Objectives:To develop evidence-based European League Against Rheumatism (EULAR) recommendations for the management of Behçet disease (BD) supplemented where necessary by expert opinion.Methods:The ...multidisciplinary expert committee, a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), consisted of nine rheumatologists (one who was also a clinical epidemiologist and one also a Rehabilitation Medicine doctor), three ophthalmologists, one internist, one dermatologist and one neurologist, representing six European countries plus Tunisia and Korea. A patient representative was also present. Problem areas and related keywords for systematic literature research were identified. Systematic literature research was performed using Medline and the Cochrane Library databases from 1966 through to December 2006. A total of 40 initial statements were generated based on the systematic literature research. These yielded the final recommendations developed from two blind Delphi rounds of voting.Results:Nine recommendations were developed for the management of different aspects of BD. The strength of each recommendation was determined by the level of evidence and the experts’ opinions. The level of agreement for each recommendation was determined using a visual analogue scale for the whole committee and for each individual aspect by the subgroups, who consider themselves experts in that field of BD. There was excellent concordance between the level of agreement of the whole group and the “experts in the field”.Conclusion:Recommendations related to the eye, skin–mucosa disease and arthritis are mainly evidence based, but recommendations on vascular disease, neurological and gastrointestinal involvement are based largely on expert opinion and uncontrolled evidence from open trials and observational studies. The need for further properly designed controlled clinical trials is apparent.
Background:
The importance of patient involvement in healthcare research is increasingly emphasized. Patients participate as research partners in designing studies and development of management ...recommendations, measurement tools and outcome measures. However, ensuring representation of the general patient population by specific patient groups may be challenging for multisystem diseases with heterogenous phenotype.
Objectives:
We aimed to evaluate whether patients with Behcet syndrome (BS) participating in a patient convention represent the actual patient population attending the clinic.
Methods:
A questionnaire was applied to 104 BS patients (Meeting group) attending the patient convention which was held during the Cerrahpasa Behcet Disease Symposium in Istanbul in February 2020. Patients had been invited to the convention through posters, advertisement on our website and social media. The questionnaire was conducted with a keypad given to the patients and it consisted of 21 items including age, gender, education level, working status, disease duration, BS manifestations, and treatment. The same questionnaire was filled by 97 consecutive patients (Clinic group) who attended our rheumatology outpatient clinic for their routine controls. Chi-square test was used to compare the groups.
Results:
Table 1 shows demographic and disease characteristics of the patient groups. The groups were similar in terms of sex and education level. There were more men in both groups, probably reflecting the more severe disease course among men in BS. There were significantly more patients who were >40 years of age and had a disease duration more than 20 years in the Meeting group. Although there were more patients who had a job in Clinic group, the difference was not significant. Central nervous system involvement, vascular involvement, genital ulcers, erythema nodosum, and arthritis were significantly more common in patients in the Meeting group compared with those in the Clinic group. The frequency of eye involvement, gastrointestinal involvement and papulopustular lesions were similar in the two groups. Cyclophosphamide use was significantly more common in Meeting group compared to the Clinic group.
Table 1.
Demographics, clinical characteristics, and treatments
Meeting Group
(n=104)
(n/N, %)
Clinic Group
(n=97)
(n, %)
P
Oral aphthous ulcers
88/97(91)
94(97)
0.13
Genital ulcers
86/104(83)
68(70)
0.045
Erythema nodosum
77/103(75)
47(48)
0.0003
Papulopustular skin lesions
69/103(67)
75(77)
0.09
Arthritis
78/102(77)
46(47)
<0.0001
Eye involvement
51/103(50)
53(55)
0.48
Vascular involvement
42/98(43)
25(26)
0.036
CNS involvement
14/103(14)
2(2)
0.016
GI involvement
14/97(14)
6(6)
0.10
Prednisolone - still using
30/104(29)
34(35)
0.37
Prednisolone - ever used
88/104 (85)
72(74)
0.08
Colchicine - still using
43/100 (43)
46(47)
0.57
Colchicine - ever used
86/100(86)
74(76)
0.10
AZA - still using
45/100 (45)
41(42)
0.77
AZA - ever used
81/100 (81)
74(76)
0.49
CYC - still using
1/96(1)
0(0)
NS
CYC - ever used
16/96(17)
7(7)
0.048
bDMARDs - still using
20/101(20)
26(27)
0.31
bDMARDs - ever used
28/101(28)
32(33)
0.44
* Adjusted
P
-values by Bonferroni correction were <0.001.
