Behçet's disease (BD) is a type of
inflammatory disorder which affects multiple parts of the body.
The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the eye, and
arthritis
Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...
.
[ The sores can last from a few days, up to a week or more.][ Less commonly there may be inflammation of the brain or spinal cord, ]blood clots
A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulati ...
, aneurysm
An aneurysm is an outward :wikt:bulge, bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also b ...
s, or blindness
Visual or vision impairment (VI or VIP) is the partial or total inability of visual perception. In the absence of treatment such as corrective eyewear, assistive devices, and medical treatment, visual impairment may cause the individual difficul ...
.[ Often, the symptoms come and go.][
The cause is unknown.] It is believed to be partly genetic.[ Behçet's is not contagious.][ Diagnosis is based on at least three episodes of mouth sores in a year, together with at least two of the following: genital sores, eye inflammation, skin sores, a positive ]skin prick test
Skin allergy testing comprises a range of methods for medical diagnosis of allergies that attempts to provoke a small, controlled, allergic response.
Methods
A microscopic amount of an allergen is introduced to a patient's skin by various mean ...
.[
There is no cure.][ Treatments may include immunosuppressive medication such as ]corticosteroids
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...
and anti-TNFs as well as lifestyle changes.[ ]Lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia and ventricular fibrillation. When used for local anae ...
mouthwash may help with the pain.[ ]Colchicine
Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonstero ...
may decrease the frequency of attacks.[
While rare in the United States and Europe, it is more common in the ]Middle East
The Middle East (term originally coined in English language) is a geopolitical region encompassing the Arabian Peninsula, the Levant, Turkey, Egypt, Iran, and Iraq.
The term came into widespread usage by the United Kingdom and western Eur ...
and Asia.[ In ]Turkey
Turkey, officially the Republic of Türkiye, is a country mainly located in Anatolia in West Asia, with a relatively small part called East Thrace in Southeast Europe. It borders the Black Sea to the north; Georgia (country), Georgia, Armen ...
, for example, about 2 per 1,000 are affected.[ Onset is usually in a person's twenties or forties.][ The disease was initially described by Turkish dermatologist Hulusi Behçet in 1937.
]
Signs and symptoms
Skin and mucosa
Nearly all people with Behçet's disease present with some form of painful ulcerations inside the mouth. They are a form of aphthous ulcer
Aphthous stomatitis, or recurrent aphthous stomatitis (RAS), commonly referred to as a canker sore or salt blister, is a common condition characterized by the repeated formation of benignity, benign and non-contagious disease, contagious mouth ...
s or non-scarring oral lesions. The oral lesions are similar to those found in inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...
and can be relapsing. Painful genital ulcerations usually develop around the anus, vulva, or scrotum and cause scarring in 75 percent of the patients. Additionally, patients may present with erythema nodosum, cutaneous pustular vasculitis, and lesions similar to pyoderma gangrenosum
Pyoderma gangrenosum is a rare, Inflammation, inflammatory skin disease where painful pustules or skin condition, nodules become ulcer (dermatology), ulcers that progressively grow. Pyoderma gangrenosum is not infectious.
Treatments may include ...
.
Eyes
Inflammatory eye disease can develop early in the disease course and lead to permanent vision loss in 20 percent of cases. Ocular involvement can be in the form of posterior uveitis, anterior uveitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and i ...
, or retinal vasculitis. 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.
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 neuropathy) 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
Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain.
Damage and death of these nerve cells, or neurons, leads to characteristic featu ...
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
A scotoma is an area of partial alteration in the field of vision consisting of a partially diminished or entirely degenerated visual acuity that is surrounded by a field of normal – or relatively well-preserved – vision.
Every normal mamm ...
, 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
Papilledema or papilloedema is optic disc swelling that is caused by increased intracranial pressure due to any cause. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare.
In ...
may be present.
Episcleritis may occur, which causes eye redness and mild pain, without a significant impact on vision.
