes current knowledge about pulmonary problems in BD, investigates the types and clinical characteristics of these problems, and discusses treatment options. PAA PAA is the most common type of pulmonary involvement in BD. Since vascular involvement in BD is more frequent among male patients,4 male gender is a risk factor for PAA. Hemoptysis is the most common symptom of PAA. PAAs may be single or multiple, unilateral or bilateral, true or false. PAAs can be complicated by bronchopulmonary artery fistulas.59,61,68 The striking clinical feature of patients with PAA is the presence of other large extrapulmonary vessel lesions, including deep and subcutaneous venous thrombi and arterial aneurysms and/or occlusions. The relationship between vascular involvement and PAA in BD has rarely been reported.43,65 The present cumulative analysis includes cases from

Table 4 —Diagnostic Procedures Used for the Evaluation, Diagnosis, or Confirmation of PAA* Diagnostic Procedures

No.

Thorax CT Angiography Scintigraphy Pathologic examination Bronchoscopy Thorax MRI/magnetic resonance angiography Echocardiography Post-mortem

107 58 36 25 12 11 12 9

*More than one diagnostic procedure was used in some cases. 2246

many countries/regions, and it shows that other large extrapulmonary vascular lesions are common among patients with BD and PAA (78%). Studies performed in Turkey (n ⫽ 2,147),9 Iran (n ⫽ 3,153),87 Japan (n ⫽ 3,316),135 and Europe (n ⫽ 714)146 have shown that the frequencies of vascular involvement (including PAAs) in BD were 17%, 9%, 9%, and 10 to 37%, respectively. The frequency of large extrapulmonary vessel injury is significantly higher in BD patients with PAA than those without PAA if we compare our finding with these studies that also include PAA (␹2 ⬎ 10, p ⬍ 0.01 for all comparisons). PAA of one the causes of deaths in BD.43,147 Hamuryudan et al43 reported that 12 of 24 patients (50%) died after an average of 10 months after the onset of hemoptysis. Figure 1 clearly demonstrates the poor prognosis of patients with PAA, and most of the deaths occurred within the first months after diagnosis. A variety of treatment modalities, such as surgery, immunosuppression, anticoagulation, or embolization, have been used in the management of PAA, and original and review articles43,132,134 recommend immunosuppression combined with embolization, surgery, anticoagulation, or low-dose antiplatelet treatment. There are no randomized controlled studies to evaluate treatment options, and these recommendations have been based on nonrandomized trials or observational studies. In order to evaluate the effect of different therapies, we roughly categorized the patients into five groups, and the prognosis and outcome of the patients based on these groups are shown in Figure 2. The interpretation of Figure 2 has some drawbacks and may lead to bias: drug doses are not the same, immunosuppressive agents are different, surgery is used for some of the severe cases in emergency situations, and many cases with bad outcome may have been underreported. The patients are classified into five groups in Figure 2, and immunosuppression was part of the treatment regime of some patients in each group. The main difference between groups II and III, and groups I and IV is the use of anticoagulation in groups III and IV (Fig 2). The comparisons of group II with group III and group I with group IV demonstrate a bad outcome in the groups in which the patients received anticoagulation. The patients treated with embolization with or without immunosuppression have a better prognosis, and the patients who underwent surgery with or without immunosuppressive therapy had the highest mortality rate. Aneurysmorrhaphy, lobectomy, bilobectomy, pleurectomy, aneurysmectomy, and pneumonectomy are surgical procedures that have been used in the management of BD. Since bilateral localization of PAAs is common, it is possible to explain some deaths after lobectomy. Lobectomy increases pulmoReviews

Figure 1. Cumulative survival of patients with BD disease and PAA.

nary artery pressure at the remaining sites, which may aggravate PAA-related hemoptysis and cause death. Besides, surgery may have been performed because of severe and life-threatening conditions in some cases. Thrombi within PAA are common. Total or partial occlusion of pulmonary arteries are shown in ⬎ 100 PAA cases. In addition, Tunaci et al27 demonstrated mural thrombotic changes during regression of PAAs. Perfusion defects on lung scintigraphy can be diagnosed as pulmonary thromboembolic (PTE), disease and the treatment of PTE disease is mainly anticoagulation. Anticoagulation of some patients caused worsening of hemoptysis36,43,57,59,62,68 or even death,43,44,65 and it has been recommended to use anticoagulation only after immunosuppression.132,134 It is reasonable to avoid use of anticoagulation because, in general, thrombi being organized are firmly adherent to the vascular lumens.43 Based on these findings, we believe that the main problem is inflammation in pulmonary arteries and recommend immunosuppression and embolization (in the presence of massive hemoptysis) in the management of PAAs. The indication of anticoagulation is questionable since thrombi are generally organized. Diagnosis of small PAAs are important and critical since such lesions may have a better outcome and immunosuppression is the only required treatment. Therefore, PAA should be diagnosed or ruled out immediately in patients with hemoptysis. The diagnosis of www.chestjournal.org

small PAAs, however, is difficult. CT of the chest and angiography are the most common diagnostic procedures used in the diagnosis or evaluation of PAAs. Initial diagnostic techniques should be MRI/angiography and spiral/helical CT since venous puncture, IV infusion, and arterial puncture can lead to vascular problems in BD131,148 and complications related to radiologic procedures in the evaluation of PAAs have been reported.38 The presence of 29 patients not meeting the ISG criteria for the diagnosis of BD or having PAA as the initial manifestation of BD is a complicated issue. The differential diagnosis of PAA includes HughesStovin syndrome, now accepted as a manifestation of BD,68,69 pulmonary hypertension, trauma, mycotic aneurysms, and polyarteritis nodosa. It seems that none of the 29 reported patients had findings compatible with these diseases. The acceptance of these patients as BD by the authors requires interrogation of the diagnostic criteria of ISG. The inclusion of PAAs to the diagnostic criteria of ISG needs further investigation. Pulmonary Parenchymal Disease and Other Problems Table 1 shows pulmonary parenchymal changes and other pulmonary problems reported with BD, but the relationship between these problems and BD has not been evaluated systematically. VascularCHEST / 127 / 6 / JUNE, 2005

