Systemic lupus erythematosus: Diagnosis and clinical management
Introduction
Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease. A complex interaction of impaired apoptotic clearance, upregulation of innate and adaptive immune system, complement activation, immune complexes, and tissue inflammation culminates in a self-sustained autoimmune process. Multiple pathogenic mechanisms likely can converge toward the clinical phenotypes that we call SLE. In fact, while many organs and tissues may be affected by SLE, the pattern of clinical manifestations and autoimmune phenomena is heterogenous among patients and even changes over time in individual patients. For this reason, diagnosis is often difficult or delayed and relies on keen clinical expertise to combine clinical and immunological findings. Here, we review classification criteria and current and future treatments with a mechanistic and evidence-based point of view.
Section snippets
Epidemiology
Lupus is a worldwide disease with a striking predilection for women of childbearing age. In women between the age of 15 and 44 years, the female to male ratio is up to 13:1 while it is only 2:1 in children and in the elderly [[1], [2], [3]]. While present across ethnicities, it is more prevalent in non-Caucasians. While prevalence in Europe and United States is higher in people of African descent, SLE is infrequent in Africa [4,5]. In the United States, it is more common in African-Americans,
Pathogenesis overview
The clinical onset of SLE requires an interaction of genetic predisposition, environmental precipitants, immunological and hormonal factors. In such a permissive environment, along with proinflammatory stimuli such as type 1 interferons and other cytokines, immune tolerance to self-antigens is lost [11]. Autoimmunity then follows driven by a complex interplay of defective clearance of apoptotic waste and immune complexes along with neutrophil extracellular traps, sensing of nucleic acids,
Diagnosis
The diagnosis of systemic lupus erythematosus is made based on a combination of typical clinical manifestations and positive serologies. Given the wide heterogeneity of clinical manifestations, several sets of classification criteria have been developed over time for epidemiological and research purposes. However, some, such as the SLICC classification criteria, which are more sensitive, and therefore particularly useful in early diagnosis, can be useful as a diagnostic framework to confirm
Principles
The goals of treatment in lupus are 1) maintain lowest degree of activity using immunomodulators, immunosuppression as appropriate and avoiding known triggers, 2) prevent organ damage from active lupus, 3) reduce comorbidities secondary to lupus and its treatment, especially accelerated atherosclerosis, the major cause of death, and 4) address fatigue and pain, which often are not associated with active lupus. Early initiation of treatment as well as partnership with the patient towards these
Future perspectives and personalized medicine
The more granular understanding of the molecular basis of lupus pathogenesis has led to several new promising treatments that are undergoing late phase clinical testing. These recent phase 2 trials underlined how targeting a specific pathway may elicit dramatically different responses in patient subgroups. Precise characterization of disease phenotypes based on molecular and clinical features is crucial to design personalized treatment. The Accelerated Medicine Partnership (AMP), for example,
Funding
The Hopkins Lupus Cohort is funded by NIH AR 69572.
Disclosures
None.
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