Complication Of Systemic Lupus Erythematosus Research Articles

P33 The successful use of Belimumab in recurrent small bowel obstruction secondary to Lupus Enteritis

P33 The successful use of Belimumab in recurrent small bowel obstruction secondary to Lupus Enteritis

Society for Maternal-Fetal Medicine Consult Series #64: Systemic lupus erythematosus in pregnancy

Systemic lupus erythematosus (SLE) is a chronic, multisystem, inflammatory autoimmune disease characterized by relapses (commonly called "flares") and remission. Many organs may be involved and although the manifestations are highly variable, the kidneys, joints, and skin are commonly affected. Immunologic abnormalities, including the production of antinuclear antibodies (ANA), are also characteristic of the disease. Maternal morbidity and mortality are substantially increased in patients with SLE, and an initial diagnosis of SLE during pregnancy is associated with increased morbidity. Common complications of SLE include nephritis, hematologic complications such as thrombocytopenia, and a variety of neurologic abnormalities. The purpose of this document is to examine potential pregnancy complications and to provide recommendations on treatment and management of SLE during pregnancy. The following are the SMFM recommendations: we recommend low-dose aspirin beginning at 12 weeks of gestation until delivery in patients with SLE to decrease the occurrence of preeclampsia (GRADE 1B); we recommend that all patients with SLE, other than those with quiescent disease, either continue or initiate HCQ in pregnancy (GRADE 1B); we suggest that for patients with quiescent disease, shared decision making is used to decide whether to initiate HCQ during pregnancy (GRADE 2B); we recommend that prolonged use (>48 hours) of NSAIDs should be avoided during pregnancy (GRADE 1A); we recommend that Cox-2 inhibitors and full dose aspirin should be avoided during pregnancy (GRADE 1B); we recommend discontinuing methotrexate and mycophenolate mofetil/mycophenolic acid at least three months prior to attempting pregnancy (GRADE 1A); we suggest against initiating newer biologic medications with pregnancy unless alternatives with better safety profiles are ineffective (GRADE 2C); we suggest treatment with a combination of prophylactic unfractionated or low molecular weight heparin and low-dose aspirin for patients without a prior thrombotic event who meet obstetric criteria for APS (GRADE 2B); we recommend therapeutic unfractionated or low molecular weight heparin for patients with a history of thrombosis and aPL antibodies (GRADE 1B); we suggest treatment with low-dose aspirin alone in patients with SLE and antiphospholipid antibodies without clinical events meeting criteria for APS (GRADE 2C); we recommend that steroids should not be routinely used for the treatment of fetal heart block due to anti-SSA/SSB antibodies, given their unproven benefit and the known risks for both the pregnant patient and fetus (GRADE 1C); we recommend that serial fetal echocardiograms for assessment of the PR interval not be routinely performed in patients with anti-SSA or anti-SSB antibodies (GRADE 1B); we recommend that patients with SLE undergo prepregnancy counseling with both maternal-fetal medicine and rheumatology specialists that includes a discussion regarding maternal and fetal risks (GRADE 1C); we recommend that pregnancy should be generally discouraged in patients with severe maternal risk, including patients with active nephritis; severe pulmonary, cardiac, renal, or neurologic disease; recent stroke; or pulmonary hypertension (GRADE 1C); we recommend antenatal testing and serial growth scans in pregnant patients with SLE due to the increased risk of FGR and stillbirth (GRADE 1B); and we recommend adherence to the Centers for Disease Control and Prevention (CDC) medical eligibility criteria for contraceptive use in patients with SLE (GRADE 1B).

Pathogenesis and treatment of neuropsychiatric systemic lupus erythematosus: A review

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with a complex pathogenesis. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication of SLE that involves the nervous system and produces neurological or psychiatric symptoms. After decades of research, it is now believed that the diverse clinical manifestations of NPSLE are associated with intricate mechanisms, and that genetic factors, blood-brain barrier dysfunction, vascular lesions, multiple autoimmune antibodies, cytokines, and neuronal cell death may all contribute to the development of NPSLE. The complexity and diversity of NPSLE manifestations and the clinical overlap with other related neurological or psychiatric disorders make its accurate diagnosis difficult and time-consuming. Therefore, in this review, we describe the known pathogenesis and potential causative factors of NPSLE and briefly outline its treatment that may help in the diagnosis and treatment of NPSLE.

