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Behcet's Syndrome☆
Behcet’s Syndrome☆ P Raval, College of Arts and Sciences, Creighton University, Omaha, NE, USA ã 2015 Elsevier Inc. All rights reserved.
Introduction Definition Classification Consequences Associated Disorders Etiology Epidemiology Pathophysiology Signs and Symptoms Standard Therapies References
1 1 1 1 1 2 2 2 2 3 3
Introduction Behcet’s syndrome (BS), or Behcet’s disease, was first described by Hulusi Behcet (Behcet, 1937a,b). It is a chronic, inflammatory disease with recurrent oral and genital ulcers and hypopyon uveitis. Behcet’s disease is common in Mediterranean countries and the Far East; especially Korea and Japan. The condition is associated with the HLA B51 gene. Vasculitis is a major, and possibly the primary, feature of BS.
Definition Behcet’s syndrome (BS) is a chronic, inflammatory disease involving blood vessels of all sizes and many organs. Genital and oral ulceration, aphthous stomatitis (recurrent ulcers), and itritis are the primary diagnostic features of this disorder.
Classification Behcet’s syndrome (BS) is a nonselective vasculitis. Whereas other vasculitic diseases involve specific size blood vessels, nearly all sizes of blood vessels are involved in BS. An international group of physicians has established guidelines to aid in the classification of BS patients. The symptoms include recurrent oral ulceration and at least two of the following four criteria: (1) recurrent genital ulceration, (2) uveitis or retinal vasculitis, (3) skin lesions (acne or erythema nodosum), or (4) a positive pathergy test (pricking skin with a sterile needle causes a red nodule). Some of these symptoms are not specific for BS. For example, many Mediterranean people show positive pathergy test without the disease, while many BS patients from other countries do not show a positive pathergy test. Oral ulcerations are also observed in many patients without the disease. However, BS patients commonly have many and recurrent oral ulcers, along with ulcers in other parts of the body.
Consequences Behcet’s syndrome (BS) is distinguished from other forms of vasculitis because it involves nearly all sizes of blood vessels. Painful sores in the mouth, genitals, and other areas of the body, aneurysms of arteries in the lungs, hemorrhage, arthritis, arthralgias (pain and swelling in joints), damage to the central nervous system, ulceration in the gastrointestinal tract, and, in females, ulceration in the vagina and labia, are some of the characteristics of BS. Although BS is not fatal, it is not curable, although its symptoms can be managed. As it can recur periodically, it should be routinely monitored.
☆
Change History: August 2014. P Raval has updated the text and references.
Reference Module in Biomedical Research
http://dx.doi.org/10.1016/B978-0-12-801238-3.04873-X
1
2
Behcet’s Syndrome
Associated Disorders Damage to the central nervous system is the most dangerous manifestation of Behcet’s syndrome. This can result in headache, confusion, stroke, and personality changes or meningitis. A study in Japan (Lakahanpal et al., 1985) suggested cerebrospinal demyelination as the most common pathologic finding, followed by encephalomalacia and cerebral atrophy. Inflammation of the aorta, pulmonary, and peripheral arteries are also serious complications of BS and are responsible for the majority of fatalities associated with this condition. Arthritis, subcutaneous thrombophlebitis, deep vein thrombosis arterial aneurysm, and central nervous system disorders may occur in 5–30% of BS patients. Gastrointestinal lesions are more common among Japanese patients, although the pathergy reaction is more prevalent among those from Mediterranean countries.
Etiology The cause of Behchet’s syndrome is unknown. The high prevalence of BS in Japan and the Mediterranean suggests that both genetic and environmental factors are involved. HLA-B51 has been found to be strongly associated with BS in Japanese, Greek, Italian, and Saudi Arabian patients (Kera et al., 1999; Koumantaki et al., 1998; Mizuki et al., 1993, 1994; Ohno et al., 1982; Yabuki et al., 1999), although not all BS patients are HLA-B51 positive. Conversely, not all HLA-B51 positive patients have B S. Poor oral hygiene, chronic tonsillitis and peridonititis is frequently present among the patients. Streptococcus sanguinis (S. sanguinis) and S. mitis may play a role in causing this condition. Most patients tend to acquire delayed hypersensitivity against streptococci (Mumcu et al., 2009, Yokota et al., 1995).
