Rheumatic manifestations of Behçet's disease

Rheumatologic manifestations are common in Beh?et's disease. Joint involvement takes the third place after mucocutaneous and ocular lesions and can be the inaugural manifestation. Monoarthritis and oligoarthritis affect essentially knees and ankles, with a marked male bias. They usually run an acute or recurrent course, with chronic forms being rare. Polyarthritis is not rare and involves the large limb joints and the small joints of the hands and feet. Arthritis in Beh?et's disease heels usually without sequelea and the aggressive treatment is not necessary. Unusual forms include arthritis with deformities and/or destruction, pseudogout, rupture of popliteal cyst (imitating deep vein thrombosis) and myositis. The association with spondylarthropathy is not common. Beh?et's disease is rarely associated with rheumatoid arthritis, Sj?gren's syndrome, systemic lupus erythematosus, relapsing polychondritis and amyloidosis. Children are more likely than adults to have joint manifestations and polyarthritis. CONCLUSION: Joint manifestations are common in Beh?et's disease. Their unusual forms deserve to be known since they can raise diagnostic problems when they are inaugural.     

Sebum production is increased in Beh?et's syndrome and even more so in rheumatoid arthritis

Sebum production is under hormonal control. We had shown that male sex is associated with more severe disease in Beh?et's syndrome and the acneiform skin lesion of this disorder is not different from ordinary acne, an androgen-dependent lesion. Sebum excretion rate was higher in patients with Beh?et's syndrome than in healthy controls, children and patients with ankylosing spondylitis. On the other hand, patients with rheumatoid arthritis had high levels of sebum excretion rate comparable to those found in patients with acne vulgaris. These suggest the presence of a sebotrophic hormone and/or other hormonal effects in Beh?et's syndrome and rheumatoid arthritis.     

Vascular manifestations of Behçet's syndrome associated with solitary ulcerations and resolved with immunosuppressants

INTRODUCTION: Beh?et's disease is a systemic inflammatory disorder characterized by vasculitis. Its typical features are recurrent oral and genital ulcerations with uveitis. Although vascular lesions are not listed among the criteria for diagnosis of Beh?et's disease, up to 25-35% of the patients develop complications in arterial and venous large vessels. EXEGESIS: We describe the case of a 45-year-old French man with Beh?et-type vasculopathy. Though only one sign of Beh?et's disease, i.e., oral ulcerations, was present, the patient had to undergo emergency surgery three times. The postoperative treatment combined corticosteroids, azathioprine, and oral anticoagulants. Three years later no therapy failure was observed. CONCLUSION: On the basis of 1) recurrent aortic aneurysms, 2) large arterial and venous occlusive lesions, 3) superficial phlebitis, and 4) ulcerations of the aorta in macro- and microscopic examination of resected aortic walls, we concluded that the patient's life threatening vasculopathy was of the Beh?et's type, even if several of the diagnostic features of Beh?et's disease were lacking. Variations in clinical features of Beh?et's disease are observed that might be due to hereditary traits, particularly to the genetic expression of an incomplete phenotype that would lead to the lack of typical clinical features.     

Behçet's disease

PURPOSE OF REVIEW: To summarize recent scientific developments in the epidemiology, genetics, pathogenesis and treatment of Beh?et's disease. RECENT FINDINGS: Important genetic and immunologic studies were performed. Tumor necrosis factor-alpha-1031C allele was associated with disease susceptibility. Polymorphisms in interleukin-10, IL-8 and CD28 genes were also associated with Beh?et's disease. Association with endothelial nitric oxide synthase gene polymorphism was confirmed but was ethnic related. Significant T helper type 1 immune reaction was reconfirmed in recent studies, especially during active phases, but T helper type 2 reaction may also play a role. Interleukin-12B heterozygosity is associated with Beh?et's disease susceptibility and plays an important role in mediating T helper type 1 antistreptococcal immune response. Selenium binding protein may be a target antigen in Beh?et's uveitis. Pathergy reaction is most frequently positive in the forearm; multiple needle pricks increase positive rate. Experience with anti-tumour necrosis factor therapy for various manifestations is increasing. Cyclosporin A treatment may be associated with new onset of neuro-Beh?et. There is a high prevalence of headaches with moderate or severe disability. Cardiac manifestations include left ventricular dysfunction and coronary flow abnormalities. Anti-Saccharomyces cerevisiae antibodies may be especially common in intestinal Beh?et's disease and are also increased in healthy relatives of patients. SUMMARY: Considerable progress has been made, particularly in understanding the immunologic and genetic basis of the disease. The importance of novel serological markers and autoantigens merits further investigations.     

