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Behcet's disease: evaluation of a new instrument to measure clinical activity
Abstract
Objective. Behcet's disease (BD) is a rare multisystem disorder characterized by vasculitis. At present, there are no laboratory markers that correlate well with the clinical activity in BD. This has led to the development of an instrument (BD Current Activity Form) to measure activity. Scoring is based on the history of new clinical features present over the preceding 4 weeks prior to assessment. Standardized questions were developed for all parts of the form. The face validity of the proforma was determined following worldwide collaboration with physicians and ophthalmologists managing patients with BD. The aim of this study was to evaluate the interobserver reliability of this form. Methods. Nineteen patients fulfilling the International Study Group criteria for BD were randomly allocated, questioned and examined independently on the same day by five physicians experienced in BD. Results. There was good agreement between the physicians' rating of oral [intraclass correlation coefficient (ICC) = 0.87] and genital (ICC = 0.95) ulceration, skin involvement (ICC = 0.62 for pustules and ICC = 0.66 for erythema nodosum), arthritis (ICC = 0.62), headache (ICC = 0.80), large vessel (kappa = 0.53), nervous system (kappa = 0.61) and eye involvement (kappa = 0.77). There was poor agreement for the question relating to the presence of bloody diarrhoea (ICC = 0.28). There was significant bias in the rating of fatigue by one of the physicians (F = 5.2, P = 0.001). Conclusion. Overall, this instrument has good interobserver reliability for assessing general disease activity. We therefore suggest that this proforma has a place in routine clinical monitoring of patients with BD, as well as assessing outcome in therapeutic trials.
... Twelve active BD patients were investigated for the expression of IL-38, IL-17, IL-10, TGFβ and NLRP3 inflammasome level during the disease activity and during their disease remission. BD activity index (BDAI) was also performed on our patients according to the method presented by Bhakta et al. and Lawton et al. [32,33]. Patients who had no symptoms related to BD in a four-week period, or less than two symptoms with a healing process and an overall wellbeing status, were grouped in inactive BD. ...
... They had normal CRP and ESR. . BD activity index (BDAI) was also performed on our patients according to the method presented by Bhakta et al. [32] and Lawtong et al. [33]. Patients who had no symptoms related to BD in a four-week period, or less than two symptoms with a healing process and an overall wellbeing status, were grouped in inactive BD. ...
... Twelve BD patients were treated and considered in the inactive stage. BD activity index (BDAI) was performed on our patients according to the method presented by Bhakta et al. [32] and Lawton et al. [33] as reported in materials and methods. Patients who presented no more than 2 symptoms or no symptoms with a healing process and general state of well-being, related to BD during a period of four weeks, were grouped under BD in inactive stage. ...
... Assessment of disease activity is based on clinical features and there is a necessity to develop a standardized activity evaluation tool for use in monitoring disease progression and the effects of therapeutic interventions [8]. The Behçet's Disease Current Activity Form (BDCAF) was developed [9], and as the BD activity is ineffectually addressed, and there is no agreement to how it should be measured, there were attempts to develop another useful simplified score [10] that was in harmony to the BDCAF index [11]. ...
... The Ar-BDCAF. The original BDCAF [9] is an index based on the presence of clinical signs related solely to BD. Fatigue, headache, oral/genital ulcers, erythema nodosum, superficial thrombophlebitis, pustules, arthralgia, arthritis, nausea, vomiting, abdominal pain, and bloody diarrhea are scored between 0 and 4 according to the duration of the symptom in the preceding 4 weeks. ...
... The Ar-BDCAF questions were understood by all the patients. Applying it with the patients was of reasonable time consumption taking on the average 5 min (ranging from 1.5 to 15 min) to calculate the score, which is consistent with the original score [9] and subsequent adaptations [17][18][19] who reported a mean time completion of BDCAF form at 4-10 min. ...
Background Behçet’s disease (BD), commonly seen in the Silk road countries, is a variable vessel vasculitis with no specific
investigation that reflects disease activity. The Behçet’s Disease Current Activity Form (BDCAF) is the most famous and
acceptable clinical activity score.
Purpose To develop a cross-cultural adaptation of the BDCAF to the Arabic language (Ar-BDCAF)—Egyptian dialect—
across the country and to consider preliminary evaluation of its reliability in assessment of BD activity.
Patients and methods The score was translated to Arabic language and revised by 3 rheumatology consultants. Reliability of
Ar-BDCAF was tested among 88 BD patients from 9 Egyptian main city centers. Patients were questioned by two specialists
at 30 min interval to evaluate inter-observer rating and twice by the same physician within 24 h to assess the intra-observer
rating.
Results Patients were 64 males and 24 females (2.7:1) with a mean age of 35 ± 10.3 years. The average time required by
the consultant to fill in the form was 5.1 ± 2.2 min (1.5–15 min). The mean Ar-BDCAF scores were 9.81 ± 6.22 (0–25) and
9.53 ± 6.13 (0–28) with an intra-observer concordance (p = 0.28) and was 9.95 ± 6.47 (0–29) for the inter-observer rating
(p = 0.89 and p = 0.66, respectively).
Conclusion The Ar-BDCAF is a measurable, easy to calculate, and reliable index for assessing disease activity in Egyptian
BD. The Ar-BDCAF score can be used in daily clinical practice to assess BD activity and its use can be extended to other
Arab countries for possible regional validation and adaptations.
... Different scoring for the eye, CNS, and major vessels is present. Also, 3 visual analog scales for both the patient's perception of wellbeing and the clinician's perception of the overall disease activity [12]. ...
... The MHAQ encompasses 8 classes that evaluate the following daily functions: dressing, grooming, rising, eating, walking, hygiene, reaching, gripping, and chores. All questions take a score from 0 to 3 according to patient capability which is graded from no difficulty in doing the function to inability to complete it respectively [12]. Data Analysis: Statistical analysis was done using SPSS software (Statistical Package for the Social Sciences) version 26 (IBM Corp. Released 2019. ...
Background: Behçet's disease (BD) activity assessment is a major concern since a treat-to-target approach may lead to a better prognosis. The first patient-reported assessment instrument, the Behçet's Syndrome Activity Score (BSAS), is useful for routine clinical use. Aim: To evaluate the validity and reliability of the translated Arabic version of BSAS (Ar-BSAS) in the assessment of BD activity and discriminate its cutoff point or disease activity. Method: Seventy BD patients were included in the study. The BSAS was translated into Arabic language. The reliability and validity were evaluated. Results: The Ar-BSAS of each item and the total score demonstrated a high internal consistency and Cronbach's alpha coefficient of 0.881, to 0.997. A significant positive correlation was found between the total score of the BSAS with the BDCAF (r =0.891, p <0.001**) and the BSAS with the MHAQ (r =0.813, p <0.001**), and between the total score of BSAS and ESR and CRP indicating high convergent validity. The BSAS cutoff value for disease activity was 15.5 in comparison with the BDCAF with high area under the curve 0.972 at 95% confidence interval (CI) on the receiver operating characteristic curve (ROC). Conclusions: The Arabic version of the BSAS (Ar-BSAS) is a reliable, valid, and accurate patient reported measure for disease activity that could be used to evaluate disease activity and enhance the therapeutic management choices in routine clinical practice.
... Different scoring for the eye, CNS, and major vessels is present. Also, 3 visual analog scales for both the patient's perception of wellbeing and the clinician's perception of the overall disease activity [12]. ...
... The MHAQ encompasses 8 classes that evaluate the following daily functions: dressing, grooming, rising, eating, walking, hygiene, reaching, gripping, and chores. All questions take a score from 0 to 3 according to patient capability which is graded from no difficulty in doing the function to inability to complete it respectively [12]. Data Analysis: Statistical analysis was done using SPSS software (Statistical Package for the Social Sciences) version 26 (IBM Corp. Released 2019. ...
Background: Behçet's disease (BD) activity assessment is a major concern since a treat-to-target approach may lead to a better prognosis. The first patient-reported assessment instrument, the Behçet's Syndrome Activity Score (BSAS), is useful for routine clinical use. Aim: To evaluate the validity and reliability of the translated Arabic version of BSAS (Ar-BSAS) in the assessment of BD activity and discriminate its cutoff point or disease activity. Method: Seventy BD patients were included in the study. The BSAS was translated into Arabic language. The reliability and validity were evaluated. Results: The Ar-BSAS of each item and the total score demonstrated a high internal consistency and Cronbach's alpha coefficient of 0.881, to 0.997. A significant positive correlation was found between the total score of the BSAS with the BDCAF (r =0.891, p <0.001**) and the BSAS with the MHAQ (r =0.813, p <0.001**), and between the total score of BSAS and ESR and CRP indicating high convergent validity. The BSAS cutoff value for disease activity was 15.5 in comparison with the BDCAF with high area under the curve 0.972 at 95% confidence interval (CI) on the receiver operating characteristic curve (ROC). Conclusions: The Arabic version of the BSAS (Ar-BSAS) is a reliable, valid, and accurate patient reported measure for disease activity that could be used to evaluate disease activity and enhance the therapeutic management choices in routine clinical practice.
... Different scoring for the eye, CNS, and major vessels is present. Also, 3 visual analog scales for both the patient's perception of wellbeing and the clinician's perception of the overall disease activity [12]. ...
... The MHAQ encompasses 8 classes that evaluate the following daily functions: dressing, grooming, rising, eating, walking, hygiene, reaching, gripping, and chores. All questions take a score from 0 to 3 according to patient capability which is graded from no difficulty in doing the function to inability to complete it respectively [12]. Data Analysis: Statistical analysis was done using SPSS software (Statistical Package for the Social Sciences) version 26 (IBM Corp. Released 2019. ...
Background: Behçet’s disease (BD) activity assessment is a major concern since a treat-to-target approach may lead to a better prognosis. The first patient-reported assessment instrument, the Behçet's Syndrome Activity Score (BSAS), is useful for routine clinical use.