Bowels
Gastrointestinal (GI) manifestations include abdominal pain, nausea, and diarrhea with or without blood, and they often involve the terminal ileum and ileocecal valve In many Animalia, including humans, an ileocolic structure or problem is something that concerns the region of the gastrointestinal tract from the ileum to the large intestine, colon. In Animalia that have cecum, ceca, the ileocecal region is a sub ...
. Some patients with BD experience abdominal tenderness, bloating, and general abdominal discomfort. When mild this can resemble irritable bowel syndrome; more severe cases bear similarities to inflammatory bowel diseases such as ulcerative colitis or Crohn's. Behçet's disease causes ulcers in the terminal ileum and ileocecal valve In many Animalia, including humans, an ileocolic structure or problem is something that concerns the region of the gastrointestinal tract from the ileum to the large intestine, colon. In Animalia that have cecum, ceca, the ileocecal region is a sub ...
. The ulcers may be aphthous or have a classic punched out appearance with undermining. Linear and fissuring ulcers up to 5 cm may be present. Biopsies show vasculitis (phlebitis or venulitis) with a neutrophilic inflammatory infiltrate. Involvement of the oesophagus, stomach and large intestine is rare.
Lungs
Lung involvement is typically in the form of hemoptysis
Hemoptysis or haemoptysis is the discharge of blood or blood-stained sputum, mucus through the mouth coming from the bronchi, larynx, vertebrate trachea, trachea, or lungs. It does not necessarily involve coughing. In other words, it is the airw ...
, 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. Pulmonary artery thrombosis may occur.
Joints
Arthritis is seen in up to half of people, and is usually a non-erosive poly or oligoarthritis primarily of the large joints of the lower extremities.
Kidneys
Behçet's disease can rarely result in renal involvement. This can manifest in the following:
* Glomerulonephritis
* Renal amyloidosis
Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weigh ...
* IgA nephropathy
* Vascular disease
* Drug side effects, such as NSAIDs (non-steroidal anti-inflammatories), cyclophosphamide, cyclosporine and tacrolimus.
Small vessel vascular disease results in renal vasculitis, whereas large vessel involvement causes aneurysm
An aneurysm is an outward :wikt:bulge, bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also b ...
s (bulging) and thrombosis
Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...
(blockages). Serious kidney problems are more common in men typically with a history of large vessel involvement in other parts of the body. Bladder and urethral involvement is rare in Behçet's disease.
Brain
Central nervous system (CNS) involvement most often occurs as a chronic meningoencephalitis. Lesions tend to occur in the brainstem, the basal ganglia and deep hemispheric white matter and may resemble those of multiple sclerosis
Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...
(MS). Brainstem atrophy is seen in chronic cases.
Neurological involvements range from aseptic meningitis to vascular thrombosis such as dural sinus thrombosis and organic brain syndrome manifesting with confusion, seizures, and memory loss. Sudden hearing loss (sensorineural) is often associated with it. They often appear late in the progression of the disease but are associated with a poor prognosis.
Heart
Chronic aortic regurgitation due to aortic root disease may also be seen. Although infrequent, myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
(heart attack) with angiographically identified acute coronary artery thrombosis has been reported, including one case with a pathologically demonstrable lesion due to arteritis found at autopsy.
Blood vessels
Blood vessel problems are observed in 7–29% of people with arterial lesions representing 15% of vascular lesions. Arterial lesions pose a greater risk. Most common arterial lesions are occlusions or stenosis and aneurysms or pseudoaneurysms.
Cause
The cause 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 autoimmune, which by definition is an overactive immune system that targets the patient's own body. The involvement of a subset of T cells ( Th17) seems to be important.[Hatemi G, Seyahi E, Fresko I, Hamuryudan V (2012). "Behçet's syndrome: a critical digest of the recent literature". ''Clin Exp Rheumatol''] The primary cause is not well known. In fact, no one knows yet 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 the expected proportion for the general population.
Research suggests that previous infections may provoke the autoimmune responses present in Behçet's disease. Heat shock protein
Heat shock proteins (HSPs) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including ex ...
s (HSPs) are present in some bacteria and serve as a "danger signal" to the immune system. However, some HSPs share a similarity in bacteria and humans. The anti- HSP60 and anti-HSP65 antibodies that target HSPs produced by ''Streptococci'' (including '' S. sanguinis'' and '' S. pyogenes'') and ''Mycobacterium tuberculosis
''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis.
