Systemic lupus erythematosus (SLE)
SLE is a multisystemic autoimmune disease that results from immune system-mediate damage. It can affect the skin, joints, kidneys, CNS, cardiovascular system, serosal membranes and the hematologic and immune systems. It can have a wide range of presentations, making it hard to spot, but the most characteristic feature is its waxing and waning clinical course, with flair ups that need to be managed.
SLE has a female to male ratio of about 10:1, and mostly individuals are diagnosed at ages between 15-44. The current understanding of SLEs pathogenesis is one that incorporates genetic susceptibility based on a threshold model involving multiple genes, and environmental triggers such as infection, sunlight and certain drugs. Genes that might account for increased lupus susceptibility/severity include those genes that code the complement pathway (C1q, C2 and C4A specifically). Additionally, polymorphic variants in the toll-like receptor (TLR) pathways that regulate interferon I production and interferon 5, have been suspected of additional complications. HLA-DR2 and HLA-DR3 have also been implicated.
Environmental triggers are then required to occur on top of our genetic predisposition. The most common trigger is viral infection, with Epstein-Barr being cited as a virus of potential importance. Additionally UV light is a well-described trigger. Possible mechanisms include DNA damage, induction of cellular stress response, and induction of apoptosis of skin cells. Fundamentally, the organism has a loss of T and B lymphocyte control leading to hyperactive B lymphocytes and non-specific antibody and autoimmune production. Patients have hypergammaglobulinemia as a result of polyclonal B-cell proliferation and T-cell dysregulation.
The most characteristic lupus antibodies target intracellular particles containing both nucleic acid and nucleic acid proteins, these are the so-called Anti-nuclear antibodies (identification of these on a titre is one of the diagnostic criteria). ANA develops prior to the anti-DNA antibody, another diagnostic antibody that can be used. Indeed, SLE has a range of antibodies that are found when we do a blood titre including:
- Anti-Ro antibody (aka anti-sjogren's syndrome related antigen A)
- Anti La antibody
- APL (antiphospholipid antibodies)
- Anti- double strand DNA
- Anti- Smith (anti-Sm)
- Anti-nRNP (anti- ribonucleoprotein antibody)
Tissue and organ damage in SLE is mediated by the deposition or in situ formation of immune complexes and subsequent complement activation and inflammation. The tissues targeted can be almost any of the systems. The key clinical signs are:
- Systemic
- Low grade fever
- Photosensitivity
- Mouth and nose
- Ulcers
- Muscles
- Aches
- Joints
- Arthritis
- Psychological
- Fatigue
- Loss of appetite