Multisystem connective tissue disease Flashcards
what is the pathology of SLE
Autoimmune condition, with autoantibodies directed at a range of tissues, however the aetiology is unknown
what is the only universal symptom of SLE
fatigue
what are some common features of SLE
Skin involvement - 75%
malar rash
photosensitivity
alopecia
Oral involvement - 20%
mucosal ulcers
CNS involvement - 60%
depression/anxiety
infarctions
grand-mal seizure
Renal involvement - 30%
glomerular disease
interstitial nephritis
Haematology
normocytic hypochromic anaemia
thrombocytopenia
leukopenia
MSK
arthritis (90%) - fingers wrists knees
myalgia
symmetrical polyarthritis
Lung - 50%
recurrent pleurisy /pleural effusions
pulmonary fibrosis
Heart involvement
myositis
pericarditis
cardiomyopathy
what investigations are done if lupus is suspected
FBC – normocytic hypochromic anaemia, thrombocytopenia, leukopenia
ESR/CRP - CRP normal, ESR may be raised
U+E – deranged if there is renal involvement
Serum ANA – almost always positive
Specific
Sm - indicates renal disease
Serum RF – positive in 25%
Anti-dsSNA – specific for SLE but only 50% sensitivity
RNA antibodies (anti ro, anti-la) often present
Serum complement levels – C3/C4 reduced In active disease
APL antibodies – many patients will have anti cardiolipin antibodies indicating a comorbid antiphospholipid antibodies
Urine Dip
Check for renal involvement
Histology
Characteristic histology/immunoflourescence scan in skin/kidney biopsies
whats the management of lupus
Avoid excessive sunlight and CV risk factors
Monitor for signs of infection and treat early
Mild disease
NSAIDS
Hydroxychloroquine - Monitor eyes as may cause retinopathy
In combination help skin disease, fatigue, and arthralgia
More severe disease Any cardiac/renal involvement Prednisolone DMARD e.g. azathioprine (child bearing age), methotrexate etc
what is antiphospholipid syndrome
Presence of autoantibodies with a specificity for phospholipids, predisposing to thrombosis
what are features of antiphospholipid syndrome
Venous thrombosis, most commonly in arms/legs predisposing to PE
Arterial thrombosis, much rarer than venous
20% of strokes in those <45 are due to APL syndrome
Pregnancy loss, particularly in 2nd or 3rd trimester
Livedo reticularis - ‘lace like’ rash in face, looks a bit like crazy paving
Thrombocytopenia
Migraines
Epilepsy
what investigations should be done if antiphospholipid syndrome considered
ESR – normal
ANA – negative
APTT – increased
Coombs test – positive
Anticardiolipin antibodies – diagnostic if +ve
2 high titres are required at least 12 weeks apart
Lupus anticoagulant antibodies (found in 20%)
how do you treat antiphospholipid syndrome in those with a history of thrombosis
Those with a history of severe thrombosis
Warfarin
Target INR 3-4
how do you treat antiphospholipid syndrome in those with no thrombotic history
With no thrombotic history Low dose aspirin Lifestyle advice Avoid prolonged immobilisation Avoid oestrogen containing drugs
how do you treat antiphospholipid syndrome in pregnancy
In pregnancy
LMWH and aspirin given throughout
Early delivery with specialist care
what is the prognosis of antiphospholipid syndrome
Poor
1/3 having organ damage within 10 years of diagnosis
what is primary sjogrens
Dry eyes (keratoconjunctivitis sicca) in the absence of autoimmune disease
what is secondary sjogrens
Presence of dry eyes + autoimmune disease
what autoimmune diseases are most commonly associated with secondary sjogrens
RA
SLE
Scleroderma
Polymyositis
what are symptoms of sjogrens
Dry eyes and mouth
Salivary and parotic gland enlargement
Vaginal dryness
Associated systemic features
Arthralgia
Raynaud’s
Oesophageal motility issues
what investigations should be done for sjogrens
Schirmers smear test
Specialised filter paper placed inside lower eyelid <1cm in 5 minutes
Indicates defective tear production
Bloods RF – usually raised ANA – raised in 70% Anti-ro – positive in 70% Anti-la – positive In 30%
what management is there for sjogrens
Artificial tears + saliva replacement solutions
identify and treat underlying disorder if secondary
what is the pathophysiology of scleroderma/systemic sclerosis
Perivascular fibrosis leads to ischaemic damage in a range of tissues
the skin is most commonly affected (dermal thickening leads to hardened skins)
Major organs (kidneys/heart/oesophagus/kidneys damaged)
what are the 2 main subtypes of scleroderma + their % split
limited cutaneous scleroderma - 70%
diffuse cutaneous scleroderma - 30%
what are some features of limited cutaneous scleroderma including early and late symptoms
Long history of raynauds with skin tightening at the extremities
