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INTRODUCTION — Beh?et’s syndrome is characterized by recurrent oral aphthae and any of several systemic manifestations including genital aphthae, ocular disease, skin lesions, gastrointestinal involvement, neurologic disease, vascular disease, or arthritis. Beh?et’s may have been described by Hippocrates, but it was brought to the attention of the modern medical community by Hulusi Beh?et in 1937 [1-3]. Most clinical manifestations of Beh?et’s syndrome are believed to be due to vasculitis. Among the systemic vasculitides, Beh?et’s syndrome is remarkable for its ability to involve blood vessels of all sizes (small, medium, and large) on both the arterial and venous sides of the circulation. The clinical manifestations, diagnosis, and differential diagnosis of Beh?et’s syndrome are reviewed here. The pathogenesis and treatment of this disorder are discussed separately. (See 'Pathogenesis of Beh?et’s syndrome' and 'Treatment of Beh?et’s syndrome'.) EPIDEMIOLOGY — Beh?et’s syndrome is more common (and often more severe) along the ancient silk road, which extends from eastern Asia to the Mediterranean [4,5]. It is most common in Turkey (80 to 370 cases per 100,000) while the prevalence ranges from 13.5 to 35 per 100,000 in Japan, Korea, China, Iran, Iraq, and Saudi Arabia [4]. By comparison, the prevalence ranges from 1 per 15,000 to 1 per 500,000 in North American (Olmsted County, Minnesota) and Northern European countries [6]. The prevalence is similar in men and women in the areas where it is more common, but women are affected more commonly in reports from the United States and northern Europe. It typically affects young adults 20 to 40 years of age but is infrequently also seen in children [7-9]. The disease appears to be more severe in young, male, and Middle- or Far-Eastern patients [10-16]. Most cases of Beh?et’s are sporadic, although families with multiple affected members, which is known as familial clustering, have been reported, and having a first-degree relative with Beh?et’s does increase risk for the disease [17,18]. Earlier onset of disease in successive generations, known as genetic anticipation, has been described [19]. CLINICAL MANIFESTATIONS — The common clinical feature in patients with Beh?et’s syndrome is the presence of recurrent and usually painful mucocutaneous ulcers. Other clinical manifestations of this disorder are more variable among different patients and populations. The severity is generally greater in men. The greatest morbidity and mortality occur with ocular disease (affecting up to two-thirds of patients), vascular disease (affecting up to one-third of patients), and central nervous system disease (affecting 10 to 20 percent of patients). Cutaneous and articular manifestations are common. Renal disease and peripheral nervous system involvement are rare compared with other vasculitides [20]. Although there are limited data on children with Beh?et's syndrome, clinical manifestations appear to generally be similar to those in adults [7-9]. Among some populations, there may be differences in the frequencies or types of certain manifestations, including neurologic disease [9,21]. Oral ulcerations — Most, but not all, patients initially manifest recurrent oral aphthous ulcerations (also known as canker sores), which are grossly and histologically similar to common oral ulcers and recurrent aphthous stomatitis (RAS), but which tend to be more extensive and often multiple (picture 1). The ulcers are painful and, in severe cases, may limit eating. They are rounded and range in size from a few millimeters to 2 cm. They have well-defined borders, have a white-yellow necrotic base, and may have surrounding erythema. Minor ulcers are defined as those less than 1 cm in diameter, and major ulcers are defined as those at least 1 cm in diameter. Major ulcers may scar. Outer portions of the lips are not involved. Healing of oral ulcers is typically spontaneous within one to three weeks; with recurrent lesions, however, some patients will have ulcers present continuously. Oral ulcers are typically the first to come and last to leave in the course of the disease; they may become less common after about 20 years [22]. They may be a less frequent manifestation in cigarette smokers [23]. (See 'Oral lesions', section on 'Beh?et's syndrome'.) Urogenital lesions — Genital ulceration, the most specific lesion for Beh?et’s syndrome, occurs in 75 percent or more of patients with Beh?et’s syndrome. The ulcers are similar in appearance to the oral aphthae and are usually painful [24]. Genital ulcers are most commonly found on the scrotum in men and the vulva in women (picture 2). Recurrence is typically less frequent than with oral