Clinical features of late-onset Behçet's disease: report of nine cases

Background Behçet's disease (BD) is usually diagnosed between the second and fourth decades. Onset after 50 years of age is extremely rare. We aimed to analyze the clinical features of late‐onset patients with BD. Method The study was conducted from 439 patients diagnosed as BD according to criteria of the International Study Group for BD. Clinical features of patients who were asymptomatic or suffered from only recurrent aphthous stomatitis (RAS) until 50 years of age but fulfilled the diagnostic criteria of BD after this age were reviewed. Results The age‐of‐onset was more than 50 years in nine patients (1.56%). Two patients developed erythema nodosum, two developed pathergy positivity, one developed papulopustules, pathergy positivity and ocular symptoms, one developed papulopustules and pathergy positivity, one developed ocular symptoms, one developed papulopustules and ocular symptoms, and one developed erythema nodosum and pathergy positivity as well as oral aphthae and genital ulcerations after the age of 50 years. The neurologic system was involved in two patients. Mucocutaneous symptoms of two patients worsened after interruption of therapy. Two patients with neurologic and ocular involvement flared during the follow up. Conclusion Since the course of the disease is regarded to be relatively mild in mature patients, it is noteworthy that systemic manifestations such as ocular and neurologic involvement and acute flares developed after the age of 50 years in the limited number of patients with late‐onset BD in our series.     

Clinical features of Behçet's disease in children

Background Behçet's disease (BD) is a systemic inflammatory vasculitis of young adults with unknown etiology. Objective The aim of this study was to determine the clinical features and outcome of BD in childhood. Patients and methods Seventeen patients with BD within a pediatric age group were studied since 1997. Results Boys : girls ratio was 12:5. Familial cases were very frequent (45%). Oral aphthous ulcers were present in all patients (100%), genital aphthous ulcers were present in 16 (94%), ocular lesions in 4 (24%), erythema nodosum in 3 (18%), papulopustules in 8 (47%), joint symptoms in 13 (76%), mild gastrointestinal symptoms in 2 (12%), neurological involvement in 2 (12%), positive pathergy reactions in 13 (76%), and thrombophlebitis in 1 (6%). We used colchicine, systemic corticosteroids, cyclosporine, nonsteroidal anti‐inflammatory drugs, sulfasalazine, and topical agents for the treatment of children with BD. Conclusion The findings of BD in children are similar as in adults, but the frequency of familial cases is significantly higher.     

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.     

Vitiligo Koebnerized by Behçet Disease Genital Ulceration

A 50-year-old man was diagnosed with Behçet disease (BD) on the basis of an 8-year history of episodes of recurrent oral aphthous ulcers, papulopustular lesions on physical examination, and a positive pathergy test. Two years prior to diagnosis of BD, vitiligo had also been diagnosed on the basis of hypopigmented lesions on the scrotum following genital ulceration. To our knowledge, this is the first case of incidental coexistence of BD and vitiligo, and, furthermore, the first case of koebnerization of genital ulceration of BD.     

间接免疫荧光检查对白塞病的临床意义

根据白塞病(BD)国际分类标准,确诊为本病的35例作为研究组,取其口腔、生殖器、皮肤和血管病损组织进行荧光检测。选用复发性阿夫他口炎(RAS)20例作为对照组。结果显示:BD88.6%患者血清中可检测出口腔粘膜的自身抗体,85.7%患者血清中可检测出病损皮肤、血管组织的自身抗体,75%患者血清中可检测出生殖器溃疡部位的自身抗体,前者与RAS比较,P<0.01。由于检测方法不同,本文用间接荧光法阳性结果较高。故用本法检测无疑对BD诊断有一定临床价值。     

Current therapy in Behcet's disease

Beh?et's disease is an inflammatory disorder of unknown cause. There is often involvement of the gastrointestinal system, the central nervous system and large vessels, which can be life-threatening. As well, ocular lesions can cause blindness. Mucocutaneous symptoms are self-limiting but more frequent. Almost all the patients have recurrent oral aphthous ulcers, and more than 70% of the patients have genital ulcers and skin symptoms, which include erythema nodosum, pseudofolliculitis, papulopustular lesions, acneiform nodules and a positive pathergy test. The pathergy test is felt to reflect cutaneous hypersensitivity. In general, topical treatment using corticosteroids is satisfactory for these mucocutaneous lesions unless eye and vital organs are involved.     