Aim: To evaluate the validity and the reliability of the translated Arabic version of BSAS (Ar-BSAS) in assessment of BD activity, and discriminate its cut-off point for disease acitivity.
Patients and methods: Seventy BD patients were included in the study. The BSAS score was translated into Arabic language. The reliability and the validity were evaluated.
Results: The Ar-BSAS each item and the total score demonstrated a high internal consistency and Cronbach’s alpha coefficient (0.881, to 0.997). A significant positive correlation between the total score of the BSAS with the BDCAF (r=0.891, p<0.001**), the BSAS with the MHAQ (r=0.813, p<0.001**) and between the total score of BSAS and ESR, CRP indicating high convergent validity. The BSAS cutoff value for disease activity was (15.5) in comparison with the BDCAFwith high area under the curve 0.972 at 95% confidence interval (CI) on the receiver operating characteristic curve (ROC).
Conclusion: The Arabic version of the BSAS (Ar- BSAS) is a reliable, valid and accurate patient reported measure for disease activity that could be used to evaluate disease activity and enhance the therapeutic management choices in routine clinical practice.
Keywords
BSAS activity validity reliability
... Monitoring disease activity is a fundamental issue of the clinical assessments to be able to elucidate health status and the care priorities of patients. It also provides information for the individual treatment plans that are often complex to coordinate [30][31][32][33][34][35]. ...
... Of note, measurement of disease activity by using a disease-specific global activity index has been challenging in BD owing to its multiple organ involvement [34,49]. Instead, the evaluation of ongoing therapies and activities of isolated organ involvement are usually assessed by organ specific activity indices [33,43,50]. ...
During the last decades the efficacy of biologic agents, mainly of anti-TNFs, in controlling the activity of serious manifestations of Behcet's Disease (BD) has been established. On the other hand, the clinical heterogeneity of BD has precluded the validation of a widely-accepted composite index for disease assessment and for target disease-state definitions, such as low disease activity and remission, and the testing of their implementation in clinical practice. Therefore, in contrast to other systemic rheumatic diseases, a treat-to-target strategy has not yet been developed in BD. There are several challenges towards this approach, including standardization of outcome measures for assessing the disease activity in each-affected organ and construction of a composite disease activity index. The challenges for the development of a treat-to-target strategy and possible solutions are discussed in this position paper, which stemmed from a round table discussion that took place in the 19th International Conference on BD.
... The disease activity on the day of evaluation was assessed by a rheumatologist using a modified Behçet's Disease Current Activity Form (BDCAF) [12] scoring system, developed by our research team, which included organ involvement over the 4 weeks preceding the assessment according to the original BDCAF, as well as information about the indication for starting biologic treatment and the follow-up assessment of disease activity, partial remission (i.e., improvement), complete remission, relapse rate, biologic-related side effects, poor outcomes, and death, 6 and 12 months after starting biologics. Our scoring system is presented as a supplementary file. ...
Introduction
The treatment of Behçet’s disease has improved significantly with the introduction of biologic therapies. However, there is still a need for more information about their use. This study aimed to evaluate the indications, response, and side effects of biologic agents in patients with refractory or severe Behçet’s disease in the south of Iran, their follow-up and reasons for changing the biologics.
Material and methods
A retrospective analysis was conducted on 44 patients aged 16–65 years who were prescribed biologic agents for at least 6 months. The clinical history, partial and complete remission at 6 and 12 months, occurrence of side effects, and need for switching to a second or third biologic agent were recorded.
Results
The most common indications for starting biologic agents were ophthalmic (68.2%), parenchymal brain involvement (15.9%), and arthritis (11.4%). Improvement was observed in various manifestations of Behçet’s disease, with complete remission in 86, 51.6, 92.8, 66.7, 42.9, 33.3, and 80.0% of oral aphthous lesions, ophthalmic activity, genital aphthous lesions, skin activity, arthritis, brain parenchymal lesions, and vascular activity, respectively, 6 months after starting biologic agents. These rates were unchanged or increased at the 12-month follow-up. In 25.0% of patients, a switch to a second biologic agent was necessary due to severe disease, side effects, or refractory disease. Side effects occurred in 16.3% and 33.3% of patients on the first and second biologic agents, respectively. The majority of side effects were not serious.
Conclusions
We found a promising improvement at 6-month and 12-month follow-ups with various biologic agents in treating Behçet’s disease with an acceptable safety profile.
... Inflammatory indices, including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, were also noted. The Behcet's Disease Current Activity Form (BDCAF) was used to evaluate disease activity [11]. ...
Background
Autoimmune responses have been suggested to involvement in patients with Behcet’s syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA) ⁺ regular T cells (Tregs) in autoimmune diseases. The role of CLA ⁺ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA ⁺ Tregs on BS.
Methods
We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA ⁺ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4 ⁺ T cells were detected using flow cytometry and compared between patients and HCs.
Results
The absolute number and proportion of CLA ⁺ Tregs among CD4 ⁺ T lymphocytes and CD4 ⁺ Tregs were lower in patients with BS than in HCs. CLA ⁺ Tregs were positively related with NK cells ( r = 0.500, P < 0.001) and B cells ( r = 0.470, P < 0.001) and negatively related with effector T cells ( r =-0.402, P < 0.001) in patients with BS. Patients with BS and arterial aneurysms had CLA ⁺ Treg cell deficiency. A decreased proportion of CLA ⁺ Tregs was associated with arterial aneurysms in patients with BS. The proportion of CLA ⁺ Tregs in patients with BS increased with corticosteroids and immunosuppressants.
Conclusion
CLA ⁺ Tregs decrease in association with arterial aneurysm in patients with BS. CLA ⁺ Tregs may be a predictor of response to BS treatment.
... Various scales have been developed to score disease activity and, among them, the Behçet's Disease Current Activity Form is the most commonly used tool. 143 Another scale is the Behçet's Syndrome Activity Scale, which measures patientreported global disease activity. 144 Furthermore, scales exist to measure organspecific outcomes, including the Oral Ulcer Composite Index, 145 the Behçet's Disease Ocular Attack Score 24 for ocular involvement, 146 and the Disease Activity Index for Intestinal Behçet's syndrome. ...
... Disease activity: Behçet Disease Current Activity Form (BDCAF) was used to evaluate disease activity (21). BDCAF scores clinical features of patients in the last 4 weeks. ...
... Most relevant studies have focused upon ocular inflammation, mucocutaneous manifestations, and arthritis as end-points, with vascular and neurological manifestations seldom being sufficiently frequent to be included in statistical analyses. There has been recent progress, however, in the development of clinical scoring systems to assess response to treatment (Bhakta et al., 1999). Table 5 summarizes the therapeutic approaches to the treatment of BD. ...
... BD was strictly diagnosed by rheumatologists according to the diagnostic criteria developed by the International Study Group for Behçet's disease [1]. BD activity was evaluated using the Behçet Disease Current Activity Form (BDCAF) [23]. Uveitis was diagnosed by an ophthalmologist. ...
Background:
This study aimed to investigate the expression profile of immune response-related proteins of Behcet's disease (BD) patients and identify potential biomarkers for this disease.
Methods:
Plasma was collected from BD patients and healthy controls (HC). Immune response-related proteins were measured using the Olink Immune Response Panel. Differentially expressed proteins (DEPs) were used to construct prediction models via five machine learning algorithms: naive Bayes, support vector machine, extreme gradient boosting, random forest, and neural network. The prediction performance of the five models was assessed using the area under the curve (AUC) value, recall (sensitivity), specificity, precision, accuracy, F1 score, and residual distribution. Subtype analysis of BD was performed using the consensus clustering method.
Results:
Proteomics results showed 43 DEPs between BD patients and HC (P < 0.05). These DEPs were mainly involved in the Toll-like receptor 9 and NF-κB signaling pathways. Five models were constructed using DEPs [interleukin 10 (IL10), Fc receptor like 3 (FCRL3), Mannan-binding lectin serine peptidase 1 (MASP1), NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (NF2), FAM3 metabolism regulating signaling molecule B (FAM3B), and O-6-methylguanine-DNA methyltransferase (MGMT)]. Among these models, the neural network model showed the best performance (AUC = 0.856, recall: 0.692, specificity: 0.857, precision: 0.900, accuracy: 0.750, F1 score: 0.783). BD patients were divided into two subtypes according to the consensus clustering method: one with high disease activity in association with higher expression of tripartite motif-containing 5 (TRIM5), SH2 domain-containing 1A (SH2D1A), phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), hematopoietic cell-specific Lyn substrate 1 (HCLS1), and DNA fragmentation factor subunit alpha (DFFA) and the other with low disease activity in association with higher expression of C-C motif chemokine ligand 11 (CCL11).
Conclusions:
Our study not only revealed a distinctive immune response-related protein profile for BD but also showed that IL10, FCRL3, MASP1, NF2, FAM3B, and MGMT could serve as potential immune biomarkers for this disease. Additionally, a novel molecular disease classification model was constructed to identify subsets of BD.
... Patients were further categorized according to disease activity into active BD group and inactive BD group according to BDCAF. BDCAF is a tool to assess disease activity through data in the last four weeks before recruitment on a scale from 0 to 12, with scores > 4 considered an active disease [9]. ...
Background
Behçet’s disease (BD) is a multi-organ disease with different systemic manifestations. While rare in the United States and Europe, it is more common in the Middle East and Asia. BD is one of the commonest encountered vasculitis in Egypt. This study aims to evaluate BD patients' sleep patterns, quality of life, and psychological aspects.
Methods
Patients suffering from Behçet’s disease (thirty patients) and 30 matched age and sex-healthy control participants were recruited in our study. The assessment included the entire clinical history and laboratory investigations, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Oxygen saturation level. Evaluation of sleep quality and presence of sleep-disordered breathing was done using the Pittsburgh Sleep Quality Index (PSQI), Insomnia severity index (ISI), and Epworth sleepiness scale (ESS). Hamilton’s anxiety (HAM-A) and depression rating scales (HAM-D) were used for psychological assessment. The Short Form 36 Quality Of Life Scale (SF-36 QOL) assessed participants' quality of life.