2247

Table 5—Frequency of Pulmonary Problems in BD Source

Country

Benamour et al138 Chajek and Fainaru97

Morocco Israel, review of published cases

Assaad Khalil122 Sanchez et al139 Sharquie et al140 Dils¸en et al123 Kaklamani et al3 Du¨ndar et al124 Du et al125 Gurler et al87 Oshima et al136 Shahram et al135 Valesini et al126 Madanat et al141 Pande et al127 Kone-Paut et al128 Mousa et al129 al-Aboosi et al88 al-Dalaan et al46 Saba et al78 Hamuryudan et al43 Raz et al59 Zouboulis7 Chung et al142 Bang et al143 Alekberova et al144

Egypt Spain Iraq Turkey Greece Turkey France Turkey Japan Iran Italy Jordan India International Kuwait Jordan Saudi Arabia Turkey Turkey Israel Europa Taiwan Korea Russia

Patients With BD, No.

Frequency of Pulmonary Involvement, %

285 41 683 180 30 58 496 64 200 250 2,147 65 3,153 155 150 58 86 29 20 119 534 2,179 72 14 103 1,527 35

3 2 Not mentioned 10 3 5 18 2 8 16 1 0 ⬍1 18 9 2 7 7 5 15 1 1* 9 0–17 3 Not mentioned 3

*Frequency of PAA.

related problems and radiologic abnormalities are the most common pulmonary parenchymal changes reported. Most of these radiologic abnormalities (such as infiltration, opacity, mass lesion, hilar enlargement) have been detected mainly by chest radiography or thorax CT, and further investigation of these abnormalities have not been reported. Infiltration and wedge-shaped, linear, or rounded opacity on a chest radiograph or CT are the most common radiologic abnormalities. These radiologic abnormalities (mass lesion, hilar enlargement, wedge-shaped, linear, or rounded opacities) are probably caused by PAA or other vascular problems. Rupturing of an aneurysm into a respiratory tract can be seen as infiltration on a chest radiograph or CT. Wedge-shaped, linear, or rounded lesions or cavities that are characteristic for infarction can be caused by thrombosis of small or medium-sized pulmonary arteries. Pulmonary infarct and hemorrhage are common vascular problems. Balduin et al92 reported a 31year-old man without any pulmonary symptoms. A thoracic CT demonstrated three opacities and a fourth nodular formation. One of the masses was sampled by needle biopsy, and a histologic study showed an infarct. Tu¨zu¨n et al83 also reported a 2248

similar case, a mass detected by a chest radiograph and CT. Pathologic examination of this lesion revealed a large area of infarction. The involved pulmonary artery showed signs of vasculitis with thrombus formation. The airspace consolidation seen on a chest radiograph or CT was diagnosed as infarction or hemorrhage in two cases.39 These case reports describing pulmonary hemorrhage and/or infarction lend credence to the notion that many of the above-mentioned radiologic abnormalities have a vascular basis. There are 33 cases reported with a diagnosis of pulmonary emboli. Clinical information has not been reported in most of the cases. Fever, which supports vasculitis rather than classical PTE disease, was reported in two cases.53,55 Treatment modalities among reported patients include anticoagulation/ thrombolysis and immunosuppression (steroids, azathioprine, cyclophosphamide, cyclosporine). In general, the outcome of patients treated with anticoagulation/thrombolysis was poor, like PAA, but a patient treated with urokinase and immunosuppression survived ⬎ 2 years.118 Pulmonary artery occlusion in BD differs from classic PTE disease since these occlusions mostly represent in situ thrombi complicating an underlying vasculitis rather Reviews

Figure 2. Cumulative survival of patients with BD and PAA according to treatment group. Group I: embolization with or without immunosuppression (n ⫽ 8); group II: immunosuppression (n ⫽ 36); group III: anticoagulation with or without immunosuppression (n ⫽ 5); group IV: embolization and immunosuppression and anticoagulation (n ⫽ 3); group V: surgery with or without immunosuppression (n ⫽ 19).

than emboli. Therefore, a single mismatched defect on ventilation/perfusion scintigraphy should not be diagnosed as pulmonary embolism in a patient with BD. In addition, there are many case reports with PAA and perfusion defects on lung scintigraphy. The interpretation of lung scintigraphy is questionable in BD. There are two studies22,85 investigating the role of lung scintigraphy in BD. One of these studies85 showed prolonged lung retention indexes of 123Imeta-iodobenzylguanidine in patients without previously reported pulmonary involvement, and the other study22 showed bilateral segmental or nonsegmental perfusion defects after IV injection of 74 Megabecquerel of 99Tcm-macroaggregated albumin in all of the patients with pulmonary involvement. No perfusion defect was observed in patients without pulmonary involvement. The role of scintigraphy in the early diagnosis of pulmonary involvement needs to be clarified. Pulmonary artery occlusion without PAA was reported in 10 cases.2,20,81 Arteriovenous shunts in the right lung and a convoluted fistula from left main coronary artery to the pulmonary artery are two other vascular pathologies that have been reported.84,119 In one of these reports, the patient had arteriovenous shunts treated by high-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation.84 www.chestjournal.org