Daily Hemodialysis Helps Critical Nephritic Lupus Patient: A Case Report

Background: Nephritic lupus is the most common and serious complication of systemic lupus erythematosus (SLE) and is associated with a worse prognosis. Hemodialysis is effective in alleviating symptoms and renal involvement in a nephritic lupus patient.
 Method: A 33-year-old female was diagnosed with SLE in September 2017. She was also diagnosed with diffuse membranous proliferative glomerulonephritis, as confirmed with a kidney biopsy. She complained of gradual onset limb weakness and peripheral edema 3 months before admission. She was treated with 6 cycles of cyclophosphamide and continued with methylprednisolone 16 mg once daily, hydroxychloroquine 200 mg once daily, and myfortic 360 mg twice daily. A day before ICU admission, her creatinine level was increased to 4.6 mg/dl with an estimated GFR of 12 ml/min and her symptoms then worsened into seizures and lung edema. Daily hemodialysis with heparin-free SLEDD was performed. About 2L was extracted for the first 6 hours with Qb 150 ml and Qd 300 ml and was continued until the day after. For the next 4 days, 3L was extracted per day with Qb 200ml and Qd 500 ml. The patients’ hemodynamic status was within normal limits during dialysis period. The condition improved and the patient was transferred to the ward.
 Discussions: Hemodialysis is a way to solve kidney problems in in nephritic lupus and SLE patients in general. It should not only be employed for mainly kidney problems but could be beneficial in autoimmune patients with conditions such as nephritic lupus. Slowly extracted dialysis type would be a good and inexpensive option to resolve nephritic lupus in compromising lupus patients. Filtration is ensured and solute removal is achieved relatively equivalent to CRRT.
 Conclusion: Daily hemodialysis could increase renal salvation by providing less creatinine serum and removing accumulated fluids. The SLEDD type could be used for critical nephritic lupus patients with reduced hemodynamic perturbations, minimal anticoagulant, and lower cost.

Comparison of mortality and its causes in patients with complicated systemic lupus erythematosus on hemodialysis versus peritoneal dialysis: A meta-analysis.

Background:Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). Ten percent to 20% of patients with SLE progress to end-stage renal disease and would require renal replacement therapy or renal transplantation. In this analysis, we aimed to systematically compare mortality and the causes of mortality in patients with complicated SLE who were treated on hemodialysis (HD) versus peritoneal dialysis (PD).Methods:Cochrane Central, Medical Literature Analysis and Retrieval System Online, Google Scholar, Web of Science, Excerpta Medica dataBASE, and http://www.ClinicalTrials.gov were searched for studies that compared HD versus PD in patients with SLE. The RevMan software version 5.4 (RevMan software, Cochrane Collaborations, United Kingdom) was used to analyze data. Heterogeneity was assessed using the Q and the I2 statistical tests. In this analysis, a random effects model was used during data assessment. Risk ratios (RRs) with 95% confidence intervals (CIs) were used to represent the results following analysis.Results:A total number of 3405 SLE participants were included in this analysis, whereby 2841 were assigned to HD and 564 participants were assigned to PD. In patients with SLE who were on dialysis, our analysis showed that the risk of mortality was similar with HD and PD (RR, 0.69; 95% CI, 0.45–1.07; P = .10). When the cause of mortality was analyzed, cardiovascular death (RR, 0.63; 95% CI, 0.31–1.31; P = .22), death due to infection (RR, 0.74; 95% CI, 0.47–1.17; P = .20), death due to a respiratory cause (RR, 1.06; 95% CI, 0.18–6.21; P = .95), cause of death due to SLE flare up (RR, 2.54; 95% CI, 0.39–16.37; P = .33), and other causes of death (RR, 0.79; 95% CI, 0.35–1.77; P = .57) were not significantly different with HD and PD.Conclusion:This current analysis showed that in SLE patients who required dialysis, the risk of mortality between HD and PD was similar, and the causes of death including cardiovascular, infective, respiratory, SLE flare up, and other causes were not significantly different. Therefore, both dialysis methods were tolerable in these patients with SLE. Further studies with larger data would be required to confirm this hypothesis.

