Use of Colchicine in the Treatment of Behçet's Disease

ABSTRACT: To date, various treatment modalities have failed to produce consistent improvement in patients having Behçet's disease. Recent reports in the literature, however, have shown promising results with the use of colchicine. Our patient, an 18-year-old white woman, satisfied the 1977 Istanbul Conference criteria for Behçet's disease by exhibiting ocular inflammation and a five-year history of severe, recurrent oral and vaginal ulcerations. She was treated with 0.6 mg of colchicine orally twice daily, and at the end of two weeks of treatment, the oral lesions had completely resolved, and the vaginal ulcers were reduced in diameter and depth to at least one half. Within one month, all oral and Vaginal ulcers were completely healed.     

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.     

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     

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.     

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.     

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.     

Recurrent Oral and Genital Ulcers in an Infant: Neonatal Presentation of Pediatric Behçet Disease

Behçet disease is a complex, multisystem disease characterized by recurrent oral and genital ulcerations. It rarely occurs in infants or children. Neonatal Behçet disease has been reported in infants whose ulcers resolve at or before 9 weeks of age. Few cases of neonatal Behçet disease persisting into childhood have previously been reported. We report the case of a 1‐month‐old infant who presented with severe recurrent genital ulcerations and at 6 months developed recurrent oral ulcerations. Her orogenital ulcerations continue to recur. Human leukocyte antigen testing revealed HLA‐B51 and B44 positivity. This is a case of pediatric Behçet disease in the neonatal period. Behçet disease should be considered in the differential diagnosis of recurrent genital and oral ulcerations in infants and children.     

Formation of arcuate crusted lesions after non-ablative 1450-nm diode laser treatment equipped with a dynamic cooling device

Abstract

Behçet's disease (BD) is a chronic systemic inflammatory disorder of unknown etiology with variable clinical manifestations. HLA-B51 allele is the most strongly associated known genetic factor. The mucocutaneous lesions (oral aphthae, genital aphthae, skin lesions such as pseudofolliculitis) constitute the hallmark of the disease, but also gastrointestinal, vascular, central nervous systems, and others may be involved. We report a case of a young man affected with Behçet's disease who presented facial telangiectasias and striae rubra in the inner region of his arms and at the level of his hips, as uncommon minor superficial vascular manifestations of BD. To manage them we have subjected the patient to a cycle of Intense Pulsed Light (IPL) therapy. Our findings showed that the use of IPL is a safe and effective treatment for telangiectasias and striae rubra, also in the complex clinical condition of Behçet's disease. In fact, the treatments were well tolerated, no sign of scarring or hyper/hypopigmentation was reported and we obtained a significant improvement of the lesions in terms of color and size of them.     

Micronucleus frequency in the oral mucosa and lymphocytes of patients with Behçet's disease

Behçet's disease (BD) is a chronic, multisystemic, inflammatory disorder characterized mainly by recurrent oral and genital aphthous ulcerations and uveitis. Our study aimed to determine the genetic damage in patients with BD. The micronucleus (MN) frequency was counted in peripheral lymphocytes and exfoliated cells of the patients with BD. MN analysis was performed in peripheral lymphocytes of 30 patients with BD and in 20 healthy controls by the cytokinesis‐block method, and on uncultured cells of the oral cavity in 10 patients and 9 healthy controls. We found significantly higher MN rates in lymphocytes of the patients than the control subjects (P = 0.000). There were no significant differences between the patients with or without treatment (P = 0.860). The MN frequency in exfoliated cells of the patients was higher than in those of healthy controls (P = 0.013), and there was no significant difference between the exfoliated cells of the treated and untreated patients (P = 0.201). Our results indicate that genetic damage may play a secondary but important part in the aetiology of BD and that treatment with colchicine does not induce MN.     