Results
Behçet’s disease patients suffered significantly higher levels of anxiety and depression compared to the control group. The prevalence of insomnia and daytime sleepiness was significantly higher among BD patients. All components of PSQI, including the global score, were significantly higher among the BD group. Physical functioning, role limitation due to physical health, and emotional problems; also, general health indices were significantly lower for the BD group. Patients with active BD showed significantly higher levels of anxiety, depression, insomnia, day time dysfunction and significantly lower all domains of the SF-36 QOL Scale.
Conclusions
BD is associated with low sleep quality and high levels of anxiety and depression.
Disease activity directly impacts anxiety, depression levels, lower sleep quality, and lower quality of life among BD patients.
Trial registration
ClinicalTrials.gov. NCT05142995. Registered November 20, 2021.
... Data about the demographic features of the patients, disease duration, manifestations of BD, laboratory findings, as well as the treatment received were collected. Disease activity according to the Behçet's Disease Current Activity Form (BDCAF) score was documented (as it could be collected from the file data) [10] . Vasculitis Damage Index score was also calculated [11] . ...
... The presence of any chronic comorbidity was also recorded (malignancy, cardiovascular and respiratory disease, metabolic disorders, major depressive disorder, other immunomediate diseases). Disease activity was evaluated by the PtGA and PGA, as well as the Behçet Disease Current Activity Form (BDCAF) [20]. PtGA and PGA were assessed through a single question ("How active was your/the patient's BS during the last week?") on an anchored 10-cm visual analogic (0.5-cm graded), where 0 corresponded to "no disease activity" and 10 to "the highest disease activity." ...
... Every patient underwent a history taking, physical examination, and lab tests. The Behcet's Disease Current Activity Form was used to assess current disease activity (BDCAF) [12] . In addition, this work included 30 healthy individuals as control group who their sex and agematched to the cases. ...
... Uveitis [38] and intestinal ulcers [39] were the most common major organ involvements, followed by cardiac [40], vascular lesions [41], and central nervous system involvement [42]. The disease activity and severity were assessed by Behçet's Disease Current Activity Form (BDCAF) [43] and Krause's score [44]. ...
T lymphocytes are the major components of adaptive immunity in Behçet's syndrome (BS) pathology. However, the precise mechanism of T cell‐induced inflammatory condition remains to be determined. We applied bulk sequencing of the T cell receptor (TCR) β chain in peripheral blood samples from 45 patients with BS and ten healthy donors as controls. TCR repertoires in BS patients displayed more clonality and less diversity than in healthy donors. Male patients exhibited lower diversity metrics of TCR and had a larger proportion in the top ten clones than females (P = 0.016). There were no TCR clonality differences in other clinical features, such as age, disease duration, organ involvement, disease severity, and activity. By “Grouping of Lymphocyte Interactions by Paratope Hotspots” (GLIPH2) for antigen prediction, we found distinct 2,477 clusters of TCRβ sequences that potentially recognize similar antigens shared between BS patients. We observed clonal T‐cell expansion in BS patients. Sexual differences in TCR clonal expansion and public TCR groups deserve further study to reveal the underline T‐cell mediated immunity in BS. This article is protected by copyright. All rights reserved
... The present study included 40 patients diagnosed with BD, according to the criteria of the International Study Group for Behçet's Disease (15) .They were selected from patients attended the Internal Medicine Department of Al-Azhar University Hospitals. The activity index was determined as described by Bhakta et al. (16) . In addition, 40 patients of Systemic lupus with and without thrombotic complications were included in the present work. ...
... All BD patients were classified as active or inactive groups according to the simplified Behcet's Disease Current Activity Form (BDCAF), which record clinical manifestations during the 4 weeks prior to the assessment. It includes 12 items (headache, mouth ulceration, genital ulceration, erythema, skin pustules, arthralgia, arthritis, nausea/vomiting/abdominal pain, diarrhea + altered frank blood per rectum, eye involvement, nervous system involvement, and major vessel involvement) the score is graded from 0 to 12 and active disease was defined with BDCAF ≥ 2 [30][31][32]. ...
Background
Behcet’s disease (BD) does not have specific laboratory finding or pathological physical examination sign, and only few studies have investigated Neutrophil to lymphocyte ratio (NLR), platelets to lymphocytes ratio (PLR), lymphocytes to monocytes ratio (LMR), or mean platelet volume (MPV) values in patients with BD. We conducted this study to investigate the relationship between these indices and Behcet’s disease (BD) and to determine their relation to BD disease activity.
Results
This study is a case-control study that included 36 Behcet’s disease patients and 36 healthy controls. BD patients showed significant increase in the mean of NLR and PLR in comparison to control ( P = 0.008 and 0.011) respectively, and highly significant decrease in LMR and MPV levels in BD patients in comparison to control ( P < 0.001 and < 0.001) respectively. Also, we found that NLR, PLR, and LMR were significantly related to BD activity, and there were significant associations between the studied hematological parameters with some of muco-cutaneous, articular, gastrointestinal, eye, and nervous system manifestations in BD patients.
Conclusion
The blood indices NLR, PLR, LMR, and MPV are potential inflammatory markers that can be used to evaluate inflammatory status and disease activity in patients with BD. NLR and PLR showed positive relation being higher in active disease and also higher in highly active disease than in low disease activity. Also, LMR was significantly decreased in Behcet’s disease patients in relation to disease activity. Furthermore, NLR and PLR levels were significantly more associated with muco-cutaneous and nervous system involvement while, LMR levels were significantly associated with muco-cutaneous, articular, gastrointestinal and eye manifestations and MPV levels were associated with articular manifestations being significantly related to disease activity. These easily evaluated markers could help in the management of this disease with multisystem affection that are sometimes serious and potentially life threatening.
... All patients with diagnosis of BD were screened consecutively for enrollment in this study between June 2021 and May 2022. Inclusion criteria were age ≥ 16; diagnosis of BD according ICBD [9], having at least two visits, and follow-up duration ≥ 1 years. The medical records of the patients were reviewed and the demographic characteristics, disease activity status, clinical manifestations, and data on organs damage were collected from all patients. ...
Objective:
In the present study, we aimed to validate the Behçet's syndrome Overall Damage Index (BODI) and compare its performance with that of vasculitis damage index (VDI) in Iranian patients with BD.
Methods:
This study included 274 patients with a diagnosis of BD and median follow-up of 40 months. The medical records of the patients were reviewed and the demographic characteristics, disease activity status, clinical manifestations, and data on organs damage were collected from all patients.
Results:
To evaluate the construct/convergent validity, BODI and VDI were applied to all participants. We found a good correlation between BODI score and VDI score. There was a significant and strong correlation between physician global assessment with BODI (r = 0.869, P = 0.001) and VDI (r = 0.817, P = 0.001). The ability of BODI to determine the accumulation of damage over time was assessed by analyzing the changes in BODI score over time. The increase in BODI score was occurred in 53 (19.3%) patients. In comparison, the increase in VDI score occurred in 36 (13.1%) patients. The increase in median BODI was significantly more than median VDI (P < 0.001). Multiple linear regression analysis showed that age at disease onset, disease duration, and disease severity were independent predictors of BODI scores. Reliability of BODI was examined by comparing the BODI scores as determined by two independent assessors in 100 patients. Cronbach's α was 0.942.
Conclusion:
The BODI demonstrated acceptable validity and reliability in assessing BD-related damage in Iranian patients with BD.
... Anahtar kelimeler: Ankilozan spondilit, hastalık aktivitesi, obezite, osteoartrit, romatoid artrit, romatizmal hastalıklar questionnaire (FIQ) for FM, the SLE disease activity index for SLE, and the BD current activity form for BD were used (7)(8)(9)(10)(11)(12). ...
Objective:Obesity is a common health problem and a complex disease that is defined as overly fat deposition in adipotic tissue. Studies conducted in our country (Turkey) have reported prevalence of obesity between 12 and 22 percent. Obesity has been shown to be associated with several rheumatic diseases and inflammation. The aim of this study is to assess the prevalence of obesity in rheumatologic diseases, and possible relationships between disease activity and accompanying obesity.Method:A total of 1064 newly patients diagnosed with osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), fibromyalgia (FM), gout, Behçet’s disease (BD), vasculitis, polymyalgia rheumatica (PMR), Sjögren’s syndrome (SS), Familial Mediterranean fever, polymyositis, and systemic sclerosis (SSc) were included in the study. Age, gender, disease activity scores, and laboratory and clinical findings were all recorded.Results:Obesity incidences were found to be 4.5% in RA, 3.2% in SLE, 1.6% in AS, 40.1% in OA, 11.2% in FM, 19.7% in gout, 1.8% in BD, 15% in vasculitis, 13.7% in PMR, 8% in SS, and 8.3% in SSc. Obesity and OA were revealed to have a statistically significant association. Disease activity scores were statistically significantly higher in obese FM patients compared to non-obese patients (p
... Activity in patients with psoriatic arthritis was measured using the PSA Disease Activity Score (PASDAS) [19]. Behcet's disease activity was evaluated by the Behçet's Disease Current Activity Form (BDCAF) [20]. Additionally, the Juvenile Arthritis Disease Activity Score (JADAS) was used to evaluate the disease activity in JIA patients [21]. ...
