Lower limb entheseal involvement in systemic lupus erythematosus patients: Relation to disease activity

BackgroundMusculoskeletal involvement is extremely common in patients with systemic lupus erythematosus (SLE). Musculoskeletal ultrasound (MSUS) is an important tool for evaluation of patients with inflammatory arthritis as well as early detection of subclinical inflammation at the joint, tendon and entheseal level.Aim of the workTo investigate the frequency and distribution of lower limb entheseal abnormalities detected by MSUS in SLE patients and to evaluate its relation to disease activity.Patients and methods50 adult SLE patients were studied. SLE Disease Activity Index-2000 (SLEDAI-2K) was assessed. High-resolution MSUS assessment of quadriceps, patellar and Achilles tendons, and plantar fascia entheses was performed. Glasgow Ultrasound Enthesitis Scoring System (GUESS) was assessed.ResultsThe median age of the patients was 30 (interquartile range 23–36.3 years) and were 49 females. The median disease duration was 4 (2–8.3 years), SLEDAI-2K was 4 (2–8) and GUESS score 3 (1–5.3). Clinical enthesitis was found in 22 (44%) patients; 58% of the patients had evident MSUS features of enthesitis and 32% had minimal or isolated entheseal abnormalities. The age and SLEDAI-2K were significantly increased in those with clinical enthesitis compared to those without (p = 0.007 and p = 0.03 respectively). GUESS significantly correlated with the age (r = 0.39, p = 0.005) and SLEDAI-2K (r = 0.29, p = 0.04).ConclusionClinical and ultrasound-proved enthesitis are prevalent in SLE patients. Quadriceps tendon insertion is the most affected enthesis. Clinical enthesitis tends to occur in older SLE patients. Enthesitis has positive correlations with; age, and SLEDAI-2K score. The presence of enthesitis may represent a potential marker for SLE disease activity.     

Evaluation of serum calprotectin level as a biomarker of disease activity in rheumatoid arthritis and osteoarthritis patients

Aim of the workTo measure the levels of serum calprotectin (CLP) in rheumatoid arthritis (RA) and osteoarthritis (OA) patients and to assess its association with disease activity, severity and functional status.Patients and methodsA total of 30 RA and30 OA patients and 30 controlswere included. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), Disease activity score (DAS28), health assessment questionnaire (HAQ) and RA medical records-based index of severity (RARBIS) were assessed in RA patients. Western Ontario and McMaster Osteoarthritis index (WOMAC) and Kellgren-Lawrence (KL) grading scale were assessed in OA patients and serum CLP levels were measured.ResultsThe mean age of RA and OA patients was 48.6 ± 8.6 and 50.8 ± 9.3 years respectively andthe majority of studied groups were females. CLP was significantly higher in RA patients in comparison to OA patients and healthy control (2.70 ± 2.08 vs. 1.18 ± 0.35 vs 1.11 ± 0.24 μg/ml); p < 0.0001). Serum CLP correlated with swollen joint count (SJC) (r = 0.7, p < 0.0001), tender joint count (TJC) (r = 0.73, p < 0.0001), patient global assessment (PGA) (r = 0.51, p = 0.004), Physician global assessment (PhGA) (r = 0.58, p = 0.001), HAQ (r = 0.6,p < 0.0001), erythrocyte sedimentation rate (ESR) (r = 0.5, p = 0.005), DAS28 (r = 0.69, p < 0.0001), RARBIS (r = 0.66, p < 0.0001). At a cut-off value of 2.5 µg/ml CLP can significantly differentiate active RA patients from those in remission (AUC 0.896; p < 0.0001) at a sensitivity of 83.3%, specificity of 88.9%, and accuracy of 86.7%.CLP was significant predictor for RA activity.ConclusionThe serum CLP levels were significantly high in RA patients compared to OA patients and controls and these high levels were associated with disease activity, severity, and functional status.     

Relation of some clinical composite indices of disease activity in rheumatoid arthritis to a simplified 12 joint power Doppler ultrasound activity index