BS: Behcet Syndrome, CNS: Central nervous system, GI: Gastrointestinal, AZA: Azathioprine, CYC: Cyclophosphamide; bDMARDs: Biologic disease-modifying anti-rheumatic drugs; NS: non-significant
Conclusion:
Patients in the Meeting group had more severe disease compared to the Clinic group. Patients with all types of involvement were adequately represented in the Meeting group.
Disclosure of Interests:
None declared
BackgroundThe quality of statistical analysis and reporting are wanting even in our most prestigious journals.1 It stands to reason that active participation of biostatisticians in data analysis and ...reporting would improve the situation.ObjectivesWe aimed to test the hypothesis that more close cooperation with biostatisticians would improve the quality of reporting randomised clinical trials in rheumatology. We defined a close cooperation as the inclusion of a formal biostatistician among the co-authors and/or a declaration of formal statistical help in the study reports.MethodsTwo independent observers screened both by reading and, when applicable, electronic scanning the texts of all randomised controlled trials (RCT) in Annals of the Rheumatic Diseases, Arthritis Care and Research, Arthritis and Rheumatology, Rheumatology Oxford published in 2015 and 2016. Using a prepared worksheet, the observers specifically tabulated, the presence of a biostatistician among the co-authors and/or formal acknowledgement of statistical help in the methods, the inclusion of effect sizes (whether they were specifically indicated as such, could be calculated or not given at all) and the corresponding confidence intervals. The instances in which an effect size was given as a number needed to treat (NNT) and number needed to harm (NNH) were separately sought. In addition at the number of times separate p values were reported for interdependent comparisons (like DAS28-CRP and DAS28-ESR), and the presence of a Bayesian analysis in the methods.ResultsThe total RCT number in these four journals was 134. In 26 trials, there was a biostatistician or an epidemiologist as a co-author and in 3, statistical help was acknowledged in the text. In the remaining 105 papers (78%) no statistical help was declared. The tabulation of effect sizes, confidence intervals and giving separate p values for interdependent variables are given in the table 1. In giving the effect sizes it is to be noted that the presence of a statistician made did not improve the explicit announcement of an effect size but made it more calculable. None of the trials used Bayesian methods for analysis. Only in one trial NNT and in another NNH (both with no acknowledged biostatistical help) were given.Abstract AB1387 – Table 1The differences of the parameters between two groupsGroup 1 (n=29) (with statistician)Group 2 (n=105) (without statistician)Calculated effect size between the Groups 1 and 2 Effect size reporting, n (%)26 (90)61 (58)32% (95% CI 13.1–43.3) p=0.001Given directly, n (%)2 (7)5 (5)Can be calculated (given HR, OR, RR, ß coefficient), n (%)24 (83)46 (44)Confidence intervals reporting, n (%)16 (55)43 (41)14% (95% CI −6–32.7) p=0.18Calculating p values for interdependent variables, n (%)14 (48)46 (44)4% (95% CI −14.9–23.9) p=0.67ConclusionsThe inclusion of a biostatistician improved the reporting of effect sizes, at least rendering them calculable. The same cannot be said for reporting confidence intervals and separate p values for interdependent variables. It was interesting that Bayesian analyses and giving NNT and NNH, rather intuitive ways of expressing effect sizes, were not popular. There were 2 main limitations. The sample size was relatively small and many authors could have obtained statistical help without acknowledging it.Reference1 Chavalarias D, et al. JAMA. 2016,315(11):1141–8Disclosure of InterestNone declared
Objectives. Behçet’s disease (BD) can be life threatening and may be refractory to corticosteroids and immunosuppressives. There has been some experience with haematopoietic stem cell transplantation ...(HSCT) in BD either for severe, refractory disease or for a haematological condition. The objectives of this study were to describe a BD patient undergoing HSCT and to evaluate the outcomes of BD patients who underwent HSCT.
