New simple way to use the classification tree for the diagnosis of Behcet's disease

Background: Behcet's Disease (BD) is a vasculitis of unknown origin. It is mainly seen around the Silk Road. The classification tree is the most sensitive and accurate criteria for the classification and diagnosis of the disease. The use of a classification tree necessitates having the diagram in hand. An arithmetic method was developed to replace the diagram by easy‐to‐remember figures. Methods: Each criterion was given an appropriate value: ocular lesions were given 5 points, oral aphthosis 4 points, genital aphthosis 3 points, pathergy phenomenon 2 points, and skin manifestations 1 point. Seven points or higher values were necessary to classify a patient as having Behcet's disease. The arithmetic method was tested in 5276 BD patients and in 2407 control patients. Results: The sensitivity of the classification tree was 97.2%, the specificity was 96.7%, and the accuracy was 97.1%. The arithmetic method gave exactly the same results. Discussion: The arithmetic extrapolation of the classification tree is a new and simple way for the diagnosis and the classification of Behcet's disease.     

Behcet’s disease: from east to west

Behcet's disease (BD) is classified among vasculitides. There are actually five nationwide surveys of BD: Iran, Japan, China, Korea, and Germany. Among case series, four are on more than 200 cases (Turkey, Morocco, Tunisia, and UK). BD was classically seen around the Silk Route. Now, it is seen everywhere. The male to female ratios were, respectively (in nationwide surveys), 1.19, 0.98, 1.34, 0.63, and 1.40 to 1. The mean age at onset was 26.2, 35.7, 33.8, 29, and 26 years. Major manifestations were seen, respectively, in nationwide surveys: mucous membrane (oral aphthosis in 97%, 98%, 98%, 99%, and 98%; genital aphthosis in 65%, 73%, 76%, 83%, and 64%); skin manifestations (pseudo-folliculitis in 57%, N/A, 31%, N/A, and 62%; erythema nodosum in 22%, N/A, 38%, N/A, and 42%; ocular manifestations in 55%, 69%, 35%, 51%, and 53%). Minor manifestations were seen, respectively, in nationwide surveys: joint manifestations in 33%, 57%, 30%, 38%, and 53%; neurological manifestations in 9%, 11%, 6.5%, 4.6%, and 11%; gastrointestinal manifestations in 7%, 15.5%, 9%, 7.3%, and 12%; vascular involvement in 8.9%, 8.9%, 7.7%, 1.8%, and 13%; pulmonary manifestations in 0.3%, N/A, 2.2%, N/A, and 3.6%; cardiac manifestations in 0.5%, N/A, 4%, N/A, and 3.2%. Laboratory tests are not useful except the pathergy test, which was positive in 54%, 44%, N/A, 40%, and 34% of cases. ESR was normal in many patients. Diagnosis is based upon clinical manifestations. The International Criteria for Behcet's Disease (ICBD, 2006) may be of help, having a sensitivity of 98.2% and a specificity of 95.6% in Iranian patients.     

Behcet's disease: global perspective

Behcet's disease (BD) is a vasculitis progressing by attacks and remissions. There are actually four nationwide surveys of BD; Iran (5059 patients), Japan (3316 patients), China (1996 patients), and Germany (590 patients). There are four major case series in the world, Turkey (2147 patients), Korea (1155 patients), Morocco (1034 patients), and UK (419 patients). Other series are based on less than 200 patients.Mucous membrane manifestationsOral aphthosis is seen in 98% of patients (average from the above-mentioned countries). Genital aphthosis occurs less frequently (73%).Skin manifestations are seen in 74% of patients. Behcet's pustulosis (pseudofolliculitis) is seen in 61% of patients in Iran. Erythema nodosum is seen in 22% of patients in Iran. They are more frequent in China and Korea.Ocular manifestations are seen in 51% of patients (anterior uveitis, posterior uveitis retinal vasculitis).Joint manifestations are seen in 39% of patients (arthralgia, monoarthritis, oligo/polyarthritis, ankylosing spondylitis).Neurological manifestations are seen in 7.3% of patients. They are mainly central manifestations due to parenchymal lesions.Gastrointestinal (GI) manifestations are seen in 9% of patients (produced by aphthous ulcers of the intestinal tract).Vascular involvement occurs in 11% of patients. Arterial involvement is rare. In Iran it is seen in 0.6% of patients. Deep vein thrombosis is seen in 6%, large vein thrombosis in 1.2%, and superficial phlebitis in 2.3%.Other lesionsOrchitis and epididymitis were seen in 5.6% of patients in Iran. Cardio-pulmonary manifestations were rare, seen in only 1.4% of patients in Iran.Laboratory findingsErythrocyte sedimentation rate was normal in 43.5% of cases in Iran. Urinary abnormalities were infrequent and transient (9.8% in Iran). Proteinuria was seen in 2%, hematuria in 4.6%, leukocyturia in 5.1%, and cast in 0.3% of cases. Pathergy test was positive in 57.4% and HLA-B51 in 34% of patients.ConclusionBD is a systemic disease with various manifestations. It progresses by attacks and remissions. Lesions usually heal without sequela, except for eyes, brain, and vascular system. The main manifestations are mucocutaneous. The major cause of morbidity is the ocular lesion, which leads to severe loss of vision or blindness.     

