Mechanistic Insights of Chemicals and Drugs as Risk Factors for Systemic Lupus Erythematosus

2020 ◽  
Vol 27 (31) ◽  
pp. 5175-5188 ◽  
Author(s):  
Qingjun Pan ◽  
Yun Guo ◽  
Linjie Guo ◽  
Shuzhen Liao ◽  
Chunfei Zhao ◽  
...  

Systemic Lupus Erythematosus (SLE) is a chronic and relapsing heterogenous autoimmune disease that primarily affects women of reproductive age. Genetic and environmental risk factors are involved in the pathogenesis of SLE, and susceptibility genes have recently been identified. However, as gene therapy is far from clinical application, further investigation of environmental risk factors could reveal important therapeutic approaches. We systematically explored two groups of environmental risk factors: chemicals (including silica, solvents, pesticides, hydrocarbons, heavy metals, and particulate matter) and drugs (including procainamide, hydralazine, quinidine, Dpenicillamine, isoniazid, and methyldopa). Furthermore, the mechanisms underlying risk factors, such as genetic factors, epigenetic change, and disrupted immune tolerance, were explored. This review identifies novel risk factors and their underlying mechanisms. Practicable measures for the management of these risk factors will benefit SLE patients and provide potential therapeutic strategies.

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7179
Author(s):  
Qingjun Pan ◽  
Xiaoqun Chen ◽  
Shuzhen Liao ◽  
Xiaocui Chen ◽  
Chunfei Zhao ◽  
...  

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that primarily affects women, especially those of reproductive age. Genetics, environment, and gene-environment interactions play key roles in the development of SLE. Despite the numerous susceptibility genes of SLE identified to date, gene therapy is far from a clinical reality. Thus, more attention should be paid to the risk factors and underlying mechanisms of SLE. Currently, it is reported that psychosocial factors and sex hormones play vital roles in patients with SLE, which still need further investigated. The purpose of this review is to update the roles and mechanisms of psychosocial factors and sex hormones in the susceptibility and development of SLE. Based on review articles and reports in reputable peer-reviewed journals and government websites, this paper summarized psychosocial factors (e.g., alexithymia, depression, anxiety, negative emotions, and perceived stress) and sex hormones (e.g., estrogens, progesterone, androgens, and prolactin) involved in SLE. We further explore the mechanisms linking these factors with SLE susceptibility and development, which can guide the establishment of practical measures to benefit SLE patients and offer new ideas for therapeutic strategies.


2021 ◽  
Vol 74 (2) ◽  
pp. 303-309
Author(s):  
Sergii V. Shevchuk ◽  
Liudmyla P. Denyshchych ◽  
Liubov I. Marynych ◽  
Inna P. Kuvikova ◽  
Iryna V. Kurilenko ◽  
...  

The aim: To study the peculiarities of bone mineral density in the Ukrainian population of women of different reproductive age with systemic lupus erythematosus and to evaluate its connection with traditional and specific (typical for systemic lupus erythematosus) risk factors. Materials and methods: A total of 91 women with systemic lupus erythematosus and 29 healthy individuals were examined. Along with the clinical study of the activity and severity of the disease, the serum levels of interleukin-6 were determined by the enzyme immunoassay. The peculiarities of bone mineral density were studied using dual-energy X-ray absorptiometry. The presence of fractures was evaluated by the X-ray method. Results: Patients with systemic lupus erythematosus frequently suffer from reduced bone mineral density. Reduced bone mineral density and the appearance of fragility fractures are associated with patients’ age, disease duration, damage index, inflammatory activity, and cumulative dose of glucocorticoids. Conclusions: Progressive reduced bone mineral density in patients with systemic lupus erythematosus occurs not only during the aging process of a woman, but is also associated with a number of systemic lupus erythematosus – related osteoporosis risk factors.


Author(s):  
Asma Al-Kindi ◽  
Batool Hassan ◽  
Aliaa Al-Moqbali ◽  
Aliya Alansari

RMD Open ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. e001299
Author(s):  
Cristina Reátegui-Sokolova ◽  
Manuel F Ugarte-Gil ◽  
Guillermina B Harvey ◽  
Daniel Wojdyla ◽  
Guillermo J Pons-Estel ◽  
...  