Hemorrhagic fibrous tissue was detected in the microscopic evaluation of a rounded opacity in a 53 year-old woman.91 Bronchoscopy showed ulceration of the bronchial mucosa. Immunosuppressive treatment resulted in symptomatic improvement. Pulmonary fibrosis or alveolitis have been reported in five cases.101,104,108,109 A histologic examination was available in three patients, and fibrotic changes were demonstrated by a chest radiograph in the remaining two patients.108 Histologic examination did not show any vascular changes in two cases,104,109 which indicates the presence of pulmonary lesions not related to vascular bed in BD, but fibrosis or alveolitis may be secondary inflammatory responses to infarction or hemorrhage. Pulmonary vasculitis (arteritis or venulitis) without PAA was reported in five cases,65,83,90,94,98 and immunofluorescence microscopy revealed prominent granular staining of the walls of occasional small veins for IgG, C3, and C4 in one patient.94 Significant perivascular adventitial fibrosis also occurs around elastic and muscular pulmonary arteries showing evidence of injury and is believed to be derived from repeated bouts of angiitis-inflicted injury.68 Bronchial stenosis was reported in one patient who had endobronchial granulomatosis and aphthous ulceration in the bronchial mucosa.120 The CHEST / 127 / 6 / JUNE, 2005

2249

patient was treated with Nd-YAG laser resection, immunosuppression, and balloon dilation. Tatsis et al112 reported the results of many parameters reflecting lung functions in 14 nonsmoking and asymptomatic patients. Physiologic dead space ventilation increased in 10 patients, which suggests the major problem with the lungs in BD is that of an obstructive pattern. Mild restrictive lung disease,113 mild small airway disease,113 chronic bronchitis and bronchiectasia,114 reversible airway obstruction,116 emphysema,107,116 and obstructive lung disease117 are other bronchial problems. The patient with chronic bronchitis and bronchiectasia also had Pneumocystis carini pneumonia. In addition, Gibson et al115 reported a patient who died because of severe and irreversible airflow obstruction. The clinical significance of abnormal lung function results in patients with BD needs further investigation. Pleural effusion can be transudative, exudative, or chylous. Pleural problems are isolated or with an another disease (PAA, venous thrombi [subclavian vein, superior vena cava]). Pericardial effusion may accompany. Pneumothorax may complicate. Pleural vasculitis has been reported in three patients.89 Table 1 indicates that most of the pulmonary problems are associated with vascular involvement. Pulmonary problems such as fibrosis and alveolitis that are not associated with vascular involvement have rarely been reported. The association between BD with infection, obstructive airway disease, or lung cancer needs further investigation. In conclusion, pulmonary vascular problems, either PAA or involvement of small-sized vessels, are the main pulmonary disorders in BD. Immunopathologic findings indicate that the underlying pathogenesis is a pulmonary vasculitis that may result in thrombosis, infarction, hemorrhage, and PAA formation. References 1 Behc¸et H. Uber rezidivierende aphthose, durch ein virus verursachte Geschwure am Mund, am Auge und an den Genitalien. Dermatol Woschenschr 1937; 105:1152–1157 2 Shimizu T, Ehrlich GE, Inaba G, et al. Behc¸et’s disease (Behc¸et’s syndrome). Semin Arthritis Rheum 1979; 8:223– 260 3 Kaklamani VG, Vaiopoulos G, Kaklamanis PG. Behc¸et’s disease. Semin Arthritis Rheum 1998; 27:197–217 4 Koc¸ Y, Gu¨llu¨ I˙, Akpek G, et al. Vascular involvement in Behc¸et‘s disease. J Rheumatol 1992; 19:402– 410 5 Akpolat T, Koc¸ Y, Yeniay I˙, et al. Familial Behc¸et’s disease. Eur J Med 1992; 1: 391–395 6 Yurdakul S, Hamuryudan V, Yazici H. Behcet’s syndrome. Curr Opin Rheumatol 2004; 16:38 – 42 7 Zouboulis CC. Epidemiology of Adamantiades-Behc¸et’s disease. Ann Med Interne 1999; 150:488 – 498 8 Lakhanpal S, Tani K, Lie JT, et al. Pathologic features of Behc¸et’s syndrome: a review of Japanese Autopsy Registry 2250

