Objectives Hydroxychloroquine (HCQ) has been used as an off label for the management of coronavirus disease (Covid-19) infection with other drugs. However, different genetic variants can affect the metabolism of HCQ leading to inter-individual differences in its efficacy. In this study, we investigated the effects of variants in CYP2D6, CYP3A4 and CYP3A5 on the risk of Covid-19 infection among patients receiving HCQ for controlling rheumatoid arthritis (RA). Methods A total of 60 patients were genotyped for CYP2D6*2XN, CYP2D6*4, CYP3A4*1B and CYP3A5*2. They were receiving HCQ for the treatment of RA. The patients were evaluated clinically for fever and dry cough, radiologically via chest computed tomography (CT) and immunologically via anti-Covid-19 IgG and IgM titers. Results Variants in CYP2D6 significantly affected the grade of ground glass (CYP2D6*4 AA carriers showed the higher risk for grade 3) and the risk of positive anti-Covid-19 IgM (CYP2D6*2XN CC and CYP3A4*1B AA had the lowest risk), the duration of HCQ, the use of corticosteroids or gender did not affect the Covid-19 status significantly. Conclusions In general, the outcome of the studied patients receiving HCQ was good (no deaths, no intubation needed). CYP2D6 variants could affect the outcome of Covid-19 infection.
BackgroundSystemic sclerosis (SSc, scleroderma) is a systemic disease characterized by fibrosis, progressive vascular obliteration and the production of autoantibodies.Ultrasound (US) imaging has advantages of simplicity, low cost, noninvasiveness, real-time capability and portability compared with traditional EDX. US imaging also offers high temporal and spatial resolutions, and can potentially provide dynamic anatomical information regarding local structures and kinesiology, few studies evaluate joint and tendons involvement in SSc by US the incidence and abnormality are differs among studiesObjectivesdescribe and determine possible correlations between US abnormalities of hand and wrist and clinical findings in SSc Egyptian patientsMethodsRandomly selected 50 Egyptian SSc patients were enrolled in the study in outpatient clinic Rheumatology department, Assuit university hospital. Clinical examination and US evaluation (Gray Scale and Power Doppler (PD)) of the tendons and joints of hands and wrists, were performed bilaterally on both dorsal and palmar sides. Joint assessment was performed on all MCP and PIP joints as well as the wrist and tendon assessment included finger flexors and extensors, wrist extensors and flexors. The scoring for synovitis was based on the EULAR/ OMERACT scoring systemResultsWithin the cohort, 100% of the patients were female; mean age and range disease duration were 40.93±11.71 (20–61) years and 8.13±5.56 (0.5–25)years, respectively. Modified Rodnan Skin Score mean and range were 23.17±9.14 (13–43), 22 patients were diffuse type (44%) and 28 patients were limited type (56%), 67% had inflammatory arthralgia as reported by patients. US examination revealed abnormalities in 76% of all cases. Synovitis was present in 74% of patients (22% wrist; 15% MCP/PIP, 63% both); with a grade 2 and 3 synovitis in 29% cases. The grade 2 or 3 synovitis was associated with a higher age (p<0.05) and disease duration (p<0.03) but not with inflammatory markers (CRP, ESR) and C3 nor with anti-CCP antibodies.Furthermore, patients with US proven grade 2 or 3 synovitis had interstitial lung disease involvement (ILD) (74%) and elevated systolic pulmonary artery pressure >35 mmHg in (46%). Grade 1 synovitis did not correlate with tenderness or joint swelling. Synovitis using PD abnormalities were present in 20% patients, but only a 25% had concomitant clinical synovitis. Bone erosions (>1mm) were observed in 15%, which located at the second and third MC heads and at the styloid process of the ulna. The presence of bone erosions was associated with the presence of grade 2 or 3 synovitis. US identified tenosynovitis in 40% of patients, involving the wrist extensors in the vast majority of cases (70%), especially of the 2nd extensor compartment.ConclusionsUS examination detects significant synovitis of the hand and wrist in the absence of clinical findings, and reveals structural damage in a number of patients. The grade 2 or 3 synovitis was associated with a higher age, and ILD involvement. Tendon involvement is f...
