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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.
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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.
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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
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Alpsoy E, Leccese P, Emmi G, Ohno S. Treatment of Behçet's Disease: An Algorithmic Multidisciplinary Approach. Front Med (Lausanne) 2021; 8:624795. [PMID: 33996847 PMCID: PMC8115406 DOI: 10.3389/fmed.2021.624795] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 03/01/2021] [Indexed: 12/22/2022] Open
Abstract
Behçet's disease (BD) is a chronic, relapsing inflammatory, multisystem disease of unknown etiology. The disease has a wide clinical spectrum of mucocutaneous lesions and ocular, vascular, articular, neurologic, gastrointestinal and cardiac involvement. Although the number of effective drugs used in the disease's treatment has increased in recent years, BD is still associated with severe morbidity because of mainly mucocutaneous, articular and ocular symptoms and an increased mortality because of large vessel, neurological, gastrointestinal and cardiac involvement. Many factors are associated with a more serious course, such as male gender and a younger age of onset. While the severity of the disease is more pronounced in the first years of the disease, it decreases in most patients after the age of forties. The primary goal of treatment should be the prevention of irreversible organ damage. Therefore, early diagnosis and appropriate treatment and close follow-up are mandatory to reduce the morbidity and mortality of the disease. Treatment varies depending on the organ involved and the severity of the involvement. For all these reasons, the treatment should be personalized and arranged with a multidisciplinary approach according to the organs involved. Treatment is mainly based on suppression of the inflammatory attacks of the disease using local and systemic immunomodulatory and immunosuppressive drugs. In this review, based on the mainly controlled studies and personal experience in clinical practice and basic research in this field, we propose a stepwise, symptom-based, algorithmic approach for the management of BD with a holistic perspective.
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Affiliation(s)
- Erkan Alpsoy
- Department of Dermatology and Venereology, School of Medicine, Akdeniz University, Antalya, Turkey
| | - Pietro Leccese
- Rheumatology Department of Lucania, Rheumatology Institute of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza and Matera, Italy
| | - Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Shigeaki Ohno
- Ophthalmology Center, Aishin Memorial Hospital, Sapporo, Japan.,Department of Ophthalmology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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Bozca BC, Alpsoy E. Experimental Therapeutic Solutions for Behcet's Disease. J Exp Pharmacol 2021; 13:127-145. [PMID: 33603502 PMCID: PMC7886245 DOI: 10.2147/jep.s265645] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 01/19/2021] [Indexed: 12/17/2022] Open
Abstract
Behcet's disease (BD) is a chronic systemic vasculitis with inflammation attacks that involve multiple organs. In addition to numerous mucocutaneous symptoms, notably recurrent oral and genital ulcers, ocular, articular, vascular, gastrointestinal, cardiac, and neurological system involvement can be observed. Mucocutaneous lesions are the primary symptom of the disease in most patients, and they usually occur before major organ involvement and other symptoms of the disease. Recognizing the disease's mucocutaneous lesions is very important to diagnose at an early stage, control with appropriate treatment and close follow-up, and prevent major organ involvement. Genome-wide association studies (GWAS) in recent years have confirmed that HLA-B*51 is the most significant genetic predisposing factor. The majority of gene polymorphisms have been detected in molecules that respond to microorganisms and genes encoding cytokines and adhesion molecules. The infectious agent S. sanguinis -commonly found in the oral mucosa of patients with BD- or the differences in the salivary or intestinal microbiome composition can trigger innate immune-mediated inflammation sustained by acquired or adaptive immune responses. In antigen-presenting cells (APCs), epistatic interactions between HLA-B*51 and endoplasmic reticulum aminopeptidase 1 (ERAP1) variants lead to the disruption of T-cell homeostasis, especially the activation of Type1 T-helper and Th17 pathway and suppression of regulatory T-cells. Recent developments to clarify the disease's etiopathogenesis provided us with a better understanding of the mechanism of action of the relatively old drugs while opening a way for many new treatment methods. Apremilast has become an important option in the treatment of mucocutaneous symptoms with its high efficacy and safety. The disease increases the mortality rate, especially in young male patients. New treatments, especially anti-TNF-α agents, have provided significant progress and decreased the mortality rates with their rapid effect and high efficacy in patients with severe organ involvement and resistance to traditional immunosuppressive and immunomodulatory therapies. The use of IL-1, IL-6, IL-17, IL-12/IL-23 antagonists in different organ involvement has gradually increased, and the quality of life has significantly improved in many patients.