Neuro-Behçet syndrome presenting as acute meningeal syndrome

Beh?et's disease is a systemic vasculitic disease characterized mainly by recurrent oral and genital aphthous ulcers, uveitis and skin findings. Central nervous system involvement is a serious manifestation. A case of acute meningeal syndrome secondary to Beh?et's disease is presented. Beh?et's disease should always be considered in differential diagnosis of acute meningeal syndrome without signs of viral infection, particularly in the context of multisystem manifestations.     

Beh?et syndrome in childhood

Beh?et's syndrome represents a multisystemic disease with vasculitic changes. It manifests mainly with oral and genital ulceration, ocular involvement mostly uveitis and typical skin lesions. Further symptoms can develop: arthritis, gastrointestinal signs, thrombophlebitis and neurologic disturbances. The disease can start already in childhood and follows a chronic recurrent course. Diagnosis is often delayed by a long interval between manifestation of each of the several symptoms. In this regard diagnostic criteria which consider clinical findings have proved helpful. Courses of Beh?et's syndrome in three juvenile patients whose disease started in childhood are demonstrated and discussed together with experience from the literature.     

Intestinal lymphoma associated with Behçet disease

The association of Beh?et's disease and non-Hodgkin's lymphoma is very rare. The first case of primary intestinal lymphoma with intestinal Beh?et's disease is reported. A 37 year-old woman had been treated for Beh?et's disease with colchicine for 2 years. In July 1997, she developed uveitis and was treated by monthly intravenous pulses of cyclophosphamide for 6 months, but uveitis persisted; so cyclophosphamide was replaced by cyclosporin 300 mg/day. One month later, she suffered from diarrhea. Colonoscopy showed ileocoecal ulcerations. Histological examination of surgical biopsy revealed B large cell type lympocytic malignant lymphoma and vasculitis lesions compatible with intestinal Beh?et's disease. Cyclosporin was stopped and treatment with prednisone was instituted. The relationship between non-Hodgkin's lymphoma and immunosuppressive drugs in Beh?et's disease is discussed.     

Neuromuscular complications of long-term treatment of inflammatory diseases. 3 cases

Chloroquine and colchicine, widely used in internal medicine practice for a variety of inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, familial Mediterranean fever, and Beh?et's disease, may induce neuromuscular complications. Physicians must be familiar with this diagnosis as this iatrogenic neuromuscular pathology may simulate polymyositis, leading thus to inappropriate treatment with prednisone whereas the only effective treatment is to discontinue the drug involved whenever possible. We report three cases of toxic myopathy and/or neuropathy related to chronic chloroquine or colchicine therapy for systemic diseases, and outline the main points to be considered in this situation.     

Neuro-Behçet's disease--rapidly reversible with early diagnosis and treatment

Beh?et's disease is an idiopathic multi-systemic, inflammatory disorder that may affect major organs, including the central nervous system. It is a clinical diagnosis, and a history of recurrent oral and genital ulcers should be elicited, especially in cases of unexplained uveitis with atypical neurological symptoms. We describe the rapid neurological recovery and neuroimaging changes following high-dose systemic corticosteroids in a 44-year-old man with recurrent oral ulcers, panuveitis, and acute neuro-Beh?et's, presenting with meningoencephalitis. Early diagnosis with the aid of appropriate neuroimaging and immunosuppressive therapy prevented long-term neurological complications. Appropriate neuroimaging can facilitate early diagnosis and treatment, and provide prognostic information on neuro-Beh?et's.     

Treatment of Beh?et's disease.

Beh?et's disease is a systemic inflammatory disorder capable of inducing thrombophlebitis. Clinicopathologically, it is characterized by neutrophil and platelet hyperfunction. Lesions are formed presumably because neutrophils infiltrating the affected tissue release active oxygen and lysosomal enzymes in large amounts. The mechanism of neutrophil hyperfunction was obscure, but in recent years attention has focused on the effects of cytokines released by mononuclear cells. As more has been learned about the etiopathogenesis of Beh?et's disease, novel anti-inflammatory drugs, immunosuppressants, anti-thrombotic agents, and anticoagulants have helped to achieve remarkable progress in treatment. Particularly notable is the effect on severe uveitis of cyclosporine, which is more effective than colchicine and conventional immunosuppressants. With the advent of cyclosporine, the number of patients with Beh?et's disease who lose their eyesight has clearly decreased.     