Methods. We report a BD patient with refractory gastrointestinal (GI) involvement who had HSCT for concomitant myelodysplastic syndrome (MDS). We also performed a systematic literature search regarding HSCT for either refractory disease or concomitant haematological conditions in BD patients.
Results. A 30-year-old woman with refractory GI BD involvement with trisomy 8 MDS underwent a successful myeloablative allogeneic HSCT resulting in complete resolution of both BD and MDS. Additionally we identified 14 manuscripts providing data on 19 patients with BD who had HSCT. Among these 20 patients, including ours, refractory disease was the indication of transplantation in 9, while 11 patients were transplanted because of accompanying haematological conditions. Transplant indications for the nine patients (four male, five female) with refractory BD were neurological involvement in five, pulmonary artery aneurysm in two, GI disease in one and not reported in one patient. Three patients with neurological disease, both patients with pulmonary artery aneurysm and the patient with intestinal involvement achieved complete remission of their disease. Six patients transplanted for haematological conditions, including the presented case, also had GI involvement of BD. All of these patients achieved complete remission of GI findings after HSCT.
Conclusion. When considering HSCT, the potential adverse events and complications, which can be fatal, need to be kept in mind.
We have previously reported distinct symptom clusters among our patients with Behçet's syndrome (BS). The presence of such clusters suggests that more than one pathogenetic mechanism might be ...operative in BS. Increases in the frequency of certain clusters in familial BS cases, if present, would further support this notion. To test this hypothesis, we compared the frequency of symptom clusters between familial (group F) and non-familial (group NF) cases of BS.
We identified 380 BS patients who had reported a first-degree relative by reviewing 6031 patient charts. We were able to contact 186 (Group F). From the same initial pool, 500 patients were randomly selected. Of those, patients who did not report a family history of BS and who had attended our clinic during the previous 3 months made up group NF (n = 221). Both groups were questioned about their symptoms within the previous 3 months. Data were analysed using factor analysis, cluster analysis and χ2 tests.
The make-up of the symptom clusters were very similar for the factor and the cluster analyses. The frequency of papulopustular lesions and joint involvement cluster was significantly higher in group F (39.2 vs. 21.5%, P < 0.001). Furthermore, the same cluster was shared in 5/17 related pairs from group F and in only 5/110 unrelated pairs from group NF 29 vs. 4.5%, P = 0.004; risk ratio (RR) = 6.47, 95% CI 2.15, 18.89.
The papulopustular lesions and arthritis cluster in BS appears to cluster in familial BS as well. This further supports the notion that the pathogenesis of BS may entail several distinct mechanisms resulting in separate phenotype clusters.
Objectives:To present and analyse the literature sources regarding the management of Behçet disease (BD) identified during the systematic literature research, which formed the basis for the European ...League Against Rheumatism (EULAR) evidence-based recommendations for the management of BD.Methods:Problem areas and related keywords regarding the management of BD were determined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A systematic literature research was performed using MedLine and Cochrane Library resources through to December 2006. Meta-analyses, systematic reviews, randomised controlled trials (RCTs), open studies, observational studies, case control studies and case series’ involving ⩾5 patients were included. For each intervention the effect size and number needed to treat were calculated for efficacy. Odds ratios and numbers needed to harm were calculated for safety issues of different treatment modalities where possible.Results:The literature research yielded 137 articles that met the inclusion criteria; 20 of these were RCTs. There was good evidence supporting the use of azathioprine and ciclosporin A in eye involvement and interferon (IFN)α in mucocutaneous involvement. There were no RCTs with IFNα or tumour necrosis factor (TNF)α antagonists in eye involvement. Similarly controlled data for the management of vascular, gastrointestinal and neurological involvement is lacking.Conclusion:Properly designed, controlled studies (new and confirmatory) are still needed to guide us in managing BD.