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Affiliation(s)
- Burçin Cansu Bozca
- Akdeniz University School of Medicine, Department of Dermatology and Venereology, Antalya, Turkey
| | - Erkan Alpsoy
- Akdeniz University School of Medicine, Department of Dermatology and Venereology, Antalya, Turkey
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Cheon JH. Advances in Management of Intestinal Behçet's Disease: A Perspective From Gastroenterologists. JOURNAL OF RHEUMATIC DISEASES 2021; 28:4-16. [PMID: 37476392 PMCID: PMC10324954 DOI: 10.4078/jrd.2021.28.1.4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 08/09/2020] [Accepted: 08/10/2020] [Indexed: 07/22/2023]
Abstract
Intestinal Behçet's disease (intestinal BD) is a rare chronic inflammatory disorder of the intestine that is characterized by recurrent intestinal manifestations with other systemic features of BD. Intestinal BD is diagnosed when a typically shaped ulcer is observed in the gastrointestinal tract, and the clinical findings meet the diagnostic criteria for BD. Owing to the small number of patients, intestinal BD is easily underestimated. On the other hand, but it often requires surgical treatment because of severe complications, including intestinal perforations or massive bleeding. The same treatment strategies used for inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, are used for intestinal BD. 5-Aminosalicylic acids, corticosteroids, and immunomodulators are considered conventional therapies, but a considerable number of patients eventually become unresponsive to these pharmaceutical treatments. Recently, biologic agents, such as anti-tumor necrosis factor-alpha inhibitors, have also been suggested as a new treatment option for intestinal BD. This article reviews the pathogenesis and diagnosis of intestinal BD and the current treatment strategies that are expected to be useful for rheumatologic specialists.
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Affiliation(s)
- Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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An Overview of Conventional and Recent Treatment Options for Behcet’s Disease. CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY 2020. [DOI: 10.1007/s40674-020-00143-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Feng R, Xu PP, Chen BL, Mao R, Zhang SH, Qiu Y, Zeng ZR, Chen MH, He Y. CYP2C19 polymorphism has no correlation with the efficacy and safety of thalidomide in the treatment of immune-related bowel disease. J Dig Dis 2020; 21:98-103. [PMID: 31916702 DOI: 10.1111/1751-2980.12842] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 12/21/2019] [Accepted: 12/23/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To explore the relationship between hepatic cytochrome P450 2C19 (CYP2C19) gene polymorphisms and the effectiveness and safety of thalidomide in the treatment of patients with immune-related bowel disease (IRBD). METHODS CYP2C19 variants in 79 patients treated with thalidomide were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The clinical response and adverse events of the thalidomide treatment were recorded. The potential influences of the CYP2C19 genotype polymorphisms on the clinical efficacy and adverse events of thalidomide were then investigated. RESULTS Altogether 79 patients with IRBD (70 with Crohn's disease, three with ulcerative colitis and six with Behcet's disease) receiving thalidomide therapy were recruited from January 2013 to February 2015 in a tertiary IBD center in China. Overall, 21.5% (17/79) of these patients had CYP2C19 poor metabolizers genotype (PM). The overall response rate and the incidence of adverse events of CYP2C19 extensive metabolizers genotype were not significantly different from that of the PM when IRBD patients were treated with thalidomide (P = 0.517 and 0.816, respectively). CONCLUSION CYP2C19 polymorphisms do not seem to be associated with efficacy of thalidomide and the incidence of adverse events in treating IRBD.
