Behçet's disease – a contemporary review

New insights into the pathogenesis of Behçet's disease.

Adult-onset Still's disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. Owing to its sporadic appearance in all adult age groups with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications, AoSD is an unsolved challenge for clinicians with limited therapeutic options. This Review provides a comprehensive insight into the complex and heterogeneous nature of AoSD, describing biomarkers of the disease and its progression and the cytokine signalling pathways that contribute to disease. The efficacy and safety of biologic therapeutic options are also discussed, and guidance for treatment decisions is provided. Improving the approach to AoSD in the future will require much closer cooperation between paediatric and adult rheumatologists to establish common diagnostic strategies, treatment targets and goals.

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Mechanisms, biomarkers and targets for adult-onset Still's disease.

Behçet's disease: Ocular effects and treatment

Objective. To investigate comprehensively the relationships between Behcet's disease (BD) clinical features and HLA-B51 or HLA-B5 (HLA-B51/B5) status using meta-analyses. Methods. Relevant publications were identified by a systematic literature search. Eligible studies had to provide frequencies for one or more BD characteristics according to HLA-B51/B5 status. Pooled relative risks (RRs) were calculated by random-effects meta-analysis for those BD characteristics for which five or more relevant studies were identified. Between-study variability was assessed with I 2 and Q-statistics, and modelled using meta-regression. Results. Among the 859 publications evaluated, 72 (representing 74 study populations) met eligibility criteria. Pooled RRs (95% CIs) of the association of HLA-B51/B5 with the 14 analysed clinical character- istics were male sex 1.14 (1.05, 1.23); eye involvement 1.13 (1.06, 1.21); genital ulcers 1.07 (1.01, 1.14); skin involvement 1.10 (1.03, 1.16); erythema nodosum 1.11 (0.96, 1.29); pseudofolliculitis 1.07 (0.93, 1.23); positive pathergy test 1.05 (0.94, 1.17); joint involvement 0.94 (0.86, 1.04); neurological involvement 0.95 (0.71, 1.27); gastrointestinal involvement 0.70 (0.52, 0.94); thrombophlebitis 1.17 (0.77, 1.76); vascular involvement 1.00 (0.68, 1.47); chest involvement 1.55 (0.75, 3.20) and orchiepididymitis 1.13 (0.59, 2.15). For most of the analysed outcomes, between-study heterogeneity was low or absent and most of the meta-regression models were statistically non-significant. Conclusion. The results of these meta-analyses showed that, in BD, HLA-B51/B5 carriage predominates in males and is associated with moderately higher prevalences of genital ulcers, ocular and skin mani- festations, and a decreased prevalence of gastrointestinal involvement.

Relationships of HLA-B51 or B5 genotype with Behçet's disease clinical characteristics: systematic review and meta-analyses of observational studies

Objective We aimed to describe the epidemiological and clinical aspects of deep vein thrombosis (DVT) in Behcet's disease (BD) and to determine the patients at high risk for this complication. Methods Among 113 patients with BD according to the international criteria for classification of BD, those with DVT were retrospectively studied. The diagnosis of DVT was made in all cases using conventional venous angiography, venous ultrasonography and/or thoracic or abdominal computed tomography. Patients were divided in two subgroups according to the occurrence of DVT other than cerebral thromboses. The medical records of these patients were reviewed in order to investigate their past medical history and evaluate their response to the treatment prescribed. Clinical and genetic factors (HLA B51 and MICA 6) that might contribute to DVT were analysed by comparing patients with and without DVT, Results of our series were compared to those of other series in the literature. Statistical analysis was by Chi square with necessary correction and Fischer tests. Results Forty-four patients (38.9%) had deep vein thrombosis of various systems with vein thrombosis of various systems with 81 localisations. There were 40 men and four women (mean age 28.1 years; range 17-60). DVT appeared after the onset of disease with a mean delay of 3.8 years. In 6 cases, DVT revealed BD. When we evaluated the risk of DVT coexistence with other clinical findings and genetic factors (HLA B51 and MICA 6), we found a significant positive correlation with sex, and positive pathergy test Conclusion In our series, occurrence of DVT was significantly associated with male gender and positive pathergy test.