Neck Pain With Abdominal Distention in a Patient With Systemic Lupus Erythematosus

Question: A 13-year-old boy admitted for systemic lupus erythematosus (SLE) presented mild neck pain, throat pain, and abdominal distention. The SLE was diagnosed 6 months previously, and he received steroid pulse therapy, tacrolimus, and hydroxychloroquine for its treatment. Prolonged steroid therapy was required for his refractory status. Three months previously, he had an episode of right-sided cervical lymphadenitis caused by Staphylococcus aureus. He had no history of trauma. The patient had a good appetite and denied having symptoms such as dyspnea, cough, abdominal pain, nausea, vomiting, diarrhea, and bloody stool. A physical examination revealed right-sided neck pain with mild subcutaneous emphysema. No abnormalities were observed in his throat. Abdominal distention without tenderness was found. Laboratory tests were negative for elevated inflammatory markers, hemoconcentration, and lactic acidosis. Radiography demonstrated linear air leaks in the neck, multiple air leaks along the trachea, free air, and a curvilinear collection of gas within the bowel wall (Figures A and B). Given these physical and radiological findings, what is the most likely diagnosis? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Additional contrast computed tomography performed for a possible intestinal perforation found pneumomediastinum (Figures C and D), massive free air in the abdomen, and extensive air accumulation within a thickened bowel wall (Figures E, F, and G). Based on the mild clinical appearance and laboratory findings, pneumatosis cystoides intestinalis and pneumomediastinum without intestinal perforation were diagnosed. Careful observation with oxygen therapy, antibiotic administration, bowel rest, and total parenteral nutrition were begun, and the steroid dosage was gradually reduced. As a result, the patient recovered in 2 weeks without surgical intervention. Based on the clinical course and follow-up radiography and computed tomography findings, we concluded that his condition was idiopathic pneumatosis cystoides intestinalis with pneumomediastinum. Idiopathic pneumatosis cystoides intestinalis is characterized by the presence of gas within the intestinal submucosa or subserosa. The condition may be asymptomatic or present mild, nonspecific clinical manifestations, such as abdominal distention, discomfort, nausea, diarrhea, and anorexia, which may lead to an underdiagnosis of this condition.1Heng Y. Schuffler M.D. Haggitt R.C. et al.Pneumatosis intestinalis: a review.Am J Gastroenterol. 1995; 90: 1747-1758PubMed Google Scholar The risk factors of pneumatosis cystoides intestinalis have not been definitively identified, but prolonged administration of steroids or immunosuppressive agents is thought to be involved in its onset.2Mizoguchi F. Nanki T. Miyasaka N. Pneumatosis cystoides intestinalis following lupus enteritis and peritonitis.Intern Med. 2008; 47: 1267-1271Crossref PubMed Scopus (23) Google Scholar Atrophy of submucosal tissue caused by prolonged steroid therapy may also occur. Gastrointestinal involvement in SLE takes various forms,3Frittoli R.B. Vivaldo J.F. Costallat L.T.L. et al.Gastrointestinal involvement in systemic lupus erythematosus: a systematic review.J Transl Autoimmun. 2021; 4100106Crossref PubMed Scopus (12) Google Scholar making the correct diagnosis particularly important. The clinical presentations of our patient were not caused by complications of SLE because his clinical SLE activity was under control with prednisolone, tacrolimus, and hydroxychloroquine. The fact that reducing the prednisolone dosage did not exacerbate his condition corroborated our diagnosis. We herein described a case of massive pneumatosis cystoides intestinalis with pneumomediastinum accompanied by mild symptoms. Appropriately evaluating the symptoms, even when they are mild, is necessary in patients with prolonged steroid therapy.

