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.

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.

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.

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.

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.

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.

HLA-B*5101 in Greek patients with Behçet's disease.

Behçet's disease (BD) is a recurrent systemic vasculitis of unknown etiology. Genetic factors and infectious agents seem to be related to the etiology and pathogenesis of the disease. BD is strongly associated with HLA-B51 antigen in many ethnic groups. As there are differences in HLA profile in different ethnic groups, we designed this case-control study to examine the association of HLA-B51 alleles and BD as well as to investigate the influence of sex, age at development of the International Study Group (ISG) for Behçet's Disease criteria and certain features of disease severity on the strength of this association. The study includes 62 Greek BD patients who fulfill the ISG criteria for Behçet's disease and 87 controls. Serological HLA Class-I typing was performed by standard microlymphocytotoxicity technique. HLA-DNA typing for the B5 group was performed in all B51 subjects and controls by PCR-SSO. Allele B*5101 was found in 80% of BD patients and in 26% of controls (odds ratio (OR) 10.48, p < 10[-6]). Males who carry this allele have a higher risk than females for BD (OR 16.97 and 5.74 respectively). B*5101 predisposes to BD at a younger age in both sexes and to the development of erythema nodosum (OR = 11, p = 0.004). This was confirmed by multiple logistic regression analysis. A weak but not significant association was found between B*5101 and uveitis (OR = 2). No association was found between B*5101 and vasculitis or skin lesions in either sex. It was concluded that in the Greek population allele B*5101 is a predisposing marker for BD, as in most ethnic groups, and that this allele predisposes to the development of the disease at a younger age in both sexes and to the development of erythema nodosum.

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.

Behçet's Disease.

OBJECTIVES: To review the new data on the epidemiology, etiopathogenesis, clinicolaboratory spectrum, prognosis, and treatments of Behçet's disease (BD). METHODS: The information concerning the etiopathogenesis of the disease is divided into infection, immune, and genetic factors. The clinical features of the disease are discussed according to the organ or system involved. Treatment is described as general, local, and systemic. RESULTS: BD is a multisystem vasculitis with recurrent symptoms. It affects mainly people living around the Mediterranean basin and in Japan. The mean age at onset is the third decade. Children are rarely affected, and few neonatal cases have been reported. In large series of patients, men predominate over women. Infectious agents, immune mechanisms, and genetic factors are implicated in the etiopathogenesis of the disease, which remains to be elucidated. The pathology of the lesions consists of widespread vasculitis. Eyes, skin, joints, the oral cavity, blood vessels, and central nervous system are usually involved, although less frequently the heart, lung, kidney, genital system, and gastrointestinal tract may be affected. The prognosis of the disease has been improved because of early diagnosis and suitable treatment. Local remedies and systemic administration of colchicine, corticosteroids, immunosuppressives, and other agents have been applied. CONCLUSION: BD is a widespread vasculitis affecting young people and involving concurrently or consecutively nearly all organs and systems. Treatment results in better prognosis even when vital organs are involved.

Raynaud's phenomenon: primary and secondary causes.

The terms "Raynaud's disease" and "Raynaud's phenomenon" are often used interchangeably, as if they were a single problem. Because prognosis and therapy are different with each of these entities, 86 patients with episodic digit ischemia were evaluated over the past five years. All patients were evaluated similarly with plethysmography, angiography, and other studies for underlying causes of the digital ischemia. From the study, it was concluded that the majority of the patients had an underlying cause for the problem even though they satisfied the commonly accepted criteria for the diagnosis of Raynaud's disease. It is clear that the diagnosis of Raynaud's disease must be one of exclusion, because it is more uncommon than is generally appreciated by the medical community.

The effect of Mycoplasma arthritidis infection on the kinetics of colloidal carbon clearance in mice.

