Sami Bahlas

Diagnostic value of FASH ultrasound and chest X-ray in HIV-co-infected patients with abdominal tuberculosis.

In human immunodeficiency virus (HIV) co-infected tuberculosis (TB) patients with negative acid-fast bacilli smears, chest radiography (CXR) is usually the first imaging step in the diagnostic work-up. Ultrasound, also in the form of focused assessment with sonography for TB-HIV (FASH), is an additional imaging modality used to diagnose extra-pulmonary TB (EPTB). Findings from 82 patients with abdominal TB diagnosed by ultrasound were analysed and compared with CXR results. Enlarged abdominal lymph nodes were seen in 75.6% of the patients, spleen abscesses in 41.2% and liver lesions in 30.6%. CXR showed a miliary pattern in 21.9% of the patients; 26.8% of the CXR had no radiological changes suggestive of pulmonary TB. This patient group would benefit from ultrasound in diagnostic algorithms for HIV-associated EPTB.In human immunodeficiency virus (HIV) co-infected tuberculosis (TB) patients with negative acid-fast bacilli smears, chest radiography (CXR) is usually the first imaging step in the diagnostic work-up. Ultrasound, also in the form of focused assessment with sonography for TB-HIV (FASH), is an additional imaging modality used to diagnose extra-pulmonary TB (EPTB). Findings from 82 patients with abdominal TB diagnosed by ultrasound were analysed and compared with CXR results. Enlarged abdominal lymph nodes were seen in 75.6% of the patients, spleen abscesses in 41.2% and liver lesions in 30.6%. CXR showed a miliary pattern in 21.9% of the patients; 26.8% of the CXR had no radiological changes suggestive of pulmonary TB. This patient group would benefit from ultrasound in diagnostic algorithms for HIV-associated EPTB.

Perceived illness stigma is associated with depression in female patients with systemic lupus erythematosus

OBJECTIVES 1) To assess the prevalence of depression in a sample of female patients with systemic lupus erythematosus (SLE) 2) To evaluate the association between perceived illness stigma and depression in those patients. METHODS In a cross-sectional study, 80 female SLE patients were evaluated for the presence of depression and perceived illness stigma. Depression was diagnosed using the Structured Clinical Interview for DSM-IV Axis Ι disorders, clinical version (SCID-I-CV), the severity of the depressive symptoms was evaluated using the Hospital Anxiety and Depression Scale-Depression Subscale (HADS-D), and the stigma of illness was assessed using the Stigma Impact Scale (SIS). RESULTS The prevalence of depression among female SLE patients was 18.75% (15/80). The perceived illness stigma was higher among the depressed group than among the non-depressed group (SIS mean scores were 43.87±7.87 and 26.62±3.79 respectively P<.001), there was a significant positive correlation between SIS and HAD-D scores (r=0.73, P=.002), and there was a significant association between perceived illness stigma and diagnosis of depression (R(2)=0.53, P=.002, odds ratio=3.2), which increased the severity of depressive symptoms (R(2)=0.64, P<.001). CONCLUSION This study demonstrates a significant association between illness stigma and depression in female SLE patients which may be important in promoting optimal coping for these women .

Periodontal findings in systemic lupus erythematosus patients and healthy controls

Objectives: To compare periodontal findings in systemic lupus erythematosus (SLE) patients and healthy controls, and to determine, whether there is a correlation between periodontal parameters and SLE biomarkers. Methods: This cross-sectional study was conducted in the Faculty of Dentistry, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia between November 2012 and February 2014. Twenty-five participants diagnosed with SLE and 50 healthy controls were selected. Periodontal assessment consisted of clinical attachment level (CAL), probing depth (PD), bleeding on probing, and plaque scores. For the SLE group, several laboratory tests were obtained, such as, white blood cell count, hemoglobin level, platelet count, anti-nuclear antibody, anti-double-stranded DNA antibody, calcium level, and vitamin D. Results: Periodontal findings in SLE patients and controls were not significantly different. The SLE patients who had no flare-ups for more than a year showed significant bleeding on probing and deeper PD compared with those who had flare-ups less than a year before starting the study. The SLE patients with arthritis symptoms showed more CAL than those without arthritis. In the SLE patients, no significant correlation was found between their periodontal findings and SLE biomarkers. Conclusion: Periodontal health was not different between SLE patients and healthy controls. In SLE patients however, flare-ups and presence of arthritis had a significant relation with periodontal health.

