Behçet's disease
Encyclopedia
Behçet's disease (Persian: 'بهجت') (Sometimes called Behçet's syndrome, Morbus Behçet, or Silk Road disease) is a rare immune-mediated systemic
vasculitis
that often presents with mucous membrane ulceration and ocular involvements. Behçet disease (BD) was named in 1937 after the Turkish dermatologist Hulusi Behçet, who first described the triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis
. As a systemic disease, it can also involve visceral organs such as the gastrointestinal tract, pulmonary, musculoskeletal, and neurological systems. This syndrome can be fatal, due to ruptured vascular aneurysms, or severe neurological complications.
s or non-scarring oral lesions. The oral lesions are similar to those found in inflammatory bowel disease
and can be relapsing. Painful genital ulcerations usually develop around the anus, vulva or scrotum and cause scarring in 75% of the patients. Additionally, patients may present with erythema nodosum
, cutaneous pustular vasculitis, and lesions similar to pyoderma gangrenosum
.
. Anterior uveitis presents with painful eyes, conjuctival redness, hypopyon
, and decreased visual acuity, while posterior uveitis presents with painless decreased visual acuity and visual field floaters. A rare form of ocular (eye) involvement in this syndrome is retinal vasculitis which presents with painless decrease of vision with the possibility of floaters or visual field defects.
) have also been reported to occur. Optic nerve atrophy has been identified as the most common cause of visual impairment. Behçet's disease may result in primary or secondary optic nerve involvement. Papilledema as a result of dural sinus thrombosis and atrophy resulting from retinal disease, have been characterized as secondary causes of optic nerve atrophy in Behçet's disease.
Signs and symptoms of acute optic neuropathy
include painless loss of vision which may affect either one or both eyes, reduced visual acuity, reduced color vision, relative afferent pupillary defect, central scotoma
, swollen optic disc, macular edema
, or retrobulbar pain. When these symptoms occur with concurrent mucocutaneous ulcerations, they raise suspicion of acute optic neuropathy in Behçet's Disease. Progressive optic atrophy may result in decreased visual acuity or color vision. Intracranial hypertension with papilledema
may be present.
, pleuritis, cough, or fever, and in severe cases can be life threatening if the outlet pulmonary artery develops an aneurysm which ruptures causing severe vascular collapse and death from bleeding in the lungs.
is seen in up to half of patients, and is usually a non-erosive poly or oligoarthritis primarily of the large joints of the lower extremities.
to vascular thrombosis such as dural sinus thrombosis and organic brain syndrome
manifesting with confusion, seizures, and memory loss. They often appear late in the progression of the disease but are associated with a poor prognosis.
labialis, and therefore clinical suspicion should be maintained until all the common causes of oral lesions are ruled out from the differential diagnosis
.
Visual acuity, or color vision loss with concurrent mucocutaneous lesions and/or systemic Behçet's symptoms should raise suspicion of optic nerve involvement in Behçet's disease and prompt a work-up for Behçet's disease if not previously diagnosed in addition to an ocular work-up. Diagnosis of Behçet's disease is based on clinical findings including oral and genital ulcers, skin lesions such as erythema nodosum, acne, or folliculitis, ocular inflammatory findings and a pathergy reaction. Inflammatory markers such ESR, and CRP may be elevated. A complete ophthalmic examination may include a slit lamp examination, optical coherence tomography
to detect nerve loss, visual field examinations, fundoscopic examination to assess optic disc atrophy and retinal disease, fundoscopic angiography, and visual evoked potentials, which may demonstrate increased latency. Optic nerve enhancement may be identified on Magnetic Resonance Imaging (MRI) in some patients with acute optic neuropathy. However, a normal study does not rule out optic neuropathy. Cerebrospinal fluid (CSF) analysis may demonstrate elevated protein level with or without pleocytosis. Imaging including angiography may be indicated to identify dural venous sinus thrombosis as a cause of intracranial hypertension and optic atrophy.
" symptoms:
Despite the inclusive criteria set forth by the International Study Group, there are cases where not all the criteria can be met and therefore a diagnosis cannot readily be made. There is however a set of clinical findings that a physician can rely upon in making a tentative diagnosis of the disease; essentially Behçet's disease does not always follow the International Study Group guidelines and so a high degree of suspicion for a patient who presents having any number of the following findings is necessary:
is not well-defined, but it is primarily characterized by auto-inflammation of the blood vessels. Although sometimes erroneously referred to as a "diagnosis of exclusion," the diagnosis can sometimes be reached by pathologic examination of the affected areas.