Aim of the workTo assess the association of some clinical composite disease activity indices with a simplified 12 joint power Doppler ultrasound (PDUS) activity index in rheumatoid arthritis (RA).Patients and methodsOne hundred RA patients who fulfilled the 2010 European league against rheumatism/American college of Rheumatology (EULAR/ACR) classification criteria for RA were recruited from the Rheumatology outpatient clinic, Cairo University Hospitals. Disease activity score (DAS28), the simplified disease activity index (SDAI), clinical disease activity index (CDAI) as well as mean overall index for RA (MOI-RA) were assessed. Grey Scale Ultrasonography (GSUS) and PDUS activity assessment was performed using a simplified 12-joint score.ResultsThe 100 patients were 80 females and 20 males (F:M 4:1). Their mean age was 44.4 ± 10.8 years with disease duration of 6.3 ± 4.7 years. Rheumatoid factor was positive in 77 %. DAS28 was 4.5 ± 1.3, SDAI 27.7 ± 22.7, CDAI 17.5 ± 13.2 and MOI-RA 86.8 ± 25.1. On US, tenosynovitis was present in 10 %, irregularity in 23 % and erosion in 62 %. The mean 12-point PDUS was 3.53 ± 4.16 and the overall US score 10.34 ± 9.3. A significant correlation was found between the US findings of overall synovitis, degree of PD and US score with DAS28 (r = 0.3, p < 0.0001; r = 0.4, p < 0.0001 and r = 0.3, p < 0.0001) with SDAI (r = 0.3, p < 0.0001; r = 0.4,p < 0.0001; r = 0.4, p < 0.0001) and with MOI-RA score (r = 0.3, p < 0.0001; r = 0.4, p < 0.0001 and r = 0.4, p < 0.0001 respectively) but the highest correlations was with CDAI (r = 0.4, p < 0.0001; r = 0.5, p < 0.0001 and r = 0.4, p < 0.0001 respectively).ConclusionSimplified 12 -joint PDUS score is well correlated with activity indices in RA patients.     

Galectin-3 and interleukin-7 as potential serologic markers in rheumatoid arthritis patients

Aim of the workTo assess the level of serum galectin-3 and interleukin-7 (Il-7) in rheumatoid arthritis (RA) patients and to study their association with disease activity as well as other disease parameters.Patients and methodsSerum samples from 66 RA patients and 20 matched controls were tested for galectin-3 and IL-7 using enzyme-linked immunosorbent assay (ELISA). Disease activity was assessed using disease activity score (DAS28).ResultsThe mean age of the patients was 46.6 ± 12.02 years, mean disease duration was 7.5 ± 7.6 years and they were 61 females and 5 males. The mean DAS28 of the patients was 4.72 ± 1.77. Serum galectin-3 and IL-7 were higher in RA patients (7.7 ± 5.7 ng/ml and 9.03 ± 5.97 pg/ml) than the control (1.5 ± 0.8 ng/ml and 1.6 ± 1.1 pg/ml) (p < 0.001). Serum galectin-3 and IL-7 significantly correlated with age (r = 0.27, p = 0.03 and r = 25, p = 0.04), DAS28 (r = 0.64, p < 0.001 and r = 39, p = 0.001), as well as to each other (r = 0.48, p < 0.001). Serum galectin-3 significantly correlated with ESR (r = 0.29, p = 0.018) and significantly higher in those with fever (p = 0.017). At a cutoff of 2.94 ng/ml, serum galectin-3 showed 84.8% sensitivity and 100% specificity (p < 0.001) and at 2.71 pg/ml, serum IL7 showed a sensitivity of 92.4% and a specificity of 95% (p < 0.001) to diagnose RA.ConclusionSerum galectin-3 and IL-7 were higher in patients than in controls and were increased with high disease activity making them promising biomarkers for RA. Both of them showed high diagnostic power for RA. This may provide further understanding of RA pathogenesis and suggest new therapeutic interventions.     

Collagen triple helix repeat containing 1 (CTHRC1) protein: A promising biomarker for evaluation of rheumatoid arthritis patients

Aim of the workTo assess serum collagen triple helix repeat containing 1 (CTHRC1) protein level in rheumatoid arthritis (RA) patients and compare it with healthy controls. In addition, to evaluate the relation of its level with RA activity and severityPatients and methodsThe study included 60 adult RA patients and 60 matched controls. Disease activity score (DAS28), modified health assessment questionnaire (MHAQ) and RA medical records-based index of severity (RARBIS) were assessed in RA patients. Serum CTHRC1 levels were measured in patients and controls by enzyme linked immunosorbent assay (ELISA)ResultsThey were 49 females and 11 males patients with a mean age of 43.6 ± 10.8 years and disease duration of 8.8 ± 0.9 years. The mean of DAS28 was 4.9 ± 2 (1.95–8.6). Serum CTHRC1 levels were significantly higher in patients than controls (1009.5 ± 79.4 vs. 470.7 ± 8.2 ng/ml, p < 0.001).The optimum cut-off value of CTHRC1 to discriminate patients from control was > 583.5 ng/ml with sensitivity of 98.3% and specificity of 100%. CTHRC1 significantly correlated with DAS28 (r = 0.81, p < 0.001), MHAQ (r = 0.14, p = 0.002), RARBIS (r = 0.41, p = 0.006), erythrocyte sedimentation rate (ESR) (r = 0.57, p < 0.001), C-reactive protein (CRP) (r = 0.41, p = 0.002), rheumatoid factor (RF) (r = 0.31, p = 0.037) and anti-cyclic citrullinated peptide (anti-CCP) (r = 0.27, p = 0.036). The significant predictors of increase CTHRC1 among patients were elevation in DAS28 (ß=287.6; p = 0.007, CI = 83.4–491.9) and MHAQ (ß=369.7; p = 0.042, CI = 14.5–724.9)ConclusionSerum CTHRC1 is a promising biomarker for evaluation of RA patients. It can be used as a marker for RA diagnosis and in monitoring the disease activity and severity.     

