Flashcards in Connective tissue diseases Deck (46):
What is systemic lupus erythamatous?
Systemic autoimmune disease where the immune system attacks the bodies own cells and tissues resulting in inflammation.
The antibody-immune complexes precipitate and cause a further immune response.
Epidemiology of SLE
Occurs in females more than males.
Afro-caribbeans more than europeans etc.
What causes SLE?
Combination of genetic factors- increased incident among relatives
Hormonal factors-incidence increased with those with higher oestrogen
Environmental factors-virus's, UV light, silica dust
Pathogenesis of SLE
Primarily due to loss of immune regulation. Increased (and defective) apoptosis is caused. The necrotic cells then release nuclear material that can act as auto-antigens.
Autoimmunity probably results from extended exposure to these.
B and T cells are stimulated
Autoantibodies are produced.
Renal disease associated with SLE pathogenesis.
Immune complexes deposit in the mesangium (structure associated with capillaries in the glomerulus). Complexes consist of nuclear antigens and anti-nuclear antibodies. Complexes then form in the circulation then they are deposited. This activates complement which attracts leukocytes (WBC) and they release cytokines.
Cytokine release perpetuates inflammation and eventually can cause necrosis and scarring.
Mucocutaneous features of SLE (region of the body where mucus transitions to skin)
Malar rash (that may or may not be associated with sun exposure)- however spares the nasolabial folds.
Discoid lupus erythamatous (may scar)- disc like plaques on scalp
Subacute cutaneous lupus (skin plaques
Painless mouth ulcers
Alopecia (non scarring)
Musculoskeletal features of SLE
Non-deforming polyarthritis/polyarthralgia_ has a rheumatoid arthritis distribution but no radiological changes.
Deforming arthropathy (deforming disease of the joint)
Erosive arthritis- rare
Myopathy- weakness, myalgia, myositis
Serositis (inflammation of the serous membrane) features of SLE
Pleural and pericardial effusions
Renal features of SLE
Proteinurea of greater than 500mg in 24 hours.
Red cell cast
Neurological features of SLE
Cranial or peripheral neuropathy
Mononeuritis multiplex- form of damage to one or more peripheral nerves
Haematological features of SLE
Leucopenia- reduction in number of white cells
Lymphopenia- reduction in number of lymphocytes
Haemolytic anaemia- reduction in RBC
Disorder of the immune system that causes blood clots.
Venous and arterial thrombosis
Livido reticularis- lace like purplish discolouration of the skin
Associated with other autoimmune conditions especially SLE
Thrombocytopenia- deficiency of platelets in the blood.
Susceptibility to infection in relation to SLE
Intrinsic factors- low complements
-Impaired cell mediated immunity
-poor antibody response to certain antigens
Other immunosuppresive drugs
Investigations into SLE
Anti-double stranded DNA
Antinuclear antibodies (ANA)
95% positive in SLE patients
Also found in conditions such as RA, HIV and hep B
When should a positive ANA test be taken seriously?
When other antinuclear antibodies are also positive such as Anti-dsDNA, Anti-Sm, Anti-Ro, Anti-RNP
When the patient presents with CTD features
Anti-double stranded DNA
Occurs in approximately 60% of patients with SLE
Highly specific to SLA
Titre correlates with overall disease activity
May be associated with lupus nephritis
Anti- extractable nuclear antigens- group of over 100 types of which
-Anti-Ro makes up- 60%
-Usually associated with anti- La
Associated with cutaneous manifestations
Secondary sjogens features
Congenital heart block and neonatal LE
Anti-Sm (10-20%) is highly specific-probably association with neurological involvement
Anti-RNP (30%)- overlap features- raynauds phenomonom, sclerodermatous skin lesions, low grade myositis
Anti- beta 2 cytokine
Must be positive on two occasions 12 weeks apart.
Once a diagnosis of SLE is established, what should you do?
Screen for organ involvement
Investigations of SLE for organ involvement
Pulmonary function tests
Urine protein quantification
Nerve conduction studies
How do you monitor SLE activity?
