1
|
Wang X, Zhang J, Wu J, Wang X, Yao X, Niu W, Li X, Li J. Clinical characteristics of coronary artery involvement in children with Behcet's syndrome. Clin Rheumatol 2025; 44:385-390. [PMID: 39585573 DOI: 10.1007/s10067-024-07228-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 10/16/2024] [Accepted: 11/04/2024] [Indexed: 11/26/2024]
Abstract
OBJECTIVES To review the clinical features, treatment, and prognosis of coronary involvement in Behcet's syndrome in children. METHODS Retrospectively analyzed medical records of BS patients admitted to our institution from 2012 to 2024. RESULTS Six children with BS with coronary involvement were admitted, including 2 males and 4 females. The mean age was 5.7 years and the mean course was 17.2 months. All of them had coronary dilatation, including 1 case with aneurysmal dilatation, 2 cases with bilateral coronary dilatation, 4 cases with unilateral dilatation, and 4 cases with valvular disease. No symptom for coronary artery dilation and all of coronary dilatation were detected by echocardiography. Manifestations of extracardiac vascular involvement included arteriovenous wall thickness and thrombosis. Five cases had only arterial involvement and one case had both artery and vein involvement. Pulmonary artery was involved in 1 case. All of them were treated with glucocorticoid and immunosuppressant, 1 child was treated with TNF-α, and 1 received aortic valvuloplasty due to a large number of aortic regurgitations. The patient with coronary aneurysm died suddenly after giving up treatment, and the other 4 cases were all improved to varying degrees. CONCLUSION Vascular involvement is an important factor affecting the prognosis of Behcet's syndrome. Patients with coronary involvement are occultic and difficult to diagnose. Both arteries and veins can be involved, and some patients have severe symptoms. Clinicians should attach great importance to early vascular screening, especially coronary artery. Early combined medication may help improve the prognosis. Key Points • Vascular involvement is an important factor affecting the prognosis of Behcet's syndrome. • Coronary involvement in BS is rare in children, which is predominantly coronary dilatation. • The onset of BS with coronary involvement is insidious and easy to be missed, so early coronary artery screening in children with BS should be emphasized. • Early combined medication may help improve the prognosis of BS with coronary involvement.
Collapse
Affiliation(s)
- Xinning Wang
- Department of Rheumatology and Immunology, Capital Institute of Pediatrics, Beijing, China
| | - Jinru Zhang
- Department of Rheumatology and Immunology, Capital Institute of Pediatrics, Beijing, China
| | - Jing Wu
- Center of Evidence-Based Medicine, Capital Institute of Pediatrics, Beijing, China
| | - Xiaolei Wang
- Department of Rheumatology and Immunology, Capital Institute of Pediatrics, Beijing, China
| | - Xin Yao
- Department of Rheumatology and Immunology, Capital Institute of Pediatrics, Beijing, China
| | - Wenquan Niu
- Center of Evidence-Based Medicine, Capital Institute of Pediatrics, Beijing, China
| | - Xiaohui Li
- Department of Cardiovascular, Capital Institute of Pediatrics, Beijing, China.
| | - Jianguo Li
- Department of Rheumatology and Immunology, Capital Institute of Pediatrics, Beijing, China.
- Department of Rheumatology and Immunology, The Affiliated Children's Hospital, Capital Institute of Pediatrics, 2 Yabao Road, Chaoyang District, Beijing, 100020, China.
| |
Collapse
|
2
|
Fazaa A, Makhlouf Y, Ben Massoud F, Miladi S, Boussaa H, Ouenniche K, Souebni L, Kassab S, Chekili S, Ben Abdelghani K, Laatar A. Behçet disease: epidemiology, classification criteria and treatment modalities. Expert Rev Clin Immunol 2024; 20:1437-1448. [PMID: 39101633 DOI: 10.1080/1744666x.2024.2388693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 06/24/2024] [Accepted: 08/01/2024] [Indexed: 08/06/2024]
Abstract
INTRODUCTION Behçet disease (BD) is an inflammatory multisystem disorder of unknown etiology, believed to be triggered by infection and environmental factors in genetically predisposed individuals. The significance of understanding BD lies in its impact on global health due to its diverse clinical manifestations and geographical distribution. AREAS COVERED This review discusses the epidemiology of BD, emphasizing its prevalence estimated at 10.3 (95% CI, 6.1, 17.7) per 100,000 population, with higher rates observed in regions historically linked to the Silk Route. The criteria for diagnosis are explored, focusing on clinical manifestations that guide healthcare professionals in identifying and managing BD. Additionally, the review encompasses treatment strategies, highlighting TNF-alpha inhibitors as pivotal biologics and newer agents like IL-1 inhibitors and Ustekinumab that broaden the therapeutic options for BD. EXPERT OPINION Our work provides insights into the evolving landscape of treatments for BD, emphasizing the expanding role of newer agents alongside established therapies like TNF-alpha inhibitors.
Collapse
Affiliation(s)
- Alia Fazaa
- Department Rheumatolgy, Mongi Slim hospital, La marsa, Tunisia
| | | | | | - Saoussen Miladi
- Department Rheumatolgy, Mongi Slim hospital, La marsa, Tunisia
| | - Hiba Boussaa
- Department Rheumatolgy, Mongi Slim hospital, La marsa, Tunisia
| | - Kmar Ouenniche
- Department Rheumatolgy, Mongi Slim hospital, La marsa, Tunisia
| | - Leila Souebni
- Department Rheumatolgy, Mongi Slim hospital, La marsa, Tunisia
| | - Selma Kassab
- Department Rheumatolgy, Mongi Slim hospital, La marsa, Tunisia
| | - Selma Chekili
- Department Rheumatolgy, Mongi Slim hospital, La marsa, Tunisia
| | | | - Ahmed Laatar
- Department Rheumatolgy, Mongi Slim hospital, La marsa, Tunisia
| |
Collapse
|
3
|
Di Cianni F, Mastrolia MV, Biancalana E, Marinello D, Emmi G, Mosca M, Simonini G, Talarico R. Challenges and opportunities in transitional care process in Behçet's syndrome. Front Med (Lausanne) 2024; 11:1456063. [PMID: 39359917 PMCID: PMC11444993 DOI: 10.3389/fmed.2024.1456063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 09/04/2024] [Indexed: 10/04/2024] Open
Abstract
Behçet's syndrome (BS) is a rare chronic multi-systemic inflammatory disorder that usually involves adults between third and fourth decades of life, while pediatric and juvenile onset are relatively rare. BS young patients (YP) often develop a full-blown disease late after onset, requiring careful diagnostic workup and regular follow-up while they grow up. In this regard, the purpose of transitional programs is to ensure continuous high-quality care to YP with chronic conditions, providing them with the skills necessary to become independent and empowered adults able to chronically self-manage their disease. EULAR/PReS released the first set of standards and recommendations for transitional care (TC) of YP with juvenile-onset rheumatic diseases, but the appropriate timing for transition, the tools to evaluate patients' readiness, and indicators of transition plans effectiveness still need to be identified. Although little is known regarding TC in BS, it is easy to assume that BS YP will benefit from developmentally and disease-specifically appropriate transition plans, which may promote continuity of care, improve perceived quality of life and prevent poor disease outcomes. This perspective article discusses the key concepts and the goals of TC, addressing the potential challenges and opportunities of TC for YP with BS in clinical practice.
Collapse
Affiliation(s)
- Federica Di Cianni
- Rheumatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Maria Vincenza Mastrolia
- Rheumatology Unit, ERN ReCONNET Center, Meyer Children’s Hospital IRCCS, Florence, Italy
- NEUROFARBA Department, University of Florence, Florence, Italy
| | - Edoardo Biancalana
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Diana Marinello
- Rheumatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Giacomo Emmi
- Department of Medical, Surgery and Health Sciences, University of Trieste, Italy, and Clinical Medicine and Rheumatology Unit, Cattinara University Hospital, Trieste, Italy
- Centre for Inflammatory Diseases, Monash University Department of Medicine Monash Medical Centre, Melbourne, VIC, Australia
| | - Marta Mosca
- Rheumatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Gabriele Simonini
- Rheumatology Unit, ERN ReCONNET Center, Meyer Children’s Hospital IRCCS, Florence, Italy
- NEUROFARBA Department, University of Florence, Florence, Italy
| | - Rosaria Talarico
- Rheumatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| |
Collapse
|
4
|
Emmi G, Bettiol A, Hatemi G, Prisco D. Behçet's syndrome. Lancet 2024; 403:1093-1108. [PMID: 38402885 DOI: 10.1016/s0140-6736(23)02629-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 11/13/2023] [Accepted: 11/21/2023] [Indexed: 02/27/2024]
Abstract
Behçet's syndrome is a rare, chronic multisystemic inflammatory disorder also known as the Silk Route disease due to its geographical distribution. Behçet's syndrome is a multifactorial disease and infectious, genetic, epigenetic, and immunological factors contribute to its pathogenesis. Its heterogeneous spectrum of clinical features include mucocutaneous, articular, ocular, vascular, neurological, and gastrointestinal manifestations that can present with a relapsing and remitting course. Differential diagnosis is often hampered by the non-specific clinical presentation and the absence of laboratory biomarkers or pathognomonic histological features. The therapeutic approach is tailored on the basis of patient-specific manifestations and relies on glucocorticoids, colchicine, and traditional and biological immunosuppressants. Despite progress in the knowledge and management of the disease, unmet needs in diagnostics, monitoring, prediction, and treatment personalisation challenge clinical practice, making Behçet's syndrome a complex disorder associated with an increased risk of morbidity.
Collapse
Affiliation(s)
- Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Melbourne, VIC, Australia.
| | - Alessandra Bettiol
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Gülen Hatemi
- Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Türkiye
| | - Domenico Prisco
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| |
Collapse
|
5
|
Bugaut H, Barete S, Bagot M, Bouaziz JD, Le Pelletier de Glatigny F, Gallien Y, Biard L, Domont F, Cacoub P, Saadoun D, Comarmond C. Neutrophilic dermatosis and hidradenitis suppurativa in patients with Behçet's disease: A neutrophilic disease in the spectrum of autoinflammatory syndromes. Semin Arthritis Rheum 2023; 61:152224. [PMID: 37207416 DOI: 10.1016/j.semarthrit.2023.152224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 05/05/2023] [Accepted: 05/10/2023] [Indexed: 05/21/2023]
Abstract
BACKGROUND Association of neutrophilic dermatosis (ND), hidradenitis suppurativa (HS) and Behçet's disease (BD) and shared efficacy of TNFα axis blockade suggests common physiopathology. OBJECTIVES To investigate the clinical features and therapeutic response of ND and HS associated with BD. METHODS We identified 20 patients with ND or HS associated with BD among 1462 patients with BD. RESULTS We analysed 20 (1.4%) patients diagnosed with ND or HS associated with BD: 13 HS, 6 pyoderma gangrenosum (PG), and 1 SAPHO. Our 6 PG cases over 1462 BD patients accounts for 400/100 000 prevalence. Thirteen had bipolar aphthosis, 6 vascular, 5 neurologic, and 4 ocular involvements. All PG occurred on limbs and had typical histology with constant dermal neutrophilic infiltrate. All HS had the classical axillary-mammary phenotype. Sixty-nine percent (69%) of HS were Hurley 1 stage. Treatment consisted mainly in colchicine (n = 20), glucocorticoids (n = 12), and anti-TNFα (n = 9). Interesting results with complete or partial responses were obtained with anti-TNFα (9 cases), ustekinumab (3 cases) and tocilizumab (1 case) to treat refractory ND or HS associated with BD. CONCLUSION PG seems overrepresented in patients with BD. Biotherapies such as anti-TNFα, ustekinumab and tocilizumab appear to be promising to treat refractory ND or HS associated with BD.
