Behcet’s disease is a type of vasculitis which presents with recurrent oral and genital aphthous ulceration, uve- itis and skin lesions. Arteries and veins of all sizes are involved in Behcet’s disease which is typified by venous and arterial occlusions and arterial aneurysms . Unlike other types of vasculitis, venous system involvement is a common manifestation of Behcet’s disease and occurs in 10% to 25% of patients . Tascilar et al.  carried out retrospective analysis of 5970 patients with Behcet’s disease and identified 882 (14.7%) patients as having vascular involvement. The incidence of vascular involvement has been shown to differ by ethnic group . Vascular involvement is a rare manifestation of Behcet’s disease in Azerbaijan and occurs in only 9% of patients . Vascular involvement is more common in young males with a male-to-female ratio of approximately four to one . The first vascular event occurs in the majority of pa- tients (75%) within five years of disease onset . The most common type of venous system involvement is deep vein thrombosis (DVT) [2,3]. Despite the high incidence of DVT, pulmonary thrombo- embolism (PTE) is a very rare complication of Behcet’s disease . Its cause relates to the specific nature of throm- bosis in Behcet’s disease . Venous thrombi are thought to develop primarily from the inﬂammation of the blood vessels . Moreover, unlike classic thrombi, they adhere to the vessel walls, making embolization difﬁcult . Despite the low incidence of PTE in Behcet’s disease, other types of pulmonary artery involvement, such as pulmo- nary artery aneurysm (PAA) and in situ pulmonary artery thrombosis (PAT) are relatively common. Due to the simi- larity of clinical and imaging findings of various forms of pulmonary artery involvement, it can be difficult to diag- nose PTE in a patient with Behcet’s disease. In this article, we report on a case of Behcet’s disease with PTE. Written consent has been obtained from the patient for this report.
A 44-year old male with known Behcet’s disease was ad- mitted to our hospital because of pleuritic chest pain and dyspnea in September 2015. Recurring painful oral ulcer- ations, bilateral panuveitis, superficial phlebitis and pos- itive pathergy had led to a diagnosis of Behcet’s disease 12 years earlier. He was followed in the Behcet’s disease clinic of the Connective Tissue Diseases Research center (CTDRC) in Tabriz, Iran and was treated with predniso- lone 30 mg/d, methotrexate 15 mg/week and a monthly pulse of cyclophosphamide because of refractory panuve- itis. With this treatment, the uveitis was controlled and he had reported no oral aphthous ulceration or phlebitis in the succeeding two months. The patient experienced lower left limb pain and swelling one week before admission. He developed sudden onset dyspnea, pleuritic chest pain and hemoptysis two days pri- or to admission. At this time, the patient had tachypnea and mild respiratory distress. His respiratory and heart rates were 26 and 112, respectively. The patient was afebrile with a blood pressure was 110/75 mmHg. Chest examina- tion was normal. Lower left limb examination showed 2+ swelling and tenderness. The laboratory data was as follows: leukocyte count: 4.5×103/µL (62.1% neutrophils; 32% lymphocytes), he- moglobin: 12.7 mg/dL; erythrocyte sedimentation rate: 28 mm/h and C-reactive protein 6.7 mg/L (normal ≤10). Urea, creatinine, urine analysis, liver function tests and electro- lytes were normal. Color Doppler ultrasonography showed subacute thrombosis in the popliteal vein of the lower left limb. The transthoracic cardiac echocardiography was nor- mal. Chest computer tomography (CT) showed no lesions in the in lung parenchyma and mediastina. CT angiog- raphy of the pulmonary arteries showed eccentric filling defects which formed acute angles with the vessel wall in the short and long axis in the interlobar arteries of both lungs with sub-segmental consolidation (Figure 1). The lung perfusion scan with 99 mTc showed multiple seg- mental and sub-segmental perfusion defects in both lungs which did not match the ventilation scan. A diagnosis of PTE was made and anticoagulation with enoxaparin and warfarin was started. The tachypnea, chest pain and hemoptysis disappeared after three days and he was discharged after 10 days with warfarin 5 mg/d. Treatment with prednisolone 30 mg/d, methotrexate 15 mg/week and a monthly pulse of cyclo- phosphamide was continued. He was followed in the Beh- cet’s disease clinic at CTDRC and, after control of the uve- itis, the prednisolone dose was decreased to 7.5 mg/d. The second ventilation perfusion scan performed three months later showed complete resolution of the perfusion defects. His disease was in complete remission by eight months after discharge.