Beh?et’s disease in Brazilian patients: demographic and clinical features

The aim of this study was to determine the demographic and clinical characteristics in patients diagnosed with Beh?et’s disease (BD) in Brazil. We performed a retrospective review of all the patients’ records with BD diagnosed from 1988 to 2010 in the Rheumatology Department at the State University of Campinas (UNICAMP). All patients had to fulfill the International Study Group for Beh?et’s disease diagnostic criteria. Eighty-seven patients were included in the study. The female/male ratio was 1.18:1, and the mean age at the onset of the disease onset was 28.03?±?7.57?years. Oral aphthosis was the most frequent manifestation (100%). Genital aphthosis was also frequent (77%), followed by pseudofolliculitis (47.67%). Ocular symptoms were present in 80% and neurological manifestations in 31.03% of the patients. Arthralgia was reported in 31.03% and arthritis in 13.79% of the cases. Vascular involvement was seen in 13.95% of the patients. Only 1.14% had gastrointestinal involvement. This series, from a South American country, showed a similar general pattern of the BD to those found in different endemic areas in the world, with a high frequency of ocular and neurological manifestations.     

Pathergy test in Behcet's disease: change in incidence over the time

Introduction: Pathergy phenomenon (PP) is used as a criterion in many diagnostic criteria for Behcet's disease (BD): Curth, Japan, Hubault and Hamza, Cheng and Zhang, Dilsen, International Study Group, Iran criteria (traditional format and the Classification Tree), Korea criteria, and the new International Criteria. PP is rather specific to BD. It has been reported with high frequency from most countries along the Silk Road, but with much lower frequency from other countries (UK, US). The incidence of PP has been reported from some countries (Japan, Turkey) to decrease gradually. The aim of this study was to test the above hypothesis in a large cohort of patients in Iran. Materials: Patients (6057) were divided into several groups by two methods. Method 1: patients were divided into six groups according to the time of their first visit. Method 2: patients were divided into four groups according to the date of the beginning of their first manifestation. Results: In method 1, the percentage of PP was 71.8% from patients 1–1000. The percentage became 55.9% from patients 1001–2000, 57.6% from patients 2001–3000, 58.8% from patients 3001–4000, 45.3% from patients 4001–5000, and 33.9% from patients 5001–6000. In method 2, the percentage of PP was 61.5% for patients with their disease onset before 1977. The percentage was 59.9% for patients with their disease starting between 1978 and 1987. The percentage dropped to 52.1% for patients with disease onset between 1988 and 1997. The percentage finally dropped to 41% for patients having their disease onset between 1998 and 2007. Conclusion: The incidence of PP is decreasing gradually. It is now 34%, which is rather low for a criterion used in many diagnosis criteria. It is important to find a surrogate for it because with the decrease in the incidence of PP the sensitivity of the diagnosis criteria will drop significantly.     

