Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.

https://ard.bmj.com/content/annrheumdis/78/6/736.full.pdf

2019 update of the EULAR recommendations for the management of systemic lupus erythematosus

Objective To update the 2012 EULAR/ERA–EDTA recommendations for the management of lupus nephritis (LN). Methods Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. Results The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria 1 g/24 hours despite renin–angiotensin–aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. Conclusions We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.

https://ard.bmj.com/content/annrheumdis/79/6/713.full.pdf

2019 Update of the Joint European League against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis

Systemic lupus erythematosus: Diagnosis and clinical management.

Introduction: Hydroxychloroquine (HCQ) is an alkalinizing lysosomatropic drug that accumulates in lysosomes where it inhibits some important functions by increasing the pH. HCQ has proved to be effective in a number of autoimmune diseases including systemic lupus erythematosus (SLE).Areas covered: In this review the mechanisms of action, the efficacy, and the safety of HCQ in the management of patients with SLE have been reviewed. HCQ may reduce the risk of flares, allow the reduction of the dosage of steroids, reduce organ damage, and prevent the thrombotic effects of anti-phospholipid antibodies. The drug is generally safe and may be prescribed to pregnant women. However, some cautions are needed to prevent retinopathy, a rare but serious complication of the prolonged use of HCQ.Expert opinion: HCQ may offer several advantages not only in patients with mild SLE but can also exert important beneficial effects in lupus patients with organ involvement and in pregnant women. The drug has a low cost ...

Hydroxychloroquine in systemic lupus erythematosus (SLE)

Systemic lupus erythematosus (SLE) patients are at high risk for depression and anxiety. However, the estimated prevalence of these disorders varies substantially between studies. This systematic review aimed to establish pooled prevalence levels of depression and anxiety among adult SLE patients. We systematically reviewed databases including PubMed, Embase, PsycINFO, and the Cochrane database library from their inception to August 2016. Studies presenting data on depression and/or anxiety in adult SLE patients and having a sample size of at least 60 patients were included. A random-effect meta-analysis was conducted on all eligible data. A total of 59 identified studies matched the inclusion criteria, reporting on a total of 10828 adult SLE patients. Thirty five and thirteen methods of defining depression and anxiety were reported, respectively. Meta-analyses revealed that the prevalence of major depression and anxiety were 24% (95% CI, 16%-31%, I2 = 95.2%) and 37% (95% CI, 12%–63%, I2 = 98.3%) according to clinical interviews. Prevalence estimates of depression were 30% (95% CI, 22%–38%, I2 = 91.6%) for the Hospital Anxiety and Depression Scale with thresholds of 8 and 39% (95% CI, 29%–49%, I2 = 88.2%) for the 21-Item Beck Depression Inventory with thresholds of 14, respectively. The main influence on depression prevalence was the publication years of the studies. In addition, the corresponding pooled prevalence was 40% (95% CI, 30%–49%, I2 = 93.0%) for anxiety according to the Hospital Anxiety and Depression Scale with a cutoff of 8 or more. The prevalence of depression and anxiety was high in adult SLE patients. It indicated that rheumatologists should screen for depression and anxiety in their patients, and referred them to mental health providers in order to identify effective strategies for preventing and treating depression and anxiety among adult SLE patients. Current Meta-analysis PROSPERO Registration Number: CRD 42016044125
 . Registered 4 August 2016.

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Prevalence of depression and anxiety in systemic lupus erythematosus: a systematic review and meta-analysis

Objective
To study the relationship between serum hydroxychloroquine (HCQ) concentrations and flares of systemic lupus erythematosus (SLE) in a longitudinal cohort of patients.

Methods
Patients who fulfilled ≥4 American College of Rheumatology classification criteria for SLE and had been treated with HCQ for >6 months were studied. Blood was assayed for HCQ levels by tandem mass spectrometry. Patients were serially assessed for disease activity, using the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and flares (SELENA flares instrument). Comparison of the mean summated SLEDAI scores over time and rates of flares in groups with different HCQ levels was performed by the Kruskal-Wallis test.

Results
A total of 276 SLE patients were studied (93% women, mean ± SD age 41.0 ± 13.8 years). The proportion of patients with HCQ levels 500 ng/ml (therapeutic) was 11%, 77%, and 12%, respectively. HCQ levels correlated significantly with the prescribed dose but not with body weight or renal function. The prescribed HCQ dose also correlated significantly with baseline SLEDAI scores, indicating that higher doses were used for more active manifestations. After a mean ± SD observation period of 32.5 ± 5.5 months, the mean summated SLEDAI score and the incidence of SLE flares was not statistically different among patients with different baseline HCQ levels. In a subgroup of 73 patients with serologic and clinical remission and having therapeutic HCQ levels, a trend of lower disease activity and fewer incidences of flares was observed.