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Deep vein thrombosis in Behçet's disease.

Summary Objectives Budd–Chiari syndrome is a rare and serious complication of Behcet's disease, and is the result of occlusion of the major hepatic veins, the adjacent inferior vena cava, or both. The aim of this study was to determine the prevalence, clinical and laboratory findings, and treatment and clinical course of Budd–Chiari syndrome associated with Behcet's disease. Methods We analyzed retrospectively the charts of 220 patients fulfilling the international diagnostic criteria of Behcet's disease. From them, we selected those with Budd–Chiari syndrome, and analyzed their epidemiological and clinical imaging features and outcomes. Results Seven male patients, mean age 29 years and already diagnosed with Behcet's disease, had Budd–Chiari syndrome. The clinical course was from subacute to chronic in all cases. Thrombosis of hepatic veins was associated with inferior vena cava thrombosis in six cases. Four patients had other venous thromboses (superior vena cava and lower limbs) and one also had pulmonary emboli. One patient was positive for anticardiolipin antibodies. All patients had anticoagulation therapy, and six had high-dose corticotherapy associated, in two cases, with monthly cyclophosphamid intravenous pulses. Clinical outcome was favourable in six cases, and one patient died of hepatic failure. Conclusion The prevalence of Budd–Chiari syndrome in patients with Behcet's disease is 3.2%, confirming that this syndrome is not uncommon in Behcet's patients. The inferior vena cava is frequently involved in combination with hepatic veins and often associated with other venous thrombosis. The prognosis may be favorable with medical interventions, including anticoagulation, treatment of the vasculitis and the use of diuretics when required.

Budd-Chiari syndrome associated with Behçet's disease

Resume Propos. – Analyser les caracteristiques cliniques de l’atteinte neurologique au cours de la maladie de Behcet (MB) et determiner un sous-groupe de patients a haut risque pour cette complication. Patients et methodes. – Cent cinq dossiers de patients atteints d’une MB repondant aux criteres diagnostiques du groupe international d’etude sur la MB ont ete retrospectivement revus. Les patients ont ete divises en 2 groupes selon l’existence (groupe 1) ou non (groupe 2) de manifestations neurologiques et/ou psychiatriques attribuees a la MB. Les differentes caracteristiques cliniques et genetiques (HLA-B51 et MICA A6) ont ete comparees au moyen des test de Kruskall Wallis et du χ2. Resultats. – Vingt-sept patients (25,7 %) ont presente des manifestations neurologiques. Il s’agissait de 20 hommes et 7 femmes ayant un âge moyen de 34,26 ± 8,79 ans. Dix-neuf patients (70,3 %) avaient une atteinte centrale meningoparenchymateuse « MP » (tronc cerebral : 9, hemispheres cerebraux : 6, moelle : 4, atteinte psychiatrique : 2, syndrome pyramidal isole : 1, meningite aseptique isolee : 1). Sept patients (25,9 %) avaient une atteinte des gros vaisseaux cerebraux qualifiee d’angio-Behcet cerebral (ABC) (hypertension intracrânienne : 5 cas dont 3 par thromboses veineuses cerebrales et 2 « idiopathiques », 1 thrombose arterielle cerebrale et 1 hemorragie cerebromeningee). Un patient (3,7 %) avait les 2 types d’atteinte. Parmi les signes cliniques les cephalees etaient significativement plus frequentes dans le groupe « MP ». Dans le groupe 1, l’evolution des manifestations neurologiques (precisee dans 21 cas) s’est faite vers la remission complete ou avec des sequelles minimes dans 13 cas, la persistance de sequelles importantes dans 3 cas, l’aggravation dans 1 cas et la non-amelioration dans 1 cas ; trois patients sont decedes. Aucun element clinique ou paraclinique n’avait de valeur pronostique significative dans le groupe 1. Par comparaison au groupe 2, les anevrismes etaient significativement plus frequents dans le sous-groupe « ABC ». L’uveite etait plus frequente dans le sous-groupe « ABC » que dans le sous-groupe « MP » de facon significative et que le groupe 2 mais avec une difference a la limite de la signifiance. Conclusion. – La frequence de l’atteinte neurologique dans la MB est elevee dans notre serie (25,7 %). Les anevrismes arteriels semblent constituer un facteur de risque pour l’angio-Behcet cerebral. L’angio-Behcet cerebral parait proteger les patients contre l’uveite.