New and innovative therapies for Behcet's disease

Background: Behcet's disease (BD) is a vasculitis progressing by attacks and remissions. Not all patients will respond even to the classical treatments. New treatments are emerging with the hope to overcome this failure. Biologic agents: Interferon‐α (IFN‐α), anti‐tumour necrosis factor‐α (TNF‐α), and tolerization have been used in BD. IFN‐α is mainly used for ocular manifestations of BD. The result seems impressive, 92% of cases had good or excellent results. It was less impressive for mucocutaneous and joint manifestations. The dosage is 6–9 million IU/day for 4 weeks, then 4.5 million daily for 4 weeks, and then 3 million/day. The maintenance dose is 3 millions, three times/week, to continue for 8 weeks after complete remission. Etanercept (anti‐TNF‐α) was effective in mucocutaneous lesions of BD at the dosage of 25 mg twice weekly for 3 months (double‐blind control study). Attacks relapsed after discontinuation. Etanercept was ineffective in ocular lesions (open study). Infliximab (anti‐TNF‐α) was very effective in many studies of ocular lesions. It dramatically suppressed the inflammatory attack. The dosage is one injection of 5 mg/kg (intravenous infusion) at weeks 0, 2, 6, and then every 8 weeks. Tolerization with oral administration of HSP peptide 336–351 seems to protect from uveitis relapse. Pentoxifylline is not particularly effective unless for oral aphthae (50% response rate). Pimecrolimus ointment may be of help in resistant genital aphthosis, reducing the healing time.     

Epidemiology and clinical characteristics of behçet's disease in the US: A population‐based study

Objective

Behçet's disease (BD) is a rare, multisystem inflammatory disorder of unknown cause. Although well‐documented in Eastern populations, epidemiologic data is scarce in North American countries. Here we describe the incidence and prevalence of BD in Olmsted County, Minnesota over 45 years.

Methods

We identified an incidence cohort of subjects age ≥18 years who had a clinical diagnosis of and/or fulfilled the International Study Group (ISG) criteria for BD from January 1, 1960 to January 1, 2005. Age‐ and sex‐specific incidence and prevalence were estimated and age‐ and sex‐adjusted to the 2000 US total population.

Results

The study population was comprised of 13 subjects with BD; 11 fulfilled ISG criteria between 1960 and 2005. Mean ± SD age was 31 ± 9 years, and 69% were white. Point prevalence in 2000 was 5.2 per 100,000 population (95% confidence interval [95% CI] 0.64–9.84). The overall annual age‐ and sex‐adjusted incidence of BD was 0.38 per 100,000 population (95% CI 0.17–0.59), with a higher incidence in women (0.51 per 100,000; 95% CI 0.17–0.84) than in men (0.26 per 100,000; 95% CI 0.004–0.52). Dermatologic lesions included oral ulcers (100%), genital ulcers (62%), erythema nodosum (46%), and papulopustular lesions (54%). Ocular lesions, vascular complications, and central nervous system involvement were present in 8, 3, and 3 subjects, respectively.

Conclusion

Our study shows an overall incidence of 0.38 per 100,000 population, which is comparable with other Western populations. The prevalence of 5.2 per 100,000 population is similar to estimates reported in Western countries, but lower than that in countries along the Silk Road.     

Prevalence of Behcet's disease in Iran: a WHO‐ILAR COPCORD stage I study

Aim: To elucidate the prevalence of Behcet's disease (BD) during the World Health Organization‐International League of Associations for Rheumatology Community Oriented Program for Control of Rheumatic Disease study in Iran. The old estimate was 16 per 100,000 inhabitants, but this was just an estimation and a more precise figure was required. Materials and methods: Tehran, the capital of Iran with 1/10th of Iran's population, was selected as the field for the COPCORD study. The population of Iran is of mixed ethnicity (Caucasians 75.4%, Turks 22%, and Semites 2.6%). The same distribution was found in Tehran's general population. Tehran has 22 districts; 50 clusters were randomly selected from them. Interviewers passed an exam by interviewing 20 subjects. The observed agreement was 0.96. The chance expected agreement was 0.531325. The kappa coefficient was 0.919 (standard error: 0.112). The z‐score was 8.19. The one tailed P‐value was < 0.0001. Rheumatologists were selected from the ‘Rheumatology Subspecialty’, that is, those who were scheduled to become a rheumatology professor in one of Iran's medical schools. Results: The response rate was 75%. From 10,291 subjects interviewed all subjects with positive questionnaires were examined; seven had definitive BD and five probable BD. The prevalence was calculated on the seven definitive cases. It was 68 for 100,000 inhabitants. The confidence interval was 33.5–137. Four patients were female and three were male. All had oral and genital aphthosis, four had ocular lesions, three had pseudo‐folliculitis, and one had joint manifestations. Conclusions: The prevalence of BD in Iran is 68 per 100,000 inhabitants, which is the second highest prevalence after Turkey (80–370) in the world, and far behind comes Saudi Arabia with 20, China 14, and Japan 13.4 per 100,000 inhabitants.     

