SLE Flashcards
What is Lupus?
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that predominately affects women of childbearing age.
What is the epidemiology of lupus?
- Sex: Females: Males is 10:1.
- Peak incidence: Women aged 20-40 years, no particular age of manifestation in men
- US prevalence: Highest in African-American, Hispanic, and Asian populations.
What is the aetiology of lupus?
Unknown
What predisposing factors of lupus have been identified?
• Genetic predisposition:
○ HLA-DR2 and HLA-DR3 are commonly present in individuals with SLE
○ Genetic deficiency of classical pathway complement proteins (C1q, C2, C4) in approx 10%
• Hormonal factors: Studies suggest that hyperstrogenic states (e.g. due to oral contraceptive use, post menopausal hormonal therapy, endometriosis) are associated with an increased risk of SLE.
Environmental factors: UV light, stimulation of immune cells through infection with bacteria and viruses (in particular EBV, which causes disease flares following infection), medications (e.g. procainamide, hydralazine).
What is the clinical presentation of lupus?
• Skin (>70% of cases)
○ Malar rash (butterfly rash) with sparing of the nasolabial folds
○ Photosensitiviy
○ Discoid rash
○ Oral ulcers
○ Alopecia
• Joints:
○ Arthritis and arthralgia (pain in a joint) (>90% of cases)
○ Mostly nonerosive polyarthritis (normal x-ray)
• Fever (>50% of cases), fatigue (>80% of cases), weight loss.
What other signs and symptoms are there of lupus?
• Musculoskeletal: Myalgia and lympadenopathy
• Serositis: Pleuritis and pericarditis, effusions and chest pain may occur
• Kidneys: nephritis with proteinuria (see lupus nephritis)
• Heart: involvement of the myocardium, pericardium, valves and coronary arteries; Libman-sacks endocarditis
• Lungs: pneumonitis, interstitial lung disease, pulmonary hypertension.
• Gastrointestinal: oesophagitis, hepatitis, pancreatitis (Although SLE may affect any gastrointestinal organ, the symptoms most often occur as side effects of lupus medication).
• Vascular: Raynaud phenomenon: vasculitis (A heterogeneous group of autoimmune diseases, all characterized by inflammation of blood vessels and potential ischemia and damage to the organs supplied by these vessels), thromboembolism (see antiphospholipid syndrome)
• Neurologic: e.g. seizures, psychosis, personality changes, aseptic meningitis, polyneuropathy, myasthenia gravis.
Hematologic: haemolytic anaemia, thrombocytopenia, leukopenia; for other features, see diagnosis.
What is the mechanism of tissue damage in lupus?
○ Type III hypersensitivity –> antibody-antigen complex formation in microvasculature –> complement activation and inflammation –> damage to the skin, kidneys, joints, small vessels.
Type II hypersensitivity –> IgG and IgM antibodies directed against antigens on cells (e.g. red blood cells) –> cytopenia.
what is the diagnostic approach for lupus?
Approach:
1. Suspect SLE in patients with symptoms in more tan two of the organ systems listed in the ACR criteria for SLE
2. Screening test: ANA titre (SLE is unlikely if the test is negative) - ANA titre of1:160is considered positive
3. Raised ANA titre –> confirm diagnosis with tests that are highly specific for SLE.
• Anti-dsDNA antibody testing: Autoantibody against double-stranded DNA (dsDNA)
○ Positive in 70% of patients and highly specific
○ Levels correlate with disease activity
○ Associated with lupus nephritis
• Anti-Sm antibody testing
○ Autoantibody against Smith antigens (nonhistamine nuclear proteins)
○ Positive in only ~30% of patients, but highly specific for SLE.
Tests listed in “other laboratory test” below may support the diagnosis.
What are the features of the ACR diagnostic criteria for SLE?
"SOAP BRAIN MD" is the acronym for the ACR diagnostic criteria for SLE: S = SEROSITIS O = ORAL ULCERS A = ARTHRITIS P = PHOTOSENSITIVITY
B = BLOOD DISORDERS R = RENAL INVOLVEMENT A = ANTINUCLEAR ANTIBODIES I = IMMUNOLOGICAL PHENOMENA N = NEUROLOGICAL DISORDER
M = MALAR RASH D = DISCOID RASH
What other investigations can be carried out in SLE?
- Complete blood count and differential: autoimmune haemolytic anaemia, thrombocytopenia, leukopenia, lymphopenia
- ESR is frequently elevated, while CRP is often normal. - If CRP is elevated in SLE, ten infection should be ruled out.
- Low C3 and C4 complement levels
- Urinalysis and urine microscopy: proteinuria and/or casts.
Additional antibody tests:
• Antiphospholipid antibodies may be elevated
• Anti-histone antibodies are elevated in drug-induced lupus erythematosus
• Anti-Ro antibodies are elevated in the majority of cases of neonatal lupus erythematosus
For a list of additional antibodies that may be elevated in SLE see antinuclear antibody diagnosis of autoimmune disease.
What is the management of SLE?
- Avoid exposure to UV light (sunlight)
- Smoking cessation
- Immunize patients before initiating immunosuppressants.
What is induction therapy?
therapy administered until disease remission is achieved
How is pregnancy affected in SLE?
• Fertility is not affected
• Pregnancy may cause flares in disease activity
Increased risk of preterm birth, hypertensive complications (preeclampdia), Intrauterine growth restriction, fetal AV block, and miscarriage
What is the prognosis of SLE?
Mortality:
• 10 year survival rate > 90%
• Mortality is highest in individuals >45 years of age (65% of deaths)
• Causes of death:
○ In early disease
§ High disease activity with renal or neurological complications
§ Infections due to immunosuppressive therapy
In late disease: cardiovascular complications, end stage renal disease (until recently, renal complications were the most common cause of death. This has changed due to improvements in the treatment of end-stage renal disease), adverse effects of long-term medication.