First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...
'' can also target human HSPs, leading to immune responses linked to uveitis and various symptoms shown in parenchymal neuro-Behçet's disease.
An association with the GIMAP ("GTPase
GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...
of the immunity-associated protein") family of genes on the long arm of chromosome 7 (7q36.1) has been reported. Gene locations of single-nucleotide polymorphism
In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a ...
s associated with Behçet's disease included '' GIMAP1'', '' GIMAP2'' and '' GIMAP4''.
Pathophysiology
Behçet's disease is considered more prevalent in the areas surrounding the old silk trading routes in the Middle East
The Middle East (term originally coined in English language) is a geopolitical region encompassing the Arabian Peninsula, the Levant, Turkey, Egypt, Iran, and Iraq.
The term came into widespread usage by the United Kingdom and western Eur ...
and in Central Asia
Central Asia is a region of Asia consisting of Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. The countries as a group are also colloquially referred to as the "-stans" as all have names ending with the Persian language, Pers ...
. 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
Small ubiquitin-related modifier 4 is a protein that in humans is encoded by the ''SUMO4'' gene.
Function
This gene is a member of the SUMO gene family. This family of genes encode small ubiquitin-related modifiers that are attached to protein ...
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 ''S. sanguinis'' has been found to have a homologous antigenicity.
Vasculitis
Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both artery, arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily c ...
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 disease may lead to intracranial hypertension most commonly due to dural venous sinus thrombosis and subsequent secondary optic atrophy.
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 simplex
Herpes simplex, often known simply as herpes, is a viral disease, viral infection caused by the herpes simplex virus. Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are Cold sore, ora ...
'' labialis, and therefore clinical suspicion should be maintained until all the common causes of oral lesions are ruled out from the differential diagnosis
In healthcare, a differential diagnosis (DDx) is a method of analysis that distinguishes a particular disease or condition from others that present with similar clinical features. Differential diagnostic procedures are used by clinicians to di ...
.
Visual acuity, or color vision loss with concurrent mucocutaneous lesions or systemic Behçet's disease 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 (OCT) is a high-resolution imaging technique with most of its applications in medicine and biology. OCT uses coherent near-infrared light to obtain micrometer-level depth resolved images of biological tissue or oth ...
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.
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 three times in any twelve-month period) along with two of the following four hallmark symptoms:
* eye
An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system.
In higher organisms, the ey ...
inflammation (iritis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and i ...
, uveitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
, retinal vasculitis, cells in the vitreous)
* genital ulcers (including anal ulcers and spots in the genital region and swollen testicle
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is Homology (biology), homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of Androgen, androgens, p ...
s or epididymitis
Epididymitis is a medical condition characterized by inflammation of the epididymis, a curved structure at the back of the testicle. Onset of pain is typically over a day or two. The pain may improve with raising the testicle. Other symptoms may ...
in men)
* pathergy reaction (papule >2 mm dia. 24–48 hrs or more after needle-prick). The pathergy test has a specificity of 95 percent to 100 percent, but the results are often negative in American and European patients
* skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different ...
lesion
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals.
Types
There is no de ...
s (papulo-pustules, folliculitis
Folliculitis is the infection and inflammation of one or more hair follicles. The condition may occur anywhere on hair-covered skin. The rash may appear as pimples that come to white tips on the face, chest, back, arms, legs, buttocks, or head.
A ...
, erythema nodosum, acne
Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...
in post-adolescents not on corticosteroids)
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:
* arthritis
Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...
/arthralgia
Arthralgia () literally means ' joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication
Medication (also called medicament, medicine, pharmaceuti ...
* cardio-vascular problems of an inflammatory origin
* changes of personality
Personality is any person's collection of interrelated behavioral, cognitive, and emotional patterns that comprise a person’s unique adjustment to life. These interrelated patterns are relatively stable, but can change over long time per ...