Lack of association between leptin G2548A gene polymorphism and Behçet''s disease

Background Behçet's disease is a chronic, multisystem, inflammatory disease characterized by the predominance of T‐helper 1 cytokines. The disease is also characterized by infiltration of lymphocytes and neutrophils into the affected tissues. Because cytokines are involved in the regulation of lymphocyte and phagocyte functions, they may play an important role in the pathogenesis of Behçet's disease. Leptin, a member of the gp 130 family of cytokines, induces a strong T‐helper 1 response and is regarded as a proinflammatory inducer. Recent studies have shown that serum leptin concentration was increased in patients with Behçet's disease and correlated with disease activity. Objectives We aimed to investigate the role of G2548A polymorphism of leptin gene in patients with Behçet's disease and compare the results with healthy controls. Patients and methods A total of 93 subjects with Behçet's disease and 125 healthy controls were included in this study. Analyses of G‐2548A polymorphism of the LEP gene were performed using the PCR‐restriction fragment length polymorphism technique. The genotypes (GG, GA, and AA of leptin G2548A) and alleles (G and A of leptin 2548) were scored and the frequency was estimated. The frequencies of the alleles and genotypes in patients and controls were compared. We analysed the correlation between leptin gene polymorphism and the clinical features of BD. Results Both genotype and allele frequencies were not significantly different between controls and Behçet's disease patients [OR = 0.67, 95% CI (0.35–1.29), P = 0.197 and OR = 0.77, 95% CI (0.52–1.15), P = 0.184]. We did not find any significant relationship between leptin gene polymorphism and the clinical features of BD (P > 0.05). Conclusion In the present case‐control study, we found no evidence of an association between the G‐2548A variant of the leptin gene and BD among Turks. Further studies are needed to investigate serum leptin level to explain the mechanisms behind the lack of association between leptin G2548A gene polymorphism and BD.     

Behçet's disease-like presentation of bullous pyoderma gangrenosum associated with Crohn's disease

A 47‐year‐old woman presented with a 2‐month history of generalized arthralgia and a 10‐day history of oral aphthous ulcers. After hospitalization, papulopustular lesions and perianal ulcerations developed. Pathergy test was positive and ophthalmological examination was normal. The presence of oral aphthous ulcers, genital ulcerations, papulopustular lesions and arthralgia, and the positive pathergy test suggested the diagnosis of Behçet's disease (BD). In a few days, positive pathergy reactions and papulopustular lesions evolved into bullous lesions, which were diagnosed dermatopathologically as pyoderma gangrenosum. Two days after the presentation of papulopustular lesions, the patient experienced diarrhoea accompanied by bloody stools and mucus. Histopathological examination of biopsy specimens showed no vasculitis but revealed findings suggestive of Crohn's disease. The patient responded well to treatment with systemic steroids and 5‐aminosalicylic acid. Our case demonstrates that the differential diagnosis of BD and inflammatory bowel disease may be perplexing and that these two diseases may be closely related.     

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.     

The Levels of Plasma Interleukin-2 and Soluble Interleukin-2R in Behçet's Disease: A Marker of Disease Activity

It is well known that patients with Behçet's disease (BD) have an activated immune system, probably mediated by soluble factors in the circulation. The purpose of our study was to examine the roles of plasma interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) in the pathogenesis of BD. Thirty-two patients with BD diagnosed according to the Criteria of the International Study Group for Behçet's Disease and 20 age-matched healthy persons were included in the study. The plasma levels of cytokines were measured by ELISA. Plasma levels of IL-2 and sIL-2R were increased in BD over controls, but the differences were not statistically significant. sIL-2R levels in patients with active disease were significantly higher than in either patients with inactive disease (p<0.001) or the control group (p<0.05). Our results suggest that the level of sIL-2R in BD seems to be related to disease activity.     

