Validation and Cultural Adaptation of Persian Version of Multidimensional Health Assessment Questionnaire in Rheumatoid Arthritis Patients.

Background: Rheumatoid arthritis (RA) is a multidimensional disease. In addition to quantitative factors, qualitative factors play an important role in the progress and outcome of the diseases. One of the most effective methods of collecting qualitative information is questionnaires reported by patients. The data obtained from the questionnaires are as important as the clinical criteria. Multidimensional health assessment questionnaire (MDHAQ) is one of the latest questionnaires that provide useful information in a short time. Objectives: To investigate the reliability and validity of the Persian form of MDAHAQ for the use of Iranian patients. Method: Two groups of participants were selected for this study. The validity test group included 110 patients, and the reliability test group included 140 patients. Translation and adaption of MDHAQ were performed by using Guillemin guidelines. The reliability was tested by using test-retest and Cronbach's alpha for internal consistency. Persian version of the health assessment questionnaire (HAQ) was used for assessing the criterion validity. The correlation between the MDHAQ score and Disease Activity Score-28 (DAS28), Clinical Disease Activity Index (CDAI), and the Persian version of the health assessment questionnaire (HAQ) was evaluated using the Spearman coefficient. Discriminant validity was tested in groups of patients based on two varied disease activities based on CDAI and DAS28. Results: Test-retest with intra-class correlation coefficient (ICC) gave a coefficient of 0.865(95% CI: 0.809, 0.904) for physical function and 0.786(95% CI: 0.698, 0.848) for psychological items. Cronbach's alpha was 0.885 and 0.705 for physical function and psychological dimensions respectively. The Persian version of the MDHAQ had a good to strong correlation with the Persian version of the HAQ (ranging from 0.604 to 0.962) and also with CDAI (ranging from 0.616 to 0.838) and a moderate correlation with DAS28 (ranging from 0.415 to 0.439). Conclusion: The Persian form of MDHAQ is a reliable and valid instrument for the routine evaluation of RA patients in rheumatology clinics in Iranian RA patients.

Successful treatment of classic pyoderma gangrenosum with intralesional infliximab injection: A case report.

Pyoderma gangrenosum (PG) is a rare dermatological disease characterized by the rapid development of painful skin ulcers. While systemic infliximab is considered a standard treatment for patients with PG, herein, we report our success with the use of intralesional infliximab in a 40-year-old woman with systemic lupus erythematosus (SLE) and PG.

Association of Large Vessel Aneurysm/Pseudo-Aneurysm/Aortitis and Deep Vein Thrombosis in Patients with Behçet's Disease: A Case Report.

BACKGROUND: Behçet's disease (BD) is a complex vasculitis with some vascular manifestations including venous thrombosis, arterial thrombosis/aneurysm/pseudoaneurysm, and co-associated venous thrombosis and arterial lesions. We present two patients with Behçet's disease came with progressive both arterial and venous involvement. CASE PRESENTATION: The first patient was a young man with recurrent oral aphthosis and skin folliculitis and referred with complaint of new abdominal pain and 2 months severe headache. He had not referred to a physician due to COVID-19 pandemic until that time. In addition, he gradually developed a lower extremity edema and eventually was diagnosed with BD complicated with brain sagittal sinus vein thrombosis, abdominal aortic aneurysms and aortitis and deep vein thrombosis (DVT) of femoral vein. The second patient was a young woman with previous history of uveitis, DVT and recurrent oral and genital aphthosis presented with a large inguinal mass due to large iliac artery pseudoaneurysm impending to rupture, and after the operation, due to poor follow-up, developed a new femoral DVT. CONCLUSION: It seems the same inflammatory process is responsible for arterial and venous involvement in patients with BD, so it should be considered that involvement in one side (venous/arterial) can be a risk factor for the other side (venous/arterial) and early immunosuppressive treatment should always be considered to improve the prognosis.