The primary mechanism of the damage is an overactive immune system that seems to target the patient's own body. The primary cause is not well known. In fact, as of now, no one knows why the immune system starts to behave this way in Behçet's disease. There does however seem to be a genetic component involved, as first degree relatives of the affected patients are often affected in more than expected proportion for the general population.
therapy such as infliximab
has shown promise in treating the uveitis associated with the disease. Another Anti-TNF agent, Etanercept
, may be useful in patients with mainly skin and mucosal symptoms.
Interferon alfa-2a may also be an effective alternative treatment, particularly for the genital and oral ulcers as well as ocular lesions. Azathioprine
, when used in combination with interferon alfa-2b also shows promise, and Colchicine
can be useful for treating some genital ulcers, erythema nodosum
, and arthritis.
Thalidomide
has also been used due to its immune-modifying effect. Dapsone
and rebamipide
have been shown, in small studies, to have beneficial results for mucocutaneous lesions.
Given its rarity, the optimal treatment for acute optic neuropathy in Behçet's disease has not been established. Early identification and treatment is essential. Response to ciclosporin
, periocular triamcinolone, and IV methylprednisone followed by oral prednisone has been reported although relapses leading to irreversible visual loss may occur even with treatment. Immunosuppressant
s such as interferon alpha and tumour necrosis factor antagonists may improve though not completely reverse symptoms of ocular Behçet's, which may progress over time despite treatment. When symptoms are limited to the anterior chamber of the eye prognosis is improved. Posterior involvement, particularly optic nerve involvement is a poor prognostic indicator. Secondary optic nerve atrophy is frequently irreversible. Lumbar puncture or surgical treatment may be required to prevent optic atrophy in cases of intracranial hypertension refractory to treatment with immunomodulators and steroids.
Behçet disease is considered more prevalent in the areas surrounding the old silk trading routes
in the Middle East
and in Central Asia
. Thus, it is sometimes known as Silk Road Disease. However, this disease is not restricted to people from these regions. A large number of serological studies show a linkage between the disease and HLA-B51
. HLA-B51 is more frequently found from the Middle East to South Eastern Siberia, but the incidence of B51 in some studies was 3 fold higher than the normal population. However, B51 tends not to be found in disease when a certain SUMO4
gene variant is involved, and symptoms appear to be milder when HLA-B27
is present. At the current time, a similar infectious origin has not yet been confirmed that leads to Behçet's disease, but certain strains of Streptococcus sanguinis
has been found to have a homologous antigenicity.
Vasculitis
resulting in occlusion of the vessels supplying the optic nerve may be the cause of acute optic neuropathy and progressive optic atrophy in Behçet's disease. Histological evaluation in a reported case of acute optic neuropathy demonstrated substitution of the axonal portion of the optic nerve with fibrous astrocytes without retinal changes. CNS involvement in Behçet's may lead to intracranial hypertension most commonly due to dural venous sinus thrombosis [8-10] and subsequent secondary optic atrophy.
, and links with tissue-types (which are under investigation) are not certain. It also does not follow the usual pattern for autoimmune diseases. However, one study has revealed a possible connection to food allergies, particularly to dairy products. An estimated 15,000 to 20,000 Americans have been diagnosed with this disease. In the UK, it is estimated to have about 1 case for every 100,000 people. Globally, males are affected more frequently than females. In the United States, more females are affected than males.
In an epidemiologic study by Krause et al., 56% of patient’s with Behçet's disease developed ocular involvement at a mean age of 30. Ocular involvement was the first manifestation of Behçet's disease in 8.6% of patients.] Ocular Behçet's with involvement of the optic nerve is rarely reported. Among patients with ocular Behçet's disease funduscopic findings of optic atrophy, and optic disc paleness have been identified with a frequency of 17.9% and 7.4%, respectively. Other fundoscopic findings include vascular sheathing(23.7%), retinal hemorrhage(9%), macular edema(11.3%), branch retinal vein occlusion(5.8%), and retinal edema(6.6%). However, optic atrophy was the most significant cause of visual impairment identified in 54% of patients with ocular Behçet's disease and permanent visual impairment.
after Hulusi Behçet
(1889–1948), the Turkish
dermatologist and scientist
who first recognized the syndrome in one of his patients in 1924 and reported his research on the disease in Journal of Skin and Venereal Diseases in 1936. The name (Morbus Behçet) was formally adopted at the International Congress of Dermatology in Geneva
in September 1947. Symptoms of this disease may have been described by Hippocrates
in the 5th century BC, in his 3rd Epidemion-book. Its first modern formal description was published in 1922.