Signal joint T cell receptor excision circles (sjTRECs) are a promising marker for age estimation and immunosenescence in different ethnic groups. Several limitations are expected to overshadow their use as accurate markers for age prediction. The current study was conducted to determine the influence of immunologic disorders, such as autoimmune diseases and COVID-19, on the accuracy of sjTRECs as molecular markers for age estimation and immunosenescence among living Egyptians. Peripheral blood sjTRECs level was measured by qPCR in 90 autoimmune patients, 58 COVID-19 patients, and 85 healthy controls. The mean dCt values were significantly (p = 0.0002) different between the three groups, with the highest values in healthy subjects, followed by autoimmune and COVID-19 patients. A significant negative correlation was identified between the sjTRECs levels and ages in all studied cases. There were significant positive correlations between chronological age and predicted age for healthy individuals, autoimmune, and COVID-19 patients with mean absolute deviations (MAD) of 9.40, 11.04, and 9.71, respectively. The two patients’ groups exhibited early immunosenescence, which was more noticeable among the young adults with COVID-19 and autoimmune patients of age range (18–49 years). Autoimmunity may represent a critical factor impacting the accuracy of sjTRECs quantitation for age prediction.
... Anahtar kelimeler: Ankilozan spondilit, hastalık aktivitesi, obezite, osteoartrit, romatoid artrit, romatizmal hastalıklar questionnaire (FIQ) for FM, the SLE disease activity index for SLE, and the BD current activity form for BD were used (7)(8)(9)(10)(11)(12). ...
... Active and cumulative clinical manifestations, previous and ongoing medications, and overall disease activity assessed by the Behçet's Disease Current Activity Form (BDCAF) [8], the Physician Global Assessment (PGA) [9], and the Patient Global Assessment (PtGA) [9] were recorded during follow-up. Furthermore, disease relapses, defined by any treatment escalation due to disease activity during follow-up, were recorded. ...
Background
This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet’s syndrome (BS) over 2 years of follow-up.
Methods
Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains.
Results
During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) ( p <0.001). The incidence rate of damage accrual was stable over time, regardless of the disease duration. Out of 61 new BODI items, 25 (41.0%) were considered related to glucocorticoid (GC) use. In multivariate analysis, duration of GC therapy (OR per 1-year 1.15, 95% CI 1.07–1.23; p <0.001) and occurrence of ≥1 disease relapse (OR 3.15, 95% CI 1.09–9.12; p 0.038) were identified as predictors of damage accrual, whereas the use of immunosuppressants showed a protective effect (OR 0.20, 95% CI 0.08–0.54, p <0.001). Damage accrual was independently associated with the impairment of different physical domains and, to a greater extent, in emotional domains of the SF-36 questionnaire. Female sex, higher disease activity, and fibromyalgia were also significantly associated with impairment in HR-QoL.
Conclusion
In BS, organ damage accrues over time, also in long-standing disease, resulting in an impairment of the perceived physical and mental health. Adequate immunosuppressive treatment, preventing disease flares and minimizing exposure to GCs have a crucial role in lowering the risk of damage accrual.
... The following information was collected at baseline: gender, age, age at cardiac lesions onset, duration of BS, duration of cardiac lesions, body mass index (BMI), diagnosis, clinical manifestations of BS (oral ulcer, genital ulcer, uveitis, erythema nodosum, pseudofolliculitis pathergy reaction, intestinal, vascular, hematologic, joint, cardiac, neurological and blood involvement). The preoperative, postoperative and surgery information of each surgery was collected: duration of BS at surgery, duration of cardiac lesions at surgery, age at surgery, smoking and drinking history, concomitant basic diseases (hypertension, diabetes, renal insu ciency, and hyperlipidemia), cardiac symptoms, New York Heart Association functional status, clinical manifestations of BS, scores of Behçet's Disease Current Activity Form (BDCAF) [10,11] , preoperative laboratory indexes [white blood cells (WBC), haemoglobin (Hb), platelets(PLT), neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)], preoperative electrocardiogram, preoperative imageological examinations (echocardiography, CT angiography), dates of surgeries, surgical procedures, preoperative and postoperative immunosuppressive therapies (oral steroid, DMARDs, JAK inhibitor, and biological agent), and postoperative complications. In addition, the outcomes of cardiac BS patients were recorded. ...
Background
Cardiac Behçet’s syndrome (cardiac BS) is rare but lethal. And the influencing factors of prognoses in cardiac BS are not clear. This study was conducted to summarize the features of cardiac BS and find the predictors of unfavourable prognoses for cardiac BS patients.
Methods
Sixty-six cardiac BS patients were included from 1467 BS patients in the Shanghai Behçet’s syndrome database. The median follow-up duration was 4.0 (2.0–7.0) years. The unfavourable prognosis was defined as a compound event containing all-cause death and rehospitalization related to worsened cardiac lesions or postoperative complications. Logistic regression analyses were performed to evaluate the predictors of unfavourable prognoses.
Results
In this study, the mortality rate of cardiac BS patients was 10.61% (7/66), and 22 (33.33%) patients experienced two or more surgeries. Ninety-six cases were collected from 66 cardiac BS patients. The effective rates of postoperative biological agents and Janus kinases (JAK) inhibitors in cardiac BS patients were 88.89% (16/18) and 81.25% (13/16) respectively. Former smoking, valve replacement or repairment and poor compliance were found to be the independent risk factors of unfavourable prognoses; preoperative immunosuppressive therapies and postoperative immunosuppressive therapies were independent protective factors for unfavourable prognoses in total cardiac BS. In 65 cases of cardiac BS after aortic valve surgeries, former smoking was an independent risk factor for unfavourable prognoses. Bentall procedure, postoperative traditional DMARDs, postoperative JAK inhibitors or biological agents were independent protective factors for unfavourable prognoses in cardiac BS patients after aortic valve surgeries.
Conclusion
Both preoperative immunosuppressive therapies and postoperative immunosuppressive therapies are necessary for cardiac BS patients. Bentall procedure is recommended to be performed in BS patients with severe AR. Besides biological agents, JAK inhibitors can be used in cardiac BS patients after aortic valve surgeries for promoting favourable outcomes.
... Patients were selected according to the new international diagnostic criteria of BD (25). Disease activity was evaluated according to Behçet's Disease Clinical Activity Form (BDCAF) (26). In clinical examination, oral ulcers, genital ulcers, ocular involvement, other skin lesions, joint findings, vascular, neurological, and gastrointestinal involvement were questioned. ...
Behçet's disease is a multi-systemic chronic
inflammatory disease and many biomarkers and
cytokines have been identified in the diagnosis and
follow-up of disease activity. Neutrophil-to-lymphocyte
ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have
been used as new inflammatory biomarkers to assess
disease severity in many autoimmune diseases. The
aim of the study is to investigate the NLR and PLR
values of the Behçet patients in the inactive period.
Material and Methods: After the clinical examination
and disease activity were evaluated by the internal
medicine clinic, the patients who met the inclusion
criteria and were considered in inactive period were
evaluated in terms of possible inflammatory and malignant diseases by other clinics (otorhinolaryngology,
ophthalmology, and dentistry). After exclusion of other
causes of increased NLR, 40 Behçet's patients and
45 healthy controls were included in the study. NLR
and PLR values of these two groups were compared.
Results: NLR values were statistically higher in the
patient group compared to the control group. PLR
values were higher in the patient group, but there was
no statistical difference
Conclusion: NLR was found to be high even though
the patients were in the inactive phase and after other
conditions that could cause NLR elevation were evaluated by other clinics. This supports an underlying
inflammatory condition in Behçet's disease, even if the
patient has no clinical findings and is in the inactive
stage.
... The distinction between active and remission periods was evaluated using Behçet's Disease Current Activity Form (BDCAF), taking into account the clinical criteria defined by Bhakta et al. BDCAF was applied to all BD patients participated in the study [40]. The BDCAF briefly consists of a score (sign/ symptom: ocular lesion = 2 points; oral aphthosis = 2 points; genital aphthosis = 2 points; skin lesions = 1 point; vascular manifestations = 1point; neurological manifestation = 1 point; and optional positive pathergy test = 1 point) and patients with a score of 4 or more were diagnosed as active Behçet's disease. ...
Purpose
The molecules human interleukin (IL-18), the soluble cluster of differentiation (sCD40), platelet factor 4 variant 1 (PF4V1), and neutrophil gelatinase-associated lipocalin (NGAL) are all markers of inflammation in biological systems and are linked to prognosis in several inflammatory diseases as well. Since there is no study in which the above-mentioned molecules are studied together in ocular Behçet's disease (OBD), the aim of this study is to reveal whether these molecules are activity markers in active (OABD) and inactive (OIBD) disease.
Methods
30 OABD and 30 OIBD and 30 healthy individuals were included in the study. IL-18, sCD40, PF4V1, and NGAL molecules were studied in blood samples by the ELISA method.
Results
When OABD and OIBD were compared to healthy individuals, the levels of IL-18, sCD40, PF4V1, and NGAL molecules were found to be statistically significant. These values were even more significantly higher in patients with OABD.
Conclusion
When ROC values of IL-18, sCD40, PF4V1, and NGAL are evaluated, it is clear that these four molecules can be used as biomarkers to aid activity and diagnosis in OBD.
... Disease activity was assessed by the BD Current Activity Form (BDCAF) over the past four weeks (21). Signs and symptoms other than the involvement of the CNS, eyes, and great vessel were scored between 0 and 4. CNS, eyes, and great vessels were measured with two diverse variables. ...
Objectives: The incidence of cardiovascular disease is increased in patients with Behcet's disease (BD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) causes the acceleration of atherosclerosis. We aimed to investigate whether there is a relationship between PCSK9 with carotid artery intima-media thickness (cIMT), a marker of subclinical atherosclerosis, and BD disease activity.
Methods: Fifty-eight patients with BD and 58 age-, gender-, and body mass index (BMI)-matched healthy control subjects were included in the study. The disease activity of the patients was estimated. Individuals' cIMT values were measured, and PCSK9 levels were studied.