Cost-Effectiveness Analysis of Biopharmaceuticals for Treating Rheumatoid Arthritis: Infliximab, Adalimumab, and Etanercept.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease that causes joint destruction. The condition imposes a significant economic burden on patients and societies. The present study is aimed at evaluating the cost-effectiveness of Infliximab, Adalimumab, and Etanercept in treating rheumatoid arthritis in Iran. METHODS: This is a cost-effectiveness study of economic evaluation in which the Markov model was used. The study was carried out on 154 patients with rheumatoid arthritis in Fars province taking Infliximab, Adalimumab, and Etanercept. The patients were selected through sampling. In this study, the cost data were collected from a community perspective, and the outcomes were the mean reductions in DAS-28 and QALY. The cost data collection form and the EQ-5D questionnaire were also used to collect the required data. The results were presented in the form of an incremental cost-effectiveness ratio, and the sensitivity analysis was used to measure the robustness of the study results. The TreeAge Pro and Excel softwares were used to analyze the collected data. RESULTS: The results showed that the mean costs and the QALY rates in the Infliximab, Adalimumab, and Etanercept arms were $ 79,518.33 and 12.34, $ 91,695.59 and 13.25, and $ 87,440.92 and 11.79, respectively. The one-way sensitivity analysis confirmed the robustness of the results. In addition, the results of the probabilistic sensitivity analysis (PSA) indicated that on the cost-effectiveness acceptability curve, Infliximab was in the acceptance area and below the threshold in 77% of simulations. The scatter plot was in the mentioned area in 81% and 91% of simulations compared with Adalimumab and Etanercept, respectively, implying lower costs and higher effectiveness than the other two alternatives. Therefore, the strategy was more cost-effective. CONCLUSION: According to the results of this study, Infliximab was more cost-effective than the other two medications. Therefore, it is recommended that physicians use this medication as the priority in treating rheumatoid arthritis. It is also suggested that health policymakers consider the present study results in preparing treatment guidelines for RA.

Pathergy test with a 23G needle with and without self-saliva in patients with Behçet's disease, recurrent aphthous stomatitis and control group compared to the 20G test.

OBJECTIVES: The pathergy test (PT) is part of the diagnostic criteria of Behçet's disease (BD). Factors like needle character and number of punctures can affect the sensitivity of PT. We tried to compare its positivity using a thinner needle with and without self-saliva in active and inactive BD, recurrent aphthous stomatitis (RAS), and healthy people. MATERIAL AND METHODS: Twenty patients with active and 13 with inactive BD, 20 with RAS, and 34 healthy controls underwent 3 types of PT: 1 - the most recommended 20G dry needle PT, 2 - 23G dry needle PT, and 3 - 23G PT with self-saliva. The positivity and diagnostic accuracy of the tests between groups were compared. RESULTS: All tests were negative in the normal healthy group. In active BD, the positivity of PT with self-saliva (70%) was higher than the 20G PT (20%) (p-value = 0.004), being more correlated to disease activity (p-value = 0.046). In the RAS group, there was no difference in the positivity of all tests (p-value = 0.068). All tests had high diagnostic accuracy in discriminating between patients with active BD and the controls (p < 0.05). The pathergy test with self-saliva showed significant diagnostic accuracy in discriminating BD from non-BD participants (p < 0.001). The results of dry 23G PT were the same as those of 20G PT. CONCLUSIONS: The self-saliva PT test was more positive in patients with active BD, correlated with disease activity, was more sensitive, had equal specificity in detecting BD from the control group, and was more sensitive but less specific in detecting BD, compared to the RAS group. The positivity and accuracy of dry 23G needle PT were the same as the 20G PT.Pathergy test with self-saliva using a thin (23G) needle is more sensitive has equal specificity in detecting patients with BD compared to the control group and is more sensitive but less specific in detecting the patients with BD compared to the RAS group. The positivity and accuracy of dry 23G needle PT is the same as the most recommended 20G dry PT. Pathergy test by wet 23G needle (with self-saliva) is more positive in patients with active BD compared to PT by dry 20G needle.

Experiences of the Patients with Behcet's Syndrom from Adherence to Treatment: A Qualitative Content Analysis.

