Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

Predictive factors for work-day loss in Behçet's syndrome: A multi-center study.

OBJECTIVE: The aim of this multi-center study was to assess predictive factors for work-day loss as an indirect cost element in Behçet's syndrome (BS). METHODS: In this cross-sectional, multi-center study, 834 BS patients (F/M: 441/393, age mean: 38.4 ± 10.9 years) were included. Data were collected by a questionnaire regarding treatment protocols, disease duration, smoking pattern, frequency of medical visits during the previous year and self-reported work-day loss during the previous year. RESULTS: Work-day loss was observed in 16.2% of patients (M/F: 103/32). The percentages of being a smoker (81.8%), using immunosuppressive (IS) medications (82%), and having disease duration <5 years (74%) were higher in male patients with work-day loss (P < .05). The majority of males (90.9%) had more than four clinic visits during the previous year. Moreover, the mean work-day loss (30.8 ± 57.7 days) was higher in patients with vascular involvement (56.1 ± 85.9) than those without (26.4 ± 50.6 days) (P = .046). In addition, increased frequency of ocular involvement (25.9%) was also observed in patients with work-day loss compared to others (8.6%) (P = .059). CONCLUSION: Work-day loss was associated with both vascular and ocular involvement. Close associations were observed among male gender, early period of the disease, frequent medical visits, being a smoker and treatment with IS medications in patients with work-day loss.

Adherence to treatment in patients with Behçet's disease.

AIM: Behçet's disease (BD) is a chronic, inflammatory disease with multisystem involvement. Adherence to treatment is low in chronic diseases as well as inflammatory and autoimmune diseases. This study assessed factors associated with non-adherence to treatment in patients with BD. METHODS: All the patients with BD who visited in the outpatient clinic of Connective Tissue Diseases Research Center in Tabriz University of Medical Sciences were included in the study. Adherence to treatment was evaluated by the consideration of medication compliance and appointment-keeping behavior. The relationships between adherence rate and six groups of variables were examined. A regression analysis was performed. RESULTS: A total of 137 patients (84 male and 53 female) were included. Totally, 50.7% of the patients were non-adherent to treatment. Side effects of medications and the high cost of treatment were the most frequent causes of non-adherence. Non-adherence was significantly more common in men, patients with low income, patients who were unaware of the disease complications, employed persons, and in patients who were on treatment with non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: Non-adherence is common in patients with BD. Male sex, low income, low knowledge about the disease, being employed and being on treatment with NSAIDs are the main risk factors for non-adherence.

Behçet's disease: A comprehensive review with a focus on epidemiology, etiology and clinical features, and management of mucocutaneous lesions.

Behçet's disease (BD) is a chronic, relapsing, inflammatory multisystem disease of unknown etiology. Oral ulcers, genital ulcers, cutaneous lesions, and ocular and articular involvement are the most frequent features of the disease. Mucocutaneous lesions are considered hallmarks of the disease, and often precede other manifestations. Therefore, their recognition may permit earlier diagnosis and treatment with beneficial results for prognosis. BD is particularly prevalent in "Silk Route" populations but has a global distribution. The disease usually starts around the third or fourth decade of life. Sex distribution is roughly equal. The diagnosis is based on clinical criteria, as there is no pathognomonic test. Genetic factors have been investigated extensively, and association with human leukocyte antigen (HLA)-B51 is still known as the strongest genetic susceptibility factor. The T-helper 17 and interleukin (IL)-17 pathways are active, and play an important role, particularly in acute attacks of BD. Neutrophil activity is increased in BD, and the affected organs show a significant neutrophil and lymphocyte infiltration. HLA-B51 association and increased IL-17 response are thought to play a role in neutrophil activation. Treatment is mainly based on the suppression of inflammatory attacks of the disease using immunomodulatory and immunosuppressive agents. Although treatment has become much more effective in recent years with the introduction of newer drugs, BD is still associated with considerable morbidity and increased mortality. Male sex, younger age of onset and increased number of organs involved at the diagnosis are associated with a more severe disease and, therefore, require more aggressive treatment.

Epidemiology and management of neuropsychiatric disorders in Behçet's syndrome.

Behçet's syndrome (BS) is a systemic, chronic, relapsing vasculitis, typically characterized by recurrent orogenital ulcers, ocular inflammation and skin manifestations; articular, vascular, gastroenteric and neurological involvement may also occur. Besides the other clinical features of BS, it seems relatively frequent that patients with BS develop a neurobehavioural syndrome, characterized by euphoria, bipolar disorders and paranoid attitudes, loss of insight/disinhibition, and indifference to their disease, defined as 'neuro-psycho-BS'. To date, the pathogenetic mechanism underlying neuro-psycho-BS has not been determined. It may be secondary to organic neurological involvement, or it may be related to poor quality of life and the relapsing course of the disease. Another engaging theory suggests that it could be related to the frequent observation of psychiatric symptoms during relapses or, in some cases, in the phases preceding reactivation of the disease; these elements suggest that psychiatric disorders in BS could represent a crucial element, whether a psychiatric subset or a distinct clinical feature of the disease. Moreover, it has been reported that cognitive impairment in BS can be seen with or without central nervous system involvement. Globally, psychiatric symptoms have been described as being multifaceted, ranging from anxiety disorders to depressive-bipolar disorders or to psychotic ones. In addition, some psychological characteristics of BS patients seem to predispose them to maladaptive stress management, which may lead to stress-related disorders, including anxiety and depression. Therefore, the aims of this review are to explore the epidemiology of neuro-psycho-BS by evaluating the relationship between the stress system and the multifaceted psychiatric manifestations in BS, and to summarize the therapeutic strategy used.