Results: Patients with BD' cIMT (0.51 ± 0.1 vs 0.41 ± 0.1 mm, p < .001) and PCSK9 (623.2 ± 101.7 ± 10.1 vs 528.3 ± 242.7 ng/ml, p = .007), values were significantly higher than the control group. In stepwise regression analysis, there was an independent relationship between cIMT with PCSK9 (β = 0.179, p < .050). There was no independent relationship between disease activities with PCSK9. Based on the ROC curve analysis, the PCSK9 optimal cutoff value for cIMT was 595.1 ng/ml, sensitivity 66.7%, specificity 64.7% (AUC = 0.672; 95% CI: 0.530-0.815, p = .040).
Conclusion: There is a strong independent association between subclinical atherosclerosis and PCSK9 in patients with BD. There may be no independent association between PCSK9 and disease activity.
... Patients were assessed at 6-week intervals and followed for 1 year from enrolment into the trial or until withdrawal. Disease activity was assessed by BVAS/WG and, in addition, for BD patients, the Behçet's disease current activity form (BDCAF) to document BD disease activity [18]. The combined damage assessment (CDA) was used to document 'all cause' damage accrual from the time of diagnosis, whilst the Short-Form 36 (SF-36) questionnaire was collected at baseline, 6 and 12 months to assess patient reported outcomes. ...
Background
Primary systemic vasculitis (PSV) is a heterogeneous group of autoimmune conditions. There is an unmet need for alternative therapies that lead to sustained remission in patients with refractory disease. Alemtuzumab, an anti-CD52 antibody, depletes lymphocytes for prolonged periods and, in retrospective studies, has induced sustained, treatment-free remissions in patients with refractory/relapsing vasculitis but has raised safety concerns of infection and secondary autoimmunity. This phase IIb clinical trial aimed to assess the efficacy and safety of alemtuzumab, at two different doses, in inducing remission in refractory vasculitis patients.
Methods
The ALEVIATE trial was a randomised, prospective, open-label, dose ranging clinical trial. Patients with refractory ANCA-associated vasculitis (AAV) or Behçet’s disease (BD) were randomised to receive either 60 mg or 30 mg alemtuzumab. Treatments were administered at baseline and 6 months or earlier where clinically appropriate. A maximum of three treatments were allowed within the 12-month study period.
Results
Twenty-three patients received at least one dose of alemtuzumab. Twelve had AAV, and 11 a diagnosis of BD. The median age was 40 years (range 28–44), with a prior disease duration of 61 months (42–103). Sixteen (70%) achieved either complete (6/23, 26%) or partial (10/23, 44%) response at 6 months. Eight (35%) maintained remission to the end of the trial without relapse. Ten severe adverse events were observed in 7 (30%) patients; 4 were related to alemtuzumab. There were no differences in clinical endpoints between the 60 and 30 mg alemtuzumab treatment groups.
Conclusion
In a selected group of refractory vasculitis patients, alemtuzumab led to remission in two thirds of patients at 6 months. Remission was maintained to 12 months in a third of the patients, and the safety profile was acceptable.
Trial registration
ClinicalTrials.gov identifier: NCT01405807, EudraCT Number: 2009-017087-17. Registered on April 07, 2011.
... BD activity was evaluated by a rheumatologist using three following indices, i.e., BDCAF [26], the nonocular IBDDAM [27], and TIAI [28], at the baseline and week 12. Quality of life was assessed using the validated Persian version of the Leeds BD quality-of-life (BD-QoL) questionnaire consisting of 30 questions with two answers, i.e., true (scored one) or not true (scored zero). Therefore, the final score ranged between 0 and 30 (0: high quality and 30: less quality) [29]. ...
Background & Aims
Toll-like receptor (TLR) 2 and 4 are involved in the pathogenesis of Behçet's disease (BD). The current study aimed to investigate the effect of zinc supplementation on TLR-2/4 expression and the clinical manifestations of BD.
Methods
In this double-blind placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day) or placebo groups for 12 weeks. Before and after the intervention, the surface and mRNA expression level of TLR-2 and TLR-4 in the leukocytes, serum level of zinc and tumor necrosis factor-α (TNF-α), quality of life, anthropometric measures, and blood pressure of patients were collected. BD activity was studied using the nonocular Iranian Behçet's disease dynamic activity measure (IBDDAM), Behçet's disease current activity form (BDCAF), and total inflammatory activity index (TIAI) at the pre-and post-intervention phases. The effect sizes were compared between two groups using analysis of covariance.
Results
There were significant decrease in TLR-2 mRNA (P=0.038) and protein expression (P=0.034) and nonocular IBDDAM score (P=0.046) in the zinc group compared to placebo at the endpoint. The serum level of zinc was increased in the zinc group (P<0.001). Zinc supplementation significantly decreased the TLR-4 surface (P=0.012) and mRNA expression (P=0.028) within the group. However, this decrease was not significant compared to the placebo group. There was no significant difference between the two groups regarding the serum level of TNF-α, BDCAF, TIAI, quality of life, anthropometric measures, and blood pressure (P>0.05).
Conclusions
The present study revealed that zinc supplementation significantly improved nonocular IBDDAM score and TLR-2 expression in BD patients.
Clinicaltrials.gov registration number
NCT05098678.
... Active disease scores range from 0 to 12. A higher score indicates a higher level of disease activity (Bhakta et al., 1999). Accordingly, patients were divided into active (patients who met at least one criterion of the ISG for BD) or inactive (no lesions for the previous 4 weeks or more) patients at the time of the study. ...
Background: Behçet’s disease (BD) is a chronic autoimmune disease. The early diagnosis of BD is very important to avoid serious and/or fatal complications such as eye damage, severe neurological involvement, and large vessel occlusion. New, sensitive biomarkers would aid in rapid diagnosis, the monitoring of disease activity, and the response to treatment.
Methods: This study’s aim is to identify two immune system-related BD biomarkers. We measured long non-coding RNAs (lncRNAs) NEAT1 (nuclear-enriched abundant transcript 1), and lnc-DC (lncRNA in dendritic cells) in serum by real-time polymerase chain reaction (RT-PCR) in 52 BD patients and 52 controls. We analyzed the association between NEAT1 and lnc-DC and the clinical parameters of BD. Receiver operating characteristic (ROC) curve analysis was performed to explore the diagnostic performance of the studied genes.
Results: Compared to controls, the significant upregulation of NEAT1 {median [interquartile range (IQR)] = 1.68 (0.38–7.7), p < 0.0001} and downregulation of lnc-DC [median (IQR) = 0.2 (0.12–1.39), p = 0.03] were detected in the sera collected from BD patients. Higher serum expression levels of NEAT1 and lnc-DC were significantly associated with the following clinical presentations: cutaneous lesions, vascular manifestations, articular manifestations, neurological manifestations, and higher disease activity score. Also, high NEAT1 levels were significantly associated with a negative pathergy test, while higher lnc-DC was significantly associated with a positive family history. ROC curves showed that NEAT1 and lnc-DC levels in serum could be used as predictors of BD with high specificity and fair sensitivity. NEAT1 had an area under the curve (AUC) of 0.692 (95% CI: 0.591–0.794, p = 0.001), and lnc-DC had an AUC of 0.615 (95% CI: 0.508–0.723, p = 0.043).
Conclusion: Serum lncRNAs NEAT1 and lnc-DC are biomarkers for BD.
... The BDCAF is a valid international instrument for the assessment BD activity in the clinic which scores the history of clinical features; headache, mouth ulcer, genital ulcer, skin lesions, eye symptoms, joint involvement, blood vessel involvement, gastrointestinal and CNS complications, which present over the preceding 4 weeks prior to the day of assessment [17]. Other factors: patients' medication, and lifestyle (e.g., stress, smoking, alcohol intake, and diet), were included. ...
Background
The aetiopathogeneses of Behçet’s Disease (BD) remains elusive with multifactorial genetic and epigenetic factors resulting in multisystemic disease. Oral and genital ulceration are common and influences disease outcome. We hypothesised that dysregulation of genital and oral microbial communities contributes to BD disease activity. 153 BD patients’ samples, 70 matched oral and genital (Female: Male, 58:12; mean age, 42±13.9: 39.3±10.3), 12 unmatched samples; 16s rRNA sequencing utilised and V1/V2 and V3/V4 regions analysed. BD outcomes: oral and genital ulcer severity and BD activity scores, Psychological and Social Well-being scales, Headache Impact Test-6 (HIT-6) were included. All the analyses were performed with R software.
Results
The alpha and beta diversity had anatomical specificity, with significant differences between genital and oral samples; p values<0.05 irrespective of presence or absence of ulcers. Interestingly, in the genital area Bacteroidota were present (G_U: 29% - 10%) and (G_nU: 27% - 14%) compared to less than 1% oral area of V1/V2 and V3/V4. Proteobacteria were uniquely present with (O_U: 9%) and (O_nU: 12%) in oral, and less than 0.01% in genital area for V3/V4 region. Gender anatomical specific communities were noted: females with genital ulcers Gardnerella, Lactobacillus, Atopobium were significantly increased compared to than males, with V3/V4 analysis indicating that Lactobacillus and Gardnerella were significantly increased by 20 times in females than males (p-adj <0.05). In contrast Peptoniphilus and Corynebacterium were significantly increased in males than females. Streptococcus was significantly increased with oral ulceration, while Veillonella was significantly decreased in patients without oral ulceration. Colchicine had a significant effect on the bacterial abundance irrespective of the presence or absence of ulceration. In this cohort, the WSAS (Work and Social Adjustment Scale) values were higher in active disease.
Conclusion
Our results suggest that dysregulated microbial communities occur in BD. V1/V2 demonstrates that during episodes of ulceration the pathogenic bacteria genus Escherichia-Shigella appear in both oral and genital ulcers. V3/V4 outcomes show that ulceration in both regions is assigned to genus; Lachnospiraceae, Saccharimonidales, Coriobacteriales. Streptococcus is related to the presence of oral ulcers, while Veillonella is presence when patients are ulcers free may be a useful marker of disease regression.