BACKGROUND: Adherence to treatment plays an important role in the effectiveness of treatment in patients with Behcet's Syndrome (BS). An in-depth understanding of the experiences of patients with BS will help to improve the patients' management. The present qualitative study aimed to explore the experiences of patients with BS from adherence to treatment. METHODS: This qualitative study was conducted during February-September 2019 at Shahid Motahari Behcet's Clinic in Shiraz, Iran. Data were collected through eight unstructured observations and 22 individual in-depth semi-structured interviews with 20 participants (15 patients with BS, three family members, and two rheumatologists). Data analysis was performed simultaneously with data collection, using the conventional content analysis as proposed by Graneheim and Lundman. Data were managed using MAXQDA 10 software. RESULTS: Data analysis resulted in 21 sub-categories, seven categories, and three themes. The themes included barriers to treatment adherence (inability to cope with treatment and challenges in access to health care), facilitators of treatment adherence (incentives, receiving support, and striving to adapt to illness), and missing aspects of the treatment program (inadequate patient education and the neglect of lifestyle modification). CONCLUSION: The barriers to and facilitators of treatment adherence as well as the missing aspects of the treatment program of patients with BS were identified. Adherence to treatment is not only determined by the patients, but also affected by the support system and relies upon the existing context and the nature of the treatment plan. These parameters should be considered during patient management to effectively promote treatment adherence.

Quality of Life Assessment in Patients with Behçet's Disease using the Persian Version of the Leeds BD-QoL Questionnaire.

BACKGROUND: Behçet's disease (BD) can negatively impact the quality of life (QoL) of the affected patients. The present study aimed to assess the QoL of BD patients using the Leeds BD-QoL and compare its results with the WHOQOL-BREF questionnaire. METHODS: In the present cross-sectional study, 179 BD patients and 304 healthy individuals (the control group) were recruited in Shiraz, 2017. The Persian version of the Leeds BD-QoL and WHOQOL-BREF questionnaires were used to assess the QoL of patients with BD. The QoL in the patient and control groups was compared after controlling the effect of some variables (age, sex, marital status, and educational level) using the multiple linear regression analysis. Spearman's correlation coefficient was calculated for the Leeds BD-QoL and WHOQOL-BREF scores. Disease activity was measured using the Behçet's Disease Current Activity Form. All the statistical analysis was performed using SPSS software (version 21.0). P<0.05 was considered statistically significant. RESULTS: The mean of the Leeds BD-QoL total score in the patient group was 12.3±8.7. The control group had significantly higher scores in the WHOQOL-BREF total score and the physical health and psychological health domains compared with the patient group; mean difference of 10.24, 10.8, and 4.62, respectively (P<0.001). The Spearman's correlation coefficient for the Leeds BD-QoL score and WHOQOL-BREF total score and its domains (physical health, psychological health, social relationships, and environment) was -0.669, -0.713, -0.714, -0.536, and -0.550, respectively. The disease activity score was correlated with the Leeds BD-QoL score (r=0.361, P<0.001). CONCLUSION: BD patients had a lower QoL than healthy individuals, specifically in the physical health and psychological health domains. An increase in disease activity and severity was associated with a reduced QoL. The Persian version of the Leeds BD-QoL questionnaire had an acceptable correlation with the WHOQOL-BREF questionnaire.

The Patients' Beliefs Regarding the Role of Food, Mucosal Trauma, Menstruation, and Psychological Stress in the Recurrence of Behçet's Disease Symptoms.

Behçet's disease is a systemic vasculitis. Mucocutaneous involvement is the most prominent finding, but triggering factors are not well-known. We decided to assess the beliefs of patients with Behçet's disease regarding the potential role of food, mucosal injury, menstruation, and stress in the appearance of symptoms. In this cross-sectional study, 60 patients with Behçet's disease who fulfilled the International Study Group criteria for Behçet's disease and referred to the outpatient Behçet's clinic of Motahari, affiliated to Shiraz University of Medical Sciences, were included. A questionnaire was designed by the research team consisting of the rheumatologist involved in the study, two dietitians, and a psychiatrist. The patients were interviewed face-to-face to fill in the questionnaire. The assessed variables were all food categories, menstruation, psychological stress, and oral mucosal injury as the potential triggers of symptoms onset. The most common foods reported as triggers for oral ulcers were eggplant (78.3%), melon (68.3%), walnut (68.2%), and cantaloupe (66.7%). Walnut was reported by three patients (5%) as the most common trigger for genital ulcers. Nervous tension (83%) and annoying arguments (45%) were the two most common psychological stress triggers for oral ulcers. Seven patients (11.7%) reported tooth brushing, as the trigger for oral ulcers. The irregular menstrual cycle was a trigger for oral ulcers in only two patients. Food items such as eggplant, walnut and melon were common self-reported triggers for mucocutaneous lesions in patients with Behçet's disease. Nervous tension and annoying arguments were also common psychological triggers for oral aphthous ulcers.