Collapse
Affiliation(s)
- Hélène Bugaut
- Department of Internal Medicine and Clinical Immunology, Sorbonne University, Pitié-Salpêtrière Hospital, APHP, 75013 Paris France, Centre de référence Maladies Autoimmunes systémiques rares, Centre de référence Maladies Autoinflammatoires et amylose, 83 boulevard de l'hôpital, Paris 75013, France
| | - Stéphane Barete
- Unit of Dermatology, Pitié-Salpêtrière Hospital, APHP, DMU3ID, Sorbonne Université, Paris 75013, France
| | - Martine Bagot
- Dermatology, Saint-Louis Hospital, Université Paris Cité, Paris 75010, France
| | - Jean-David Bouaziz
- Dermatology, Saint-Louis Hospital, Université Paris Cité, Paris 75010, France
| | | | - Yves Gallien
- Biostatistic, Saint-Louis Hospital, Université Paris Cité, Paris 75010, France
| | - Lucie Biard
- Biostatistic, Saint-Louis Hospital, Université Paris Cité, Paris 75010, France
| | - Fanny Domont
- Department of Internal Medicine and Clinical Immunology, Sorbonne University, Pitié-Salpêtrière Hospital, APHP, 75013 Paris France, Centre de référence Maladies Autoimmunes systémiques rares, Centre de référence Maladies Autoinflammatoires et amylose, 83 boulevard de l'hôpital, Paris 75013, France
| | - Patrice Cacoub
- Department of Internal Medicine and Clinical Immunology, Sorbonne University, Pitié-Salpêtrière Hospital, APHP, 75013 Paris France, Centre de référence Maladies Autoimmunes systémiques rares, Centre de référence Maladies Autoinflammatoires et amylose, 83 boulevard de l'hôpital, Paris 75013, France
| | - David Saadoun
- Department of Internal Medicine and Clinical Immunology, Sorbonne University, Pitié-Salpêtrière Hospital, APHP, 75013 Paris France, Centre de référence Maladies Autoimmunes systémiques rares, Centre de référence Maladies Autoinflammatoires et amylose, 83 boulevard de l'hôpital, Paris 75013, France.
| | - Cloé Comarmond
- Department of Internal Medicine and Clinical Immunology, Lariboisière Hospital, Université Paris Cité, Paris 75010, France
| |
Collapse
|
6
|
Grzybowski A, Pawlikowska-Łagód K, Altenburg A, Zouboulis CC. Adamantiades-Behçet disease: Between dermatology and ophthalmology. Clin Dermatol 2023; 41:469-475. [PMID: 37572969 DOI: 10.1016/j.clindermatol.2023.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/14/2023]
Abstract
Adamantiades-Behçet disease is an inflammatory, vascular disease of unknown etiology. The disease is named after two physicians, Benediktos Adamantiades and Hulȗsi Behçet, who both made significant contributions to the study of the disease. It was probably first described by Hippocrates in 500 BCE. Adamantiades-Behçet disease is most common in the region encompassing the ancient trade route known as the Silk Road. In Turkey, the disease is estimated to affect 80 to 370 people per 100,000 inhabitants, and it is also the country with the highest incidence rate. The frequency of the disease associated with the clinical picture differs from the origin of the onset. The disease is characterized by recurrent aphthous ulcers of the mouth, genitals, skin lesions, and eye lesions. The disease process can also involve other organs, including the joints, nervous system, large vessels, heart, and gastrointestinal tract. Aphthous oral ulcers appear as the first harbinger of the disease and affect almost all patients (97%-99%). The scientific interest in Adamantiades-Behçet disease has increased exponentially in the past decade.
Collapse
Affiliation(s)
- Andrzej Grzybowski
- Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland; Institute for Research in Ophthalmology, Poznan, Poland
| | | | - Andreas Altenburg
- Departments of Dermatology, Venereology, Allergology, and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Dessau, Germany
| | - Christos C Zouboulis
- Departments of Dermatology, Venereology, Allergology, and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Dessau, Germany
| |
Collapse
|
7
|
Kötter I, Krusche M. [Inflammatory rheumatic diseases in migrants]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2023; 64:426-434. [PMID: 37099225 DOI: 10.1007/s00108-023-01514-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Accepted: 04/04/2023] [Indexed: 04/27/2023]
Abstract
The immigration of people from other countries or even from other continents represents new challenges even for rheumatologists. Although all inflammatory rheumatic diseases that occur in this country also exist in the countries of origin of immigrants, the frequencies are different. Diseases such as familial Mediterranean fever (FMF) or Behçet syndrome (BS) are rare in western Europe but are often more frequent than rheumatoid arthritis (RA) and spondylarthritis (SPA) in North Africa and Mediterranean countries. Furthermore, FMF is associated with the occurrence of spondyloarthritis, which is then frequently negative for the human leucocyte antigen B27 (HLA-B27). There is also an association with BS. Rheumatic fever also still occurs relatively frequently especially in African countries, whereas it is almost eradicated in Europe. Possible differential diagnoses such as rheumatic symptoms in genetically determined anemia or infections such as human immunodeficiency virus (HIV) infections, hepatitis, tuberculosis and parasitosis need to be considered as they are all much more frequent in the countries of origin of immigrants than in northwestern Europe. Last but not least, the treatment situation with modern diagnostic and treatment modalities is different in the countries of origin of the migrants, either because these possibilities are unavailable due to limited resources or because the situation has dramatically deteriorated due to acute events, such as the recent war in Ukraine.
Collapse
Affiliation(s)
- Ina Kötter
- III. Medizinische Klinik, Sektion für Rheumatologie und Entzündliche Systemerkrankungen, Universitätsklinikum Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland.
- Klinik für Rheumatologie und Immunologie, Klinikum Bad Bramstedt, Oskar-Alexander Str. 26, 24576, Bad Bramstedt, Deutschland.
| | - Martin Krusche
- III. Medizinische Klinik, Sektion für Rheumatologie und Entzündliche Systemerkrankungen, Universitätsklinikum Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland
| |
Collapse
|
8
|
Abstract
Behçet's disease is a rare and poorly understood vasculitis affecting blood vessels of all types and sizes. Uveitis and oral and genital ulcers represent the typical clinical triad. Populations along the ancient trading route connecting the Mediterranean basin with the Middle and Far East are most affected. Up to a quarter of the cases has a pediatric onset, typically around puberty. The aim of the treatment is early intervention to control inflammation, with symptom relief and prevention of relapses, damage, and complications. The heterogeneous clinical presentation often requires a multidisciplinary and tailored approach. Ocular, neurological, gastrointestinal, and vascular involvement is associated with a worse prognosis and needs more aggressive treatments. In young patients with expected prolonged disease, treatment should also focus on preventive measures and lifestyle advice. In recent years, the pharmacological armamentarium has grown progressively, although only a limited number of drugs are currently authorized for pediatric use. Most evidence for these drugs still derives from adult studies and experience; these are prescribed as off-label medications and are only available as adult formulations. Corticosteroids frequently represent the mainstay for the management of the initial acute phases, but their potential serious adverse effects limit their use to short periods. Different conventional disease-modifying anti-rheumatic drugs have long been used. Many other biologic drugs targeting different cytokines such as interleukin-1, interleukin-6, and interleukin-17 and treatments with small molecules including the phosphodiesterase 4 and Janus kinase inhibitors are emerging as novel promising therapeutic agents. In recent years, a growing interest has developed around anti-tumor necrosis factor agents that have often proven to be effective in severe cases, especially in those with a gastrointestinal and ocular involvement.
Collapse
|
9
|
Vitale A, Berlengiero V, Caggiano V, Barneschi S, Mourabi M, Sota J, Gentileschi S, Maggio MC, Gaggiano C, Tarsia M, Tosi GM, Lopalco G, Fabiani C, Frediani B, Cantarini L. The diagnostic role of pathergy test in patients with Behçet's disease from the Western Europe. Intern Emerg Med 2023; 18:77-83. [PMID: 36542302 DOI: 10.1007/s11739-022-03117-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 09/29/2022] [Indexed: 12/24/2022]
Abstract
The aim of the study is to evaluate the frequency and features of positive pathergy test (PPT) in Italy, its role in the diagnosis of Behçet's disease (BD), and any association with other BD-related manifestations. 52 BD patients, 52 patients with axial spondyloarthritis (ax-SpA), and 26 healthy controls (HCs) underwent intradermal injection of normal saline and intradermal needle soaked with fresh self-saliva. The results of pathergy tests were statistically analysed in the light of demographic, clinical, and therapeutic features of subjects enrolled. Pathergy test performed with saline resulted always negative in all groups. Skin prick test using self-saliva resulted in the occurrence of a papule in 3 (5.8%) BD patients and in 1 (1.9%) patient with ax-SpA. A ≥ 15 mm erythematous area surrounding the needle prick site was observed in 22 (42.3%) BD patients, 5 (9.6%) patients with ax-SpA, and 2 (7.7%) HCs (p = 0.00002). The frequency of skin erythema was significantly more frequent in patients with BD than those with ax-SpA (p < 0.0001) and HCs (p = 0.003). No statistically significant differences were observed between ax-SpA patients and HCs (p = 1.000). The occurrence of skin erythema at pathergy test was not associated with any BD-related clinical manifestation. Erythema at self-saliva prick test presented a sensitivity of 42.31% (CI 28.73-56.80%) and a specificity of 91.03% (CI 82.38-96.32%). The development of a ≥ 15 mm erythematous area at self-saliva prick test could be sufficient to unveil the hyper-reactivity of the innate immune system in BD patients from Western Europe, where the development of skin erythema shows good sensitivity and specificity toward the diagnosis of BD.
Collapse
Affiliation(s)
- Antonio Vitale
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Policlinico ''Le Scotte'', University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Virginia Berlengiero
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Policlinico ''Le Scotte'', University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Valeria Caggiano
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Policlinico ''Le Scotte'', University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Sara Barneschi
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Policlinico ''Le Scotte'', University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Mariam Mourabi
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Policlinico ''Le Scotte'', University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Jurgen Sota
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Policlinico ''Le Scotte'', University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Stefano Gentileschi
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Policlinico ''Le Scotte'', University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Maria Cristina Maggio
- University Department Pro.Sa.M.I. "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Carla Gaggiano
- Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, Italy
| | - Maria Tarsia
- Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, Italy
| | - Gian Marco Tosi
- Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Giuseppe Lopalco
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Claudia Fabiani
- Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Bruno Frediani
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Policlinico ''Le Scotte'', University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Luca Cantarini
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Policlinico ''Le Scotte'', University of Siena, Viale Bracci 16, 53100, Siena, Italy.
| |
Collapse
|
10
|
Jo YG, Ortiz-Fernández L, Coit P, Yilmaz V, Yentür SP, Alibaz-Oner F, Aksu K, Erken E, Düzgün N, Keser G, Cefle A, Yazici A, Ergen A, Alpsoy E, Salvarani C, Kısacık B, Kötter I, Henes J, Çınar M, Schaefer A, Nohutcu RM, Takeuchi F, Harihara S, Kaburaki T, Messedi M, Song YW, Kaşifoğlu T, Martin J, González Escribano MF, Saruhan-Direskeneli G, Direskeneli H, Sawalha AH. Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients. J Autoimmun 2022; 132:102882. [PMID: 35987173 PMCID: PMC10614427 DOI: 10.1016/j.jaut.2022.102882] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/17/2022] [Accepted: 07/20/2022] [Indexed: 12/24/2022]
Abstract
OBJECTIVES Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. METHODS A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. RESULTS Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10-8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10-8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10-7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. CONCLUSIONS Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease.
