Systemic Lupus
Erythematosus
(SLE)
Prof EK Njelesani
MB, ChB (UNZA), MRCP (UK), FRCP Edin,
FCP (ECSA), FRCP London
SLE
At the end of this lecture you should be
able to internalize the following:
1. Overview of SLE
2. Pathophysiology of SLE
3. Etiology of SLE
4. Clinical presentation including
multisystem
involvement/Complications
5. Management, Treatment and
Rehabilitation of Pts with SLE
Pathology
A systemic auto immune disease
Can affect any part of the body
Antibodies to nuclear and cytoplasmic antigens
Immune system attacks its own cells and
tissues
A type 3 Hypersensitivity reaction
Caused by Immune complex formation
Immune complexes deposited in tissues
Results in multisystem inflammation and tissue
damage
Pathology
SLE harms:
Blood vessels
The heart
Lungs
Joints
Skin
Kidneys
Liver and
The Central and Peripheral Nervous systems
Pathology
Course of the disease is unpredictable
Flares and remissions
Nine times more in women than men
Child bearing age: 15-35
More common in those of non European
descent
Childhood SLE between 3-15 years
Girls/Boys 4:1
Pathophysiology/Etiology
Pathophysiology/Etiology
Genetics:
Runs in families, multiple genes involved,
located in the HLA region of chromosome 6
HLA class 1, 2 and 3 associated with SLE
Environmental:
viruses, bacteria, Ultra violet light
Drugs:
Hydralazine, Isoniazid, quinidine, Phenytoin
Pathophysiology
Abnormalities in apoptosis:
Programmed cell death
Preservation of homeostasis
In SLE apoptosis is increased in monocytes
and keratinocytes
Immune cells are normally deactivated to
avoid affinity for self tissues
In SLE they are abnormally activated by
signaling sequences of antigen-presenting
cells
Clearance of damaged cells is overwhelmed
Pathophysiology
Triggers include:
Viruses,
Bacteria,
Allergens, such as IgE
Ultraviolet light
Drugs
Pathophysiology
Reaction leads to destruction of cells in the
body
Exposure of their DNA, histones, and other
proteins, in the cell nucleus.
The sensitized B-lymphocytes cells produce
antibodies against nuclear proteins.
Antibodies clump into antibody-protein
complexes which stick to surfaces and
damage blood vessels
Signs and symptoms
Great imitator
Fever, malaise,
Joint pains
Myalgia
Fatigue
Signs and Symptoms
Dermatological
Occurs in 30% of SLE patients
Malar/Butterfly rash on the cheeks
Discoid lupus- thick, red scaly skin patches
Alopecia
Mouth, Nasal, Urinary tract and Vaginal
ulcers
Tiny skin tears around the eyes and mouth
Malar/Butterfly Rash
Musculoskeletal
Non erosive arthritis commonest
presentation
Small joints of the hand usually affected
Other joints can be affected
Myalgia
SLE patients at particular risk of developing
osteoarticular tuberculosis
Haematological
Anaemia in 50% of SLE patients
Pancytopoenia is common
Antiphosphlipid syndrome: a thrombotic
disorder with autoantibodies to
phospholipids, may be associated with
repeated abortions
Cardiac
Pericarditis
Pericardial effusion
Myocarditis
Sterile Libman-Sacks endocarditis affecting
mitral and tricuspid valves
Atherosclerosis
Pulmonary
Pleuritis
Pleural effusion
Lupus pneumonitis
Chronic diffuse interstitial lung disease
Pulmonary embolism
Pulmonary hypertension
Pulmonary haemorrhage
Shrinking lung syndrome
Renal
Haematuria
Proteinuria
Glomerulonephritis, lupus nephritis with
wire loop abnormalities on histology
Immune complexes deposited along the
basement membrane leading to damage
Nephrotic syndrome
Renal failure
Neuropsychiatric
Affects both central and peripheral nervous
systems
Headache
Seizures
Cognitive dysfunction
Mood disorder
Cerebral vascular disease
Polyneuropathy, Peripheral neuritis
Neuropsychiatric
Psychosis
Anxiety disorder
Intracranial hypertensive syndrome( raised
ICP. Papilloedema, headache)
Acute confusional state
Guillan-Barre syndrome
Aseptic meningitis
Demyelinating syndrome
Laboratory Investigations
Anti nuclear antibody test
Anti-extractable nuclear antigen (anti-ENA)
Subtypes of antinuclear antibodies:
Anti-Smith Ab
Anti-double stranded DNA (dsDNA) Abs
Anti-histone Ab linked to drug-induced lupus
Anti-dsDNA antibodies are highly specific for
SLE
Laboratory Investigations
Complement system levels (low levels
suggest consumption by the immune system)
NB:Complement system:
enhances/complements ability of Abs and
phagocytes to clear microbes and damaged
cells from an organism, promote
inflammation and attack the pathogen’s cell
membrane.