Inflammatory and T Helper 17/ Regulatory T Cells Related Cytokines Balance in Cutaneous Lupus Erythematosus (CLE).

The cutaneous lupus erythematosus (CLE) is a common manifestation among systemic lupus erythematosus (SLE) patients. Malar rash and discoid lupus (DLE) are in the category of acute and chronic CLE, respectively. The pathogenesis of CLE is multifactorial, and cytokine imbalances contribute to immune dysfunction and the induction of organ damage. Many aspects of cytokine dysregulation are still unclear in SLE and in particular CLE. Therefore, we concurrently measured the inflammatory [Tumor necrosis factor-alpha (TNF-α) and Interleukin (IL)-6)], T helper (Th)-17 (IL-17 and IL-23) and regulatory T cells [Transforming growth factor-beta (TGFß) and IL-10)]-related cytokines in patients with CLE (patients with malar rash and/or DLE) and compared them with SLE patients and healthy individuals (n=25 in each group, a total of 75 patients). The serum levels of cytokines were assessed by Enzyme-Linked Immunosorbent Assay (ELISA) method. IL-6 cytokine was significantly higher in SLE, DLE, and malar rash patients compared to those in healthy controls (p=0.025) and in patients with arthralgia (p=0.038), and gastrointestinal involvement (p=0.048). IL-17 was significantly higher in malar rash patients compared to normal individuals (p=0.023), SLE (p=0.008) and DLE patients (p=0.019) and in patients with oropharyngeal ulcer (p=0.05) but, IL-23 was significantly higher only in DLE patients than healthy controls (p=0.019). In conclusion, inflammatory cytokines such as IL-6 involved in inflammation and differentiation of Th17 cells are probably responsible in part for Th17 activity in CLE. IL-17, IL-23, and IL-6/IL-6R (IL-6 receptor) inhibitors may be good treatments for CLE patients. So targeting these cytokines activity pathways can improve the CLE treatment strategy and may open a novel guideline for SLE and CLE treatment.

IL-38 serum levels in patients with Behcet's disease and the relationship with clinical features.

Behcet's disease (BD) is a chronic multisystem autoimmune disorder. Various cytokines take part in the pathogenesis of this disease. Interleukin (IL)-38, a new member of IL-1 cytokine family, has been reported to have anti-inflammatory properties; however, its role in BD has not been investigated yet. In this study, we aimed to examine the probable role of IL-38 in the clinical context of BD. A total of 81 patients with BD and 81 age- and sex-matched healthy subjects as controls were included in this study. The serum levels of IL-38 were measured in patients and controls sera using enzyme-linked immunosorbent assay. The relationship between the serum levels of IL-38 and clinical and laboratory characteristics of the patients were determined. IL-38 serum levels were significantly lower in patients in comparison with healthy controls at P = 0.003. We found significant differences between IL-38 levels in BD patients with positive and negative pathergy tests (P = 0.048) and patients with and without eye involvement (P = 0.046). Despite the absence of significant differences in serum levels between male and female patients, IL-38 levels were higher in female patients with a positive pathergy test (P = 0.048) and those patients with eye involvement (P = 0.046). As healthy controls showed higher IL-38 serum levels than patients, a protective anti-inflammatory role of IL-38 in BD is suggested. Together, these results suggest that the positive relationship between IL-38 serum levels and eye involvement that IL-38 may play a role in this clinical feature of the disease.

Frequency of HLA-B5, HLA-B51 and HLA-B27 in patients with idiopathic uveitis and Behçet's disease: a case-control study.