Background Interleukin 34 (IL-34) is a recently discovered proinflammatory cytokine that can promote inflammation and osteoclastogenesis in arthritic joints. In this study, we tried to assess the serum and synovial fluid (SF) levels of IL-34 in rheumatoid arthritis (RA) patients, and to determine its relationship with disease activity and radiographic damage. Patients and methods ELISA was used to evaluate IL-34 levels in the serum of RA patients (n=50), osteoarthritis (OA) patients (n=28), and healthy control subjects (n=20) and in SF isolated from RA and OA patients. Disease activity in RA patients was assessed using the disease activity score-28 (DAS 28). The extent of radiographic joint damage, narrowing, and erosions was assessed. Results Serum IL-34 level was significantly elevated in RA patients compared to that in OA patients and healthy controls (P<0.0001). Synovial IL-34 level was also significantly elevated in RA patients compared to that in OA patients (P=0.0004). Serum and synovial IL-34 levels were significantly higher in cases that were rheumatoid factor (RF) positive (n=28) compared to the levels in RF-negative RA cases (n=22) (P=0.03 and P=0.04, respectively). Serum and synovial IL-34 levels were positively correlated with RF (r=0.43, P=0.02 and r=0.39, P=0.03, respectively), and with the extent of radiological damage (SENS) (P=0.0002 and P<0.0001, respectively). However, no significant correlation between IL-34 levels and disease activity was found. Conclusion IL-34 appears to play a key role in the pathogenesis of RA and contribute to bone destruction, making it a potential therapeutic target in the management armamentarium of the disease.
Background: Osteoporosis (OP) is a growing health problem not only in women but also in men. Subjects and methods: This study was carried out on 100 healthy men, age range 30–65 years (mean ± SD, 44.65 ± 8.3). All were randomly recruited from Assiut city during the period January 2005 to January 2006. Complete clinical history included occupational history, smoking habit, physical activity and calcium intake. Complete clinical examination and anthropometric measurments were done. Laboratory investigations for serum calcium, phosphorus and osteocalcin were performed. Bone mineral density (BMD) was measured by calcaneal ultrasound. Results: Sixty‐three percent of participants had normal BMD, 37% had low BMD, (26% had quantitative bone ultrasound [QUS] T‐score –1 to –2.5 and 11% had QUS T‐score ≤ –2.5). Smoking and low physical activity were risk factors for low BMD. Significant positive correlations were found between BMD and body mass index, serum calcium, and osteocalcin and negative correlation with phosphorus. We concluded that low BMD occurs with high frequency in Egyptian men. Smoking, physical inactivity and low body index are significant risk factors. Low serum calcium, low serum osteocalcin and high serum phosphorus are biochemical risk factors of low BMD in males.
Background Interstitial pneumonia (IP) may precede the clinical onset of connective tissue diseases (CTD). Idiopathic pulmonary fibrosis (IPF) is fibrosing pneumonia of an unknown cause, and has a poor prognosis. The differentiation between IP and IPF, raises a considerable diagnostic challenge as they share overlapping features. High resolution computed tomography (HRCT) has been put forth as a surrogate to recognize pathological IP, assessing distribution and predominance of key radiological findings such as ground glass opacities (GGOs) (Mink and Maycher, 2012 and Walash, et al., 2013). Objectives To examine whether the radiographic features of idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia (IP) of connective tissue diseases (CTD), as assessed by high resolution computed tomography (HRCT) which can be used to distinguish between these two entities. Methods This study included 100 selected patients with CTD, with clinical diagnosis with IP, 27males and 73 females, (68 rheumatoid arthritis, 18 systemic lupus erythematosus, 7 scleroderma, and 7 ankylosing spondylitis), 40 patients with IPF and 20 controls. Those patients were recruited from Out-patients clinics of Rheumatology and Chest Departments of Assiut and Alazhar university hospitals. A standardized pulmonary evaluation was systematically conducted and included determination of patient's smoking history, occupation, environmental exposure and determination of pulmonary symptoms. Pulmonary function tests (PFTs) were done and included FEV1, FVC, RV, TLC, FEF 25-75%, FEF50% and FEF75%, and DLCO. ANA, anti-dsDNA, ENA (Sm, and La), U1-snRNP, C3, C4, RF, Acl, LA and plain radiography for chest and HRCT were done. HRCT scans were reviewed at 5 levels scored by 2 observers working independently. They evaluated the extent and distribution (reticulation, honeycombing and GGOs, were estimated to the nearest 5%). The relative proportions of interstitial lung disease (up to the total of 100%) made up of reticular pattern and GGOs were quantified. Results The median extent of IP in patients with CTD was less than that in patients with IPF (P<0.001). The coarseness of fibrosis was significantly less course in patients with CTD than in patients with IPF (P<0.001).The proportion of GGOs was greater in patients with CTD than in those with IPF (P<0.001). IPF was characterized by a lower proportion of GGOs (P<0.001). Comparing groups of patients, a significant decrease of fibrosis, and a higher proportion of GGOs were found in CTD (P<0.001), while there was a significant increase of fibrosis and a lower proportion of GGOs in IPF (P<0.001). There was HRCT evidence of emphysema in 19.4% of IP patients and 12% of IPF patients. Conclusions High resolution computed tomography has a beneficial role in diagnosing and differentiation between idiopathic pulmonary fibrosis and interstial pneumonia of connective tissue diseases. References Mink SN,and Maycher B (2012): Comparative manifestations and diagnostic accuracy of HRCT in usual interstitial pneumonia...
