Global Meta-Analysis on the Association between Behcet Syndrome and Polymorphisms from the HLA Class I (A, B, and C) and Class II (DRB1, DQB1, and DPB1) Genes

Behcet syndrome (BS) is a multisystemic perivasculitis whose genetic susceptibility is linked to HLA region. We first meta-analysed all HLA class I and II genes involved in BS susceptibility in all ethnic groups worldwide. We identified 1141 articles and finally included 31 case-control studies after multiple rounds of selection. We analysed frequencies for 24 HLA-A alleles (3 alleles for HLA-A ∗ 26 at four digits), 50 HLA-B alleles (11 alleles for HLA-B ∗ 51 at four digits), 15 HLA-C alleles, 16 HLA-DRB1 alleles, 6 HLA-DQB1 alleles, and 15 HLA-DPB1 alleles. We meta-analysed only HLA allelic frequencies from at least three studies; therefore, we investigated 21 alleles out of 140. Going from 7.00 to 1.6 OR, we found 11 class I alleles conferring risk for BS: B ∗ 51 : 08 , B ∗ 51 , B ∗ 51 : 01 , B ∗ 51 : 02 , DQB 1 ∗ 03 , A ∗ 26 : 01 , Cw ∗ 14 , Cw ∗ 15 , Cw ∗ 16 , B ∗ 15 , and A ∗ 26 . Overall, the studies included populations from Europe (Greece, Spain, Italy, Germany, and Ireland), Asia (Korea, China, China Han, and Thailand), Middle East (Israel, Saudi Arabia, and Iran), and Morocco (as no other North-African population was included). We collected a number of ethnical groups sufficient to conduct an ethnic-specific meta-analysis where Europeans showed 11.25 OR for B ∗ 51:08 and Japan 3.50 OR for A ∗ 26 : 01 . A remarkable result was that the most frequent HLA − B ∗ 51 two-digit alleles associated with BS were different among populations: HLA − B ∗ 51 : 08 in Europe, HLA − B ∗ 51 : 01 in Turkey, and HLA − B ∗ 51 : 02 in Japan. Overall, we discussed our real-world results with other imputation studies.

A Young Woman With Vessel Dissection and Brainstem Lesions

A 21-year-old woman with baseline depression, 1-year history of recurrent, painful, oral and vaginal ulcers, and cellulitis had a new, severe, acute-onset, left posterior headache with left shoulder pain. On neurologic examination, she had mild right oculomotor and abducens nerve weakness and marked left upper extremity and moderate left lower extremity upper motor neuron–type paresis. Initial brain magnetic resonance imaging showed acute ischemia involving the right pons, right midbrain, right cerebral peduncle, and internal capsule, extending into the right diencephalic region. Neck computed tomography angiography identified a right vertebral artery dissection at the C3 level. Cerebrospinal fluid analysis showed a marked neutrophilic pleocytosis with a reported “high” white blood cell count. HLA-B51 testing was positive. Biopsies of her ulcers indicated nonspecific inflammation with no infectious sources. Her severe headache preceding the manipulations, along with recurrent, painful, oral and genital ulcers (recurrent aphthous stomatitis), cerebrospinal fluid pleocytosis, and brainstem involvement after a vertebral artery dissection, raised concern for Behçet syndrome and eventually neurologic involvement of Behçet syndrome. Recurrent corticosteroid-responsive oral ulcers plus recurrent genital ulcers and skin lesions (cellulitis) fulfill the criteria for Behçet syndrome, with possible neurologic involvement (neuro-Behçet syndrome). The positive HLA-B51 testing was consistent with the diagnosis of Behçet syndrome. Treatment was initiated with low-dose aspirin and intravenous methylprednisolone, after which her neurologic status started to improve. Oral prednisone and azathioprine were added for long-term treatment. At age 25 years, she discontinued azathioprine because she planned pregnancy. At age 27 years, she started having recurrence of oral and genital ulcers, along with axillary ulcerative skin lesions. New-onset diplopia and left-sided weakness also developed before corticosteroid and azathioprine could be reinitiated. Magnetic resonance imaging of the brain showed a new left pontine and cerebellar peduncle lesion with subtle contrast enhancement. Intravenous methylprednisolone was initiated, followed by reinitiation of oral prednisone and the azathioprine regimen for long-term maintenance immunotherapy. The prednisone was slowly tapered after 3 months. The final diagnosis for this patient was relapsing neuro-Behçet syndrome because she had 2 recurrent neurologic episodes associated with 1) vertebral artery dissection and 2) brainstem involvement. If she were to have further relapses, the plan was to administer a tumor necrosis factor-α‎ inhibitor. The case of this patient highlights 3 aspects of Behçet syndrome: 1) diagnosis of systemic Behçet syndrome is made on clinical grounds only, but even if the diagnostic criteria are not fulfilled, once neuro-Behçet syndrome develops, treatment should be initiated to curtail significant morbidity; 2) although rare, arterial involvement in neuro-Behçet syndrome should be recognized; and 3) there are notable sex-dependent factors in the evolution of Behçet syndrome.

Getting to the heart of the matter: diagnostic tools and therapeutic approach to cardiac involvement in Behçet syndrome A Tunisian case series

The aim was to investigate the frequency and spectrum of cardiac involvement (CI) in patients with Behçet syndrome (BS) in the Tunisian context, and to assess the clinical and imaging features, treatment, and outcomes. We retrospectively retrieved the medical records of patients with CI among 220 BS patients admitted to the hospital internal medicine department between February 2006 and April 2019, who fulfilled the International Study Group diagnostic criteria for BS. Ten patients (8 men, 2 women) were eligible for the study. Mean age was 37.3 years. Three patients had 2 isolated episodes of cardiac BS. The different types of CI were coronary artery disease (5/10), intracardiac thrombus (4/10), pericarditis (1/10), myocarditis (1/10), and myocardial fibrosis (1/10). Five patients had associated vascular involvement (50%). Medical treatment was based on corticosteroids and colchicine in all patients (100%), anticoagulants in 8 (80%), and cyclophosphamide followed by azathioprine in 9 (90%). The clinical course was favorable in 9 patients; 1 patient died. CI remains an important feature of BS because of its association with increased risk of mortality and morbidity. Therefore, early screening and detection with imaging methods are paramount. Also, better cooperation between rheumatologists and cardiologists could improve outcomes.