Systemic sclerosis (SSc) represents extremely rare disease with majority of data coming from adults. Studies comparing juvenile- (jSSc) and adult-onset (aSSc) patients are limited. We aimed to ...compare clinical features, treatment modalities and survival rates of jSSc and aSSc patients.
A retrospective study among pediatric and adult Scl patients has been performed. Demographic characteristics, clinical features, autoantibody profiles, and treatment data were retrieved from the databases. Survival analysis was done using Kaplan-Meier plot and factors associated with mortality were identified with multiple regression analysis.
A total of 158 adults and 58 juvenile Scl patients were identified. The mean age at the disease onset was 37±14.7 vs. 8.8 ± 4.1 years, mean age at diagnosis 42±15.2 vs. 10.4 ± 3.8 years and mean follow-up duration was 6.3 ± 4.9 years vs. 6.6 ± 4.9 years for aSSc and jSSc patients, respectively. The frequency of interstitial lung disease (ILD) (50.9% vs 30%, p<0.001) and systemic hypertension (17.9% vs 0, p = 0.009) was significantly higher among aSSc. While aSSc patients had presented mostly with limited cutaneous subset (74.1%), diffuse cutaneous subset was the dominant subset among jSSc (76.7%), (p<0.001). The mortality rate was significantly higher among adults (p = 0.005). The ILD (p = 0.03) and cardiac insufficiency (p = 0.05) were independent risk factors of mortality in both aSSc and jSSc patients.
Juvenile and adult-onset Scl represent rarely seen conditions with different clinical phenotypes. Pediatric patients with LS are more commonly seen by pediatric rheumatologists, in contrary to adults. Diffuse disease subset is the dominant form among juvenile patients, whereas limited form is the main disease subset among adults. On the other hand, juvenile-onset patients have a better survival than those with adult-onset.
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BackgroundAortic involvement (AI) is an important complication of relapsing polychondritis (RP). Current literature is based on case reports and small case series.ObjectivesTo delineate the clinical ...characteristics and outcome of AI in RP through a systematic literature review (SLR).MethodsThe SLR covered all English articles retrieved with relevant keyword combinations listed in PubMed until October 2017. Initially the titles and abstracts were screened by two investigators and articles considered to be relevant (involvement of the aorta and the aortic valve) were identified. Data extraction was done by the same investigators.ResultsThe SLR revealed 352 papers of which162 were discarded at the first step and a further 114 after full reading. After excluding 5 articles reporting on the same patient, we finally had 71 papers reporting 97 patients. The sex distribution was identifiable in 79 patients of whom 39 were men and 40 were women. The median age at the first symptom of RP was 31.5 years IQR:24–43 years, the median age at RP diagnosis was 36 years IQR: 28–43 years; median age at the diagnosis of AI was 37 years IQR:29–49 years. Median duration from first RP diagnosis to AI diagnosis was less than 1 year Range:0–21. AI was the presenting symptom in 3 patients.Seventy patients (73%) had involvement of thoracic aorta and 16 (23%) had involvement of the abdominal aorta. Other involved arteries were: coronary (8 patients), subclavian (5 patients), renal (3 patients), iliac (3 patients) and others (8 patients). Two patients had neurologic and renal involvement, respectively.The most common symptoms were dyspnea (40%), followed by chest pain (13%), abdominal pain (13%) and fever (9%).The diagnosis of AI was made during surgery in 6 patients and with different radiologic methods ranging from chest x-ray to PET-CT.All patients excluding 1 received corticosteroids either alone or in combination with classical immunosuppressives (cyclophosphamide, azathioprine, methotrexate, mycophenolate-mofetil) or biologics (infliximab, tocilizumab, adalimumab).The majority of the patients (53/87 patients (61%) underwent surgery including aortic graft replacement, coronary by-pass, aortic valve or mitral valve replacement operations.16 patients died after a median follow up of 24 IQR:11–43 months. The reasons for deaths were mainly vascular (acute myocardial infarction, heart failure, cardiovascular operation, abdominal aorta dissection, aortic rupture and acute aortic valvular dysfunction).Information on follow-up was known in 30 patients for a median of 18.5 months IQR 10–48 months.ConclusionsAI is less frequently recognised but prognostically important complication of RP. Thoracic aorta is the most frequently involved site. Surgery is needed in the majority of patients. Medical treatment is empirical and is based on glucocorticoids and immunosuppressives including biologic agents. Despite treatment, mortality is high (18% during a median of 24 months).Disclosure of InterestNone declared
