Behçet Hastalığı: İki Farklı Tedavi Yaklaşımı
Turan ACICAN, Özlem URAL GÜRKAN, Banu ERİŞ, Peri ARBAK, Akın KAYA, Belma ÇOBANLI
Vena kava superior içinde trombüsleri olan ve intestinal, nöral ve pulmoner tutulumlu iki adet Behçet olgusunu sunuyoruz. Birinci olgu; 47 yaşında erkek, 7 yıllık Behçet hastası ve kolşisin kullanmakta idi. Dispne, öksürük ve yüzde ödem yakınmaları ile kliniğimize yatırıldı. Fizik muayenede vena kava superior sendromu mevcut ve Akciğer grafisinde üst mediasten genişti. Hastaya verilen kolşisin dozunu yükselterek predisolon ilave ettik. Bu tedavi altında hastanın yakınmaları, fizik ve radyolojik bulguları geriledi. İkinci olgu; 45 yaşında 10 yıllık Behçet hastası olan bir erkek idi. Son 6 yıldır enterobehçet tanısı olan hasta 3 kez incebarsak perforasyonu nedeni ile opere edilmiş idi. Olgu dispne, göğüs ağrısı, hemoptizi ve abdominal ağrı yakınmaları ile kliniğimize yatırıldı. Akciğer grafisi ve bilgisayarlı tomografisinde sağda plevral sıvı ve perfüzyon/ventilasyon sintigrafisinde pulmoner emboli saptandı. Steroid tedavi başlandı ancak bir hafta sonra melena gelişmesi üzerine kesildi. Konfüzyon ortaya çıkan hastaya yapılan serebral MR incelemesinde iskemik lezyonlar saptandı. Hasta nörobehçet tanısı aldı. İnterferon tedavisi başlandı. Tedavinin birinci ayı sonunda relatif olarak stabil olan hasta tedavinin üçüncü ayında kaybedildi.
Anahtar Kelimeler: Behçet hastalığı, interferon tedavisi, nörobehçet
Behçets Disease: Two Different Therapy Modalities
We presented here two patients with Behçets disease (BD) with thrombi in superior vena cava (SVC) and involvement of intestinal, neural and pulmonary systems. First patient was a 47 year old male with BD for 7 years and was treated with colchicine. He was admitted with dyspnea, cough and facial oedema. Superior vena cava syndrome (SVCS) was observed and chest X-ray revealed widening of superior mediastinum. Thorax CT demonstrated chronic thrombi in the SVC and other main veins of mediastinum. We increased dosage of colchicine and added prednisolone. Complaints of the patient, physical and radiographic findings regressed with this therapy. Second patient was a 45 year-old male with BD for ten years. He had enterobehçet for the last 6 years and was operated three times for perforation of intestinum. He was admitted with dyspnea, chest pain, hemoptysis, abdominal pain. Chest X-ray and thorax CT showed pleural effusion on the right side and perfusion lung scanning revealed pulmonary embolism. Steroid therapy was initiated but it had to be ceased after one week because melena had developped. Confusion occurred and cranial MR revealed ischemic lesions. The patient was diagnosed as neurobehçet. Interferon therapy was started. Although the patient was relatively stable after one month, he died at the third month of the therapy.
Key Words: Behçets disease, interferon therapy, neurobehçet
Behçets disease is a chronic multisystem disease of unknown aetiology affecting many organs. The histologic hallmark of Behçets disease is nonspesific vasculitis involving all size of veins, capilleries and arteries of both systemic and pulmonary circulations (1). Diagnostic criteria of this disease according to the International Study Group are the aphtous lesions plus any two of the genital ulcerations, typical defined skin lesions, eye lesions or a positive pathergy test (2,3). Pulmonary involvement of the disease is about 5-10% (4,5).
We presented here two patients with Behçets Disease; one with thrombi in superior vena cava and the other with the involvement of intestinal, neural and pulmonary systems.
A 47 year old man was admitted to our clinic with dyspnea, cough and swelling in the neck, eyelids and pretibial edema. He had the history of recurrent oral and genital ulcers, thrombophlebitis. Pathergy test was positive. A diagnosis of Behçets disease was made according to the International Study Group Criteria (2).
Physical examination revealed swelling in the face and the neck and dilated veins over the anterior chest. There was edema also in the right leg which was further found to be a sign of deep venous thrombosis.
Chest radiographs revealed widening of the upper mediastinum and bilateral hilar enlargement (Figure 1). Thorax CT demonstrated chronic thrombi in the superior vena cava and other main veins of mediastinum (Figure 2).