Data. Hum Pathol 1985; 16:790 –795 9 Sakane T, Takeno M, Suzuki N, et al. Behcet’s disease. N Engl J Med 1999; 341:1284 –1291 10 Akpolat T, Akkoyunlu M, Akpolat I, et al. Renal Behc¸et’s disease: a cumulative analysis. Semin Arthritis Rheum 2002; 31:317–337 11 Houman M, Ksontini I, Ben Ghorbel I, et al. Association of right heart thrombosis, endomyocardial fibrosis, and pulmonary artery aneurysm in Behcet‘s disease. Eur J Intern Med 2002; 13:455– 457 12 Duzgun N, Anil C, Ozer F, et al. The disappearance of pulmonary artery aneurysms and intracardiac thrombus with immunosuppressive treatment in a patient with Behcet’s disease. Clin Exp Rheumatol 2002; 20(suppl):S56 –S57 13 Cohle SD, Colby T. Fatal hemoptysis from Behcet’s disease in a child. Cardiovasc Pathol 2002; 1:296 –299 14 Mahendran C, Singh P, Mani NB, et al. Successful treatment of pulmonary artery aneurysms secondary to possible Behcet’s disease. Respiration 2002; 69:355–358 15 Aksu K, Kocanaogulları H, Keser G, et al. A case of Behcet’s disease with pulmonary arterial aneurysm and secondary amyloidosis. Rheumatology 2002; 41:831– 832 16 Ozcan H, Aytac SK, Yagmurlu B, et al. Color Doppler examination of a regressing pulmonary artery pseudoaneurysm due to Behcet disease. J Ultrasound Med 2002; 21:697–700 17 Cantasdemir M, Kantarci F, Mihmanli I, et al. Emergency endovascular management of pulmonary artery aneurysms in Behcet‘s disease: report of two cases and a review of the literature. Cardiovasc Intervent Radiol 2002; 25:533–537 18 Bozkurt AK. Embolisation in Behcet’s disease. Thorax 2002; 57:469 – 470 19 Aktogu S, Erer OF, Urpek G, et al. Multiple pulmonary arterial aneurysms in Behcet‘s disease: clinical and radiologic remission after cyclophosphamide and corticosteroid therapy. Respiration 2002; 69:178 –181 20 Adler OB, Rosenberger A. Vascular aspects of Behcet’s disease: case presentations and review of the literature. Ann Radiol 1984; 143:343–345 21 Acican T, Gurkan OU. Azathiopine-steroid combination therapy for pulmonary arterial aneurysms in Behcet’s disease. Rheumatol Int 2001; 20:171–174 22 Caglar M, Ergun F, Emri S. 99Tcm-MAA lung scintigraphy in patients with Behcet’s disease: its value and correlation with clinical course and other diagnostic modalities. Nucl Med Commun 2000; 2:171–179 23 Filiz A, Dikensoy O. Lethal aneurysm formation of pulmonary arteries in a woman with Behcet‘s disease. Rheumatology 2000; 39:222–224 24 Gul A, Yilmazbayhan D, Buyukbabani N, et al. Organizing pneumonia associated with pulmonary artery aneurysms in Behcet’s disease. Rheumatology 1999; 38:1285–1289 25 Berkan O, Ozturkcan S, Dogan K, et al. Pulmonary arterial aneurysm in Behcet‘s disease. J Eur Acad Dermatol Venereol 1999; 13:140 –141 26 Celenk C, Celenk P, Akan H, et al. Pulmonary artery aneurysms due to Behcet’s disease: MR imaging and digital subtraction angiography findings. AJR Am J Roentgenol 1999; 172:844 – 845 27 Tunaci M, Ozkorkmaz B, Tunaci A, et al. CT findings of pulmonary artery aneurysms during treatment for Behcet‘s disease. AJR Am J Roentgenol 1999; 172:729 –733 28 Basoglu T, Canbaz F, Bernay I, et al. Bilateral pulmonary artery aneurysms in a patient with Behcet syndrome: evaluation with radionuclide angiography and V/Q lung scanning. Clin Nucl Med 1998; 23:735–738 29 Greene RM, Saleh A, Taylor AK, et al. Non-invasive assessReviews