Behcet's disease (BD) is a systemic vasculitis characterized by recurrent episodes of inflammation with aphthous stomatitis, genital ulcers, skin, joint and internal organ involvement. Currently, there are no reliable laboratory markers that can be used to monitor BD activity. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have low sensitivity, so the search for new biomarkers continues. Neutrophil reactivity intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), immature granulocytes (IG), neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII) are new inflammatory indicators whose role in BD is not well studied.
Objective : to evaluate and compare the efficacy of the determination of NEUT-RI, NEUT-GI, IG, SII, NLR, ESR and CRP in the diagnosis of active BD.
Material and methods . 84 patients with a reliable diagnosis of BD and 38 healthy controls were included in the study. BD activity was assessed using the Behcet’s Disease Current Activity Form (BDCAF). Patients with BD were divided into two groups according to activity: Group I included 41 patients with high activity (BDCAF >5) and Group II included 43 patients with low activity (BDCAF ≤5). A complete blood count with determination of NEUT-RI, NEUT-GI, IG, SII and NLR was performed in all patients and healthy donors using the Sysmex XN 1000 automated haematology analyzer (Sysmex Сorp, Japan). ESR was determined using the Westergren method. High-sensitivity serum CRP level was determined in all patients with BD (normal range ≤5) by immunonephelometric method.
Results and discussion . Patients with active BD had significantly higher levels of neutrophils, SII, NLR, NEUT-RI, IG, ESR and CRP compared to patients with low disease activity. ROC analysis was performed to compare the significance of these inflammatory markers in the assessment of BD activity. The SII had the largest area under the ROC curve (AUC =0.816). The sensitivity and specificity of the SII at a value of 509.75 or higher for determining the active form of BD were 79.4% and 71.8%, respectively.
Conclusion . The new inflammatory parameters (SII, NLR, NEUT-RI and IG) and the traditional inflammatory parameters (ESR, CRP, neutrophils) can serve as laboratory markers for BD activity. SII is the most informative parameter to determine BD activity with optimal sensitivity and specificity.
OBJECTIVES
To evaluate the prevalence, magnitude, and potential determinants of work productivity impairment in patients with Behçet's Syndrome (BS), focusing on the role of irreversible organ damage.
METHODS
A post-hoc analysis of the BS overall damage index (BODI) prospective validation study was performed. Demographics and clinical features were recorded in all patients. The Work Productivity and Activity Impairment: General Health (WPAI: GH) questionnaire was administered to assess the work limitation and the BODI to measure organ damage. The independent effect of BS features on WPAI: GH outcomes was evaluated by regression analysis.
RESULTS
Out of 148 patients, 34.5% were unemployed, with age (OR 1.035) and BODI score (OR 1.313 for 1-unit increase) as the only factors significantly (p< 0.05) associated with the unemployment state. An overall work impairment was reported in about 64.2% of the employed patients. Indeed, 22.7% reported missing work h due to their health (absenteeism), with a mean time loss of 34.4%; whereas 60.2% declared a reduced performance at work because of their health (presenteeism), with a mean productivity impairment of 45.4%. Ocular damage was associated with absenteeism (β 0.225); female sex (β 0.260), physician global assessment of disease activity (β 0.502) and an increased BODI score (β 0.166 for 1-point increase) with presenteeism; fibromyalgia (β 0.246), physician global assessment (β 0.469), and musculoskeletal damage (β 0.325) with overall work impairment.
CONCLUSIONS
Disease activity and organ damage accrual remarkably affect work productivity in BS patients. Achieving remission and preventing damage accrual are crucial and complementary objectives.
Background:
Behçet's disease (BD) has a growing prevalence in Silk Road countries. The aim of our cross-sectional study was to explore the clinical and molecular predictors of quality of life in BD patients.
Material and methods:
One hundred and fifty consecutive Iranian BD patients with an age range between 20-50 years were included. The Leeds Behçet's disease quality of life (BDQoL) in Persian form was fulfilled to evaluate quality of life. Anthropometric measurements were carried out using the calibrated scales. Iranian Behcet's Disease Dynamic Activity Measure (IBDDAM), Behcet's disease current activity form (BDCAF), and Total Inflammatory Activity Index (TIAI) were used to assess BD activity. mRNA expression of toll-like receptors 2 and 4 (TLR2 and TLR4) and tumor-necrosis-factor-alpha (TNF-α) level in serum were measured by real-time polymerase-chain-reaction (PCR) and ELISA, respectively. Multiple linear backward regression at P=0.1 was used to study on the potential predictors of quality of life.
Results:
TLR2 and BDCAF were shown to be the most important predictors of quality of life in BD patients by 22%. There were the positive associations between them (β = 0.326, p = 0.013 for BDCAF; β = 0.366, p = 0.006 for TLR2) and BDQoL value.
Conclusion:
Higher TLR2 expression as a key protein in recognition of pathogens by innate immunity and BDCAF value as a comprehensive BD assessing scale contribute to poor quality of life among BD patients. Emphasizing on therapeutically approaches associated with lower TLR2 expression and BDCAF value can be considered in future studies.
Background:
Behçet's disease is a systemic vasculitis affecting both arteries and veins, as well as caus- ing recurrent inflammatory multiorgan disease. Vascular involvement is associated with increased mortality and morbidity. Matrix metalloproteinases are released at sites of inflammation and degrade various components of the extracellular matrix. Increased levels of metalloproteinase-9 and metal- loproteinase-2 have been previously reported in Behçet's disease.
Methods:
In this cross-sectional study, metalloproteinase-2 and metalloproteinase-3 serum levels were investigated in 103 patients with Behçet's disease and 69 healthy controls, using Invitrogen immunoassay human metalloproteinase-2 and metalloproteinase-3 ELISA kits.
Results:
Serum metalloproteinase-2 and metalloproteinase-3 levels were significantly higher in the Behçet's disease group compared to healthy controls. Besides, serum metalloproteinase-3 levels were significantly higher in subgroups of Behçet's disease with aneurysmal vascular involvement and with neurological involvement. However, metalloproteinase-2 and metalloproteinase-3 serum levels did not show a positive correlation with disease activity.
Conclusion:
Metalloproteinase-2 and -3 may contribute to the complex pathogenesis of Behçet's dis- ease. More importantly, the detection of very high serum levels of metalloproteinase-3 may predict the formation of an aneurysm, or possibly the presence of neurological involvement in Behçet's dis- ease and may lead the clinician to make an earlier diagnosis of these complications in young male patients with high risk.
Unlabelled:
Almost 90% of Behçet's patients present with oral and/or genital ulcers which influence the disease outcome. We hypothesised that the dysregulation of the oral and genital microbiome, coupled with dysregulation of the immune response, contributes to the aetiopathogenesis of Behçet's Disease (BD) and drives disease activation.
Method:
152 BD patient samples; 70 matched oral and genital samples plus 12 unmatched samples (Female: Male, 58:12; mean age, 42 ± 13.9: 39.3 ± 10.3) to profile microbial community high-throughput sequencing of the microbiome using 16 s rRNA sequencing targeting the V1/V2 and V3/V4 hyper variable regions were used and results reviewed in relation to disease severity, Work and Social Adjustment Scale (WSAS) outcomes and medication.
Results:
Alpha and beta diversity were significantly decreased in genital compared to oral samples; p value<0.05. However, grouping the samples as to whether ulceration was present was not significant. Escherichia-Shigella was the only Amplicon Sequence Variants (ASVs) in the V1/V2 region that was shared between the oral mucosa with ulcer (O_U) and genital mucosa with ulcer (G_U) groups. This was in contrast to the V3/V4 region which indicated that Lachnospiraceae, Saccharimonadales, and Coriobacteriales were shared between the O_U and G_U groups. In addition, gender had no impact on the bacterial abundance in V1/V2 analysis of the oral and genital samples. V3/V4 analysis of genital samples demonstrated that Lactobacilli and Gardnerella were significantly increased in females (20 times) compared to the males in samples; p-adj <0.05. Interestingly in BD patients, Rothia which is commonly found in the mouth was present in both oral and genital samples. Streptococci were significantly increased while Veillonella significantly decreased in the presence of oral ulceration in the BD cohort. The clinical phenotype had no effect on V1/V2 and V3/V4 on the bacterial abundance of oral samples. However, medication e.g. colchicine had a significant effect on the oral microbial abundance (V1/V2; P = 0.020, V3/V4; P = 0.003). There was no relationship between colchicine and the presence/absence of genital ulcers. BD patients with active disease had higher WSAS scores, and their bacterial abundance differed significantly from the non-active BD patients (ADONIS, R2 = 0.05, p value =0.029).
Conclusion:
The presence of the microbes Streptococcus, Veillonella, Gardnerella, Lactobacillus, Atopobium, Peptoniphilus, Corynebacterium and Staphylococcus may provide early evidence of BD patients are with active disease.
To evaluate the intima media thickness of carotid arteries (IMT) and its clinical, laboratory and treatment correlates in Behcet’s disease (BD). Systematic search of EMBASE and PubMed databases from January 2016 to October 2022; we employed random effect meta-analyses for continuous outcomes and Peto’s odds ratio for rare events. The meta-analysis included 36 case control studies: the IMT was greater in BD (n = 1103) than in controls (n = 832) (p < 0.0001) with wide heterogeneity (I² = 86.9%); a sensitivity analysis that included mean age of BD participants, gender, disease duration and activity, atherogenic index of plasma, blood pressure, C-reactive protein, ethnicity, smoking status, anti-inflammatory and immune suppressive agents, revealed that male gender, mean age of participants and azathioprine use (the latter two in inverse fashion) partly explained the heterogeneity variance (p = 0.02, p = 0.005, and p = 0.01). The IMT was greater in vascular (n = 114) than in non-vascular BD (n = 214) (p = 0.006). BD patients (n = 782) had a greater pooled prevalence of carotid plaques than controls (n = 537) (13.1% vs. 2.97%, p < 0.0001). Subclinical carotid artery atherosclerosis represents a vascular feature of BD, independently of the traditional cardiovascular risk factors. The inverse correlations between IMT, age and azathioprine use suggest that thicker carotid arteries at disease onset eventually regress with immune suppressive treatment: this assumption needs verification on adequately designed clinical trials.
