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.     

EXPERIMENTAL BEHÇET'S DISEASE AND ULTRASTRUCTURAL X-RAY MICROANALYSIS OF PATHOLOGICAL TISSUES

Environmental chemicals (benzene hexachloride(BHC) and dichlor diphenyl trichlor ethane(DDT) as organic chlorides, Sumithion as an organic phosphorated compound and copper powder) were mixed together and administered orally to pedigreed Pitman-Moor's strain miniature swine for a period of about one year. Oral aphthae, folliculitis, cutaneous and subcutaneous nodules, genital ulcers, hyperemia of conjunctiva and intestinal ulcers were observed in all treated animals. Biopsy and autopsy specimens obtained from the experimental animals showed typical histopathological findings of human Behçet's disease. By ultrastructural X-ray microanalysis of peripheral neutrophils, vascular endothelial cells and infiltrated cells in affected lesions obtained from the experimental animals, highly significant amounts of chlorine and phosphorus were detected, mainly in the lysosomes. The incidence of Behçet's disease has been reported in countries where pesticides made from organic chlorine, organic phosphorus, arsenic and copper compounds have been used in massive amounts. Therefore, our findings suggest that these environmental chemicals play a main role in the pathogenesis of Behçet's disease.     

The clinical course of Behçet's disease in pregnancy: a retrospective analysis and review of the literature

Although Behçet's disease is mainly diagnosed during the reproductive periods of life, we know little about the influence of pregnancy on the clinical course of Behçet's disease. Therefore, we analyzed the relationship between Behçet's disease and pregnancy retrospectively, in order to detect any possible interaction between the two multisystemic processes, particularly in regard to the influence of pregnancy on the clinical course of Behçet's disease. We studied 44 pregnancies in 28 women with Behçet's disease. The diagnoses were made according to the criteria of the International Study Group for Behçet's disease. The patients were observed during pregnancy and puerperium periods at monthly intervals. The existence and incidence of symptoms were recorded during these periods. There was remission of Behçet's disease during 23 (52.3%) pregnancies, although the disease had been in a stage of exacerbation before pregnancy. The disease became exacerbated during 12 (27.3%) pregnancies, although it had been in a stage of remission before pregnancy. There were no changes in the clinical course of Behçet's disease in 9 (20.4%) pregnancies. The most frequent manifestations of the clinical exacerbation were increases in the intensity and severity of outbreaks of oral ulcers during pregnancy. Outbreaks of genital ulcers, eye inflammations, and arthritis were other signs of exacerbation. Other than spontaneous abortion in three patients, we did not observe maternal or fetal complications. Although Behçet's disease tends toward remission during pregnancy, the influence of pregnancy on its clinical course is quite variable between patients and even during different pregnancies in the same patient. On the basis of our and previous results, we speculate that pregnancy in general does not seem to markedly affect the natural course of Behçet's disease.     

A comparison between the effects of low (1 µg) and standard dose (250 µg) ACTH stimulation tests on adrenal cortex functions with Behçet's disease

Introduction Behçet's disease is a rare, chronic disorder. The cause of Behçet's disease is unknown. It is believed to be caused by an autoimmune reaction. As in other chronic autoimmune diseases, Behçet's disease may show a subclinical adrenal failure and some changes in cortisol levels. We aimed to evaluate adrenal gland function in Behçet's disease patients. Material and method This study included 18 Behçet's disease patients and 15 healthy controls. Patient and control groups were administered i.v. 1 µg low dose test (LDT) and 250 µg standard dose test (SDT) adrenocorticotropic hormone (ACTH) stimulation test after 12 h of night fasting with an interval of 3‐days and cortisol responses in the 0th, 30th and 60th minutes were evaluated. Results There was no statistically significant difference between basal cortisol values of Behçet's disease and control groups. Cortisol values in the 60th minute in LDT were significantly lower in Behçet's disease group than in the control group. In the peak cortisol responses to LDT, a significant decrease was found in Behçet's disease group. Conclusion These findings suggest that hypothalamo‐pituitary adrenal axis is partially suppressed in Behçet's disease.     

