Connective Tissue + Tendon Disease Flashcards
Connective tissue diseases
- What are they not?
- Characterized by?
- Associated with?
NOT diseases of connective tissue
Characterized by the presence of spontaneous over-activity of the immune system
Often associated with specific auto-antibodies which can help define the diagnosis
Systemic lupus erythethmatosus
What is it?
What causes it?
This is a multisystemic autoimmune disease that can affect any part of the body.
The immune system attacks the body’s cells and tissue, resulting in inflammation and tissue damage.
Antibody-immune complexes precipitate and cause a further immune response.
SLE epidemiology
- Male:female ratio?
- Typical patient?
- Where in world is prevalence higher?
Females more than males 9:1
Typical patient is woman of childbearing age
Prevalence is higher (and disease is typically more severe in) in Asians, Afro-Americans, Afro-Caribbean’s and Hispanic Americans compared with Americans of European descent
Aetiology of SLE?
This is an interplay between several different things – someone has to be genetically predisposed to it, and other things trigger it, e.g. hormonal factors (like being on the pill).
Genetic factors: high concordance in monozygotic twins, increased incidence amongst relatives, identification of gene abnormalities predisposing to lupus.
Hormonal factors: incidence increased in those with higher oestrogen exposure - early menarche, on oestrogen containing contraceptives and HRT.
Environmental factors
- Viruses e.g. Epstein-Barr Virus
- UV light may stimulate skin cells to secrete cytokines stimulating B-cells
- Silica dust (found in cleaning powders, cigarette smoke and cement) may increase risk of developing SLE
Function of T cells?
T cells do a couple of things – 1. They stimulate B cells to produce antibodies against the antigen; 2. They stimulate toxic T cells to destroy cells that express the antigen.
Pathophysiology of SLE?
In a healthy human, when cells break down they are cleared very quickly. In lupus, that process stops working effectively and that means that the cell contents float about in the system for much longer than they would do otherwise. If there is prolonged exposure to the contents of the cell nucleus, the immune system starts to see them as being alien to the body and starts producing antibodies against them.
I.e. there is increased and defective apoptosis (programmed cell death) -> necrotic cells release nuclear material which act as potential auto-antigens -> autoimmunity probably results from the extended exposure to nuclear and intracellular auto-antigens -> B and T cells are stimulated -> autoantibodies are produced.
Pathophysiology of renal SLE?
- Likely due to deposition of immune complexes in mesangium
- Complexes consist of nuclear antigens and anti-nuclear antibodies
- Complexes form in circulation then are deposited
- Once present they activate complement which attracts leucocytes which release cytokines
- Cytokine release perpetuates inflammation which, over time, causes necrosis and scarring
How do complement levels in the blood relate to SLE disease activity?
Immune complex deposition lowers complement levels -> measure this in the blood and if it is low, then disease activity is likely to be high.
Diagnostic criteria for SLE?
Four criteris with at least one criteria + one immunologic
Which systems does SLE affect?
Mucocutaneous Musculoskeletal (Serositis) Renal Neurological Haematological
Constitutional symptoms of SLE?
Fever Malaise Poor appetite Weight loss Fatigue
Mucocutaneous symptoms of SLE? Fever Malaise Poor appetite Weight loss Fatigue
Photosensitivity Malar rash - may or may not be associated with sun exposure – tends to come out after being in the sun and then lasts for quite a while; spares the naso-lablial folds Discoid lupus erythematosus (may scar) Subacute cutaneous lupus Mouth ulcers (painless) Alopecia (non-scarring)
Musculoskeletal features of SLE?
Non-deforming polyarthritis/polyarthralgia RA distribution but no radiological erosion
Deforming arthropathy - Jaccoud’s arthritis
Erosive arthritis - rare
Myopathy - weakness, myalgia & myositis
Despite hands looking very deformed, x-rays typically look very normal.
SLE patients are able to form a fist; rheumatoid patients are not.
SLE cause serositis.
What is this?
What does it cause?
Serositis – basically just inflammation of the lining of something Pericarditis Pleurisy Pleural effusion Pericardial effusion
What are the symptoms of renal SLE?
Renal features – typically don’t cause symptoms
- Proteinuria of >500mg in 24 hours
- Red cell casts
- Only get microscopic visible haematuria
- You need to actively screen for renal disease, otherwise you won’t know it’s there
Neurological features of SLE?
These are less common than other features
Depression/psychosis
Not always related to disease activity – difficult to tell
Migrainous headache
Seizures
Cranial or peripheral Neuropathy
Mononeuritis multiplex – caused by destruction of the blood vessels which supply nerves i.e. vasculitis
Haematological features of SLE
Lymphadenopathy - ~25% of all patients during their course of illness Leucopenia Lymphopenia Haemolytic anaemia Thrombocytopenia
Antiphospholipid syndrome
Which condition is this associated with?
What antibodies are involved?
Pnemonic for remembering symptoms?
Can be associated with SLE (20-30%) Anticardiolipin & lupus anticoagulant
Causes CLOTS:
Coagulation defect
Livedo reticularis - strange skin colour pattern, typically on the thighs, as shown opposite
Obstetric – recurrent miscarriage
Thrombocytopaenia - ↓platelets
This condition causes venous and arterial thrombosis
How do caucasians tend to present?
Caucasian patients tend to be at the mild end of the spectrum.
