Major organ damage in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by disease flares and damage accrual. The increased longevity allows SLE patients to accrue damage which has retarded their survival improvement since the 1980s. In the first study of this thesis, meta-analyses of observational studies revealed that renal and neuropsychiatric damage has been adversely affecting the survival of lupus patients in the past fifty years. While confirmatory studies are required, targeting at renal and neuropsychiatric involvement early might hopefully further improve the survival of SLE patients.

As the survival of SLE patients improves, their psychosocial well-being becomes increasingly important. In the second study, anxiety symptoms were found to be significantly more frequent in lupus patients than those with other common inflammatory rheumatic conditions. Additionally, damage accrual and cumulative glucocorticoids accurately predicted anxiety in SLE patients.

Related to neuropsychiatric damage, event-related functional brain imaging in the third study showed that new-onset SLE patients had poorer strategic planning skill that required compensatory cortical recruitment for executing comparable cognitive function as in healthy subjects. Even after sufficient control of SLE, they remained to demonstrate inferior strategic planning skill which necessitated compensatory recruitment of cortical areas to boost their executive function. These findings illustrated that cognitive dysfunction persists even after adequate control of SLE.

Early recognition of the prognostically challenging renal, cardiovascular and musculoskeletal damage and their predictors is imperative. The fourth study revealed that failure to achieve complete renal remission 12 months after renal presentation predicted renal damage, irrespective of age and the choice of immunosuppressants. As to whether mycophenolate (MMF) or cyclophosphamide (CYC) is better; by meta-analysis, the fifth study concluded that MMF offers similar efficacy as CYC in inducing renal remission and preventing renal damage.

As for the cardiovascular system, endothelial dysfunction exerts its impact very early during atherogenesis. As shown in the sixth study, SLE patients na?ve for cardiovascular disease had significantly poorer endothelial function than demographically and anthropometrically matched healthy controls. Higher serum high-sensitivity C-reactive protein level independently predicted poorer endothelial function in SLE patients.

Osteoporotic fracture is a major lupus musculoskeletal damage which occurred in 9% of SLE patients as found in the seventh study. Increasing age and duration of corticosteroid use independently predicted osteoporotic fracture. While hormonal replacement therapy appeared fracture protective, its unfavorable long-term consequences limit its indication for fracture prevention.

Mitigating fracture risk before fractures occur is the current management strategy. The eighth study found that the significantly higher FRAX? 10-year risk of major osteoporotic and hip fractures amongst SLE patients na?ve for clinical fracture compared with their demographically and anthropometrically matched healthy counterparts was driven by chronic glucocorticoid use and premature menopause. Modifiable factors including low hip bone mineral density (BMD), cumulative glucocorticoids and higher serum anti-dsDNA level independently predicted higher fracture risks.

Finally, the relationship between lumbar bone loss and endothelial dysfunction was hitherto identified. Although potential drivers of this relationship remain to be identified, our findings serve to alert physicians to early atherosclerosis in lupus patients particularly in those with low lumbar BMD.