Collapse
Affiliation(s)
- Yun Gun Jo
- Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Lourdes Ortiz-Fernández
- Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Patrick Coit
- Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Vuslat Yilmaz
- Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Sibel P Yentür
- Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Fatma Alibaz-Oner
- Division of Rheumatology, Department of Internal Medicine, Marmara University, School of Medicine, Istanbul, Turkey
| | - Kenan Aksu
- Division of Rheumatology, Department of Internal Medicine, Ege University, School of Medicine, Izmir, Turkey
| | - Eren Erken
- Division of Rheumatology, Department of Internal Medicine, Çukurova University, School of Medicine, Adana, Turkey
| | - Nursen Düzgün
- Division of Rheumatology, Department of Internal Medicine, Ankara University, School of Medicine, Ankara, Turkey
| | - Gokhan Keser
- Division of Rheumatology, Department of Internal Medicine, Ege University, School of Medicine, Izmir, Turkey
| | - Ayse Cefle
- Division of Rheumatology, Department of Internal Medicine, Kocaeli University, School of Medicine, Kocaeli, Turkey
| | - Ayten Yazici
- Division of Rheumatology, Department of Internal Medicine, Kocaeli University, School of Medicine, Kocaeli, Turkey
| | - Andac Ergen
- Ophthalmology Clinic, Okmeydanı Research and Education Hospital, Istanbul, Turkey
| | - Erkan Alpsoy
- Department of Dermatology and Venereology, Akdeniz University, School of Medicine, Antalya, Turkey
| | - Carlo Salvarani
- Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia and Università di Modena e Reggio Emilia, Modena, Italy
| | - Bünyamin Kısacık
- Division of Rheumatology, Department of Internal Medicine, Gaziantep University, Faculty of Medicine, Gaziantep, Turkey
| | - Ina Kötter
- Division of Rheumatology and Systemic Inflammatory Diseases, University Hospital Eppendorf, Hamburg, and Clinic for Rheumatology and Immunology, Bad Bramstedt, Germany
| | - Jörg Henes
- Center for Interdisciplinary Rheumatology, Immunology and Autoinflammatory Diseases (INDIRA) and Internal Medicine II (hematology, Oncology, Rheumatology and Immunology), University Hospital Tuebingen, Tuebingen, Germany
| | - Muhammet Çınar
- Division of Rheumatology, Department of Internal Medicine, University of Health Sciences Turkey, Gulhane Faculty of Medicine, Ankara, Turkey
| | - Arne Schaefer
- Department of Periodontology, Oral Medicine and Oral Surgery, Institute for Dental and Craniofacial Sciences, Charité-University Medicine Berlin, Berlin, Germany
| | - Rahime M Nohutcu
- Department of Periodontology, Faculty of Dentistry, Hacettepe University Sihhiye, Ankara, Turkey
| | - Fujio Takeuchi
- School of Pharmaceutical Science, University of Shizuoka, Shizuoka, Japan
| | - Shinji Harihara
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan
| | - Toshikatsu Kaburaki
- Department of Ophthalmology, Jichi Medical University Saitama Medical Center, Japan
| | - Meriam Messedi
- Research Laboratory of Molecular Bases of Human Diseases, 12ES17, Faculty of Medicine of Sfax, University of Sfax, 3029 Sfax, Sfax, Tunisia
| | - Yeong-Wook Song
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, And College of Medicine, Medical Research Center, Seoul National University, Seoul, South Korea
| | - Timuçin Kaşifoğlu
- Division of Rheumatology, Department of Internal Medicine, Osmangazi University, School of Medicine, Eskisehir, Turkey
| | - Javier Martin
- Instituto de Parasitología y Biomedicina 'López-Neyra', IPBLN-CSIC, PTS Granada, Granada, Spain
| | | | | | - Haner Direskeneli
- Division of Rheumatology, Department of Internal Medicine, Marmara University, School of Medicine, Istanbul, Turkey
| | - Amr H Sawalha
- Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Lupus Center of Excellence, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
| |
Collapse
|
11
|
Ashman A, Tucker D, Williams C, Davies L. Behçet's disease in Wales: an epidemiological description of national surveillance data. Orphanet J Rare Dis 2022; 17:347. [PMID: 36068543 PMCID: PMC9449262 DOI: 10.1186/s13023-022-02505-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 09/04/2022] [Indexed: 12/01/2022] Open
Abstract
Objectives Behçet’s disease is a rare, chronic, incurable, multisystemic disease. It causes significant morbidity, with patients experiencing symptoms including mucous membrane ulcers, and joint pain and swelling. It is an important cause of avoidable blindness due to ocular involvement. The aetiology is unknown. The aims were to identify population prevalence of Behçet’s disease in Wales in comparison to other endemic and non-endemic regions, and provide an epidemiological profile of a case series of adult patients. This is the first analysis of data from the Adult Rare Diseases Surveillance Registry for Wales, established in 2020 as part of the COVID-19 pandemic response. Results Between 1995 and 2020, 347 adults and 5 children were recorded in Wales with a diagnosis of Behçet’s disease. Population prevalence was calculated as 11.1 per 100,000 population. Of the adult cases, 76.9% were female, and 6.6% died before the end of the study period. When comparing genders, there were no statistically significant differences in age at diagnosis, mortality or socioeconomic status. There was no evidence that the age at which cases were diagnosed had changed over time. Survival analyses showed no significant differences in durations of survival between genders or individuals residing in different WIMD 2019 quintiles. Age at diagnosis was the only factor significantly and independently associated with poorer durations of survival (p < 0.001).
Collapse
Affiliation(s)
- Annie Ashman
- Public Health Wales, Capital Quarter 2, Tyndall Street, Cardiff, CF10 4BZ, UK.
| | - David Tucker
- Congenital Anomaly Register and Information Service, Public Health Wales, Capital Quarter 2, Tyndall Street, Cardiff, CF10 4BZ, UK
| | - Ceri Williams
- Congenital Anomaly Register and Information Service, Public Health Wales, Capital Quarter 2, Tyndall Street, Cardiff, CF10 4BZ, UK
| | - Llion Davies
- Public Health Wales, Capital Quarter 2, Tyndall Street, Cardiff, CF10 4BZ, UK
| |
Collapse
|
12
|
Jalali KS, Alhazzaa MA, Alqahtani S, Alattas MY. Pontine Infarction and Vertebral Artery Dissecting Aneurysm as the First Presentation of Behçet's Disease: A Case Report. Cureus 2022; 14:e29204. [PMID: 36259031 PMCID: PMC9572958 DOI: 10.7759/cureus.29204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/15/2022] [Indexed: 11/06/2022] Open
Abstract
Behçet's disease (BD) is a systemic disease of inflammatory origin that appears most often in the third or fourth decade of life. Behçet's disease is hallmarked predominantly by mucocutaneous lesions and ocular involvement. Vertebral artery dissection and neurological manifestations are rare complications in Behçet's disease. We examine the case of a medically free 33-year-old male who was admitted to the emergency department complaining of sudden-onset dizziness, vomiting, and tinnitus. Neurological examination revealed fluctuating consciousness, multiple gaze nystagmus, motor deficit in the upper and lower limbs, bilateral Babinski sign, and truncal ataxia. Magnetic resonance imaging (MRI) showed a right pontine hyperintense lesion on T2-weighted images (T2WI). A right vertebral angiogram four months after the incident showed a dissection in the mid-cervical third of an anomalous duplicated origin arm of the right vertebral artery. This case describes an uncommon form of initial presentation of Behçet's disease via a pontine infarction triggered by a dissecting aneurysm in an anatomically rare variant of the vertebral artery.
Collapse
Affiliation(s)
- Kafaf S Jalali
- Internal Medicine, Prince Mohammed Bin Abdulaziz Hospital/Saudi Commission for Health Specialties, Medina, SAU
| | | | - Sultan Alqahtani
- Interventional Neuroradiology, Medical Imaging Administration, King Fahad Medical City, Riyadh, SAU
| | | |
Collapse
|
13
|
Agarwal K, Patel C, Long R, Cornford PA. Spontaneous retroperitoneal haemorrhage as a first presentation of Behçet disease. JOURNAL OF CLINICAL UROLOGY 2022. [DOI: 10.1177/2051415819837437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Level of evidence – Level 5 (case report)
Collapse
Affiliation(s)
- Ketan Agarwal
- Department of Urology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, UK
| | - Chirag Patel
- Department of Urology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, UK
| | - Ronan Long
- Department of Urology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, UK
| | - Philip A Cornford
- Department of Urology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, UK
| |
Collapse
|
14
|
FACANALI CBG, FACANALI JUNIOR MR, RIBEIRO JUNIOR U, QUEIROZ NSF, SOBRADO JUNIOR CW, SAFATLE-RIBEIRO AV. SMALL BOWEL IS LARGELY AFFECTED IN BEHÇET’S DISEASE: A LONG-TERM FOLLOW-UP OF GASTROINTESTINAL SYMPTOMS. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:117-122. [PMID: 35442321 DOI: 10.1590/s0004-2803.202200001-20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 10/07/2021] [Indexed: 11/21/2022]
Abstract
ABSTRACT Background Behçet’s disease is a rare immune-mediated disorder that can affect the gastrointestinal tract. The prevalence and extension of small bowel involvement is largely unknown. Objective The aim of this study was to describe the small bowel lesions diagnosed by double-balloon enteroscopy (DBE) and to verify if these findings were associated to the presence of gastrointestinal symptoms and disease activity after long-term follow-up. Methods This study included 19 Behçet’s disease patients who underwent DBE. After a mean follow-up of 15 years the endoscopic findings were associated to the presence of gastrointestinal symptoms, disease activity and current therapy through collection of electronic medical records. Results A total of 63.2% patients were female and the mean age was 37 years at the time of DBE. Mean disease duration at baseline was 24 years. 11 patients had no gastrointestinal symptoms and eight patients presented either abdominal pain, gastrointestinal bleeding or diarrhea. The average procedure time was 1 hour and 30 minutes and the ileum was achieved in all patients but one. Small bowel ulcers were diagnosed in 78.9%, with 63.1% of jejunal involvement. Two patients presented only small bowel edema and two were normal by DBE. Eight patients had concomitant gastric ulcers. Gastrointestinal symptoms prior to DBE were present in 36.8% of the patients and, after follow-up, all of them persisted with some of the symptoms. Bleeding was reported by three patients at baseline and persisted in only one patient. The frequency of treatment with steroids and immunomodulators was 31.6% and 57.9% at baseline, respectively, and 21% in both at the end of the follow-up. No patient was treated with biologics at the time of the DBE procedure and the current rate of biologic use is 21%. Conclusion Small bowel involvement in Behçet’s disease was frequently demonstrated by DBE even in asymptomatic patients. Understanding clinical evolution of the disease over the years and the impact of such diagnosis still represents a challenge, possibly with the need for novel treatment.
Collapse
|
15
|
Burns E, Cooper E, Peterson R, Diaz LZ. Pediatric Behҫet disease: Update in diagnosis and management. Pediatr Dermatol 2022; 39:173-181. [PMID: 35060179 DOI: 10.1111/pde.14859] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 10/06/2021] [Accepted: 10/24/2021] [Indexed: 11/26/2022]
Abstract
Behҫet disease is a multisystem inflammatory disease and variable vessel vasculitis involving primarily the oral and genital mucosa, skin, and eyes. Diagnosis is challenging due to the lack of a specific diagnostic test and overlap with other autoinflammatory diseases. Treatment of pediatric Behҫet disease aims to reduce inflammation and prevent future flares. The goal of this review is to provide guidance on the diagnostic workup and multidisciplinary approach of pediatric Behҫet disease and review evidence-based treatment strategies for patients with refractory mucocutaneous manifestations.
