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.     

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     

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.     

Guidelines for the treatment of skin and mucosal lesions in Behçet's disease: A secondary publication

In the current study, we present guidelines for the diagnosis and treatment of the mucocutaneous lesions of Behçet's disease, which is a chronic inflammatory disease characterized by the involvement of various organs, including mucocutaneous, ocular, vascular, intestinal and central nervous system lesions. It is often identified in the Middle East Mediterranean to East Asia region. Skin manifestations include erythema nodosum, papulopustular lesions and thrombophlebitis, and mucosal manifestations include oral and genital ulcers. These mucocutaneous lesions are characteristically the first signs of Behçet's disease and are important to be recognized for the early diagnosis of the disease. Moreover, these manifestations also recur and persist over the long-term course of the disease. The management of mucocutaneous lesions is important to prevent recurrence. We developed consensus guidelines that provide recommendations for general practitioners and dermatologists and physicians on the management of the mucocutaneous lesions of Behçet's disease.     

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 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.     

Histopathologic Study of Cutaneous Lesions in Behçet's Syndrome

Light microscopic studies of 55 patients with complete and incomplete types of Behçet's syndrome were reviewed. We reported here 39 skin biopsies from 30 patients with cutaneous lesions of oral, and genital ulcers, folliculitis, erythema multiforme, and thrombophlebitis. Leukocytoclastic vasculitis was seen in 5 of 12 (42%) cases of oral ulcers and 2 of 7 (29%) of genital ones. Lymphocytic vasculitis was demonstrated in 3 of 12 (25%) cases of oral ulcers and 4 of 7 (57%) of genital ulcers. However, the vasculitis was observed only locally in the areas with moderate or severe inflammation. From the biopsy specimens of our cases with fully developed mucocutaneous lesions of Behçet's syndrome, it appears that the forms of vasculitis that are often emphasized in the literature are a phenomenon secondary to the intense inflammation seen in such cutaneous lesions.     

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.     

Colchicine therapy in Behçet's syndrome—a report of five cases

Five patients with Behçet's syndrome of varying duration were treated with colchicine (500 μg b.i.d.). All improved clinically and one has remained clear for 1 year after cessation of therapy, although in one patient who had neurological symptoms, paraesthesiae have persisted throughout treatment.     

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.     

Dapsone in Behçet's disease: a double-blind,placebo-controlled,cross-over study

The study was designed to investigate the effects of dapsone in the treatment of mucocutaneous manifestations of Behçet's disease and the possible prophylactic role of dapsone in a double blind/placebo controlled clinical trial. Twenty patients diagnosed according to the International Study Group criteria as Behçet's disease were included in the study. Patients were randomly allocated to receive either dapsone 100 mg daily or placebo for three months in a double‐blind manner. After three months, patients were crossed over and followed for a further three months. Patients were followed up in each visit by assessing the number, size, duration and frequency of oral and genital ulcers, other cutaneous manifestations, and systemic manifestations of the disease. A pathergy test was done on each visit. Laboratory investigations included hemoglobin concentration, white blood cell count, ESR, and C‐reactive protein. In dapsone‐treated patients, there were significant reductions in the oral and genital ulcer parameters as well as the incidence of other cutanous and systemic manifestations. In the placebo‐treated group, there were no significant changes in these parameters. The pathergy test result as well as those of other laboratory tests were all decreased in the dapsone‐treated group. Although this study was a small scale study, it shows that dapsone was effective in treatment of mucocutaneous manifestations of Behçet's disease and possibly in prophylaxis against systemic manifestations of the disease. This result should lead to a larger scale study with a longer duration of follow‐up.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Entero‐Behçet's disease coexisting with long‐term epilepsy and schizophrenia‐like symptoms

Entero‐Behçet's disease coexisting with long‐term epilepsy and schizophrenia‐like symptoms is presented. A 43‐year‐old woman presented with repeatedly occurring aphthous stomatitis for several years. She had been treated for absence seizures, epilepsy and schizophrenia since she was 9 years old. She presented with multiple aphthous stomatitis on her gingiva, erythema nodosum‐like symptoms on the right lateral aspect of her leg and genital ulcers on her perianal area. She also showed polyarthritis. Laboratory examinations revealed elevated C‐reactive protein, elevated neutrophil counts, decreased serum Fe and elevated serum Cu. Histological examination showed perivascular neutrophil and mononuclear cell infiltrates and eosinophilic change of the vessel wall in the lobules of subcutaneous fat tissue. Six weeks after the oral prednisolone therapy, she showed resolution of aphthous stomatitis, folliculitis‐like eruption and genital ulcer. She experienced severe abdominal pain after the start of treatment of Behçet's disease. Plain computed tomography revealed edematous change in the appendix, and ascending and transverse colon. These results led to the diagnosis of entero‐Behçet's disease acute exaggeration. Treatment with infliximab (300 mg/once) was started. Eight weeks after the start of infliximab, her abdominal pain disappeared and C‐reactive protein decreased, followed by the successful change to adalimumab infusion therapy.