30

31 32 33 34 35

36 37

38 39 40 41 42 43 44 45 46 47

48

49 50 51

ment of bleeding pulmonary artery aneurysms due to Behcet disease. Eur Radiol 1998; 8:359 –363 Berkmen T. MR angiography of aneurysms in Behcet disease: a report of four cases. J Comput Assist Tomogr 1998; 22:202–206 Malik KJ, Weber SL, Sohail S, et al. Hilar mass and papilledema on presentation. Chest 1998; 113:227–229 Lacombe P, Qanadli SD, Jondeau G, et al. Treatment of hemoptysis in Behcet syndrome with pulmonary and bronchial embolization. J Vasc Interv Radiol 1997; 8:1043–1047 Roguin A, Edoute Y, Milo S, et al. A fatal case of Behcet’s disease associated with multiple cardiovascular lesions. Int J Cardiol 1997; 59:267–273 Tuzun H, Hamuryudan V, Yildirim S, et al. Surgical therapy of pulmonary arterial aneurysms in Behcet‘s syndrome. Ann Thorac Surg 1996; 61:733–735 de Montpreville VT, Macchiarini P, Dartevelle PG, et al. Large bilateral pulmonary artery aneurysms in Behcet’s disease: rupture of the contralateral lesion after aneurysmorrhaphy. Respiration 1996; 63:49 –51 Mouas H, Lortholary O, Lacombe P, et al. Embolization of multiple pulmonary arterial aneurysms in Behcet‘s disease. Scand J Rheumatol 1996; 25:58 – 60 Park JY, Park JG, Won JH, et al. Effects of corticosteroid and chlorambucil on multiple pulmonary artery aneurysms in Behcet’s syndrome: a case report. J Korean Med Sci 1995; 10:470 – 473 Le Thi Huong D, Wechsler B, Papo T, et al. Arterial lesions in Behcet‘s disease: a study in 25 patients. J Rheumatol 1995; 22:2103–2113 Ahn JM, Im JG, Ryoo JW, et al. Thoracic manifestations of Behcet syndrome: radiographic and CT findings in nine patients. Radiology 199; 194:199 –203 Uh S, Kim JO, You YK, et al. A case of Behcet’s disease combined with pulmonary artery aneurysm in a Korean female patient. Korean J Intern Med 1994; 9:47–50 Numan F, Islak C, Berkmen T, et al. Behcet disease: pulmonary arterial involvement in 15 cases. Radiology 1994; 192:465– 468 Gokcora N, Ilgin N, Isik S, et al. Behcet‘s disease: aggressive pulmonary involvement. Int J Dermatol 1994; 33:131–132 Hamuryudan V, Yurdakul S, Moral F, et al. Pulmonary arterial aneurysms in Behcet’s syndrome: a report of 24 cases. Br J Rheumatol 1994; 33:48 –51 Winer-Muram HT, Headley AS, Menke P, et al. Radiologic manifestations of thoracic vascular Behcet‘s disease in African-American men. J Thorac Imaging 1994; 9:176 –179 Puckette TC, Jolles H, Proto AV. Magnetic resonance imaging confirmation of pulmonary artery aneurysm in Behcet’s disease. J Thorac Imaging 1994; 9:172–175 al-Dalaan AN, al Balaa SR, el Ramahi K, et al. Behcet’s disease in Saudia Arabia. J Rheumatol 1994; 21:658 – 661 Ko¨se AA, Kayabalı M, Sarıca R, et al. G. Pulmonary artery involvement in Behc¸et’s disease. In: Zouboulis CC, ed. Proceedings of the 10th International Conference on Behc¸et’s disease. New York, NY: Kluwer Academic/Plenum Publishers, 2003; 419 – 422 Sayin AG, Vural FS, Bozkurt AK, et al. Right atrial thrombus mimicking myxoma and bilateral pulmonary artery aneurysms in a patient with Behcet‘s disease: a case report. Angiology 1993; 44:915–918 Almog Y, Polliack G, Dranitzki Elhalel M, et al. Bilateral pulmonary artery aneurysms in Behcet’s disease. Eur Respir J 1993; 6:1067–1069 Erkan F, Cavdar T. Pulmonary vasculitis in Behcet‘s disease. Am Rev Respir Dis 1992; 146:232–239 Lakhkar BN, Nagaraj MV, Shenoy DP, et al. Bilateral

www.chestjournal.org

52

53 54 55 56 57

58 59 60 61 62

63 64 65 66 67 68 69 70 71 72

73 74 75

pulmonary aneurysm in Behcet’s disease (a case report). J Postgrad Med 1992; 38:47– 49 Jerray M, Benzarti M, Rouatbi N. Possible Behcet‘s disease revealed by pulmonary aneurysms. Chest 1991; 99:1282– 1284 el-Ramahi KM, Fawzy ME, Sieck JO, et al. Cardiac and pulmonary involvement in Behcet’s disease. Scand J Rheumatol 1991; 20:373–376 Sahin AA, Kalyoncu AF, Selcuk ZT, et al. Behcet’s disease with half and half nail and pulmonary artery aneurysm. Chest 1990; 97:1277 Vansteenkiste JF, Peene P, Verschakelen JA, et al. Cyclosporin treatment in rapidly progressive pulmonary thromboembolic Behcet‘s disease. Thorax 1990; 45:295–296 Bowman S, Honey M. Pulmonary arterial occlusions and aneurysms: a forme fruste of Behcet’s or Hughes-Stovin syndrome. Br Heart J 1990; 63:66 – 68 Stricker H, Malinverni R. Multiple, large aneurysms of pulmonary arteries in Behcet‘s disease: clinical remission and radiologic resolution after corticosteroid therapy. Arch Intern Med 1989; 149:925–927 Winer-Muram HT, Gavant ML. Pulmonary CT findings in Behcet’s disease. J Comput Assist Tomogr 1989; 13:346 –347 Raz I, Okon E, Chajek-Shaul T. Pulmonary manifestations in Behcet’s syndrome. Chest 1989; 95:585–589 Barbas CS, de Carvalho CR, Delmonte VC, et al. Behcet’s disease: a rare case of simultaneous pulmonary and cerebral involvement. Am J Med 1988; 85:576 –568 Lie JT. Cardiac and pulmonary manifestations of Behcet syndrome. Pathol Res Pract 1988; 183:347–355 Salamon F, Weinberger A, Nili M, et al. Massive hemoptysis complicating Behcet’s syndrome: the importance of early pulmonary angiography and operation. Ann Thorac Surg 1988; 45:566 –567 Augarten A, Apter S, Theodor R. Right ventricular thrombus and pulmonary arteritis in Behcet‘s disease. Isr J Med Sci 1987; 23:900 –901 Barberis M, Casadio C, Borghini U. Massive haemoptysis in Behcet syndrome: case report. Respiration 1987; 52:303– 307 Efthimiou J, Johnston C, Spiro SG, et al. Pulmonary disease in Behcet’s syndrome. Q J Med 1986; 58:259 –280 Gibson RN, Morgan SH, Krausz T, et al. Pulmonary artery aneurysms in Behcet’s disease. Br J Radiol 1985; 58:79 – 82 Park JH, Han MC, Bettmann MA. Arterial manifestations of Behcet disease. AJR Am J Roentgenol 1984; 143:821– 825 Slavin RE, de Groot WJ. Pathology of the lung in Behcet‘s disease: case report and review of the literature. Am J Surg Pathol 1981; 5:779 –788 Durieux P, Bletry O, Huchon G, et al. Multiple pulmonary arterial aneurysms in Behcet’s disease and Hughes-Stovin syndrome. Am J Med 1981; 71:736 –741 Grenier P, Bletry O, Cornud F, et al. Pulmonary involvement in Behcet disease. AJR Am J Roentgenol 1981; 137:565–569 Davies JD. Behcet’s syndrome with haemoptysis and pulmonary lesions. J Pathol 1973; 109:351–356 Beattie JM, Hall AJ. Multiple embolic aneurysms of pulmonary arteries following thrombosis of vein of leg: death from rupture of aneurysm into lung. Proc R Soc Med 1911; 12.5(III):147–152 Pirani CL, Ewart FE, Wilson AL. Thromboendarteritis with multiple mycotic aneurysms of branches of the pulmonary artery. Am J Dis Child 1949; 77:460 – 473 Charlton RW, DuPlessis LA. Multiple pulmonary artery aneurysms. Thorax 1961; 16:364 –371 Bank H. Thrombotic pulmonary manifestations in Behcet’s CHEST / 127 / 6 / JUNE, 2005

