Connective Tissue Diseases 09/10/18 Flashcards
Name some connective tissue diseases
SLE Sjogren's syndrome Systemic sclerosis Dermatomyositis Polymositis Mixed connective tissue disease Anti-phospholipid syndrome
What are connective tissue diseases?
NOT diseases of the connective tissue
Spontaneous over activity of the immune system
Specific auto-antibodies
Evolve over years
What is Systemic Lupus Erythematosus (SLE)?
Systemic autoimmune disease
Where does SLE affect?
Any part of the body
What is the pathogenesis of SLE?
The immune system attacks the bodys cells and tissue resulting in inflammation and tissue damage
Antibody-immune complexes precipitate and cause a further immune response
Loss of immune regulation
Increased and defective apoptosis
Necrotic cells act as auto-antigens
Autoimmunity
Who gets SLE?
Females more than males
Asians, Afro-americans and afro-caribbeans
What is the pathogenesis of renal disease from SLE?
Deposition of immune complexes in mesangium
Complexes of nuclear antigens and anti-nuclear antibodies
Complexes form in circulation then are deposited
Activate complement which attracts leucocytes which release cytokines
Cytokine release perpetuates inflammation which causes necrosis and scarring
What are the clinical criteria for SLE?
Acute cutaneous lupus Chronic cutaneous lupus Oral or nasal ulcers Non-scarring alopecia Arthritis Serositis Renal Neurological Haemolytic anaemia Leukopenia Thrombocytopaenia
What are the immunologicall criteria for SLE?
ANA Anti-DNA Anti-SM Antiphospholipid Ab Low complement Coomb's test
What systems feature in the SLE classification criteria/
Mucocutaneous Musculoskeletal Serositis Renal Neurological Haematological
What are continuous symptoms of SLE?
Fever Malaise Poor appetite Weight loss Fatigue
What are some mucocutaneous features of SLE?
Photosensitivity Malar rash Discoid Lupus Subacture cutaneous lupus Mouth ulcers Alopecia
What are some musculoskeletal features of SLE?
Non-deforming polyarthritis/polyarthralgia Deforming arthropathy Myopathy Weakness Myalgia Myositis
What is serositis?
Inflammation of the serous membrane
What does serositis cause?
Pericarditis
Pleurisy
Pleural effusion
Pericardial effusion
What are renal features of SLE?
Proteinuria of >500mg in 24 hours
Red cell casts
What are the neurological factors of SLE?
Depression/Psychosis Migranous headaches Seizures Cranial or peripheral neuropathy Mononeuritis multiplex
What are haematological features of SLE?
Lymphadenopathy Leucopenia Lymphopenia Haemolytic anaemia Thrombocytopenia
What is anti-phospholipid syndrome?
Venous and arterial thrombosis Recurrent misscarriage Livido reticularis Association with SLE Thrombocytopaenia Prolonged APTT
What intrinsic factors increase susceptibility to infection?
Low complement
Impaired cell mediated immunity
Defective phagocytosis
Poor antibody response to antigens
What extrinsic factors increase suscptibility to infection?
Steroids
Immunosuppression
Nephrotic syndrome
How sensitive is ANA in lupus?
98% of lupus patients
20% of normal
When should +ve ANA be taken seriously
\+Ve: Anti-DsDNA Anti-SM Anti-Ro Anti-RNP
How sensitive is anti dsDNA in lupus?
60%
Highly specific
Anti-ENA?
Anti-Ro (60%) Usually associated with anti-La Cutaneous manifestations Secondary Sjogren’s features Congenital heart block and neonatal LE
What must be done once diagnosis is established?
Screen for organ involvement
What are some investigations for SLE?
CXR Pulmonary function tests CT chest Urine protein quantifications Renal biopsy Echocardiogram Nerve conduction studies MRI brain
How is SLE activity monitered?
Clinical assessment
Anti-dsDNA level positively correlates with activity
Urine examination - protein, cells and casts
FBC
Blood biochemistry
What is the general management for lupus?
Counselling
Monitoring
Avoid excess sun
Pregnancy issues?
What is the drug treatment for lupus?
NSAIDs and analgesia
Anti-malarials - hydroxychloroquinine
Are steroids used for Lupus?
Useful but associated with numerous side effects
Variable doses
Name 4 immunosuppressants
Azathiprine
Cyclophosphamide
Methotrexate
Mycopheolate mofetil
What are 3 side effects to immunosuppresion?
Bone marrow suppression
Increased susceptibility to infection
Teratogenic
Name 2 biologics
Anti-CD20 - Rituximab
Anti-Blys (Belimumab)
What is the treatment of mild lupus?
HCQ
Topical steroids
NSAIDs
What is the treatment for moderate lupus?
Oral steroids
Azathioprine
Methotrexate
What is the treatment for sever lupus?
IV steroids
Cyclophophamide
Rituximab
Belimumab