Some sources use the term "Adamantiades’ syndrome" or "Adamandiades-Behçet syndrome", for the work done by Benediktos Adamantiades. However, the current World Health Organization
/ICD-10
standard is "Behçet's disease". In 1991, Saudi Arabia
n medical researchers described "neuro-Behçet's disease", a neurological
involvement in Behçet's disease, considered one of the most devastating manifestations of the disease as investigated by an Egyptian researcher Sahar Saleem. The mechanism can be immune-mediated, or thrombotic. The term dates back to at least 1990.
Systemic
Systemic refers to something that is spread throughout, system-wide, affecting a group or system such as a body, economy, market or society as a whole. Systemic may also refer to:-In medicine:...
vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
that often presents with mucous membrane ulceration and ocular involvements. Behçet disease (BD) was named in 1937 after the Turkish dermatologist Hulusi Behçet, who first described the triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
. As a systemic disease, it can also involve visceral organs such as the gastrointestinal tract, pulmonary, musculoskeletal, and neurological systems. This syndrome can be fatal, due to ruptured vascular aneurysms, or severe neurological complications.
Integumentary system (Skin and mucosa)
Nearly all patients present with some form of painful oral mucocutaneous ulcerations in the form of aphthous ulcerAphthous ulcer
An aphthous ulcer , also known as a canker sore, is a type of mouth ulcer which presents as a painful open sore inside the mouth or upper throat characterized by a break in the mucous membrane. Its cause is unknown, but they are not contagious...
s or non-scarring oral lesions. The oral lesions are similar to those found in inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
and can be relapsing. Painful genital ulcerations usually develop around the anus, vulva or scrotum and cause scarring in 75% of the patients. Additionally, patients may present with erythema nodosum
Erythema nodosum
Erythema nodosum is an inflammation of the fat cells under the skin characterized by tender red nodules or lumps that are usually seen on both shins...
, cutaneous pustular vasculitis, and lesions similar to pyoderma gangrenosum
Pyoderma gangrenosum
Pyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds...
.
Eyes
Inflammatory eye disease can develop early in the disease course and lead to permanent vision loss in 20% of cases. Ocular involvement can be in the form of posterior uveitis, anterior uveitis, or retinal vasculitisRetinal vasculitis
Retinal vasculitis is inflammation of the vascular branches of the retinal artery, caused either by primary ocular disease processes, or as a specific presentation of any systemic form of vasculitis such as Behçet's disease, sarcoidosis, multiple sclerosis, or any form of systemic nectrozing...
. Anterior uveitis presents with painful eyes, conjuctival redness, hypopyon
Hypopyon
Hypopyon is pus in the eye.It is a leukocytic exudate, seen in the anterior chamber, usually accompanied by redness of the conjunctiva and the underlying episclera. It is a sign of inflammation of the anterior uvea and iris, i.e. iritis, which is a form of anterior uveitis...
, and decreased visual acuity, while posterior uveitis presents with painless decreased visual acuity and visual field floaters. A rare form of ocular (eye) involvement in this syndrome is retinal vasculitis which presents with painless decrease of vision with the possibility of floaters or visual field defects.
Optic Nerve
Optic nerve involvement in Behçet's disease is rare, typically presenting as progressive optic atrophy and visual loss. However, cases of acute optic neuropathy (specifically anterior ischemic optic neuropathyAnterior ischemic optic neuropathy
Anterior ischemic optic neuropathy is a medical condition involving loss of vision due to damage to the optic nerve from insufficient blood supply. AION is generally divided into two types: arteritic AION and non-arteritic AION...
) have also been reported to occur. Optic nerve atrophy has been identified as the most common cause of visual impairment. Behçet's disease may result in primary or secondary optic nerve involvement. Papilledema as a result of dural sinus thrombosis and atrophy resulting from retinal disease, have been characterized as secondary causes of optic nerve atrophy in Behçet's disease.