Conclusion
Noncompliance and subtherapeutic serum HCQ levels were seen frequently in these SLE patients, which was partly due to the low prescribed dose. In patients in remission, higher HCQ concentrations were associated with a trend showing fewer flares over time.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/acr.22837

Hydroxychloroquine serum concentrations and flares of systemic lupus erythematosus: A longitudinal cohort analysis

Objectives To study the prevalence of remission and its effect on damage and quality of life (QOL) in Chinese patients with systemic lupus erythematosus (SLE). Methods Patients who fulfilled ≥4 American College of Rheumatology criteria for SLE were identified. Their remission status at last clinic visits was determined by the European consensus criteria (complete/clinical remission ± immunosuppressive drugs). The increase in SLE damage index (SDI) in the preceding 5 years was compared between patients who were and were not in remission for ≥5 years. QOL of patients as assessed by the validated Chinese version of the Medical Outcomes Study Short-Form-36 (SF36) and the LupusPRO was also compared between the remission and non-remission groups by statistical analysis. Results 769 SLE patients were studied (92% women; age: 46.4±14.6 years; SLE duration: 12.6±8.1 years). At last visit, clinical remission was present in 259 (33.7%) patients and complete remission was present in 280 (36.4%) patients. Clinical and complete remissions for ≥5 years were achieved in 64 (8.3%) and 129 (16.8%) of the patients, respectively. Patients remitted for ≥5 years were older, and had significantly lower prevalence of renal involvement, leucopenia or thrombocytopaenia. Fifty-three (6.9%) patients in remission ≥5 years were taken off all medications, including hydroxychloroquine (HCQ) (drug-free). Patients who remitted for ≥5 years but off-therapy (except HCQ) had significantly less SDI increment than those who did not remit (0.17±0.53 vs 0.67±1.10; p Conclusions Durable remission can be achieved in a quarter of patients with SLE. Patients with remission for ≥5 years have significantly less damage accrual and better QOL. Prolonged remission is an appropriate criterion for outcome assessment in SLE.

https://ard.bmj.com/content/annrheumdis/76/8/1420.full.pdf

Prevalence of remission and its effect on damage and quality of life in Chinese patients with systemic lupus erythematosus

ObjectivesThe aim of this study was to study the relationship between immunosuppressive drug treatment and survival in patients with systemic lupus erythematosus (SLE).MethodsPatients who fulfilled...

Effect of immunosuppressive therapies on survival of systemic lupus erythematosus: a propensity score analysis of a longitudinal cohort.

OBJECTIVES To study the association of depressive/anxiety symptoms with health-related quality of life (HRQoL) and work ability in Chinese patients with systemic lupus erythematosus (SLE). METHODS Consecutive patients with ≥4 ACR criteria for SLE were recruited. Depressive and anxiety symptoms were assessed by the Hospital Anxiety and Depression scale (HADS). HRQoL was assessed by the Chinese version of MOS-Short Form (SF)-36. Disease activity of SLE was assessed by the SLE disease activity index (SLEDAI) and organ damage was assessed by the ACR/SLICC damage index (SDI). The relationship between HAD scores, work ability and HRQoL was studied. RESULTS A total of 367 SLE patients were studied (95% women; age 40.2±12.9 years; disease duration 9.3±7.2 years). Fifty-five (15%) patients had HADS-depression score ≥10 and 70 (19%) patients had HADS-anxiety score ≥10. Patients with either score ≥10 had significantly lower SF36 score (physical and mental component) than those with score <10. In separate linear regression models, the mental and physical component scores of SF36 were significantly associated with the HAD-depression and HAD-anxiety score after adjustment for age, sex, SLE duration, years of education, religious belief, marital status, employment status, poverty, SDI and mean SLEDAI score in the preceding year. Among those who were working in the preceding year (n=190), 30(16%) patients either quitted their job (n=22) or reduced working hours (n=8). Patients with work disability had significantly higher HAD-depression score than those without (6.31±5.51 vs 3.93±3.72; p=0.03). CONCLUSIONS Depressive/anxiety symptoms were fairly common in SLE patients and independently associated with poorer HRQoL. Patients with more depressive symptoms were more likely to experience work disability.

Association of depressive/anxiety symptoms with quality of life and work ability in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age. The infrequency of SLE in men and disease onset in prepubertal or postmenopausal women suggests a role of estrogen in the predisposition to the disease. Patients with hypergonadotrophic hypogonadism are prone to the development of SLE, and the use of exogenous estrogens in women increases the relative risk of SLE onset and disease flares. These observations provide indirect evidence for an opposite role of estrogens and androgens in the pathogenesis of SLE. We report on a male-to-female transsexual who developed SLE 20 years after sex-reassignment surgery and prolonged estrogen therapy. The role of sex hormones in SLE is revisited.

K.L. Chan

Papers

Hydroxychloroquine serum concentrations and flares of systemic lupus erythematosus: A longitudinal cohort analysis

Prevalence of remission and its effect on damage and quality of life in Chinese patients with systemic lupus erythematosus

Effect of immunosuppressive therapies on survival of systemic lupus erythematosus: a propensity score analysis of a longitudinal cohort.

Association of depressive/anxiety symptoms with quality of life and work ability in patients with systemic lupus erythematosus.

Development of systemic lupus erythematosus in a male-to-female transsexual: the role of sex hormones revisited.