Thorough clinical examination and BP
Anti-dsDNA correlates with disease intensity
C3/C4 levels negatively correlate
Urine examination including protein cells and casts
FBC and blood biochemistry
General management of SLE
Counselling family, patient etc.
Avoiding excessive sunlight exposure
Drug treatment for SLE
NSAIDS and simple analgesia
Biologics (in severe disease)
Anti-malarials in the treatment of SLE
Useful for arthritis, cutaneous manifestations and constitutional symptoms
May reduce systemic complications
Steroids in the treatment of SLE
Useful but may cause unwanted side-effects
Various doses are needed for different manifestations.
Low dose e.g. prednisolone (<15mg/day) for skin rashes, arthritis and serositis
Medium dose e.g. (0.5mg per kg/d) for resistant serositis, haemotological abnormalities etc.
High dose (1mg per kg/d) for severe haematological changes, major organ damage.
Immunosupressive therapy for treatment of SLE
Side effects of immunosupressive therapy for treatment of SLE
Can cause bone marrow suppression
Can cause increased susceptibility to infection
Potentially teratogenic (disturb the development of the embryo)
Biologics in the treatment of SLE
Treatment of mild SLE
Topical steroids, NSAIDs and HQC
Treatment of moderate SLE
Treatment of severe SLE
Define a connective tissue disease
Characterised by the presence of spontaneous overactivity of the immune system.
Often associated with specific auto-antibodies which can help define the condition.
How do connective tissue diseases related to systemic lupus erythamatous
They can all be features of SLE. E.g. antiphospholipid syndrome could manifest on its own or could be part of SLE.
Antiphospholipid syndrome diagnosis
Positive anticardiolipin antibodies
Lupus anticoagulant activity
Anti- beta2 glycoprotein
Affects of antiphospholipid syndrome on pregnant women?
Responsible for 15% of recurrent foetal loss
Or placental insufficiency
Other features of antiphospholipid syndrome
Superficial thrombophlebitis and livedo reticularis
Mild/moderate thrombocytopenia (deficiency of platelets)
Neurological features – migraine, transverse myelitis
Catastrophic anti-phospholipid syndrome
Treatment of antiphospholipid syndrome
For the thrombosis- life long anticoagulation
Pregnancy loss- aspirin and heparin during pregnancy to prevent eclampsia.
Attention to vascular risk factors.
Lymphocyte infiltration of exocrine glands causing xerostomia (stress in the mouth caused by change in composition of saliva) and keratoconjunctivitis sicca (dryness of the conjunctiva)
May be primary or secondary to other autoimmune conditions
Classification of primary sjogrens syndrome
Subjective ocular symptoms(daily for > 3 months)
Subjective oral symptoms (daily for > 3 months)
Objective evidence of ocular dryness
Objective evidence of salivary gland involvement
Immunology – either Ro, La or both
Biopsy evidence of lymphocytic infiltrate
Need 4 of 6 and must include either immunology or biopsy evidence
Other manifestations of sjogrens syndrome
Skin and vaginal dryness
Interstitial lung disease
Lymphoma (x40 risk)
Renal tubular acidosis
Neonatal complete heart block (anti-Ro)
Primary sjogrens disease
Prevalence of 1-3%
Most people remain undiagnosed
Serious complications are very rare.
Treatment of sjogrens disease
Eye drops, punctal plugs
Steroids and immunosuppression
Attention to cardiovascular risk factors
Vasculopathy (Raynaud’s Syndrome)
Fibrosis – excess deposition of collagen in skin and internal organs
CREST-Calconosis, Raynaud’s, Esophageal dysmotilty, Sclerodactyly, Telangiectasia. Can also feature pulmonary hypertension in ~30%
Organ manifestations of systemic sclerosis
GI- Oesophageal hypomobility
Small bowel hypomobility, bacterial overgrowth
Interstitial lung disease
Chest wall restriction
Hypertensive renal crisis
Raynaud’s with digital ulceration