Behcet's disease in Iran: analysis of 6500 cases

Objective: To identify the clinical picture of Behcet’s disease in a large cohort of patients (6500) in Iran, over a period of 35 years, and compare them with other large series from around the world. Methods: Patients with Behcet’s disease from all over Iran were seen in the Behcet’s Disease Research Unit by a multidisciplinary team (rheumatologists, dermatologists, and ophthalmologists). Diagnosis was based on ‘expert opinion’. Data were collected on a standardized data sheet (105 items), and stored in an electronic database. Data were updated at each follow‐up. Results: Male to female ratio was 1.22 : 1.00. The mean age at onset was 26 years ± 11.3. The frequency of symptoms were: oral aphthosis 97.3%, genital aphthosis 64.6%, skin manifestations 64.9% (pseudofolliculitis 54.5%, erythema nodosum 22.5%, other lesions 7%), pathergy phenomenon 52.5%, ophthalmologic manifes‐tations 56.8% (anterior uveitis 41.2%, posterior uveitis 44.9%, retinal vasculitis 32.1%), joint manifestations 37.4% (arthralgia 17.2%, monoarticular arthritis 7.6%, oligoarthritis 16.8%, ankylosing spondylitis 2%), neurological manifestations 3.8% (central manifestations 3.5%, mononeuritis multiplex 0.3%), gastrointestinal manifestations 7.4%, vascular involvement 8.3% (phlebitis 5.7%, superficial phlebitis 2.2%, large vein thrombosis 1.1%, arterial thrombosis 0.154%, aneurysm 0.5%), epididymitis 4.7%, cardiac involvement 0.6%, and pulmonary involvement 0.9%. Sedimentation rate was normal in 46.5% of patients. Abnormal urine sediment was detected in 12.2%. HLA‐B5 was present in 53.3% and HLA‐B51 in 47.9% of patients. Conclusion: Behcet’s disease is mainly seen in young people. The most frequent symptoms are mucocutaneous, ocular and joint manifestations. Comparison with large series did not show major differences.     

Faraway from the Silk Route: demographic and clinical features of Beh?et’s disease in 106 Brazilian patients

To describe clinical and epidemiological data of Behçet’s disease (BD) in Brazil, we retrospectively reviewed records of all patients seen between 2006 and 2007 at the BD outpatient clinic of University of Sao Paulo. One hundred and six patients fulfilled the International Study Group for Behçet’s Disease diagnostic criteria and they were included in this study. There was a female/male ratio of 2.2:1 and mean age at diagnosis was 31.9?±?9.2 years. In order of frequency, oral (100%) and genital ulcerations (92.5%), pseudofolliculitis (59.4%), erythema nodosum (49.1%), ocular lesions (47.2%), and musculoskeletal complaints (35.8%) were the most common manifestations. Blindness and major vessel involvement (18.2% vs. 5.5%, p?=?0.038 and 27.3% vs. 9.6%, p?=?0.019) were more frequent among male than female patients. We concluded that in Brazil, a South American country faraway from the Silk Route, BD follows the same pattern exhibited on its usual endemic area.     

Diagnostic value of pathergy test in Behcet’s disease according to the change of incidence over the time