Case Report: Extensive digital gangrene as a primary manifestation of late-onset systemic lupus erythematosus

Background: Digital gangrene is a rare but serious complication of systemic lupus erythematosus (SLE). It occurs usually in middle-aged patients with longer disease duration. Case: Herein we report the case of a 56-year-old man (with no history suggestive of Raynaud’s phenomenon, diabetes mellitus, smoking, trauma, infection, or chemical exposure), who presented with SLE and digital gangrene was among the first signs. He presented with a one-month history of joint pain, hair loss, photosensitivity, mouth ulcers, malar rash, dyspnea, and digital pain. Physical examination revealed painful and diffuse erythematous skin lesions in the extremities and back, as well as cyanosis in the fingers. We noted lymphocytopenia (600 cells/mm3), and an elevated C-reactive protein (15.1 mg/l) on laboratory tests. Immunological tests were positive for antinuclear antibodies (ANA) with Title 1:400. Pulmonary computed tomography revealed pulmonary fibrosis, and pulmonary function tests revealed the restrictive pulmonary disease. Diagnosis of SLE with lung involvement was retained. The immunological assessment in search of elements in favor of a vascular origin of the patient's skin lesions was negative. Treatment was initiated with 200 mg/day hydroxychloroquine. For dermal and pulmonary involvement, intravenous (IV) pulse therapy was used with methylprednisolone (1,000 mg/d for three consecutive days monthly) and cyclophosphamide (1 g/month). Calcium blocking agents were also prescribed. However, the lesions did not improve. The patient was given two infusions of rituximab (1 g) at a 14-day interval with a marked improvement of the majority of vasculitis lesions, and a partial improvement of dyspnea. Conclusions: Digital gangrene is a rare complication of late-onset SLE, especially as a primary manifestation.

Silent Lupus Nephritis in Adolescent Male: A Case Report

Systemic lupus erythematosus (SLE) is a multisystemic disorder, one of several diseases known as ‘the great imitators,’ because it often mimics or is mistaken for other illnesses. SLE symptoms vary widely and appear and disappear unpredictably. Diagnosis can thus be elusive, with some patients having unexplained symptoms of untreated SLE for years. Autoimmunity plays a major role in the pathogenesis of lupus nephritis (LN). LN is one of the most serious complications of SLE since it is the major predictor of poor prognosis. The immunologic mechanisms include the production of autoantibodies directed against nuclear elements. Here is a case report of a young male patient who presented with fever, and alopecia and was diagnosed as an SLE with LN.

Infection profile and risk factors for mortality in patients with end-stage renal disease attributable to systemic lupus erythematosus: a two-center integrated study.

ObjectiveRenal impairment is a significant complication of systemic lupus erythematosus (SLE). Additionally, infection in patients with end-stage renal disease (ESRD) attributable to SLE is common, and it increases the risk of mortality. This study explored the infection profile and risk factors for mortality in patients with ESRD attributable to SLE.MethodsIn this retrospective, observational study of 125 hospitalized patients, demographic, clinical, laboratory, treatment, and prognosis data were retrieved and analyzed.ResultsThe 125 cases included 98 pulmonary infections (78.4%), 14 urinary infections (11.2%), and 13 intestinal infections (10.4%). Twenty-six patients died within 1 month after enrollment. Univariate Cox regression and Kaplan–Meier analyses revealed several possible indicators potentially influencing patient survival. Furthermore, multivariate Cox regression analysis identified a higher SLE Disease Activity Index-2000 score, recent higher-dose glucocorticoid use, hypertension, and catheter indwelling as risk factors for higher mortality.ConclusionsInfections were common in patients with advanced SLE and ESRD, and several risk factors might increase the risk of mortality. Once infection is identified, empiric antibiotics should be initiated immediately, and subsequent antibiotics should be applied per the results of drug sensitivity testing to clear the infection.

Assessment of Serum Neutrophil Gelatinase Associated Lipocalin (NGAL) levels in patients of Systemic Lupus Erythematosus (SLE) with and without Lupus Nephritis (LN)

Background: Lupus nephritis (LN) can occur as a complication of SLE causing further distress to patient. NGAL levels can help in foreseeing kidney injury in such afflicted. Thus, the study aimed to estimate serum NGAL levels in SLE patients with and without Lupus Nephritis. Methods: A cross sectional study was conducted at immunology Department, University of Health Sciences (UHS) Lahore. Purposive sampling technique was used to collect samples of patients diagnosed with SLE with and without Lupus Nephritis LN. Results: Study showed statistically significant results (p=0.00) with mean ±SD value of NGAL measured in patients of SLE with LN & without Lupus Nephritis LN. Conclusion: The study indicated that NGAL level was observed to be significantly raised in the patients of SLE with lupus nephritis as compare to the patients of SLE without lupus nephritis. Keywords: Acute kidney injury, Anti-double stranded DNA antibody, Chronic kidney disease, Lupus nephritis