Ultrasound findings in cases of extrapulmonary TB in patients with HIV infection in Jeddah, Saudi Arabia

Objective To report ultrasound (US), laboratory and chest radiograph (CXR) findings of patients with extra-pulmonary tuberculosis (EPTB) and discuss the diagnostic relevance of US in EPTB in high-risk individuals.

Analysis of CD95 and CCR7 expression on circulating CD4+ lymphocytes revealed disparate immunoregulatory potentials in systemic lupus erythematosus

Emerging data have implicated a critical role for CD4 in the pathogenesis of systemic lupus erythematosus (SLE). This study was designed to delineate the contribution of CD4+ T cells in the pathogenesis of SLE disease. Forty-four patients (3 male: 41 female) and 20 healthy volunteers (4 male: 16 female) were included in the study. CD4+ lymphocytes analysis was done using three-color flow cytometry with antibodies against human-CD95, a prototype cell death receptor, and the chemokine receptor-7 (CCR7) after gating for lymphocytes based on the forward and side scatter. Serum levels of IL-6, IL-12, IL-17, TNF-α and IL-10 cytokines were assayed using ELISA. Disease activity was assessed using the SLE disease activity index (SLEDAI). Based on the expression of CCR7 and CD95, CD4+ lymphocytes were subdivided into three particular subsets; CD4+CD95+CCR7+ cells, CD4+CD95−CCR7+ cells and CD4+CD95+CCR7− cells. Percentage of CD4+CD95+CCR7+ cell subset was significantly higher in patients with SLE with active disease (SLEDAI > 6) and inactive (SLEDAI < 6) as compared with controls (P = 0.005), and it showed a significant positive correlation with ANA titer (P = 0.01), and a negative correlation with WBCs count (P = 0.001). CD4+CD95+CCR7− cell subset was significantly higher in active SLE patients in comparison to patients with inactive disease and controls (P = 0.05, P = 0.005 respectively), and it correlates positively with SLEDAI, IL-6 and IL-17 levels (P = 0.001, 0.05, 0.01 respectively), and negatively with blood WBCs counts (P = 0.001). The third CD4+CD95−CCR7+cell subset was found significantly lower in SLE patients compared with controls, and it was found negatively correlated with IL-10, IL-6, and IL-17. The results show that CD4+CD95+subset lacking expression of CCR7 is associated with cell mediated inflammatory response as manifested by its correlation with signs of inflammation, inflammatory cytokines and disease activity index. Whereas, CD4+CD95+CCR7+ correlate more with antibody immune responses as manifested by association with serum ANA. These data suggest disparate roles of these cell subsets in the pathophysiology of SLE. A better understanding of the characteristics of CD4 cell subsets may shed light on the pathogenesis of autoimmune diseases, particularly SLE.

Psoriatic arthritis comorbidity index: development and validation of a new specific tool for classifying prognostic comorbidity in psoriasis and psoriatic arthritis patients