Collapse
Affiliation(s)
- Emily Burns
- Baylor College of Medicine, Houston, Texas, USA
| | - Elizabeth Cooper
- Department of Internal Medicine, Division of Dermatology, Dell Medical School at UT Austin, Austin, Texas, USA
| | - Rosemary Peterson
- Department of Pediatrics, Division of Pediatric Rheumatology, Dell Medical School at UT Austin, Austin, Texas, USA
| | - Lucia Z Diaz
- Department of Pediatrics, Division of Pediatric Dermatology, Dell Medical School at UT Austin, Austin, Texas, USA
| |
Collapse
|
16
|
Kul Cinar O, Romano M, Guzel F, Brogan PA, Demirkaya E. Paediatric Behçet's Disease: A Comprehensive Review with an Emphasis on Monogenic Mimics. J Clin Med 2022; 11:1278. [PMID: 35268369 PMCID: PMC8911352 DOI: 10.3390/jcm11051278] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/22/2022] [Accepted: 02/24/2022] [Indexed: 02/01/2023] Open
Abstract
Behçet's disease (BD) is a polygenic condition with a complex immunopathogenetic background and challenging diagnostic and therapeutic concepts. Advances in genomic medicine have provided intriguing insights into disease pathogenesis over the last decade, especially into monogenic mimics of BD. Although a rare condition, paediatric BD should be considered an important differential diagnosis, especially in cases with similar phenotypes. Emerging reports of monogenic mimics have indicated the importance of genetic testing, particularly for those with early-onset, atypical features and familial aggregation. Treatment options ought to be evaluated in a multidisciplinary setting, given the complexity and diverse organ involvement. Owing to the rarity of the condition, there is a paucity of paediatric trials; thus, international collaboration is warranted to provide consensus recommendations for the management of children and young people. Herein, we summarise the current knowledge of the clinical presentation, immunopathogenetic associations and disease mechanisms in patients with paediatric BD and BD-related phenotypes, with particular emphasis on recently identified monogenic mimics.
Collapse
Affiliation(s)
- Ovgu Kul Cinar
- Department of Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK; (O.K.C.); (P.A.B.)
- Division of Medicine, National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK
| | - Micol Romano
- Department of Pediatrics, Division of Pediatric Rheumatology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5W9, Canada;
- Canadian Behcet and Autoinflammatory Disease Center (CAN-BE-AID), University of Western Ontario, London, ON N6A 4V2, Canada
| | - Ferhat Guzel
- Molecular Genetics Laboratories, Department of Research and Development, Ant Biotechnology, Istanbul 34775, Turkey;
| | - Paul A. Brogan
- Department of Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK; (O.K.C.); (P.A.B.)
- Great Ormond Street Institute of Child Health, University College London, 30 Guildford Street, London WC1N 1EH, UK
| | - Erkan Demirkaya
- Department of Pediatrics, Division of Pediatric Rheumatology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5W9, Canada;
- Canadian Behcet and Autoinflammatory Disease Center (CAN-BE-AID), University of Western Ontario, London, ON N6A 4V2, Canada
- Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5W9, Canada
| |
Collapse
|
17
|
Hassouna SS, Tayel MY, Elzawawy AI, Amin RM, Tahoun M. MicroRNA548ac expression level in relation to BDCAF scored Behçet’s disease activity and history of treatment response. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-022-00107-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Behçet’s disease gives a challenge to be diagnosed and followed up due to lack of specific biomarkers. MicroRNAs showed relations to different disease states including immunological and inflammatory illnesses. In this study, we are estimating microRNA548ac levels for the first time to be tested in the disease to see if there is a link to disease activity and if microRNA548ac can be used as a biomarker for activity or remission and prognosis of Behçet’s disease. MicroRNA548ac has been shown to have a role in autoimmunity and some inflammatory conditions. Blood samples were taken from patients to measure white blood cells expression of microRNA548ac, and compared to its expression in healthy subjects, disease activity was assessed by usage of Behçet’s Disease Current Activity Form (BDCAF).
Results
MicroRNA548ac expression decreased but not significantly with increased Behçet’s disease activity, and expression was having a significant positive correlation with increased treatment response history.
Conclusions
MicroRNA548ac appeared not to be related to disease activity which needs confirmation in further studies, but it may predict response to treatment so that patients having higher expression of microRNA548ac may have a better response to treatment. Here, microRNA548ac could be used as a disease biomarker for disease prognosis.
Collapse
|
18
|
Abstract
The many forms of vasculitis are characterized by inflammation of blood vessels, leading to potentially long-term sequelae including vision loss, aneurysm formation and kidney failure. Accurate estimation of the incidence and prevalence has been hampered by the absence of reliable diagnostic criteria and the rarity of these conditions; however, much progress has been made over the past two decades, although data are still lacking from many parts of the world including the Indian subcontinent, China, Africa and South America. Giant cell arteritis occurs in those aged 50 years and over and seems to mainly affect persons of northern European ancestry, whereas Takayasu arteritis occurs mainly in those aged under 40 years. By contrast, Kawasaki disease mainly occurs in children aged under 5 years and is most common in children of Asian ancestry, and IgA vasculitis occurs in children and adolescents. Although much less common than giant cell arteritis, the different forms of antineutrophil cytoplasmic antibody-associated vasculitis are being increasingly recognized in most populations and occur more frequently with increasing age. Behçet syndrome occurs most commonly along the ancient silk road between Europe and China. Much work needs to be done to better understand the influence of ethnicity, geographical location, environment and social factors on the development of vasculitis.
Collapse
Affiliation(s)
- Richard A Watts
- Norwich Medical School, University of East Anglia, Norwich, UK.
| | - Gulen Hatemi
- Department of Internal Medicine, Division of Rheumatology and Behçet's Disease Research Centre, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Jane C Burns
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Aladdin J Mohammad
- Department of Clinical Sciences, Division of Rheumatology, Lund University and Department of Rheumatology, Skåne University Hospital, Lund, Sweden
- Department of Medicine, University of Cambridge, Cambridge, UK
| |
Collapse
|
19
|
Zając H, Turno-Kręcicka A. Ocular Manifestations of Behçet's Disease: An Update on Diagnostic Challenges and Disease Management. J Clin Med 2021; 10:5174. [PMID: 34768694 PMCID: PMC8584626 DOI: 10.3390/jcm10215174] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/30/2021] [Accepted: 11/03/2021] [Indexed: 11/16/2022] Open
Abstract
Behçet's disease is a systemic vasculitis that affects multiple organs. The most common manifestations are oral and genital ulcerations and recurrent uveitis. Uveitis can be an initial symptom in 10-20% of cases and leads to blindness in 16-25% of patients. The management of this disease is evolving due to the clinical phenotypes recently described in the literature and increasing focus on the detection of subclinical inflammation to enable correct therapeutic decisions. The first line treatment is azathioprine, followed by various immunosuppressive and biological agents as alternatives in severe or refractory cases. This review summarizes scientific articles about the etiology of, diagnostic tools for and treatment of the ocular manifestations of Behçet's disease available in the PubMed database from 1 January 2016 to 1 May 2021. A multidisciplinary approach is necessary to effectively prevent permanent damage and thus improve the life quality of the patients. Therefore, it is crucial to raise awareness of the common clusters of symptoms, use of modern imaging methods, such as ocular computed tomography and fluorescein angiography, and novelty treatment algorithms to enable early diagnosis and appropriate management.
Collapse
Affiliation(s)
- Hanna Zając
- Department of Ophthalmology, University Clinical Hospital in Wroclaw, 50-556 Wroclaw, Poland
| | - Anna Turno-Kręcicka
- Department of Ophthalmology, University Clinical Hospital in Wroclaw, 50-556 Wroclaw, Poland
- Department of Ophthalmology, Wroclaw Medical University, 50-556 Wroclaw, Poland
| |
Collapse
|
20
|
Daoud F, Rachdi I, Somai M, Zaouak A, Hammami H, Ouederni M, Maamouri R, Zoubeidi H, Tougorti M, Ksouri J, Dhaou BB, Aydi Z, Fenniche S, Cheour M, Boussema F. Epidemiological, clinical, and therapeutic characteristics of Behçet's disease: a monocentric study in Tunisia. Pan Afr Med J 2021; 40:13. [PMID: 34733381 PMCID: PMC8531968 DOI: 10.11604/pamj.2021.40.13.19146] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 05/23/2020] [Indexed: 11/11/2022] Open
Abstract
INTRODUCTION to describe the epidemiological, clinical, therapeutic and evolving characteristics of Behçet´s disease and identify prognostic factors. METHODS we have realized a retrospective, single-center study, conducted over a period of 26 years and including 130 patients presenting Behçet´s disease and hospitalized in an Internal Medicine Department. RESULTS the mean age of the Behçet´s disease at onset was 30.3 ±8.8 years and that at diagnosis was 34.6 ±9.4 years. The sex ratio (male/female) was 2.5. The mean delay of diagnosis was 53.5 months. Oral aphthosis was constant. The frequency of the manifestations was: genital aphtosis 71.5%, pseudofolliculitis 84.6%, erythema nodosum 11.5%, positive pathergy test 50%, ocular disease 36.9%, venous thrombosis 30%, arterial disease 4.6%, joint damage 30.8%, neurological disease 19.2% and digestive disease 0.8%. The male gender was significantly associated with ocular involvement (p =0.02), venous disease (p =0.01) and occurrence of relapses (p =0.01). The mean follow up was 68.5 ± 77.3 months. The poor survival prognostic factors were male gender, ocular involvement, venous disease, cardiovascular disease, a duration of follow up ≤12 months and a diagnostic delay ≤ 24 months. Conclusion: improving the prognosis of Behçet´s disease requires a shortening of the time to diagnosis, multidisciplinary collaboration, intensive treatment of functional threats, regular monitoring, and patient adherence.
Collapse
Affiliation(s)
- Fatma Daoud
- Internal Medicine Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Imène Rachdi
- Internal Medicine Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Mehdi Somai
- Internal Medicine Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Anissa Zaouak
- Department of Dermatology, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Houda Hammami
- Department of Dermatology, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Meriem Ouederni
- Ophthalmology Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Rym Maamouri
- Ophthalmology Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Hana Zoubeidi
- Internal Medicine Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Molka Tougorti
- Internal Medicine Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Jihène Ksouri
- Internal Medicine Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Besma Ben Dhaou
- Internal Medicine Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Zohra Aydi
- Internal Medicine Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Samy Fenniche
- Department of Dermatology, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Monia Cheour
- Ophthalmology Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Fatma Boussema
- Internal Medicine Department, Habib Thameur Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| |
Collapse
|
21
|
Hammam N, Li J, Evans M, Kay JL, Izadi Z, Anastasiou C, Gianfrancesco MA, Yazdany J, Schmajuk G. Epidemiology and treatment of Behçet's disease in the USA: insights from the Rheumatology Informatics System for Effectiveness (RISE) Registry with a comparison with other published cohorts from endemic regions. Arthritis Res Ther 2021; 23:224. [PMID: 34461986 PMCID: PMC8404295 DOI: 10.1186/s13075-021-02615-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 08/23/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Behçet's disease (BD), a chronic systemic vasculitis, has distinct geographical and ethnic variation. Data regarding the epidemiology of patients with BD in the U.S. are limited; therefore, we sought to describe BD patient characteristics and medication use in the U.S., and compared them with data from patients from endemic regions. METHODS We conducted a cross-sectional study using data from the RISE registry (2014-2018). Patients aged ≥ 18 years with BD were included. Sociodemographic and treatment information was extracted. We compared patients from the RISE registry to data from other published studies of patients with BD from endemic areas. RESULTS One thousand three hundred twenty-three subjects with BD from the RISE registry were included. Mean age was 48.7 ± 16.3 years, female to male ratio was 3.8:1, and 66.7% were White. The most frequently used medications included glucocorticoids (67.6%) and colchicine (55.0%). Infliximab and adalimumab were the most used biologics (14.5% and 14.1%, respectively); 3.2% of patients used apremilast. The RISE registry had more women (79.3%), and patients were older compared to previously published BD studies from endemic areas. Methotrexate and TNFi were more commonly reported in RISE (21.8% and 29.4%) compared to studies from Egypt and Turkey. Colchicine, cyclosporine, and cyclophosphamide were more commonly used in cohorts from Egypt, Turkey, and Iran. CONCLUSIONS Findings from the largest BD dataset in the U.S. suggest that BD patients are predominantly female. Further research is needed to explore the reasons for the higher prevalence of BD among women in the U.S. and its possible impact on disease severity and management.