ulcerations. Scar formation is frequent for genital lesions. Scrotal scarring secondary to ulcers is rarely, if ever, seen in conditions other than Beh?et’s syndrome. Epididymitis, salpingitis, varicocele, and other genitourinary inflammatory conditions may also occur in patients with this disorder [25,26]. Urethritis is an unusual feature. Cutaneous lesions — Cutaneous lesions also occur in over 75 percent of patients with Beh?et’s syndrome. The skin manifestations vary and may include acneiform lesions, papulo-vesiculo-pustular eruptions, pseudofolliculitis, nodules, erythema nodosum (septal panniculitis), superficial thrombophlebitis, pyoderma gangrenosum-type lesions, erythema multiforme-like lesions, and palpable purpura. Biopsy of erythema nodosum lesions reveals a septal panniculitis, with medium vessel vasculitis in up to half of lesions [27]. Acneiform lesions may be more common in those with associated arthritis [28,29]. These lesions consist of papules and pustules that are indistinguishable from ordinary acne and share characteristic microbiologic flora with papulopustular lesions of acne [30]. Pustular skin lesions are often not sterile and may contain Staphylococcus aureus and Prevotella spp [30]. Pathergy refers to an erythematous papular or pustular response to local skin injury. It is defined as a pustule-like lesion or papule that appears 48 hours after skin prick by a 20-gauge needle. Pathergy is less common in North American and North European patients with Beh?et’s disease (10 to 20 percent) than in patients from more endemic areas (50 to 75 percent). Dermographism is a response to light scratching of the skin that may be present in some patients [31]. A vascular pathergy-like response may be evident after vascular procedures, resulting in phlebitis or aneurysms [32,33]. (See 'Vascular disease' below.) Nailfold capillary abnormalities, mainly enlarged capillaries, may also be observed in patients with Beh?et’s syndrome [34,35]. Ocular disease — Ocular disease occurs in 25 to 75 percent of patients with Beh?et’s syndrome, depending upon the population studied, and in most cases progresses to blindness if not treated. Ocular disease typically is less severe in North American populations, resulting in a lower incidence of vision loss [36]. Male patients are more likely to get eye disease, with about 75 to 80 percent developing involvement, and also have worse visual outcomes, even with treatment. ●Uveitis is often the dominant feature of Beh?et’s disease. It is typically bilateral and episodic, often involves the entire uveal tract (pan uveitis), and may not resolve completely between episodes. (See 'Uveitis: Etiology, clinical manifestations, and diagnosis'.) ●Hypopyon is a severe anterior uveitis with purulent material in the anterior chamber that is characteristically seen in about 20 percent of patients with Beh?et’s disease. Many patients with hypopyon will demonstrate retinal vasculitis [37]. ●Posterior uveitis, retinal vasculitis (picture 3A-B), vascular occlusion, and optic neuritis require systemic immunosuppressive treatment and may irreversibly impair vision and progress to blindness if untreated. Other changes that can be seen include neovascularization, secondary cataracts, glaucoma, frosted branch angiitis, and, in approximately 3 percent of patients, conjunctival ulceration [38,39]. Neovascularization most commonly occurs due to inflammation, and treatment with immunosuppression, particularly with interferon, may be beneficial [40]. Conjunctivitis, scleritis, episcleritis, and sicca syndrome are uncommon. Ocular signs may be helpful in making the diagnosis of Beh?et’s syndrome, even in the absence of other clinical symptoms [41]. In a retrospective review of 880 Turkish patients with Beh?et’s uveitis, 68 percent were male, and the mean age of onset was 28.5 years for men and 30 for women. Ocular disease was bilateral in 78.1 percent, and panuveitis was the most common finding. Risk of losing useful vision at 10 years was 30 percent for men and 17 percent for women, but prognosis was better in the 1990s than in the 1980s [42]. A retrospective review of childhood-onset uveitis in 36 Beh?et’s patients reported diagnostic and treatment findings similar to those seen in adults [8]. Neurologic disease — Neurologic disease occurs in less than 10 percent of patients with Beh?et’s syndrome in most series [43-46]. It is observed more frequently in men than women. Neurologic disease is classified as parenchymal or non-parenchymal: ●Parenchymal disease is subdivided into brainstem disease, multifocal (diffuse) disease (including brainstem, cerebral, or spinal cord disease), myelopathy, cerebral disease (including encephalopathy, hemiparesis, hemisensory loss, seizures, dysphagia, and