Genome-wide association study for systemic lupus erythematosus in an egyptian population.

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.

Ultrasonographic assessment of entheseal sites of upper and lower extremities in hemodialysis patients using Madrid Sonography Enthesitis Index.

BACKGROUND: There is no much information about the entheseal involvement among hemodialysis (HD) patients. The aim of this study was to assess the frequency and distribution of ultrasonographic (US) entheseal alterations in HD patients and to evaluate the association between US abnormalities and both clinical and laboratory data. METHODS: This study was conducted on 41 HD patients and 23 sex- and age- matched controls. All participants were evaluated clinically for any signs of enthesopathy. Six entheses sites were scanned bilaterally using grey scale (GS) and power Doppler (PD) US and were scored using Madrid Sonography Enthesitis Index (MASEI) scoring system. RESULTS: In HD patients, at least one clinical sign suggestive of enthesopathy was found in 69 (14%) of 492 entheses. HD patients had statistically significant higher scores of structural tendon abnormalities (p < 0.001), enthesis thickening (p < 0.001), bone erosions (p < 0.001) and calcification (p = 0.037) than the healthy controls. Total MASEI score was higher in HD patients than healthy controls (median;18 vs 8, p < 0.001), also, MASEI-inflammatory (median;11 vs 3, p < 0.001) and damage scores (median;6 vs 0, p < 0.001). There was a statistically significant positive association between total MASEI score and both age (p = 0.032) and duration of HD (p = 0.037). Duration of HD was predictive for both MASEI-damage component (p = 0.004) and total MASEI score (p = 0.014). CONCLUSION: There is a high prevalence of subclinical enthesopathy in HD patients. The entheseal US alterations is much higher in HD patients than in healthy subjects. The duration of HD is the significant predictor of enthesopathy in HD patients.

Ultrasound detected synovitis, tenosynovitis and erosions in hand and wrist joints: a comparative study between rheumatoid and psoriatic arthritis.

OBJECTIVES: Musculoskeletal ultrasound (MSUS) has been introduced as a valuable simple imaging tool for arthritis. The objective was to assess the role of ultrasound (US) in the differential diagnosis between rheumatoid arthritis (RA) and psoriatic arthritis (PsA) at the wrist and hand joints and tendons. MATERIAL AND METHODS: Thirty-five patients (20 RA and 15 PsA) with symptomatic involvement of at least one of the hand and/or wrist joints for > 6 weeks were included. Bilateral wrists (distal radioulnar, radiocarpal and midcarpal joints), hands (1st-5th metacarpophalangeal [MCP], 2nd-5th proximal interphalangeal [PIP] and 1st-5th distal interphalangeal [DIP] joints), flexor tendons and extensor compartments at the level of the wrist joint were examined sonographically. Synovial hypertrophy, joint effusion, erosions and tenosynovitis were diagnosed according to Outcome Measures in Rheumatology definitions. The findings were correlated with clinical, laboratory and disease activity indices. RESULTS: Among 680 and 510 joints examined in RA and PsA respectively, certain US features such as synovitis and erosions at the DIP were exclusively detected in PsA (p < 0.001). Synovitis was frequently detected at the distal radioulnar joints (DRUJ) in RA in comparison to PsA patients (52.5% vs. 26.7% respectively, p = 0.029). Joint effusion was more frequently detected at radiocarpal and midcarpal joints in RA compared to PsA (p = 0.047, 0.039 respectively), whereas erosions were significantly more frequently detected at radiocarpal joints in RA versus PsA patients (45% vs. 20% respectively, p = 0.029). Tenosynovitis was significantly more frequently detected at the extensor tendons in RA and at the flexor tendons in PsA patients (p = 0.021, 0.022 respectively). CONCLUSIONS: There are significant differences in the musculoskeletal US findings of the hand and wrist that joints help to distinguish between RA and PsA.

Clinical and histopathological features and short-term outcomes of lupus nephritis: a prospective study of 100 Egyptian patients.

OBJECTIVE: The short-term outcomes of lupus nephritis (LN) are variable and unpredictable among individuals. We aimed to evaluate the clinical and histopathological features and short-term renal outcomes in LN patients. METHODS: This was a prospective cohort study carried out at nephrology and rheumatology units in Egypt between 2018 and 2019. A total of 100 patients with biopsy-proven LN were studied. Patients were evaluated for response after six months. RESULTS: The female-to-male ratio was 8.1:1. About 70% of patients were hypertensive at disease onset, with rates for classes I, II, III, IV, V and VI LN being 1%, 7%, 20%, 53%, 14% and 6%, respectively. Among the immunosuppressive drugs used for induction, mycophenolate mofetil (MMF) represented the most commonly used (44%) followed by cyclophosphamide (CYC; 37%). After six months of follow-up, about two thirds of patients achieved remission. There was no significant difference in remission rate between MMF and CYC. On multivariate analysis, serum creatinine (SCr) at presentation was the most significant predictor of renal recovery. According to the receiver operating characteristic curve, the cut-off value of SCr was 1.6 mg/dL, with a sensitivity of 76% and specificity of 71% predicting renal recovery. Repeat renal biopsy was needed in 10 patients; class and treatment strategy changed in 40% and 70% of them, respectively. CONCLUSION: Our findings in Egyptian LN patients compare favourably with most studies.

