Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease of diverse manifestations, with onset usually in young women in the third to fourth decade of life. The chronic nature of this relapsing remitting disease leads to organ damage accrual over time. Mortality and morbidity are increased in patients with SLE compared with the general population. Therapeutic advances over the last few decades have led to significant improvements in patient outcomes. Five-year survival has improved to over 90% from a low of 50% in the 1950s. However, multiple aspects of the management of SLE patients are still far from optimal. Early diagnosis remains a challenge; diagnostic delays leading to delay in definitive treatment are common. Monitoring treatment remains problematic due to the paucity of sensitive biomarkers. Current treatment regimens rely heavily on corticosteroids, even though corticosteroids are well known to cause organ damage. Treatment of refractory disease manifestations such as nephritis, recalcitrant cutaneous lesions and neurological involvement require new approaches with greater efficacy. Cognitive dysfunction is common in SLE patients, but early recognition and adequate treatment are yet to be established. Premature accelerated atherosclerosis remains a leading cause of morbidity and mortality. Fatigue is one of the most disabling symptoms, and contributes to the poor quality of life in patients with SLE. Ongoing research in SLE faces many challenges, including enrollment of homogeneous patient populations, use of reliable outcome measures and a standard control arm. The current review will highlight some of the outstanding unmet challenges in the management of this complex disease.
Highlights
Systemic lupus erythematosus (SLE) is a complex autoimmune disease, predominantly affecting young women during the prime years of their life
The management of SLE remains a challenge despite significant advances in the treatment
The new Systemic Lupus International Collaborating Clinics (SLICC) classification criteria with better sensitivity will probably help in better identification of patients, but we have not yet reached the stage where early diagnosis can be universally achieved
Summary
Systemic lupus erythematosus (SLE) is a complex autoimmune disease, predominantly affecting young women during the prime years of their life. There are numerous unmet medical needs in SLE, this review will focus on some of the major outstanding issues – including early diagnosis, biomarkers in SLE, management of refractory disease, atherosclerosis in SLE, corticosteroid-associated damage, QoL in SLE, and clinical research in SLE. The Systemic Lupus International Collaborating Clinics (SLICC) group recently developed another set of revised criteria. These new criteria include 17 variables derived by expert consensus (SLICC committee members) and statistical analysis, using real-life patient scenarios. A large randomized controlled trial (LUNAR) did not show any significant differences in outcomes with rituximab compared with placebo [23] This trial excluded patients with refractory disease, the very subset in which evidence of benefit was shown in open-label studies. Genome-wide association studies have identified many loci, mostly related to immune regulatory genes
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