Background:
Despite enormous clinical improvements, due to better management strategies and the availability of biologicals, immune-mediated inflammatory diseases (IMIDs) still have a significant impact on patients' lives. To further reduce disease burden, provider- as well as patient-reported outcomes (PROs) should be taken into account during treatment and follow-up. Web-based collection of these outcomes generates valuable repeated measurements, which could be used (1) in daily clinical practice for patient-centered care, including shared decision-making; (2) for research purposes; and (3) as an essential step toward the implementation of value-based health care (VBHC). Our ultimate goal is that our health care delivery system is completely aligned with the principles of VBHC. For aforementioned reasons, we implemented the IMID registry.
Objective:
The IMID registry is a digital system for routine outcome measurement that mainly includes PROs to improve care for patients with IMIDs.
Methods:
The IMID registry is a longitudinal observational prospective cohort study within the departments of rheumatology, gastroenterology, dermatology, immunology, clinical pharmacy, and outpatient pharmacy of the Erasmus MC, the Netherlands. Patients with the following diseases are eligible for inclusion: inflammatory arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, uveitis, Behçet disease, sarcoidosis, and systemic vasculitis. Generic and disease-specific (patient-reported) outcomes, including adherence to medication, side effects, quality of life, work productivity, disease damage, and activity, are collected from patients and providers at fixed intervals before and during outpatient clinic visits. Data are collected and visualized through a data capture system, which is linked directly to the patients' electronic health record, which not only facilitates a more holistic care approach, but also helps with shared decision-making.
Results:
The IMID registry is an ongoing cohort with no end date. Inclusion started in April 2018. From start until September 2022, a total of 1417 patients have been included from the participating departments. The mean age at inclusion was 46 (SD 16) years, and 56% of the patient population is female. The average percentage of filled out questionnaires at baseline is 84%, which drops to 72% after 1 year of follow-up. This decline may be due to the fact that the outcomes are not always discussed during the outpatient clinic visit or because the questionnaires were sometimes forgotten to set out. The registry is also used for research purposes and 92% of the patients with IMIDs gave informed consent to use their data for that.
Conclusions:
The IMID registry is a web-based digital system that collects provider- and PROs. The collected outcomes are used to improve care for the individual patient with an IMID and facilitate shared decision-making, and they are also used for research purposes. The measurement of these outcomes is an essential step toward the implementation of VBHC.
International registered report identifier (irrid):
DERR1-10.2196/43230.
Aim: This study aims to determine the effect of common symptoms on Quality of Life (QoL) in patients with Behcet Disease (BD) and complementary and integrative health approaches used by patients to cope with these symptoms. Methods: The population of this descriptive study consisted of all patients with BD (n = 330) who are registered with the Behçet’s Disease and Familial Mediterranean Fever Patients Association. The data were collected by the researcher and the president of the association, via an online form between 31.08.2020-06.12.2020. The sample consisted of all patients with BD who met the inclusion criteria (n=247). The data were collected using the Patient Information Form, BD Current Activity Form (BDCAF) and Behçet's Disease Quality of Life Scale (BDQoL). Findings: Joint involvement, rectal bleeding, eye involvement, number of attacks, and disease activity are determinants of 42.5% in affecting QoL (R2 = 0.425, p <0.001). 37.5% of patients with BD have been using CIHA for the last 1 year. They use black mulberry molasses (32%), coriander (9.3%), and thyme juice mouthwash (4%) for mouth sores, wet cupping (24%), and St. John’s wort oil (19%) for genital wounds among CIHA methods. Conclusion: The decisive factor in the use of CIHA in patients with BD was to have genital wounds or loss of sensation in the arm. Therefore, the results of this study are important in terms of leading to further experimental studies to determine the CIHA to be used for symptoms in patients with BD.
Aim of the work
To investigate protein Z (PZ) gene polymorphic variations; PZ G79A (rs3024735) and PZ G-103A (rs3024719) in Behçet's disease (BD) patients and their possible relation with disease manifestations, activity and damage.
Patients and methods
This study included 100 BD patients and 100 controls. BD current activity form (BDCAF) and the BD damage index (BDI) were assessed. Genomic DNA analysis of PZ G79A (rs3024735) and PZ G-103A (rs3024719) single nucleotide polymorphisms, was assessed by Real-time PCR-TaqMan SNP genotyping assay.
Results
The mean age of patients was 33.4 ± 6.8 years and median disease duration was 9 years. AA and GA genotypes of PZ G79A polymorphism were significantly higher in patients than controls (p = 0.003 and p = 0.004 respectively). The frequency of A allele was significantly higher in patients than controls (p < 0.001). There was no difference between patients and controls regarding AA and GA genotypes of PZ G-103A polymorphism (p = 0.5 and p = 0.2 respectively). There was a significant association between AA and GA genotypes of PZ G79A polymorphism with retinal vascular occlusion (RVO) (p < 0.001) and deep vein thrombosis (DVT) (p = 0.003), neutrophil–lymphocyte ratio (p < 0.001) and BDI (p < 0.001). There was no association between PZ G79A genotypes and BDCAF (p = 0.8). A allele of PZ G79A polymorphism was associated with increased BD susceptibility (p < 0.001), RVO (p = 0.001) and DVT (p = 0.01).
Conclusion
PZ G79A (rs3024735) polymorphism A allele was associated with increased susceptibility to BD with increased risk of developing RVO, DVT and damage, while AA and GA genotypes of PZ G-103A polymorphism were not significantly increased in BD patients.
Objective
To assess apremilast’s impact on patient quality of life (QoL) in active Behçet’s syndrome and correlations between improvement in patients’ QoL and efficacy measures in the phase 3 RELIEF study.
Methods
QoL measures included Behçet’s Disease QoL (BDQoL), 36-Item Short-Form Health Survey V.2 (SF-36v2) Physical/Mental Component Summary (PCS/MCS) and eight subscale scores, focusing on Physical Functioning (PF). Pearson’s correlation coefficients assessed relationships between efficacy endpoints (oral ulcer count, oral ulcer pain, Behçet’s Syndrome Activity Scale (BSAS), Behçet’s Disease Current Activity Form (BDCAF)) and QoL endpoints for apremilast at Week 12.
Results
Apremilast (n=104) demonstrated significantly greater improvements versus placebo (n=103) in SF-36v2 PCS (3.1 vs 0.9), MCS (4.6 vs ─0.7) and PF (2.9 vs 0.14), respectively (all p<0.05). Mild correlations were observed in improvements of SF-36v2 measures (PCS, MCS, PF) with oral ulcer count (r=−0.11, PCS), and change in oral ulcer pain from baseline (r=−0.28, PCS; r=−0.10, PF) and BSAS (r=−0.38, PCS; r=−0.20, PF; r=−0.16, MCS). Correlations among BDCAF and SF-36v2 components and BDQoL were variable. BDQoL showed mild/moderate correlations with SF-36v2 components (r=−0.18, PCS; r=−0.13, PF; r=−0.45, MCS).
Conclusions
Apremilast was associated with significant improvements in QoL measures of SF-36v2 PCS, MCS and PF and BDQoL in patients with Behçet’s syndrome. Correlations of improvement among QoL endpoints support the beneficial clinical effects of apremilast in Behçet’s syndrome.
Trial registration number
NCT02307513 .
Background
Metabolic syndrome (MetS) is characterized by insulin resistance, high blood pressure/sugar, dyslipidemia, and obesity. Whether MetS and its components affect the development of Behçet's Disease (BD) remains unclear.
Aims
The aim was to determine the frequency of MetS among BD patients and to study its relation to the disease characteristics.
Methods
The study included 1028 adult BD patients recruited from 18 specialized rheumatology centers. 51 healthy matched control were considered. Behçet Disease Current Activity Form (BDCAF) and the BD damage index (BDI) were estimated. Adult Treatment Panel-III criteria were used to define MetS.
Results
The mean age of patients was 36.8±10.1 years, M:F 2.7:1 and disease duration 7.01±5.2 years. Their mean BDCAF was 5.1±4.6 and BDI 5.5±2.8. MetS was present in 22.8% of patients and in 5.9% of control (3.9 fold higher-risk). Patients with MetS had a significantly increased age at onset (31.8±9.2 vs 29±8.5 years) and higher frequency of genital ulcers (96.2% vs 79.7%), skin involvement (73.1% vs 50.4%), arthritis (48.3% vs 29.1%)(p<0.0001) and CNS manifestations (18.8% vs 13%)(p=0.042) compared to those without. Eye involvement was significantly increased in those with MetS (82.1% vs 74.2%)(p=0.003) with increased frequency of posterior uveitis (67.1% vs 43.5%), retinal vessel occlusion (35.9% vs 21.3%), retinal vasculitis (41.9% vs 26.4%)(p<0.0001) and vitritis (37.2% vs 24%)(p=0.001). BDCAF was significantly lower (3.9±4.3 vs 5.6±4.6) and BDI higher (7.4±2.7vs5±2.6)(p<0.0001).
Conclusion
BD patients with MetS are predisposed to mucocutaneous, musculoskeletal, neuropsychiatric and ocular manifestations with consequently increased damage. The affection of the deeper structures of the eye should alarm rheumatologists to keep in mind that all patients should have an eye examination especially those with MetS.