The activity of phagocytes from A/J mice was estimated by the carbon clearance test following injection of Mycoplasma arthritidis. Phagocytic activity was significantly depressed 12 h post-infection (P = 0.001) and returned to normal values at 24 h. For animals examined 2 and 7 days post-infection, the overall phagocytic activity increased significantly (P < 10(-4). Phagocytic activity gradually decreased and returned to that of the control group by the end of the fourth week. The relative weights of liver and spleen were significantly increased from the 2nd day post infection (P = 0.0028 and P = 0.0014 respectively) and remained increased until the end of the experiment. The early depressive effect on phagocytic activity may be related to superantigen activity with the production of mediators such as macrophage deactivating factor. The later expansion of the macrophage population might bring about the stimulation of autoreactive clones of T and B cells and be responsible for the chronic arthritis that developed in the mycoplasma treated mice.

Angioid streaks in homozygous beta thalassemia.

One hundred patients with homozygous beta thalassemia (62 had beta thalassemia major and 38 had beta thalassemia intermedia) were examined by ophthalmoscopy for angioid streaks. Angioid streaks were found in 20 patients from both the beta thalassemia major and beta thalassemia intermedia groups (nine and 11 patients, respectively). A positive correlation was found between age and angioid streaks (P = .0017), as was a difference in the prevalence of angioid streaks between the two forms of the disease (P = .079). Additionally, a significant correlation was noted between chelating therapy and the prevalence of angioid streaks (P = .039). However, using multivariate analysis to correct for the effects of age, the correlation of angioid streaks with the form of disease disappeared, whereas the level of significance between chelation therapy and angioid streaks was reduced (P = .05). The high frequency of angioid streaks observed in patients with beta thalassemia and the severe complications observed in one patient render a thorough ophthalmoscopic examination and follow-up of such patients necessary for both early diagnosis and possible therapeutic intervention.

Rheumatoid arthritis with periarticular calcifications.

A rare case of rheumatoid arthritis with periarticular calcifications, lung involvement, pericarditis, nodules, Sjögren's syndrome and various drug side-effects is described. Over a period of more than 10 years of observation, the patient's arthritis has been characterized by remissions and exacerbations.

HLA antigens and Adamantiades-Behçet's disease (A-BD) in Greeks.

The distribution frequency of HLA-A and B antigens was determined in 24 Greek individuals with Adamantiades-Behçet's disease (A-BD) as well as in 280 controls. The standard NIH technique was used for tissue typing. There was an increased incidence of HLA-B5 in the patients group (75% compared to controls 32%). The calculated P corrected value was Pc less than 0.02, the relative risk (RR) was 6.23 and the aetiological fraction (EF) 0.68. This study agrees with the reported association between A-BD and HLA-B5 in other populations from the Mediterranean basin, the Middle East and Far East.

Renal involvement in Adamantiades-Behçet's disease. Case report and review of the literature.

A patient with Adamantiades-Behçet's disease with renal involvement is reported. This patient fulfilled the International Study Group criteria for the disease. Kidney biopsy was performed and proliferative glomerulonephritis with deposition of IgA and IgM immunoglobulins were demonstrated. Review of the literature demonstrates that renal involvement in this disease is not so rare as it was believed. Crescent formation and IgA nephropathy are infrequently observed. Treatment of renal involvement may require immunosuppressive drugs.

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.

Clinical features of juvenile Adamantiades-Behçet's disease in Greece.

Adamantiades-Behçet's disease (A-BD) is a chronic relapsing vasculitis of unknown etiology. This disease is relatively rare in children and only recently have series of patients been reported. The objective of this study was to describe the clinical features of the disease in juvenile patients, and to compare them with adult cases and with those juveniles reported in the literature.

Asymptomatic pericarditis in Adamantiadis-Behçet's disease.

Pericardial involvement in Adamantiadis-Behçet's disease (ABD) is uncommon. A 14-year-old boy presented with fever of unknown origin, as the initial and only manifestation of his disease. Other features were leukopenia, abdominal lymphadenopathy and asymptomatic pericarditis, which is a very rare finding of the disease. A review of pericarditis is presented.