The frequency of arthritis in Adamantiades-Behçet's disease in Greek patients.

BACKGROUND/OBJECTIVES: Musculoskeletal manifestations are frequent in Adamantiades-Behçet's disease (ABD) but only represent non-specific clinical findings. They have not been included in the two commonly used sets of classification criteria. The occurrence of musculoskeletal manifestations at ABD onset may even delay or obscure the diagnosis; therefore, detailed knowledge of the different musculoskeletal manifestations is essential. Our objective was to describe musculoskeletal signs and their clinical course in Greek ABD patients. METHODS: We conducted a retrospective cohort study, which included all patients with ABD, who had been examined in our Rheumatology Outpatient Division from 1995 to 2010. The study included 224 ABD patients (140 male, 84 female) that fulfilled the International Criteria for the diagnosis of BD. For statistical analysis, we have used chi-square and Fisher's exact tests. RESULTS: Arthritis as a presenting sign was seen in 10.2% of our patients. During the follow-up period, the frequency of arthritis was 58.4%. Monoarthritis was found in 32.8% and 22.6% of male and female patients, respectively (ns). During the follow-up period, polyarthritis was only occasionally observed in male patients (2.14%). Oligoarthritis was assessed in 20.0% and 41.6% of male and female patients, respectively (P < 0.001), and was the only significantly different manifestation between sexes. CONCLUSIONS: Musculoskeletal manifestations are common in ABD both at presentation and during the disease course. The most frequent sign is mooarthritis. Oligoarthritis was the only significantly different articular manifestation between sexes (more common in women) in our study group.

Mediterranean fever gene mutations in Greek patients with Behcet's disease.

OBJECTIVE: It is known that clinical similarities between Behcet's disease and Familial Mediterranean Fever have led to the hypothesis of a common pathogenesis. Familial Mediterranean Fever is caused by MEFV gene mutations coding for pyrin. Therefore, we examined whether these pyrin mutations are also associated with Behcet's disease. METHODS: Molecular testing for pyrin mutations was performed in 96 unrelated Greek patients with an established diagnosis of Behcets disease. The results were compared with an analysis for pyrin mutations in 140 unrelated healthy Greek controls. RESULTS: We found no pyrin mutations among the Behcet cases tested; this result is comparable with the control group. CONCLUSIONS: Pyrin gene mutations in Greek patients with Behcet's disease are not more common than those in the general population. This finding is not in agreement with the findings in other populations. It is suggested that screening for pyrin mutations not be included in the evaluation of Greeks suspected to have Behcet's disease.

Mediterranean fever gene mutations in greek patients with Behcet's disease / Mutacionesen el gen de la fiebre mediterránea en pacientes griegos con la enfermedadde Behçet

OBJECTIVE: It is known that clinical similarities between Behcet's disease and Familial Mediterranean Fever have led to the hypothesis of a common pathogenesis. Familial Mediterranean Fever is caused by MEFV gene mutations coding for pyrin. Therefore, we examined whether these pyrin mutations are also associated with Behcet's disease. METHODS: Molecular testing for pyrin mutations was performed in 96 unrelated Greek patients with an established diagnosis of Behcet's disease. The results were compared with an analysis for pyrin mutations in 140 unrelated healthy Greek controls. RESULTS:We found no pyrin mutations among the Behcet cases tested; this result is comparable with the control group. CONCLUSIONS: Pyrin gene mutations in Greek patients with Behcet's disease are not more common than those in the general population. This finding is not in agreement with the findings in other populations. It is suggested that screening for pyrin mutations not be included in the evaluation of Greeks suspected to have Behcet's disease.

OBJETIVO:Se sabe que las similitudes clínicas entre la enfermedad de Behçet y la fiebre mediterránea familiar han llevado a la hipótesis de una patogénesis común. La fiebre mediterránea familiar es causada por mutaciones en el gen MEFV que codifica la pirina. Por lo tanto, examinamos si estas mutaciones de la pirina se hallan también asociadas con la enfermedad de Behçet. MÉTODOS: La prueba molecular para la detección de las mutaciones de la pirina se realizó en 96 pacientes griegos no relacionados, y diagnosticados con la enfermedad de Behçet. Los resultados se compararon con un análisis de las mutaciones de la pirina en 140 controles formados por individuos griegos saludables. RESULTADOS: No se encontraron mutaciones de pirina entre los casos de Behçet sometidos a prueba. Este resultado es comparable con el grupo control. CONCLUSIONES: Las mutaciones del gen de la pirina en los pacientes griegos con la enfermedad de Behçet no son más comunes que las de la población general. Este hallazgo no concuerda con los hallazgos en otras poblaciones. Se sugiere que el tamizaje para la detección de las mutaciones de pirina no se incluya en la evaluación de pacientes griegos sospechosos de padecer la enfermedad de Behçet.