Behçet's syndrome: disease manifestations, management, and advances in treatment

The acne lesions characteristic of Beh?et's syndrome are not sterile and are commonly observed in combination with arthritis. The two main nodular skin lesions--superficial thrombophlebitis and erythema nodosum--are equally frequent, and rather difficult to distinguish. Superficial thrombophlebitis is usually observed in combination with thrombosis in large veins, and thrombosis of the large veins usually clusters with dural sinus thrombi, which make up approximately 20% of all central nervous system (CNS) lesions of Beh?et's syndrome. The remaining CNS lesions are parenchymal, mainly located in the brainstem, and associated with a graver prognosis than dural sinus thrombi. The presence of clinical clusters indicates that there are at least two pathogenetic pathways in Beh?et's syndrome: a reactive arthritis pathway and a thrombophilia pathway. Research into the pathogenesis of Beh?et's syndrome has shown that the most consistent genetic marker of Beh?et's syndrome is HLA-B51; however, the genetic association of this true-to-form 'complex' disorder with HLA-B51 is only 20%, and a whole-genome study showed associations with 16 different loci. The severity of Beh?et's syndrome and the mortality associated with it tend to decrease with time, and there is no associated increase in incidence of atherosclerosis. Although treatment of skin-mucosa manifestations, eye disease and pulmonary artery aneurysms has improved significantly in the past decades, the treatment of CNS lesions and thrombophilia are still problematic.     

Uveitis as a cause of visual loss in arthritides and comparable conditions

OBJECTIVE: To examine the role of inflammatory rheumatic diseases and comparable conditions in the etiology of severe uveitis leading to visual impairment and blindness. METHODS: A retrospective study based on the Finnish Register of Visual Impairment. At the end of 1996, the Finnish Register of Visual Impairment included 296 uveitis patients in whom uveitis was the main cause of visual impairment. The patient records were examined retrospectively to investigate the etiology of severe uveitis. Due to the incompleteness of data obtained of the patients blinded a long time ago, we included only 174 uveitis patients whose visual handicap (best corrected visual acuity in the better eye < 20/60 or severe visual field loss) was stated during 1980-1996. RESULTS: A total of 174 uveitis patients were found, 72 male and 102 female. A diagnosed or presumed inflammatory rheumatic disease or comparable condition was found in 38/174 (22%) patients: juvenile rheumatoid arthritis in 14 (8%), spondyloarthropathy (ankylosing spondylitis or reactive arthritis) in 10 (6%), sarcoidosis in 5 (3%), seronegative rheumatoid arthritis in 4 (2%); Beh?et's disease was diagnosed in 2 (1%), 1 patient had polymyositis, 1 polyarteritis nodosa, and 1 juvenile systemic lupus erythematosus. In addition to the above, 10 (6%) patients had chronic back pain and 5 (3%) patients various noninflammatory joint problems. Diverse other ophthalmologic or systemic disease was detected in 38 (22%) cases. Trauma or surgery caused uveitis in 9 (5%) patients. For 74/174 (43%) uveitis patients no specific associating condition could be shown. Legal blindness was documented in 65/174 (37%) patients, including 8 totally blind persons. CONCLUSION: This study provides first data on the relative importance of inflammatory rheumatic diseases and comparable conditions in the etiology of severe uveitis leading to visual handicap and blindness.     