The spectrum of mucocutaneous manifestations in Adamantiades‐Behçet’s disease in Greece

Background This is the largest specific demographic and clinical study performed until now in Greece. Objectives To analyse the spectrum of mucocutaneous manifestations in 202 patients with Adamantiades‐Behçet’s disease (ABD) in Greece. Methods Any mucocutaneous symptom at disease onset and during the follow‐up was recorded in a particular questionnaire that included 58 items. All patients fulfilled the International Study Group Criteria for BD. Results Consecutive patients (130 men and 72 women) were included in this study. Their mean age was 42.03 ± 12.41 and 44.96 ± 11.99 years for male and female patients respectively. Pathergy test was positive in 38%, whereas HLA‐B5 (51) positivity was evident in 76% of patients. Onset signs: oral aphthous ulcers were found in 64.36%, genital ulcers in 6.93%, skin lesions in 8.91%, erythema nodosum in 7.42% and pseudofolliculitis in 1.5%. One patient had leg ulcers. During the follow‐up, oral aphthous ulcers were found in 100%, genital ulcers in 65.4% and in 51.4%, erythema nodosum in 42.9% and in 78.1%, whereas pseudofolliculitis in 57.1% and in 21.9% in men and women respectively. Significant differences pointing to a different course of mucocutaneous disease were found between men and women. Conclusions The nature and frequency of mucocutaneous manifestations at presentation are important for the diagnosis of ABD, whereas significant differences were found between genders in this Greek patient cohort. Significant differences were also observed when our results were compared with those of four other series, probably explained by genetic and environmental factors.     

Chromosome and sister chromatid exchange studies in Behcet's patients

Behcet's disease is a chronic multisystemic disease of unknown pathogenesis characterized by four major symptoms: oral aphthous ulcers, skin lesions, ocular symptoms and genital ulcerations. The disease is spread throughout the world, but it is most frequent in Turkey, Japan, Korea and China. Although HLA-Bw51 has been found to predominate in Behcet's cases, the genetic etiology has not yet been clarified. In this study, we investigated the chromosomal abnormalities and sister chromatid exchange rates in patients with Behcet's diseases. Thirty-eight patients with Behcet's disease (diagnosed for the first time) and 30 healthy subjects (as controls) were included in this study. Although numerical and structural chromosomal abnormalities were not detected in our patients, we found an increased rate of sister chromatid exchange in patients over the control groups (P < 0.01). On the basis of these results, we discuss the genetic etiology of Behcet's disease.     

Clinical features and natural course of Behçet's disease in 661 cases: a multicentre study

Background Behçet’s disease (BD) is a systemic inflammatory disease with unpredictable exacerbations and remissions. The natural course of BD is not fully known. Objectives We aimed retrospectively to determine the occurrence of the symptoms in chronological order. We also evaluated the influence of the treatment and follow‐up on the clinical severity and tried to identify the factors determining severe organ involvement. Methods Six hundred and sixty‐one patients were involved in this multicentre study. The symptoms of the disease were recorded retrospectively in the time order of the manifestations in each patient. Results Oral ulcers were the most common manifestation (100%), followed by genital ulcers (85·3%), papulopustular lesions (55·4%), erythema nodosum (44·2%), skin pathergy reaction (37·8%), and articular (33·4%) and ocular involvement (29·2%). Oral ulcers were the most common onset manifestation (88·7%). The mean ± SD duration between the onset symptom and the fulfilment of diagnostic criteria was calculated to be 4·3 ± 5·7 years. The clinical severity score was significantly increased in the noncompliant treatment group compared with the compliant group with the passage of time (P < 0·001). The frequency of ocular involvement and genital ulcers was significantly higher in patients whose disease onset was at < 40 years. Genital ulcers, ocular involvement, papulopustular lesions, thrombophlebitis and skin pathergy reaction were found to be significantly more frequent in males. Conclusions Mucocutaneous lesions are the hallmarks of the disease, and especially oral ulcers precede other manifestations. The increase in clinical severity score is more pronounced in patients without regular treatment and follow‐up. Male sex and a younger age at onset are associated with more severe disease.     

Direct immunofluorescence in recurrent aphthous ulcers and Beh?et's disease

Direct immunofluorescence (IF) investigations in oral aphthae were performed in 17 patients with recurrent aphthous ulcers (RAU) and in 9 patients with Beh?et's disease (BD). In addition, cutaneous hyperreactivity lesions from 2 BD patients were examined. The results were compared to direct IF findings in 28 patients with nonaphthous oral diseases. There was no difference between direct IF on oral aphthae in RAU compared to BD. Deposition of C3 in vessel walls of the subepithelial connective tissue was observed in 13 of 17 patients with RAU and in all patients with BD. IgM deposits in vessel walls were found in 5 RAU and 3 BD patients. Deposition of C1q or C4 was not present. By contrast, IgG and/or IgM, C1q, C3 and C4 were detected in dermal vessel walls of skin hyperreactivity lesions from 2 BD patients. This finding is considered to be a true immune complex vasculitis. Compared to nonaphthous oral lesions, oral aphthae of BD and RAU were characterized by C3 deposition in the subepithelial vessel walls.     