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Affiliation(s)
- Rui Feng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Ping Ping Xu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.,Department of Gastroenterology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Bai Li Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Sheng Hong Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Yun Qiu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Zhi Rong Zeng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Min Hu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Yao He
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
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8
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Abstract
Behçet syndrome is considered to be a multisystemic vasculitis involving the skin, mucosa, eyes, joints, nervous system, cardiovascular system, and gastrointestinal system. The exact pathogenesis of the disease is unknown, but autoimmune factors are thought to play the main role. Vasculitis in Behçet syndrome can involve any kind and size of vessels, and this explains why the disease has the ability of multisystemic involvement. The commonest clinical presentation of Behçet syndrome is recurrent and painful mucocutaneous ulcerations known as aphthosis. The other clinical manifestations vary among patients and populations. The disease tends to be more severe in men. Ocular, vascular, and central nervous system involvements are the major causes of morbidity and mortality. Behçet syndrome is a mimicker of many diseases with its several faces and considered as one of the great imitators in dermatology.
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Affiliation(s)
- Necmettin Akdeniz
- Department of Dermatology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Ömer Faruk Elmas
- Department of Dermatology, Faculty of Medicine, Ahi Evran University, Kırşehir, Turkey.
| | - Ayşe Serap Karadağ
- Department of Dermatology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
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9
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Park YE, Cheon JH. Updated treatment strategies for intestinal Behçet's disease. Korean J Intern Med 2018; 33:1-19. [PMID: 29207867 PMCID: PMC5768550 DOI: 10.3904/kjim.2017.377] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Accepted: 11/20/2017] [Indexed: 02/08/2023] Open
Abstract
Behçet's disease (BD) is a chronic, idiopathic, relapsing immune-mediated disease involving multiple organs, and is characterized by recurrent oral and genital ulcers, ocular disease, gastrointestinal ulcers, vascular diseases, and skin lesions. In particular, gastrointestinal involvement in BD is followed by severe complications, including massive bleeding, bowel perforation, and fistula, which can lead to significant morbidity and mortality. However, the management of intestinal BD has not yet been properly established. Intestinal BD patients with a severe clinical course experience frequent disease aggravations and often require recurrent corticosteroid and/or immunomodulatory therapies, or even surgery. However, a considerable number of patients with intestinal BD are often refractory to conventional therapies such as corticosteroids and immunomodulators. Recently, there has been a line of evidence suggesting that biologics such as infliximab and adalimumab are effective in treating intestinal BD. Moreover, new biologics targeting proteins other than tumor necrosis factor α are emerging and are under active investigation. Therefore, in this paper, we review the current therapeutic strategies and new clinical data for the treatment of intestinal BD.
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Affiliation(s)
- Yong Eun Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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10
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Hisamatsu T, Hayashida M. Treatment and outcomes: medical and surgical treatment for intestinal Behçet's disease. Intest Res 2017; 15:318-327. [PMID: 28670228 PMCID: PMC5478756 DOI: 10.5217/ir.2017.15.3.318] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 03/19/2017] [Accepted: 03/20/2017] [Indexed: 12/12/2022] Open
Abstract
Behçet's disease (BD) is a chronic relapsing disease involving multiple organ systems. BD is characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. It is widely recognized that the presence of intestinal lesions may be a poor prognostic factor in intestinal BD, increasing the risk of surgery and decreasing the quality of life. Despite this, the management of intestinal BD has not been standardized. Empirical therapies including 5-aminosalicylic acid and corticosteroids have been used anecdotally to treat intestinal BD, but recent studies have provided evidence for the efficacy of anti-tumor necrosis factor α monoclonal antibodies. The development of agents targeting tumor necrosis factor α continues, it seems likely that they will change the therapeutic strategy and clinical outcomes of intestinal BD and inflammatory bowel disease. Monitoring disease activity such as endoscopic evaluation will become more important to obtain better outcomes. Here, we review current and future perspectives in the treatment and outcomes of intestinal BD.