Fas (CD95) and bcl-2 expression in active skin lesions of Behçet''s disease

Over‐expression of bcl‐2 in lymphocytes has an important role in some immunological and inflammatory diseases. Fas (CD95) is a cell surface molecule that mediates receptor‐triggered apoptosis in various cells including autoreactive T cells. In this study we investigated bcl‐2 and Fas (CD95) expression in dermal lymphocytes in active skin lesions of Behçet's disease (BD) and in skin biopsy samples with chronic, non‐specific inflammations. Tissue sections of 29 skin lesions of Behçet's disease and of 10 chronic non‐spesific inflammatory process cases from the archives of the Ondokuz May?s University's Pathology Department were immunohistochemically stained for bcl‐2 and Fas (CD95), and lymphocytes in the dermal infiltrate were evaluated for cytoplasmic staining. bcl‐2 staining was observed in the skin lesions of 22 cases (75.8%) of Behçet's disease. bcl‐2 staining was detected in two (20%) control skin biopsy samples with non‐specific chronic inflammation. Fas (CD95) positivity was not detected in lymphocytes in Behçet's disease‐related skin lesions. Fas (CD95) staining was observed in only three skin biopsy samples with non‐specific chronic inflammation. bcl‐2 and Fas (CD95) staining values in Behçet's and non‐specific inflammation groups were significantly different (P < 0.01); differences in the bcl‐2 staining values between Behçet's patients with mucocutaneous involvement only and mucocutaneous and other systemic involvements were not significant (P > 0.05). Expression of bcl‐2 and loss of Fas (CD95) expression in dermal lymphocytes may play a role in the development of skin lesions and may account for the chronic course with periodic exacerbations in BD.     

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.     

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.     

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 histopathology of pathergy: a chronologic study of skin hyperreactivity in Behçet's disease

Background many patients with Behçet's disease (BD) demonstrate hyperreactivity (pathergy), and the induced skin lesions may serve as a model for the disease. Objective This study examined the sequence of histopathologic changes after needle prick trauma. Methods Eight patients fulfilling the International Study Group Criteria for Behçet's Disease, two patients with recurrent aphthous stomatitis, and two healthy controls each underwent intradermal injections with subsequent biopsies at 0, 4, 24, and 48 h. Hematoxylin and eosin sections were evaluated in a blinded fashion according to 11 histopathologic criteria. Results At time zero, normal skin was seen. By 4 h, neutrophils were present usually admixed with lymphocytes (8 out of 10). The inflammatory cell density peaked by 24 h in 8 out of 10 patients and at 48 h in 2 out of 10 patients. Sparse leukocytoclasis was identifiable from 4 to 48 h, but was not associated with fibrin. True vasculitis (as evidenced by fibrin within vessel walls and/or intraluminal thrombi) was not seen. Intraepidermal pustules (IEPs) and polymorphonuclear (PMN) aggregates within the needle tract were seen as early as 4 h. The control patients and three out of eight of the BD patients failed to develop clinical lesions. Among this group histopathologic IEPs were lacking in all but two BD patients. Conclusions These data suggest that early pathergy is mediated by PMNs and lymphocytes without vasculitis. Hyperchemotaxis may explain the rapid accumulation of PMNs along the injection site.     

Prevalence of Behçet's disease in Istanbul, Turkey

Background The prevalence of Behçet's disease (BD) is much higher in countries along the ancient Silk Route, extending from Japan to Mediterranean countries including Turkey, than in northern Europe and the USA. Three previous epidemiologic surveys have been carried out in different regions of Turkey. Patients and methods This study investigated the cross‐sectional prevalence of BD in individuals aged > 12 years in Istanbul, Turkey, in two stages. The first stage aimed to identify individuals with recurrent oral ulcers (ROUs) by visiting them in their homes, and the second stage aimed to further examine those with ROUs for the presence of other BD‐related manifestations under hospital conditions. The sample size was determined to be 24,000 with an expected BD prevalence rate of 1/1000 and a sampling error of 4/10,000, with a 95% confidence interval (CI) of 6–14/10,000. The number of individuals to be screened in each district was determined in proportion to the population of all districts in Istanbul. Results The standard questionnaire was applied to a total of 23,986 individuals at their homes. A history of ROU was recorded in 2289 individuals (9.5%), and a previous diagnosis of BD was recorded in 47. The diagnosis of ROU was confirmed in 700, and the diagnosis of BD was established in 101 according to the International Study Group criteria. The prevalence rate of BD was estimated as 42/10,000 (95% CI, 34–51/10,000) in Istanbul, Turkey. Conclusions This survey conducted in Istanbul, the largest cosmopolitan city in Turkey with immigrants from all over the country, has a larger sample size than other previous studies, and therefore the reported prevalence rate of BD has a more acceptable confidence interval. This study aids in the estimation of the prevalence of BD in Turkey, and supports previous findings that Turkey has the highest prevalence rate of the disease in the world.