Pathergy test (PT) is used for the diagnosis of Behcet’s disease (BD). It is a criterion in many classification/diagnosis criteria. PT is mainly seen in BD but can be seen in other conditions too. PT has been reported with high frequency from most countries along the Silk Road. The sensitivity of pathergy phenomenon (PP) is declining over the time. The aim of this study was to look for the diagnostic value of PT in the past and at the present time. The BD registry (Rheumatology Research Center, Tehran University of Medical Sciences) has the data of 6,607 BD and 4,292 control patients. Patients and controls were divided in four groups of 1,650 BD and 1,073 controls. Sensitivity, specificity, positive and negative predictive value (PPV-NPV), positive and negative likelihood ratio (PLR-NLR), diagnostic odds ratio (DOR), and Youden’s index (YI) were calculated for each group. The first and the fourth quartiles were compared. Sensitivity of PT decreased from 64.2% (first quartile) to 35.8% (fourth quartile). Specificity improved from 86.6% to 98.4%. PPV improved from 82.7% to 95.7%. NPV decreased from 82.7% to 60.5%. PLR improved from 4.8 to 22.4, while NLR deteriorated from 0.41 to 0.65. DOR improved from 11.6 to 34.3. Yuden’s index worsened from 0.5 to 0.34. Although sensitivity of PP decreased, the increase of specificity is a plus value for diagnosis. As a result, PPV, PLR, and DOR improved, while NPR, NLR, and YI deteriorated. Although the pathergy test lost its sensitivity during the past 35 years, it has not lost its value as a diagnostic test, improving many of its characteristics. In a practical view, the chances of getting a positive test have decreased over the time. However, a positive test is rather the synonym of Behcet’s disease, with a probability of 98.4%.     

Development of an Arabic version of the Behçet’s Disease Current Activity Form (Ar-BDCAF): cross-cultural adaptation and validation initiative in Egypt

Clinical Rheumatology - Behçet’s disease (BD), commonly seen in the Silk road countries, is a variable vessel vasculitis with no specific investigation that reflects disease activity....     

Thromboses artérielles multiples au cours de la maladie de Behçet

Behcet's disease (BD) is a multisystemic vasculitis. Its etiopathogeny remains unknown. Vascular involvement in BD is frequent and venous thrombosis is the most common manifestation (30 % of cases). Arterial involvement is rare (2.7 to 7 %). The latter is often severe and considered as a life threatening complication. Pathogenesis of thrombosis occurring in BD remains unclear. We report a 45-year-old man, from south of Tunisia, who presented a BD with a bifocal arterial involvement: right internal carotid thrombosis and bilateral proximal thrombosis of the two pulmonary arteries. Therapeutic strategies to address this multiple arterial involvement and the pathogenesis of thrombosis raise many questions.     

Fever revealing Behçet's disease: Two new cases

Behçet's disease (BD) is an uncommon cause of fever of unknown origin. We report two cases, both involving 42-year-old males, who initially presented with prolonged fever and who were ultimately diagnosed as having BD after a delay of 12 and 21 months, respectively. Both patients developed pulmonary aneurysms. Although fevers resolved after therapy, both patients died within the first year after diagnosis. Clinicians should be aware that long-term fever may be an inaugural sign of BD, especially in individuals living in countries along the ancient Silk Road or Mediterranean basin.     

Update on the epidemiology,risk factors and disease outcomes of Behçet's disease

Behçet's disease (BD) may be regarded as a polygenic autoinflammatory disease although adaptive immune system has also been implicated in pathogenesis. Different classification criteria sets exist for BD, including the new “International Criteria for BD.” The pooled prevalence of BD was calculated as 10.3 per 100,000 population globally. BD is common along the Silk Road, including Turkey. Male sex and early onset are associated with a more severe disease course. For the follow-up of BD, there are five disease activity scales, one disease severity scale, and one QOL scale.     

Adalimumab for the treatment of Behcet's disease: experience in 19 patients

Objective. To describe the experience of two tertiary Spanish centres (Hospital Clínico San Cecilio, Granada and Hospital Clínic, Barcelona) with the use of adalimumab for the treatment of severe clinical manifestations in patients with Beh?et's disease (BD) in whom immunosuppressive therapy had failed. Methods. Retrospective chart review from patients with BD treated with adalimumab in two specialized Spanish centres (Hospital Clínico San Cecilio, Granada and Hospital Clínic, Barcelona). Results. From November 2006 to February 2011, 19 patients with BD were treated with adalimumab. The reason to initiate adalimumab was refractory disease in 17 (89.5%) patients and adverse events to CSA and infliximab in two (10.5%) patients, respectively. The main clinical manifestations leading to adalimumab administration were panuveitis in eight patients, severe bipolar aphthosis in eight, retinal vasculitis in three and severe folliculitis in three. Overall, adalimumab achieved clinical improvement in 17 of the 19 patients. Of note, ocular manifestations (panuveitis and retinal vasculitis) responded rapidly in all cases. In addition to clinical improvement, treatment with adalimumab was associated with reduction in the number and dose of standard immunosuppressive agents. Of interest, seven patients had received TNF-α inhibitors before adalimumab, five infliximab and the remaining two etanercept. Adalimumab was withdrawn in only one patient due to severe infusional reaction in the form of urticaria and angioedema. Conclusion. Adalimumab is a valid option for patients with BD and recalcitrant non-controlling manifestations with good safety profile.     