2251

syndrome. Isr J Med 1973; 9:955 76 Ceyran H, Akc¸ali Y, Kahraman C. Surgical treatment of vasculo-Behcet’s disease: a review of patients with concomitant multiple aneurysms and venous lesions. VASA 2003; 32:149 –153 77 Huong DL, Dolmazon C, De Zuterre D, et al. Complete recovery of right intraventricular thrombus and pulmonary arteritis in Behcet’s disease. Br J Rheumatol 1997; 36:130 – 132 78 Saba D, Saricaog˘lu H, Bayram AS, et al. Arterial lesions in Behcet’s disease. VASA 2003; 32:75– 81 79 Urayama A, Sakuragi S, Sakai F, et al. Angio-Behcet’s syndrome. In: Inaba G, ed. Proceedings of the International Conference on Behc¸et’s disease. Tokyo, Japan: University of Tokyo Press, 1981; 171–176 80 Basak M, Gu¨l S, Yazgan Y, et al. A case of rapidly progressive pulmonary aneurysm as a rare complication of Behcet’s syndrome. Angiology 1998; 49:403– 408 81 Bayraktar Y, Balkancı F, Demirkazık F, et al. Type of vessel involvement in patients with Behcet’s disease. In: Wechsler B, Godeau P, eds. Proceedings of the 6th International Conference on Behc¸et’s disease. Amsterdam, the Netherlands: Elsevier Science, 1993; 517–522 82 Hamza M, Angio Behcet. In: Wechsler B, Godeau P, eds. Proceedings of the 6th International Conference on Behc¸et’s disease. Amsterdam, the Netherlands: Elsevier Science, 1993; 522–526 83 Tu¨zu¨n H, Yaman M, Gemicioglu B, et al. Behcet‘s disease presenting with a pulmonary mass lesion. Chest 1993; 104:1635–1636 84 Hensel M, Breitbart A, Ho AD. Autologous hematopoietic stem-cell transplantation for Behcet’s disease with pulmonary involvement. N Engl J Med 2001; 4:344: 69 85 Unlu M, Akincioglu C, Yamac K, et al. Pulmonary involvement in Behcet’s disease: evaluation of 123 I-MIBG retention. Nucl Med Commun 2001; 22:1083–1088 86 Korkmaz C, Aydinli A, Erol N, et al. Widespread nocardiosis in two patients with Behcet’s disease. Clin Exp Rheumatol 2001; 19:459 – 462 87 Gurler A, Boyvat A, Tursen U. Clinical manifestations of Behcet’s disease: an analysis of 2147 patients. Yonsei Med J 1997; 38:423– 437 88 al-Aboosi MM, al Salem M, Saadeh A, et al. Behcet’s disease: clinical study of Jordanian patients. Int J Dermatol 1996; 35:623– 625 89 Tunacı A, Berkmen YM, Gokmen E. Thoracic involvement in Behcet’s disease: pathologic, clinical and imaging features. AJR Am J Roentgenol 1995; 164:51–56 90 Koga T, Yano T, Ichikawa Y, et al. Pulmonary infiltrates recovered by FK 506 in a patient with Behcet’s disease. Chest 1993; 104:309 –311 91 Fairly C, Wilson JW, Barraclough D. Pulmonary involvement in Behcet’s syndrome. Chest 1989; 96:1428 –1429 92 Balduin R, Murer L, Drigo R, et al. Behcet’s syndrome: a rare case of pulmonary involvement. Eur J Respir Dis 1986; 69:288 –290 93 Santo M, Levy A, Levy MJ, et al. Pneumonectomy in pulmonary mucormycosis complicating Behcet’s disease. Postgrad Med J 1986; 62:485– 486 94 Gamble CN, Weisner KB, Shapiro RF, et al. The immune complex pathogenesis of glomerulonephritis and pulmonary vasculitis in Behcet’s disease. Am J Med 1979; 66:1031–1039 95 Petty TL, Scoggin CH, Good JT. Recurrent pneumonia in Behcet’s syndrome: roentgenographic documentation during 13 years. JAMA 1977; 238:2529 –2530 96 Cadman EC, Lundberg WB, Mitchell MS. Pulmonary manifestations in Behcet’s syndrome: case report and review of 2252