Collagen triple-helix repeat containing 1 (CTHRC1) protein in rheumatoid arthritis patients: Relation to disease clinical,radiographic and ultrasound scores

Aim of the workto study the relationship between collagen triple helix repeat containing 1 (CTHRC1) protein serum levels and disease activity, patients’ well-being, as well as ultrasonographic and radiological scores in patients with rheumatoid arthritis (RA).Patients and methodsThe work included 70 RA patients and 70 age and gender matched controls. The disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Modified Larsen's score was used to score the hands and feet digital radiographs and musculoskeletal ultrasound (MSUS) examination using ultrasound-7 score was carried out. Serum CTHRC1 levels were measured by ELISA.ResultsPatients were 62 females and 8 males (F: M 7.8:1), their mean age was 42.2 ± 17.7 years and median disease duration 15 years. The median CTHRC1 serum levels were significantly higher in patients (453 ng/dl; 158–688 ng/dl) than control (99 ng/dl; 67–179 ng/dl) (p < 0.001). CTHRC1 was significantly increased in those with high activity (p < 0.001).CTHRC1 levels significantly correlated with DAS28 (r = 0.87,p < 0.001), CRP (r = 0.43,p < 0.001) and total ultrasound-7 score (r = 0.27,p = 0.03). Only total US7 score (p = 0.003) and CTHRC1 (p < 0.001) were significant predictors of activity. Serum CTHRC1 could significantly differentiate between patients and controls at cut off 179 ng/ml; sensitivity 95.7 % and specificity 100 % (p < 0.001) and between patients active and in remission at cut off 324 ng/ml; sensitivity 92.2 % and specificity 94.7 % (p < 0.001).ConclusionsPatients with RA have significantly elevated serum levels of CTHRC1. In the process of structural bone ultrasonographic abnormalities as well as disease activity in RA patients, elevated CTHRC1 levels play a key role.     

Cutaneous immunohistochemical expression of interleukin-23 receptor (IL-23R) in psoriasis and psoriatic arthritis patients: Relation to musculoskeletal ultrasound findings

Aim of the workTo assess the immunohistochemical expression of cutaneous interleukin-23 receptor (IL-23R) in psoriasis and psoriatic arthritis (PsA) patients and study its relation to musculoskeletal ultrasound (MSUS) findings.Patients and methodsThe study was conducted on 40 patients: 20 with PsA and 20 with psoriasis only. The psoriasis area severity index (PASI) was estimated. Synovitis was assessed by Power Doppler ultrasound and enthesitis by Glasgow Ultrasound Enthesitis Scoring System (GUESS).ResultsThe mean age of PsA and psoriasis only patients (49.9 ± 11.6 and 44.9 ± 13 years) and gender (12 males and 8 females each) were comparable. IL-23R expression in the epidermal keratinocytes and dermal inflammatory cells of PsA patients scored 5 in 40% and 4 in 45% respectively while in psoriasis only the highest frequency of cases (40%) scored 2 in both. In psoriasis only, dermal and epidermal IL-23R were significantly associated to effusion (5 ± 0 vs 2.2 ± 0.7 and 4 ± 0 vs 1.5 ± 0.5, p < 0.001 respectively) and synovitis (5 ± 0 vs 2.4 ± 1 and 4 ± 0 vs 1.7 ± 0.8, p < 0.001 respectively) (p < 0.001) and both significantly correlated with erosions (r = 0.64, p = 0.002 and r = 0.64, p = 0.003) and GUESS (r = 0.68, p = 0.001 and r = 0.61, p = 0.005). Dermal IL-23R was significantly associated with the PASI score in PsA patients (r = 0.59, p = 0.01). On regression, IL-23R significantly predicted PsA (epidermal: p = 0.001 and dermal: p = 0.018).ConclusionIL-23R is highly expressed in psoriatic skin and strongly associated with psoriatic skin, joints and entheses findings. MSUS is valuable in the detection of subclinical arthritis. Cutaneous IL-23R expression may refer to early joint affection and with MSUS may allow early prediction and management.     

