Expression of cytokeratins, adhesion and activation molecules in oral ulcers of Beh?et's disease.

BACKGROUND: Beh?et's disease (BD) is a multisystemic inflammatory disorder of which oral aphthous ulceration is a major feature. AIMS/HYPOTHESIS. This study sought to determine the role of cytokeratins, differentiation and proliferation markers, gammadelta T-cell adhesion and activation molecules, and apoptotic markers in oral ulcers of this disease. METHODS: Expression patterns for cytokeratins (K1, K6, K14, K15, K16), integrins (beta1 and alpha6), CD3 T-cell and gammadelta T-cell adhesion and activation markers [CD40, CD44, CD54, ICAM-1, CD58, leucocyte function-associated antigen (LFA)-3, vascular cell adhesion molecule-1 (VCAM-1), CD86], and cellular proliferation and differentiation markers (Ki67 and involucrin), and apoptotic markers (CD95 and Bcl-2) in oral ulcers of nine patients with BD and four healthy controls were analysed by immunohistochemistry. RESULTS: K14, K15 and involucrin expression were unchanged, whereas Ki67, the proliferation marker, was reduced by around 50%. K1, K6, K16, beta1 integrin and the apoptotic marker CD95 were upregulated, whereas alpha6 integrin and Bcl-2 were downregulated in BD samples. CD3 and gammadelta T-cell expression and other adhesion molecules including CD44, CD86, CD58 (LFA-3), VCAM-1 and intercellular adhesion molecule-1 (CD54) were upregulated, whereas CD40 showed little change. CONCLUSIONS: Our data demonstrates changes in cell-cell and cell-extracellular matrix interactions that affect cell homeostasis and may participate in the formation of oral ulcers in BD.     

The efficacy of topical 0.2% hyaluronic acid gel on recurrent oral ulcers: comparison between recurrent aphthous ulcers and the oral ulcers of Behçet's disease

Background Hyaluronic acid (HA) is a primary component of the extracellular matrix, and the efficacy of HA on oral ulcers is rarely reported. Objective To observe the efficacy and safety of the topical application of 0.2% HA gel on recurrent oral ulcers and to compare its effects in patients with recurrent aphthous ulcers (RAU) and the oral ulcers of Behçet's disease (BD) Materials and methods Thirty‐three outpatients with recurrent oral ulcers were included in the study (17 patients: BD, 16 patients: RAU). The patients used topical 0.2% HA gel twice daily for 2 weeks. The subjective parameters of patients [number of ulcers, healing period, visual analogue scale (VAS) for pain] were investigated and objective assessments (number of ulcers, maximal area of ulcer and inflammatory signs) were inspected by a physician. Results A subjective reduction in the number of ulcers was observed in 72.7% of the patients. A decrease in the ulcer healing period was observed in 72.7% of the patients; 75.8% experienced improvement in VAS for pain. Objective inspection of the ulcers showed a reduction of numbers in 57.6% of the patients, and 78.8% of the ulcers showed a decrease in area. Among the inflammatory signs, swelling and local heat were significantly improved after treatment. No significant differences were found between the BD group and RAU group in subjective and objective parameters, except for inflammatory signs. No side‐effects were observed. Conclusions The topical application of 0.2% HA gel seems to be an effective and safe therapy in patients with recurrent oral ulcers; the study supports the use of HA in BD with oral ulcers.     

Mucosal presentation of Behçet's disease

Behçet's disease is a multisystem disease with both mucosal and systemic presentations, infrequently seen in the UK and Northern Europe. We present the case of a 23-year-old Caucasian girl who presented with mucosal ulceration and in whom diagnosis was assisted by HLA testing.     

Lytic effect of cytotoxic lymphocytes on oral epithelial cells in Behçet's disease

The effect of blood lymphocytes on syngeneic oral epithelial cells was studied in twelve patients with Behçet's disease (BD) and twenty-one patients with recurrent aphthous ulcers (RAU). The control group consisted of twenty-five patients with non-aphthous skin disease and eight healthy individuals. Primary cell lines obtained from oral mucosa by suction blistering and subsequent enzymatic dissociation were used as target cells. Using a modified ⁵¹chromium release macro-assay, a significant lytic effect due to antibody-independent lymphocytotoxicity could be demonstrated in patients with BD, but no significant lysis of target cells was found in the RAU patients compared with the control group. These results provide further evidence that antibody-independent lymphocytotoxicity may play an important role in oral ulceration in BD.     

Sweet's syndrome associated with Behçet's disease

A case of acute febrile neutrophilic dermatosis (Sweet's syndrome) associated with Behçet's disease occurring in a 48 year old woman is reported. She fulfilled the diagnostic criteria for both Sweet's syndrome and Behçet's disease. There have been several reports of this association. Herpes simplex virus was isolated from a genital ulcer in our patient. The possible role of herpes simplex virus in this interesting association of Behçet's disease and Sweet's syndrome is discussed and a review of the literature is made.     