Vascular endothelial growth factor levels are increased and associated with disease activity in patients with Behçet's syndrome

Background/aims Vascular endothelial growth factor (VEGF) is a cytokine participating in inflammation with potent endothelial cell effects. It is produced by macrophages, neutrophils and vascular endothelial cells and can alter vessel permeability. Behçet's syndrome is a systemic inflammatory disorder with unknown etiology. Vascular endothelial dysfunction is one of the prominent features of the disease. We previously demonstrated the possible involvement of proinflammatory cytokines [tumor necrosis factor (TNF)‐α, soluble interleukin‐2 receptor (sIL‐2R), interleukin (IL)‐6 and IL‐8], nitric oxide (NO) and adrenomedullin in the etiopathogenesis of Behçet's syndrome. Since VEGF expression is induced by these cytokines and VEGF itself is a potent stimulator of NO production with endothelial cell effects, this study aimed to investigate whether VEGF was affected during the course of Behçet's syndrome. We also assessed the possible involvement of VEGF in ocular Behçet's syndrome or in disease activity. Methods This multicenter case–control study included a total of 39 patients with active (n = 22) or inactive (n = 17) Behçet's syndrome (mean age, 38.1 ± 10.4 years; 21 men and 18 women) satisfying International Study Group criteria, and 15 healthy hospital‐based control volunteers (mean age, 39.2 ± 9.3 years; eight men and seven women) matched for age and gender from a similar ethnic background. Patients were examined by a dermatologist and an ophthalmologist with an interest in Behçet's syndrome. Plasma VEGF concentrations were measured using a newly established enzyme‐linked immunosorbent assay. Clinical findings and acute‐phase reactant parameters such as erythrocyte sedimentation rate, α₁‐antitrypsin, α₂‐macroglobulin, and neutrophil count were used to classify the disease in Behçet's patients as active or inactive. The Wilcoxon test or the Mann–Whitney U‐test was used for statistical analysis as indicated and the results were expressed as mean ± SD, with range. Results The mean plasma VEGF level in patients with Behçet's syndrome (291.9 ± 97.1 pg/mL; range 121–532 pg/mL) was higher than that in control subjects (103.0 ± 43.6 pg/mL; range 25–187 pg/mL) and the difference was significant (P < 0.001). Patients with active disease had significantly (P < 0.001) higher VEGF levels than patients with inactive disease (347.6 ± 87.1 vs. 219.9 ± 51.6 pg/mL). In addition, ocular Behçet's patients (n = 23) had higher VEGF levels (315.7 ± 92.1 pg/mL) than nonocular patients (n = 16, 257.8 ± 96.6 pg/mL) and the difference was of borderline significance (P = 0.041). The levels of all acute‐phase reactant parameters were significantly higher in the active stage than in the inactive stage (for each, P < 0.01) or in control subjects (for each, P < 0.001). Conclusions VEGF may participate in the course of Behçet's syndrome, especially in the active stage, and elevated levels of VEGF may be an additional risk factor for the development of ocular disease, contributing to poor visual outcome.     

Caspase-9 expression is increased in endothelial cells of active Behçet's disease patients

Background Behçet's disease is a multisystem disease of unknown etiology. Caspase‐9 is responsible for initiating the caspase activation cascade during apoptosis. The aim of this study was to examine caspase‐9 expression in both endothelial and perivascular infiltrates of patients with active Behçet's disease. Methods Fifteen patients with active Behçet's disease, attending the First Dermatology Department, Ankara Numune Hospital, Ankara, Turkey between June 2003 and December 2005, were included in the study. Oral biopsy specimens from nine healthy volunteers were taken as the healthy control group, and skin biopsies from 18 psoriasis patients were used as the inflammatory control group. The specimens were examined with caspase‐9 primary antibody. Statistical analyses were performed using SPSS 11.5. Results The mean caspase‐9‐positive endothelial cell counts were 7.17 ± 2.45 in active Behçet's disease, 4.81 ± 0.76 in healthy controls, and 4.35 ± 1.34 in inflammatory controls. The difference between Behçet's disease and healthy controls was statistically significant, with increased endothelial staining in active Behçet's disease (P = 0.049). The difference between Behçet's disease and inflammatory controls was also statistically significant; the rate of staining was higher in Behçet's disease (P = 0.006). The mean caspase‐9‐positive dermal perivascular cell counts were 5.15 ± 2.32 in Behçet's disease, 3.32 ± 0.82 in healthy controls, and 5.54 ± 4.95 in inflammatory controls. These values did not show any statistically significant difference (P = 0.407). Conclusion Endothelial cells are one of the key cells in Behçet's disease, and our findings support the role of endothelial cells in the etiopathogenesis of Behçet's disease.     