The spectrum of mucocutaneous manifestations in Adamantiades-Behçet's disease in Greece.

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

Are clusters of patients with distinct clinical expression present in Behçet's disease?

OBJECTIVE: Studies from Israel and Turkey have proposed that patient clusters with discriminating clinical features may exist in Behçet's disease (BD); such clusters could help to better understand pathogenetic mechanisms and guide therapeutic decisions. Herein, we searched for specific associations between each disease manifestation to all other manifestations in Greek patients with BD. METHODS: Specific clinical features were retrospectively recorded in 142 consecutive patients (80 men) fulfilling the International Study Group criteria, seen between 2000-2008 in our Departments (mean follow-up of 37 months). All possible associations between distinct clinical features were examined; further analysis in relation to HLA-B51 status and pathergy test positivity, available in 89 patients, was performed. RESULTS: No significant associations between various manifestations of BD were found, either among all patients, or among men or women analysed separately. Uveitis was present more frequently in men, but not women, who were HLA-B51 carriers (p<0.02). A positive pathergy reaction was associated with oral ulcers (p<0.001) and central nervous involvement (p=0.008) in women, and folliculitis in men (p=0.046). CONCLUSION: In contrast to studies from other countries, no subgroups of patients with distinct positive or negative associations between clinical features were found. HLA-B51 may have some prognostic significance in men only. Whether differences in disease expression between geographical areas may reflect different triggers of pathogenetic mechanisms operating among ethnic groups could be further explored in comparative studies.

EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT.

OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.

Infliximab treatment-induced formation of autoantibodies is common in Behçet's disease.

OBJECTIVE: To study autoantibody formation in patients with Behçet's disease (BD) who received long-term treatment with the anti-TNF monoclonal antibody infliximab. METHODS: Serial sera from infliximab-treated patients (5 mg/kg at weeks 0, 4, 8, and every 6-8 weeks thereafter) were tested for various autoantibodies, using commercially available methods, at baseline and at 6 months (n = 20), at 12 months (n = 16), and at 18 months post-baseline (n = 12). Thirty-five age- and sex-matched BD patients, not treated with infliximab, served as controls. RESULTS: Autoantibodies were rarely seen in controls, as well as in infliximab treated patients at baseline. Formation of antinuclear antibodies (ANA) at low titers was evident in 13/20 (65%) patients at 6 months post-baseline; one additional patient developed anti-beta2 glycoprotein-I IgM antibodies (anti-beta(2)GPI). Of the 13 ANA-positive sera, low titers-IgM of anti-dsDNA or anti-beta(2)GPI were detected in 7 (35%) and 6 (30%) patients, respectively. Additional measurements at 12 and 18 months showed that the persistence and/or increasing titers of these autoantibodies depended on continuation of treatment. Antibodies to extractable nuclear antigens (anti-RNP, anti-SS-A/Ro, anti-SS-B/La, anti-Sm), rheumatoid factors, anti-cyclic citrullinated peptide antibodies and antineutrophil cytoplasmic antibodies, were never detected. No antibody-related symptoms, lupus-like disease, or thrombosis were observed in any patient up to 18 months of follow-up. CONCLUSION: Early induction of ANA and specific autoantibodies is common in BD patients treated with infliximab, including low titers of non-pathogenic anti-dsDNA and anti-Beta2GPI antibodies. A possible clinical significance of these findings needs to be documented in further studies, including more patients and longer follow-up periods.

EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVES: To develop evidence based recommendations for the management of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group comprised 16 rheumatologists, one physiatrist, one orthopaedic surgeon, two allied health professionals, and one evidence based medicine expert, representing 15 different European countries. Each participant contributed up to 10 propositions describing key clinical points for management of hand OA. Final recommendations were agreed using a Delphi consensus approach. A systematic search of Medline, Embase, CINAHL, Science Citation Index, AMED, Cochrane Library, HTA, and NICE reports was used to identify the best available research evidence to support each proposition. Where possible, the effect size and number needed to treat were calculated for efficacy. Relative risk or odds ratio was estimated for safety, and incremental cost effectiveness ratio was used for cost effectiveness. The strength of recommendation was provided according to research evidence, clinical expertise, and perceived patient preference. RESULTS: Eleven key propositions involving 17 treatment modalities were generated through three Delphi rounds. Treatment topics included general considerations (for example, clinical features, risk factors, comorbidities), non-pharmacological (for example, education plus exercise, local heat, and splint), pharmacological (for example, paracetamol, NSAIDs, NSAIDs plus gastroprotective agents, COX-2 inhibitors, systemic slow acting disease modifying drugs, intra-articular corticosteroids), and surgery. Of 17 treatment modalities, only six were supported by research evidence (education plus exercise, NSAIDs, COX-2 inhibitors, topical NSAIDs, topical capsaicin, and chondroitin sulphate). Others were supported either by evidence extrapolated from studies of OA affecting other joint sites or by expert opinion. Strength of recommendation varied according to level of evidence, benefits and harms/costs of the treatment, and clinical expertise. CONCLUSION: Eleven key recommendations for treatment of hand OA were developed using a combination of research based evidence and expert consensus. The evidence was evaluated and the strength of recommendation was provided.

