Recomendaciones SER sobre el tratamiento del síndrome de Behçet refractario / SER recommendations on treatment of refractory Behçet's syndrome

Objetivo: Elaborar recomendaciones multidisciplinares, basadas en la evidencia disponible y el consenso de expertos, para el manejo terapéutico de los pacientes con síndrome de Behçet refractario (difícil de tratar, resistente grave, recidivante grave) al tratamiento convencional. Métodos: Un panel de expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO –paciente, intervención, comparación, outcome o desenlace–. A continuación, se realizaron revisiones sistemáticas; la evaluación de la calidad de la evidencia se realizó siguiendo la metodología del grupo internacional de trabajo Grading of Recommendations, Assessment, Development, and Evaluation. Tras esto, el panel multidisciplinar formuló las recomendaciones. Resultados: Se seleccionaron 4 preguntas PICO relativas a la eficacia y seguridad de los tratamientos farmacológicos sistémicos en los pacientes con síndrome de Behçet con manifestaciones clínicas refractarias a terapia convencional, relacionadas con los fenotipos mucocutáneo y/o articular, vascular, neurológico-parenquimatoso y gastrointestinal. Se formularon un total de 7 recomendaciones estructuradas por pregunta, con base en la evidencia encontrada y el consenso de expertos. Conclusiones: El tratamiento de las manifestaciones clínicas más graves del síndrome de Behçet carece de evidencia científica sólida y no existen documentos de recomendaciones específicas para los pacientes con enfermedad refractaria a la terapia convencional. Con el fin de aportar una respuesta a esta necesidad, se presenta el primer documento de recomendaciones de la Sociedad Española de Reumatología específicas para el abordaje terapéutico de estos pacientes, que servirá de ayuda en la toma de decisiones clínica y la reducción de la variabilidad en la atención.(AU)

Objective: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. Methods: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. Results: Four PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. Conclusions: The treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.(AU)

SER recommendations on treatment of refractory Behçet's syndrome.

OBJECTIVE: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment. METHODS: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations. RESULTS: 4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. CONCLUSIONS: The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.

Recurrent myocardial infarction associated with vasculo-Behçet's disease: a case report.

A 39-year-old Japanese man presented with chest oppression in February 2017. Electrocardiogram showed ST-elevation myocardial infarction (MI), and cardiac catheterisation revealed thrombotic occlusion of the right coronary artery (RCA), which was treated with thrombectomy, and he received warfarin. Three days after discharge, he complained of chest oppression again, and re-cardiac catheterisation showed thrombi occlusion of the circumflex artery (LCX) and 90% stenosis with thrombosis in the proximal site of the anterior descending artery (LAD) and RCA. Drug eluting stent was implanted in the LAD and RCA; aspirin and prasugrel hydrochloride were added to warfarin. Before discharge, coronary computed tomography angiography (CTA) found new thrombi in the RCA, LAD, and LCX, and he was referred to our hospital on suspicion of Behçet's disease (BD). Past medical history was notable for recurrent aphthous stomatitis, a pudendal ulcer, and Crohn's disease, for which he had been taking infliximab (5 mg/kg) every 8 weeks until December 2016. Notably, his C-reactive protein (CRP) level increased before and after each MI, suggesting that the thrombi were caused by inflammation. Consequently, we concluded that his abnormalities were manifestations of vasculo-BD. After 3 days of hospitalisation, treatment with prednisolone and colchicine was started. His CRP and D-dimer levels decreased, and coronary CTA after 8 days showed disappearance of the thrombi. We tapered the prednisolone dose, and cardiovascular events have not been observed for 7 months after the treatment initiation. In summary, we report a rare case of MI associated with vasculo-BD and review the relevant literature.

Complete occlusion of right pulmonary artery in Behçet disease.

When a patient with Behçet disease presents with haemoptysis, pulmonary vascular involvement should be considered.

