DR. CORA LIM-MEDICAL INSIDER
Systemic Lupus ErythematosuS
PART 2
Let us continue with our discussion of Systemic Lupus Erythematosus
Aetiology. While there is no single causative agent, the disease arises from a complex interplay of genetic, epigenetic and environmental factors.
Genome wide association studies have identified over 60 risk loci involved in the susceptibility of SLE. Monozygotic twin studies show incomplete concordance in the development of SLE, indicating that there are other influences on susceptibility.
Epigenetics, inherited changes in gene expression apart from alterations in the sequence of DNA bases that affect the phenotype, also influence the risk of SLE development. This includes DNA methylation, microRNA regulation and post-translational modification of histones.
Key points. SLE is highly heterogeneous and may mimic many other diseases and the following have to be noted:
- Most patients with SLE will demonstrate ANA positivity at some point during their disease
- All patients with SLE should be treated with antimalarials such as hydroxychloroquine, unless contraindicated
- Corticosteroids should be used at the lowest effective dose for the shortest duration of time to avoid long-term complications
- Comorbidities such as cardiovascular risk, infections and osteoporosis must be addressed in all patients
Genetic factors alone are insufficient to explain the onset of SLE and there is likely to be an interaction with environmental factors for the disease to develop in a genetically susceptible individual.
Environmental triggers include ultraviolet light, demethylating drugs and viruses. Sunlight is the most common trigger for a flare of disease, especially cutaneous manifestations.
Epstein-Barr virus infection may be an
environmental risk factor for the development of SLE, especially in juveniles. Autoantibodies in the sera can precede the development of clinical features of lupus by many years.
Chronic Epstein-Barr virus infection may cause interferon alpha production, which is a feature of SLE. Many drugs, especially those that undergo acetylation such as hydralazine and procainamide, can cause drug-induced lupus, which is usually self-limiting and regresses on withdrawal of the drug. The majority of these patients do not develop SLE.