Pyodermatitis-pyostomatitis vegetans associated with autoimmune hepatitis: unreported co-existence.

Pyodermatitis-pyostomatitis vegetans (PD-PSV) is a very rare inflammatory disease characterized by exudative pustular lesions of the skin and mucous membranes. The pathogenesis is unknown, but it may be related to immune or infectious processes. It is usually associated with inflammatory bowel disease (IBD). We describe a 32-year-old male with PD-PSV associated with manifestations suggestive of autoimmune hepatitis (AIH). To the best of our knowledge, this association has not been reported previously.

Musculoskeletal Symptoms in Hemodialysis Patients and their Effect on Health-Related Quality of Life.

BACKGROUND/AIMS: Hemodialysis (HD) represents one of the most commonly used modalities as a renal replacement therapy. Health-related quality of life (HRQoL) is much lower in HD patients than general population. Musculoskeletal (MSK) symptoms are one of the most important health problems that affect patients on maintenance HD. The main purpose of this study was to investigate the association between MSK symptoms and HRQoL among HD patients. METHODS: The study was carried out on 200 patients with chronic renal failure on chronic HD at different nephrology units in Egypt. They completed the Arabic version of the Kidney Disease and Quality of Life-Short Form 1.3 Questionnaire and answered the questions of MSK discomfort form based on the Nordic MSK Questionnaire. RESULTS: The mean age of the patients was 50.6 years, 61% were males. Of the 200 HD patients, 180 patients (90%) had MSK manifestations. The most commonly affected part was knee joint (51.5%). Regarding HRQoL, patients with MSK symptoms had significantly lower scores than did patients without on the physical role (p = 0.035), pain domain (p = 0.003), general health (p = 0.017), quality of social interaction (p = 0.046), and sleep domain (p = 0.022). CONCLUSION: MSK manifestations have a negative impact on HRQoL in HD patients. So, early identification and treatment are highly recommended.

Urinary biomarkers for early detection of platinum based drugs induced nephrotoxicity.

BACKGROUND: Nephrotoxicity is a major hazard complicating the use of platinum based drugs (PBD), which can hinder using higher doses protocols to maximize the therapeutic gain. Shortage of serum creatinine level as an accurate biomarker for acute kidney injuries (AKI) necessitates searching for novel biomarkers with better sensitivity and specificity in patients on PBD. METHODS: In a prospective cohort design, 132 patients receiving PBD were selected for the study. AKI was diagnosed by continuous follow up of serum creatinine level according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 2012. Serum creatinine and urinary biomarkers (KIM-1, NGAL and cystatin C) was measured in the day of treatment and for 3 days after PBD cycle. RESULTS: AKI occurred in 35 patients (26.52% of patients). KIM-1, Cystatin C, and NGAL showed significant increase in samples collected in the day of AKI in comparison to their corresponding basal levels (P <  0.0001). In addition, significant increase in urinary levels of the biomarkers in samples collected 1 day before AKI in comparison to their basal levels (P <  0.0001, P <  0.0001, and P = 0.013 for KIM-1, NGAL and Cystatin C respectively). Furthermore KIM-1 data showed a significant increase 2 days before serum creatinine rise in comparison to the corresponding KIM-1 levels in patients who developed AKI (P = 0.001). CONCLUSIONS: Urinary KIM-1, Cystatin C and NGAL can predict PBD induced AKI in earlier stages than serum createnine. KIM-1 is the most sensitive biomarker for early detection of AKI in patients receiving PBD.