mental changes such as psychosis and cognitive dysfunction), and optic neuropathy. ●Non-parenchymal disease includes cerebral venous thrombosis, intracranial hypertension syndrome (pseudotumor cerebri), acute meningeal syndrome, and uncommonly stroke due to arterial thrombosis, dissection, or aneurysm [51]. Vascular disease — Most clinical manifestations of Beh?et’s syndrome are believed to be due to vasculitis, and Beh?et’s is remarkable for its ability to involve blood vessels of all sizes (small, medium, and large) on both the arterial and venous sides of the circulation (table 1). Vascular involvement is one of the major causes of morbidity and mortality in Beh?et’s syndrome. In particular, pulmonary artery aneurysm carries a high mortality of approximately 25 percent, and early recognition is important [55]. Prevalence — Vascular disease in Beh?et’s syndrome is more common in men. A study of 2319 Turkish patients with Beh?et’s found a prevalence of vascular disease of 14.3 percent and was most common in males. In this study, 53.3 percent suffered superficial venous thrombosis, 29.8 percent deep venous thrombosis, and 3.6 percent arterial disease [56]. Another study of 796 Chinese patients with Beh?et's found vascular involvement in 12.8 percent of patients. The male-to-female ratio was approximately 4:1 and the mean age of onset was 29.5 years. Vascular disease was the presenting manifestation of Beh?et’s in 25.5 percent of cases; 54.9 percent had arterial disease, 70.6 percent had venous disease, and 25.5 percent had both. Women were more likely to have arterial disease. Patients with vascular manifestations of Beh?et's were more likely to have cardiac involvement [57]. Arterial disease — Arterial disease is most commonly a small vessel vasculitis, but medium and large vessel disease may also develop. Large vessel vascular involvement occurs in approximately one-third of patients with Beh?et’s syndrome [58]. In these patients, perivascular and endovascular inflammation may lead to hemorrhage, stenosis, aneurysm formation, thrombus formation in both arteries and veins, and varices. Progression and recurrence are more likely in these patients, and immunosuppressive treatment of this inflammation has been found to be beneficial, though patients may also require vascular surgery intervention [59]. (See 'Treatment of Beh?et’s syndrome', section on 'Large artery disease'.) Carotid, pulmonary, aortic, iliac, femoral, and popliteal arteries are most commonly involved; cerebral and renal arteries are uncommonly involved [37]. Acute myocardial infarction can occur due to coronary artery vasculitis but is uncommon. Atherosclerosis does not appear to occur at an accelerated rate in Beh?et’s syndrome, as has been observed in autoimmune diseases such as systemic lupus erythematosus [13]. Pulmonary artery aneurysms involving the large proximal branches of the pulmonary arteries are the most common pulmonary vascular lesion in Beh?et’s and are uncommonly seen in diseases other than Beh?et’s. Hemoptysis is the most common presenting symptom; cough, dyspnea, fever, and pleuritic pain are other presenting symptoms [60,61]. A misdiagnosis of pulmonary embolism and subsequent anticoagulation can lead to a poor outcome if the underlying inflammatory large vessel vasculitis is not appreciated [60]. Although pulmonary artery aneurysms may be suspected on chest radiograph and echocardiography, a computed tomography (CT) angiogram, MR angiogram, or plain angiogram are the usual imaging modalities in which pulmonary artery aneurysms are identified. Pulmonary infarction does not commonly occur. Hemoptysis may be the result of pulmonary artery-bronchus fistulae and frequently coexists with venous obstruction elsewhere [62]. Pulmonary artery thrombosis and aneurysms in association with peripheral thrombophlebitis are known as Hughes-Stovin syndrome, and this syndrome most commonly occurs in Beh?et’s syndrome and may represent a part of the spectrum of manifestations seen in Beh?et’s [63,64]. Pulmonary artery thrombosis may occur with pulmonary artery aneurysms or may occur independently; a study of 47 patients with pulmonary artery disease and Beh?et’s identified 26 patients with pulmonary artery aneurysms, 13 with pulmonary artery thrombosis, and 8 with both. Presenting manifestations were similar. Most patients had active Beh?et’s at presentation, 85 percent had pulmonary nodules, 13 percent had cavitation, and 77 percent had peripheral venous thrombosis [61]. Venous disease — Venous disease resulting in venous thrombosis is more common than arterial involvement, and is often an early feature of Beh?et’s. Superior and inferior vena cava occlusion, Budd-Chiari syndrome, dural sinus thrombosis, and