BackgroundNail fold capillaroscopy (NFC) is a non invasive diagnostic tool to detect early changes of microcirculation of different collagen diseases as rheumatoid arthritis associated interstitial lung disease (RA-ILD), systemic sclerosis interstitial lung disease (SS-ILD) and idiopathic ILD (Ting et al., 2020).ObjectivesThe study aimed to evaluate role of NFC in RA-ILD, SS-ILD and idiopathic ILD, and to determine if there is a correlation of it to disease activity.MethodsA case control study conducted on 100 patients with ILD, where 30 patients with RA-ILD, 30 patients with SS-ILD and 40 patients with idiopathic-ILD, fulfilling ACR/EULAR criteria, 2013. They were examined clinically and radiologicaly. Pulmonary function tests (PFT) and NFC were done.ResultsPleural irregularities were found in 42% of RA-ILD, 30% of SS-ILD where subpleural irregularities were found in 31% of RA-ILD and 46.7% of SS-ILD. Ground glass opacity was in 13% of RA-ILD, 76.7% in SS-ILD and70% in idiopathic –ILD. Honeycomb appearance was in 11.5% of RA-ILD, 30% in SSILD and 65% of idiopathic ILD.SS-ILD showed the highest capillary changes especially patients with pneumonia. A significant correlation was found between NFC and PFT in idiopathic-ILD.ConclusionNFC is a sensitive and specific adjuvant tool in monitoring micro vascular changes in rheumatologic diseases and can be used as assessment tool in severity of the disease.Reference[1]Ting Z, Lin F and Chen H (2020): Pattern of NFC in patients with SLE. Archives of Rheumatology, 35(4), 568Acknowledgements:NIL.Disclosure of InterestsNone Declared.
Background Systemic lupus erythematosus (SLE) is a rare complex autoimmune disease with a multisystem involvement [1]. Although pulmonary involvement is relatively frequent in adult patients; it has been rarely reported in children with SLE. It may be an initial and/or life-threatening complication [2]. There is a scarcity of published literature on pulmonary function tests (PFTs) in patients with JSLE manifestations of pulmonary disease. Objectives To verify a subclinical pulmonary disease in juvenile onset SLE using laboratory parameters, pulmonary functions tests and multislice CT Methods Twenty five patients with JSLE were studied. All fulfilled updated American College of Rheumatology criteria for SLE [3]. All patients had the disease at or before the age of 16 years. Assessment of disease activity was done through SLE Disease Activity Index (SLEDAI) [4]. PFTs were done using (ZAN 100 Flow Handy II) pulmonary function apparatus. PFTs were done according to Grippi and Tino [5]. They included forced expiratory volume in 1 s as FEV1 (liter/min) and forced expiratory flow rate FEV1% of predicted FEV1, forced vital capacity FVC, residual volume RV, total lung capacity TLC, FEF 25-75%, FEF50% and FEF75%, and diffusion capacity of carbon monoxide DLCO. Abnormal PFTs were categorized into restrictive, obstructive, mixed restrictive, and obstructive, and small airway disease. Laboratory and immunological parameters were done for ANA, anti-dsDNA, ENA including Sm, and La, U1-snRNP, C3, C4, RF, Acl and LA. Plain radiography for chest and multislice CT were done. Results Twelve patients (48%) had abnormal results of PFTs, 5 (20%) had an isolated (DLCO) impairment and 6 (24%) had a restrictive pattern. Neurological lupus was significantly associated with decreased FEF25-75% (P<0.04) and FEF75% (P<0.001) respectively. Radiography was normal. Abnormal PFTs were not significantly associated with other parameters. Multislice CT examination of JSLE patients demonstrated a pleural effusion and thickening in 16%, also ground glass opacities found in 16% suggesting early interstitial lung disease. Conclusions A mandatory performance of pulmonary function tests have to be done early in JSLE, without findings of pulmonary involvement. References Torre O, Harari S. Pleural and pulmonary involvement in SLE Presse Med 2011;40 1 Pt 2):e19–29. Diane L, Kamen MD, Strange C. Pulmonary Manifestations of SLE Clin Chest Med 2010;31:479–88.2004; 43:587–91. Hochberg MC. Diagnostic and therapeutic criteria committee of the American college of rheumatology updating the American college of rheumatology revised criteria for the classification of SLE. Arthritis Rheum 1997; 40:1725. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAIA disease activity index for lupus patients. The committee on prognosis studies in SLE. ArthritisRheum 1992;35:630–40. Grippi MA, Tino G. Pulmonary function testing. In: Fishman AP, Elias JA, Fishman JA, Grippi MA, Senior RM, Pack AI, editors. Fishman’s pulmonary diseases and disorders...
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