OBJECTIVES: Idiopathic uveitis is the most common form of uveitis in most countries. Uveitis affects about 40-80% of patients with Behçet's disease (BD). Class I, HLA-B5, and its subclass B51 allele have the strongest association with BD, but its role in idiopathic uveitis is unclear. The aim of this study was to determine the frequency of HLA-B5, HLA-B51 and HLA-B27 in patients with idiopathic uveitis, BD and the control group. MATERIAL AND METHODS: Forty-eight patients with idiopathic uveitis, 62 patients with BD, and 49 control subjects were compared. The presence of HLA-B5, HLA-B51 and HLA-B27 was checked by reviewing the charts of patients with idiopathic uveitis and Behçet's disease referred to the rheumatologic center of Shiraz University of Medical Sciences. The control group consisted of a sex-matched normal control population, among which HLA typing was done. RESULTS: HLA-B5 was significantly higher in patients with idiopathic uveitis and BD compared to the control group (p = 0.029 and 0.0001). It was significantly higher in patients with BD compared to those with idiopathic uveitis (p = 0.001). The difference of HLA-B51 between the groups was not statistically significant although it was higher in the BD group than the controls. The presence of HLA-B51 was significantly associated with ocular involvement in the BD group (p = 0.013). HLA-B27 was the least common type of HLA in all groups. CONCLUSIONS: HLA-B5 was the most common, compared to HLA-B51 and HLA-27, in patients with idiopathic uveitis and BD. There was an association between HLA-B51 positivity and ocular involvement in patients with BD. It seems that the pattern of HLA in our patients with idiopathic uveitis was different from that observed in some other studies.

Temperament and character in patients with systemic lupus erythematosus.

BACKGROUND: In addition to identified neuropsychiatric characteristic of systemic lupus erythematosus (SLE), changes in personality seem to occur in patients with SLE. Even in absence of an axis I psychiatric diagnosis, personality variations play important role in general wellbeing of these patients. This study investigated personality features in patients with SLE using Temperament and Character Inventory (TCI). METHOD: In this case-control study personality features of 59 patients with confirmed diagnosis of SLE were evaluated using Persian version of TCI-125 questionnaire. Collected data from patients with SLE were statistically compared with normative data for Iranian population. RESULTS: Among four subscales of temperament, reward dependence (RD) and harm-avoidance (HA) were significantly lower than general population. Self-directedness (SD) character dimension was significantly lower in SLE patients compared to normative data. No significant difference was noted in novelty-seeking (NS) and persistence (PS) temperament scales and cooperativeness (CO) and self-transcendence (ST) character scales. CONCLUSION: Personality changes in SLE is characterized by higher HA and RD along with low SD. These features are associated with higher anxiety, social withdrawal and lower resourcefulness and purposefulness.

Recalcitrant cases of pyoderma gangrenosum, responding dramatically to systemic tacrolimus.

Pyoderma gangrenosum (PG) is an uncommon ulcerative cutaneous disease, without any well-known specific and effective treatment. Here we report two patients with severe recalcitrant perineal pyoderma gangrenosum, successfully treated with low dose systemic tacrolimus. Tacrolimus can be a safe effective drug in the management of recalcitrant PG.

An elevated pro-inflammatory cytokines profile in Behcet's disease: A multiplex analysis.

The serum levels of sixteen cytokines related to innate immunity, Th1, Th2 and Th17 cells in the sera of 44 patients with Behcet's Disease (BD) and 44 healthy controls have been investigated using the cytokine array technique. Among the cytokines related to innate immunity, the levels of IL-1α, IL-1 ß, IL-6, IL-12, IL-15 and TNF-α were statistically higher in BD patients than healthy controls. In the case of Th1- and Th17-related cytokines, IL-2, IFN-γ, IL-17 and IL-23 were significantly higher in patients. From Th2-related cytokines, only IL-13 showed statistically higher levels in patients than controls. Among different evaluated cytokines, the differences in IL-1 α, IL-1 ß, IL-6 and Æ©innate-related cytokines were more prominent between cases and controls. In addition, the results showed that Æ©innate- and Æ©Th17-related cytokines are better indicators of cytokines imbalances in BD than each one of the innate- and Th17-related cytokines. Moreover, disease activity score and clinical activity index can also be affected by the levels of pro-inflammatory (IL-6) and anti-inflammatory (IL-4) cytokines. In conclusion, the results revealed that imbalances in the expression of innate immunity- as well as Th1- and Th17-related cytokines may play not only a pivotal role in BD pathogenesis but also can be important in disease severity.