U and E and Cre
Liver function tests
FBC
SLE Criteria for Classification
The European League Against Rheumatism
(EULAR) and the
American College of Rheumatology (ACR)
Published new Criteria for classification of SLE
in 2009
Both require ANA of at least1:80 on HEP-02
cells ( a native protein array with hundreds of
antigens) for Pt to have SLE
At least one Clinical criterion point and 10 or
more points Immunological domain needed to
classify a condition as SLE
Table 1. EULAR/ACR Clinical Domains and Criteria for SLE
Domain Criteria Points
Constitutional Fever 2
Leukopenia 3
Hematologic Thrombocytopenia 4
Autoimmune hemolysis 4
Delirium 2
Neuropsychiatric Psychosis 3
Seizure 5
Table 1. EULAR/ACR Clinical Domains and Criteria for SLE (ctd)
Non-scarring alopecia 2
Oral ulcers 2
Mucocutaneous
Subacute cutaneous or discoid
4
lupus
Acute cutaneous lupus 6
Pleural or pericardial effusion 5
Serosal
Acute pericarditis 6
Musculoskeletal Joint involvement 6
Proteinuria > 0.5 g/24 h 4
Renal biopsy class II or V lupus
8
Renal nephritis
Renal biopsy class III or IV lupus
10
nephritis
Table 2. EULAR/ACR Immunologic Domains and Criteria for SLE
Domain Criteria Points
Antiphospholipid antibodies Anti-cardiolipin antibodies or 2
Anti-β2GP1 antibodies or
Lupus anticoagulant
Complement proteins Low C3 or low C4 3
Low C3 and low C4 4
SLE-specific antibodies Anti-dsDNA antibody or 6
Anti-Smith antibody
Diagnostic Criteria
Mainly used in clinical trials (ACR 4/11):
Malar rash Anaemia
Discoid rash Proteinuria/cellular casts
Serositis ANA
Oral ulcers Anti-Smith, anti-ds DNA,
Arthritis Antiphospholipid Ab
Photosensitivity Seizures, Psychosis
Treatment
1. Life style change: avoid sunlight
2. NSAIDs for pain
3. Disease-modifying antirheumatic
drugs: (DMARDs) Used to reduce
flares
Hydroxychloroquine
Methotrexate
Cyclophosphamide
Corticosteroids
Prognosis
SLE is considered incurable but highly
treatable
Treat high blood pressure
Reduce high cholesterol levels
Use lowest possible doses of steroids
High serum creatinine, hypertension,
nephrotic syndrome, anemia and
seizures are poor prognostic factors
SLE
At the end of this lecture you should be
able to internalize the following:
1. Overview of SLE
2. Pathophysiology of SLE
3. Etiology of SLE
4. Clinical presentation including
multisystem involvement
5. Management, Treatment and
Rehabilitation of Pts with SLE
6. THANK YOU