BackgroundThe fecal calprotectin (FC) level is widely used as a non-invasive method for identifying patients with active Crohn's disease (CD) and ulcerative colitis. Gastrointestinal involvement of ...Behçet's syndrome (GIBS) shows clinical and endoscopic similarities to CD. A previous study in a small number of Behçet's syndrome (BS) patients with mainly mucocutaneous lesions showed that serum calprotectin levels did not differ between active and inactive patients (1). Another study suggested that FC may help to diagnose GIBS patients (2). We are not aware of studies addressing whether FC levels help to distinguish active GIBS patients from those in remission.ObjectivesTo determine whether FC levels help predict active disease in GIBS patients.MethodsWe collected fecal specimens from 23 GIBS (11 M, 12 F and mean age 44±9 years) patients before colonoscopy. The reasons for colonoscopy were assessing active disease in patients presenting with abdominal pain (with or without diarrhea) (n=9) or confirmation of a remission in asymptomatic patients (n=16). Four symptomatic and 3 asymptomatic patients had active ulcers by endoscopy. On the other hand, 5 symptomatic and 13 asymptomatic patients did not have ulcers by endoscopy. We also included 22 active and 25 inactive CD patients as controls. We used 150 μg/g as the cut-off for a positive FC level. We also looked at the correlation between FC and serum CRP levels, Crohn's disease activity index (CDAI) and disease activity index for intestinal Behçet's disease (DAIBD) scores.ResultsFC was >150 μg/g in all of the 7 GIBS patients with ulcers compared to 4/16 of GIBS patients without ulcers (OR, 95%CI: 42 to 888). The mean FC was 1125±800 μg/g (95%CI: 341 to 1908) among symptomatic patients with ulcers (n=4) and 209±213 μg/g (95%CI: 22 to 396) among symptomatic patients without ulcers (n=5). On the other hand, the mean FC was 243±73 μg/g (95%CI: 158 to 328) among asymptomatic patients with ulcers (n=3) and 95±160 μg/g (95%CI: 0.4 to 189) among asymptomatic patients without ulcers (n=11). Among CD patients, 16/25 active patients and 3/22 patients in remission had FC level >150 μg/g (OR, 95%CI: 11 to 49). There was a low correlation between FC and serum CRP levels (r=0.3, p=0.1), a moderate correlation between FC levels and CDAI scores (r=0.5, p=0.02) and very low correlation between FC and DAIBD scores (r=0.01, p=0.9). Among the 4 GIBS patients who had high FC levels despite being in remission for gastrointestinal involvement, 1 had active mucocutaneous lesions, 1 had concomitant macrophage activation syndrome, and 1 had polycythemia vera with trisomy 8. None of the patients were receiving NSAIDs that could increase FC levels.ConclusionsPending the study of more number of patients, FC may turn out to be a useful non-invasive tool for ruling out active gastrointestinal lesions in asymptomatic GIBS patients. A high FC level demands caution for the presence of active ulcers especially in symptomatic patients, but whether the presence of other BS manifestations can cause false positive results remains to be studied.ReferencesOktayoglu P et al. Scand J Clin Lab Invest. 2015Kim DH et al. ECCO.2014Disclosure of InterestNone declared
Background:
The causes of hospitalization may provide important information on the course of diseases and treatment-related adverse effects.
Objectives:
We aimed to determine the causes and outcome ...of hospitalizations among patients with Behçet Syndrome (BS) in a dedicated center.
Methods:
We surveyed hospitalization records in our clinic between January 2002 and December 2019 and identified those with a diagnosis of BS. The records of these patients were reviewed for demographic and clinical features, causes of hospitalization and outcome. We divided hospitalization causes into 2 as being BS related (organ involvement or deterioration) and non-BS related (treatment complication or others).