Epidemiology Behcet’s syndrome (BS) is most prevalent in the Mediterranean basin, Korea, and Japan. It is not common in northern Europe, Australia, northern Asia, Africa, or the Americas. Although BS has been reported in every race, the African population appears to be least affected. Although the condition can occur at any age, it is rare in children and in those over 50 years of age. Although men and women are equally susceptible, the disease may be more severe in men. The condition usually first appears during the fourth decade of life and is not specific to any socio-economic class. As overall prevalence and manifestation of symptoms are geographically related, genetic factors may play a role in the development of this condition. For example, gastrointestinal involvement is common in Japan (Shimizu et al., 1979), while pathergy (sensitivity to minor trauma) is observed more often with those from Mediterranean countries.
Pathophysiology Vasculitis is a major characteristic of Behcet’s syndrome and may be the primary pathologic feature. As an increased prevalence of neutrophils and immune complexes has been observed in the circulation, these may be important mediators of the vascular damage. Anti-endothelial cytoplasmic antibodies (AECA) have been observed in some patients. In BS patients, elevated endothelin-1 (ET-1), a potent vasoconstricting peptide, may be responsible for thrombosis. However, it is not known whether patients with thrombosis in the absence of BS have elevated levels of ET-1. Decreased levels of nitrous oxide and increased levels of von Willebrand factor are also observed in BS patients. These results suggest endothelial dysfunction. The condition may be triggered by exogenous agents, such as bacteria, viruses, or other microorganisms, with increased CD4 + cells found in perivascular inflammatory exudates. Activation of TH1 cells produces IFN-gamma, IL-2, and TNF (Valente et al., 1997). Moreover, increased levels of gamma-delta T lymphocytes are observed in some patients (Esin et al., 1997; Hamzaoui et al., 1994). Histopathological examination of ulcers associated with BS reveals lymphatic and monocytic inflammatory infiltrates in the basal layer and dermis, with active neutrophils present in later stages.
Signs and Symptoms Painful, numerousoral and genital ulcers, and other skin lesions, are the initial sign of B S. Uveitis of anterior and posterior ocular chambers is major problem associated with this condition. Loss of vision may occur even with therapy. Although nonspecific hyper-reactivity to minor trauma (pathergy) is observed in many BS patients from Turkey and other Mediterranean regions, it is uncommon in those from other countries.
Behcet’s Syndrome
3
Standard Therapies Therapy for Behcet’s syndrome (BS) largely depends on the signs, symptoms, and severity of the disease. Although there is no standard therapy because the pathogenetic mechanism is unknown, a great deal of progress has been made in the management of this condition. For example, although loss of vision was reported in almost three quarters of BS patients in 1986 (BenEzra and Cohen, 1986), it now occurs in less than one-fifth (Yazici et al., 1996). A survey conducted during the International Symposium on BS in Reggio Emilia, Italy (October 1998), indicated no consensus on treatment for this condition. However, it is generally agreed that glucocorticoids are effective in treating retinal vasculitis. In contrast, the use of anticoagulants to treat deep vein thrombosis is still a matter of debate. Ten clinical trials including 679 patients were conducted in the 1990s. Together, they concluded that there is insufficient evidence to support or deny the value of some of the classic treatments for BS including colchicine, cyclophosphamide, steroids, and azapropazone. However, they may be of value in controlling disorders associated with BS. Agent Name
Discussion
Glucocorticoids
Glucocorticoids are a standard therapy for Behcet’s syndrome, with a brief course of prednisolone (20 mg/day) being employed. As potent anti-inflammatory agents, glucocorticoids bring prompt relief to those suffering from B S. These drugs also suppress the destruction of platelets by the immune system (idiopathic thrombocytopenia purpura and autoimmune diseases). Glucocorticoid therapy should be tapered once the condition is under control. BS patients with responded well to a 100–300 mg/day dose of thalidomide. However, its use is limited because of its teratogenic potential. It is believed that thalidomide suppresses the immune system. Intralesional injection of recombinant human granulocyte-macrophage colony-stimulating factor (GMCSF) may be useful in the treatment of oral and genital ulcers. GMCSF helps to repair blood-forming tissues, blood vessels, and it induces synthesis of hematopoietic cells. Colchicine (1.5 mg/day), which has been used for the treatment of Behcet’s syndrome since 1980, is effective in controlling some of the conditions associated with this disorder, including erythema nodosum and arthritis. Colchicine is an anti-inflammatory agent that influences the migration of cells associated with inflammation. The antibiotic benzathine penicillin is reported to be superior to colchicine alone in managing mucocutaneous and arthritic episodes in Behcet’s syndrome. Interferon-alpha has been used in the treatment of uveitis associated with Behcet’s syndrome. It also displays some benefit in the treatment of mucocutaneous lesions, arthritis, and gastrointestinal symptoms (Zouboulis and Orfanos, 1998). Interferons are produced by the immune system in response to infection. Interferonalpha induces production of cytotoxic molecules, including tumor necrosis factor-gamma, interleukins, and other cytokines. Azathioprine, 2.5 mg/kg/day, is effective in treatment of bilateral eye disease and in decreasing the glucocorticoid dose in those with established eye disease. It is also effective in reducing the severity of eye disease in young male Behcet’s patients. Azathioprine is a potent immunosuppressant. Cyclosporine, an immunosuppressant, induces a rapid anti-inflammatory effect at doses of 2–5 mg/kg/day. Cyclophosphamide therapy, 2 mg/kg orally, adjusted to maintain a white blood cell count of approximately 5000, is normally continued for 6 months. Cyclophosphamide, which is converted to two active compounds, acrolein and phosphoramide, that interfere with DNA synthesis, reduce the production of erythrocytes in bone marrow and suppress the immune system.