Objective: 1. identify comorbidities with greatest impact on PsA patients’ health status. 2.develop and validate a prospectively applicable comorbidity index for classifying PsA patients according to their comorbid conditions. Methods: This was a retrospective multicenter cohort analysis of PsA patients in a rheumatology clinical registry, assessing the effect of different comorbidities measured at patients’ visits over 10-years period. Outcomes of interest included functional ability, quality of life, medications induced complications, hospitalization/ death. A weighted index that was developed in a cohort of 1707 PsA patients. Internal and external validation were carried out. Results: PsA patients who had higher incidence of comorbid condition and were at high risk of hospitalization were men, with older age at disease onset, high BMI (p < 0.05). Multivariate regression analysis identified 29 comorbidities. A comorbidity index weighted according to the regression coefficient of the variables was developed (the score range: 0-37). A cut off point of 8 was associated with a sensitivity of 97.5% and a specificity of 87%. The developed PsACI correlated significantly with the 4 tested comorbidity indices: Charlson comorbidity index, Functional comorbidity index, Rheumatic Diseases comorbidity index, and Multimorbidity index at 1-, 3-, 5and 10-years. Similar significant correlation was seen on external validation assessment. Conclusion: The PsA-comorbidity index is a valid method for estimating comorbidity risk in PsA patients. It enables the clinicians to include comorbidities assessment and management in their practice. It can be used to predict resource utilization, identify targets for reducing costs, by prospectively identifying PsA patients at high risk. Correspondence to: Y. El Miedany, Rheumatology, Darent Valley Hospital, Dartford, United Kingdom, E-mail: drelmiedany@rheumatology4u.com Received: March 14, 2017; Accepted: April 10, 2017; Published: April 13, 2017 Introduction Rheumatic diseases are chronic progressive conditions which may result in significant physical disability and, in several cases, accelerated mortality [1-3]. While the primary disease accounts for much of the heightened death risk and the majority of morbidity, other factors such as comorbid conditions play a major contributing role [4, 5]. A widely accepted definition of comorbidity is “the existence or occurrence of any distinct additional entity during the clinical course of a patient who has the index disease under study” [6]. These additional entities are categorized according to the comorbidity ‘three Cs’ classification scheme: causality, complication, and coincidence. Causality is when an inflammatory disease like rheumatoid (RA), psoriatic arthritis (PsA) or systemic lupus erythematosus (SLE) is followed by patho-physiologically linked abnormalities, such as cardiovascular disorders; complications are comorbidities therapeutically linked to illnesses such as diabetes mellitus or osteoporosis (glucocorticoid-induced) or peptic ulcer (NSAIDinduced). Coincidence means that comorbidities occur independently and are unrelated to the index disease (for example, inflammatory arthritis and appendicitis) [7,8]. Separate patterns of comorbidity have been identified in patients with rheumatic diseases whether they have inflammatory arthritic conditions (such as RA, PsA, and SLE); or those with non-inflammatory rheumatic disorders such as fibromyalgia or osteoarthritis [9]. As these comorbidities contribute to increased early mortality, affect disease activity, response to treatments, and generate costs in these populations, they should be considered when managing patients with inflammatory arthritic conditions [10-12]. Furthermore, medications used to manage the underlying inflammatory condition, including diseasemodifying antirheumatic drugs (whether synthetic (sDMARD), or biologic therapy (bDMARD), corticosteroids, and NSAID, may also increase or, conversely, decrease the likelihood of comorbidities. People with psoriasis (PsO) and PsA were reported to have an elevated risk of developing comorbidities. A recent review noted that over half of the PsA patients have more than one comorbidity; which had a significant negative impact on their functional ability as well as quality of life [13]. There is currently no standardized, and validated instrument for recording and collecting comorbidity data in patients with PsO and PsA, which is relevant to contemporary and routine rheumatology practice. El Miedany Y (2017) Psoriatic arthritis comorbidity index: development and validation of a new specific tool for classifying prognostic comorbidity in psoriasis and psoriatic arthritis patients Volume 2(2): 2-7 Rheumatol Orthop Med, 2017 doi: 10.15761/ROM.1000117 The purpose of the study is to identify comorbidities with greatest impact on PsO and PsA patients’ health status. Also, to develop and validate a prospectively applicable comorbidity index for classifying these patients according to their comorbid conditions which might alter their risk of hospitalization and mortality.

Association of Apa I polymorphism of vitamin d receptor gene with type 2 diabetes mellitus in Saudi population

Vitamin D deficiency has been associated with the acceleration of the onset of T2DM. The biological effects of vitamin D are mediated by binding to the vitamin D receptor (VDR) which belongs to the steroid receptor superfamily. Although many polymorphisms exist in the VDR gene, their effect on VDR protein function and signalling is unknown. An association between VDR polymorphism and T2DM has been reported in some studies; however, it appears to vary across different populations around the world. Hence this study was carried out to investigate the relationship between VDR gene polymorphisms at three restriction sites ApaI, BsmI, and TaqI and the risk of T2DM in Saudi population. The volunteers were classified according to Fasting Blood Glucose (FBG) test as two groups, T2DM and normal group. The VDR gene was amplified by polymerase chain reaction (PCR). PCR products were digested using restriction enzymes: ApaI, TaqI, and BsmI and the bands were visualised by agarose gel electrophoresis and ethidium bromide dye under UV. The results of the current study showed a significant difference in genotypes and allele frequencies of the VDR gene polymorphisms at the ApaI site between T2DM patients and control groups. Archana P. Iyer 1,2,* , Susan Lanham New 2,3 , Sawsan Khoja 1,2 , Maryam A.AL-Ghamdi 1,2 and Sami Bahlas 2,4