, psychoses
* deep vein
Veins () are blood vessels in the circulatory system of humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are those of the pulmonary and feta ...
thrombosis
Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...
* epididymitis
Epididymitis is a medical condition characterized by inflammation of the epididymis, a curved structure at the back of the testicle. Onset of pain is typically over a day or two. The pain may improve with raising the testicle. Other symptoms may ...
* extreme exhaustion – chronic fatigue
* inflammatory problems in chest
The thorax (: thoraces or thoraxes) or chest is a part of the anatomy of mammals and other tetrapod animals located between the neck and the abdomen.
In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main di ...
and lungs
The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...
* mouth
A mouth also referred to as the oral is the body orifice through which many animals ingest food and animal communication#Auditory, vocalize. The body cavity immediately behind the mouth opening, known as the oral cavity (or in Latin), is also t ...
ulcers
An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing ...
* nervous system
In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...
symptoms
* problems with hearing or balance
* stomach
The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...
or bowel
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...
inflammation
* superficial thrombophlebitis
Thrombophlebitis is a phlebitis (inflammation of a vein) related to a thrombus (blood clot). When it occurs repeatedly in different locations, it is known as thrombophlebitis migrans (migratory thrombophlebitis).
Signs and symptoms
The following ...
* any other members of the family with a diagnosis of Behçet's disease.
Treatment
Current treatment is aimed at easing the symptoms, reducing inflammation, and controlling the immune system. The quality of the evidence for treating the oral ulcers associated with Behçet's disease, however, is poor.
High-dose corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
therapy is often used for severe disease manifestations. Anti-TNF therapy such as infliximab
Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing ...
has shown promise in treating the uveitis associated with the disease. Infliximab
Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing ...
as well as other anti-TNF therapies including etanercept and adalimumab
Adalimumab, sold under the brand name Humira and others, is a disease-modifying antirheumatic drug and monoclonal antibody used to treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn' ...
may be useful in treating mucocutaneous disease according to several case reports and prospective studies, as well as one randomized trial for etanercept. Apremilast may also be used to treat oral ulcers associated with Behçet's disease.
Interferon alpha-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 alpha-2b also shows promise, and colchicine
Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonstero ...
can be useful for treating some genital ulcers, erythema nodosum, and arthritis. Benzathine-penicillin may also reduce new arthritic attacks.
Thalidomide
Thalidomide, sold under the brand names Contergan and Thalomid among others, is an oral administered medication used to treat a number of cancers (e.g., multiple myeloma), graft-versus-host disease, and many skin disorders (e.g., complication ...
has also been used due to its immune-modifying effect. Dapsone
Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment an ...
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 are essential. Response to ciclosporin
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken Oral administration, orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephr ...
, periocular triamcinolone, and IV methylprednisolone followed by oral prednisone has been reported although relapses leading to irreversible visual loss may occur even with treatment. Immunosuppressant
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.
Classification
Immunosuppressive drugs can be classified ...
s such as interferon-alpha and tumour necrosis factor antagonists may improve though not completely reverse symptoms of ocular Behçet's disease, 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.
Intravenous immunoglobulin therapy (IVIg) could be a treatment for severe or complicated cases.
A recent 2024 reports that infliximab improved the likelihood of achieving a complete response at 22 weeks for patients with severe Behçet’s syndrome compared to cyclophosphamide, according to head-to-head trial data. Mild to moderate adverse events, primarily infections, were reported in 29.6% of patients on infliximab and 64% on cyclophosphamide. Serious adverse events occurred in 15% and 12% of patients, respectively.
Surgery
Surgical treatment of arterial manifestations of BD bears many pitfalls since the obliterative endarteritis of vasa vasorum causes thickening of the medial layer and splitting of elastin fibers. Therefore, anastomotic pseudoaneurysms are likely to form, as well as pseudoaneurysms at the site of the puncture in case of angiography or endovascular treatment; furthermore, early graft occlusion may occur.