The significance of immunohistochemistry in the skin pathergy reaction of patients with Behçet''s syndrome

Background Behçet's syndrome is a chronic systemic immuno‐inflammatory disorder affecting multiple organs with generalized vasculitis of arteries and veins. Although the aetiology is still unknown, endothelial dysfunction is one of the most prominent features in Behçet's syndrome. The skin pathergy reaction (SPR) is a non‐specific hyperreactive lesion formation that is one of the major features and diagnostic criteria of the disease. It develops after 24–48 h at the site of the needle‐prick, especially in the exacerbation period, and it is very similar to the erythematous papules or pustules that appear spontaneously in patients with Behçet's syndrome. Therefore, an investigation into the formation of the SPR lesion may contribute to the pathophysiology of skin lesions of this unique disorder. Objective To evaluate the immunological features of SPR formation by assessing the immunohistochemical staining of cell adhesion molecules and endothelial growth factor markers such as E‐selectin, P‐selectin and endoglin (CD 105). Methods Patients with Behçet's syndrome showing positive (n = 15) or negative (n = 10) SPR and 15 age‐ and sex‐matched hospital‐based healthy control subjects from a similar ethnic background were included in this study. Patients were divided into active and inactive stage by clinical findings and acute‐phase reactant parameters including erythrocyte sedimentation rate (ESR) and neutrophil count. Punch biopsy specimens were obtained both from the lesion site on the forearms at 48 h and from normal skin approximately 5 cm adjacent to the SPR site. A biopsy was also obtained from the test application site in Behçet's syndrome patients with negative SPR and healthy volunteers. Biopsy specimens were then evaluated by immunohistochemical staining. Results Immunohistochemical examination demonstrated a mixed inflammatory cell infiltrate around the vessels and skin appendages that extended somewhat into the deep dermis. A positive segmental staining of E‐selectin and P‐selectin was noted in the endothelial cells of biopsies obtained from the patients with positive SPR. A positive segmental staining of CD 105 in the endothelial cells was also observed in the same group of patients. However, the immunostaining of the same markers was found to be negative in the biopsies obtained from normal skin of SPR‐positive patients, SPR‐negative patients and healthy control subjects. Both acute‐phase reactant levels were significantly higher in the active stage than in inactive patients or healthy controls. Conclusion Interaction of cellular adhesion molecules together with endothelial proliferation may play an important role in the formation of SPR lesions in patients with Behçet's syndrome. The involvement of the vascular endothelium in a large number of diseases including Behçet's syndrome supports the importance of vascular‐specific adhesion molecules for their aetiopathogenesis.     

A case of pediatric Behçet's disease with intestinal involvement

We report a 6-year-old girl with recurrent oral aphthae, genital and perianal ulcers, and folliculitis-like erythema followed by intestinal symptoms. No ocular lesions were found. Her ailment was diagnosed as incomplete Behçet's disease with intestinal involvement. According to the literature, pediatric Behçet's disease is characterizesd by a low incidence of ocular lesions and a high incidence of intestinal involvement, as exhibited in this case. As intestinal lesions in pediatric Behçet's disease are often life-threatening, a barium enema must be given to exclude the possibility of intestinal involvement when pediatric patients with Behçet's disease complain of abdominal pain     

Serum β2 microglobulin in recurrent aphthous stomatitis and Behçet's syndrome

β₂Microglobulin (β₂m), a constituent of cell surface histocompatibility antigens, was measured in scrum from twenty-eight patients with recurrent aphthous stomatitis, twenty-four patients with Behçet's syndrome and twenty-eight matched controls. Serum β₂m concentrations were significantly greater in recurrent aphthous stomatitis and in Behçet's syndrome than controls, but failed to differentiate the two diseases.     