Diffuse ulcerative lesions in the colon with intestinal Beh?et's disease

Ileocecal region is most commonly affected in intestinal Beh?et's disease. Localized deep ulcerations which have a punched-out or undermining appearance with well-defined margin placing in this region had been noted in many cases. 41 patients with intestinal Beh?et's disease were observed by colonofiberscope in Teikyo University Hospital from January 1982 to June 1988. In 10% (4 cases) of these patients, diffuse ulcerative lesions in the transverse colon and the distal colon were found. These diffuse lesions in the colon with Beh?et's disease were seemed to be much like those associated with inflammatory bowel disease as ulcerative colitis and Crohn's disease in morphological characteristics. The clinical symptoms of these four cases with Beh?et's disease including oral aphtha, genital ulcer, joint pain, skin eruptions, and eye involvement, preceded each colonic ulceration. The first two cases were affected with ulcerative lesion in the distal portion of the recto-sigmoid colon and the descending colon. And the last two were involved in the whole transversing colon by multiple deep ulcerations. Wide-spreading ulcerative lesion in the colon with Beh?et's disease is a rare condition in the Japanese, and only two papers has been reported previously. Because clinical manifestations between Beh?et's disease and inflammatory bowel disease are very similar in many points as oral aphthous ulcers, arthritis, eye involvement, skin eruptions, phlebitis, arterial occlusions, then, an overlapping field or a part of a spectrum of disease has been suggested by some authors. But, in the present circumstances, they are distinct disease entities, we think that these four cases are in an atypical condition with intestinal Beh?et's disease.     

Comparison of Synovial MMP-1 and TIMP-1 Levels in Patients with Various Inflammatory Arthritides: Is There Any Difference Between Rheumatoid Arthritis,Behçet’s Disease and Familial Mediterranean Fever?

The purpose of this study was to investigate synovial levels of matrix metalloproteinase-1 (MMP-1), known to break down collagen, and tissue inhibitor of metalloproteinase (TIMP-1), its natural antagonist, in patients with various inflammatory disorders. Eighty-five patients with different inflammatory arthritides (20 Beh?et's disease, 20 familial Mediterranean fever, 26 rheumatoid arthritis and 19 osteoarthritis) were enrolled in the study. Synovial MMP-1 and TIMP-1 levels were measured by two-step sandwich ELISA. There were significant differences between study and control groups regarding erythrocyte sedimentation rate, C-reactive protein, MMP-1 and TIMP-1 values. The synovial MMP-1 levels of patients with Beh?et's disease and familial Mediterranean fever were no different from those in patients with rheumatoid arthritis, but significantly higher than those of patients with osteoarthritis. The synovial TIMP-1 levels in patients with osteoarthritis were higher than those of patients with the other three diseases, among which the difference was not statistically significant, and the difference between osteoarthritis and the others was statistically significant. Because of the detection of similar levels of synovial MMP-1 in patients with familial Mediterranean fever, Beh?et's disease and rheumatoid arthritis, we conclude that the absence of erosions in patients with familial Mediterranean fever and Beh?et's disease may be explained by MMP-1 being a marker of cytokine-driven inflammation, or by the short-lived and transient nature of the arthritis observed in these patients.     

Beh?et's disease

Recent studies have revealed the important role of streptococci in the etiology of Beh?et's disease. Among patients with Beh?et's disease, there is a high incidence of a history of streptococcal infections. Certain antigens of streptococci induced not only cutaneous, delayed-type hypersensitivity, but also systemic attacks of Beh?et's disease when skin tests were performed. Neutrophil-activating lymphokines are produced when streptococcal antigen reacted with lymphocytes from patients with Beh?et's disease. The first international diagnostic criteria for Beh?et's disease were prepared by multicenter studies and published recently. With recent progress in diagnostic imaging techniques, magnetic resonance imaging and position emission tomography are particularly important for the diagnosis of neuro-Beh?et's disease. In Japan, cyclosporin was also proved to be effective for eye lesions of Beh?et's disease in a double-blind clinical trial comparing this drug with colchicine.     

Therapy of chronic non infectious uveitis

PURPOSE: Chronic non infectious uveitis represents two-thirds of the causes of chronic uveitis referred in tertiary referral ophthalmology centre. One case out of 5 may evolve towards blindness. Therapy should be discussed on the basis of the uveitis severity and the diagnosis; it uses topics or systemic drugs, mainly corticosteroids and immunosuppressors. CURRENT KNOWLEDGE AND KEY POINTS: Besides corticosteroids and ciclosporin, use of immunosuppressors and biotherapy in chronic non infectious uveitis is not an indication of the Autorisation de Mise sur le Marché. However, immunosuppressors and biotherapy were the subjects of several studies, although controlled studies are scarce. Controlled studies concerned cyclosporine, azathioprine and intravenous cyclophosphamide in Beh?et's disease, ciclosporine and tacrolimus in uveitis of various causes. Therapy of chronic non infectious uveitis was recently enriched by new drugs: mycophenolate mofetil, initially used in transplantation, has its indications extended to systemic diseases; TNF inhibitors initially used in therapy of systemic diseases; interferon efficacy revealed in Beh?et's disease is now used in uveitis due to other causes. FUTURE PROSPECTS AND PROJECTS: Controlled studies are suitable in order to determinate the respective part of immunosuppressors and biotherapies in the treatment of chronic non infectious uveitis.     