Clinical significance of serum survivin in rheumatoid arthritis patients: Relation to disease activity,functional status and radiological damage

Aim of the workTo measure the levels of serum survivin in rheumatoid arthritis (RA) patients and to assess its relation to disease activity, functional impairment, and radiological damage.Patients and methodsThis study included 58 RA patients and 34 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), modified Larsen radiological score and serum survivin level were assessed.ResultsThe mean age of the patients was 43.5 ± 11.5 years; 43 females and 15 males (F:M 2.9:1) with a mean disease duration of 2.6 ± 1.13 years. RF was positive in 79% Survivin level was significantly increased in patients compared to the controls (171.8 ± 74.4 pg/ml vs. 98.7 ± 16 pg/ml, p < 0.001) and in those with activity (203.1 ± 69.1 pg/ml) compared to those in remission (102.1 ± 12.1 pg/ml). Survivin level tended to be higher in females (177.1 ± 79.5 pg/ml) compared to males (156.4 ± 57 pg/ml) (p = 0.36) and was significantly higher in those with positive RF (183 ± 75.9 pg/ml) compared to those with a negative test (128.6 ± 50.5 pg/ml) (p = 0.02). A significant correlation was detected between survivin and disease duration, DAS28, ESR, CRP, VAS, HAQ, RF, and modified Larsen scores (p < 0.001). On univariate logistic regression the RF, HAQ, modified Larsen and survivin level were significant predictors but were insignificant on multivariate analysis.ConclusionIn RA patients the serum survivin is significantly increased compared to the controls. The disease activity, functional impairment, and radiological joint damage were associated with these high concentrations.     

The role of musculoskeletal ultrasound in assessment of disease activity in rheumatoid arthritis patients with fibromyalgia

IntroductionFibromyalgia (FM) is frequently present in rheumatoid arthritis (RA) patients and this can lead to an overestimation of disease activity and consequently overtreatment. Musculoskeletal ultrasound (MSUS) can aid in evaluating synovitis for assessment of disease activity with more precision.Aim of the workTo verify the potential role of MSUS in the assessment of disease activity in RA patients with and without FM.Patients and methodsThis study was conducted on 100 active RA patients. Disease activity score (DAS28) and clinical disease activity index (CDAI) were assessed. MSUS was assessed using the 12 joint simplified score.ResultsThe 100 patients were 88 females and 12 male (F:M 7.3:1) with a mean age of 44.82 ± 11.4 years and disease duration of 6.88 ± 5.77 years. 67 RA patients had associated secondary FM and 33 did not. DAS-28 and CDAI were significantly higher in those with FM (4.99 ± 0.82 and 30.49 ± 10.59) compared to those without (4.22 ± 0.96 and 18 ± 10.68)(p < 0.001). Regarding ultrasonographic finding, no significant difference was found between those with and without FMS. DAS28 and CDAI significantly correlated (p = 0.006, p = 0.002 respectively) with grey scale ultrasound (GS-US12) in patients without FMS while DAS28 only significantly correlated with GS-US12 in those with FMS (r = 0.28, p = 0.022).ConclusionSecondary FM is common in RA patients and associated with a higher disease activity making it a potential influencer on the treatment strategy. MSUS can complement physical examination in the assessment of disease activity but had a limited role to delineate RA patients with FM from those without.     

Detection of hearing loss in rheumatoid arthritis patients using extended high frequency audiometry: Is it related to disease activity and severity?

Aim of the workTo evaluate audiological characteristics in rheumatoid arthritis (RA) patients compared with controls using extended high frequency audiometry and analyze their correlations with RA activity and severity to identify patients at higher risk of hearing loss.Patients and methodsThe study was carried out on 95 RA patients and 100 controls. Every subject underwent pure tone audiometry (PTA) from 250 through 8000 Hz, speech audiometry and extended high frequency audiometry (EHFA) from 10,000 to 20000 Hz. Disease activity score (DAS28) and RA medical records-based index of severity (RARBIS) were assessed.ResultsPatients were 85 females and 10 males with age mean 46.5 ± 1.1 years and disease duration of 9.57 ± 0.61 years. The hearing thresholds (HT) of patients were significantly higher than those of controls at all PTA (p < 0.001) and EHFA frequencies (p < 0.001). Hearing loss (HL) was detected in 68.4% and 64.2% by using PTA, while EHFA revealed it in 100% and 97.9% of right and left ears of RA patients respectively. Hearing loss was bilateral, symmetrical and sensorineural in all cases. HT of EHFA significantly correlated with age (r = 0.63, p < 0.001), age at onset (r = 0.51, p < 0.001), disease duration (r = 0.3, p = 0.03), DAS28 (r = 0.31, p = 0.01) and RARBIS (r = 0.21, p = 0.03).ConclusionBilateral symmetrical sensorineural hearing loss (SNHL) is significantly more frequent in RA patients compared to control. EHFA is valuable test to detect HL in patients with RA. Older age, longer disease duration, higher disease activity and severity are important factors for the development of HL in RA.     