Thalidomide Granulocyte-macrophage colonystimulating factor Colchicine
Penicillin Interferon gamma
Azathioprine
Cyclosporine Cyclophosphamide
References Journal Citations Behcet H (1937a) U¨ber rezidivierende, aphthous durch ein Virus verusachte Geschwure am Mund, am Auge und an den Genitalien. Dermatol Wochenschri 105: 1152–1157. Mizuki N, Inoko H, Ando H, Nakamura S, Kashiwase K, Akaza T, et al. (1993) Behcet’s disease associated with one of the HLA-B51 subantigens, HLA-B 5101. American Journal of Ophthalmology 116: 406–409. Mizuki N, Inoko H, Ishihara M, Ando H, Nakamura S, Nishio M, et al. (1994) A complete type patient with Behcet’s associated with HLA-V 5102. Acta Ophthalmologica 72: 757–758. Koumantaki Y, Stavropoulos C, Spyropoulou M, Messini H, Papademetropoulos M, Giziaki E, et al. (1998) HLA-B 5101 in Greek patients with Behcet’s disease. Human Immunology 59: 250–255. Shimizu T, Ehrlich GE, Inaba G, and Hayashi K (1979) Behcet’s disease. Seminars in Arthritis and Rheumatism 8: 223–260. Esin S, Gul A, Hodara V, Jeddi-Tehrani M, Dilsen N, Konice M, et al. (1997) Peripheral blood T cell expansions in patients with Behcet’s disease. Clinical and Experimental Immunology 107: 520–527. Hamzaoui K, Hamzaoui A, and Hentati F (1994) Phenotype and functional profile of T cells expressing gamma-delta receptor from patients with active Behcet’s disease. Journal of Rheumatology 21: 2301–2306. BenEzra D and Cohen T (1986) Treatment and visual prognosis in Behcet’s disease. The British Journal of Ophthalmology 70: 589–592. Yazici H, Basaran G, Hamuryudan V, Hizli N, Yurdakul S, Mat C, et al. (1996) The ten-year mortality in Behcet’s syndrome. The British Journal of Ophthalmology 35: 139–141. Zouboulis CC and Orfanos CE (1998) Treatment of Adamantiades-Behcet’s disease with systemic interferon-alpha. Archives of Dermatology 134: 1010–1016.