Collapse
Affiliation(s)
- Nevin Hammam
- Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Jing Li
- Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Michael Evans
- Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Julia L Kay
- Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Zara Izadi
- Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Christine Anastasiou
- Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Milena A Gianfrancesco
- Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Jinoos Yazdany
- Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Gabriela Schmajuk
- Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
- Philip R. Lee Institute for Health Policy Research, San Francisco, USA.
- San Francisco Veterans Affairs Medical Center, 4150 Clement St 111R, San Francisco, CA, 94121, USA.
| |
Collapse
|
22
|
Wassef AMA, Abdelhakim MASE, Macky TA, Raafat KA, Youssef MM. Post-remission retinal microvascular and choroidal thickness changes in eyes with Behḉet's disease posterior uveitis: an OCTA longitudinal study. Int Ophthalmol 2021; 41:4163-4174. [PMID: 34324102 DOI: 10.1007/s10792-021-01968-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 07/17/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE To investigate the retinal microvascular and choroidal thickness changes in eyes with active Behḉet's disease posterior uveitis and post-remission. PATIENTS AND METHODS A prospective longitudinal observational analytic study where patients with active Behḉet's posterior uveitis (BU) were assessed by optical coherence tomography angiography (OCTA) and enhanced depth imaging OCT during activity and after remission, for retinal microvascular and subfoveal choroidal thickness (SFCT) changes. RESULTS 26 eyes of 20 patients were included. With remission of active posterior uveitis, capillary density in both layers increased, only being significant in the superficial capillary plexus (SCP) 1.81 ± 3.57% (p = 0.025), while the foveal avascular zone (FAZ) area increased by 0.036 ± 0.069 mm (p = 0.023). CONCLUSION OCTA can be used to monitor the activity of Behḉet's posterior uveitis. Comparing the retinal microvascular changes during activity and after remission, the superficial capillary plexus was found to be more indicative of the activity status, while the deep capillary plexus and foveal avascular zone area-being more irreversible-are more useful as prognostic indicators. Subfoveal choroidal thickness, on the other hand, proved to be a consistent indictor of visual function; however, its change doesn't accurately reflect the activity status.
Collapse
Affiliation(s)
- Amr Mohamed Abdelaziz Wassef
- Department of Ophthalmology, Kasr Al Ainy Hospital, Cairo University, El Saray Street, Manial, Cairo, 11956, Egypt.
| | | | - Tamer Ahmed Macky
- Department of Ophthalmology, Kasr Al Ainy Hospital, Cairo University, El Saray Street, Manial, Cairo, 11956, Egypt
| | - Karim Adly Raafat
- Department of Ophthalmology, Kasr Al Ainy Hospital, Cairo University, El Saray Street, Manial, Cairo, 11956, Egypt
| | - Maha Mohamed Youssef
- Department of Ophthalmology, Kasr Al Ainy Hospital, Cairo University, El Saray Street, Manial, Cairo, 11956, Egypt
| |
Collapse
|
23
|
Leyens J, Bender TTA, Mücke M, Stieber C, Kravchenko D, Dernbach C, Seidel MF. The combined prevalence of classified rare rheumatic diseases is almost double that of ankylosing spondylitis. Orphanet J Rare Dis 2021; 16:326. [PMID: 34294115 PMCID: PMC8296612 DOI: 10.1186/s13023-021-01945-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/02/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Rare diseases (RDs) affect less than 5/10,000 people in Europe and fewer than 200,000 individuals in the United States. In rheumatology, RDs are heterogeneous and lack systemic classification. Clinical courses involve a variety of diverse symptoms, and patients may be misdiagnosed and not receive appropriate treatment. The objective of this study was to identify and classify some of the most important RDs in rheumatology. We also attempted to determine their combined prevalence to more precisely define this area of rheumatology and increase awareness of RDs in healthcare systems. We conducted a comprehensive literature search and analyzed each disease for the specified criteria, such as clinical symptoms, treatment regimens, prognoses, and point prevalences. If no epidemiological data were available, we estimated the prevalence as 1/1,000,000. The total point prevalence for all RDs in rheumatology was estimated as the sum of the individually determined prevalences. RESULTS A total of 76 syndromes and diseases were identified, including vasculitis/vasculopathy (n = 15), arthritis/arthropathy (n = 11), autoinflammatory syndromes (n = 11), myositis (n = 9), bone disorders (n = 11), connective tissue diseases (n = 8), overgrowth syndromes (n = 3), and others (n = 8). Out of the 76 diseases, 61 (80%) are classified as chronic, with a remitting-relapsing course in 27 cases (35%) upon adequate treatment. Another 34 (45%) diseases were predominantly progressive and difficult to control. Corticosteroids are a therapeutic option in 49 (64%) syndromes. Mortality is variable and could not be determined precisely. Epidemiological studies and prevalence data were available for 33 syndromes and diseases. For an additional eight diseases, only incidence data were accessible. The summed prevalence of all RDs was 28.8/10,000. CONCLUSIONS RDs in rheumatology are frequently chronic, progressive, and present variable symptoms. Treatment options are often restricted to corticosteroids, presumably because of the scarcity of randomized controlled trials. The estimated combined prevalence is significant and almost double that of ankylosing spondylitis (18/10,000). Thus, healthcare systems should assign RDs similar importance as any other common disease in rheumatology.
Collapse
Affiliation(s)
- Judith Leyens
- Center for Rare Diseases Bonn (ZSEB), University Hospital, Bonn, Germany
- Department of Neonatology and Pediatric Care, Children's University Hospital, Bonn, Germany
| | - Tim Th A Bender
- Center for Rare Diseases Bonn (ZSEB), University Hospital, Bonn, Germany
- Institute of Human Genetics, University Hospital, Bonn, Germany
| | - Martin Mücke
- Center for Rare Diseases Bonn (ZSEB), University Hospital, Bonn, Germany
| | - Christiane Stieber
- Institute of General Practice and Family Medicine, University Hospital, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Dmitrij Kravchenko
- Center for Rare Diseases Bonn (ZSEB), University Hospital, Bonn, Germany
- Department of Radiology, University Hospital, Bonn, Germany
| | - Christian Dernbach
- Division of Medical Psychology and Department of Psychiatry, University Hospital, Bonn, Germany
| | - Matthias F Seidel
- Department of Rheumatology, Spitalzentrum-Centre hospitalier, Biel-Bienne, Switzerland.
| |
Collapse
|
24
|
Alpsoy E, Bozca BC, Bilgic A. Behçet Disease: An Update for Dermatologists. Am J Clin Dermatol 2021; 22:477-502. [PMID: 34061323 DOI: 10.1007/s40257-021-00609-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/04/2021] [Indexed: 12/13/2022]
Abstract
Behçet disease (BD) is a chronic, relapsing, systemic vasculitis of unknown etiology with the clinical features of oral and genital ulcers, cutaneous vasculitic lesions, ocular, articular, vascular, gastrointestinal, neurologic, urogenital and cardiac involvement. BD usually appears around the third or fourth decade of life. Gender distribution is roughly equal. The disease is much more frequent in populations along the ancient 'Silk Road', extending from Eastern Asia to countries in the Middle East and the Mediterranean, compared with Western countries, but has universal distribution. Mucocutaneous manifestations are the clinical hallmarks of BD. The diagnostic criteria widely used in the disease's diagnosis are based on mucocutaneous manifestations because of their high sensitivity and/or specificity. Genetic factors are the key driver of BD pathogenesis, and HLA-B51 antigen is the strongest genetic susceptibility factor. Streptococcus sanguinis (S. sanguinis) or microbiome change can trigger innate immune system-mediated inflammation sustained by adaptive immune responses. Epistatic interaction between HLA-B51 and endoplasmic reticulum aminopeptidase 1 (ERAP1) in antigen-presenting cells disrupt T-cell homeostasis leading to downregulation of Tregs and expansion of Th1 and Th17. Thus, neutrophil activation and intense neutrophil infiltration of the affected organs develop in the early stage of inflammation. BD has a variable clinical course with unpredictable exacerbations and remissions. The disease is associated with a high mortality rate, especially in young male patients, and large-vessel, neurological, gastrointestinal system and cardiac involvement are the most important causes of death. The principal aim of treatment should be to prevent irreversible organ damage, especially during the disease's early, active phase. A better understanding of the disease's pathogenesis has provided important information on its management. New drugs, especially apremilast and anti-TNF-α agents are effective in the management of BD and have the potential to improve patients' quality of life, prognosis and survival.
Collapse
Affiliation(s)
- Erkan Alpsoy
- Department of Dermatology and Venereology, Akdeniz University School of Medicine, 07059, Antalya, Turkey.
| | - Burcin Cansu Bozca
- Department of Dermatology and Venereology, Akdeniz University School of Medicine, 07059, Antalya, Turkey
| | - Asli Bilgic
- Department of Dermatology and Venereology, Akdeniz University School of Medicine, 07059, Antalya, Turkey
| |
Collapse
|
25
|
Ahn HS, Kim HJ, Kazmi SZ, Kang T, Jun JB, Kang MJ, Kim KB, Kee SH, Kim DS, Hann HJ. Familial risk of Behçet's disease among first-degree relatives: a population-based aggregation study in Korea. Rheumatology (Oxford) 2021; 60:2697-2705. [PMID: 33241295 DOI: 10.1093/rheumatology/keaa682] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 09/19/2020] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVE Previous studies have indicated that Behçet's disease (BD) has a genetic component, however population-level familial risk estimates are unavailable. We quantified the familial incidence and risk of BD in first-degree relatives (FDR) according to age, sex and type of family relationship. METHODS Using the Korean National Health Insurance database, which has full population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 individuals comprising 12 million families, which were followed for a familial occurrence of BD from 2002 to 2017. Age- and sex-adjusted incidence risk ratios for BD were calculated in individuals with affected FDR compared with those without affected FDR. RESULTS Among the total study population, 53 687 individuals had affected FDR, of whom 284 familial cases developed BD with an incidence of 3.57/104 person-years. The familial risk (incidence) for BD was increased to 13.1-fold (2.71/104 person-years) in individuals with an affected father, 13.9-fold (3.11/104 person-years) with affected mother, 15.2-fold (4.9/104 person-years) with an affected sibling and the highest risk was 165-fold (46/104 person-years) with an affected twin. Familial risks showed age dependence, being higher in younger age groups. The sex-specific familial risk was similar in males and females. CONCLUSION This study provides quantified estimates of familial incidence and risk in FDR of BD patients in an entire population. Familial risks were higher within generation (sibling-sibling) vs between generations (parent-offspring). This implicates complex interactions between genetic factors and shared childhood environmental exposures in the pathogenesis of BD.