Quality of sleep in rheumatoid arthritis patients: Relationship with disease activity,depression and functional status

Aim of the workTo assess sleep quality in Egyptian patients with rheumatoid arthritis (RA) and its relationship with disease activity, depression and functional status.Patients and methodsThis cross-sectional study included 133 RA patients and 76 age and sex matched controls. Sleep using the Pittsburg Sleep Quality Index (PSQI), Beck depression inventory (BDI), functional status using health assessment questionnaire (HAQ), visual analogue scale-pain (VAS), and disease activity score (DAS28) were assessed.ResultsPatients were 125 females and 8 males with a mean age of 42.5 ± 9.5 years and disease duration of 3.9 ± 1.3 years. 76 age and sex matched control were also included. Poor sleep quality was detected in 54.1% of patients. Patients had significantly higher scores in the subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, day-time dysfunction domains and in terms of the total PSQI score compared to the control (p < 0.05). A significant difference was found between RA patients with poor sleep quality and those with good sleep quality as regards marital status, HAQ, erythrocyte sedimentation rate (ESR), VAS, DAS28, morning stiffness duration, anti-cyclic citrullinated peptide (anti-CCP) (p < 0.05), and the BDI (p < 0.001). The multivariate regression analysis found that disease activity, functional disability and depression were predictors for poor sleep quality (p = 0.04, p = 0.01 and p < 0.001; respectively).ConclusionThe sleep quality is impaired in RA patients. The poor sleep quality is associated with disease activity, depression and functional disability. Systemic psychiatric screening, holistic assessment and targeted interventions are required to improve sleep quality and quality of life.     

Nail affection as a central part of the entheseal organ in psoriasis patients for early detection of psoriatic arthritis

Aim of the workTo evaluate nail unit and detect subclinical enthesitis at extensor tendons in psoriatic patients for early detection of psoriatic arthritis (PsA).Patients and methodsThe study included 60 PsO patients and 60 matched healthy controls. Patients underwent history, clinical examination, assessment of Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Leeds Enthesitis Index (LEI), musculoskeletal ultrasound (MSUS) both grey and power Doppler (PD) for measuring nail bed thickness (NBT), nail vessels resistive index (NVRI), extensor digitorum tendon insertion for enthesitis and distal interphalangeal joints for synovitis.ResultsPatients were 38 females and 22 males (F:M 1.7:1) with mean age 45.1 ± 13.5 years. Nail irregularities were in all cases. The mean NBT of right thumb and index were significantly increased in patients (2.3 ± 0.6 and 1.9 ± 0.4) compared to control (1.5 ± 0.2 and 1.2 ± 0.2; p < 0.001 respectively). The mean NVRI was significantly increased (0.7 ± 0.1) in cases compared to control (0.4 ± 0.1; p < 0.001). NBT > 1.8 mm would differentiate cases from control (sensitivity 76.7% and specificity 100%). Frequency of tendons hypoechogenicity and thickness were significantly increased (73% and 93.3%) in patients. A significant correlation was found between disease duration and NAPSI (r = 0.4, p = 0.04). Enthesophyte with PD significantly correlated with PASI (r = 0.6, p = 0.02). Enthesophyte without PD significantly correlated with PASI (r = 0.6, p = 0.001) and with tendon thickness (r = 0.5, p = 0.01). A significant correlation was found between NBT and LEI (r = 0.7, p = 0.01).ConclusionMSUS is an important tool for examining nail as part of the entheses in psoriasis. There is a significantly increased frequency of extensor tendon enthesopathy in fingers with involved nails.     

Serum calprotectin as a potential biomarker for subclinical enthesitis in psoriatic patients

Aim of the workTo assess serum calprotectin level in psoriatic patients and investigate its potential relation to clinical and ultrasonographic enthesitis.Patients and methodsThe study included 45 psoriatic patients and 20 matched healthy controls. Enthesitis was assessed clinically, by musculoskeletal ultrasound (MSUS) and power Doppler, by Leeds Enthesitis Index (LEI), Maastricht Ankylosing Spondylitis Enthesitis (MASES), Spondyloarthritis Research Consortium of Canada (SPARCC) and Madrid Sonography Enthesitis Index (MASEI) scores. The Psoriasis Area, Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were evaluated. Serum calprotectin was measured using enzyme-linked immunosorbent assay.ResultsThe study included 45 psoriatic patients with a mean age of 49.9 ± 7.8 years and they were 23 males and 22 females with disease duration of 5.2 ± 3 years, (0.5–11 years). Patients were categorized into those with enthesitis (n = 25; 20 clinically and 5 subclinically diagnosed by MSUS) and those without (n = 20). Serum calprotectin was significantly higher among patients with enthesitis (clinical 593.7 ± 192.5 ng/ml and subclinical 692 ± 265.9 ng/ml) compared to those without (381.2 ± 198.5 ng/ml) and to the control (111.1 ± 15 ng/ml) (p = 0.001). The DLQI was significantly severer in patients with clinical enthesitis compared to those subclinically detected or without (p < 0.001). The acute phase reactants (erythrocyte sedimentation rate and C-reactive protein) were comparable between patients and control. Serum calprotectin significantly correlated with MASES, LEI, SPARCC and MASEI score in psoriatic patients (p < 0.001). At cutoff 141 ng/ml, calprotectin yielded specificity 69% and sensitivity 75% to detect enthesitis (p = 0.008).ConclusionCalprotectin may be considered as a potential biomarker for detection of enthesitis in psoriatic patients.     