Background
Behçet’s disease gives a challenge to be diagnosed and followed up due to lack of specific biomarkers. MicroRNAs showed relations to different disease states including immunological and inflammatory illnesses. In this study, we are estimating microRNA548ac levels for the first time to be tested in the disease to see if there is a link to disease activity and if microRNA548ac can be used as a biomarker for activity or remission and prognosis of Behçet’s disease. MicroRNA548ac has been shown to have a role in autoimmunity and some inflammatory conditions. Blood samples were taken from patients to measure white blood cells expression of microRNA548ac, and compared to its expression in healthy subjects, disease activity was assessed by usage of Behçet’s Disease Current Activity Form (BDCAF).
Results
MicroRNA548ac expression decreased but not significantly with increased Behçet’s disease activity, and expression was having a significant positive correlation with increased treatment response history.
Conclusions
MicroRNA548ac appeared not to be related to disease activity which needs confirmation in further studies, but it may predict response to treatment so that patients having higher expression of microRNA548ac may have a better response to treatment. Here, microRNA548ac could be used as a disease biomarker for disease prognosis.
Interleukin-32 (IL-32) is a pro-inflammatory cytokine that induces other cytokines involved in inflammation, including tumour necrosis factor (TNF)-a, IL-6 and IL-1β. The objective of this study was to evaluate IL-32, NLRP3 inflammasome, IL-1β, IL-6, IL-17A, TNF-a, IL-10 and IL-37 in cerebrospinal fluid (CSF) and paired serum samples of patients with neuro-Behcet disease (NBD) by ELISA, RT-PCR and Western blotting analysis. A receiver operating characteristic (ROC) curve was employed to explore of the predictive value of IL-32 levels. IL-32, IL-1β, IL-6, IL-17 and TNF-α, were highly expressed in CSF of NBD and multiple sclerosis (MS) patients contrasting with their low levels in patients with noninflammatory neurological diseases (NIND) and Headache attributed to BD (HaBD). IL-32 and NLRP3 inflammasome in NBD, correlate significantly with CRP and ESR. IL-32 should be studied further as potential BD biomarkers of inflammation in NBD.
Background
T lymphocytes are one of the major components of the adaptive immunity in Behçet’s syndrome (BS) pathology. To further understand of the role of T cells in Behçet’s syndrome (BS), we explore disease related T cell receptor (TCR) repertoires.
Methods
We performed a bulk sequencing of the TCR beta chain (TRB) of peripheral T-cells collected from 45 BS patients with panuveitis, intestinal involvement, and cardiovascular lesions and 10 cases of healthy controls (HC). Data analysis included peptide sequences, diversity analysis, variable (V)-joining (J) gene usage and K-nearest neighbor algorithm.
Results
We found significant differences in V, J and V-J combinations between the BS patients and HC. The decrease in TCR clone diversity indicates clonal expansion in BS. Although no significant difference in TCR clone diversity was observed among patient subgroups, the patients with panuveitis displayed the highest heterogeneous TCR distribution. In addition, a set of V-J genes could effectively discriminate between active and inactive BS patients with an area under the receiver operating characteristics (ROC) curve of 0.88 (95% CI: 0.77-1.00).
Conclusions
Clonal T cell expansion has been observed in BS patients. TCR profiles could help in the discrimination between active and inactive BS.
Eight patients with stable Behçet's disease were studied by means of multimodality evoked potentials and magnetic resonance imaging to evaluate the possibility of an earlier and objective demonstration of clinical and subclinical Central Nervous System (CNS) involvement. It was shown that both diagnostic techniques are useful for quantitative evaluation of neurological involvement in Behçet's disease; of particular interest was the demonstration of subclinical CNS changes.
Thirty one patients with Behçet's disease and neurological manifestations were prospectively studied with MRI. Cerebral venous thrombosis was diagnosed in 10 patients. MRI performed during the acute illness in eight patients showed an abnormally high signal on the T2 weighted sequences in the occluded sinus. MRI showed minor flow abnormalities suggestive of partial recanalisation of the sinus in two cases at a later clinical stage. MRI can be an alternative, non-invasive, investigation to intravenous cerebral angiography. In 13 patients with central nervous system involvement, MRI performed during the acute illness showed multiple hyperintense lesions on T2 weighted sequences. They were usually less than 5 mm, scattered and confluent, mainly in the white matter, distributed in the hemispheric white matter in nine cases, brainstem in eight, basal ganglia and thalamus in five, and cortex in two. MRI abnormalities were usually associated with appropriate clinical deficits, but were larger and more disseminated than expected.
• A multicentric crossover randomized trial of 100 mg of thalidomide vs placebo each for 2 months was conducted in patients with severe aphthous stomatitis of more than 6 months' duration. Seventy-three patients were included. Complete remission was obtained in 32 patients who received thalidomide and in 6 patients who received placebo. The confidence interval of the difference between the two treatments ranged from 25% to 53%. Most of the patients who did not achieve a complete remission had a dramatic improvement with regard to the number of aphthae when they were receiving thalidomide. Thirteen of 17 patients who had a complete remission while they were receiving thalidomide had a recurrence with placebo, 19 ± 9 (mean ± SD) days after stopping this drug. Side effects were significantly more frequent with thalidomide, especially drowsiness and constipation. We concluded that thalidomide in a dosage of 100 mg/d is an effective treatment of severe aphthous stomatitis but is not without some risk.
(Arch Dermatol. 1990;126:923-927)
No fewer than five sets of diagnostic criteria for Behçet's disease are currently in use. The International Study Group have therefore undertaken an extensive study of existing criteria and have developed recommended new international criteria based on the collection of data from 914 patients with Behçet's disease and 308 controls, of whom 886 (97%) and 97 respectively had mouth ulceration. It is recommended that these new criteria should replace the existing criteria sets although further studies are required to evaluate their performance in new patient groups.
Six systems for defining and evaluating disease activity in patients with systemic lupus erythematosus (SLE) (the Ropes system, the National Institutes of Health [NIH] system, the New York Hospital for Special Surgery system, the British Isles Lupus Assessment Group [BILAG] scale, the University of Toronto SLE Disease Activity Index [SLE-DAI], and the Systemic Lupus Activity Measure [SLAM]) were tested on 25 SLE patients who were selected to represent a range of disease activity. The patients were evaluated independently by 2 physicians on 2 occasions approximately 1 month apart. Differences between patients demonstrated the largest source of variation in scores, accounting for 56–84% of the total variance, depending on the instrument. Differences between physicians (i.e., error) showed the next largest variation, 11–28% of the total variance, and differences between visits made up 5–16% of the total. The BILAG, SLE-DAI, and SLAM had the best inter-visit and inter-rater reliability. Convergent validity was shown by the strong correlations of scores among the different instruments (r = 0.81–0.97). All instruments correlated highly with the physicians' clinical impression of disease but less well with their evaluation of disease severity. The number of American Rheumatism Association criteria for SLE that were met by the patients correlated poorly with the physicians' global evaluation and with the scores of the instruments. The patients' self-reported disease activity scores correlated highly with the physicians' assessments of disease activity (r = 0.85–0.91), and the mean values from self-reports and from physicians' assessments were nearly equal. In contrast, severity scores correlated less well between self-reports and physician assessments (r = 0.49–0.69), and mean self-reported severity values were lower than the means from physicians. The BILAG, SLE-DAI, and SLAM systems appear to have better psychometric properties than the others for clinical research.
A multicentric crossover randomized trial of 100 mg of thalidomide vs placebo each for 2 months was conducted in patients with severe aphthous stomatitis of more than 6 months' duration. Seventy-three patients were included. Complete remission was obtained in 32 patients who received thalidomide and in 6 patients who received placebo. The confidence interval of the difference between the two treatments ranged from 25% to 53%. Most of the patients who did not achieve a complete remission had a dramatic improvement with regard to the number of aphthae when they were receiving thalidomide. Thirteen of 17 patients who had a complete remission while they were receiving thalidomide had a recurrence with placebo, 19 +/- 9 (mean +/- SD) days after stopping this drug. Side effects were significantly more frequent with thalidomide, especially drowsiness and constipation. We concluded that thalidomide in a dosage of 100 mg/d is an effective treatment of severe aphthous stomatitis but is not without some risk.
Five centres in Great Britain and the Republic of Ireland have collaborated to produce a computerized index of clinical disease activity in systemic lupus erythematosus, based on the principle of the physician's intention to treat. The index assesses separately eight organ-based systems. The index has proved quick and easy to use despite a comprehensive database and compares favourably with two other indices of disease activity. It has great potential for use in multicentre studies of disease outcome and new therapies in systemic lupus erythematosus.
In a prospective study of 150 patients with Behçet's disease, significant associations were shown between CRP positivity and the presence of erythema nodosum (p less than 0.02) and acute thrombophlebitis (p less than 0.05) and between ESR and erythema nodosum (p less than 0.01), acute thrombophlebitis (p less than 0.001), and acute arthritis (p less than 0.01). Mucocutaneous, ocular, or central nervous system activities did not show significant associations with these indices of inflammation. In 50 patients in whom quantitative CRP determinations were performed, clinical disease activity was accompanied by slight to moderate increases in CRP and ESR.
Magnetic resonance imaging (MRI) was performed in 25 patients with Behçet's disease, of whom 15 had clinical involvement of the central nervous system (CNS). Brain MRI was abnormal in 11/15 with and in 1/10 without CNS involvement. The most common sites of MR lesions were the cerebral white matter and brainstem. Lesions were also seen in the basal ganglia, cerebellum, optic nerves and spinal cord. The cerebral white matter lesions were always asymptomatic and usually small, whereas the brainstem lesions were often symptomatic and sometimes extensive. Follow-up MRI in 2 patients presenting with brainstem syndromes and treated with immunosuppression showed resolution of a large lesion in 1 patient in whom there was clinical remission, and the development of marked brainstem atrophy in the other who became severely disabled. The pattern of MRI abnormalities may assist the diagnosis and suggests a role for MRI in monitoring the effect of treatment in patients with neurological Behçet's disease.
Int Congress Series 1037, 611 Amsterdam: Elsevier 1. International Study Group for Behçet's Disease
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