Les manifestations neurologiques de la maladie de Behçet : analyse d'une série de 27 patients

But. - Etudier les caracteristiques cliniques, paracliniques et evolutives des thromboses caves (TC) au cours de la maladie de Behcet (MB) ainsi que leur association avec d'autres atteintes severes de la maladie. Patients et methodes. - Parmi 121 patients atteints d'une MB, nous avons selectionne ceux ayant une TC. Nous avons analyse retrospectivement plusieurs donnees cliniques et paracliniques (dont le taux de l'antithrombine III, des proteines C et S, des anticorps anticardiolipine (aCL) chez 9 patients et des anticorps anti-beta-2-glycoproteine 1 (a β 2GPI)) chez 3 patients. Nous avons compare les resultats des patients avec TC avec ceux sans TC. La comparaison des resultats faite avec le test du X 2 avec correction de Yates. Resultats. - Dix patients avaient une thrombose cave (8,2 % Ils etaient tous de sexe masculin et avaient un âge moyen de 35 ans (extremes: 30-42 ans). Il s'agissait d'une thrombose cave inferieure isolee dans 6 cas, d'une thrombose cave superieure isolee dans 3 cas et d'une TC double (superieure et inferieure) dans un cas. Dans tous les cas, la TC avait une traduction clinique qui s'est manifestee de facon insidieuse et progressive. La TC etait associee a une phlebite d'un membre inferieur chez 4 patients et a un syndrome de Budd-Chiari chez 6 patients. Parmi les differentes manifestations cliniques etudiees, seule l'atteinte neurologique etait significativement plus frequente dans le groupe avec TC (p = 0,001). Le taux des proteines C, S et celui de l'antithrombine III etait normal dans tous les cas. La recherche des aCL etait positive dans 1 cas, alors que celle des a β 2GPI etait negative 3 fois sur 3. Tous nos patients ont ete traites par des anticoagulants et des corticoides a fortes doses associes au cyclophosphamide intraveineux chez six patients. Un patient est decede par une insuffisance hepatocellulaire. Les 9 autres se sont soit ameliores (6 cas), soit stabilises, avec un recul moyen est de 2,5 ans.

[Vena cava thrombosis in Behçet's disease. Analysis of a series of 10 cases].

Adult-onset Still's disease (AOSD) is an uncommon inflammatory condition of unknown origin. In chronic disease, joint involvement is often predominant and erosions are noted in one third of patients. Therapeutic strategies derive from observational data. Corticosteroids are usually the first-line treatment. With inadequate response to corticosteroids, methotrexate appears the best choice to control disease activity and allow for tapering of steroid use. For refractory disease, biological therapy seems the most promising. We report here the case of a 38-year-old female patient with AOSD refractory to cytotoxic agents, treated by rituximab infusion therapy with favorable outcome.

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I. Ben Ghorbel

Papers

Deep vein thrombosis in Behçet's disease.

Budd-Chiari syndrome associated with Behçet's disease

Les manifestations neurologiques de la maladie de Behçet : analyse d'une série de 27 patients

[Vena cava thrombosis in Behçet's disease. Analysis of a series of 10 cases].

Successful treatment of refractory adult onset Still's disease with rituximab.