4
Behcet’s Syndrome
Lakahanpal S, Tani K, Lie JT, Katoh K, Ishigatsubo Y, and Ohokubo T (1985) Pathologic features of Behcet’s syndrome. A review of Japanese autopsy registry data. Human Pathology 16: 790–795. Behcet H (1937b) Ueber rezidivierende aphtose durch ein virus verursachte geschwuere am mund, am auge und anden genitalien. Dermatologische Woschenschrift 105: 1152–1157. Ohno S, Ohguchi M, Hirose S, Matsuda H, Wakisaka A, and Aizawa M (1982) Close association of HLA-Bw51 with Behcet’s syndrome. Archives of Ophthalmology 100: 1455–1458. Yabuki K, Mizuki N, Ohno S, Ando H, Tabbara KF, Ishihara M, et al. (1999) HLA class I and class II typing of the patients with Behcet’s disease in Saudi Arabia. Tissue Antigens 54: 273–277. Kera J, Mizuki N, Ota M, Katsuyama Y, Pivetti-Pezzi P, Ohno S, and Inoko H (1999) Significant association of HLA-B 5101 and B 5108 and the lack of association of class II alleles with Behcet’s disease in Italian patients. Tissue Antigens 54: 565–571. Mumcu G, Inanc N, Aydin SZ, Ergun T, and Direskeneli H (2009) Association of salivary S. mutans colonization and mannose-binding lactin deficiency with gender in Behcet’s disease. Clinical and Experimental Rheumatology 27(supplement 53): S32–S36. Yokota K, Hayashi S, Araki Y, et al. (1995) Characterization of Streptococcus sanguis isolated from pateints with Behcet’s disease. Microbiology and Immunology 39(No. 9): 729–732. Book Citations Valente RM, Hall S, O’Duffy JD, and Conn DL (1997) Vasculitis and related disorders: Behcet’s disease. In: Kelly H and Ruddy S (eds.) Textbook of Rheumatology, Vol II pp. 1114–1122. Philadelphia, PA: Saunders.
Further Reading Yazici H, Fresko I, Tunc R, and Melikoglu M (2002) Behcet’s syndrome: Pathogenesis, clinical manifestations and treatment. In: Ball GV and Brides SL Jr. (eds.) Vasculitis, pp. 406–432. Oxford: Oxford University Press. Mizuki N and Inoko H (2002) Behcet’s Syndorme: Immunogenetics. In: Ball GV and Brides SL Jr. (eds.) Vasculitis, pp. 433–440. Oxford: Oxford University Press. Azizlerli G (2002) Juvenile Behcet’s Syndrome. In: Ball GV and Brides SL Jr. (eds.) Vasculitis, pp. 441–444. Oxford: Oxford University Press.
Relevant Websites http://www.behcets.org.uk/ – This site is hosted by a non-profit patient support group in the U K. Patients can find information regarding the disease and can discuss problems associated with this condition. www.ninds.nih.gov/health_and_medical/disorders/behcet_doc.htm – This site is maintained by the National Institute of Neurological Disorders and Stroke. It provides a description of the disease, available treatments, and current research.
Introduction Definition Classification Consequences Associated Disorders Etiology Epidemiology Pathophysiology Signs and Symptoms Standard Therapies References
1 1 1 1 1 2 2 2 2 3 3
Introduction Behcet’s syndrome (BS), or Behcet’s disease, was first described by Hulusi Behcet (Behcet, 1937a,b). It is a chronic, inflammatory disease with recurrent oral and genital ulcers and hypopyon uveitis. Behcet’s disease is common in Mediterranean countries and the Far East; especially Korea and Japan. The condition is associated with the HLA B51 gene. Vasculitis is a major, and possibly the primary, feature of BS.
Definition Behcet’s syndrome (BS) is a chronic, inflammatory disease involving blood vessels of all sizes and many organs. Genital and oral ulceration, aphthous stomatitis (recurrent ulcers), and itritis are the primary diagnostic features of this disorder.
Classification Behcet’s syndrome (BS) is a nonselective vasculitis. Whereas other vasculitic diseases involve specific size blood vessels, nearly all sizes of blood vessels are involved in BS. An international group of physicians has established guidelines to aid in the classification of BS patients. The symptoms include recurrent oral ulceration and at least two of the following four criteria: (1) recurrent genital ulceration, (2) uveitis or retinal vasculitis, (3) skin lesions (acne or erythema nodosum), or (4) a positive pathergy test (pricking skin with a sterile needle causes a red nodule). Some of these symptoms are not specific for BS. For example, many Mediterranean people show positive pathergy test without the disease, while many BS patients from other countries do not show a positive pathergy test. Oral ulcerations are also observed in many patients without the disease. However, BS patients commonly have many and recurrent oral ulcers, along with ulcers in other parts of the body.
Consequences Behcet’s syndrome (BS) is distinguished from other forms of vasculitis because it involves nearly all sizes of blood vessels. Painful sores in the mouth, genitals, and other areas of the body, aneurysms of arteries in the lungs, hemorrhage, arthritis, arthralgias (pain and swelling in joints), damage to the central nervous system, ulceration in the gastrointestinal tract, and, in females, ulceration in the vagina and labia, are some of the characteristics of BS. Although BS is not fatal, it is not curable, although its symptoms can be managed. As it can recur periodically, it should be routinely monitored.