AimA decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria.MethodsWe included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed.ResultsFive hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence.ConclusionsEarly response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1551.1-1552
Author(s):  
V. Mazurov ◽  
O. Shadrivova ◽  
M. Shostak ◽  
L. Martynova ◽  
M. Tonkoshkur ◽  
...  

Background:Invasive aspergillosis (IA) is a severe opportunistic infection that is not well understood in rheumatological patients.Objectives:To study risk factors, etiology, clinical manifestations and results of treatment of IA in adult rheumatological patients.Methods:Retrospective analysis of 830 patients (1998-2019) with “proven” and “probable” IA (EORTC / MSG, 2019), adults - 699 (84%). The main group included 18 (3%) adult rheumatological patients with IA, a control group included 610 (87%) adult hematological patients. Rheumatological patients were older, the average age was 59 years (21–75) vs 45 years (18–79), p = 0.005, and among them there were more women – 56% vs 42%, p = 0.01.Results:In rheumatological patients with IA, underlying diseases were ANCA-associated vasculitis (28%), granulomatosis with polyangiitis (22%), periarteritis (11%), systemic lupus erythematosus (22%), rheumatic heart disease (11%) and ankylosing spondylitis (6%). In the control group, underlying diseases were acute leukemia (45%), lymphomas (34%), chronic leukemia (9%), multiple myeloma (7%), myelodysplastic syndrome (3%), and other hematological diseases (2%).The main risk factors for IA development in rheumatological patients were: systemic steroids use (89% vs 69%), prolonged lymphocytopenia (76% vs 65%, median - 14 vs 12 days), treatment in ICU (44% vs 18%, p = 0.01), acute or chronic renal failure (39% vs 1%, p = 0.0008) and immunosuppressive therapy (28% vs 25%). Severe neutropenia was noted significantly less frequently (18% vs 83%, p = 0.0001). Additional risk factors were decompensated diabetes mellitus (17% vs 2%, p = 0.004), previous surgery (17% vs 1%, p = 0.001) and organ transplantation (6% vs 0%). In rheumatological patients, lung (83% vs 98%, p = 0.0001) and ≥2 organs (6% vs 8%) involvement were less common. Heart (11% vs 0%), sinuses (6% vs 5%) and central nervous system (6% vs 4%) involvement more often developed. In rheumatological patients, respiratory failure (61 vs 37%, p = 0.03), hemoptysis (28% vs 7%, p = 0.0001) and chest pain (17% vs 7%, p = 0, 04) were noted more often, less often - fever ≥380С (67% vs 85%, p = 0.01) and cough (61% vs 70%). CT signs of lung damage were similar in both groups, but rheumatologic patients were more likely to show an «air crescent» sign and / or destruction cavity (44% vs 10%, p = 0.0001). In rheumatologic patients, IA was more often confirmed by isolation ofAspergillusspp. from BAL (80% vs 45%, p = 0.005) and by histological examination (22% vs 7%, p = 0.01). The main pathogens wereA. fumigatus(50% vs 43%),A. niger(29% vs 32%), andA. flavus(14% vs 17%).Rheumatological patients were less likely to receive antifungal therapy 89% vs 99%, p = 0,0003. The main drug in both groups was voriconazole. The overall 12-week survival did not significantly differ between groups, but was lower in rheumatological patients with IA (69% vs 81%).Conclusion:In rheumatological patients, invasive aspergillosis more often developed at an older age, mainly in women. The main background diseases were ANCA-associated vasculitis, granulomatosis with polyangiitis, and systemic lupus erythematosus. Typical risk factors were steroids and immunosuppressants use, prolonged lymphocytopenia, ICU stay, and renal failure. The main causative agents wereA. fumigatus,A. niger, andA. flavus. The main localization of infection were lungs. Respiratory failure, hemoptysis and heart involvement were typical. The overall 12-week survival of rheumatological patients with invasive aspergillosis was 69%.Disclosure of Interests:None declared


Lupus ◽  
2021 ◽  
pp. 096120332110211
Author(s):  
Yin Long ◽  
Shangzhu Zhang ◽  
Jiuliang Zhao ◽  
Hanxiao You ◽  
Li Zhang ◽  
...  