Optic neuropathy
The optic nerve contains axons of nerve cells that emerge from the retina, leave the eye at the optic disc, and go to the visual cortex where input from the eye is processed into vision. There are 1.2 million optic nerve fibers that derive from the retinal ganglion cells of the inner retina. Optic...
include painless loss of vision which may affect either one or both eyes, reduced visual acuity, reduced color vision, relative afferent pupillary defect, central scotoma
Scotoma
A scotoma is an area of partial alteration in one's field of vision consisting of a partially diminished or entirely degenerated visual acuity which is surrounded by a field of normal - or relatively well-preserved - vision.Every normal mammalian eye has a scotoma in its field of vision, usually...
, swollen optic disc, macular edema
Macular edema
Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye and causes it to thicken and swell. The swelling may distort a person's central vision, as the macula is near the center of the retina at the back of the eyeball...
, or retrobulbar pain. When these symptoms occur with concurrent mucocutaneous ulcerations, they raise suspicion of acute optic neuropathy in Behçet's Disease. Progressive optic atrophy may result in decreased visual acuity or color vision. Intracranial hypertension with papilledema
Papilledema
Papilledema is optic disc swelling that is caused by increased intracranial pressure. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare....
may be present.
Gastrointestinal tract (bowels)
GI manifestations include abdominal pain, nausea, and diarrhea with or without blood, and they often involve the ileocecal valve.Pulmonary (lungs)
Lung involvement is typically in the form of hemoptysisHemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...
, pleuritis, cough, or fever, and in severe cases can be life threatening if the outlet pulmonary artery develops an aneurysm which ruptures causing severe vascular collapse and death from bleeding in the lungs.
Musculoskeletal system (muscle, joint)
ArthralgiaArthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
is seen in up to half of patients, and is usually a non-erosive poly or oligoarthritis primarily of the large joints of the lower extremities.
Neurological system
Neurological involvements range from aseptic meningitisAseptic meningitis
Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings...
to vascular thrombosis such as dural sinus thrombosis and organic brain syndrome
Organic Brain Syndrome
Organic brain syndrome , also known as organic brain disease or organic brain disorder, is an older and nearly obsolete general term from psychiatry, referring to many physical disorders that cause impaired mental function. It usually does not include psychiatric disorders...
manifesting with confusion, seizures, and memory loss. They often appear late in the progression of the disease but are associated with a poor prognosis.
Diagnosis
There is no specific pathological testing or technique available for the diagnosis of the disease, although the International Study Group criteria for the disease are highly sensitive and specific, involving clinical criteria and a pathergy test. Behçet's disease has a high degree of resemblance to diseases that cause mucocutaneous lesions such as Herpes simplexHerpes simplex
Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 and type 2 . Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever...
labialis, and therefore clinical suspicion should be maintained until all the common causes of oral lesions are ruled out from the differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...
.
Visual acuity, or color vision loss with concurrent mucocutaneous lesions and/or systemic Behçet's symptoms should raise suspicion of optic nerve involvement in Behçet's disease and prompt a work-up for Behçet's disease if not previously diagnosed in addition to an ocular work-up. Diagnosis of Behçet's disease is based on clinical findings including oral and genital ulcers, skin lesions such as erythema nodosum, acne, or folliculitis, ocular inflammatory findings and a pathergy reaction. Inflammatory markers such ESR, and CRP may be elevated. A complete ophthalmic examination may include a slit lamp examination, optical coherence tomography
Optical coherence tomography
Optical coherence tomography is an optical signal acquisition and processing method. It captures micrometer-resolution, three-dimensional images from within optical scattering media . Optical coherence tomography is an interferometric technique, typically employing near-infrared light...
to detect nerve loss, visual field examinations, fundoscopic examination to assess optic disc atrophy and retinal disease, fundoscopic angiography, and visual evoked potentials, which may demonstrate increased latency. Optic nerve enhancement may be identified on Magnetic Resonance Imaging (MRI) in some patients with acute optic neuropathy. However, a normal study does not rule out optic neuropathy. Cerebrospinal fluid (CSF) analysis may demonstrate elevated protein level with or without pleocytosis. Imaging including angiography may be indicated to identify dural venous sinus thrombosis as a cause of intracranial hypertension and optic atrophy.