☆
Change History: August 2014. P Raval has updated the text and references.
Reference Module in Biomedical Research
http://dx.doi.org/10.1016/B978-0-12-801238-3.04873-X
1
2
Behcet’s Syndrome
Associated Disorders Damage to the central nervous system is the most dangerous manifestation of Behcet’s syndrome. This can result in headache, confusion, stroke, and personality changes or meningitis. A study in Japan (Lakahanpal et al., 1985) suggested cerebrospinal demyelination as the most common pathologic finding, followed by encephalomalacia and cerebral atrophy. Inflammation of the aorta, pulmonary, and peripheral arteries are also serious complications of BS and are responsible for the majority of fatalities associated with this condition. Arthritis, subcutaneous thrombophlebitis, deep vein thrombosis arterial aneurysm, and central nervous system disorders may occur in 5–30% of BS patients. Gastrointestinal lesions are more common among Japanese patients, although the pathergy reaction is more prevalent among those from Mediterranean countries.
Etiology The cause of Behchet’s syndrome is unknown. The high prevalence of BS in Japan and the Mediterranean suggests that both genetic and environmental factors are involved. HLA-B51 has been found to be strongly associated with BS in Japanese, Greek, Italian, and Saudi Arabian patients (Kera et al., 1999; Koumantaki et al., 1998; Mizuki et al., 1993, 1994; Ohno et al., 1982; Yabuki et al., 1999), although not all BS patients are HLA-B51 positive. Conversely, not all HLA-B51 positive patients have B S. Poor oral hygiene, chronic tonsillitis and peridonititis is frequently present among the patients. Streptococcus sanguinis (S. sanguinis) and S. mitis may play a role in causing this condition. Most patients tend to acquire delayed hypersensitivity against streptococci (Mumcu et al., 2009, Yokota et al., 1995).
Epidemiology Behcet’s syndrome (BS) is most prevalent in the Mediterranean basin, Korea, and Japan. It is not common in northern Europe, Australia, northern Asia, Africa, or the Americas. Although BS has been reported in every race, the African population appears to be least affected. Although the condition can occur at any age, it is rare in children and in those over 50 years of age. Although men and women are equally susceptible, the disease may be more severe in men. The condition usually first appears during the fourth decade of life and is not specific to any socio-economic class. As overall prevalence and manifestation of symptoms are geographically related, genetic factors may play a role in the development of this condition. For example, gastrointestinal involvement is common in Japan (Shimizu et al., 1979), while pathergy (sensitivity to minor trauma) is observed more often with those from Mediterranean countries.
Pathophysiology Vasculitis is a major characteristic of Behcet’s syndrome and may be the primary pathologic feature. As an increased prevalence of neutrophils and immune complexes has been observed in the circulation, these may be important mediators of the vascular damage. Anti-endothelial cytoplasmic antibodies (AECA) have been observed in some patients. In BS patients, elevated endothelin-1 (ET-1), a potent vasoconstricting peptide, may be responsible for thrombosis. However, it is not known whether patients with thrombosis in the absence of BS have elevated levels of ET-1. Decreased levels of nitrous oxide and increased levels of von Willebrand factor are also observed in BS patients. These results suggest endothelial dysfunction. The condition may be triggered by exogenous agents, such as bacteria, viruses, or other microorganisms, with increased CD4 + cells found in perivascular inflammatory exudates. Activation of TH1 cells produces IFN-gamma, IL-2, and TNF (Valente et al., 1997). Moreover, increased levels of gamma-delta T lymphocytes are observed in some patients (Esin et al., 1997; Hamzaoui et al., 1994). Histopathological examination of ulcers associated with BS reveals lymphatic and monocytic inflammatory infiltrates in the basal layer and dermis, with active neutrophils present in later stages.
Signs and Symptoms Painful, numerousoral and genital ulcers, and other skin lesions, are the initial sign of B S. Uveitis of anterior and posterior ocular chambers is major problem associated with this condition. Loss of vision may occur even with therapy. Although nonspecific hyper-reactivity to minor trauma (pathergy) is observed in many BS patients from Turkey and other Mediterranean regions, it is uncommon in those from other countries.
