Connective tissue diseases Flashcards
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
Immunological factors
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)
Photosensitivity
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
Pericarditis
Pleurisy
Pleural and pericardial effusions
Renal features of SLE
Proteinurea of greater than 500mg in 24 hours.
Red cell cast
Neurological features of SLE
Depression/ psychosis Migrainous headache Siezures Cranial or peripheral neuropathy Mononeuritis multiplex- form of damage to one or more peripheral nerves
Haematological features of SLE
Lymphadenopathy
Leucopenia- reduction in number of white cells
Lymphopenia- reduction in number of lymphocytes
Haemolytic anaemia- reduction in RBC
Thrombocytopenia
Antiphospholipid syndrome
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
- defective phagocytosis
- poor antibody response to certain antigens
Extrinsic factors-
steroids
Other immunosuppresive drugs
Investigations into SLE
Antinuclear antibodies
Anti-double stranded DNA
Anti- ENA
Antiphospholipid antibodies
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- ENA
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
Antiphospholipid antibodies
Anti-cardiolipin antibodies
Lupus anticoagulant
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
CXR Pulmonary function tests CT chest Urine protein quantification Renal biopsy Echocardiogram Nerve conduction studies MRI brain
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.
Regular monitoring
Avoiding excessive sunlight exposure
Pregnancy issues
Drug treatment for SLE
NSAIDS and simple analgesia Steroids Antimalarials Immunosupressive therapy 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
Azathioprine
Cyclophosphamide
Methotrexate
Mycophenolate mofetil
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
Anti-CD20 (Rituximab)
Anti-Blys (Belimumab)
Treatment of mild SLE
Topical steroids, NSAIDs and HQC
Treatment of moderate SLE
Oral steroids
Azathioprine
Methotrexate
Treatment of severe SLE
IV steroids
Cyclophosphamide
Rituximab
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 AND/OR Lupus anticoagulant activity AND/OR Anti- beta2 glycoprotein
Affects of antiphospholipid syndrome on pregnant women?
Responsible for 15% of recurrent foetal loss
Or eclampsia
Or placental insufficiency
Other features of antiphospholipid syndrome
Superficial thrombophlebitis and livedo reticularis
Mild/moderate thrombocytopenia (deficiency of platelets)
Neurological features – migraine, transverse myelitis
Libman-Sacks endocarditis
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.
Sjogrens syndrome
Autoimmune condition
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
Fatigue Arthralgia Raynauds Salivary swelling Lymphadenopathy Skin and vaginal dryness Interstitial lung disease Neuropathy 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 Saliva replacement Pilocarpine Hydroxychloroquine Steroids and immunosuppression Attention to cardiovascular risk factors
Systemic sclerosis
Autoimmune
Vasculopathy (Raynaud’s Syndrome)
Inflammation
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
Pancreatic insufficiency
Rectal hypomobility
Respiratory-
Interstitial lung disease
Pulmonary hypertension
Chest wall restriction
Renal
Hypertensive renal crisis
Ischaemic
Cardiovascular
Raynaud’s with digital ulceration
Atherosclerotic disease
Hypertensive cardiomyopathy
Treatments of systemic sclerosis
Calcium channel blockers Prostacyclin (Iloprost) ACE inhibitors Prednisolone Immunosuppression Bosentan, Sildenafil