MSD 2.85-92 Flashcards
What type of AI disease are CTD?
Systemic! Because involve nuclear Ag found ubiquitously
How does CTD start?
as uCTD, then usually becomes one of: SLE, DM/PM, Sjogrnes, SSc, MCTD.
Symptoms of SLE?
- Lungs: tachypnoea, cough, pleural inflammation and effusion, PE
- Skin: photosensitive rash, butterfly rash over cheeks (sparing nasolabial folds), livedo, discoid, alopecia. SICCA, mucosal ulcers.
- Systemic inc. lymphadenopathy, anaemia, thrombocytopenia, leukopenia
- CVD: Raynaud’s, pericarditis, vasculitis, thrombosis (particularly if have APS)
- Renal: lupus nephritis, proteinuria, haematuria
- CNS: neuro disorders, migrainous headaches, seizures, aseptic meningitis
- MSK (arthralgia, arthritis, myositis)
- Reproductive: menorrhagia/amenorrhoea, prematurity, stillbith, recurrent miscarriage. Lupus more likely to flare during pregnancy.
Risk factors for SLE?
F, child-bearing age, FHx, genes (HLA-DR2/3), Afro Caribbean>Asian>Caucasian, drug-induced
Key pathophysiology?
Defective clearance of apoptotic cells exposes nuclear antigens to IS; following DNA damage, get autoantibodies to nuclear proteins, forming immune complexes and recruiting complement to damage tissue, releasing more Ag. Autoantibodies opsonise DS DNA.
Natural history of SLE?
Preclinical; autoantibodies form. Clinical get inflammation and involvement of first organs. Then get flares, more organs involved, damage. Eventually to disease and treatment get irreversible organ damage, malignancy, atherosclerosis, diabetes, osteoporosis. Incurable.
Joints affected in SLE?
Typically small joints of hands and feet. Non-erosive
LE cells?
(Lupus erythematous cell) are PMNs or macrophages that have ingested another cells nuclear material; classically seen in SLE.
VDRL test in SLE?
Get false positive
ANA patterns?
Homogenous, nucleolar, speckled and centromere-B; associated with different ANAs and therefore different CTD.
Use of ANA?
Autoantibodies; sensitive but not specific for SLE; umbrella term which can be differentiated into ENAs. Presence detected with ELISA. Increased frequency with age, so titre is important as not all ANA = AI. Get +ve ANA then do ENA panel.
dsDNA? And its signifiance?
Fairly specific for SLE; low levels in RA/MCTD/AIH. Important in SLE because associated with risk of ESRD in SLE.
Homogenous ANA?
Associated with dsDNA staining and therefore SLE
Sm (smith)?
Very specific for SLE but no very sensitive
Ro/La? And significance of Ro?
Associated with Sjogrens and SLE (particularly with skin disease); get speckled ANA. Ro can cross placenta and cause congenital heart block
Anti-RNP?
Associated with SLE and MCTD. Nucleolar ANA.
Antiphospholipid antibodies?
Anti-cardiolipin, lupus anticoagulant (DRVVT), anti-B2 glycoprotein. Prothrombotic. Need two +ves 3 months apart. Can be used to support SLE diagnosis too.
APLS?
Livedo rash, CNS disease, obstetric problems, worse prognosis in LN.
Antibodies for drug-induced SLE?
Anti-histone antibodies!
Drugs causing drug-induced SLE?
Minocyclie, procainamide, sulfasalazine, AEDs, anti-TNFa (infliximab) for RA, Crohns, eye disease.
Why are cell counts low in SLE?
Ab mediated; get haemolysis etc. (direct Coombes test) Platelets low due to this and APLS Abs.
Differentiating SLE flare and infection?
Neutrophils normal in SLE! And discordant rise in ESR
ESR and CRP in SLE?
CRP often slightly raised; ESR often very high.
SLICC criteria SLE?
- Biopsy proven lupus nephritis and ANA/dsDNA
- Or 4 criteria, at least 1 immunological. Clinical = acute/chronic cutaneous LE, oral ulcer, alopecia, synovitis, serositis, renal, neurlogi, haemolytic anaemia, lecopenia/lymphopenia, thrombocytopenia.
Immune = ANA, dsDNA, Anti Sm, APLS Abs, Low complement, direct Coombs.
Why do you need low threshold for infection in SLE?
Drugs may mask immune response
Four types of epidermal rashes?