Association of serum osteoprotegerin and osteoprotegerin gene polymorphism with subclinical carotid artery atherosclerosis and disease activity in rheumatoid arthritis patients

Aim of the workTo investigate the association of single nucleotide polymorphism (SNP) (rs2073618) of the OPG gene and of serum OPG with subclinical carotid atherosclerosis in RA patients.Patients and methodsEighty RA patients with no previous history of a cardiovascular disease were studied and forty healthy controls were enrolled in the study. Carotid atherosclerosis was evaluated by high-resolution B-mode ultrasound and the carotid intimal medial thickness (CIMT) measured. rs2073618 OPG genotyping was performed by polymerized chain reaction (PCR) and serum OPG concentrations were measured. The high sensitive C reactive protein (hs-CRP), rheumatoid factor (RF) titer and anti-cyclic citrullinated peptide (anti-CCP) were assessed. The disease activity score (DAS28) was evaluated.ResultsThe patients mean age was54.1 ± 6.2 years, disease duration of 12.5 ± 8.5 years and were 72 females and 8 males. Increased IMT was found in 38 patients, 40 age and sex matched controls were included. Patients with atherosclerosis (n = 38) had longer disease duration, higherDAS28, hs-CRP, RF titer and anti-CCP. The serum OPG levels were higher in patients with atherosclerosis (1106.4 ± 1157.1 ng/l) compared to those without (658.3 ± 151.1 ng/l)(p = 0.001). Serum OPG significantly correlated with disease duration (r = 0.42, p = 0.005), DAS28 (r = 0.53, p = 0.001), hs-CRP (r = 0.41, p = 0.007), anti-CCP (r = 0.47, p = 0.003) and mean CIMT (r = 0.37, p = 0.02). The frequencies of CC, CG and GG genotypes were comparable between those with and without atherosclerosis (39.5%, 50%, 10.4% vs 42.9%, 47.6% and 9.5% respectively).Conclusionrs2073618 OPG gene may not be associated with subclinical atherosclerosis, although the serum level could be a reliable marker for disease activity and for early detection of carotid artery atherosclerosis in RA.     

The relationship of serum calprotectin with disease activity,functional status,ultrasonographic findings and radiological damage in rheumatoid arthritis patients

Aim of the workTo measure the levels of serum calprotectin (CLP) in rheumatoid arthritis (RA) patients and to assess its association with disease activity, functional status, ultrasonographic findings, and radiological damage.Patients and methodsThis study included 47 RA patients and 33 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score (DAS28), health assessment questionnaire (HAQ), modified Larsen radiological score, musculoskeletal ultrasound and serum CLP levels were assessed.ResultsThe mean age of the patients was 42.5 ± 12.8 years; 34 females and 13 males (F:M 2.6:1) with a mean disease duration of 2.6 ± 1.1 years. RF was positive in 72%. CLP level was significantly increased in patients compared to control (2.78 ± 0.89 μg/ml vs. 0.84 ± 0.5 μg/ml; p < 0.001) and in those with activity (3.27 ± 0.75 μg/ml) compared to those in remission (1.92 ± 0.15 μg/ml). A significant correlation was detected between CLP and DAS28, ESR, CRP, HAQ, and modified Larsen scores (p < 0.001). On regression, tender and swollen joint counts, ESR, CRP, HAQ, modified Larsen, ultrasound 7 score and CLP level were significant predictors of activity but were insignificant on multivariate analysis. At a cut-off value of 2.35 μg /ml CLP can significantly differentiate active RA patients from those in remission (AUC 0.95; p < 0.001) at a sensitivity of 90%, specificity of 100%, and accuracy of 95%.ConclusionThe serum CLP levels were significantly high in RA patients and these high levels were associated with disease activity, functional status, ultrasonographic findings, and radiological damage.     

Vitamin D status in ankylosing spondylitis patients: Relation to bone health,disease activity,functional status,spine mobility and enthesitis