Palisaded neutrophilic granulomatous dermatitis presenting as an unusual skin manifestation in a patient with Behçet's disease

A 32-year-old Korean woman with painful oral ulcers and a sore throat presented with multiple erythematosus papules on both legs. Histological examination of the papular lesions on the legs demonstrated palisaded granuloma with degeneration of collagen fibres in the dermis, compatible with palisaded neutrophilic granulomatous dermatitis (PNGD). This condition is known to be an unusual disease entity associated with various systemic autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, other connective tissue diseases, and systemic vasculitis. To our knowledge a case with typical Beh?et's disease coinciding with PNGD among systemic autoimmune diseases has not been described before.     

Treatment of primary systemic vasculitis with TNF alpha-antagonists

After the introduction of the TNF alpha blocking drugs Etanercept and Infliximab for the standard therapy of rheumatoid arthritis these effective substances have also been used successfully in many patients with primary systemic vasculitides, who were unresponsive to standard therapy. From pathophysiologic findings their use is justified by the prominent role of TNF alpha in the inflammation of small and large vessels. So far only open studies with a maximum of 20 patients and case reports are published. In summary there are reports of the successful treatment of 7 patients with rheumatoid vasculitis, 39 patients with Wegener's granulomatosis, 3 patients each with microscopic Polyangiitis, and 5 patients each with temporal Arteritis or Takayasu disease with Etanercept as well as with Infliximab. In addition, Infliximab was also used with a good response in severe Polymyalgia rheumatica in 4 cases and in one case of a cryoglobulinemic vasculitis. More than 60 patients with Panuveitis and other manifestations of Beh?et's disease were treated with Infliximab or Etanercept according to preliminary reports. Because of the overall positive reports with TNF alpha collected in this review controlled investigations for their use in primary systemic vasculitis are necessary.     

Mesangial glomerulonephritis and intermediate uveitis

Uveitis in children are less frequent than in adults. Their prognosis is variable because it may be found as an isolated and idiophatic condition or in association with definite clinical entities. The associated noninfectious diseases with predominantly renal involvement are tubulointerstitial nephritis and uveitis syndrome (TINU syndrome), mesangial glomerulonephritis isolated or in association with Beh?et's disease. A case of 14-years-old girl with intermediate uveitis (pars planitis) and mesangial glomerulonephritis is presented. The ocular symptoms was eye redness and ocular pain and she has snow-banks in pars plana. She showed microscopic hematuria and intermitent proteinuria that increased during the ocular clinical exacerbation. Renal biopsy revealed both mild mesangial matrix increase and mesangial celullarity with normal tubulointerstitial structure and mesangial deposition of IgA and IgG immunoglobulins. This case is de first pediatric patient report in the literature with intermediate uveitis and mesangial glomerulonephritis with immune deposition. Mesangial glomerulonephritis were observed in patients whit Beh?et disease, known etiological cause of uveitis in adults and children. These findings may suggest that uveitis and glomerulonephritis have common immunological pathogenesis including circulatory immune complexes. In uveitis patients, screening for associated extra-ocular and renal manifestations is mandatory and should have careful long-term follow-up with regular systemic evaluation.     

Prolonged fever of unknown origin in Behçet's disease. Pay attention to vessels!

Beh?et's disease is a systemic vasculitis characterized by the association of recurrent oral and genital ulcers to systemic involvements, particularly ocular, nervous and vascular manifestations. Contrary to other vasculitis, prolonged fever of unknown origin is rare in Beh?et's disease. We report a case of a 26-year-old man presenting prolonged fever for two months. Physical examination showed oral, genital ulcers and pseudofolliculitis. The sedimentation rate was increased. Chest and abdominal computed tomography revealed thrombus in the inferior vena cava and portal vena. Outcome was favorable with glucocorticoid and anticoagulant therapy. Prolonged fever occurring during Beh?et's disease should prompt a search for a vascular injury.