For these reasons, invasive treatment should not be performed in the acute and active phases of the disease when inflammation is at its peak. The evaluation of disease's activity is usually based on relapsing symptoms, ESR (erythrocyte sedimentation rate), and serum levels of CRP (C-reactive protein).
Endovascular treatment can be an effective and safe alternative to open surgery, with less postoperative complications, faster recovery time, and reduced need for intensive care, while offering patency rates and procedural success rates comparable with those of surgery. This notwithstanding, long-term results of endovascular treatment in BD are still to be determined.
Epidemiology
The syndrome is rare in the United States, Africa and South America, but is common in Asia, suggesting a possible cause endemic to those areas. A theory suggested that past exposure to lethal infectious agents might have fixed the genetic susceptibility factors to Behçet's disease in those area. 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 an epidemiologic study, 56 percent of patients 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 percent of patients. Ocular Behçet's disease 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 percent and 7.4 percent, 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 percent of patients with ocular Behçet's disease and permanent visual impairment.
Pregnancy
With Behçet's disease as a pre-existing disease in pregnancy or acquired, the pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
does not have an adverse effect on the course of Behçet's disease and may possibly ameliorate its course. Still, there is a substantial variability in clinical course between patients and even for different pregnancies in the same patient. Also, the other way around, Behçet's disease confers an increased risk of pregnancy complications, miscarriage
Miscarriage, also known in medical terms as a spontaneous abortion, is an end to pregnancy resulting in the loss and expulsion of an embryo or fetus from the womb before it can fetal viability, survive independently. Miscarriage before 6 weeks ...
and Cesarean section.
Behçet's can cause male infertility
Male infertility refers to a sexually mature male's inability to impregnate a fertile female. Male infertility can wholly or partially account for 40% of infertility among couples who are trying to have children. "A problem with the male is the s ...
, either as a result of the condition itself or of a side effect of concomitant medication such as colchicine
Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonstero ...
, which is known to lower sperm count.
History
The first modern formal description of the symptoms was made by H.Planner and F.Remenovsky and published in 1922 in the '' Archiv für Dermatologie und Syphilis''. Behçet's disease is named after Hulusi Behçet (1889–1948), the Turkish dermatologist
Dermatology is the branch of medicine dealing with the skin.''Random House Webster's Unabridged Dictionary.'' Random House, Inc. 2001. Page 537. . It is a speciality with both medical and surgical aspects. A dermatologist is a specialist medi ...
and scientist who first recognized the three main symptoms of 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 ( , ; ) ; ; . is the List of cities in Switzerland, second-most populous city in Switzerland and the most populous in French-speaking Romandy. Situated in the southwest of the country, where the Rhône exits Lake Geneva, it is the ca ...
in September 1947. Symptoms of this disease may have been described by Hippocrates
Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...
in the 5th century BC, in his ''Epidemion'' (book 3, case 7).
Some sources use the term "Adamantiades's syndrome" or "Adamantiades–Behçet syndrome", for the work done by Benediktos Adamantiades. However, the current World Health Organization
The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
/ICD-10
ICD-10 is the 10th revision of the International Classification of Diseases (ICD), a medical classification list by the World Health Organization (WHO). It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social cir ...
standard is "Behçet's disease". In 1991, Saudi Arabia
Saudi Arabia, officially the Kingdom of Saudi Arabia (KSA), is a country in West Asia. Located in the centre of the Middle East, it covers the bulk of the Arabian Peninsula and has a land area of about , making it the List of Asian countries ...
n medical researchers described neuro-Behçet's disease, a neurological
Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
involvement in Behçet's disease, considered one of the most devastating manifestations of the disease. The mechanism can be immune-mediated or thrombotic. The term dates back to at least 1990.
References
Further reading
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External links
Questions and answers about Behçet's disease
nbsp;– US National Institute of Arthritis and Musculoskeletal and Skin Diseases
{{DEFAULTSORT:Behcet's disease
Autoimmune diseases
Autoinflammatory syndromes
Conditions of the mucous membranes
Inflammations
Rare diseases
Steroid-responsive inflammatory conditions
Syndromes
Systemic connective tissue disorders
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Diseases named after discoverers