Immunopathogenic characterization of cutaneous inflammation in Behçet’s disease

Background Behçet’s disease (BD) is a recurrent multisystemic inflammatory disease characterized by recurrent oral aphthous and genital ulcers, ocular lesions and cutaneous lesions. Although many studies of cytokine levels in sera of BD patients have been conducted, there are only limited number of studies about the cytokine expression and cellular infiltration in the BD‐related skin lesions. Objectives To investigate the immunophenotypes and cytokine profiles of BD‐related skin lesions. Methods Twenty patients who fulfilled the diagnostic criteria for BD with BD‐related skin lesions were enrolled in this study. We assessed the histopathological features of BD‐related skin lesions by immunohistochemical studies with anti‐human CD4, CD8, CD68, FoxP3, CD‐11b, IFN‐γ and IL‐4 antibodies. Results Immunophenotyping of inflammatory infiltrating cells showed that CD68+ macrophages were the most common type of infiltrated cells in erythema nodosum‐like lesions, erythema multiforme‐like lesions and Sweet’s syndrome‐like lesions, whereas neutrophils were the main population of inflammatory infiltrating cells in papulopustular lesions. In all of the four types of BD‐related skin lesions, the percentage of CD8+ T cells was higher than that of CD4+ T cells (P < 0.05), and IL‐4 expression was stronger than IFN‐γ expression (P < 0.05). Conclusion In this study, we assessed the infiltrating inflammatory cells and cytokine expression of acute cutaneous lesions in BD through immunohistochemical staining of BD‐related skin lesions. Further studies about the disease activity and the molecular biology underlying the cutaneous inflammation are needed to understand the detailed pathogenesis of BD.     

Recurrent aphthous ulceration: an epidemiological study of etiological factors,treatment and differential diagnosis

Background:Recurrent aphthous ulcerations are common benign ulcerated lesions on the mouth, whose etiology is poorly understood, with controversial treatment and difficult to control in clinical practice.Objective:To evaluate the cases of recurrent aphthous ulcerations with a focus on treatment, diagnosis and etiology.Methods:This is a retrospective study of the cases of the Oral Diagnosis service of the Rio Grande do Norte Federal University in Natal/RN. Data such as sex, age, race, location, smoking habits, types of treatment, relapsing episodes, laboratory test results and clinical characteristics were collected. The associations between the variables were analyzed using the Pearson Chi-square test (p <0.05).Results:A total of 4895 patients were seen in the service over a period of 11 years. Of these, 161 (3.3%) had complaints of oral aphthous ulcerations, of which 76 (47.2%) were diagnosed as suffering from recurrent aphthous ulcerations and 68 (42.2%) with clinical information necessary for evaluation. The tongue was the most affected anatomical region, with 27 individuals (39.7%), followed by the buccal mucosa, with 22 cases (32.3%).Study limitations:Retrospective study with data from medical records.Conclusion:Dental surgeons, dermatologists and otorhinolaryngologists are the main responsible for the first contact with patients with this disease and should be attentive to the clinical aspects and treat each patient in an individualized way, since the therapy is palliative, its diagnosis is by exclusion and its etiology is unknown.     

Serum lipoprotein (a) levels and Behçet's disease: is there an association?

Background Behçet's disease (BD) is a multisystemic inflammatory disorder found in individuals with a particular genetic background. Hemostatic studies in BD support an imbalance towards a prothrombotic state at different levels. Lipoprotein (a) (Lp(a)) has atherogenic and thrombogenic properties. It is mostly under genetic regulation. We investigated the possible relationship between Lp(a) and BD. Methods Forty patients diagnosed with BD and 40 healthy controls were enrolled. The clinical characteristics of the patients were recorded. Serum total cholesterol, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), apolipoprotein A1, apolipoprotein B, and Lp(a) levels of the two groups were assessed and compared statistically. Results All patients (100%) had oral aphthous ulcers. Thirty (75%) had genital ulceration, 37 (92.5%) had either erythema nodosum or papulopustular lesions, and 10 (25%) had eye involvement. Twelve (30%) had a positive pathergy test. Four (10%) had vascular involvement. The Lp(a) level of the patient population was 19.6 ± 18.8 mg/dL. This level was higher than that of the controls, but not statistically significant. The Lp(a) levels of the four patients with vascular complications were within normal limits. Conclusions Lp(a) is of interest, as it is a genetically determined parameter that was found to be high in BD patients in our study group. The levels were independent of thrombotic complications, perhaps suggesting a different role for this lipoprotein in the etiopathogenesis of BD. Further studies with a larger number of patients are essential to discover the exact role of Lp(a) in BD.     