Results:
Three-hundred and thirty BS patients (75% men, mean age 37.7 ±11.4 SD years) were hospitalized for a total of 456 times during 18 years. The mean disease duration was 10.8± 8.8 SD years. Two-hundred and ninety-one (64%) patients were using immunosuppressives (IS) with or without corticosteroids (CSs) and 72 (16%) of them were under biologic treatment at the time of hospitalization. The mean duration of hospitalization was 12.7±10.7 SD days. The reasons for hospitalization were directly related to BS in 259 patients (57%) and non-related to BS in 191 (42%). Six patients were hospitalized for both BS and non-BS related reasons at the same time. The most common reasons were vascular involvement (n=169, 64%) for BS related reasons and infections (n=64, 32%) for non-BS related reasons (Table 1). Patients hospitalized for BS related causes were younger (35.2±10.6 vs 41.1±11.7, p<0.001), had short mean disease duration (8.5±7.5 vs. 13.6±9.4 years, p<0.001), stayed shorter in the hospital (11.6±8.6 vs 14.0±12.9 days p=0.03) and had less frequent IS±CSs use (59% vs 70%, p=0.02) compared to those with non-BS related hospitalizations. There were no differences between the groups regarding gender distribution (203 M/62 F vs. 143 M/54 F) and use of biologic agents (15% vs 17%). Three patients died during hospitalization. The reasons were malignancy, infection and right heart failure due to pulmonary artery thrombosis and pulmonary hypertension, respectively.
Conclusion:
Vascular involvement is the leading cause of hospitalization among BS patients, followed by infections. The predominance of men among hospitalized patients underlines the relatively severe course of BS in men. The retrospective design and inclusion of patients who were hospitalized only in the rheumatology unit are limitations of this study.
Table 1.
Distributions of BS related and non-BS related reasons of hospitalizations
BS patients hospitalized with BS related reasons
(n of pts=195, n of hospitalizations=265)*
BS patients hospitalized with non-BS related reasons
(n of pts=170, n of hospitalizations=197)*
Causes of hospitalizations (per hospitalization)
Vascular inv. (n=169, 64 %)
Pulmonary artery inv. (n=64, 24 %
)
Deep vein thrombosis (n=39, 15 %
)
Budd-Chiari synd. (n=24, 9%
)
Vena cava inf. thrombosis (n=19, 7 %
)
Peripheral artery inv. (n=15, 6 %
)
Vena cava sup. thrombosis (n=14, 5 %
)
Aorta inv. (n=14, 5%
)
Coronary artery inv. (n=4, 2 %
)
Infection (n=64, 32%)
Pneumonia (n=17, 8%
)
Tuberculosis (n=8, 4%
)
Urinary tract inf (n=7, 4%
)
Gastroenteritis (n=4, 2%
)
Osteomyelitis (n=3, 2%
)
Septic arthritis (n=3, 2%
)
Aspergillosis (n=2, 1%
)
Nocardia (n=1, 1%
)
Salmonella (n=1, 1%
)
Others (n=18, 9%
)
Neurologic inv. (n=50, 19 %)
Parenchymal inv. (n=37, 14%
)
Dural sinus thrombosis (n=13, 5%
)
Drug side effects other than infections (n=29, 15 %)
Interferon (n=10, 5%
)
Azathioprine (n=7, 4%
)
Cyclosporine (n=5, 3%
)
Steroid (n=3, 2%
)
TNF antagonists (n=3, 2%
)
IVIG (n=1, 1%
)
GI inv. (n=18, 7%)
Additional rheumatologic diseases (n=17, 9%)
Joint inv. (n=12, 5%)
Renal disease (n=16, 8 %)
Mucocutaneous inv. (n=10, 4%)
Cardiovascular dis. (n=12, 6%)
Eye inv. (n=8, 3%)
Avascular necrosis (n=4, 2%)
Others (n=8, 3%)
Malignancy (n=11, 6%)
Others (n=40, 20%)
*Some patients were hospitalized more than one times and for both BS related and non-BS related reasons at different time and had more than one type of BS related and/or non-BS related reasons.
Disclosure of Interests:
None declared
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