Successful treatment of adalimumab for older Behçet's disease complicated with pulmonary artery thrombosis: A case report.

Abstract

Behçet's disease (BD) is a chronic systemic disorder characterized by inflammation of multiple organs, such as eyes, mucosa, skin, brain, joints, and vessels.1 Vascular manifestations, which consist of arterial involvements and venous involvements, affect 15%-40% of patients with BD.2 Pulmonary involvements, including pulmonary thrombosis and pulmonary aneurysms, are less common, but associated with poor prognosis and severe cases and are most common among younger men.3 Anti-tumor necrosis factor (anti-TNF) inhibitors have been recommended for the treatment of severe cases of vascular BD.4 However, the use of TNF inhibitors has been reported to cause adverse effects such as infections, especially for older patients.5 Herein, we present a case of an older patient with BD, who developed refractory pulmonary artery thrombosis, improved with adalimumab (ADA), and sustained remission for 1 year without adverse effects. A 80-year-old man admitted to our hospital with fever, dyspnea and erythema nodosum. He had a history of recurrent erythema nodosum in lower limbs and recurrent oral aphthous ulcers for over 4 years. He was diagnosed with BD 6 months ago with oral aphthous ulcers, anterior uveitis, erythema nodosum, and arthritis. As treatment of colchicine and prednisolone (PSL) 30 mg/d was started, his clinical symptoms rapidly improved. The dose of PSL was decreased to 15 mg/d, but he suffered from dyspnea and fever 1 month later. A physical examination at admission revealed a fever of 37.0°C, arthralgia, erythema nodosum in both legs, and left leg edema. Respiratory rate was 20 breaths/min, pulse rate was 108 beats/min, and oxygen saturation was 93% in room air. No dry cough, oral ulcers, inflammatory back pain, psoriasis, or abdominal pain were seen. Laboratory data showed C-reactive protein (CRP) of 8.33 mg/dL and erythrocyte sedimentation rate of 70 mm/h. D-dimer (D-D) was elevated to 2.3 μg/mL. White blood cell count was 6300/μL, hemoglobin was 11.7 g/dL and the platelet count was 23.8 × 104/μL. Human leucocyte antigen (HLA)-B26 was positive and HLA-B27 was negative. Anti-nuclear antibodies, anticardiolipin antibodies, and lupus anticoagulant were negative. Enhanced chest computed tomography (CT) showed multiple thrombi on right pulmonary artery (Figure 1). He was diagnosed as having pulmonary artery thrombosis complicated with BD. The dose of PSL was increased from 15 to 20 mg/d, and heparin was started. However, chest CT performed 1 week after the first scan showed exacerbation of thrombosis (Figure 1). He was administered subcutaneous ADA (160 mg at first week and from then 80 mg every 2 weeks; Figure 2). Immediately after treatment, his clinical symptoms improved. Four days after first injection of ADA, CRP and D-D was decreased. Chest CT revealed improvement of pulmonary thrombosis after 2 weeks. We could taper PSL dose from 20 to 4 mg/d without recurrence after a year. He had no adverse effect, such as injection site reactions or infections. We present a case of an older patient with vascular BD who received ADA treatment without adverse effect. Pulmonary artery manifestation is rare, and affects mainly young man, but predicts a poor prognosis. Pulmonary artery aneurysms and pulmonary artery thrombosis are the two most common manifestations in pulmonary artery manifestations, the prevalence of which is <5%.6 However, vascular involvement is the most common cause of morbidity and mortality in BD.7 The underling pathogenesis of pulmonary involvements of BD has remained unknown. It has been reported that TNF-α, INF-γ and interleukin-8 are associated with disease activity and vascular involvement.8 Treatment of pulmonary artery thrombosis is mainly immunosuppressive drugs. Recommended treatment is pulse corticosteroid therapy followed by prednisolone of 1 mg/kg/d. Azathioprine, cyclophosphamide, cyclosporine A and mycophenolate mofetil are also recommended for thrombosis in BD. In refractory cases, anti-TNF-α inhibitors including adalimumab or infliximab might be useful4, 9 in addition to immunosuppressive drugs. Further, anti-TNF inhibitors have corticosteroid-sparing effect in vascular BD.9 In patients with rheumatoid arthritis, the most common adverse events were infections during anti-TNF-α inhibitors treatment, particularly in older patients.5 In BD patients including vascular BD with anti-TNF-α inhibitors treatment, infections are also the most important issues.10 However, previous reports about BD with anti-TNF-α inhibitors treatment included mainly those for younger patients. There are few reports of anti-TNF-α inhibitors treatment for BD patients older than 80 years. In this case, we reported successful treatment with ADA in a 80-year-old BD patient without adverse events including infections. In conclusion, this case suggests that anti-TNF-α treatment is an effective and safe therapy for older vascular BD patients. None. No potential conflict of interest is reported by the authors. The patient provided written informed consent for publication of his data.