other venous obstructive lesions can occur in addition to the more common superficial and deep vein thrombosis. Recurrent thrombosis of the lower extremities may lead to a post-thrombophlebitic syndrome [37]. In one study of 493 cases of Beh?et’s syndrome, 53 were found to have one or more large vessel thrombosis [65]. Fourteen of these 53 patients had hepatic vein thrombosis, 8 also had inferior vena cava thrombosis, and 2 had both inferior vena cava and portal vein thrombosis. A case-control study of 73 Beh?et’s patients found a 14-fold increased risk of venous thrombosis compared with controls [66]. Venous thrombosis, thrombophlebitis, folliculitis, and retinal vasculitis were more common in men than in women. Venous disease may also be more common in patients with a positive pathergy test or ocular involvement. Pulmonary disease — In addition to pulmonary vascular lesions, already discussed (see 'Vascular disease' above), radiographic abnormalities including loss of lung volume, well-defined opacities, and indistinct nodular or reticular shadows have been noted, but only rarely has histopathologic correlation been available. Among the various pathologic findings are pulmonary infarction, hemorrhage, and both organizing and eosinophilic pneumonias [67]. Miscellaneous other pulmonary findings found in Beh?et’s patients include pleural effusion, pulmonary arteritis or venulitis, bronchial stenosis, abscess, obstructive airway disease, chronic bronchitis, and fibrosis [60]. Arthritis — A nonerosive, asymmetric, usually nondeforming arthritis occurs in about one-half of patients with Beh?et’s syndrome, particularly during exacerbations. The arthritis most commonly affects the medium and large joints, including the knee, ankle, and wrist. Inflammation is evident on synovial fluid and biopsy specimens [68]. In many patients, the arthritis is intermittent, lasting one to three weeks, though manifestations may be persistent. As an example, in a study of Greek patients, the arthritis was oligoarticular in about two-thirds, monoarticular in about one-third, and polyarticular in less than 5 percent [20]. Despite its nonerosive and nondeforming character, one study using the multidimensional Health Assessment Questionnaire showed that arthritis was associated with overall functional impairment and pain similar to that seen in patients with rheumatoid arthritis [69]. Renal disease — Renal involvement in Beh?et’s syndrome is less frequent and often less severe than in other types of vasculitis. Patients with renal disease may have proteinuria, hematuria, or mild renal insufficiency but can progress to renal failure. The spectrum of renal diseases associated was illustrated in a review of 159 patients with Beh?et’s: AA (secondary) amyloidosis was present in 69, glomerulonephritis in 51, vascular disease (mostly renal arterial aneurysms) in 35, and interstitial nephritis in 4 [70]. Among the patients with glomerulonephritis, there was a spectrum of lesions ranging from immunoglobulin A (IgA) nephropathy to crescentic glomerulonephritis. Patients with AA amyloidosis typically present with nephrotic syndrome or at least significant proteinuria. In a series of 14 cases, the mean time from Beh?et’s onset to amyloid nephropathy was eight years (range 3 to 15 years) [71]. Cardiac disease — Symptomatic cardiac disease is uncommon in Beh?et’s syndrome. Abnormalities that can occur include pericarditis, myocarditis, coronary arteritis with or without myocardial infarction, coronary artery aneurysms, atrial septal aneurysm, conduction system disturbances, ventricular arrhythmias, endocarditis, endomyocardial fibrosis, mitral valve prolapse, intracardiac thrombosis, and valvular insufficiency [72-76]. Atherosclerosis does not appear to occur at an accelerated rate as has been observed in autoimmune diseases such as systemic lupus erythematosus [13]. Gastrointestinal involvement — Symptoms of intestinal Beh?et’s syndrome include abdominal pain, diarrhea, and bleeding. Gastrointestinal involvement can be difficult to differentiate from inflammatory bowel disease, as other clinical signs and symptoms may also overlap, leading to difficult diagnostic issues. Gastrointestinal ulcerations occur in some patients with Beh?et’s syndrome, and intestinal perforation can occur. Discrete ulcerations can be found throughout the gastrointestinal tract but are most often seen in the terminal ileum, cecum, and ascending colon [77]. Oral ulcers that frequently occur in patients with inflammatory bowel disease are indistinguishable from the oral aphthae of Beh?et’s syndrome; thus, inflammatory bowel disease must be considered before making the diagnosis of Beh?et’s. (See 'Gastrointestinal manifestations of vasculitis' and 'Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults' and 'Clinical manifestations, diagnosis and prognosis of Crohn disease in adults'.) The clinical course of intestinal Beh?et’s is variable. In a study of 130 patients with intestinal Beh?et's, 75 percent had mild clinical activity or remission at five years, while 16 percent had multiple relapses or chronic symptoms. The group with multiple relapses or chronic symptoms was younger and had a higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity index, and a lower albumin at presentation [78]. Other — Patients with Beh?et’s syndrome may suffer from constitutional symptoms including fever and malaise [79]. Problems with urinary and erectile function may be due to neural or vascular disease [80]. Inner ear involvement may cause tinnitus, deafness or hearing loss, or dizziness [81,82]. Amyloidosis may occur [71]. A possible association with myelodysplasia has been discussed [83,84]. A factitious 'pseudo-Beh?et’s' syndrome has also been described, with predominant mucocutaneous involvement. Fibromyalgia co-occurs in many patients with Beh?et’s. A study of 70 Beh?et’s patients found that 37.1 percent of patients met the American College of Rheumatology (ACR) criteria for fibromyalgia. Fibromyalgia was associated with anxiety and depression but not with Beh?et’s disease activity [85]. Another study of 104 Beh?et's patients found fibromyalgia in 18 patients. Fibromyalgia was not associated with disease activity but was associated with increased fatigue, headache, pain, arthralgia, and the patient’s impression of disease activity [86]. CLINICAL MANIFESTATIONS IN PREGNANCY — Studies suggest that in many patients with Beh?et’s, disease activity is somewhat reduced during pregnancy; however, the risk of complications may be higher in Beh?et’s patients than in matched controls without Beh?et’s [87-90]. In a retrospective analysis of 76 pregnancies in 46 patients with Beh?et’s syndrome, 36 percent of pregnancies were associated with flares, and the annual incidence of flares per patient was approximately threefold lower during pregnancy than before or after pregnancy [89]. The overall rate of pregnancy complications was 16 percent. Complications included miscarriages, caesarean section, medical termination of pregnancy, HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count), and immune thrombocytopenia. Complications were more common in patients with history of deep venous thrombosis, and flares were less common in patients on colchicine. A case control study of 31 patients during 135 pregnancies demonstrated higher rates of miscarriage, pregnancy complications, and caesarean sections in Beh?et’s patients compared with controls [87]. DIAGNOSIS When to consider the diagnosis — Because oral aphthous ulcers are so common in the general population and Beh?et’s syndrome is so rare, Beh?et’s is best diagnosed in the context of recurrent aphthous ulcerations along with characteristic systemic manifestations. Systemic manifestations which should raise suspicion for Beh?et’s include ocular disease, especially hypopyon, panuveitis, or retinal vasculitis; neurologic disease including characteristic central nervous system parenchymal findings; vascular disease, particularly pulmonary artery aneurysms, Budd-Chiari syndrome, and cerebral venous thrombosis; and patients with pathergy manifestations. Oral ulcerations also tend to be more frequent and severe in patients with Beh?et’s syndrome. Genital ulcerations are more specific and less sensitive for the detection of Beh?et’s. Beh?et’s syndrome should also be considered more strongly in patients with the aforementioned symptoms who live along the Silk Road from eastern Asia to the Mediterranean Sea [91,92]. Our diagnostic criteria — There are no pathognomonic laboratory tests in Beh?et’s syndrome; as a result, the diagnosis is made on the basis of the clinical findings. In the absence of other systemic diseases, we diagnose Beh?et’s syndrome in patients with recurrent oral aphthae (at least three times in one year) plus two of the following clinical features: ●Recurrent genital aphthae (aphthous ulceration or scarring). ●Eye lesions (including anterior or posterior uveitis, cells in vitreous on slit lamp examination, or retinal vasculitis observed by an ophthalmologist). ●Skin lesions (including erythema nodosum, pseudo-vasculitis, papulopustular lesions, or acneiform nodules consistent with Beh?et’s). ●A positive pathergy test. Pathergy is defined by a papule 2 mm or more in size developing 24 to 48 hours after oblique insertion of a 20-gauge needle 5 mm into the skin, generally performed on the forearm. This approach is consistent with the International Study Group (ISG) criteria published in 1990 (table 