Expression of bcl-2 protein in active skin lesions of Behçet's disease

Abstract Background Expression of bcl‐2 protein has been shown to play an important role in the pathogenesis of some inflammatory as well as neoplastic disorders. In this study we have investigated the presence of bcl‐2 protein in active skin lesions of Behçet's disease and compared these results with normal skin samples of Behçet's disease (BD) patients and BD unrelated leukocytoclastic vasculitis. Methods Active skin lesions of 23 Behçet's disease patients, normal skin samples of seven Behçet's disease patients, and archival biopsy specimens of 23 cutaneous leukocytoclastic vasculitis were investigated for the presence of bcl‐2 protein by immunohistochemical methods. Results of staining were assessed semiquantitatively. Chi‐square tests were used for statistical analysis. Results Expression of bcl‐2 protein were demonstrated in 16 of 23 (69.5%) and 8 of 23 (34.7%) patients with Behçet's disease and leukocytoclastic vasculitis, respectively. There were statistically significant difference between two groups (x² = 4.27, P < 0.05). None of the normal skin samples of Behçet's disease patients showed bcl‐2 expression. Conclusion Expression of bcl‐2 protein may play a particular role in the development of skin lesions in Behçet's disease by causing prolonged survival of infiltrating lymphocytes.     

The quantification and significance of mast cells in lesions of Behçet's disease

Mast cells in the upper dermis and mucosal subepithelial layer were counted in thirty consecutive light microscopy oil-immersion fields of the following: thirty-four skin and oral specimens from lesions in patients with active Behçet's disease, eight specimens of apparently uninvolved skin of the same patients, and 102 lesions of a variety of other skin diseases. The results revealed a significant increase in the number of mast cells in Behçet's lesions. Furthermore, the histamine content of five reactive lesions showed a two-fold increase compared with that in apparently uninvolved skin of patients with active Behçet's disease. It is suggested that mechanisms similar to cutaneous basophil hypersensitivity may be involved in the production of Behçet's lesions.     

Can specific vessel‐based papulopustular lesions of Behçet's disease be differentiated from nonspecific follicular‐based lesions clinically?

Background Although papulopustular lesions are one of the diagnostic criteria for Behçet's disease, controversy exists as to the nature of these lesions. Specific vessel‐based papulopustular lesions as well as nonspecific follicular lesions may be seen in patients with Behçet's disease. Some authors suggest that papulopustular lesions should be considered a positive criterion only if they exhibit a vessel‐based neutrophilic reaction. Objective To determine whether specific vessel‐based papulopustular lesions can be differentiated clinically from nonspecific follicular lesions in patients with Behçet's disease. Methods Twenty‐three papulopustular lesions in 20 patients with Behçet's disease were initially examined clinically by two dermatologists blind to each other's diagnosis. Biopsies taken from these lesions were examined by a pathologist unaware of the patient data. Results Leukocytoclastic vasculitis or perivascular infiltration was observed in 10 lesions, perifollicular and perivascular infiltration was noted in nine lesions, and perifollicular inflammation was seen in four biopsy specimens. Most of the lesions interpreted clinically as specific papulopustular lesions of Behçet's disease had predominantly perivascular infiltration or leukocytoclastic vasculitis; however, three papulopustular lesions evaluated by both observers as specific papulopustular lesions had only perifollicular inflammation, and one lesion diagnosed clinically as a nonspecific follicular eruption revealed perivascular neutrophilic reaction. Interobserver variance was noted in three papulopustular lesions. Conclusions Clinical examination may not be sufficient to predict the dermatopathologic pattern in all lesions. Papulopustular lesions with no specific clinical and histopathologic features may create problems in the diagnosis of Behçet's disease.     