Upper gastrointestinal abnormalities and Helicobacter pylori in Behçet's disease

Background  There are few published clinical trials concerning upper gastrointestinal (GI) involvement in Behçet's disease (BD), and most have been performed on patients with upper GI tract symptoms.
Aim  We sought to determine whether routine endoscopy is indicated in asymptomatic patients with BD and whether Helicobacter pylori plays a role in the pathogenesis of BD.
Methods  Forty consecutive patients with BD and 40 age- and gender-matched controls with tinea pedis were studied. All patients underwent fiberoptic esophagogastroduodenoscopy. Urea breath test was used to identify H. pylori .
Results  Abnormalities were noted in 37 patients (93%): hiatal hernia (53%), antral gastritis (33%), pan-gastritis (23%), gastric ulceration (8%), and duodenal ulceration (8%). Helicobacter pylori was found in 26 patients (65%) with BD and in 28 controls (70%) (no significant difference by chi-squared test, P  > 0.05). We found a high incidence of upper GI abnormalities in BD, but the abnormalities were not specific for the disorder.
Conclusions  Routine endoscopy and screening for H. pylori infection may not be necessary in asymptomatic patients with BD.     

Wound healing in Behçet's syndrome

Background Because there is an increased inflammatory response to trauma, particularly of the skin, in patients with Behçet's syndrome (BS), an alteration in wound healing in BS is expected. The aim of this study was to investigate the healing features of punch biopsy wounds in BS and acne vulgaris (AV) patients used as controls.
Method Full-thickness skin punch biopsies (4 mm) were taken from the hairless sites of the non-dominant forearms in 20 BS and 20 AV patients. Each patient was examined on days 1, 2, 3, 4, 5, 8, and 10, and the biopsy wound area and induration were marked on sterile glass slides. Other inflammatory changes, such as suppuration and pain, were also recorded. No antiseptic solutions or ointment, except saline, were used.
Results The wound area healed similarly in both groups ( p > 0.05). Thirteen (65%) BS patients had erythematous haloes around the wound on the first day. The number of patients presenting inflammatory changes reached 18 (90%) on the second day in the BS group. The area of erythema around the wound in BS patients was significantly greater than that in AV patients (5; 25%). It gradually decreased day by day. Purulent changes were observed in four BS patients on day 1, and induration around the biopsy wound in six patients on day 2. Only one patient with AV had suppuration, which appeared on the second day, while no AV patient displayed induration.
Conclusion Biopsy-induced trauma may cause increased inflammation in BS, but wound healing is not altered.     

Histological and direct immunofluorescence study of cutaneous hyperreactivity in Behçet's disease

The mechanism of skin hyperreactivity (pathergy) in Behcet's disease is unknown. It has been suggested that the response is due to an Arthus-like reaction. In 18 patients with active Behçet's disease, pathergy was induced and the skin biopsied after 24 h. The histological reaction was that of mild to intense round cell infiltration, perivascular in type. Direct immunofluorescence failed in all 18 patients to demonstrate the local presence of immunoglobulins and complement at the site of lesion. A marked increase in the number of mast cells was observed at the site of reaction and scattered throughout the dermis, the role of which is to be further investigated. The study failed to demonstrate a humoral mechanism in the production of the cutaneous hyperreactivity.     

The multiple faces of Behçet's disease and its aetiological factors

Behçet’s disease (BD) is a chronic, inflammatory multisystemic condition of unknown aetiology. It is clinically characterized by recurrent orogenital ulcerations and skin eruptions; ocular manifestations; arthritis; vasculitis and in some cases neurological and large vessel involvement. Aetiology has not been defined, but genetic, environmental, viral, bacterial and immunological factors have been proposed as causative agents. Treatment includes colchicine, thalidomide, steroids and immunosuppressive agents and it is based on the severity of systemic manifestations, such as central nervous system involvement, arterial aneurysms and thrombosis of the major veins. Mortality is related to major system involvement. In this article the different clinical features, the multiple faces of BD and a list of currently suspected aetiological factors of the disease are discussed, and treatment modalities summarized.     

Sister chromatid exchange and micronucleus studies in patients with Behçet's disease

Background:  Genetic factors that predispose individuals to Behçet's disease (BD) are considered to play important roles in the development of the disease. The aim of this study was to determine, by counting sister chromatid exchange (SCE) and micronucleus (MN) frequencies, whether DNA damage have an effect on the pathogenesis of BD. Furthermore, our aim was to show if there is an association between oxidative stress and chromosome instability in BD.
Methods:  We analyzed lymphocytes from patients with BD (16 in active and 14 in inactive periods) and 20 healthy controls for SCE and MN frequencies. In addition, malondialdehyde (MDA) level, superoxide dismutase (SOD) level, glutathione peroxidase (GSH-Px) activity, erythrocyte sedimentation rate (ESR) and polymorphonuclear leukocyte (PMNL) count were determined in the all subjects.
Results:  The SCE and MN frequencies were significantly higher in both the active and inactive period patients than in the controls (p < 0.00001, p < 0.0001, p < 0.01 and p < 0.05, respectively), and the MDA level was significantly higher in both the active and inactive period patients than in the controls (p < 0.01 and p < 0.05, respectively). In contrast, the SOD and GSH-Px levels were significantly lower in both the active and inactive period patients than in the controls (p < 0.01, p < 0.05, p < 0.01 and p < 0.05, respectively).
Conclusions:  Our results suggest that increased plasma MDA level and decreased plasma GSH-Px and SOD levels reflect the increased levels of oxidative stress in BD patients, and this situation may impair genetic stability in BD patients.     

Colchicine in the treatment of the cutaneous manifestations of Behçet's disease

Five patients with Behçet's disease were satisfactorily treated with colchicine. Oral aphthosis, erythema nodosum-like lesions and genital erosions improved greatly within a month as did laboratory findings. We believe colchicine to be the first choice in the management of the cutaneous and ocular lesions of Behçet's disease.