Aim of the workTo evaluate serum levels of vitamin D in ankylosing spondylitis (AS) patients in relation to bone mineral density, bone metabolism, and disease activity, functional status, spine mobility and extent of enthesitis.Patients and methodsSixty AS patients and 60 controls were included. Bath AS disease activity index (BASDAI), functional index (BASFI), metrology index (BASMI), AS disease activity score (ASDAS), and Maastricht AS enthesitis score (MASES) were assessed. Serum levels of vitamin D3, carboxy-terminal telopeptide of type-I collagen (CTX-1), alkaline phosphatase (ALP) and bone alkaline phosphatase (bALP) were measured. Dual-energy X-ray absorptiometry (DXA) was assessed.ResultsPatients mean age was 31.7 ± 9.1 years, disease duration 7.8 ± 4.4 years and were 46 males and 14 females. The mean BASDAI was 3.9 ± 1.02, ASDAS 2.7 ± 0.98, BASFI 3.6 ± 2.1, BASMI 4.5 ± 1.6 and MASES 4.4 ± 3.2. Patients had significantly (p = 0.001) lower levels of vitamin D (13 ± 7.8 vs 29.9 ± 9.5 ng/mL) and higher CTX-1 (547.5 ± 130.1 vs 230.1 ± 34.9 pg/mL), ALP (195.8 ± 100.8 vs 120.8 ± 10 IU/L) and bALP (48.4 ± 7.3 vs 21.03 ± 3.2 IU/L) compared to controls. Vitamin D significantly correlated with BMD (p = 0.04), inversely with CTX-1 (r = −0.22,p < 0.001), ALP (r = −0.03,p = 0.005), bALP (r = -0.22,p = 0.049), BASDAI (r = −0.57,p < 0.001), ASDAS (r =−0.37,p = 0.04), BASMI (r = −0.18,p = 0.03), MASES (r = −0.03,p = 0.008) and sacroiliitis grading (r = −2.4,p < 0.001). Vitamin D deficiency was associated with peripheral joints affection, enthesitis and not receiving sulfasalazine.ConclusionSerum vitamin D levels were decreased in patients with AS and were more deficient in relation to disease activity and bone turnover. Vitamin D may play a role in the pathogenesis and progression of AS in Egyptian patients which should be more comprehensively investigated.     

Gender-related differences in axial spondyloarthritis (axSpA) patients

Aim of the workTo explore the gender-related differences in axial spondyloarthritis (axSpA) patients.Patients and methodsSeventy-six male and 38 female patients with axSpA were assessed regarding disease characteristics and treatment. Disease activity, functional and radiologic severity index were measured using the Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis radiology index (BASRI-s) respectively, and enthesitis was assessed using Maastricht Ankylosing Spondylitis Enthesitis Score (MASES).ResultsThe mean age of the patients was 37.8 ± 10 years with a male: female ratio (2:1). Females had more delay in diagnosis (9.2 ± 3.9 years vs males 6.7 ± 3.4 years; p < 0.001) and they had enthesitis, peripheral arthritis, widespread pain and fibromyalgia as initial presentations more often than males. The mean BASDAI and BASFI was higher in females (6.3 ± 1.3 vs 5.2 ± 1.4; p < 0.001 and 6.1 ± 1.4 vs 5.3 ± 1.3; p = 0.003 respectively). Enthesitis increased in females (n = 18, 47% vs n = 12, 15.8%; p < 0.001) with higher MASES than men (3.7 ± 4 vs 1.8 ± 2; p < 0.001).Peripheral arthritis was markedly higher in females (n = 15, 39.5%vs n = 16, 21.1%; p = 0.03).Females more frequently used methotrexate and sulphasalazine (p = 0.003). BASRI-s and sacroiliitis grading were higher in males (7.2 ± 1.9 vs 4.6 ± 1.9; p < 0.001 and 3 ± 0.6 vs 2 ± 0.3; p < 0.001 respectively) with cervical syndesmophyte predominance in females (p = 0.005).ConclusionThe clinical and initial presentations differ between the two genders and the disease activity, functional limitation, and enthesitis score are higher in females. While radiologic severity is worse in men, there is predominant cervical spine involvement in women.     

Upregulation of microRNA-93-5p/microRNA-4668-5p,and promoter methylation of matrix metalloproteinase-3 and interleukin-16 genes in Turkish patients with rheumatoid arthritis

Aim of the workTo investigate promoter methylation of matrix metalloproteinase-3 (MMP-3) and interleukin-16 (IL-16) genes with the expression of miRNA-93-5p and miRNA-4668-5p which target these genes in rheumatoid arthritis (RA), respectively.Patients and methodsThe study included 49 RA patients and 38 healthy controls. Promoter methylation of MMP-3 and IL-16 was analyzed by methylation-specific PCR. The expression of miRNA-93-5p and miRNA-4668-5p were determined. Disease activity score (DAS28) was assessed.ResultsThe 49 patients (38 female, 11 male) mean age was 50.4 ± 10.5 years and disease duration of 9.1 ± 7.4 years. The mean DAS28 was 3.9 ± 1.4. The MMP-3 gene methylation frequency was significantly lower in patients (n = 37;75.5%) compared to control (n = 37;97.4%) (p = 0.004) while they were comparable for IL-16 gene (n = 46;93.9% vs n = 37;97.4%)(p = 0.45). The relative normalized expression of miRNA-93-5p and miRNA-4668-5p were significantly increased (p < 0.001) in patients (2.28 ± 3.71 and 2.47 ± 4.17-fold) compared to controls (1.12 ± 0.18 and 1.28 ± 0.53-fold) and both tended to decrease with high disease activity (r =  ? 0.104, p = 0.52; r = ?0.24, p = 0.15, respectively). There was no significant difference of miRNA-93-5p (p = 0.45), and miRNA-4668-5p (p = 0.26) expressions between patients receiving treatment and those not. A negative correlation was observed between disease activity and change in expression levels of miRNA-93-5p (r = ?0.104, p = 0.52) and miRNA-4668-5p (r = ?0.24, p = 0.15). The ROC curve analysis of target miRNAs showed the diagnostic potential of miRNA-93-5p and miRNA-4668-5p (p = 0.003 and p < 0.001 respectively).ConclusionsThe methylation status of MMP-3 promoter and expression levels of miRNA-93-5p and miRNA-4668-5p could be useful biomarkers for the pathogenesis of RA and might reflect disease activity.     