Erythema nodosum-like lesions in Behçet''s syndrome: a histopathologic study of 30 cases

Thirty patients who fulfilled the criteria for complete and incomplete types of Behçet's syndrome were studied to determine the histopathologic changes of erythema nodosum-like lesions. Lymphocytic vasculitis was observed in 12 (40%) of the cases, but it was only focal in areas of severe lymphocytic inflammation and only mild in degree. No diffuse vasculitis was seen. It is our opinion that the observed lymphocytic vasculitis is only secondary to moderate or severe lymphocytic inflammation. Twelve cases (40%) revealed septal panniculitis, 10 cases (33%) demonstrated lobular panniculitis with moderate to marked inflammation and fat cell necrosis, and 8 cases (27%) showed mild and nonspecific inflammation in the panniculus. Therefore, there is a spectrum of histopathologic changes of erythema nodosum-like lesions in Behçet's syndrome, similar to that of erythema nodosum secondary to other systemic disorders.     

Clinical Spectrum of Behçet's Disease

Behçet's disease is a chronic systemic inflammatory disease involving mucous membranes, skin, eyes, the gastrointestinal tract, joints, blood vessels, and the neurologic system. Behçet's disease occurs endemically in the Middle East and Mediterranean regions. It is also distributed in the Central and Far Eastern Asian countries including Korea, Japan, and China. With the volume of clinical information obtained from over 5,000 patients who visited the Behçet's Disease Specialty Clinic, Severance Hospital, Yonsei University College of Medicine, informative and educational viewpoints of Behçet's disease including dermatologic and other systemic manifestations were introduced.     

BEHÇET'S DISEASE: CLINICAL STUDY OF JORDANIAN PATIENTS

Background. Behçet's disease is a chronic, recurrent, inflammatory disorder characterized by the triad of oral and genital ulcers and ocular lesions. The etiology is unknown. This is the first report giving details of the clinical manifestations of Behçet's disease in Jordanian patients. Methods. Twenty patients with Behçet's disease were studied to determine the clinical pattern in the North of Jordan. The patients were seen in Princess Basma Teaching Hospital in North Jordan. They presented to various clinics and underwent full clinical examination. Data for each patient on all features of Behçet's disease were recorded on a standard form. A comparison was made between Behçet's disease in Jordan and other countries in the region. Results. Of the 20 patients, 14 were men and six women, giving a ratio of 2.3:1. Their ages ranged from 14 to 58 years. All had mouth ulcers, 65% genital ulcers, 65% ocular involvement, 55% joint involvement, 35% skin lesions, 20% vascular lesions, and 5% gastrointestinal involvement. The oral ulcers were the first manifestation of the disease process in 70% of our patients. Skin lesions, genital ulcers, and involvement of the central nervous system and the pulmonary system were less frequent in our study. Conclusions. Although it is difficult to obtain figures as to the incidence and prevalence of Behçet's disease in Jordan, the clinical manifestations, with a few exceptions, are similar to those in other countries in the region.     

The frequency of scarring after genital ulcers in Behçet's syndrome: a prospective study

Background Although genital ulceration with or without scar formation is an important manifestation of Behçet's syndrome, formal data on the rate of genital scarring are lacking. Objective To study prospectively the frequency of genital scar formation after genital ulcers in patients with Behçet's syndrome. Methods One hundred and two patients (72 males and 30 females) with fresh genital ulcers presenting at a dedicated Behçet's syndrome outpatient clinic were followed for 6 weeks. The ulcer location, size, and frequency of scar formation were noted. All patients were treated with similar topical therapy. Results Two hundred and ten genital ulcers were followed in both sexes. The rate of scar formation was 66.2% (102/154) in male patients and 60.7% (34/56) in female patients. When genital ulcers were stratified as a function of size, large genital ulcers (≥ 1 cm in diameter) developed scars more frequently than did smaller ulcers (< 1 cm). The rate of scar formation in male patients with large genital ulcers was 89.4% (59/66) and with small ulcers was 48.9% (43/88) (P < 0.001). In females, all 19 large ulcers healed with scarring, and the same was true for 40.5% (15/37) of the small ulcers (χ² = 18.61, P < 0.001). Conclusion About two‐thirds of genital ulcers in Behçet's syndrome leave scars. The rate of scar formation depends on the ulcer size.     

