Connective tissue disorders Flashcards
(41 cards)
What is SLE?
AKA Lupus. Multi-system inflammatory autoimmune disorder.
What is the aetiology of SLE? (x3)
- Unknown
- Genetic: HLA clustering and more common in those with complement deficiencies
- Hormonal: female preponderance
- Exogenous factors: drugs such as hydralazine and procainamide that can cause a reversible SLE-like disorder
What is the pathophysiology of SLE?
SLE is characterised by autoimmune IgG antibodies to ds-DNA and nuclear proteins. This leads to tissue damage as a result of vascular immune complex deposition.
What is the epidemiology of SLE: Age? Ethnicity? Gender?
More common in your (20-40 years), Afro-Caribbean and Chinese. Nine times more common in females.
!!! What are the signs and symptoms of SLE? (x10)
- SOAP BRAIN MD can be used to remember the symptoms highlighted
- GENERAL: fever, fatigue, weight loss, lymphadenopathy
- RAYNAUD’S PHENOMENON
- ORAL ULCERATION
- SKIN: malar rash, discoid lupus (red and scaly patches, often on face, which later heal with scarring and pigmentation), photosensitive rash, hair loss, vasculitis (digital infarcts), urticaria, purpura, bullae (fluid-filled sac), livedo reticularis (blotchy red/blue skin appearance from cutaneous thrombosis), Rowell’s syndrome (atypical erythema multiforme-like rash)
- MUSCULOSKELETAL: non-erosive arthritis, tendonitis, myopathy, avascular necrosis of femur head
- HAEMATOLOGICAL CYTOPENIAS: haemolytic anaemia, leukopenia, thrombocytopenia
- HEART: pericarditis, myocarditis, Libman-Sacks endocarditis (non-infective mitral valve disease), aortic valve lesions
- LUNG: pleuritis, pleural effusions, basal atelectasis, restrictive picture
- NEUROLOGICAL: headache, stroke, CN palsies, peripheral neuropathy, seizures
- RENAL: glomerulonephritis
Note about SLE and serous tissue?
SLE causes serositis – inflammation of serous tissues of the body (lining of body cavities that secretes serum for lubrication). For example, pleuritis, pericarditis.
What are the investigations for SLE? (x4 +3)
- BLOOD: cytopenias, U&Es (renal manifestations), high CRP (and ESR),
- AUTOANTIBODIES: next flashcard
- URINE: haematuria, proteinuria, and microscopy for CASTS
- X-RAYS: CXR for effusions, infiltrates and cardiomegaly, joint x-rays show inflammation but no erosion
- There are loads: Renal biopsy if glomerulonephritis suspected, MRI scan/LP for CNS manifestations, ECG for heart manifestations
What are the autoantibodies in SLE? (x7 +2)
- ANA: 100% of cases
- Anti-dsDNA: 60% of cases
- RF: 30-50% of cases
- Anti-RNP: 30% of cases
- Anti-Sm: 30% of cases
- Anti-Ro: an ANA in 30% of cases and found in Sjogren’s syndrome
- Anti-La: an ANA in 15% of cases and found in Sjogren’s syndrome
- Positive anti-phospholipid antibodies
- Positive Coomb’s test
How is SLE diagnosed?
Positive ANA when it occurs together with the ACR 1997 revised criteria for the classification of SLE.
What is Sjogren’s syndrome?
Characterised by inflammation and destruction of exocrine glands (usually salivary and lacrimal glands.
What is the aetiology of Sjogren’s syndrome? (x2)
- PRIMARY: unknown but associated with HLA-B8, HLA-A1, and HLA-DR3
- SECONDARY: RA, scleroderma, SLE, organ-specific autoimmune diseases such as hepatitis, thyroid disease and myasthenia gravis
What is the epidemiology of Sjogren’s syndrome: Age? Gender?
Bimodal age distribution: post-menarche in 20-30s and post-menopause in 50s. 9x more common in females.
What is the pathophysiology of Sjogren’s syndrome?