Behcet’s Syndrome
3
Standard Therapies Therapy for Behcet’s syndrome (BS) largely depends on the signs, symptoms, and severity of the disease. Although there is no standard therapy because the pathogenetic mechanism is unknown, a great deal of progress has been made in the management of this condition. For example, although loss of vision was reported in almost three quarters of BS patients in 1986 (BenEzra and Cohen, 1986), it now occurs in less than one-fifth (Yazici et al., 1996). A survey conducted during the International Symposium on BS in Reggio Emilia, Italy (October 1998), indicated no consensus on treatment for this condition. However, it is generally agreed that glucocorticoids are effective in treating retinal vasculitis. In contrast, the use of anticoagulants to treat deep vein thrombosis is still a matter of debate. Ten clinical trials including 679 patients were conducted in the 1990s. Together, they concluded that there is insufficient evidence to support or deny the value of some of the classic treatments for BS including colchicine, cyclophosphamide, steroids, and azapropazone. However, they may be of value in controlling disorders associated with BS. Agent Name
Discussion
Glucocorticoids
Glucocorticoids are a standard therapy for Behcet’s syndrome, with a brief course of prednisolone (20 mg/day) being employed. As potent anti-inflammatory agents, glucocorticoids bring prompt relief to those suffering from B S. These drugs also suppress the destruction of platelets by the immune system (idiopathic thrombocytopenia purpura and autoimmune diseases). Glucocorticoid therapy should be tapered once the condition is under control. BS patients with responded well to a 100–300 mg/day dose of thalidomide. However, its use is limited because of its teratogenic potential. It is believed that thalidomide suppresses the immune system. Intralesional injection of recombinant human granulocyte-macrophage colony-stimulating factor (GMCSF) may be useful in the treatment of oral and genital ulcers. GMCSF helps to repair blood-forming tissues, blood vessels, and it induces synthesis of hematopoietic cells. Colchicine (1.5 mg/day), which has been used for the treatment of Behcet’s syndrome since 1980, is effective in controlling some of the conditions associated with this disorder, including erythema nodosum and arthritis. Colchicine is an anti-inflammatory agent that influences the migration of cells associated with inflammation. The antibiotic benzathine penicillin is reported to be superior to colchicine alone in managing mucocutaneous and arthritic episodes in Behcet’s syndrome. Interferon-alpha has been used in the treatment of uveitis associated with Behcet’s syndrome. It also displays some benefit in the treatment of mucocutaneous lesions, arthritis, and gastrointestinal symptoms (Zouboulis and Orfanos, 1998). Interferons are produced by the immune system in response to infection. Interferonalpha induces production of cytotoxic molecules, including tumor necrosis factor-gamma, interleukins, and other cytokines. Azathioprine, 2.5 mg/kg/day, is effective in treatment of bilateral eye disease and in decreasing the glucocorticoid dose in those with established eye disease. It is also effective in reducing the severity of eye disease in young male Behcet’s patients. Azathioprine is a potent immunosuppressant. Cyclosporine, an immunosuppressant, induces a rapid anti-inflammatory effect at doses of 2–5 mg/kg/day. Cyclophosphamide therapy, 2 mg/kg orally, adjusted to maintain a white blood cell count of approximately 5000, is normally continued for 6 months. Cyclophosphamide, which is converted to two active compounds, acrolein and phosphoramide, that interfere with DNA synthesis, reduce the production of erythrocytes in bone marrow and suppress the immune system.