Diagnostic performance of an immunoassay for simultaneous detection of HCV core antigen and antibodies among haemodialysis patients

Nosocomial transmission of HCV is a concern in haemodialysis (HD) units worldwide. Diagnosis of HCV infection among dialysis patients is currently based on the detection of anti HCV antibodies by ELISA, and is confirmed by HCV RNA. The average window period between HCV infection and seroconversion with new generations of HCV antibody tests remains approximately 70 days with more prolonged period among dialysis patients. In this study we assessed the diagnostic performance of an immunoassay designed for simultaneous detection of anti HCV antibodies and core antigen in one step in comparison to qualitative RT-PCR and anti HCV antibodies detection test among Egyptian haemodialysis patients. The studied patients were 39 chronic renal failure patients on maintenance haemodialysis. The results obtained in the present study revealed HCV infection of 56.4 percent. Combined Ag/Ab test detected 3 out of the 4 anti-HCV negative viraemic patients who were in the window period. The sensitivity, specificity and accuracy of the test were higher than that of anti HCV antibodies detection test (95.45 percent, 94.1 percent and 94.87 percent versus 81.8 percent, 88.23 percent and 84.6 percent) and they were raised to 100 percent on combining its positivity with liver enzymes elevation results. Therefore, this simple combined Ag/Ab test can be applied for early detection of HCV infection during window period among HD patients as an alternative to HCV RNA detection.

Diagnostic Performance of an Immunoassay for Simultaneous Detection of Hcv Core Antigen and Antibodies among Haemodialysis Patients.

Nosocomial transmission of HCV is a concern in haemodialysis (HD) units worldwide. Diagnosis of HCV infection among dialysis patients is currently based on the detection of anti HCV antibodies by ELISA, and is confirmed by HCV RNA. The average window period between HCV infection and seroconversion with new generations of HCV antibody tests remains approximately 70 days with more prolonged period among dialysis patients. In this study we assessed the diagnostic performance of an immunoassay designed for simultaneous detection of anti HCV antibodies and core antigen in one step in comparison to qualitative RT-PCR and anti HCV antibodies detection test among Egyptian haemodialysis patients. The studied patients were 39 chronic renal failure patients on maintenance haemodialysis. The results obtained in the present study revealed HCV infection of 56.4%. Combined Ag/Ab test detected 3 out of the 4 anti-HCV negative viraemic patients who were in the window period. The sensitivity, specificity and accuracy of the test were higher than that of anti HCV antibodies detection test (95.45%, 94.1% and 94.87% versus 81.8%, 88.23% and 84.6%) and they were raised to 100% on combining its positivity with liver enzymes elevation results. Therefore, this simple combined Ag/Ab test can be applied for early detection of HCV infection during window period among HD patients as an alternative to HCV RNA detection.

Insulin resistance in early untreated rheumatoid arthritis patients.

OBJECTIVES: To assess insulin resistance in early untreated rheumatoid arthritis patients and its relation to the clinical, inflammatory and biochemical characteristics of these patients. PATIENTS AND METHODS: Sixty-six untreated rheumatoid arthritis (RA) patients with disease duration less than 1 year along with age and sex matched controls were studied. Disease activity score (DAS28) was used to assess disease activity. Plasma levels of C- reactive protein (CRP), glucose, insulin and complete lipid profile were measured. Insulin resistance (IR) was estimated by the homeostasis model assessment for insulin resistance (HOMA-IR). RESULTS: RA patients revealed high grade systemic inflammation compared to control group p<0.0001. Patients with high disease activity were more insulin resistant than patients with moderate disease activity P<0.0001. CONCLUSION: The findings of the present study showed that early untreated RA patients are characterized by a severe insulin resistant state that is driven primarily by disease activity and systemic inflammation.

Clinical significance of antibody to hepatitis B core antigen in multitransfused hemodialysis patients.

BACKGROUND: In spite of the progress made in the prevention of transfusion transmitted infections over the last few years, transmission of HBV infection through transfusion of HBsAg negative blood has been documented. OBJECTIVES: To assess the frequency and clinical significance of anti-HBc in multitransfused hemodialysis patients. MATERIALS AND METHODS: One hundred and forty-three hemodialysis patients who had been receiving blood regularly with an average of 39.4 +/- 7.579 months on hemodialysis were enrolled in this study. HBV markers (HBsAg, anti-HBc, anti-HBs) were measured in these patients and in 100 healthy controls by the ELISA technique. The following data were obtained for all patients: socio demographic data, number of blood transfusions and some laboratory investigations. RESULTS: In our patients, anti-HBc was positive in 9%, anti HBs in 7%, coexistant HbsAg/anti-HBc in 2.8% and anti HBc/anti HBs in 18.9%, meanwhile no patients were positive for HBsAg alone. In patients with only positive anti-HBc, the levels of anti-HBc were significantly related to abnormal results of liver function. In patients with positive anti-HBs/anti-HBc (n = 27), 18 patients had abnormal liver function, and 9 patients had normal liver function with no significant difference between them. CONCLUSIONS: This study suggests that hepatitis B prevalence in our multitransfused hemodialysis patients is far in excess of that anticipated on the basis of HBsAg prevalence. Absence of HBsAg in the blood of hemodialyzed patients may not be sufficient to ensure lack of circulating HBV, and isolated positivity of anti-HBc may be a possible indicator of active hepatitis B infection.