Complement factor B inhibitor LNP023 improves lupus nephritis in MRL/lpr mice

BackgroundLupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE), and the abnormal activation of the alternative complement pathway is associated with the pathogenesis of LN. As an inhibitor of complement factor B (CFB) in the alternative pathway, LNP023 has been used in the treatment of a variety of renal diseases with abnormal complement system involvement, such as paroxysmal nocturnal hemoglobinuria, IgA nephropathy, and membranous nephropathy. The aim of our study was to explore whether LNP023 improved LN in MRL/lpr mice by inhibiting the activation of the alternative complement pathway. MethodsThe mice were divided into a normal control group (Normal group) (n = 6), MRL/lpr model group (n = 6), and LNP023 group (n = 6). The LNP023 group was administered LNP023 for 2 weeks by gavage; the MRL/lpr model group was administered saline for 2 weeks by gavage; and the Normal group was administered saline for 2 weeks by gavage. External signs, renal pathology, renal function, renal immune complex and complement deposition, serum anti-dsDNA, serum ANA concentration, and the expression of core complement factors in the alternative complement pathway were analyzed in the 3 groups of animals. The core targets of LNP023 in the treatment of LN were screened using network pharmacology. The pathogenicity of the core targets in LN was verified by analyzing the mRNA expression of the core targets in the peripheral blood mononuclear cells (PBMCs) of normal individuals, SLE patients, and LN patients. The mRNA and protein expression of core targets in the Normal group, MRL/lpr group, and LNP023 group were analyzed to verify whether LNP023 exerted it LN therapeutic effect through the regulation of core targets. ResultsCompared with the MRL/lpr group, the LNP023 group had reduced lupus-like signs, improved renal function, decreased serum anti-dsDNA and ANA concentrations, and reduced renal IgM, IgG, IgG1, C1q, C3, and C4 deposition. Renal pathology showed that LNP023 attenuated pathological damage in the kidneys of MRL/lpr mice. Compared with the MRL/lpr model group, the treatment group had no crescent formation, less immune deposition, no nuclear fragmentation, and less inflammatory cell infiltration. The expression of complement proteins C3, C3b, CR1, CFB, and C5b-9 in kidney tissues and liver was decreased, and the expression of C5 was increased. Network pharmacology screening indicated that AKT, TNF-α, MDM2, UBC, STST3, ESR1, and TP53 were core targets of LNP023 in the treatment of LN. Compared with that in the Normal group, the mRNA expression of the core target in the SLE and LN groups was different; compared with the MRL/lpr group, the LNP023 treatment group showed different mRNA and protein expression levels of AKT, TNF-α, and STST3. ConclusionLNP023 improves LN in MRL/lpr mice. The mechanism is as follows: LNP023 binds to CFB to inhibit the activation of the alternative complement pathway. LNP023 treatment for LN may also play a role in regulating the protein expression of AKT, TNF-α, and STST3.

Intestinal pseudo-obstruction in systemic lupus erythematosus: an analysis of nationwide inpatient sample.