the literature. Arch Intern Med 1976; 136:944 –947 97 Chajek T, Fainaru M. Behcet’s disease: report of 41 cases and a review of the literature. Medicine 1975; 54:179 –196 98 Ohta G, Nishino T, Onchi K, et al. An autopsy case of Behcet’s syndrome associated with pulmonary arteritis and tuberculosis. Jpn Circ J 1974; 38:35– 45 99 Kansu E, Ozer FL, Akalin E, et al. Behcet’s syndrome with obstruction of the vena cava. Q J Med 1972; 41:151–168 100 Kohno S, Fujikawa M, Kanda T, et al. A case of Behcet’s syndrome with rupture of a pulmonary aneurysm: autopsy findings and a literature review. Jpn J Med 1986; 25:293–300 101 Decroix AG. Thoracic manifestations of Behcet’s syndrome. Thorax 1969; 24:380 102 Beroniade V. Amyloidosis and Behcet’s disease. Ann Intern Med 1975; 83:904 –905 103 Hills EA. Behcet’s syndrome with aortic aneurysms. BMJ 1967; 4:152–154 104 Boe J, Dalgaard JB, Scott D. Mucocutaneus-ocular syndrome with intestinal involvement. Am J Med 1958; 25:857– 867 105 Candan I, Erol C¸, Sonel A, et al. Behcet’s disease: cardiac and pulmonary involvement. Eur Heart J 1986; 7:999 –1002 106 Konishi T, Takeuchi H, Iwata J, et al. Behcet’s disease with chylothorax: case report. Angiology 1988; 39:68 –71 107 Akkaynak S, Enacar N, C¸obanlı B, et al. Behcet’s disease and ¨ vu¨l N, eds. Proceedings of lungs. In: Dils᝺en N, Konic¸e M, O an International Symposium on Behc¸et’s disease. Amsterdam, the Netherlands: Oxford, 1977; 160 –161 108 Dils᝺en N, Konic¸e M, Gaziog˘lu K, et al. Pleuropulmonary manifestations in Behcet’s disease. In: Dils᝺en N, Konic¸e M, ¨ vu¨l N, eds. Proceedings of an International Symposium on O Behc¸et’s disease. Amsterdam, the Netherlands: Oxford, 1977; 162–169 109 Sulheim O, Dalgaard JB, Andersen RY. Behcet’s syndrome. Acta Pathol Microbial Scand 1959; 45:145–159 110 Oz N, Sarper A, Erdogan A, et al. Video-assisted thoracic surgery for the management of pleural and pericardial effusion in Behcet’s syndrome. Tex Heart Inst J 2000; 27:304 –306 111 Abadog˘lu O, Osma E, Uc¸an ES, et al. Behcet’s disease with pulmonary involvement, superior vena cava syndrome, chloptysis and chlous ascites. Respir Med 1996; 90:429 – 431 112 Tatsis G, Vaipoulos G, Tassiopoulos T, et al. Lung function in Adamantisdes-Behcet’s disease. Rheumatology 1999; 38: 1018 –1019 113 Formiga F, Vidaller A, Mitjavila F, et al. Pulmonary function in Behcet’s disease (BD) [abstract]. VIIth International Conference on Behcet’s disease, Tunis, Tunisia, October 10 –11, 1996, Rev Rheum 1996; 63:557. 114 Corren J. Acute interstitial pneumonia in a patient with Behcet’s syndrome and common variable immunodeficiency. Ann Allergy 1990; 64:15–20 115 Gibson JM, O’hara MD, Beare JM, et al. Bronchial obstruction in a patient with Behcet’s disease. Eur J Respir Dis 1982; 63:356 –360 116 Evans WV, Jenjkins RM. Pulmonary function in Behcet’s syndrome. Scand J Respir Dis 1979; 60:314 –316 117 Ahonen AV, Stenius-Aarniala BS, Viljanen BC, et al. Obstructive lung disease in Behcet’s syndrome. Scand J Respir Dis 1978; 59:44 –50 118 Sanchez-Burson J, Corzo JE, Marenco JL, et al. Thrombolytic therapy in pulmonary embolism of Behcet’s disease. Acta Haematol 1996; 96:181–183 119 Siepmann M, Kirch W. Coronary anomaly in Behcet‘s syndrome. Rheumatol Int 1997; 17:39 – 42 120 Witt C, John M, Martin H, et al. Behcet’s syndrome with pulmonary involvement-combined therapy for endobronReviews