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Affiliation(s)
- Tadakazu Hisamatsu
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Mari Hayashida
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
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Lopalco G, Rigante D, Venerito V, Fabiani C, Franceschini R, Barone M, Lapadula G, Galeazzi M, Frediani B, Iannone F, Cantarini L. Update on the Medical Management of Gastrointestinal Behçet's Disease. Mediators Inflamm 2017; 2017:1460491. [PMID: 28210071 PMCID: PMC5292121 DOI: 10.1155/2017/1460491] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 01/04/2017] [Indexed: 02/07/2023] Open
Abstract
Behçet's disease (BD) is a multisystemic disorder of unknown etiology mainly defined by recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis, all of which represent the "stigmata" of disease. However, many other organs including the vascular, neurological, musculoskeletal, and gastrointestinal systems can be affected. The gastrointestinal involvement in Behçet's disease (GIBD), along with the neurological and vascular ones, represents the most feared clinical manifestation of BD and shares many symptoms with inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. Consequently, the differential diagnosis is often a daunting task, albeit the presence of typical endoscopic and pathologic findings may be a valuable aid to the exact diagnosis. To date, there are no standardized medical treatments for GIBD; therefore therapy should be tailored to the single patient and based on the severity of the clinical features and their complications. This work provides a digest of all current experience and evidence about pharmacological agents suggested by the medical literature as having a potential role for managing the dreadful features of GIBD.
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Affiliation(s)
- Giuseppe Lopalco
- Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Donato Rigante
- Institute of Pediatrics, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Largo A. Gemelli 8, 00168 Rome, Italy
| | - Vincenzo Venerito
- Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Claudia Fabiani
- Department of Ophthalmology, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Rossella Franceschini
- Ophthalmology and Neurosurgery Department, University of Siena, Viale Bracci 1, 53100 Siena, Italy
| | - Michele Barone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Giovanni Lapadula
- Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Mauro Galeazzi
- Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Viale Bracci 1, 53100 Siena, Italy
| | - Bruno Frediani
- Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Viale Bracci 1, 53100 Siena, Italy
| | - Florenzo Iannone
- Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Luca Cantarini
- Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Viale Bracci 1, 53100 Siena, Italy
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Efficacy of Adalimumab in a Girl with Refractory Intestinal Behcet's Disease. Case Rep Rheumatol 2015; 2015:716138. [PMID: 26609459 PMCID: PMC4644826 DOI: 10.1155/2015/716138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Revised: 06/10/2015] [Accepted: 06/14/2015] [Indexed: 01/21/2023] Open
Abstract
We describe our experience with a juvenile patient who had refractory intestinal Behcet's disease that responded to adalimumab, a fully humanized antibody against soluble TNF-α and its receptor. The patient, a 13-year-old girl, presented with oral aphthous ulcers, vulvar pain, and rashes on the lower extremities. She gradually developed a low-grade fever, abdominal pain, diarrhea, and hematochezia. Lower gastrointestinal endoscopy revealed ulcers in the terminal ileum, consistent with intestinal Behcet's disease. Methylprednisolone pulse therapy was initiated, after which the symptoms transiently improved, but, during the corticosteroid taper, the abdominal pain recurred. The symptoms resolved soon after the administration of adalimumab. Of importance, the dose of corticosteroids was successfully reduced without exacerbation during 8 months of observation. This is the first reported case in which adalimumab was used for pediatric gastrointestinal Behcet's disease. Adalimumab is a good choice for intestinal Behcet's disease refractory to conventional treatment.
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Lim YK, Keating JP, Steele R. Sucessful use of thalidomide in severe gastrointestinal Behçet's disease. ANZ J Surg 2015; 85:496. [PMID: 26031928 DOI: 10.1111/ans.12978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Yu Kai Lim
- Department of General Surgery, Wellington Hospital, Wellington South, New Zealand
| | - John Patrick Keating
- Department of General Surgery, Wellington Hospital, Wellington South, New Zealand
| | - Richard Steele
- Department of Immunology, Wellington Hospital, Wellington South, New Zealand
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14
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Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behçet's disease: A review. World J Gastroenterol 2015; 21:3801-3812. [PMID: 25852265 PMCID: PMC4385527 DOI: 10.3748/wjg.v21.i13.3801] [Citation(s) in RCA: 129] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Revised: 01/14/2015] [Accepted: 01/30/2015] [Indexed: 02/07/2023] Open
Abstract
Behçet’s disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet’s disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time.