Intestinal pseudo-obstruction (IPO) is a rare gastrointestinal complication of systemic lupus erythematosus (SLE). We aimed to determine the prevalence and in-hospital outcomes of SLE-related intestinal pseudo-obstruction (SLE-IPO) using a large national database. This is a retrospective study using Nationwide Inpatient Sample (NIS) from 2016 to 2018. We included adult patients with SLE using International Classification of Diseases 10th Revision (ICD-10) code M32 in combination with codes for IPO, and we determined the in-hospital mortality, occurrence of sepsis, length of hospitalization, use of total parenteral nutrition (TPN), and frequency of surgical gastrointestinal procedures. The prevalence of IPO among hospitalized adult SLE patients was 1.7%, and the in-hospital mortality of SLE-IPO was 5.04%. Compared with SLE patients without IPO (group 2), SLE-IPO patients had higher in-hospital mortality (OR 2.07, 95%CI 1.60-2.64), higher risk of sepsis (OR 1.63, 95%CI 1.42-1.87), longer in-hospital stay (β 3.09, 95%CI 2.76-3.42), and higher frequency of TPN (OR 16.20, 95%CI 11.62-22.21) and gastrointestinal procedures (OR 5.47, 95%CI 4.62-6.43). SLE-IPO was associated with increased risk of sepsis (OR 1.29, 95%CI 1.12-1.49), compared with idiopathic IPO patients (group 3), and a possible increase in the frequency of gastrointestinal procedures (OR 1.14, 95%CI 0.96-1.34) compared with IPO secondary to diabetes mellitus (group 4), although not statistically significant. SLE-IPO patients were at twofold risk of in-hospital mortality compared with SLE patients without IPO. SLE-IPO was also associated with longer in-hospital stay and increased frequency of TPN and gastrointestinal procedures. Key Points • The prevalence of IPO in adult SLE patients was 1.7% in this US-based database. • In-hospital mortality rate of SLE-IPO was 4.95%. SLE-IPO patients were associated with twofold risk of in-hospital mortality compared with those without IPO. •SLE-IPO patientswere also at increasedrisk of sepsis, and they had higher rate of TPN and gastrointestinal procedures.

Investigating the Mechanisms of Jieduquyuziyin Prescription Improves Lupus Nephritis and Fibrosis via FXR in MRL/lpr Mice.

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) and one of the leading causes of death. An alternative effective treatment to ameliorate and relieve LN and delay the process of renal tissue fibrosis is urgently needed in the clinical setting. Jieduquyuziyin prescription (JP) has been successfully used to treat SLE, but its potential mechanisms are not sufficiently understood. In this study, we treated MRL/lpr mice with JP for 8 weeks and treated human renal tubular epithelial cells (human kidney 2 (HK-2)) with drug-containing serum to observe the antagonistic effects of JP on inflammation and fibrosis, as well as to investigate the possible mechanisms. Results demonstrated that JP significantly reduced urinary protein and significantly improved pathological abnormalities. Metabolomics combined with ingenuity pathway analysis illustrated that the process of kidney injury in lupus mice may be closely related to farnesoid X receptor (FXR) pathway abnormalities. Microarray biomimetic analysis and LN patients indicated that FXR may play a protective role as an effective therapeutic target for LN and renal fibrosis. JP significantly increased the expression of FXR and inhibited the expression of its downstream targets, namely, nuclear transcription factor κB (NF-κB) and α-smooth muscle actin (α-SMA), in the kidney of MRL/lpr mice and HK-2 cells, as confirmed by in vitro and in vivo experiments. In conclusion, JP may mediate the activation of renal FXR expression and inhibit NF-κB and α-SMA expression to exert anti-inflammatory and antifibrotic effects for LN prevention and treatment.

1,25-dihydroxyvitamin D3 ameliorates lupus nephritis through inhibiting the NF-κB and MAPK signalling pathways in MRL/lpr mice

BackgroundLupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus (SLE). However, the aetiology and pathogenesis of LN remain unknown. 1,25-dihydroxyvitamin D3 [1,25-(OH)2-VitD3] is the active form of vitamin D, and it has been shown to perform important functions in inflammatory and immune-related diseases. In this study, we investigated the time-dependent effects of 1,25-dihydroxyvitamin D3 and explored the underlying mechanism in MRL/lpr mice, a well-studied animal model of LN.MethodsBeginning at 8 weeks of age, 24-h urine samples were collected weekly to measure the levels of protein in the urine. We treated female MRL/lpr mice with 1,25-dihydroxyvitamin D3 (4 μg/kg) or 1% DMSO by intraperitoneal injection twice weekly for 3 weeks beginning at the age of 11 weeks. The mice were separately sacrificed, and serum and kidney samples were collected at the ages of 14, 16, 18, and 20 weeks to measure creatinine (Cr) levels, blood urea nitrogen (BUN) levels, histological damage, immunological marker (A-ds DNA, C1q, C3, IgG, IgM) levels, and inflammatory factor (TNF-α, IL-17, MCP-1) levels. Furthermore, the nuclear factor kappa B (NF-κB) and the mitogen-activated protein kinase (MAPK) signalling pathways were also assessed to elucidate the underlying mechanism.ResultsWe found that MRL/lpr mice treated with 1,25-dihydroxyvitamin D3 displayed significantly attenuated LN. VitD3-treated mice exhibited significantly improved renal pathological damage and reduced proteinuria, BUN, SCr, A-ds DNA antibody and immune complex deposition levels (P < 0.05) compared with untreated MRL/lpr mice. Moreover, 1,25-dihydroxyvitamin D3 inhibited the complement cascade, inhibited the release of proinflammatory cytokines, such as TNF-α, IL-17, and MCP-1, and inhibited NF-κB and MAPK activation (P < 0.05).Conclusion1,25-dihydroxyvitamin D3 exerts a protective effect against LN by inhibiting the NF-κB and MAPK signalling pathways, providing a potential treatment strategy for LN. Interestingly, the NF-κB and MAPK signalling pathways are time-dependent mediators of LN and may be associated with lupus activity.