121 122

123 124

125

126

127 128 129 130 131 132 133

134

chial stenosis using neodym-YAG laser, balloon dilation and immunosupression. Respiration 1996; 63:195–198 Akpolat T, Yildiz L, Akpolat I, et al. Small-cell carcinoma as a cause of superior vena cava syndrome in a patient with Behcet’s disease. Respiration 2000; 67:593 Assaad Khalil SH. Clinical, genetic, immunological, and biochemical features of 180 Egyptian patients with Behcet’s disease. In: O’Duffy JD, Kokmen E, eds. Behcet’s disease: basic and clinical aspects. New York, NY: Marcel Dekker, 1991; 269 –277 Dils᝺en N, Konice A, Aral O, et al. Risk factors for vital organ involvement in Behcet’s disease. Amsterdam, the Netherlands: Elsevier Science, 1993; 165–169 ¨ nal S, Sivri B, et al. Behcet’s disease in Turkish Du¨ndar S, U popultion: analysis of 200 cases. In: Lehner T, Barnes CG, ed. Recent advances in Behcet’s disease. New York, NY: Royal Society of Medicine Services, 1986; 219 –221 Du LTH, Bletry O, Wechsler B, et al. Arterial manifestations in Behcet’s disease: fifteen cases in a series of 250 patients. In: O’Duffy JD, Kokmen E, eds. Behcet’s disease: basic and clinical aspects. New York, NY: Marcel Dekker, 1991; 145–153 Valesini G, Pezzi PP, Catarinelli G, et al. Clinical manifesations of Behcet’s disease in Italy: study of 155 patients at Rome University. In: O’Duffy JD, Kokmen E. Behcet’s disease: basic and clinical aspects. New York, NY: Marcel Dekker 1991; 279 –289 Pande I, Uppal SS, Kailash S, et al. Behcet’s disease in India: a clinical, immunological, immunogenetic and outcome study. Br J Rheumatol 1995; 34:825– 830 Kone-Paut I, Yurdakul S, Bahabri SA, et al. Clinical features of Behcet’s disease in children: an international collaborative study of 86 cases. J Pediatr 1998; 132:721–725 Mousa AR, Marafie AA, Rifai KM, et al. Behcet’s disease in Kuwait, Arabia: a report of 29 cases and review. Scand J Rheumatol 1986; 15:310 –332 Benamour S, Chaoui L, Zeroual B, et al. Study of 673 cases of Behc¸et’s disease. Milano, Italy: VIIIth International Congress on Behc¸et’s Disease, October 7–9, 1998; 232 Akpolat T, Danaci M, Belet U, et al. MR imaging and MR angiography in vascular Behcet’s disease. Magn Reson Imaging 2000; 18:1089 –1096 Erkan F, Gul A, Tasali E. Pulmonary manifestations of Behcet’s disease. Thorax 2001; 56:572–578 Plotkin GR. Miscellaneous clinical manifestations: Part I. Cardiac, vascular, renal, and pulmonary features. In: Plotkin GR, Calabro JJ, O’Duffy JD, eds. Behc¸et’s disease: a contemporary synopsis. Mount Kisco, NY: Futura Publishing, 1988; 203–237 Erkan F, Kiyan E, Tunaci A. Pulmonary complications of Behc¸et’s disease. Clin Chest Med 2002; 23:493–503

www.chestjournal.org

135 Shahram F, Davatchi F, Akbarian M, et al. The 1996 Survey of Behc¸et’s disease in Iran: study of 3153 cases [abstract]. VIIth International Conference on Behc¸et’s Disease. Revue du Rhumatisme, English ed, 1996; 63:538 136 Oshima Y, Shimizu T, Yokohari R, et al. Clinical studies on Behc¸et’s syndrome. Ann Rheum Dis 1963; 22:36 – 45 137 International Study Group for Behc¸et’s disease. Criteria for diagnosis of Behc¸et’s disease. Lancet 1990; 335:1078 –1080 138 Benamour S, Bennis R, Amraoui A. A study of 285 cases of Behc¸et’s disease. In: O’Duffy JD, Kokmen E, eds. Behc¸et’s disease: basic and clinical aspects. New York, NY: Marcel Dekker, 1991; 259 –267 139 Sanchez BJ, Grandal Y, Mendoza M, et al. Clinical characteristics, HLA antigen and mortality in Behc¸et’s syndrome in Spain. Milano, Italy: VIIIth International Congress on Behc¸et’s Disease, October 7–9, 1998; 102 140 Sharquie K, Al-Araji A, Al-Rawi Z, et al. Behc¸et’s disease in Iraqi patients: a prospective study from a newly established Behc¸et’s Disease Multidiscipline Clinic [abstract]. IXth International Conference on Behc¸et’s Disease. Yonsei Med J 2000: 41:10S 141 Madanat W, Fayyad F, Zureikat H, et al. Analysis of 150 cases of Behc¸et’s disease from Jordan. Milano, Italy: VIIIth International Congress on Behc¸et’s Disease, October 7–9, 1998; 255 142 Chung YM, Yeh TS, Sheu MM, et al. Behcet‘s disease with ocular involvement in Taiwan: a joint survey of six major ophthalmological departments. J Formos Med Assoc 1990; 89:413– 417 143 Bang D, Lee JH, Lee ES, et al. Epidemiologic and clinical survey of Behcet’s disease in Korea: the first multicenter study. J Korean Med Sci 2001; 16:615– 618 144 Alekberova Z, Madanat W, Prokaeva T, et al. Clinical and genetic features of 35 patients with Behc¸et’s disease from Commonwealth Independent states. Proceedings of the 6th International Conference on Behc¸et’s disease. Amsterdam, the Netherlands: Elsevier Science, 1993; 171–174 145 Maeda K, Nakae K. Epidemiological study on dead cases of ¨ vu¨l N, Behc¸et’s disease in Japan. In: Dils᝺en N, Konic¸e M, O eds. Proceedings of an International Symposium on Behc¸et’s Disease. Amsterdam, the Netherlands: Oxford, 1977; 47–51 146 Zouboulis CC, Kotter I, Djawari D, et al. Epidemiological features of Adamantiades-Behcet’s disease in Germany and in Europe. Yonsei Med J 1997; 38:411– 422 147 Yazici H, Bas᝺aran G, Hamuryudan V, et al. The ten-year mortality in Behc¸et’s syndrome. Br J Rheumatol 1996; 35:139 –141 148 Kingston M, Ratcliffe JR, Alltree M, et al. Aneurysm after arterial puncture in Behcet’s disease. BMJ 1979; 1:1766 – 1767

CHEST / 127 / 6 / JUNE, 2005

2253