Evaluation of pro-atherogenic lipid profile and high atherohenic indexes in patients with Behçet's disease: A case–control study

Background

Behçet's disease is a systemic auto-immune and auto-inflammatory chronic disease in which genetic and environmental factors play a role. Patients with Behçet's are at significant risk for developing many comorbidities, including cardiovascular diseases.

Aims

It was aimed to investigate the relationship between serum lipid parameters and atherogenic indexes to evaluate the cardiovascular risk status in patients with Behçet's disease.

Patients/Methods

This study was designed as a single-center, retrospective case–control study. The study was conducted with 212 patients over 18 years of age, 106 in the case group and 106 in the control group.

Results

There was a significant difference in lipid values between the patients with Behçet's disease and the control group. While the serum triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (NHC) levels were significantly higher, the high-density lipoprotein cholesterol (HDL-C) level was low in patients with Behçet's disease. From atherogenic indexes, Atherogenic Index of Plasma (AIP) (0.03 ± 0.27 vs. −0.07 ± 0.23, p = 0.003), Castelli Risk Index I (CRI-I) (4.24 ± 1.07 vs. 3.02 ± 0.96, p < 0.001), Castelli Risk Index II (CRI-II) (2.65 ± 0.81 vs. 1.84 ± 0.59, p < 0.001) and Atherogenic Coefficient (AC) (3.24 ± 1.07 vs. 2.02 ± 0.96, p < 0.001) levels were significantly higher in patients with Behçet's disease.

Conclusion

Our study shows that patients with Behçet's have a higher pro-atherogenic lipid profile and atherogenic indexes at high risk. Patients with Behçet's have an increased risk of cardiovascular diseases associated with atherosclerosis.     

Serum interleukin-8 as a serologic marker of activity in Behçet's disease

Background Immune dysregulation has been shown to be one of the major aspects of the yet unknown pathogenesis of Behçet's disease. Interleukin-8 (IL-8), a major chemokine with pivotal effects concerning leukocytes and endothelial cells, has been found to be elevated in patients with Behçet's disease. Aim To evaluate the significance of elevated levels of IL-8 with respect to the activity of Behçet's disease. Methods Sixty-seven consecutive patients with Behçet's disease (37 males, 30 females; 32.5 ± 9.3 years) were enrolled in our study. The number of active clinical manifestations at the time of serum sampling was recorded. The degree of association between disease activity and IL-8, C-reactive protein, and erythrocyte sedimentation rate was assessed. Results Serum levels of IL-8 increased as the number of clinically involved organs increased (P < 0.05). C-reactive protein and the erythrocyte sedimentation rate showed no correlation with disease activity. Conclusions Our study confirms that the IL-8 level is a more sensitive marker of disease activity than the erythrocyte sedimentation rate and C-reactive protein. It may be assumed that IL-8 plays an important role in the pathophysiology of Behçet's disease.     

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.     

Association of class I HLA antigens with the clinical manifestations of Turkish patients with Behçet's disease

Summary Genetic factors appear to be important in the pathogenesis of Behçet's disease. Although it is known to be strongly associated with HLA‐B51, the association of HLA class I antigens with specific clinical findings of the disease has not been studied extensively and the few studies are conflicting. The aim of this study was to investigate the association of HLA class I alleles with the manifestations of Behçet's disease in Turkish patients. Eighty‐five patients with Behçet's disease were typed for HLA‐A, B, and C antigens with the serologic, standard microlymphocytotoxicity technique. Possible associations of the HLA complex with clinical findings of Behçet's disease were examined. Statistically significant findings are as follows (P < 0.05): increased HLA‐B51 and decreased HLA‐B35 frequency in patients with thrombophlebitis, increased HLA‐A29 and decreased HLA‐Bw6 frequency in patients with ocular involvement, decreased HLA‐Cw2 frequency in patients with erythema nodosum, and decreased HLA‐Cw7 frequency in patients with genital ulceration. Of particular note, the results of this study suggest that the presence of HLA‐B51 and the absence of HLA‐B35 can be regarded as laboratory risk factors of venous thrombosis in patients with Behçet's disease.