2) [24]. These remain the most widely used and well-accepted criteria among experts in Beh?et’s syndrome. (See 'Classification criteria' below.) Pathergy is less common in Northern European and North American patients. Thus, it has been suggested that other features might be substituted for pathergy in these populations, including aseptic meningoencephalitis, cerebral vasculitis, recurrent phlebitis, arteritis, synovitis, or focal bowel ulceration [93]. There are patients who do not meet these criteria in whom the diagnosis of Beh?et’s syndrome is still made, and establishing the diagnosis in such patients is much more difficult. Thus, it is often appropriate to refer a patient in whom the diagnosis of Beh?et’s is suspected to a rheumatologist with experience in this disease. Classification criteria — Several diagnostic and classification criteria have been developed for Beh?et’s syndrome. Like other sets of criteria, these were developed to categorize patients for study purposes and were not developed to diagnose disease in individuals [24,94,95]. It has been suggested that their accuracy is better in populations with low prevalence than in those with high [95]. As mentioned above, we prefer the International Study Group (ISG) criteria published in 1990 (table 2) [24]. These criteria appear to be relatively sensitive and specific [93,96]. As an example, in one report of 32 clinically diagnosed patients with Beh?et’s syndrome and 56 controls with other rheumatic diseases, the sensitivity and specificity were 95 and 100 percent, respectively [93]. Crohn's disease, ulcerative colitis, and familial Mediterranean fever share some clinical manifestations with Beh?et’s syndrome. Including patients with these disorders among controls did not lead to substantially different sensitivity of specificity of the criteria [97]. The International Criteria for Beh?et’s disease (ICBD) were developed in 2006 in an effort to improve sensitivity compared with the ISG criteria, but they are not widely accepted [98]. Each of several findings is assigned a point value; the criteria require a total of at least three points for diagnosis of Beh?et’s: ●Genital aphthosis – Two points ●Ocular lesions (anterior uveitis, posterior uveitis, or retinal vasculitis) – Two points ●Oral aphthosis – One point ●Skin lesions (pseudofolliculitis or erythema nodosum) – One point ●Vascular lesions (superficial phlebitis, deep vein thrombosis, large vein thrombosis, arterial thrombosis, or aneurysm) – One point ●Pathergy – One point Validation studies have estimated a sensitivity of 87 to 96.5 percent, a specificity of 88.9 to 97.3 percent, and an accuracy of 74.2 to 85.5 percent for these criteria [99]. DIFFERENTIAL DIAGNOSIS — The differential diagnosis varies with each patient's clinical features [100,101]. While it is beyond the scope of this review to provide a comprehensive list of all the possible alternative diagnoses for Beh?et's syndrome, we present several here. Oral aphthae — Oral aphthae are present in almost all patients with Beh?et’s syndrome, but can also be observed in a variety of other conditions. The differential diagnosis of recurrent oral ulcers include rheumatologic diseases such as systemic lupus erythematosus (SLE) and reactive arthritis; gastrointestinal diseases such as inflammatory bowel diseases and celiac disease; autoinflammatory conditions such as periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome and hyperimmunoglobulin D syndrome; infections such as herpes simplex virus (HSV) and human immunodeficiency virus (HIV); dermatologic diseases such as Stevens-Johnson syndrome, pemphigoid, pemphigus, lichen planus, and linear immunoglobulin A (IgA) bullous dermatosis; hematologic conditions such as cyclic neutropenia; as well as a variety of other conditions such as recurrent aphthous stomatitis (RAS) and nutritional deficiencies (table 3). Medications such as methotrexate and other chemotherapeutic agents can cause oral ulcers. Dental prosthetics and oral hygiene products can cause oral irritation and ulceration. (See 'Oral lesions'.) Genital ulcerations — Other causes of genital ulceration and an approach to the differential diagnosis and evaluation of genital ulcers are discussed in detail elsewhere. (See 'Approach to the patient with genital ulcers'.) Gastrointestinal symptoms — Many patients with Beh?et's syndrome experience abdominal pain and symptoms that may be similar to inflammatory bowel disease. In addition, gastrointestinal involvement from inflammatory bowel disease can be difficult to differentiate from Beh?et's syndrome. As an example, patients with Crohn’s disease may have gastrointestinal ulcerations that are indistinguishable from Crohn’s disease unless granulomas are identified