Hyper-reactive B cells infiltrate into salivary and lacrimal glands. Infiltration leads to cytokine secretion, production of autoantibodies, and secretion of metalloproteinases
What are the signs and symptoms of Sjogren’s syndrome? (x6 and x5 extra-exocrine)
- KERATOCONJUNCTIVITIS SICCA: dry eyes with secondary conjunctivitis
- XEROSTOMIA: dry mouth, with secondary dysphagia and increased incidence of oral fungal/bacterial infections
- Parotid/salivary gland enlargement
- DRY UPPER AIRWAYS: dry cough, recurrent sinusitis
- DRY VAGINA: may cause dyspareunia (painful sex)
- Reduced GU mucus secretion causing symptoms of reflux, gastritis and constipation
- NB: that dry mucous membranes is also a sign of systemic sclerosis, but not the chief symptom unlike in Sjogren’s syndrome
- GENERAL: fatigue, fever, depression
- VASCULITIS
- Arthralgias and myalgias
- Interstitial nephritis
- Lymphoma
What are the investigations for Sjogren’s syndrome? (x6)
- SCHIRMER’S TEST: filter paper strip places under eyelid and positive if less than 5 mm of the strip is wet in 5 mins.
- SIALOMETRY: measures salivary flow. Can also use PAROTID SIALOGRAPHY (x-ray after radio-opaque contrast medium into duct system; shows retention and abnormal duct anatomy from enlargement), and SALIVARY GLAND SCINTIGRAPHY (radioactive measure of salivary flow)
- AUTOANTIBODIES: next flashcard
- BLOOD: raised ESR, raised amylase if salivary glands involved
- LISSAMINE GREEN/FLUORSCEIN STAINS: show punctate or filamentary keratitis (clumps of mucus on the cornea), and corneal abrasion/ulceration, respectively. Both signs of keratoconjunctivitis sicca
- SALIVARY GLAND BIOPSY: mononuclear (B and T cell) infiltrates in perivascular and periductal areas
What are the auto-antibodies for Sjogren’s syndrome? (x5)
Anti-Ro (SS-A) and anti-La (SS-B). Not specific to Sjogren’s as found in other conditions such as SLE. ANA, anti-thyroglobulin and RF also present in many.
What is systemic sclerosis?
Rare connective tissue SPECTRUM disease characterised by widespread small blood vessel damage and fibrosis in skin and internal organs. AKA scleroderma.
What is the aetiology of systemic sclerosis?
Unknown. Genetic and environmental factors (silica dust, epoxy resins, solvents)
What is the pathophysiology of systemic sclerosis? (x3)
Characterised by three disease processes: (1) vasculopathy associated with endothelial cell damage, platelet activation, myointimal cell proliferation and narrowing of blood vessels; (2) fibrosis including deposition of collagen in the dermis and organs; (3) immune system activation (humoral and cell-mediated). Activated T cells produce pro-fibrotic cytokines.
What are the types of systemic sclerosis? (x3)
- LIMITED CUTANEOUS SS: previously known as CREST (calcinosis (calcium deposits in soft tissue), Raynaud’s, oesophageal dysmotility, sclerodactyly (skin fibrosis of the fingers), telangiectasia). Skin changes are distal to the elbow and knees
- DIFFUSE CUTANEOUS SS: Raynaud’s phenomenon followed by skin changes with truncal involvement, tendon friction and joint contractures, early lung, heart, GI and renal disease, nail-fold capillary dilation. Skin changes affects the trunk, and both proximal and distal to elbow and knees
- SCLERODERMA SINE SCLERODERMA: internal organ disease with no skin changes
What is the epidemiology of systemic sclerosis: Age? Gender?
Age of onset is 30-60 years. Three times more common in females.
What are the SKIN signs and symptoms of systemic sclerosis? (x7)
- Raynaud’s phenomenon.
- Hands are initially oedematous, painful
- Later sclerodactyly with changes in pigmentation, digital pits and finger ulcers (ischaemia).
- May also see calcinosis present as firm masses on fingers or forearms with chalky overlying skin
- Nail-fold capillary dilation.
- Telangiectasia (widened venules leading to thread-like red lines on skin)
- Face has microstomia
What are the other signs and symptoms of systemic sclerosis? (x9 (x6 gut))
- LUNG: fibrosis leading to pulmonary HTN
- HEART: pericarditis, pericardial effusion, myocardial fibrosis
- GI: oesophageal dysmotility (dysphagia), reflux oesophagitis, watermelon stomach (telangiectasia of lining leading to bleeding and watermelon appearance in endoscopy), pseudo-obstruction, constipation from gut hypomotility, anal incontinence
- RENAL: hypertensive RENAL CRISIS and CKD
- NEUROMUSCULAR: trigeminal neuralgia, wasting
- Tendon friction rub
- Dyspareunia – dry mucous membranes
- Hypothyroidism
- Impotence
What is Raynaud’s syndrome?
Exaggerated response to cold temperature or emotional stress (vasoconstriction of digital arteries and cutaneous arterioles). Presents with colour changes of the digits: white > blue (cyanosis) > crimson (reactive hyperaemia).