Eczematous, psoriasiform, lichenoid, vesiculobullous. Lichenoid seen in SLE. Barrier disrupted so either wet or dry
Eczematous rash?
Gaps in epidermis; spongiosis. Fluid comes up from dermis, get weeping, blisters and dry flakes. Variable blisters suggests eczema.
Psoriasiform rash?
Skin proliferates and thickens; get scale
Lichenoid rash?
Epidermal. More serious/AI link. May get in SLE with discoid rash. Get purple, interface dermatitis.
Vesiculobullous rash?
Destruction of proteins holding dermis and epidermis; epidermis lifts off. Can be due to external (burns) or internal (pemphigoid, AI).
Dermal rashes?
Get raised lesion but skin smooth. Granulomatous, vasculopathic, tissue deposition.
Granulomatous rash?
Ring-like; histiocytes involved. Purple-brown. Seen in Tb and sarcoid (lupus pernio), and granuloma annulare (reaction to collagen).
Vasculopathic rash?
Death/blockage or leakage of blood vessels (e.g. leakage could be urticaria. Linked to SLE/CT ie IC can block vessels; red cells leak into dermis. Palpable purpura.
What can infiltrate the skin?
Extracellular substances, or inflammatory cells (eosinophils, neutrophils, lymphocytes)
Anti-Scl70?
Diffuse systemic sclerosis. (aka anti-topoisomerase)
RhF?
RA
Anti-Ro/La?
Sjogrens, SLE.
HLA-B27?
Ank spond and other seronegative spondlyoarthropathies
Anti-Jo1?
Polymyositis
MPO/P-ANCA?
EGPA and MPA (AND PSC/UC)!!!
PR3/C-ANCA?
GPA
Jaccoud’s arthropathy?
Deformity of hands post SLE arthritis
Contraception in SLE?
Progesterone only or barrier; COC pro-thrombotic.
Monitoring lupus activity?
DSDNA, ESR, C3 and C4, BP, urinalysis, basic bloods
Differentials for LRT problems in SLE patients?
Pneumonia (IC), PE (hypercoagulable), pleuritis, pulmonary oedema secondary to renal failure
Lupus nephritis?
Can cause ESRD.
Chronic pain syndromes?
Multiple hyperalgesic sites, often associated with other physical and psych symptoms, no identifiable organic cause. Fatigue prominent, poor sleep. Cognitive problems! Plethora of somatic symptoms
Conditions associated with fibromyalgia?
TMJ, Sjogrens, anxiety and depression, headaches and migraines, panic disoders, IBS
Risk factors for fibromyalgia?
Female, 30-50, previous physical trauma, previous viral infection, psychological stress
FIBRO?
Fatigue, insomnia, blues, rigidity, ow (widespread pain)
Common features in fibromyalgia?
Often waited years for diagnosis, may feel that have been passed around, frustration at negative investigation, underlying mental health and social issues, limited evidence based treatments. Good sleep hygeine key!
Yellow flags in FM?
Inappropriate treatment expections, sickness behaviour, belief that pain and activity are always harmful, withdrawal, emotional problems, problems related to time off work
Two causes of vasculitis?
Bacteria i.e. mycotic, or AI.
How can LVV give organ-specific disease?
If origin of visceral vessels is affected (i.e. where SMA joins aorta)
Most common vasculitis in UK?
HSP including paeds; GCA in adults
GCA basics?
> 50, usually 70s. F:M 2:1. Sight loss in 20%. Northern European highest risk.
Takayasus basics?
Rare in UK, commoner in Japan. Younger women; 5-40, 9:1.
Cranial GCA symptoms?
Headache; severe, debilitating, there all day, analgesia not helpful. Scalp tenderness, jaw claudication, neck ache (not with movement) [vertebral artery involvement], PMR (limb girdle pain, no weakness, worse in morning), VISUAL SYMPTOMS. May have isolated occipital headache.
Systemic GCA symptoms?
Constituional, weight loss, fever, limb claudication (SCA), abdominal pain (SMA/IMA), HTN. More likely to be male with existing PVD.
Neuro exam in PMR?
Should be normal
Cranial or systemic GCA more problematic?
Systemic more likely to be insidious and then present with visual involvement, paradoxically.
Signs of GCA?
Thickened temporal artery, visual involvement
Managing GCA?
Any visual involvement = refer to opthalmology. Otherwise, urgent medical review and start oral steroids.
Optic presentations of GCA?