Erythema nodosum induced by the synergism of acupuncture therapy and flu-like infection

A 32-year-old female patient developed erythema nodosum-like lesions at needle prick sites after acupuncture therapy. Over the next few days, she developed similar new lesions over the extremities, trunk and face along with flu-like symptoms. There were neither genital ulcerations nor eye lesions. A skin biopsy specimen from an extremity lesion showed the characteristic findings of erythema nodosum. Treatment with oral potassium iodide at a dose of 750 mg/day was effective, and there has not been any recurrence to date. We diagnosed this case as erythema nodosum induced by a synergism between acupuncture therapy and a flu-like infection.     

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.     

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.     

Prognosis and Clinical Relevance of Recurrent Oral Ulceration in Behçet's Disease

There is no way of predicting whether a patient with recurrent oral ulcerations (ROU) will develop Behçet's disease (BD). In the absence of a valid laboratory test to exclude BD, such oral ulcerations result in a diagnostic problem when they occur as the sole and earliest manifestation of disease. We assessed the prognosis of ROU by performing prospective evaluations of 67 patients who had only a history of ROU and were registered at the Behçet's Disease Specialty Clinic at Severance Hospital of Yonsei University, Seoul, Korea. Thirty-five patients (52.2%) developed overt manifestations of BD at an average of 7.7 years after the onset of ROU. The frequency of recurrence was 9.8 times per year in progressive cases. From these results, it appears that highly recurrent ROU is a warning signal for BD. Careful examinations of patients, including their minor symptoms, additional laboratory tests, and regular follow-ups by physicians are required for proper diagnosis.     

Combination therapy with infliximab and methotrexate in recalcitrant mucocutaneous Behçet disease

Beh?et disease is a multisystem inflammatory disease with features of vasculitis. It undergoes periods of spontaneous remission and relapse. It often affects the skin, blood vessels, central nervous system, joints, gastrointestinal system, eyes, mucous membrane, and other systems, and it can cause substantial morbidity and mortality. The etiology of Beh?et disease remains unknown. Current treatment of Beh?et disease involves symptomatic relief with prevention of relapse. We describe the treatment of a recalcitrant case of Beh?et disease with infliximab and methotrexate. The patient is a 40-year-old Korean woman with tender lesions on the lower extremities of 1.5 years' duration and intermittent oral and genital ulcerations that failed multiple conventional therapies. The patient was placed on a trial of infliximab. She reported resolution of the tender lower extremity lesions and the oral and vaginal ulcerations shortly after the initiation of the anti-tumor necrosis factor agent. The patient was symptom free for 2 years following the initiation of infliximab. She subsequently reported mild breakthrough oral ulcers and joint pain. The treatment regimen was modified by adding methotrexate 7.5 mg weekly, prednisone 5 mg daily, and a shortened treatment interval of infliximab infusion that resulted in resolution of her symptoms.     

白塞病42例临床分析

目的：探讨白塞病（BD）的临床特点。方法：回顺性分析42例BD患者的临床及实验室资料。结果：BD好发于青壮年，多慢性起病，可累及多个器官系统，各受累部位的频率依次为：口腔42例（100％），生殖器29例（69．0％），皮肤28例（66．7％），关节18例（42．9％），眼18例（42．9％），神经系统6例（14．3％），消化道4例（9．5％），大血管3例（7．1％），呼吸系统2例（4．8％），肾脏1例（2．4％），心脏1例（2．4％）。针刺反应阳性32例（76．2％）。皮肤组织活检12例，病理改变均符合皮肤血管炎。随访发现5例死亡个案中2例为BD肠病，1例为BD肺病，1例为BD脑病。结论：BD是一种以血管炎为基础的可累积全身多器官系统的免疫性疾病，重要脏器受累预后不良。皮质类固醇激素或联合应用免疫抑制剂有较好的临床疗效，但亦带来一定的副作用。     

HLA-B51与白塞病相关性研究

目的 探讨HLA-B51等位基因和白塞病的相关性。方法 应用PCR-SSP（序列特异性引物）技术对61例中国汉族白塞病患者及100例正常人对照的HLA-B5101 ～ HLA-B5109等位基因进行检测。结果 与对照组（11例阳性,11%）相比,白塞病组HLA-B51频率（18例阳性,29.5%）明显增高（χ2 = 8.79,P < 0.01,RR = 3.39）,且白塞病组与对照组中HLA-B51阳性者均为HLA-B5101等位基因。HLA-B51阳性者中男15例,女3例,HLA-B51阴性者中男22例,女21例,两组男女比例差异有统计学意义（P < 0.05）;HLA-B51阳性者平均发病年龄为（28.4 ± 10）岁,HLA-B51阴性者（37.3 ± 12）岁,二者间差异亦有统计学意义（P < 0.05）。在其他各临床表现中,包括类型、病程、皮损、生殖器溃疡、眼部损害、针刺反应、关节受累及皮损类型等均未见到二者差异有统计学意义。结论 HLA-B5101等位基因与中国汉族白塞病发病相关,并与患者性别及发病年龄有明显相关性。