Behçet's disease associated with malignancies. Report of two cases and review of the literature.

OBJECTIVE: To investigate the incidence of malignancies in a cohort of Behçet's disease patients and review the world literature. METHODS: Our database of 128 patients was searched and the age standardized rate (ASR) for cancer was calculated. Furthermore, we performed a MEDLINE search from 1970 through 2003, as well as, a search in the proceedings of international conferences for cases of malignancies associated with Behçet's disease. RESULTS: Two of our 128 patients with Behçet's disease were found to have solid tumors. One male had lung cancer and the other female had kidney cancer. The ASR for cancer cases in our population was investigated and it was found to be 1,600 per 100,000 in 10 years. The ASR for cancer cases in Greece according to WHO is 272.51 per 100,000 per year and therefore 2,725 per 100,000 in 10 years. In the world literature 112 cases of malignancies associated with Behçet's disease were found: Sixty five cases were of male patients and 46 of female with 1 case of unknown gender. The solid malignancies associated with Behçet's disease included cases of bladder, breast, uterus, thyroid and stomach cancer, whereas haematological malignancies included leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma, Hodgkin's disease and lymphosarcoma. The treatment administered in these patients with their disease is also reported. CONCLUSION: The age standardized rate of cancer in our population was lower than that of the general population in Greece, although the difference was not statistically significant. However, there is discrepancy in the world literature and the possibility of development of malignancies in Behçet's disease patients should not be ignored.

EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To develop evidence based recommendations for the management of hip osteoarthritis (OA). METHODS: The multidisciplinary guideline development group comprised 18 rheumatologists, 4 orthopaedic surgeons, and 1 epidemiologist, representing 14 European countries. Each participant contributed up to 10 propositions describing key clinical aspects of hip OA management. Ten final recommendations were agreed using a Delphi consensus approach. Medline, Embase, CINAHL, Cochrane Library, and HTA reports were searched systematically to obtain research evidence for each proposition. Where possible, outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. Effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were calculated. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation was assessed using the traditional A-D grading scale and a visual analogue scale. RESULTS: Ten key treatment propositions were generated through three Delphi rounds. They included 21 interventions, such as paracetamol, NSAIDs, symptomatic slow acting disease modifying drugs, opioids, intra-articular steroids, non-pharmacological treatment, total hip replacement, osteotomy, and two general propositions. 461 studies were identified from the literature search for the proposed interventions of efficacy, side effects, and cost effectiveness. Research evidence supported 15 interventions in the treatment of hip OA. Evidence specific for the hip was strikingly lacking. Strength of recommendation varied according to category of research evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of hip OA were developed based on research evidence and expert consensus. The effectiveness and cost effectiveness of these recommendations were evaluated and the strength of recommendation was scored.

EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT).

OBJECTIVES: To update the EULAR recommendations for management of knee osteoarthritis (OA) by an evidence based medicine and expert opinion approach. METHODS: The literature search and guidelines were restricted to treatments for knee OA pertaining to clinical and/or radiological OA of any compartment of the knee. Papers for combined treatment of knee and other types of OA were excluded. Medline and Embase were searched using a combination of subject headings and key words. Searches for those treatments previously investigated were conducted for January 1999 to February 2002 and for those treatments not previously investigated for 1966 to February 2002. The level of evidence found for each treatment was documented. Quality scores were determined for each paper, an effect size comparing the treatment with placebo was calculated, where possible, and a toxicity profile was determined for each treatment modality. RESULTS: 497 new publications were identified by the search. Of these, 103 were intervention trials and included in the overall analysis, and 33 treatment modalities were identified. Previously identified publications which were not exclusively knee OA in the initial analysis were rejected. In total, 545 publications were included. Based on the results of the literature search and expert opinion, 10 recommendations for the treatment of knee OA were devised using a five stage Delphi technique. Based on expert opinion, a further set of 10 items was identified by a five stage Delphi technique as important for future research. CONCLUSION: The updated recommendations support some of the previous propositions published in 2000 but also include modified statements and new propositions. Although a large number of treatment options for knee OA exist, the evidence based format of the EULAR Recommendations continues to identify key clinical questions that currently are unanswered.