Cardiovascular Complications in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an auto-immune disease of a relapsing-remitting nature that can cause multiorgan damage depending on several factors, mainly the disease activity. Young age women are the most likely to be affected by the disease and the female-to-male prevalence ratio is approximately 1:10. As the number of SLE patients has been increasing in the last few decades, the annual number of deaths due to the disease and its complications has increased as well, and one of the most important systems to which high mortality is attributed is the cardiovascular system, leading to premature atherosclerosis and other events such as endocarditis and valve disease. In addition to the classical cardiovascular risk factors, studies have found a positive correlation between SLE and other cardio-harmful diseases such as metabolic syndrome and dyslipidemia. Moreover, some of the medications used in the treatment of SLE place a heavy burden on the heart. The article reviews the shared pathophysiology of SLE and cardiovascular disease along with the most common SLE- associated cardiac risks, events, and management.

Diffuse myometrium thinning and placenta accreta spectrum in a patient with systemic lupus erythematosus (SLE): a case report and review of the literature

BackgroundCases of uterine wall thinning and placental abnormalities complicated with systemic lupus erythematosus (SLE) during pregnancy have been reported in Asian countries for ten years. Long-term steroid use can cause muscle degeneration, but the mechanism of myometrium thinning was not known. Through the review of published articles, this report is the first review of cases to discuss the pathogenesis and clinical features of thinned myometrium and placenta accreta spectrum (PAS) in pregnant patients with SLE.Case presentationA twenty-nine-year-old primigravida with a history of lupus enteritis and paralytic ileus had a natural conception after less than two years of steroid treatment. An ultrasonographic study showed a thin uterine wall with a widespread thick placenta on the entire surface of the uterine cavity in the third trimester. At the 39th gestational week, she underwent a cesarean section due to the failure of the uterus to contract, even though the injection of oxytocin. There were several engorged vessels on the surface of the anterior uterine wall at the time of laparotomy. We decided to perform a hysterectomy because diffuse PAS replaced her uterus.ConclusionA review of reported cases and our case shows an unusual complication of SLE that might be related to the particular condition of the estrogen-mediated immune system. Clinicians should always pay attention to the possibility of uterine wall thinning as uterine atony and the structural abnormality of the placenta for SLE patients with the unscarred uterus.

Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial

ObjectivesLupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target...

Management practice and treatment outcomes of adult patients with Lupus Nephritis at the Renal Clinic of St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia

BackgroundLupus nephritis (LN) is the most common severe complication of systemic lupus erythematosus (SLE) which results in high morbidity and mortality. Up to 60% of adult patients with SLE develop the renal disease with different severity. Even with potent anti-inflammatory and immunosuppressive therapies, many LN patients still progress to chronic kidney disease or end-stage renal disease. Thus, this study aimed to assess the management practice, treatment outcomes and to identify the associated factors of poor renal outcome in adult LN patients at the renal clinic of St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia.MethodsA retrospective cross-sectional study design was used to collect the data using an abstraction tool from patients’ records. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to diagnose LN among SLE patients. Logistic regression was used to determine crude and adjusted odds ratio and a p-value of < 0.05 was considered statistically significant. Ethical approval was obtained from the ethical review committee of the School of Pharmacy, Addis Ababa University and institutional review board of St. Paul’s Hospital Millennium Medical College.ResultsOut of 168 study participants enrolled from September 1, 2016 to October 30, 2020, a total of 114 adult LN patients were included for final analysis. The mean (± SD) age of the LN patients at onset was 29.10 ± 9.67 years and 99 (86.8%) of all the patients were females. More than three-fourths (78.9%) of the LN patients had a good prognosis. However, 24 (21.1%) of the patients who didn’t achieve complete or partial remission had a poor prognosis. A kidney biopsy was done for 71 patients at initial presentation with class IV and III as the commonest class. The commonly prescribed immunosuppressive medications were cyclophosphamide as induction therapy in 67 (58.7%) and mycophenolate mofetil (MMF) as maintenance therapy in 76 (66.7%). Gastrointestinal intolerances like abdominal pain, nausea, or diarrhea from MMF were the most common 27(31.2%) treatment-related adverse events reported. Acute kidney injury (AKI) at onset (AOR = 4.83, P = 0.026), high serum creatinine (SCr) at six months (AOR = 0.12, P = 0.003), no response at six months to attain complete remission (AOR = 0.05, P = 0.041) and presence of flare (AOR = 0.04, P = 0.004) were predictors poor treatment outcomes.ConclusionDespite good response with the present immunosuppressive regimens, relapse, treatment-related complications and adverse events are major problems that require close monitoring. The results and identified gaps of this study are used as an input to improve the management practice of LN in the study setting. Overall, this study is comparable with other findings and strengthen the present available literatures.

A Histology-Guided Approach to the Management of Patients with Lupus Nephritis: Are We There Yet?

Renal involvement is a frequent complication of systemic lupus erythematosus (SLE). It occurs in up to two-thirds of patients, often early during the disease course, and is the most important predictor of the morbidity and mortality of SLE patients. Despite tremendous improvements in the approach of the lupus nephritis (LN) therapy, including the recent approval of two new disease-modifying therapies, up to 50% of patients do not obtain a renal response and up to 25% will eventually progress to end-stage renal disease (ESRD) within 10 years of diagnosis. Given the lack of correlation between clinical features and histological lesions, there is an increasing need for a histology-guided approach to the management of patients with LN. Apart from the initial diagnosis of type and severity of renal injury in SLE, the concept of a repeat kidney biopsy (either in a for-cause or a per-protocol scenario) has begun to gain increasing popularity in the nephrology community. Herein, we will provide a comprehensive overview of the most important areas of utility of the kidney biopsy in patients with LN.

Omics-based integrated analysis identified IKZF2 as a biomarker associated with lupus nephritis

Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE). IKZF2 was identified as a lupus susceptibility locus, while its exact molecular function in LN is unknown. We aimed to explore the relationship between IKZF2 and LN based on multi-omics data. In our study, we carried out a meta-analysis of publicly available data, including not only tubulointerstitium, but also glomerulus tissue samples from LN patients and controls. Based on the common differentially expressed genes (co-DEGs) and previous researches, we selected IKZF2 for further analysis. Then, we analyzed potential molecular mechanisms of co-DEGs and IKZF2 in LN. To explore the possible targets of IKZF2, protein–protein interaction network (PPI) network and ceRNA network of IKZF2 were also constructed. Moreover, we performed immune infiltration analysis and evaluated clinical value of IKZF2. A total of 26 co-DEGs were observed in the integration of the above DEGs coming from the four sets of data, of which IKZF2 was selected for further analysis. Functional enrichment analysis from IKZF2 and related PPI network confirmed the tight relationship between IKZF2 and the immune reaction. Moreover, immune filtration analysis revealed the significant correlation between IKZF2 and naïve B cell, NK cell activation, NK cell rest and other immune cells. Receiver operating characteristic (ROC) analysis showed that the areas under the ROC curves were 0.721, 0.80, 0.682, and 0.859 for IKZF2 in four datasets, which demonstrated the clinical value of IKZF2. Our study revealed that IKZF2 may play an essential role in the molecular function and development of LN, and might be a potential biomarker for distinguishing LN patients and healthy ones.