in biopsy samples. (See 'Clinical manifestations, diagnosis and prognosis of Crohn disease in adults' and 'Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults'.) Ocular inflammation — Uveitis, a feature of Beh?et's syndrome, can also occur with Crohn’s disease, ulcerative colitis, spondyloarthritis, and other conditions. However, conjunctivitis, scleritis, episcleritis, and sicca syndrome are uncommon and should increase the suspicion for an alternative diagnosis. (See 'Uveitis: Etiology, clinical manifestations, and diagnosis'.) Arthritis — The asymmetric, non-erosive arthritis that can be observed in patients with Beh?et's syndrome can also be seen with other systemic rheumatic diseases including systemic lupus erythematosus (SLE), reactive arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, psoriatic arthritis, and some vasculitides. An asymmetric, non-erosive arthritis can also be a manifestation of sarcoid and inflammatory bowel disease. (See 'Evaluation of the adult with polyarticular pain'.) INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.) ●Basics topic (see 'Patient information: Beh?et’s syndrome (The Basics)') ●Beyond the Basics topic (see 'Patient information: Vasculitis (Beyond the Basics)') Patient information can also be obtained from The American Beh?et’s Disease Association: The American Beh?et’s Disease Association PO Box 19952 Amarillo, Texas 79114 Telephone: 1-800-7BEHCET SUMMARY AND RECOMMENDATIONS ●Beh?et’s syndrome is a rare disease characterized by recurrent oral aphthae and any of several systemic manifestations including genital aphthae, ocular disease, skin lesions, gastrointestinal disease, neurologic disease, vascular disease, and arthritis. Most clinical manifestations of Beh?et’s syndrome are believed to be due to vasculitis. ●Beh?et’s syndrome is more common (and often more severe) along the ancient silk road, which extends from eastern Asia to the Mediterranean; it is most common in Turkey, while the prevalence is much lower in North America and northern Europe. It typically affects young adults 20 to 40 years of age. (See 'Epidemiology' above.) ●The common clinical feature in patients with Beh?et’s syndrome is the presence of recurrent and usually painful mucocutaneous ulcers. Other clinical manifestations of this disorder are more variable among different patients and populations. (See 'Clinical manifestations' above and 'Oral ulcerations' above and 'Urogenital lesions' above.) ●The greatest morbidity and mortality occur with ocular disease (affecting up to two-thirds of patients), including uveitis and other changes; with vascular disease, including pulmonary artery aneurysms; and with central nervous system disease, including focal parenchymal lesions, complications of vascular thrombosis, and other abnormalities. Vasculitis in patients with Beh?et’s syndrome is remarkable for its ability to involve blood vessels of all sizes and to involve both arteries and veins (table 1). (See 'Vascular disease' above and 'Ocular disease' above and 'Neurologic disease' above.) ●Cutaneous manifestations are common, which included acne, folliculitis, and erythema nodosum lesions. Pathergy may be seen as an erythematous papular or pustular response to local skin injury. Arthritis may be present which is characteristically intermittent, inflammatory but nonerosive, asymmetric, and, usually, nondeforming; it often occurs during disease exacerbations and most commonly affects the medium and large joints. A variety of gastrointestinal symptoms may also occur. (See 'Cutaneous lesions' above and 'Arthritis' above and 'Gastrointestinal involvement' above.) ●Less common manifestations include renal disease and peripheral nervous system involvement. Cardiac and pulmonary disease may also be present. (See 'Renal disease' above and 'Neurologic disease' above and 'Cardiac disease' above and 'Pulmonary disease' above.) ●There are no pathognomonic laboratory tests in Beh?et’s syndrome; as a result, the diagnosis is made on the basis of the clinical findings. In the absence of other systemic diseases, we diagnose Beh?et’s syndrome in patients with recurrent oral aphthae (at least three times in one year) plus two of the following clinical features: ·Recurrent genital aphthae ·Eye lesions (including anterior or posterior uveitis, cells in vitreous on slit lamp examination, or retinal vasculitis observed by an ophthalmologist) ·Skin lesions (including erythema nodosum, pseudo-vasculitis, papulopustular lesions, or acneiform nodules consistent with Beh?et’s) ·A positive pathergy test. This approach is consistent with the International Study Group (ISG) criteria published in 1990 (table 2). (See 'Diagnosis' above.) |
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