CTDs/ Muscle Disease/ Vasculitis Flashcards
Examples of Connective Tissue Diseases
> SLE
> Sjögren’s syndrome
> Systemic sclerosis
> Dermatomyositis
> Polymyositis
> Mixed Connective Tissue Disease
> Anti-phospholipid syndrome
Connective Tissue Diseases
NOT diseases of connective tissue
Presence of spontaneous over activity of the immune system.
Specific auto-antibodies
Evolve over a number of years —> organ failure –> death
SLE
General definition
Aetiology
Systemic autoimmune disease that can affect any part of the body.
Immune system attacks the body’s cells and tissues, resulting in inflammation and tissue damage
Antibody immune complexes precipitate and cause further immune response.
More females than males
> Genetic factor
- high concordance in monozygotic twins
- increased incidence amongst relatives
> Hormonal
- increased oestrogen exposure. Oestrogen containing contraceptives and HRT
> Environmental factors:
Viruses e.g. Epstein Barr virus
UV light may stimulate skin cells to secrete cytokines stimulation B cells
Silica dust
Asians, afro-americans, afro-caribbeans, Hispanics
SLE Pathogenesis
> Loss of immune regulation
> Increased and defective apoptosis
> Necrotic cells release nuclear material which act as potential auto antigens
> Autoimmnity probably results from extended exposure to nuclear and intracellular auto-antigens
> B & T cells are stimulated.
> Autoantibodies are produced.
SLIC Classification Criteria
Criteria for Systemic Lupus Erythematosus
Clinical Criteria
Immunologic criteria
SLE - constitutional symptoms
> Fever > Malaise > Poor appetite > Weight loss > Fatigue
Mucocutaneous features of SLE
> Photosensitivity
Malar rash
– may or may not be associated with sun exposure
– 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
> Erosive arthritis
> Myopathy - weakness, myalgia & myositis
SLE - serositis
> Pericarditis
Pleurisy
Pleural effusion
Pericardial effusion
SLE - renal features
> Proteinuria of >500mg in 24 hours
> Red cell casts
SLE - neurological features
> Depression/psychosis
- not always related to disease activity
> Migranous headache
> Seizures
> Cranial or peripheral neuropathy
> Mononeuritis multiplex
SLE - Haematological features
> Lymphadenopathy
~25% of all patients during their course of illness
> Leucopenia
> Lymphopenia
> Haemolytic anaemia
> Thrombocytopenia
Anti phospholipid antibodysyndrome
> Venous and arterial thrombosis
> Recurrent miscarriage
> Livedo reticular (mottled, reticulated skin pattern)
> Association with other autoimmune conditions especially SLE
> Thrombocytopoenia
> Prolonged APTT (activated partial thromboplastin time)
> Can be primary or secondary
suspect when:
occurrence of one or more otherwise unexplained venous or arterial events, esp. in young patients
Foetal death after 10 weeks, premature birth due to severe pre-eclampsia or placental insufficiency/multiple embryonic losses
Otherwise unexplained thrombocytopenia or prolonged APTT
SLE susceptibility to infection
> Intrinsic factors
- Low complements
- Impaired cell mediated immunity
- Defective phagocytosis
- Poor antibody response to certain antigens
> Extrinsic factors
- steroids
- other immunosuppressive drugs
- nephrotic syndrome
SLE - investigation
> Confirm/establish diagnosis
> Determine degree of organ involvement
> Anti nuclear antibody (positive in titre of 1:160 or greater in almost all SLE patients) — ANA
> If other antinuclear antibodies are positive –> take ANA test seriously.
- anti dsDNA
- anti Sm
- Anti - Ro
- Anti RNP
> anti dsDNA
– anti double stranded DNA antibody
- highly specific for SLE
- titre correlates with overall disease activity
> Anti-phospholipi antibodies
- anti-cardiolipin antibody
- lupus anticoagulant
- antibeta 2 glycoprotein
– must be positive on 2 occasions 12 weeks apart
Anti phospholipids antibodies should be positive on how many occasions?
2 occasions 12 weeks apart.
IgM or IgG anticardiolipin abs
Lupus anticoagulant
IgM or IgG beta 2 glycoprotein
Serum C3/C4 levels and SLE
These levels NEGATIVELY correlate with disease activity
SLE - management & Drug treatment
> Counselling
Regular monitoring
Avoid excessive sun exposure
Pregnancy issues
Drug Treatment
> NSAIDs and simple analgesia
> Anti malarias, hydroxxychloroquine
- useful for arthritis, cutaneous manifestations and constitutional symptoms
- may reduce systemic complications
> Steroids
- side effects
- variable doses for different manifestations
> Immunosuppressants
- Azathioprine
- Cyclophosphamide
- Methotrexate
- Mycophenolate mofetil
> Biological agents
- anti CD20 (Rituximab)
- anti Blys (belimumab)
SLE - steroid doses
small doses (prednisolone <15 mg/d) for skin rashes, arthritis and serositis
moderate doses (0.5 mg/kg/d) for resistant serositis, haematologic abnormalities and class V GN
high doses (1mg/kg/d or IV) for severe/resistant haematologic changes, diffuse GN and major organ involvement
SLE Spectrum of disease treatmnet
MILD
- Hydroxychloroquine
- topical steroids
- NSAIDs
MODERATE
- oral steroids
- azathioprine
- methotrexate
SEVERE
- IV steroids
- Cyclophosphamide
- Rituximab
Wire loop lesion in the kidneys is indicative of?
Lupus nephritis
Anti-phospholipid antibody syndrome - treatment
Lifelong anticoagulation for thrombosis
Aspirin/heparin to prevent pregnancy complications
Hydroxychloroquine
Sjögren’s Syndrome
> Chronic autoimmune inflammatory disorder
> Diminished lacrimal and salivary gland function resulting in dry eyes, dry mouth
> Primary or secondary
> Women in 50s/60s
> Extra glandular involvement
Sjögren’s syndrome - symptoms
> Dry eyes, gritty feeling
> Dry mouth
> Dry throat
> Vaginal dryness
> Bilateral parotid gland enlargement
> Joint pains
> Fatigue
> Unexplained increase in dental caries
Sjögrens syndrome - antibodies
Anti-Ro
Anti-La
High IgG, ESR and rheumatoid factor
Other tests:
- salivary gland US
- Labial gland biopsy
Sjögren’s syndrome - treatment
> Artificial tear supplements
> Ciclosporin eye drops
> Punctual plugs
> Saliva supplements
> Pilocarpine
> Hydroxychloroquine
> Immunosuppression w/ methotrexate, leflunomide, B cell depleters — if major organ involvement
Diffuse Cutaneous Systemic Sclerosis
Vascular endothelial changes
Fibrosis
Skin involvement proximal to forearms & involving torso
Rapid skin changes
Early organ involvement
Interstitial lung disease more common than pulmonary hypertension
Renal crisis can occur
Anti-topoisomerase or anti SCL-70 or anti RNA III polymerase antibody
Anti-topoisomerase or anti SCL-70 or anti RNA III polymerase antibody are associated with?
Diffuse cutaneous systemic sclerosis
systemic scelrosis
Limited SSc
Skin involvement distal to elbows and NOT involving torso
Used to be called CREST (Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasia)
Raynaud’s seen in 90% of patients
Pulmonary hypertension is a common complication
Small intestinal bacterial overgrowth
Anti centromere antibody
Sclerodactyly
Localised thickening and tightening of the skin of the fingers/toes