Collapse
Affiliation(s)
- Hyeong Sik Ahn
- Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Hyun Jung Kim
- Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Sayada Zartasha Kazmi
- Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Taeuk Kang
- Korean Research-based Industry Association (KRPIA), Seoul, Korea
| | - Jae-Bum Jun
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
| | - Min Ji Kang
- Department Public Health, Graduate School, Korea University, Seoul, Korea
| | - Kyoung-Beom Kim
- Department Public Health, Graduate School, Korea University, Seoul, Korea
| | - Sun-Ho Kee
- Department of Microbiology, College of Medicine, Korea University, Seoul, Korea
| | - Dong-Sook Kim
- Health Insurance Review and Assessment service (HIRA), Seoul, Korea
| | - Hoo Jae Hann
- Medical Research Institute, School of Medicine, Ewha Woman's University, Seoul, Korea
| |
Collapse
|
26
|
Mumcu G, Fortune F. Oral Health and Its Aetiological Role in Behçet's Disease. Front Med (Lausanne) 2021; 8:613419. [PMID: 34095159 PMCID: PMC8172597 DOI: 10.3389/fmed.2021.613419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 04/26/2021] [Indexed: 12/31/2022] Open
Abstract
Behçet's disease (BD) is a chronic multi-systemic inflammatory disorder characterised by oro-genital ulcers, cutaneous manifestations, ocular, vascular, neurologic and gastrointestinal involvement. Complex interactions operating on the genetic background e.g.(HLA51), of infectious and other environmental agents, together with immune dysregulation impacts on the pathogenesis of BD. This suggests that the environmental factors triggering immune responses may activate clinical manifestations in genetically susceptible individuals. Since oral health forms the basis of all general health both dental and systemic, it is an important component of both Dentistry and Medicine. Oral ulcers are the most common clinical manifestation of oral mucosal health. Changes in the oral environment consequently acts as an infective and immune trigger. In this review, complex interactions between the oral ulcers, the oral microbiome and immune responses together with the course of oral and systemic disease manifestations in BD are discussed in the context of the aetiologic role of oral health.
Collapse
Affiliation(s)
- Gonca Mumcu
- Department of Health Management, Faculty of Health Science, Marmara University, Istanbul, Turkey
| | - Farida Fortune
- Centre for Immuno-Biology and Regenerative Medicine, Behçet's Centre of Excellence, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| |
Collapse
|
27
|
Hammami AS, Jellazi M, Arfa S, Daada S, Ben Hamda K, Achour A, Ouali S. Getting to the <em>heart</em> of the matter: diagnostic tools and therapeutic approach to cardiac involvement in Behçet syndrome A Tunisian case series. Reumatismo 2021; 73:32-43. [PMID: 33874645 DOI: 10.4081/reumatismo.2021.1369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 02/23/2021] [Indexed: 11/23/2022] Open
Abstract
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.
Collapse
Affiliation(s)
- A S Hammami
- Department of Internal Medicine, Geriatric Unit, Hospital Fattouma Bourguiba of Monastir, Monastir, Tunisia; Biochemistry Laboratory, LR12ES05 LR-NAFS Nutrition - Functional Food and Vascular Health, Faculty of Medicine, University of Monastir, Monastir.
| | - M Jellazi
- Department of Internal Medicine, Geriatric Unit, Hospital Fattouma Bourguiba of Monastir, Monastir.
| | - S Arfa
- Department of Internal Medicine, Geriatric Unit, Hospital Fattouma Bourguiba of Monastir, Monastir.
| | - S Daada
- Department of Internal Medicine, Geriatric Unit, Hospital Fattouma Bourguiba of Monastir, Monastir.
| | - K Ben Hamda
- Department of Cardiology, Hospital Fattouma Bourguiba of Monastir, Monastir.
| | - A Achour
- Department of Radiology, Hospital Fattouma Bourguiba of Monastir, Monastir.
| | - S Ouali
- Department of Internal Medicine, Geriatric Unit, Hospital Fattouma Bourguiba of Monastir, Monastir, Tunisia; Biochemistry Laboratory, LR12ES05 LR-NAFS Nutrition - Functional Food and Vascular Health, Faculty of Medicine, University of Monastir, Monastir.
| |
Collapse
|
28
|
Rajaei E, Jalali MT, Pezeshki SMS, Rezaeeyan H, Maniati M, Elyasi M, Zayeri ZD. Dose HLA-B5, 7, 8, 27, and 51 Antigens Associated to Behcet's disease? A Study in Southwestern Iran. Curr Rheumatol Rev 2021; 16:120-124. [PMID: 31533601 DOI: 10.2174/1573397115666190918153721] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 04/16/2019] [Accepted: 08/09/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Behcet's disease is a potentially life threatening autoimmune disease with recurrent ulcers and unknown pathogenesis. Gender and human leukocyte antigen-B51 seem to have an effective role in the clinical features of the disease. OBJECTIVE The aim of this study is to evaluate the frequency of HLA-B5, 7, 8, 27 and 51 in behçet's disease in southwestern Iranian patients who visited the rheumatology clinic and to find the association between these HLA types and the disease. METHODS 63 patients with behcet's disease participated in this study and peripheral blood samples were collected from them. The expression of each HLA antigen was evaluated by standard lymphocytotoxicity technique. RESULTS Compared to other studied antigens, the expression of HLA-B5 and HLA-B51 was more prevalent among our patients. According to the results, 25% and 21% of patients were positive for HLA-B5 and HLA-B51, respectively. CONCLUSIONS HLA-B5 and HLA-B51 are dominant positive HLA antigens among behcet's disease patients in the southwest of Iran; however, we cannot conclude that these antigens are valuable diagnostic or prognostic biomarkers due to our study limitations. We suggest studying the association between HLA-B antigens and inflammation severity in patients to determine the possible prognostic value of HLA-B antigens in Iranian population in the southwest and this region needs more studies in HLA subject among BD patients because of the frequency of BD to evaluate the value of HLA typing in BD prognosis.
Collapse
Affiliation(s)
- Elham Rajaei
- Golestan Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad T Jalali
- Hyperlipidemia Research Center, Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed M Sadegh Pezeshki
- Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hadi Rezaeeyan
- Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mahmood Maniati
- Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Milad Elyasi
- Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Zeinab D Zayeri
- Golestan Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| |
Collapse
|
29
|
Abstract
Systemic vasculitides are multisystem blood vessel disorders, which are defined by the size of the vessel predominantly affected, namely small, medium, or large vessels. The term "large vessel" relates to the aorta and its major branches; "medium vessel" refers to the main visceral arteries and veins and their initial branches. The most common causes of large-vessel vasculitis are giant cell arteritis and Takayasu arteritis, and those of medium-vessel arteritis are polyarteritis nodosa and Kawasaki disease. However, there is some overlap, and arteries of any size can potentially be involved in any of the 3 main categories of dominant vessel involvement. In addition to multisystem vasculitides, other forms of vasculitis have been defined, including single-organ vasculitis (eg, isolated aortitis). Prompt identification of vasculitides is important because they are associated with an increased risk of mortality. Left undiagnosed or mismanaged, these conditions may result in serious adverse outcomes that might otherwise have been avoided or minimized. The ethnic and regional differences in the incidence, prevalence, and clinical characteristics of patients with vasculitis should be recognized. Because the clinical presentation of vasculitis is highly variable, the cardiovascular clinician must have a high index of suspicion to establish a reliable and prompt diagnosis. This article reviews the pathophysiology, epidemiology, diagnostic strategies, and management of vasculitis.
Collapse
Affiliation(s)
- David Saadoun
- Sorbonne Universités, Assistance Publique Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière University Hospital, Department of Internal Medicine and Clinical Immunology, Centre national de Référence des Maladies Auto-Immunes Systémiques Rares, Centre national de Référence des Maladies Auto-Inflammatoires et de l'Amylose inflammatoire, Paris, France (D.S., M.V.).,Institut National de la Santé et de la Recherche Médicale (INSERM), Unité mixte de recherche (UMR) S 959, and Recherche Hospitalo-Universitaire en santé (RHU) Interleukin-2 Therapy for autoimmune and inflammatory diseases, Paris, France (D.S., P.C.)
| | - Mathieu Vautier
- Sorbonne Universités, Assistance Publique Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière University Hospital, Department of Internal Medicine and Clinical Immunology, Centre national de Référence des Maladies Auto-Immunes Systémiques Rares, Centre national de Référence des Maladies Auto-Inflammatoires et de l'Amylose inflammatoire, Paris, France (D.S., M.V.)
| | - Patrice Cacoub
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité mixte de recherche (UMR) S 959, and Recherche Hospitalo-Universitaire en santé (RHU) Interleukin-2 Therapy for autoimmune and inflammatory diseases, Paris, France (D.S., P.C.)
| |
Collapse
|
30
|
Mahmoudi M, Aslani S, Meguro A, Akhtari M, Fatahi Y, Mizuki N, Shahram F. A comprehensive overview on the genetics of Behçet's disease. Int Rev Immunol 2020; 41:84-106. [PMID: 33258398 DOI: 10.1080/08830185.2020.1851372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Behçet's disease (BD) is a systemic and inflammatory disease, characterized mainly by recurrent oral and genital ulcers, eye involvement, and skin lesions. Although the exact etiopathogenesis of BD remains unrevealed, a bulk of studies have implicated the genetic contributing factors as critical players in disease predisposition. In countries along the Silk Road, human leukocyte antigen (HLA)-B51 has been reported as the strongest genetically associated factor for BD. Genome-wide association studies, local genetic polymorphism studies, and meta-analysis of combined data from Turkish, Iranian, and Japanese populations have also identified new genetic associations with BD. Among these, other HLA alleles such as HLA-B*15, HLA-B*27, HLA-B*57, and HLA-A*26 have been found as independent risk factors for BD, whereas HLA-B*49 and HLA-A*03 are independent protective alleles for BD. Moreover, other genes have also reached the genome-wide significance level of association with BD susceptibility, including IL10, IL23R-IL12RB2, IL12A, CCR1-CCR3, STAT4, TNFAIP3, ERAP1, KLRC4, and FUT2. Also, several rare nonsynonymous variants in TLR4, IL23R, NOD2, and MEFV genes have been reported to be involved in BD pathogenesis. According to genetic determinants in the loci outside the MHC region that are contributed to the host defense, immunity, and inflammation pathways, it is suggested that immune responses to the pathogen as an important environmental factor and mucosal immunity contribute to BD susceptibility.
Collapse
Affiliation(s)
- Mahdi Mahmoudi
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Aslani
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Akira Meguro
- Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Maryam Akhtari
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Yousef Fatahi
- Faculty of Pharmacy, Department of Pharmaceutical Nanotechnology, Tehran University of Medical Sciences, Tehran, Iran.,Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Nobuhisa Mizuki
- Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Farhad Shahram
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
31
|
Ekinci RMK, Esen E, Erol AH, Sızmaz S, Karagoz D, Altintas DU, Balcı S. Evaluation of different classification criteria in children with Behcet disease: results from a single referral center. Expert Rev Clin Immunol 2020; 16:1093-1097. [PMID: 33047996 DOI: 10.1080/1744666x.2021.1834853] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OBJECTIVES Behcet Disease (BD) is a systemic vasculitis, first described with a triad of oral aphthous ulcers, genital ulcers, and uveitis. The authors aimed to share the clinical properties and utilities of three distinct classification criteria for BD in this study. METHODS This case-control study was conducted in pediatric BD patients, diagnosed between January 2012 and July 2019. The control group included 53 children with other rheumatic disorders. Sensitivity and specificity for International Study Group (ISG), International Criteria for BD (ICBD), and pediatric criteria for BD (PEDBD) criteria were tested. RESULTS The mean age at symptom onset and diagnosis of the 16 BD patients (6 females, 10 males) were 11.2 ± 3.6 and 13 ± 3.1 years, respectively. The sensitivity and specificity of ISG criteria were 87.5% and 100%. Furthermore, ICBD criteria had a sensitivity and specificity of 93.7% and 98.1%, whereas the authors found sensitivity and specificity as 93.7% and 96.2% for PEDBD. CONCLUSION ICBD and PEDBD reached higher sensitivity for pediatric BD diagnosis and ICBD had the highest specificity. The authors speculate that the utilization of ICBD may provide early diagnosis of BD in childhood, prevent related morbidities and misdiagnosis.