Biologic agents and oral diseases -- an update on clinical applications.

Biologic agents are targeted immune modulating agents that have been widely used in the treatment of inflammatory and neoplastic conditions with favorable results. The purpose of this review is to provide an update on the biologic agents that have been used in the treatment of diseases that affect the oral mucosa. Identification of relevant data, case reports and case series was performed using the PubMed-MEDLINE database and electronic databases of accredited organizations such as the European Medical Agency, US Food and Drug Administration, and clinicaltrials.gov (USA). According to the literature, the use of biologic agents in patients with oral diseases is limited mainly to patients suffering from refractory forms of immune-mediated diseases of the oral cavity. Biologic agents were used in all cases as off-label indications. Patient's response varied, but in general biologic agents could be considered as a therapeutic option in patients with no other alternative. A point requiring extra precaution is their safety profile because severe life threatening infections are among their side effects. Another aspect that limits their broader use is their high economic cost. We aimed to provide a practical update for the clinicians who deal with oral diseases, covering as many aspects as possible of the applications of biologic agents in oral diseases reported to date.

Assessment of minimal clinically important improvement by using Oral Health Impact Profile-14 in Behçet's disease.

OBJECTIVE: The aim of this prospective study was to detect minimal clinically important improvement (MCII) of oral health impact profile-14 (OHIP-14) for assessing the effect of treatments for oral ulcers in Behçet's disease (BD). METHODS: BD patients with active oral ulcers (F/M:36/22) were selected. Baseline and follow-up data were collected by clinical examinations and questionnaires. Patients rated their global impression of change (PGIC) measured by a transitional question. MCII was defined as the difference in mean change from baseline in OHIP-14 between patients with no response to therapy and patients with next higher level of response. RESULTS: Approximately one third (29.3 %) of the patients expressed an improvement during control examinations. A significant correlation was observed between raw change in OHIP-14 score and change in number of oral ulcers (r=0.69 p=0.017). Inactive patients increased from 44.1% in baseline to 58.8% in follow-up examination. A trend towards decreased number of oral ulcers was observed in follow-up (0.64+/-0.93) compared to baseline (1.44+/-1.92) in the improved group (p=0.096). According to regression analysis, PGIC was a significant predictor of change in raw OHIP-14 score. The threshold levels generated from the ROC analyses in OHIP-14 score best associated with clinically important improvement were -3.5 points (sensitivity: 80%, specificity: 88.6%) and -38.1% (sensitivity: 86.7%, specificity: 97.1%) respectively. CONCLUSION: Changes in OHIP-14 scores seem to be a sensitive and valuable tool for the determination of MCII during follow-up of Behçet's disease patients for oral disease assessment.

Can a Multi-Dimensional Health Assessment Questionnaire (MDHAQ) and Routine Assessment of Patient Index Data (RAPID) scores be informative in patients with all rheumatic diseases?

A multidimensional health assessment questionnaire (MDHAQ) is useful in standard care of patients with all rheumatic diseases in a busy clinical setting. The MDHAQ was adapted from the classical health assessment questionnaire (HAQ) for feasibility in standard clinical care, with reduction of the number of activities from 20 to 10, visual analog scales (VAS) as 21 circles rather than 10 cm lines, availability of all core data set patient self-report measures and scoring templates on the front side, and a review of systems symptom checklist and review of recent medical history on the reverse side of a single page. Scoring templates are also available for routine assessment of patient index data (RAPID) scores, based on a composite of the three patient reported outcome (PRO) measures from the core data set included on the HAQ and MDHAQ, physical function pain, and patient estimate of global status. Flow sheets illustrating use of the MDHAQ in standard clinical care of patients with various rheumatic diseases, including psoriatic arthritis, systemic lupus erythematosus, ankylosing spondylitis, gout, scleroderma, vasculitis, fibromyalgia, inflammatory bowel disease arthritis, Behcet's syndrome, and familial Mediterranean fever, are presented to illustrate use of this simple questionnaire to add to clinical decisions and document patient courses and outcomes in standard clinical care of patients with all rheumatic diseases.

The assessment of oral health-related quality of life by factor analysis in patients with Behcet's disease and recurrent aphthous stomatitis.