Screening of patients with juvenile idiopathic arthritis and those with rheumatoid arthritis for celiac disease in southwestern Iran.

BACKGROUND/AIMS: Celiac disease (CD) is a common enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. It is frequently found in conjunction with other autoimmune diseases. The purpose of this study was to investigate the prevalence of CD in patients with juvenile idiopathic arthritis (JIA) and those with rheumatoid arthritis (RA) in southwestern Iran. MATERIALS AND METHODS: A total of 53 children with JIA and 55 adults with RA were enrolled. Anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A serum levels were measured by performing an enzyme-linked immunosorbent assay. Patients with anti-tTG IgA serum levels of >15 U/mL were considered seropositive and subjected to upper gastrointestinal endoscopy. Duodenal biopsies were histopathologically evaluated based on the modified Marsh classification. RESULTS: One child with JIA (1.8%) and six adults with RA (11.3%) were positive for the anti-tTG IgA antibody, but the histopathological evaluations of the duodenal biopsies in these patients revealed no evidence of CD-related enteropathy. CONCLUSION: Although the investigation of anti-tTG antibodies is widely used as a noninvasive serologic test for the initial diagnosis of CD, because of the high positive predictive value, the clinical utility of this test alone for making a diagnosis is doubtful. We found no cases of CD among our patients with JIA and RA. The periodic screening of rheumatologic patients with positive anti-tTG IgA for CD can be helpful in making an early diagnosis of CD in these patients.

Randomized clinical trial of peganum oil for knee osteoarthritis.

Osteoarthritis affects about 50% of people aged older than 65 years. Pain is the most important symptom in this disease. Today public interest in the use of complementary medicine, especially traditional herbal medicines has increased. The present study was designed to investigate the efficacy of traditional preparation of Peganum harmala L oil on patients with knee osteoarthritis. The product has been analyzed and standardized by high-performance liquid chromatography. A double blind controlled randomized clinical trial consisting of 54 patients were performed. Patients rubbed the drug or control (olive oil) on the knee 4 drops 3 times a day for 4 weeks. The patients were asked to fill out the Western Ontario and McMaster Universities Arthritis Index and Visual Analogue Scale questionnaires at week 0 and 4. The adapted results from the questionnaires showed that pain and difficulty in function were significantly decreased in Peganum oil group after 4 weeks. There was no significant difference in stiffness change between 2 groups.

High prevalence of Helicobacter pylori infection in Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a multisystem disease of unknown etiology. There are several clues which may indicate an ethiopathogenesis role for Helicobacter pylori infection in this disease. METHODS: In a case control study in an out patient department, 48 patients with BD were compared to age, sex matched controls regarding presence of H. pylori infection by serology and urea breath test (UBT). RESULTS: Ongoing H. pylori infection was more prevalent among patients with BD using result of UBT with odds ratio of 3.1 (95% CI: 1.34 - 7.26, PV < 0.001). CONCLUSION: H. pylori infection may have a role in the pathogenesis of BD.

Association of FCRL3 genotypes with susceptibility of Iranian patients to rheumatoid arthritis.

Rheumatoid arthritis (RA) is a complex disease, the hallmark of which is synovial joint inflammation. The substantial contribution from genetic factors in susceptibility to RA has been well-defined. The Fc receptor-like3 (FCRL3) gene is one of the genes that have recently shown a significant association with RA. To determine the possible role of FCRL3-169 C/T and FCRL3-110 A/G gene polymorphisms in the development of RA in Iranian patients, 320 RA patients and 302 healthy subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. No significant difference was found in genotype and allele frequencies of FCRL3-169 C/T between patients and controls. In contrast, at position -110 A/G, the frequency of the AA genotype and A allele was significantly decreased in RA patients compared to controls (p = 0.005). After Bonferroni correction for multiple testing, no significant correlations between FCRL3-169 C/T and -110 A/G polymorphism and laboratory and clinical features of the patients was observed. In conclusion, the results of this study showed a significant association between FCRL3-110 A/G polymorphism and susceptibility to RA.