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In medicine, vasculitis (plural: vasculitides) is a group of diseases featuring inflammation of the wall of blood vessels. Its main causes are autoimmune disorders and (occasionally) infections. Treatment depends on the cause. While most vasculitides are rare diseases, they generally affect several organ systems and can cause severe disability. more...

VACTERL association
Van der Woude syndrome
Van Goethem syndrome
Varicella Zoster
Variegate porphyria
Vasovagal syncope
VATER association
Velocardiofacial syndrome
Ventricular septal defect
Viral hemorrhagic fever
Vitamin B12 Deficiency
VLCAD deficiency
Von Gierke disease
Von Hippel-Lindau disease
Von Recklinghausen disease
Von Willebrand disease


The types of vasculitis are distinguished by the type of blood vessel affected (aorta, large arteries, arterioles, capillaries and veins), the appearance of biopsy tissue of affected organs on light microscopy, and if necessary, with the help of immunohistochemistry (use of monoclonal antibodies against specific inflammatory protein markers).

Other diagnostic tools are the detection of circulating antibodies that are associated with forms of vasculitis. While these measurements have a low positive and negative predictive value (due to the high rates of both false positives and false negatives), they can direct the clinician to specific causes for vasculitis.


Infectious vasculitis is generally treated with directed antibiotics, while autoimmune forms often require treatment with immune suppression: steroids, DMARDs ("steroid-sparing agents") or cyclophosphamide (a mild form of chemotherapy). For very severe forms, bone marrow transplantation is presently being investigated as the ultimate silencing of the immune system.

Causes and types

  • Large vessel vasculitis
    • Giant cell arteritis (also temporal arteritis)
    • Takayasu's arteritis
  • Medium-sized vessel vasculitis
    • Polyarteritis nodosa
    • Kawasaki's disease
    • Cerebral vasculitis (primary granulomatous)
  • Small-vessel vasculitis
    • Associated with ANCAs (anti-neutrophil cytoplasmatic antibody):
      • Microscopic polyangiitis
      • Wegener's granulomatosis
      • Churg-Strauss syndrome
      • Drug-induced
    • Associated with deposition of immune complexes:
      • Henoch-Schönlein purpura (HSP)
      • Cryoglobinemic vasculitis
      • Lupus erythematosus vasculitis
      • Rheumatoid vasculitis
      • Sjögren's syndrome vasculitis
      • Urticarial vasculitis associated with decreased complement
      • Behçet's disease
      • Goodpasture's syndrome
      • Serum sickness-vasculitis
      • Drug-induced
      • Infection-induced (not infectious)
    • Paraneoplastic
      • Lympho- and myeloproliferative neoplasm associated
      • Carcinoma-associated
    • Inflammatory bowel disease vasculitis


  • Jenette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997; 337(21):1512-23. PMID 9366584.


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Pulmonary vasculitis in Behcet disease : a cumulative analysis
From CHEST, 6/1/05 by Oguz Uzun

Study objectives: The aims of this study were to investigate the frequency of pulmonary problems in Behcet 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.

Key words: anticoagulation; Behcet disease; immunosuppression; pulmonary artery aneurysm; pulmonary thromboembolic disease; vasculitis

Abbreviations: BD = Behcet disease; ISG = International Study Group; PAA = pulmonary artery aneurysm; PTE = pulmonary thromboembolic


Behcet disease (BD) is a multisystem disorder characterized by vasculitis first described by Hulusi Behcet in 1937, (1) and consists of a triad of recurrent ulcers of the oral and genital mucosa with relapsing uveitis. Since its first description, involvement 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 are a few articles (100,132-134) 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 review (8) 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. 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, prognosis, 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.


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) criteria (137) 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.


Mann-Whitney U test and [chi square] 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.


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."


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.



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 problems have been presented in the literature, a cumulative analysis of these eases has not previously been done. This study includes nearly 90% of the published eases. It should be kept in mind that this cumulative analysis includes only the reported cases. In addition, the reported eases 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 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 earl 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 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 ([chi square] > 10, p < 0.01 for all comparisons).

PAA of one the causes of deaths in BD. (43,147) Hamuryudan et al (43) 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 articles (43,132,134) recommend immunosuppression combined with embolization, surgery, anticoagulation, or low-close 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 pulmonary 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 al (27) 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 hemoptysis (36,43,57,59,62,68) or even deathy, (43,44,65) and it has been recommended to use anticoagulation only after immunosuppression. (132,134) It is reasonable to avoid use of anticoagnlation 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 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 BD (131,148) 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 Hughes-Stovin 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. Vascular-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 in'titration 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 al (92) reported a 31-year-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. Tuzun et al (83) also reported a 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 anticoagnlation/ thrombolysis and immunosuppression (steroids, azathioprine, cyclophosphamide, cyclosporine). In general, the outcome of patients treated with anticoagnlation/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 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 studies (22,85) investigating the role of lung scintigraphy in BD. One of these studies (85) showed prolonged lung retention indexes of [sup.123]I-meta-iodobenzylguanidine in patients without previously reported pulmonary involvement, and the other study (22) showed bilateral segmental or nonsegmental perfusion defects after IV injection of 74 Megabecquerel of [sup.99][Tc.sup.m]-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)

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. (101,104,10s,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 patient was treated with Nd-YAG laser resection, immunosuppression, and balloon dilation.

Tatsis et al (112) 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 disease (117) are other bronchial problems. The patient with chronic bronchitis and bronehiectasia also had Pneumocystis carini pneumonia. In addition, Gibson et al (115) 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. Pleura] 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.

* From Departments of Pulmonary Medicine (Drs. Uzun and Erkan) and Internal Medicine (Dr. Akpolat), Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.

Manuscript received April 6, 2004; revision accepted December 1, 2004.


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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml).

Correspondence to: Oguz Uzun, MD, 19 Mayas Universitesi, Tip Fak, Gogus Hst. ABD 55139, Kurupelit-Samsun, Turkey; e-mail:

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