Collapse
Affiliation(s)
| | - Ebru Esen
- Department of Ophthalmology, Cukurova University Faculty of Medicine, Adana, Turkey
| | - Ahmet Hakan Erol
- Department of Pediatrics, Cukurova University Faculty of Medicine , Adana, Turkey
| | - Selcuk Sızmaz
- Department of Ophthalmology, Cukurova University Faculty of Medicine, Adana, Turkey
| | - Dilek Karagoz
- Department of Pediatric Allergy and Immunology, Cukurova University Faculty of Medicine , Adana, Turkey
| | - Derya Ufuk Altintas
- Department of Pediatric Allergy and Immunology, Cukurova University Faculty of Medicine , Adana, Turkey
| | - Sibel Balcı
- Department of Pediatric Rheumatology, Cukurova University Faculty of Medicine , Adana, Turkey
| |
Collapse
|
32
|
Marvisi C. The geographic and clinical clusters of Behçet's syndrome. Intern Emerg Med 2020; 15:933-934. [PMID: 32227285 DOI: 10.1007/s11739-020-02319-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 03/20/2020] [Indexed: 12/01/2022]
Affiliation(s)
- Chiara Marvisi
- Rheumatology Department, University of Modena and Reggio Emilia, Modena, Italy.
| |
Collapse
|
33
|
Kim H, Cho SK, Kim JW, Jung SY, Jang EJ, Bae SC, Yoo DH, Sung YK. An increased disease burden of autoimmune inflammatory rheumatic diseases in Korea. Semin Arthritis Rheum 2020; 50:526-533. [DOI: 10.1016/j.semarthrit.2019.11.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Revised: 09/26/2019] [Accepted: 11/08/2019] [Indexed: 12/17/2022]
|
34
|
Bozkurt E, Muhafiz E, Sengul D, Uçak T, Atum M. Can the CRP/albumin Ratio be Used as a New Indicator of Activation in Patients with Uveitis? Ocul Immunol Inflamm 2020; 29:1017-1022. [PMID: 32125910 DOI: 10.1080/09273948.2020.1714061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Purpose: To evaluate whether the C-reactive protein (CRP)/albumin ratio (CAR) in patients with uveitis during an attack is a marker that can give information about the activity, severity and prognosis of the disease.Methods: This study included 35 patients with an uveitis attack and 35 healthy volunteers. The localization and severity of uveitis were recorded. Patients' complete blood count (CBC) during the attack, CRP, CAR, erythrocyte sedimentation rate(ESR), neutrophil/lymphocyte ratio(NLR), and platelet/lymphocyte ratio(PLR) were recorded.Results: The mean age was 34.1 ± 12.5 years for the 35 uveitis cases and 30.1 ± 4.1 years for the healthy volunteers. CRP and CAR were significantly higher in uveitis patients (p = .015 and 0.011, respectively). While CRP and CAR were significantly higher in severe anterior uveitis than mild anterior uveitis (p = .036 and 0.022, respectively), only CAR was significantly higher in severe posterior and panuveitis than mild ones(p = .017).Conclusion: CAR may be an important parameter in determining the activation of the uveitis.
Collapse
Affiliation(s)
- Erdinç Bozkurt
- Faculty of Medicine, Department of Ophthalmology, Kafkas University, Kars, Türkiye
| | - Ersin Muhafiz
- Faculty of Medicine, Department of Ophthalmology, Kafkas University, Kars, Türkiye
| | - Dilek Sengul
- Faculty of Medicine, Department of Ophthalmology, Kafkas University, Kars, Türkiye
| | - Turgay Uçak
- Department of Ophthalmology, Mengücek Training and Research Hospital, Erzincan, Türkiye
| | - Mahmut Atum
- Department of Ophthalmology, Sakarya Training and Research Hospital, Sakarya, Türkiye
| |
Collapse
|
35
|
Pahlavan Y, Samadi N, Ansarin K, Khabbazi A. Phosphorylation Modulates Survivin Function in Behcet's Disease. Adv Pharm Bull 2020; 10:278-283. [PMID: 32373497 PMCID: PMC7191240 DOI: 10.34172/apb.2020.033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Revised: 09/29/2019] [Accepted: 09/30/2019] [Indexed: 12/11/2022] Open
Abstract
Purpose: Survivin is critical for proliferation, maturation, homeostasis and differentiation of effector and memory lymphocytes. In this study the baculoviral inhibitors of apoptosis proteins (IAPs) repeat containing 5 (BIRC5) mRNA, survivin, and phosphorylated survivin expression were evaluated in peripheral blood mononuclear cells (PBMCs), and plasma of patients with Behcet’s disease (BD). Methods: In this study, 26 Iranian Azari patients diagnosed with BD and 30 healthy controls were recruited. Total RNA was extracted from PBMCs. The expression level of survivin was measured by quantitative real-time polymerase chain reaction (PCR). Survivin plasma levels were measured using survivin Enzyme-linked immunosorbent assays. Also, western blotting analysis was performed to measure phosphorylated-survivin and survivin levels in PBMCs and plasma of patients with BD. Results: In a pilot study, we showed that BIRC5 gene expression increased in BD patients compared with healthy controls (P<0.05). Western blotting analysis indicated that there was an increase in phosphorylated survivin expression in PBMCs of BD patients. Our data from western blot analysis showed survivin level in plasma samples of BD patients was similar to healthy controls. No significant differences were observed between plasma survivin levels in the BD patients compared with control group (P>0.05). The expression of phosphorylated survivin at Thr34 in PBMCs of BD patients with active disease was increased. Plasma phosphorylated survivin levels in having BD patients were also downregulated compared to healthy individuals. Conclusion: Analysis of PBMCs indicated increasing expression level of phosphorylated survivin in PBMCs of BD patients. There was also a downregulation in phosphorylated survivin levels in plasma of BD patients.
Collapse
Affiliation(s)
- Yasamin Pahlavan
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Students Research Committee, University of Tabriz Medical Sciences, Tabriz, Iran
| | - Naser Samadi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Khalil Ansarin
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Rahat Breath and Sleep Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Khabbazi
- Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
36
|
Yıldız M, Köker O, Adrovic A, Şahin S, Barut K, Kasapçopur Ö. Pediatric Behçet's disease - clinical aspects and current concepts. Eur J Rheumatol 2020; 7:S38-S47. [PMID: 31556871 PMCID: PMC7004268 DOI: 10.5152/eurjrheum.2019.19121] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 07/30/2019] [Indexed: 12/14/2022] Open
Abstract
Behçet's Disease was first described by a Turkish dermatologist, Hulusi Behçet, in 1937 as a triple symptom complex; aphthous stomatitis, genital ulcers, and uveitis. Today, in light of current trials and experiments, we know that the disease may have a wider involvement with a multisystemic recurrent course, causing significant morbidity and mortality. However, there are still unanswered questions, particularly about Pediatric Behçet's Disease. Although several immunological and genetic associations have been demonstrated, the real etiologic mechanism of the disease is unclear. The diagnosis is difficult due to its rarity in childhood, the lack of validation of the diagnostic criteria obtained from adult studies, and the inadequacy of large case-controlled studies. Also, the management is challenging and controversial due to the various geographic distribution of clinical spectrum. New therapeutic options under development in light of pathogenetic hypothesis seem to be promising.
Collapse
Affiliation(s)
- Mehmet Yıldız
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Oya Köker
- Department of Pediatric Rheumatology, İstanbul University, İstanbul School of Medicine, İstanbul, Turkey
| | - Amra Adrovic
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Sezgin Şahin
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Kenan Barut
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Özgür Kasapçopur
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| |
Collapse
|
37
|
Gong HB, Wu XJ, Pu XM, Kang XJ. Association of Interleukin-23R Gene Polymorphisms with Behcet’s Disease Susceptibility: A Meta-Analysis of Case-control Studies. Immunol Invest 2019; 49:648-661. [PMID: 31814470 DOI: 10.1080/08820139.2019.1698600] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Hai-Bo Gong
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
| | - Xiu-Juan Wu
- Department of Dermatology, Shanghai Xuhui Central Hospital, Shanghai, China
| | - Xiong-Ming Pu
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
| | - Xiao-Jing Kang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
| |
Collapse
|
38
|
Investigation of POU5F1 gene in sample of Egyptian patients with Behçet disease, pilot study. Meta Gene 2019. [DOI: 10.1016/j.mgene.2019.100604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
|
39
|
Balcı-Peynircioğlu B, Kaya-Akça Ü, Arıcı ZS, Avcı E, Akkaya-Ulum ZY, Karadağ Ö, Kalyoncu U, Bilginer Y, Yılmaz E, Özen S. Comorbidities in familial Mediterranean fever: analysis of 2000 genetically confirmed patients. Rheumatology (Oxford) 2019; 59:1372-1380. [DOI: 10.1093/rheumatology/kez410] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 08/08/2019] [Indexed: 01/08/2023] Open
Abstract
Abstract
Objectives
FMF is the most common periodic fever syndrome, characterized by recurrent episodes of fever and serosal inflammation accompanied with high acute phase reactants. The analysis of possible comorbidities is important to understand the impact of these conditions on clinical care and whether they share a common aetiological pathway. In this study, we aimed to evaluate the comorbidities associated with FMF patients in a large genetically diagnosed cohort.
Methods
We retrospectively evaluated the medical and genetic records of FMF patients who were followed up by rheumatologists in Hacettepe University for 15 years. The FMF patients who had homozygous or compound heterozygous mutations were included in the study. Comorbidities associated with FMF were divided into three groups: (i) comorbidities directly related to FMF, (ii) comorbidities due to increased innate inflammation, and (iii) comorbidities that were regarded as being incidental.
Results
A total of 2000 patients with a diagnosis of FMF were enrolled in the study. Among them 636 were children (31.8%) and M694V was the most common mutation in patients with associated inflammatory conditions. The frequency of AS, Iga Vasculitis (Henoch–Schönlein purpura), juvenile idiopathic arthritis, polyarteritis nodosa, multiple sclerosis and Behçet’s disease were increased in patients with FMF when compared with those in the literature.
Conclusion
This study represents the largest genetically confirmed cohort and compares the frequencies with existing national and international figures for each disease. The increased innate immune system inflammation seen in FMF may be considered as a susceptibility factor since it predisposes to certain inflammatory conditions.
Collapse
Affiliation(s)
| | - Ümmüşen Kaya-Akça
- Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Zehra Serap Arıcı
- Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Edibe Avcı
- Department of Medical Biology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Z Yeliz Akkaya-Ulum
- Department of Medical Biology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ömer Karadağ
- Department of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Umut Kalyoncu
- Department of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Yelda Bilginer
- Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Engin Yılmaz
- Department of Medical Biology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Seza Özen
- Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| |
Collapse
|
40
|
Characteristics of Behcet's Disease in the American Southwest. Semin Arthritis Rheum 2019; 49:296-302. [DOI: 10.1016/j.semarthrit.2019.03.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 02/23/2019] [Accepted: 03/04/2019] [Indexed: 11/23/2022]
|
41
|
Investigation of the relationship between Tbx21 and MYH7B genes polymorphisms in rs10514934 and rs2425012 regions in Behçet patients: The first report from Iran. GENE REPORTS 2019. [DOI: 10.1016/j.genrep.2019.100383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
42
|
Abstract
Behçet syndrome (BS) is a multi-systemic complex disorder with unknown etiology and a unique geographic distribution. It could not be possible to include it into specific classification schemes and it is certainly not a uniform disease. Several cluster and association studies revealed that it has been composed of multiple phenotypes ascribing the principal problem such as skin-mucosa, joint, eye, vascular, neurological and gastrointestinal involvement. Each phenotype has its own characteristic demographic and clinical features as such their management strategies and prognosis differ substantially. Actually, the concept of phenotyping has been well known for some time and is considered one of the basic elements of the still continuing debate whether to call this entity 'disease' or 'syndrome'. Further supporting evidence comes from the observation of the geographical differences of disease expression. In this setting, BS resembles rather a construction made of several dynamic and interactive LEGO pieces of different shapes and colors. These pieces presenting phenotypes with their own disease mechanism have presumably different genetic determinants. The analysis of phenotyping could help us to identify this disorder and hence could contribute to find better ways of treatment.