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15
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Ozguler Y, Yazici H. Behçet's syndrome: New insights into pathogenesis and management. INDIAN JOURNAL OF RHEUMATOLOGY 2014. [DOI: 10.1016/j.injr.2014.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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16
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Abstract
Behçet disease is a chronic inflammatory systemic disorder, characterized by a relapsing and remitting course. It manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size. The cause of this disease is presumed to be multifactorial involving infectious triggers, genetic predisposition, and dysregulation of the immune system. As the clinical expression of Behçet disease is heterogeneous, pharmacological therapy is variable and depends largely on the severity of the disease and organ involvement. Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials.
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Affiliation(s)
| | - Thurayya Arayssi
- Weill Cornell Medical College-Qatar, Education City, PO Box 24144, Doha, Qatar
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17
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Hisamatsu T, Naganuma M, Matsuoka K, Kanai T. Diagnosis and management of intestinal Behçet's disease. Clin J Gastroenterol 2014; 7:205-12. [PMID: 24883128 PMCID: PMC4037558 DOI: 10.1007/s12328-014-0488-0] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Accepted: 04/01/2014] [Indexed: 12/12/2022]
Abstract
Behçet’s disease (BD) is a chronic relapsing disease with multiple organ system involvement characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. Little clinical evidence is available regarding the management of patients with intestinal BD, despite recognition that the presence of intestinal lesions is a poor prognostic factor, causing perforation and massive bleeding. Many recent case reports have suggested that anti-tumor necrosis factor alpha (TNF)α monoclonal antibodies (mAbs) are effective in patients with intestinal BD. Adalimumab, a fully human anti-TNFα mAb, has been approved in Japan for the treatment of intestinal BD. Here, we review the pathogenesis, diagnosis and management of intestinal BD, including evidence of the efficacy of anti-TNFα mAbs.
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Affiliation(s)
- Tadakazu Hisamatsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
| | - Makoto Naganuma
- Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
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Leite ACL, Barbosa FF, Cardoso MVDO, Moreira DRM, Coêlho LCD, da Silva EB, Filho GBDO, de Souza VMO, Pereira VRA, de C. Reis L, Ferreira PMP, Pessoa C, Wanderley AG, Mota FVB, da Silva TG. Phthaloyl amino acids as anti-inflammatory and immunomodulatory prototypes. Med Chem Res 2013. [DOI: 10.1007/s00044-013-0730-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Abstract
Behçet's syndrome (BS) shows a peculiar distribution, with a much higher prevalence in countries along the ancient Silk Road compared with rest of the world. BS also seems to follow a more severe course in ethnic groups with higher prevalence. Diagnosis depends on clinical findings. Criteria sets may not help in patients with less frequent types of involvement. Management strategies should be modified according to the age and sex of the patient and the organs involved. Being a serious health problem in endemic areas, BS also attracts global attention as a model to study inflammatory diseases of unknown cause.
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Affiliation(s)
- Gulen Hatemi
- Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University, Cerrahpasa, Istanbul 34089, Turkey
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20
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Zhang Z, Jian X, Liu H, Zhang W, Zhou Q. Recurrent aortic aneurysm due to Behcet's disease: a case report from China. Ann Thorac Cardiovasc Surg 2012; 19:173-5. [PMID: 22971707 DOI: 10.5761/atcs.cr.12.01923] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
In this report, we present a twenty-nine year old patient with a five-year history of Behcet's disease (BD), who developed an ascending aortic aneurysm. Chest enhanced computed tomography scanning demonstrated a saccular aneurysm of the ascending aorta, with a maximum diameter of 11 cm. The patient was administered with prednisone, thalidomide and anticoagulant. A regular follow up was carried out. The patient lived well with blood sedimentation and C-reactive protein in the normal range.
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Affiliation(s)
- Zhongchen Zhang
- Department of Poisoning and Occupational Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China
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21
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Jain R, L. Thiele D. Gastrointestinal and Hepatic Manifestations of Systemic Diseases. SLEISENGER AND FORDTRAN'S GASTROINTESTINAL AND LIVER DISEASE 2010:557-592.e11. [DOI: 10.1016/b978-1-4160-6189-2.00035-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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