Sweet's syndrome with arthritis and vasculitis.

Acute febrile neutrophilic dermatosis or Sweet's syndrome is a rare disease. We describe a patient with oligoarthritis, increased liver enzymes and vasculitis. One year later the patient is free of symptoms. Diseases mimicking Sweet's syndrome have been excluded.

Onset signs, clinical course, prognosis, treatment and outcome of adult patients with Adamantiades-Behçet's disease in Greece.

OBJECTIVES: To examine the onset signs, clinical course, prognosis, treatment and outcome of Adamantiades-Behçet's disease in adult Greek patients during a 10-year follow-up period, and to compare the results with those of other series reported. METHODS: The studied population consisted of 82 adult patients (54 male and 28 female) of Greek origin. Patients filled out a standard questionnaire and were followed up regularly. The findings during the follow-up of these patients were compared with those of other series. RESULTS: The most frequent onset sign was oral aphthae, both in our patients and in those of other published series. Eye involvement, joint involvement, genital ulcers and skin lesions followed in frequency. During a 10-year follow-up differences were observed between men and women, with arthritis being more frequent in females compared to males and with an overall more severe course in males. Eye involvement occurred earlier than neurological and vascular manifestations. A few differences were found in the clinical parameters in comparison to previously reported ethnic series. HLA-B51 positive patients presented an odds ratio of 9.5, the activity index was 5.17 +/- 2.56 and the mean severity score 5.96 +/- 2.32. Early treatment led to improvement of the disease. CONCLUSION: The pattern of Adamantiades-Behçet's disease in adult Greek patients provides major similarities when compared to patterns in various other national groups.

Effect of infliximab on sight-threatening panuveitis in Behçet's disease.

Permanent loss of vision resulting from relapsing ocular inflammation occurs frequently in patients with Behçet's disease, despite intensive, chronic immunosuppressive therapy. Since tumour necrosis factor (TNF) might have an important pathogenetic role in Behçet's disease, we decided to give a single infusion of infliximab-a monoclonal antibody against TNF-to five patients with relapsing panuveitis, at the immediate onset of last relapse. Remission of ocular inflammation was evident within the first 24 h, and complete suppression was seen 7 days after treatment in all patients. No side-effects were noted. We suggest that infliximab is a rapid and effective new therapy for sight-threatening ocular inflammation in Behçet's disease.

Treatment of Behçet's disease--an update.

OBJECTIVES: To report the experience of the investigators and review the major treatment trials conducted for Behçet's disease (BD). METHODS: A MEDLINE literature review from 1970 to date was performed on the drugs prescribed for the treatment of BD. Open and controlled clinical studies and indications for the treatment of affected organs are analyzed. RESULTS: Glucocorticoids are indicated for the treatment of BD, although no controlled studies have been reported. The combination of corticosteroids and immunosuppressant drugs is used when vital organs are involved. Nonsteroidal anti-inflammatory drugs are of little value in arthritis. In controlled trials, colchicine was efficacious for erythema nodosum and arthritis, particularly in women. Cyclosporine A has a rapid action and when combined with azathioprine is effective in patients with severe uveitis and extraocular manifestations. Chlorambucil is indicated for uveitis and meningoencephalitis. In controlled studies, azathioprine prevented unilateral uveitis from becoming bilateral and improved extraocular symptoms. Pulse cyclophosphamide combined with corticosteroids improves severe systemic vasculitis. Interferon alpha benefits ocular and extraocular manifestations, but controlled studies are lacking. Methotrexate is indicated for uveitis and arthritis, and sulfasalazine improves gastrointestinal vasculitis. In controlled trials, thalidomide was effective for mucocutaneous manifestations, but on its discontinuation the disease exacerbated. Orogenital manifestations are treated with local application of corticosteroids or other medications. CONCLUSIONS: Combination therapy is not always efficacious in controlling inflammation. The goal of management is to treat early to avoid recurrences and irreversible damage to the vital organs. With proper management of BD, loss of useful vision was reduced from 75% to 20% of the affected eyes. However, less favorable results are seen for central nervous system and large artery and vein involvement.