Collapse
Affiliation(s)
- Emire Seyahi
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical Faculty, University of Istanbul, 81310, Istanbul, Turkey.
| |
Collapse
|
43
|
Abstract
OBJECTIVE Uveitis is the most common ophthalmological finding in the practice of rheumatology and clinical immunology. The condition is frequently idiopathic but about 60 causes of uveitis have been described. Our aim was to analyze the clinical patterns and etiologies of uveitis in a tertiary referral center. METHODS The records of 912 consecutive patients referred to the department of internal medicine (Lyon University Hospital, Lyon, France) for the diagnostic work-up of uveitis were examined. Demographic, clinical, anatomical, and etiological features of uveitis were analyzed. RESULTS The mean age at onset was 48.8 years; 59.8% of the patients were women and 78.2% were Caucasians. Anterior uveitis was the most common type of uveitis (40.6%), followed by panuveitis (31.7%), posterior (18.75%) and intermediate uveitis (9%). 46.9% of the patients had idiopathic uveitis. The most common etiologies were systemic diseases (37.3%), such as sarcoidosis (17.1%), HLA-B27-related uveitis and/or spondyloarthritis (12.5%), and tuberculosis (7.5%). CONCLUSION We describe one of the largest cohorts of consecutive uveitis patients referred to a department of internal medicine. The high percentage of uveitis associated with underlying (systemic) diseases highlights the need for a multidisciplinary approach, in order to reduce the diagnostic delay.
Collapse
|
44
|
Chen H, Zhang Y, Li C, Wu W, Liu J, Zhang F, Zheng W. Coronary involvement in patients with Behçet’s disease. Clin Rheumatol 2019; 38:2835-2841. [DOI: 10.1007/s10067-019-04640-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 05/10/2019] [Accepted: 06/04/2019] [Indexed: 11/28/2022]
|
45
|
Salmaninejad A, Zamani MR, Shabgah AG, Hosseini S, Mollaei F, Hosseini N, Sahebkar A. Behçet's disease: An immunogenetic perspective. J Cell Physiol 2019; 234:8055-8074. [PMID: 30341905 DOI: 10.1002/jcp.27576] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 09/17/2018] [Indexed: 12/31/2022]
Abstract
Behçet's disease (BD) is a chronic and rare multisystemic disorder defined by autoimmunity and inflammatory characteristics, manifested by ocular lesions, recurrent genital and oral ulcers, skin symptoms and arthritis as well as neurological, intestinal, and vascular involvement. Despite the unknown cause of BD, there is some strong documentation for immunological, genetic, environmental, and infectious factors playing a role in the pathogenesis of BD. While the nature of the genetic variants remains unidentified, many genetic risk factors are considered to contribute to BD susceptibility. Along with human leukocyte antigen gene encoding B*51 (HLA-B*51) and areas including the major histocompatibility complex class I, genome-wide association studies have recognized numerous other BD susceptibility genes including those encoding interleukin (IL)-10, IL-12 receptor β 2 (IL-12RB2), IL-23 receptor (IL-23R), C-C chemokine receptor 1 gene, signal transducer and activator of transcription 4 (STAT4), endoplasmic reticulum aminopeptidase (ERAP1), and genes encoding killer cell lectin-like receptor family members (KLRC4-KLRK1). It is believed that BD could be considered as a disorder lying in between autoimmune and autoinflammatory syndromes. The positive responses to classical immunosuppressive agents like azathioprine and cyclosporine and involvement of autoantigens in the initiation of the disorder are the main BD features that reflect the autoimmune nature of the disorder. In this review, we address recent findings on the role of common cytokines, antibodies and immunogenetic factors in BD.
Collapse
Affiliation(s)
- Arash Salmaninejad
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Genetics, Medical Genetics Research Center, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Zamani
- Department of Immunology and Biology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Arezoo Gowhari Shabgah
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyedmojtaba Hosseini
- Department of Medical Genetics, Medical Genetics Research Center, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Mollaei
- Department of Medical Genetics, Medical Genetics Research Center, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nayyerehalsadat Hosseini
- Department of Medical Genetics, Medical Genetics Research Center, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
46
|
Gheita TA, El-Latif EA, El-Gazzar II, Samy N, Hammam N, Abdel Noor RA, El-Shebeiny E, El-Najjar AR, Eesa NN, Salem MN, Ibrahim SE, El-Essawi DF, Elsaman AM, Fathi HM, Sallam RA, El-Shereef RR, Abd-Elazeem MI, Said EA, Khalil NM, Shahin D, El-Saadany HM, ElKhalifa MS, Nasef SI, Abdalla AM, Noshy N, Fawzy RM, Saad E, Moshrif AH, El-Shanawany AT, Abdel-Fattah YH, Khalil HM. Behçet’s disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature. Clin Rheumatol 2019; 38:2565-2575. [DOI: 10.1007/s10067-019-04570-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 04/14/2019] [Accepted: 04/18/2019] [Indexed: 12/19/2022]
|
47
|
Fouad NA, Ahmed TI, Shaker OG, Abdelaleem OO. Relation of ischemia-modified albumin to disease manifestations and activity in Egyptian patients with Behçet’s disease. EGYPTIAN RHEUMATOLOGY AND REHABILITATION 2019. [DOI: 10.4103/err.err_66_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
|
48
|
Abbara S, Grateau G, Ducharme-Bénard S, Saadoun D, Georgin-Lavialle S. Association of Vasculitis and Familial Mediterranean Fever. Front Immunol 2019; 10:763. [PMID: 31031761 PMCID: PMC6473328 DOI: 10.3389/fimmu.2019.00763] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Accepted: 03/22/2019] [Indexed: 01/24/2023] Open
Abstract
Certain types of vasculitis occur more frequently and present differently in patients with familial Mediterranean fever (FMF). We assessed the characteristics of patients with FMF and systemic vasculitis through a systematic review of the literature. Medline was searched by two independent investigators until December 2017. We screened 310 articles and selected 58 of them (IgA vasculitis n = 12, polyarteritis nodosa (PAN) n = 25, Behçet's disease (BD) n = 7, other vasculitis n = 14). Clinical case reports were available for 167 patients (IgA vasculitis n = 46, PAN n = 61, BD n = 46, other vasculitis n = 14), and unavailable for 45 patients (IgA vasculitis n = 38, PAN n = 7). IgA vasculitis was the most common vasculitis in FMF patients with a prevalence of 2.7-7%, followed by PAN with a prevalence of 0.9-1.4%. Characteristics of FMF did not differ between patients with and without vasculitis. Patients with FMF and IgA vasculitis displayed more intussusception (8.7%) and possibly less IgA deposits on histological analysis than patients with IgA vasculitis alone. Patients with FMF and PAN had a younger age at vasculitis onset (mean age = 17.9 years), as well as more perirenal hematomas (49%) and CNS involvement (31%) than patients with PAN alone. Glomerular involvement was noted in 33% of patients diagnosed with PAN, suggesting an alternative diagnosis. Sequencing of the MEFV gene confirmed the presence of two pathogenic variants in 73% of FMF patients with IgA vasculitis or PAN. The majority of patients with BD were from one case series, and presented more skin, gastrointestinal, and CNS involvement than patients with isolated BD. In conclusion, FMF, particularly when supported by two pathogenic MEFV mutations, could predispose to IgA vasculitis, or a PAN-like vasculitis with more perirenal bleeding and CNS involvement.
Collapse
Affiliation(s)
- Salam Abbara
- Sorbonne Université, INSERM UMRS_933, AP-HP, Hôpital Tenon, Service de Médecine Interne, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses d'Origine Inflammatoire (CEREMAIA), Paris, France
| | - Gilles Grateau
- Sorbonne Université, INSERM UMRS_933, AP-HP, Hôpital Tenon, Service de Médecine Interne, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses d'Origine Inflammatoire (CEREMAIA), Paris, France
| | - Stéphanie Ducharme-Bénard
- Sorbonne Université, INSERM UMRS_933, AP-HP, Hôpital Tenon, Service de Médecine Interne, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses d'Origine Inflammatoire (CEREMAIA), Paris, France
| | - David Saadoun
- Sorbonne Université, AP-HP, Hôpital Pitié-Salpêtrière, Service de Médecine Interne, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses d'Origine Inflammatoire (CEREMAIA), Paris, France
| | - Sophie Georgin-Lavialle
- Sorbonne Université, INSERM UMRS_933, AP-HP, Hôpital Tenon, Service de Médecine Interne, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses d'Origine Inflammatoire (CEREMAIA), Paris, France
| |
Collapse
|
49
|
Abstract
The vasculitides are diseases characterized by inflammation of blood vessels and inflammatory leukocytes in vessel walls. There is an increased propensity for ischemic stroke, resulting from compromise of vessel lumina with distal tissue ischemia; and hemorrhagic or nonhemorrhagic stroke, and aneurysmal formation and bleeding, due to loss of vessel integrity.
Collapse
Affiliation(s)
- David S Younger
- Department of Neurology, Division of Neuro-Epidemiology, New York University School of Medicine, New York, NY, USA; School of Public Health, City University of New York, New York, NY, USA.
| |
Collapse
|
50
|
Muhammad JS, Ishaq M, Ahmed K. Genetics and Epigenetics Mechanism in the Pathogenesis of Behçet's Disease. Curr Rheumatol Rev 2019; 15:7-13. [PMID: 29779484 DOI: 10.2174/1573397114666180521090335] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 04/20/2018] [Accepted: 05/13/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Behçet's Disease (BD) is characterized by numerous systemic manifestations and is known for its ability to affect both, arteries and the veins. However, the etiology of BD is only partially understood, and previous studies have demonstrated a role for genetic and epigenetic factors that contribute to disease pathophysiology. Several studies have implicated T cells and monocytes in the pathogenesis of BD especially when these cells are stimulated by heat shock proteins and streptococcal antigen. Furthermore, during disease exacerbations adenosine deaminase has an important role in activating lymphocyte proliferation, maturation, and differentiation in BD. This article presents a review of the published literature mainly from the last 20 years. The topics of main concern were the role of genetic and epigenetic factors as contributing factors in disease pathophysiology. RESULT AND CONCLUSION The authors used MeSH terms "Behçet's disease" with "pathophysiology," "pathogenesis," "genetic" or "epigenetic" to search the PubMed database. All the relevant studies identified were included and are described according to the aforementioned subheadings.
Collapse
Affiliation(s)
- Jibran Sualeh Muhammad
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Muhammad Ishaq
- Department of Internal Medicine, Jinnah Medical College Hospital, Korangi, Karachi, Pakistan
| | - Khalid Ahmed
- Department of Biological and Biomedical Sciences, the Aga Khan University Hospital, Karachi, Pakistan
| |
Collapse
|