Pulmonary involvement is not common in Behcet’s disease, but is one of the main causes of mortality and morbidity in this disease . Pulmonary vascular involvement such as PAA, in situ PAT, pulmonary hemorrhage, pulmo- nary infarction, PTE, arteriovenous shunt in the lung and aneurysmal fistula are the most common pulmonary dis- orders in Behcet’s disease [3, 5, 6]. Pleural effusion, pneu- monia, alveolitis, cavitary lesions, pulmonary obstructive airway disease and fibrosis are other forms of pulmonary involvement . The pulmonary arteries are the second most-common sites of arterial involvement in Behcet’s disease . The most common form of pulmonary artery involvement in Behcet’s disease is PAA and in situ PAT is less common . Differentiation of the types of pulmonary artery involve- ment is very important because the mainstay of the treat- ment of PAA and PAT is aggressive immunosuppressive therapy . Some case reports have shown a useful effect of anti-TNF agents in the management of resistant cases of pulmonary vasculitis [7, 8]. The use of anticoagulants by these patients is questionable, because the thrombi are generally organized  and anticoagulation of such pa- tients may cause worsening of hemoptysis and increase mortality . In cases of PTE, however, anticoagulation may be necessary . It is not clear what percentage of vascular lung lesions in Behcet’s disease are related to pulmonary emboli . Thirty-three cases of PTE in Behcet’s disease have been re- ported (Table 1) , but clinical data has not been reported in most of them. Cough, fever, hemoptysis, pleuritic chest pain and dyspnea are the main clinical manifestations of PTE, in situ thrombosis and pulmonary artery aneurysms. Although angiography is the gold standard diagnostic method in vascular disease, it is invasive and has limita- tions for pulmonary vasculitis caused by Behcet’s disease . Newer imaging methods like CT angiography and MR angiography are less invasive and also permit physicians to evaluate lung parenchyma . CT angiography can di- agnose pulmonary artery aneurysms, but the angiographic findings of in situ thrombosis are very similar to PTE . However, the shape of the filling defects in the CT angiog- raphy largely contribute to the differentiation of PTE from PAT. In the PTE, CT angiography shows multiple eccentric filling defects that form acute angles with the vessel wall . Ventilation–perfusion scanning is very helpful to the diagnosis of PTE in the absence of cardiopulmonary dis- ease. A scan suggesting a high probability of acute pulmo- nary embolism should be considered diagnostic . How- ever, interpretation of lung scintigraphy is questionable in Behcet’s disease because, unlike classic PTE, pulmonary artery occlusion in Behcet’s disease most often represents in situ thrombosis. A single mismatched defect on the ven- tilation/perfusion scintigraphy should not be diagnosed as PTE in a patient with Behcet’s disease . In addition, many case reports show PAA and perfusion defects on the lung scintigraphy . Our patient developed dyspnea, pleuritic chest pain and hemoptysis in the lower limb five days after DVT. CT an- giography of the pulmonary arteries showed eccentric fill- ing defects which formed acute angles with the vessel wall in the inter-lobar arteries of both lungs with sub-segmental consolidation. The perfusion scan with multiple segmental and sub-segmental perfusion defects in the both lungs did not match the ventilation scan. These findings suggested a high probability of PTE. The resolution of the perfusion defects in the second ventilation perfusion scan confirmed the diagnosis of PTE.
In conclusion, patients with BD may develop PTE. The diagnosis may be difficult due to the rarity of PTE in BD and nonspecific clinical manifestations; thus, a high degree of suspicion and appropriate imaging studies are essential for diagnosis. PTE can be differentiated from PAT through observation of eccentric filling defects in the pulmonary arteries which form acute angles with the vessel wall in CT angiography and multiple segmental and sub-segmental perfusion defects which do not match the ventilation scan.