Vasculo-Behçet disease complicated by conversion disorder diagnosed with 18F-fluoro-deoxy-glucose positron emission tomography combined with computed tomography (PET/CT).

Vasculitis in Behçet's disease, termed "vasculo-Behçet's disease," is a major cause of mortality and morbidity. We report a case of vasculo-Behçet's disease complicated by conversion disorder, in which 18F-fluoro-deoxy-glucose positron emission tomography combined with computed tomography (FDG PET/CT) was useful for the diagnosis. A twenty-two-year-old woman recently diagnosed with tonsillitis presented with fever, right foot pain, left equinovarus foot, and numbness in both hands and feet. Laboratory data showed elevated levels of c-reactive protein (CRP). The patient was positive for HLA B51; pathergy testing was also positive. Nerve conduction velocity and electromyography were normal. MRI showed swelling of the left crural muscle group. PET/CT showed intense FDG uptake in the left popliteal artery, demonstrating active vasculitis. The patient was diagnosed with vasculo-Behçet's disease and treated with corticosteroids, colchicine, and infliximab, which led to obvious improvement of the MRI findings and reduction in CRP. However, left equinovarus foot and numbness in the extremities persisted. She also developed aphonia. They were attributed to psychogenic dystonia and conversion disorder, and psychiatric treatment was effective in relieving those symptoms. We suggest that PET/CT may be useful for the early diagnosis of medium-sized vessel vasculitis in patients with Behçet's disease.

Superior Mesenteric Artery Vasculitis in Behçet's Disease: A Case Report and Literature Review.

A 55-year-old male presented with abdominal pain that had begun about 5 days ago. Physical examination revealed oral aphtha, genital aphthosis, and pseudofolliculitis, and the patient was diagnosed with incomplete Behçet's disease (BD). Contrast-enhanced computed tomography (CECT) showed dilation of the superior mesenteric artery and mesenteric infiltration of inflammation, indicating vasculo-BD. The symptoms were improved by 3-day of intravenous methylprednisolone pulse therapy followed by oral prednisolone. A literature review suggested that vasculo-BD should be included as a differential diagnosis in cases with unexplained abdominal pain, arterial dilation, and mesenteric invasion, and CECT examination and steroid therapy should be considered.

Associated arterial and venous cerebral manifestations in Behçet's disease.

Behçet's disease is a rare multisystemic vasculitis with an etiology that is still unknown. Neurological manifestations may be seen in approximately 5-15% of patients, and both parenchymal and extraparenchymal neurological involvement has been described. When cerebral venous thrombosis (CVT) is the main extraparenchymal manifestation of Behçet's disease, the condition is then dubbed "angio-Behçet's syndrome". However, arterial involvement is extremely rare, with only one reported case of vasculo-neuro-Behçet's disease, characterized by both venous and intracranial arterial involvement - until now. This report is of two patients diagnosed with Behçet's disease characterized by the concomitant presence of both cerebral arterial manifestations and CVT.

Case of Behçet's disease complicated by oculomotor nerve palsy associated with internal carotid artery-posterior communicating artery aneurysm.

Behçet's disease (BD) is a relapsing systemic inflammatory disorder of unknown etiology involving systemic vasculitis. Vasculitis in BD results from the involvement of arteries, veins and blood vessels of all sizes, which leads to the three major manifestations of this condition: venous occlusion, arterial occlusion and aneurysm formation. Therefore, whole-body vascular involvement should always be considered in BD patients. Here, we describe the first appearance of an internal carotid-posterior communicating artery aneurysm, resulting in complete oculomotor nerve palsy in a BD patient. A 44-year-old Japanese man suffered from recurrent episodes of erythema nodosum that had presented on the lower extremities for the past 2 years. His condition was diagnosed as an incomplete type of BD based on relapsing oral and genital ulcers, skin eruptions, such as erythema nodosum and folliculitis, a positive pathergy test and systemic arthralgia. Ten years after his initial clinical presentation, he had manifestations of right-sided ptosis and cyclic dull pain in his right temporal region. Magnetic resonance imaging and angiography revealed a right internal carotid artery-posterior communicating artery aneurysm. Although oculomotor nerve palsy associated with internal carotid artery-posterior communicating artery aneurysm in a BD patient has not been reported previously, our report highlights the fact that this abnormal manifestation should be considered in those with vasculo-BD.