BACKGROUND: The aim of the study was to test multidimensional properties of oral health impact profile-14 (OHIP-14) in Behcet's disease (BD) and recurrent aphthous stomatitis (RAS) patients with active oral ulcers. METHODS: Ninety-six BD patients, 28 patients with RAS and 117 healthy controls (HC) were included in this study. In patients with active oral ulcers, the frequency and healing time of ulcers were recorded. Multidimensional properties of OHIP-14 were examined by factor analysis. RESULTS: Factor analysis revealed three subscales and explained 66.49% of overall variance in these patients with active oral ulcers. The score of Subscale 1 was positively correlated with the recurrence of oral ulcers per month (P = 0.037). Subscale 3 scores of the patients treated with colchicine were worse than those treated with immunosuppressives (P = 0.035). CONCLUSIONS: The factor structure of OHIP-14 was found to be reliable and sensitive to clinical parameters and treatment modalities in active patients.

Neoral--new cyclosporin for old?

Cyclosporin A is now well established as an effective second-line drug to treat rheumatoid arthritis. In April 1995, the microemulsion-based formulation of cyclosporin (Neoral) was introduced based on its increased bioavailability at 'no extra cost'. There may have been concerns that with increased bioavailability of Neoral, some patients might experience increased toxicity, particularly if transferring from Sandimmun to Neoral at the same dose. We describe our experience of 51 patients treated with Neoral--39 with rheumatoid arthritis, six with psoriatic arthritis and the remainder with a variety of diseases, including Behçet's, systemic lupus erythematosus and juvenile chronic arthritis. All patients continued their other medication including non-steroidal anti-inflammatory drugs and analgesics. Five continued low dose prednisolone (average 7.5 mg per day) all patients were monitored for safety and efficacy throughout their treatment according to standard protocol. Five patients were enrolled in a study of efficacy and safety where the dose of cyclosporin was reduced to 2.5 mg/kg/day at the time of conversion, i.e. to Neoral 2.5 mg/kg/day; 19 patients were converted dose for dose, cyclosporin A dose range 2.5-4 mg/kg/day converted to Neoral dose range 2.5-4 mg/kg/day and 27 patients started Neoral de novo. We conclude that cyclosporin is a useful disease modifying anti-rheumatic agent, and our experience suggests that the new formulation, Neoral, has a similar safety and efficacy profile to the original preparation (Sandimmun). Neoral was relatively easy to manage and we noted a slight reduction in dose when compared to Sandimmun. With dose adjustments over 18 months the mean dose for patients with RA fell from 3.2 to 2.7 mg/kg/day and of the 27 patients starting Neoral de novo only seven required an increased dose above 2.5 mg/kg/day in order to establish efficacy.

Risk factor assessment and prognosis of eye involvement in Behcet's disease in Turkey.

BACKGROUND: Behcet's disease (BD) shows great regional differences in clinical manifestations and prognosis, including eye involvement. Thus, it is hard to predict in which patient the eyes will be involved and what the outcome will be. In this study we assessed various risk factors for eye involvement and attempted to predict the visual outcome in our patient population in Turkey. METHODS: Data from a total of 224 patients with BD, diagnosed between 1982 and 1996, were analyzed retrospectively. A detailed physical examination and ophthalmologic work up were performed on each patient. Factors that might contribute to eye involvement were investigated, after which prognostic factors for vision were evaluated. RESULTS: Eighty-eight patients had eye involvement during a median follow-up of 32 months. The risk of involvement was highest within the first year of diagnosis. Young age was the most significant factor for eye involvement (P < 0.0001), but vascular thrombosis, central nervous system (CNS) involvement, and male gender were other risk factors (P < 0.001; P < 0.01; and P < 0.05, respectively). The most important determinant for the prognosis of vision was CNS involvement (P < 0.0001). Vascular thrombosis and an age of < or = 32 were other risk factors for visual impairment (P < 0.001 and P < 0.05, respectively). The risk of eye involvement and prognosis for vision were similar with different treatment regimens (P > 0.05). CONCLUSION: It is suggested that the first 2 years after diagnosis is the most critical period for eye involvement, and conventional forms of therapy generally are unsuccessful in preventing such involvement. It seems reasonable to treat patients who are at increased risk for eye involvement more aggressively, especially within the first 2 years of disease onset.

Behçet's syndrome. Immunopathologic and histopathologic assessment of pathergy lesions is useful in diagnosis and follow-up.

Behçet's syndrome is a complex multisystem disease that, due to the absence of a pathognomonic laboratory test, must be diagnosed using clinical criteria. Clinical pathergy testing, the induction of a sterile pustule 24 hours after cutaneous trauma, has been proposed as a useful adjunct to diagnosis. We have expanded this concept by showing the usefulness of examining pathergy lesions by routine and immunofluorescence microscopy in the diagnosis of nine patients with Behçet's syndrome. Furthermore, histopathologic pathergy assessments correlated with clinical disease activity and/or response to experimental oral thalidomide therapy in five of six patients with Behçet's syndrome who were retested.