Thalidomide Granulocyte-macrophage colonystimulating factor Colchicine
Penicillin Interferon gamma
Azathioprine
Cyclosporine Cyclophosphamide
References Journal Citations Behcet H (1937a) U¨ber rezidivierende, aphthous durch ein Virus verusachte Geschwure am Mund, am Auge und an den Genitalien. Dermatol Wochenschri 105: 1152–1157. Mizuki N, Inoko H, Ando H, Nakamura S, Kashiwase K, Akaza T, et al. (1993) Behcet’s disease associated with one of the HLA-B51 subantigens, HLA-B 5101. American Journal of Ophthalmology 116: 406–409. Mizuki N, Inoko H, Ishihara M, Ando H, Nakamura S, Nishio M, et al. (1994) A complete type patient with Behcet’s associated with HLA-V 5102. Acta Ophthalmologica 72: 757–758. Koumantaki Y, Stavropoulos C, Spyropoulou M, Messini H, Papademetropoulos M, Giziaki E, et al. (1998) HLA-B 5101 in Greek patients with Behcet’s disease. Human Immunology 59: 250–255. Shimizu T, Ehrlich GE, Inaba G, and Hayashi K (1979) Behcet’s disease. Seminars in Arthritis and Rheumatism 8: 223–260. Esin S, Gul A, Hodara V, Jeddi-Tehrani M, Dilsen N, Konice M, et al. (1997) Peripheral blood T cell expansions in patients with Behcet’s disease. Clinical and Experimental Immunology 107: 520–527. Hamzaoui K, Hamzaoui A, and Hentati F (1994) Phenotype and functional profile of T cells expressing gamma-delta receptor from patients with active Behcet’s disease. Journal of Rheumatology 21: 2301–2306. BenEzra D and Cohen T (1986) Treatment and visual prognosis in Behcet’s disease. The British Journal of Ophthalmology 70: 589–592. Yazici H, Basaran G, Hamuryudan V, Hizli N, Yurdakul S, Mat C, et al. (1996) The ten-year mortality in Behcet’s syndrome. The British Journal of Ophthalmology 35: 139–141. Zouboulis CC and Orfanos CE (1998) Treatment of Adamantiades-Behcet’s disease with systemic interferon-alpha. Archives of Dermatology 134: 1010–1016.
4
Behcet’s Syndrome
Lakahanpal S, Tani K, Lie JT, Katoh K, Ishigatsubo Y, and Ohokubo T (1985) Pathologic features of Behcet’s syndrome. A review of Japanese autopsy registry data. Human Pathology 16: 790–795. Behcet H (1937b) Ueber rezidivierende aphtose durch ein virus verursachte geschwuere am mund, am auge und anden genitalien. Dermatologische Woschenschrift 105: 1152–1157. Ohno S, Ohguchi M, Hirose S, Matsuda H, Wakisaka A, and Aizawa M (1982) Close association of HLA-Bw51 with Behcet’s syndrome. Archives of Ophthalmology 100: 1455–1458. Yabuki K, Mizuki N, Ohno S, Ando H, Tabbara KF, Ishihara M, et al. (1999) HLA class I and class II typing of the patients with Behcet’s disease in Saudi Arabia. Tissue Antigens 54: 273–277. Kera J, Mizuki N, Ota M, Katsuyama Y, Pivetti-Pezzi P, Ohno S, and Inoko H (1999) Significant association of HLA-B 5101 and B 5108 and the lack of association of class II alleles with Behcet’s disease in Italian patients. Tissue Antigens 54: 565–571. Mumcu G, Inanc N, Aydin SZ, Ergun T, and Direskeneli H (2009) Association of salivary S. mutans colonization and mannose-binding lactin deficiency with gender in Behcet’s disease. Clinical and Experimental Rheumatology 27(supplement 53): S32–S36. Yokota K, Hayashi S, Araki Y, et al. (1995) Characterization of Streptococcus sanguis isolated from pateints with Behcet’s disease. Microbiology and Immunology 39(No. 9): 729–732. Book Citations Valente RM, Hall S, O’Duffy JD, and Conn DL (1997) Vasculitis and related disorders: Behcet’s disease. In: Kelly H and Ruddy S (eds.) Textbook of Rheumatology, Vol II pp. 1114–1122. Philadelphia, PA: Saunders.
Further Reading Yazici H, Fresko I, Tunc R, and Melikoglu M (2002) Behcet’s syndrome: Pathogenesis, clinical manifestations and treatment. In: Ball GV and Brides SL Jr. (eds.) Vasculitis, pp. 406–432. Oxford: Oxford University Press. Mizuki N and Inoko H (2002) Behcet’s Syndorme: Immunogenetics. In: Ball GV and Brides SL Jr. (eds.) Vasculitis, pp. 433–440. Oxford: Oxford University Press. Azizlerli G (2002) Juvenile Behcet’s Syndrome. In: Ball GV and Brides SL Jr. (eds.) Vasculitis, pp. 441–444. Oxford: Oxford University Press.
Relevant Websites http://www.behcets.org.uk/ – This site is hosted by a non-profit patient support group in the U K. Patients can find information regarding the disease and can discuss problems associated with this condition. www.ninds.nih.gov/health_and_medical/disorders/behcet_doc.htm – This site is maintained by the National Institute of Neurological Disorders and Stroke. It provides a description of the disease, available treatments, and current research.