What is SLE
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune condition caused by a type 3 hypersensitivity reaction due to a complex interplay between genetic and environmental factors.
Epidemiology
- Most commonly affects women in their reproductive years
- Most common in African-Caribbean and Asians
- Peak age of onset is between 15 and 45 years old
Aetiology
- Genetics
- Environmental triggers e.g.
- UV light
- Smoking
- Medications e.g. procainamide, hydralazine, isoniazid
- Sex hormones e.g. oestrogen
- EBV
RF
- iddle-aged: peak age of onset is between 15 and 45 years old
- Female gender: SLE is 12 times more common in females
- African and Afro-Caribbean: SLE is more common and more severe in these patients; incidence amongst black Americans ishigherthan black Africans for unknown reasons
- Family history
- Drugs: procainamide, isoniazid, hydralazine may cause drug-induced Lupus
- HLA associations: HLA-B8, -DR2, -DR3
Pathophysiology
Environemental triggers (e.g UV light) cause cell death and apoptotic bodies - due to genes reduced clearance of apoptotic bodies and cellular debris
Immune system of patients dont recognise cellular debris as self so attack cell material forming nuclear antigen-antibody complex
These complexes deposit in diff tissues and activate complement causing inflammation and damage - type III hypersensitivy reaction
Where can the deposition occur
deposition can occur anywere so multiple organs are affected e.g. skin, joints, kidneys, heart and brain.
What do many patients also develop?
develop antibodies targeting other cells like red and white blood cells, and molecules like various phospholipids, which can mark them for phagocytosis and destruction, leading to additional symptoms.
This is considered a type II hypersensitivity reaction.
Classic presentation
Malar ‘butterfly’ rash (across cheeks but not nose), fatigue and widespread musculoskeletal pain in a middle-aged, African female.
- photosensitive rash
The disease follows a relapsing and remitting course.
General symptoms
- Fatigue
- Fever
- Lymphadenopathy
- Weight loss
Many clinical manifestations
Photosensitivity
Arthralgia
PE
Pericarditis
Neonatal heart block
Lupus
Psychosis
Seizures
Thrombocytopenia
1st line investigations
- FBC
- activated partial thromboplastin time
- urea and electrolytes
- ESR and CRP
Other investigations to consider
- Urinalysis: lupus nephritis may cause proteinuria and haematuria
- Skin or renal biopsy
- Imaging:consider joint X-rays in the presence of arthralgia or a chest X-ray if respiratory symptoms are present
Clinical criteria
- Malar rash
- Discoid
- Oral and nasal ulcers
- Synovitis
- Serositis
- Urinalysis (presence of proteinuria or haematuria)
- Neurological features
- Thrombocytopenia
Lab criteria
- +ve ANA
- Anti-dsDNA
- Anti-smith antibodies
- Antiphospholipid antibodies
- Low complement
- +ve direct Coombs test - detects antibodies that are stuck to the surface of RBCs
DD
- Scleroderma
- Rheumatoid arthritis
- Antiphospholipid syndrome
- Mixed connective tissue diseases (CTDs)
- Raynaud’s syndrome
- Sjögren’s syndrome
Acute management
Mild: Prednisolone (corticosteroid) + hydroxychloroquine + NSAIDs
Moderate and severe: Prednisolone and hydroxychloroquine and an immunosuppressant (methotrexate, Azathioprine, Ciclosporin)
Refractory cases - biologics such as belimumab or rituximab may be considered
Maintenance therapy
- Initially, use the flare-up medication at a reduced dose
- Then switch to therapy with just hydroxychloroquine
Prognosis
The mortality associated with SLE is improving and fortunately, the majority of people with lupus can expect a normal or near-normal life expectancy.
However, patients do have an overall increased risk of premature death compared to the general population. Early mortality is predominantly due to renal and central nervous system involvement, thrombosis and infection. Later mortality is due to infection and premature atherosclerotic vascular disease.
~80% survival at 15 years