Amaurosis fugax, vision loss. Usually due to occlusion of posterior ciliary arteries (arteritic anterior ischaemic optic neuropathy). May see reduced VA, RAPD, reduced colour vision and visual field defects.
Cranial nerve palsies in GCA?
Compromised supply to extraocular muscles or CNs; get opthalmoplegia, + anisocoria and ptosis if 3rd nerve involved. Can just be transient diplopia!
Opthalmic complications of systemic steroids?
Raised IOP (significant if have/at risk for glaucoma, cataracts, worsening of infection if have existing keratitis, worsening of diabetic eye disease
GCA investigations?
ESR >50, CRP >20. Normocytic anaemia, raised platelets, neutrophilia, elevated ALP, U&E usually normal tho renal impairment possible. TA USS and biopsy.
Further useful IX in GCA?
CXR (occult malig), electrophoresis (myeloma)
TA USS and biopsy?
USS alone can be enough to diagnose if have history and inflammatory markers. However, steroids make signs disappear very quickly. Can be useful to find biopsy site!
GCA pathology?
Activated DCs present Ag to CD4 T cells; Th1/17 recruit macrophages which coalesce to form multinucleate giant cells (hallmark); granulomatous thickening. Get oedema, SM proliferation, occlusion. Elastic lamina disrupted, meaning damage is permanent. Giant cells not always seen!
Difficulties with steroid related diabetes?
Tend to get unusual peak in afternoon sugars; overtreating can lead to hypoglycaemia in the morning
GCA with no headache?
Incidental diagnosis when investigating anaemia, weight loss, raised inflammatory markers, arm pain/change in colour/claudication, PUO, thoracic aneurysm, stroke.
Investigations for non-cranial GCA symptoms?
e.g. arm claudication, aortic aneurysm. Do PET; patchy inflammation in atherosclerosis is consistent here.
Stages of Takayasu’s arteritis?
- Systemic (prevasculitic)
- Vascular (inflammatory, get stenosis and aneurysms)
- Burnout (ischaemia, pulseless phase).
Aim to pick up in one or two.
Takayasu’s is?
A granulomatous pan-arteritis with two/three clinical phase. LVV. Pan means whole of arterial wall affected
Presentation of Takayasu?
Arthralgia, myalgia, chest wall pain. Fever, weight loss, dizzines &/or visual symptoms, SOB. Get upper limb claudication with BP R-L >20mmHg. HTN, CAROTIDYNIA, aortic root dilatation. May have coronary involvement. May just be unexplained acute phase response, PUO.
Investigating Takayasu?
CTA, MRA, Doppler USS, CT PET. See cuff of inflammatory tissue around aorta, and see stenosis explainign dizziness/visual/CN problems
Difference between vasculitic and embolic rash?
Vasculitic is palpable (painful) purpura!
Causes of purpura?
- Blood: platelet or clotting problem (leakage)
2. Vessel wall: thombus/vasculitis/meningoccaemia (death) or steroids (leakage)
Infarction of whole finger?
Likely to be mid vessel.
HSP?
Small vessel vasculitis. Triad of petechial rash on buttocks and ankle, abdominal pain and renal involvement (IgA nephropathy). Often follows URTI/sore throat. Usually self limiting; bad prognosis if have severe abdo pain/bloody diarrhoea, renal involvement, persistent rash >1/12. May get chronic renal disease. M>F.
Mechanism of vessel death in vasculitis?
T3 HS; get IC lodging in small vessels, causing purpura as inflammatory cells extravasate. Also may get blistering as epidermis dies and lifts off, then dermis dies and get ulcers. Purple spots, then blisters, then black/necrotic.
Larger vasculitis lesions?
More worrying than multiple petechiae because suggests larger vessel involvement so could wipe out entire renal/coronary artery.
Mechanism of livedo?
Normal in cold; get constriction of ascending arterioles between superficial and deep plexi, with blood trapped by the skin. White areas are well-perfused (ish), purple rings are at dangerous watershed areas; a map of quite large vessels so worrying. Patchy livedo more worrying; uniform and bilateral physiological. Can lead to ulceration. Get pink-blue mottling. More prominent on legs and in cold.
APLS Abs cause?
CLOT: Coagulation defect, livedo, obstretic complications, thrombocytopenia.
Causes of livedo?
Vasculitis/CTD: SLE, PAN, ANCA, RA, dermatomyositis, PAN, infection, malignancy, drugs (amantadine), hypercoagulable states e.g. APLS, polycythaemia.