An autopsy case of refractory vasculo-Behçet's disease.

Pulmonary vascular involvement in Behçet's disease is a rare complication with a poor prognosis. We present an autopsy case of vasculo-Behçet's disease complicated by pulmonary hemorrhage, possibly caused by rupture of pulmonary artery aneurysms. The patient was treated with a combination of high-dose steroids and pulse cyclophosphamide, but he died from massive hemoptysis. This case highlights the need for potent new therapies for patients with vasculo-Behçet's disease refractory to conventional immunosuppressive therapy, such as a combination of steroids and cyclophosphamide.

Successful Treatment of Vasculo-Behcet's Disease Presenting as Recurrent Pseudoaneurysms: the Importance of Medical Treatment.

INTRODUCTION: Vasculo-Behcet's disease is a subtype of Behcet's disease, characterized by cases in which vascular complications are present and often dominate the clinical features. In this disease, there are four different vascular complications: arterial occlusion, arterial aneurysm or pseudoaneurysm, venous thrombosis, and variceal formation. It is rare that arterial lesions are multiple, but without venous involvement. So far, the optimal treatment of the disease has not been established. CASE REPORT: The authors report a rare case of vasculo-Behcet's disease with multiple and recurrent pseudoaneurysms in large arteries, but without affecting the venous system. The patient underwent three rounds of surgery, but developed a new pseudoaneurysm after each operation in short term. However, the patient was successfully treated with a combination of prednisone and immunosuppressive agents. CONCLUSION: For Vasculo-Behcet's disease, surgical and endovascular interventions alone increased the incidence of pseudoaneurysm. Early diagnosis and early initiation of prednisone in combination with immunosuppressive therapy are critical for inhibiting the progression of vascular lesions and provide a good prognosis.

Vasculo-Behçet's Disease that Began with Femoral Arterial Pseudoaneurysm Followed by Deep Venous Thrombosis: Report of a Case.

Vasculo-Behçet's disease mainly affects the venous system and central or peripheral arteries. It is often difficult to diagnosis this due to the complexity of symptoms and the rarity. A 35-year-old man with refractory inguinal lymphadenitis was admitted to our hospital. He was diagnosed with left femoral arterial pseudoaneurysm by enhanced CT scan of the lower legs, and we performed an emergency operation. Seven months postoperatively, he suddenly developed deep venous thrombosis, and then, symptoms such as aphthous stomatitis and pudendal ulcer started to develop progressively, complicating his uveitis. Finally, he was diagnosed with vasculo-Behçet's disease.

Vasculo-Behcet's Disease Developing in a Patient with Ebstein Anomaly / 대한류마티스학회지

Behcet's disease (BD) is a chronic inflammatory disease, involving several organs. It is well known that there are the marked regional differences in the disease expression of BD. In case of the vascular involvement in BD, the frequency rate has been described in 25~30% among the patients from the MiddLe East, whereas it has been noted in 5~15% in our country. In general, BD associated with large vessel lesions is named vasculo-BD. On the other hand, the cardiac involvement in BD has rarely been reported in the literature. Ebstein anomaly is a kind of malformation that is characterized by a downward displacement of the tricuspid valve into the right ventricle. We reported a 54-year-old male patient with vasculo-BD who had inferior vena cava obstruction and Ebstein anomaly. The association of Ebstein anomaly with vasculo-BD is considered to be coincidental. To the best of our knowledge, this is the first case of Ebstein anomaly associated with BD.