International Study Group diagnostic guidelines
According to the International Study Group guidelines, for a patient to be diagnosed with Behçet's disease, the patient must have oral (aphthous) ulcers (any shape, size or number at least 3 times in any 12 months period) along with 2 out of the following 4 "hallmarkHallmark
A hallmark is an official mark or series of marks struck on items made of precious metals — platinum, gold, silver and in some nations, palladium...
" symptoms:
- genital ulcers (including analAnusThe anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
ulcers and spots in the genital region and swollen testicleTesticleThe testicle is the male gonad in animals. Like the ovaries to which they are homologous, testes are components of both the reproductive system and the endocrine system...
s or epididymitisEpididymitisEpididymitis is a medical condition in which there is inflammation of the epididymis . This condition comprises gradual onset of testicular pain that can vary from mild to severe, and the scrotum may become red, warm and swollen...
in men) - skinSkin-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
lesionLesionA lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
s (papulo-pustules, folliculitisFolliculitisFolliculitis is the inflammation of one or more hair follicles. The condition may occur anywhere on the skin with the exception of the palms of the hands and soles of the feet.- Causes :...
, erythema nodosumErythema nodosumErythema nodosum is an inflammation of the fat cells under the skin characterized by tender red nodules or lumps that are usually seen on both shins...
, acneAcneAcne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...
in post-adolescents not on corticosteroids) - eyeHuman eyeThe human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
inflammation (iritisIritisIritis is a form of anterior uveitis and refers to the inflammation of the iris of the eye.-Types:There are two main types of iritis: acute and chronic. They differ in numerous ways....
, uveitisUveitisUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, retinal vasculitis, cells in the vitreous) - pathergy reaction (papule >2 mm dia. 24-48 hrs or more after needle-prick). The pathery test has a specificity of 95% to 100%, but the results are often negative in American and European patients
Despite the inclusive criteria set forth by the International Study Group, there are cases where not all the criteria can be met and therefore a diagnosis cannot readily be made. There is however a set of clinical findings that a physician can rely upon in making a tentative diagnosis of the disease; essentially Behçet's disease does not always follow the International Study Group guidelines and so a high degree of suspicion for a patient who presents having any number of the following findings is necessary:
- mouthMouthThe mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....
ulcersSoreSore may refer to:* A mild pain or ache* A small skin ulcer, usually open from skin infection* A slang term for angry* Sore , an Indonesian rock band* Sore, Landes, a village in the Landes département of France* Sore , by Buzzov*en... - arthritisArthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
/arthralgiaArthralgiaArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication.... - nervous systemNervous systemThe nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
symptoms - stomachStomachThe stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
and/or bowel inflammation - deep veinVeinIn the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
thrombosisThrombosisThrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss... - superficial thrombophlebitisThrombophlebitisThrombophlebitis is phlebitis related to a thrombus . When it occurs repeatedly in different locations, it is known as "Thrombophlebitis migrans" or "migrating thrombophlebitis".-Signs and symptoms:...
- epididymitisEpididymitisEpididymitis is a medical condition in which there is inflammation of the epididymis . This condition comprises gradual onset of testicular pain that can vary from mild to severe, and the scrotum may become red, warm and swollen...
- cardio-vascular problems of an inflammatory origin
- inflammatory problems in chestChestThe chest is a part of the anatomy of humans and various other animals. It is sometimes referred to as the thorax or the bosom.-Chest anatomy - Humans and other hominids:...
and lungs - problems with hearing and/or balance
- extreme exhaustion
- changes of personality, psychoses
- any other members of the family with a diagnosis of Behçet disease.
Pathogenesis
The etiologyEtiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
is not well-defined, but it is primarily characterized by auto-inflammation of the blood vessels. Although sometimes erroneously referred to as a "diagnosis of exclusion," the diagnosis can sometimes be reached by pathologic examination of the affected areas.
The primary mechanism of the damage is an overactive immune system that seems to target the patient's own body. The primary cause is not well known. In fact, as of now, no one knows why the immune system starts to behave this way in Behçet's disease. There does however seem to be a genetic component involved, as first degree relatives of the affected patients are often affected in more than expected proportion for the general population.