The patient was treated with colchicine, furosemide, pentoxyphylline and prednisolone. Methyl prednisolone had been started 40 mg per day initially for the first month and then reduced 4 mg per week. When it was 16 mg per day, therapy was completed to six months and then it was tapered slowly. After the second month of therapy, control thorax CT was performed and it revealed chronic thrombi in the superior vena cava, but a slight narrowing in the upper mediastinum is observed in the posteroanterior chest radiographs (Figure 3), the radiologic appearance in the second month hadnt changed at the end of the steroid therapy.
The patient is still on follow-up and he has no complaints since then.
A 45 year old man referred to our department with progressive dyspnea, cough and hemoptysis. He had edema in the legs, scrotum and the abdomen for one month.
He had a ten-year history of recurrent oral aphtosis and genital ulcerations, arthralgias, cutaneous lesions. The pathergy test was positive. A diagnosis of Behçets disease was made. He was operated three times for intestinal perforation in the last six years in which he was diagnosed as enterobehçet.
Physical examination revealed tachycardia and tachypnea and dilated veins over the anterior chest. Hepatosplenomegaly, pretibial and scrotal edema was observed and the lung sounds in the base of the right lung was diminished.
Chest X-ray showed pleural effusion on the right side (Figure 4) and perfusion/ventilation lung scanning revealed pulmonary embolism. Prednisolone was initiated but it had to be ceased after one week because of gastrointestinal bleeding. Meanwhile confusion occurred and cranial MRI revealed ischemic lesions (Figure 5a ,5b). The patient was diagnosed as neurobehçet.
Cyclophosphamide was contraindicated since the patient had elevated hepatic enzyme levels and anti-HCV positiveness. Interferon therapy was given three times weekly for two months (3 MU interferon alpha 2-a subcutaneously). After the first month he was relatively stable and the radiologic appearence improved slightly (Figure 6), but at the third month after his discharge he died.
Behçets disease is a multisystem disorder with an underlying pathology of nonspesific vasculitis including mucocutaneous, ocular, cardiovascular, neurologic, pulmonary and gastrointestinal involvement (1). The organ system involvement is shown in Table 1(1,4).
Behçets disease is frequently observed in Oriental and Mediterranean countries. The prevalance is higher in Turkey, Israel, Lebanon, Iran, Japan, Korea and China (6). The disease usually occurs in adults between 20 and 40 years of age (1). The male to female ratio ranges from 2:1 to 5:1 in Mediterranean and Middle Eastern and far Eastern countries (7) and is reversed in the United States and Great Britain, ranging from 1/5 to 1/2 (8). The disease has a more severe course in young men (9).
The etiology of the disease is undetermined, but it is likely that both environmental agents, possibly viral, and genetic predisposition play a role (10). HLA B5 and HLA-Bw51 are often associated with Behçets disease (1,10,11).
Pulmonary manifestations include pulmonary embolism and infarction, pulmonary artery thrombosis, thromboembolism of the superior vena cava and /or mediastinal veins and pulmonary artery aneurysm. The radiologic reflection of these manifestations are transient alveolar infiltration, pleural fluid representing haemorrhage or infarction, enlargement of superior mediastinum and central round opacities signifying pulmonary artery aneurysms (12-16).
Hemoptysis is the worst prognostic sign in Behçets syndrome leading to death in 30% patients, most of them die within 2 years (17). Our second patient had a mild hemoptysis.
The other main pulmonary symptoms were dyspnea, pleuritic chest pain and cough occurring in about 60% of patients (17). Both of our patients had dyspnea and cough and the second patient had pleuritic chest pain at the right side.
No standard therapy has been established (18). The usual treatments are corticosteroids, colchicine and immunosuppresants (19).
Although there have been many reports about the effectiveness of cyclosporine in the treatment of ocular complications of Behçets disease, a few reports also describe the efficacy of cyclosporine on mucocutaneous and musculoskeletal involvement (19-21). In pulmonary involvement, corticosteroids are recommended initially. We treated our first patient with colchicine and prednisolone and complaints of the patient, physical and the radiologic findings improved with this therapy. Interferon have antiviral, immunomodulatory, antiproliferative and anti tumoral effects, they might have potential for the treatment of Behçets disease. A study with 16 patients, treated with interferon alpha-2 during two months, suggests that interferon therapy appears to be effective for patients with Behçets Disease (18).
The second patient was treated with prednisolone and colchicine initially, but it had to be ceased after one week because of the melena. The immunosuppressive drugs were not given because of the patients hepatic status. Interferon therapy had been started. The patient was relatively stable after one month, but at the third month after his discharge he died.
We experienced that colchicine plus corticosteroid may be an effective treatment modality in SVC syndrome in Behçets disease. Besides that interferon could be the choice of treatment in conditions which immunosupressants are contrindicated.
ADRESS FOR CORRESPONDING:
Dr. Turan ACICAN
Oyak Sitesi, 38. Giriş, Daire 18,