Chemokine receptors expression on peripheral CD4-lymphocytes in rheumatoid arthritis: Coexpression of CCR7 and CD95 is associated with disease activity.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation triggered by infiltrating CD4 lymphocytes. The positioning and activation of lymphocyte in inflamed synovial tissues are dependent on a number of factors including their chemokine receptor expression profile. We aimed to investigate which chemokine receptors pattern correlate with serum cytokine levels and with disease activity. Forty patients with RA (34 female and 6 male) with age range from 21 to 68 years were included. Twenty healthy volunteers (16 female and 4 male) with matched age (range 21–48 years) were served as healthy controls (HCs). Expression of chemokine receptors (CCR5, CX3CR1 and CCR7) together with the apoptosis-related marker (CD95) was analyzed using three-color flow cytometry analysis after gating on CD4+ peripheral blood lymphocytes. Plasma levels of IL-6, IL-10, IL-12 and TNF-α cytokines were measured in all participants using ELISA. Disease activity score (DAS28-CRP) system was assessed and active disease was defined as DAS28 ⩾3.2. Twenty-five (62.4%) patients were classified as active RA (ARA) and 15 (37.5%) patients with inactive RA (IRA). Percentages of CD4+ lymphocytes expressing CD95 with either of CCR7 or CCR5 were significantly higher in ARA compared to IRA and HCs groups, while the expression of CX3CR1 on T-cells was found significantly lower in both CD95− and CD95+ T-cells in RA groups than HC. Percentages of CD4+CD95+CCR7+ cells correlated positively with IL-6 (r = 0.390). Whereas CD4+CD95+CX3CR1+ were negatively correlated with TNF-α (r = −0.261). Correlation of CD4+CD95+CCR7+ T cell subset with disease activity and inflammatory cytokines suggests a role for this cell subset in the pathogenesis of RA. Further investigation will be required to fully characterize this cell subset and its role in disease progression.

ASSOCIATION OF THE METABOLIC SYNDROME AND VITAMIN D RECEPTOR GENE POLYMORPHISMS: A CROSS SECTIONAL STUDY

The Vitamin D Receptor gene (VDR) expressed in many tissues and are able to modulate the expression of several other genes. The purpose of this study was to assess the association between the metabolic syndrome (MetSyn) and the presence of VDR genes ApaI, BsmI, TaqI and FokI polymorphisms as well as serum levels of vitamin D. Total eighty two (82) individuals were assessed in a cross-sectional study. Enzymatic digestion method was used to detect the VDR polymorphisms and established by allele specific PCR or amplification of refractory mutation. MetSyn was classified based on the National Cholesterol Education Program – Adult Treatment Panel III Assessment of the association of VDR, as well as serum vitamin D level, with MetSyn components was also evaluated. Serum vitamin D levels were significantly low (p < 0.01) in MetSyn patients. The occurrence of the genotypes in Apal was significantly different as compared to individuals with MetSyn and the control group (P <0.05). A negative correlation was reported between MetSyn and 25(OH) vitamin D levels, type-2 diabetes and glucose homeostasis. Further, as compared to individuals without MetSyn, subjects with MetSyn who carry AA genotype had higher waist circumference and BMI. Serum Vitamin D level was also inversely associated with waist circumference (P < 0.001), triglycerides (P < 0.01), haemoglobin A1c (P < 0.01), * Corresponding author KEYWORDS

Association of Paraoxonase 1 Polymorphism and Serum 25-Hydroxyvitamin D with the Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis

BACKGROUND Patients with rheumatoid arthritis (RA) have significantly increased cardiovascular (CV) morbidity and mortality that are not accounted for by traditional risk factors alone. Paraoxonase 1 (PON1) and 25-hydroxyvitamin D have been shown to be involved in the pathogenesis of CV diseases. Objective: This study aimed to investigate PON1 gene polymorphism and serum 25-hydroxyvitamin D concentrations in RA patients, and to determine their association with CV risk in RA. METHODS Serum samples from 46 RA patients and 45 healthy controls were tested for PON1 R192Q genotypes and serum vitamin D concentrations. The cardiovascular risks were assessed by Q-risk. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease activity status were also assessed. RESULTS PON1 polymorphism and low serum 25-hydroxyvitamin D were significantly associated with increased CV risk (p < 0.05). Compared to patients with either the PON1 QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased CV risk on multivariate analysis, controlling for traditional CV risk factors, C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (p < 0.05). CONCLUSIONS There was a relationship of the genetic determinants of paraoxonase 1 (PON1 192) and serum 25-hydroxyvitamin D to CV risk in RA patients. Paired measurement of paraoxonase 1 genotype and serum 25-hydroxyvitamin D can be used as biomarkers of CV risk in RA patients.