Familial Behçet’s disease

Behçet’s disease (BD) is a multisystemic vasculitis syndrome characterized by a course of remissions and exacerbations of unpredictable frequency and duration. The disease has a worldwide distribution, but the majority of cases cluster along the ancient Silk Road, which extends from eastern Asia to the Mediterranean basin. The etiopathogenesis of BD is still unknown, but familial aggregation and peculiar geographical distribution have been regarded as evidence supporting genetic influence on the pathogenesis of BD. In this article, we describe a patient with BD, who had four members of his family associated with BD.     

CNS involvement occurs more frequently in patients with Behçet's disease under cyclosporin A (CSA) than under other medications—results of a retrospective analysis of 117 cases

The aim of this study was to evaluate the incidence of neurological manifestations of Behçet's disease (BD) in patients on cyclosporin A (CSA) compared with those on other medications. The records of 117 patients with BD who visited our hospital between 1990 and 2003 were reviewed with respect to symptoms and medication. All episodes of constant therapy prior to central nervous system (CNS) involvement were counted, and then the associations were analysed by the exact Fisher–Freeman–Halton test and adjusted for multiple tests by the Bonferroni–Holm method. We observed ten new cases of CNS manifestations in our patients with BD being regularly seen and treated in our tertiary care centre. The overall prevalence of neuro-BD in our patient group was 8.5%. In a retrospective analysis, the incidence of new-onset neurological disease (neuro-BD) in all patients with BD who regularly visited our hospital was significantly higher in patients on CSA than in those on other medications (6 of 21 vs 0 of 175 episodes, P<0.0001). This contrasts the obvious efficacy of CSA on extracerebral manifestations of BD, such as severe ocular disease, mucocutaneous lesions or arthritis. CSA exerts differential efficacy on various manifestations of BD. It is very effective for severe ocular and other moderate to severe manifestations of BD, but its efficacy for the prevention of neuro-BD seems to be inferior to that of other medications used in BD, such as azathioprine or interferon-α. The reasons for this are unclear, but the potential toxic effects of CSA on the CNS may be a predisposing factor for CNS vasculitis in BD.     

Behçet's disease in Israel: the influence of ethnic origin on disease expression and severity

OBJECTIVE: To evaluate the relationship between ethnic origin and manifestations of Beh?et's disease (BD) in Israel. METHODS: We studied 100 Israeli patients with BD, 66 Jews and 34 Arabs. The 3 largest ethnic groups of Jewish patients originated from Iran/Iraq (n = 21), Turkey (n = 12), and North African countries (n = 21). Patients were evaluated with respect to the entire spectrum of disease manifestations, and a systemic severity score for BD was calculated for each patient. Disease expression was compared between Jewish and Arab patients and among Jewish ethnic groups. RESULTS: There were no statistically significant differences between Jewish and Arab patients with respect to male:female ratio, prevalence of HLA-B5, age of disease onset, or disease duration. Disease expression and severity score were also similar in the 2 groups, but Arab patients had a higher rate of posterior uveitis (20.6 vs 4.6%; p < 0.03). Among the 3 largest Jewish ethnic groups, patients of North African origin had a significantly higher rate of ocular disease (p < 0.01), mainly in the form of anterior uveitis (p < 0.01). These patients also had higher rates of arthritis, overall vascular disease, deep vein thrombosis, and neuro-Beh?et without reaching statistical significance. The disease severity score in this group was significantly higher compared to the other Jewish ethnic groups (p < 0.02). CONCLUSION: The expression of BD is similar in Israeli Jewish and Arab patients but the latter have more severe eye disease. The disease in Israeli Jewish patients is most severe in those originating from North African countries.