Treatment
Current treatment is aimed at easing the symptoms, reducing inflammation, and controlling the immune system. High dose Corticosteroid therapy (1 mg/kg/d oral prednisone) is indicated for severe disease manifestations. Anti-TNFTNF inhibitor
Tumor necrosis factor promotes the inflammatory response, which in turn causes many of the clinical problems associated with autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, hidradenitis suppurativa and refractory asthma. These disorders are...
therapy such as infliximab
Infliximab
Infliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...
has shown promise in treating the uveitis associated with the disease. Another Anti-TNF agent, Etanercept
Etanercept
Etanercept is a drug that treats autoimmune diseases by interfering with the tumor necrosis factor by acting as a TNF inhibitor. Pfizer describes in a SEC filing that the drug is used to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis...
, may be useful in patients with mainly skin and mucosal symptoms.
Interferon alfa-2a may also be an effective alternative treatment, particularly for the genital and oral ulcers as well as ocular lesions. Azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
, when used in combination with interferon alfa-2b also shows promise, and Colchicine
Colchicine
Colchicine is a medication used for gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum...
can be useful for treating some genital ulcers, erythema nodosum
Erythema nodosum
Erythema nodosum is an inflammation of the fat cells under the skin characterized by tender red nodules or lumps that are usually seen on both shins...
, and arthritis.
Thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
has also been used due to its immune-modifying effect. Dapsone
Dapsone
Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...
and rebamipide
Rebamipide
Rebamipide, an amino acid derivative of 2-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis...
have been shown, in small studies, to have beneficial results for mucocutaneous lesions.
Given its rarity, the optimal treatment for acute optic neuropathy in Behçet's disease has not been established. Early identification and treatment is essential. Response to ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
, periocular triamcinolone, and IV methylprednisone followed by oral prednisone has been reported although relapses leading to irreversible visual loss may occur even with treatment. Immunosuppressant
Immunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
s such as interferon alpha and tumour necrosis factor antagonists may improve though not completely reverse symptoms of ocular Behçet's, which may progress over time despite treatment. When symptoms are limited to the anterior chamber of the eye prognosis is improved. Posterior involvement, particularly optic nerve involvement is a poor prognostic indicator. Secondary optic nerve atrophy is frequently irreversible. Lumbar puncture or surgical treatment may be required to prevent optic atrophy in cases of intracranial hypertension refractory to treatment with immunomodulators and steroids.
Pathophysiology
Silk Road
The Silk Road or Silk Route refers to a historical network of interlinking trade routes across the Afro-Eurasian landmass that connected East, South, and Western Asia with the Mediterranean and European world, as well as parts of North and East Africa...
in the Middle East
Middle East
The Middle East is a region that encompasses Western Asia and Northern Africa. It is often used as a synonym for Near East, in opposition to Far East...
and in Central Asia
Central Asia
Central Asia is a core region of the Asian continent from the Caspian Sea in the west, China in the east, Afghanistan in the south, and Russia in the north...
. Thus, it is sometimes known as Silk Road Disease. However, this disease is not restricted to people from these regions. A large number of serological studies show a linkage between the disease and HLA-B51
HLA-B51
HLA-B51 is an HLA-B serotype. The serotype identifies the more common HLA-B*51 gene products.B51 is a split antigen of the broad antigen B5, and is a sister serotype of B52. There are a large number of alleles within the B*51 allele group...
. HLA-B51 is more frequently found from the Middle East to South Eastern Siberia, but the incidence of B51 in some studies was 3 fold higher than the normal population. However, B51 tends not to be found in disease when a certain SUMO4
SUMO4
Small ubiquitin-related modifier 4 is a protein that in humans is encoded by the SUMO4 gene.-Further reading:...
gene variant is involved, and symptoms appear to be milder when HLA-B27
HLA-B27
Human Leukocyte Antigen B27 is a class I surface antigen encoded by the B locus in the major histocompatibility complex on chromosome 6 and presents antigenic peptides to T cells...
is present. At the current time, a similar infectious origin has not yet been confirmed that leads to Behçet's disease, but certain strains of Streptococcus sanguinis
Streptococcus sanguinis
Streptococcus sanguinis, formerly known as Streptococcus sanguis, is a Gram-positive facultative aerobic coccus species of bacteria and a member of the Viridans Streptococcus group. S...
has been found to have a homologous antigenicity.
Vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
resulting in occlusion of the vessels supplying the optic nerve may be the cause of acute optic neuropathy and progressive optic atrophy in Behçet's disease. Histological evaluation in a reported case of acute optic neuropathy demonstrated substitution of the axonal portion of the optic nerve with fibrous astrocytes without retinal changes. CNS involvement in Behçet's may lead to intracranial hypertension most commonly due to dural venous sinus thrombosis [8-10] and subsequent secondary optic atrophy.
Epidemiology
The syndrome is rare in the United States, but is common in the Middle East and Asia, suggesting a possible cause endemic to the tropical areas. It is not associated with cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, and links with tissue-types (which are under investigation) are not certain. It also does not follow the usual pattern for autoimmune diseases. However, one study has revealed a possible connection to food allergies, particularly to dairy products. An estimated 15,000 to 20,000 Americans have been diagnosed with this disease. In the UK, it is estimated to have about 1 case for every 100,000 people. Globally, males are affected more frequently than females. In the United States, more females are affected than males.
In an epidemiologic study by Krause et al., 56% of patient’s with Behçet's disease developed ocular involvement at a mean age of 30. Ocular involvement was the first manifestation of Behçet's disease in 8.6% of patients.] Ocular Behçet's with involvement of the optic nerve is rarely reported. Among patients with ocular Behçet's disease funduscopic findings of optic atrophy, and optic disc paleness have been identified with a frequency of 17.9% and 7.4%, respectively. Other fundoscopic findings include vascular sheathing(23.7%), retinal hemorrhage(9%), macular edema(11.3%), branch retinal vein occlusion(5.8%), and retinal edema(6.6%). However, optic atrophy was the most significant cause of visual impairment identified in 54% of patients with ocular Behçet's disease and permanent visual impairment.
History
Behçet disease is namedEponym
An eponym is the name of a person or thing, whether real or fictitious, after which a particular place, tribe, era, discovery, or other item is named or thought to be named...
after Hulusi Behçet
Hulusi Behçet
Hulusi Behçet was a Turkish dermatologist and scientist. He described a disease of inflamed blood vessels in 1937, which is named after him as the Behçet's disease.- Professional works :...
(1889–1948), the Turkish
Turkish people
Turkish people, also known as the "Turks" , are an ethnic group primarily living in Turkey and in the former lands of the Ottoman Empire where Turkish minorities had been established in Bulgaria, Cyprus, Bosnia and Herzegovina, Georgia, Greece, Kosovo, Macedonia, and Romania...
dermatologist and scientist
Scientist
A scientist in a broad sense is one engaging in a systematic activity to acquire knowledge. In a more restricted sense, a scientist is an individual who uses the scientific method. The person may be an expert in one or more areas of science. This article focuses on the more restricted use of the word...
who first recognized the syndrome in one of his patients in 1924 and reported his research on the disease in Journal of Skin and Venereal Diseases in 1936. The name (Morbus Behçet) was formally adopted at the International Congress of Dermatology in Geneva
Geneva
Geneva In the national languages of Switzerland the city is known as Genf , Ginevra and Genevra is the second-most-populous city in Switzerland and is the most populous city of Romandie, the French-speaking part of Switzerland...
in September 1947. Symptoms of this disease may have been described by Hippocrates
Hippocrates
Hippocrates of Cos or Hippokrates of Kos was an ancient Greek physician of the Age of Pericles , and is considered one of the most outstanding figures in the history of medicine...
in the 5th century BC, in his 3rd Epidemion-book. Its first modern formal description was published in 1922.
Some sources use the term "Adamantiades’ syndrome" or "Adamandiades-Behçet syndrome", for the work done by Benediktos Adamantiades. However, the current World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
/ICD-10
ICD-10
The International Statistical Classification of Diseases and Related Health Problems, 10th Revision is a medical classification list for the coding of diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases, as maintained by the...
standard is "Behçet's disease". In 1991, Saudi Arabia
Saudi Arabia
The Kingdom of Saudi Arabia , commonly known in British English as Saudi Arabia and in Arabic as as-Sa‘ūdiyyah , is the largest state in Western Asia by land area, constituting the bulk of the Arabian Peninsula, and the second-largest in the Arab World...
n medical researchers described "neuro-Behçet's disease", a neurological
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
involvement in Behçet's disease, considered one of the most devastating manifestations of the disease as investigated by an Egyptian researcher Sahar Saleem. The mechanism can be immune-mediated, or thrombotic. The term dates back to at least 1990.