Objective Osteonecrosis (ON), which can lead to physical disability, is a common complication of systemic lupus erythematosus (SLE). The purpose of this study was to determine the prevalence of ON and identify possible risk factors in Chinese SLE patients. Methods SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were recruited from the Peking Union Medical College Hospital. The chi-square test (χ 2 test) and multivariate regression analyses were used to evaluate risk factors. The Cox proportional-hazards model was used to construct the survival curves and estimate the simultaneous effects of prognostic factors on survival. Results We consecutively enrolled 1,158 patients, of which 88 patients (7.6%) developed ON. Among ON patients, 57.1% of patients had isolated femoral head necrosis and 42.9% had multiple joint involvement. The mean age of ON patients (24.62 ± 8.89 years) was significantly younger than SLE patients without ON (27.23 ± 10.16 years, p = 0.09). The ON group presented with a much longer disease course (10.68 ± 5.97 years, p < 0.001) and increased incidence of arthritis, kidney, and central nervous system (CNS) involvement (65.9% [ p < 0.05], 57.6% [ p < 0.05], and 16.5% [ p < 0.05], respectively, in the ON group). ON patients were more likely to be treated with glucocorticoid (GC) and to receive a high dose of prednisolone at the initial stage of SLE ( p < 0.05). The percentage of patients who received hydroxychloroquine was much higher in the control group ( p < 0.001). Cox regression analysis suggested that CNS involvement and GC therapy were two independent risk factors for ON in SLE patients. The presence of anti-phospholipid antibodies (aPLs) was a risk factor for multiple joint necrosis (odds ratio: 6.28, p = 0.009). Conclusions ON remains a serious and irreversible complication in SLE. In addition to glucocorticoid therapy, we found that CNS system involvement was a risk factor for ON, while the administration of hydroxychloroquine was a protective factor. The clinical characteristics of multiple site ON patients were distinct from isolated femoral head necrosis patients. The presence of aPLs was a risk factor for multiple site osteonecrosis.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 360.1-361
Author(s):  
M. Hassanien ◽  
E. Talaat ◽  
H. Abdellatif

Background:Systemic Lupus erythematosus and antiphospholipid disease are very common autoimmune diseases in women at reproductive age.Objectives:Evaluate the neuro-developmental outcome in children born to mothers with SLE or APS and to assess and characterize memory impairment in children’s born to mother with systemic lupus erythematosus or APS using children’s memory scale and the relation between tetrahydrobiopterin concentration range of children with developmental and neurological disorders.Methods:Women attending rheumatology clinics University of Asyut, SLE patients were eligible if they met the American College of Rheumatology (ACR) criteria for SLE and APL prior to pregnancy, and had at least one live birth following SLE diagnosis. Maternal history Data collected using a structured format that included medical and obstetric history. A detailed history of medication exposures and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) during pregnancy was obtained. Offspring history Medical and developmental histories of the offspring including antenatal, delivery, prenatal and pediatric histories, as child’s cognitive, physical or social maturity compared with established age-appropriate norms. Speech or hearing delays, diagnosis of attention- deficit hyperactivity disorder (ADHD), or any special educational needs (eg, occupational or speech therapy, behavioral counseling) was recorded. Assessment and characterization of memory impairment using children’s memory scale by neurologists. Tetrahydrobiopterin was measured by ELISA compared to children born to control healthy subjects of the same age and sex.Results:Data on 38 mothers and 60 offspring were analysed: ADHD was reported for 15 of 60 (25%) offspring. Recent memory delay was detected in 93% (14/15) Speech delay 40% (6/15). Maternal APS history was significantly associated with increased use special educational need among offsprings, including after adjustment for lupus anticoagulant (LA) positivity (39.4% for delays age >2 years; p<0.05). Anticardiolipin and anti-BETA2GP1 were not detected to be associated with delays. Recent memory delay was associated with increased Tetrahydrobiopterin level (P=0.01).Conclusion:The prevalence of neurodevelopmental abnormalities in children born to mothers with SLE or APS seems to be higher than normal population and more educational attention is important in these children, and need long-term follow-up.Disclosure of Interests:None declared


Sign in / Sign up

Export Citation Format

Share Document