Matrix metalloproteinase-3 as a marker of subclinical activity in rheumatoid arthritis patients: Relation to ultrasonographic activity

BackgroundRheumatoid arthritis (RA) is a chronic disease which may result in progressive joint destruction even with clinical remission. Ultrasound (US) can detect subclinical disease activity and matrix metalloproteinase 3 (MMP-3) has a role in disease activity in RA.Aim of the workTo evaluate the level of MMP-3 in RA patients and its ability to predict sonographic activity in patients with clinical remission or low disease activity (LDA).Patients and methodsThis study included 45 RA patients with a disease activity score (DAS28) <3.2 and 45 matched healthy control. US evaluation using modified German US7 score was performed and accordingly patients were classified into those with sonographic remission (grey scale 0–1) or activity. MMP-3 level was assessed by enzyme-linked immunosorbent assay. Results.The mean age of the patients was 45 ± 9.5 years and 86.7% were females. Sonographic remission was achieved in 20 (44.4 %) patients. There was a significant difference in serum MMP-3 between patients and control (17 ± 4.5 vs 6.3 ± 2.2 ng/ml; p < 0.0001). There was no difference between patients with clinical remission (n = 37) and those with LDA (n = 8). Serum MMP-3 tended to be higher in patients with sonographic activity than in those with sonographic remission (18 ± 5.3 vs 15.6 ± 2.8 ng/ml; p = 0.3). Serum MMP-3 significantly correlated with erythrocyte sedimentation rate (p = 0.002) and synovitis score (p = 0.002).ConclusionSerum MMP-3 was higher in RA patients than in control and was associated with the ultrasound synovitis score. However, serum MMP-3 was not able to differentiate patients with sonographic remission from those with subclinical activity.     

Clinical implications of milk fat globule-epidermal growth factor 8 (MFG-E8) and vitamin D levels in patients with rheumatoid arthritis and primary knee osteoarthritis

Aimof the work to determine serum levels of vitamin D and Milk fat globule-epidermal growth factor 8 (MFG-E8) in rheumatoid arthritis (RA) and primary knee osteoarthritis (OA) compared to healthy controls and their possible associations. Patients and methods: The study included 30 RA and 30 primary knee OA patients as well as 25 control. The  disease activity was measured by disease activity score 28 (DAS28) in RA. The functional status was estimated by Western Ontario and McMaster Universities index (WOMAC index) in OA. While the assessment of pain was measured by the visual analog scale (VAS) in both RA and OA. Serum vitamin D and MFG-E8 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: The mean age of RA patients was 41.1 ± 9.2 years; 25 females and 5 males (F:M 5:1) and a disease duration of 6.9 ± 4.6 years. The mean age of OA patients was 48.7 ± 8.3 years; 28 females and 2 males (F:M 14:1) and disease duration was 5.4 ± 3.3 years. The mean vitamin D was significantly lower in RA (9.7 ± 5.04 ng/ml) than OA (16.4 ± 4 ng/ml) and controls (17.7 ± 3.4 ng/ml), p < 0.0001. The mean MFG-E8 serum level was significantly lower in RA and OA patients (4.9 ± 2.4 ng/mland 5.3 ± 1.2 ng/ml) than in controls (9.1 ± 3 ng/ml), p < 0.0001.Vitamin D significantly correlated with MFG-E8 (r = 0.6, p = 0.002) in RA and both inversely correlated with DAS28 (r = -0.66, p < 0.0001 and r = -0.58, p < 0.0001 respectively). Vitamin D (9.7 ng/ml) and MFG-E8 (4.9 ng/ml) significantly predicted RA (p < 0.0001) at specificity (100%) and sensitivity (66.7%). MFG-E8 at cut-off 5.3 ng/ml significantly predicted OA at specificity of 88% and sensitivity 86.7%.Conclusion: An association between low serum vitamin D and MFG-E8 levels with RA and the disease activity has been determined. Low MFG-E8 was associated with OA.