Face may be involved causing microstomia (smaller oral cavity due to tightening)
Early symptoms
Fatigue
GORD
Ulcers on digital tips
Later symptoms
Oesophageal strictures
Small bowel malabsorption
Pulmonary fibrosis/hypertension
what was scleroderma previously known as, and what does it stand for
CREST syndrome
C - calcinosis R - reynauds E - oesophageal dysmotility S - sclerodactlyl T - telangectasia
what is the main life threatening feature of scleroderma
pulmonary hypertension
whats the management for limited cutaneous scleroderma
Digital sympathectomy /vasodilators for the Raynauds
Procedure where the nerves to the fingers are cut
Removal of calcinoses
Treatment of oesophageal problems
what are features of diffuse sytemic sclerosis
Short history of Raynauds
Rapidly progressive skin sclerosis – peaking at about 2 years
Systemic symptoms greater Lethargy Weight loss Anorexia Complications will occur within the first 3 years Myocardiac fibrosis Pulmonary fibrosis Renal fibrosis
whats the management for diffuse systemic sclerosis
Immunosuppression
Aiming to prevent complications so can be gradually withdrawn after a year if the disease subsides
Sympathectomy/vasodilators helpful for symptoms
what investigations tend to be diagnostic in scleroderma
Limited cutaneous scleroderma
Anti-centromere antibodiy positive in 60%
Diffuse cutaneous scleroderma
Anti-SCL-70 antibodies In 40%
Anti-RNA polymerase antibodies
These can be present in limited cutaneous scleroderma however less commonly
whats the prognosis of scleroderma
Highest mortality of any of the autoimmune rheumatic diseases
Limited cutaneous scleroderma has the better survival rate (70% 10 year) due to its limited organ involvement compared to diffuse scleroderma
what are examples of inflammatory myopathies
polymyositis
dermatomyositis
what gene phenotype is associated with inflammatory myopathies
HLA-B8/DR3
what type of muscle is affected in polymyositis
striated muscle
what are features of polymyositis
Inflammation of striated muscle, causing proximal muscle weakness
Generally causes weakness in absence of any pain
There may be associated muscle wasting
Onset can be insideous or acute
Associated with malaise, fever and weight loss
Patient will have difficulty
Squatting
Climbing stairs
if left untreated respiratory muscle involvement will lead to respiratory failure
what is the presentation of dermatomyositis
polymyositis + associated skin involvement
Classic heliotropic rash (purple colouration of eyelids)
Associated periorbital oedema
Vasculitis patches over the knuckles (Gottron’s papules)
what conditions are inflammatory myopathies associated with
RA
SLE
systemic sclerosis
various malignancies (most commonly breast, lung and colorectal)
what investigations should be done in inflammatory myopathies
Bloods Serum CK – raised ESR – rarely raised (5%) ANA – most are positive RF – positive in 50% Myositis specific antibodies
Electromyography EMG shows characteristic pattern Fibrillations Myotonic discharges Positive sharp waves
MRI
Detects area of abnormal muscle
Needle muscle biopsy
Fibre necrosis with inflammatory infiltrate
Further investigations for malignancy screening
Full body CT
how do you manage inflammatory myopathies
Prednisolone/DMARDS until myositis is clinically inactive
If not working IVIG is sometimes used
what is inclusion body myositis
Affects white males over 50 , with the insideous onset of proximal and distal muscle wasting, which may be asymmetrical
ANA frequently less positive
Myositis specific antigens will not be positive
Muscle biopsy shows inflammatory infiltrate and vacuoles containing beta-amyloid (inclusion bodies)
Progressive and rarely responds to prednisolone/DMARD combos
what are features of systemic vasculitis
General malaise Fever Weight loss Myalgia Arthralgia
Skin
Palpable purpura
Ulceration
GI
Ulcers
Abdominal pain
Diarrhoea
Respiratory
Haemoptysis
Dyspnoea
ENT
Epistaxis
Crusting
Cardiac
Chest pain
Neuropathies
what are some examples of large vessel vasculitides
Giant cell arteritis/temporal arteritis
Takayasu’s arteritis
what are features of takayasu’s arteritis
Young adults
Presents with upper limb claudication and stroke
what are some examples of medium vessel vasculidities
classic polyarteritis nodosa
kawasakis disease
what are some features of polyarteritis nodosa
Multiple systemic symptoms
Multiple microaneurysms on angiography
Systemic vasculitic symptoms in the presence of hepatitis B signs and in the absence of pulmonary symptoms/signs suggests a diagnosis polyarteritis nodosa
what are some features of kawasakis disease
Fever
Rash
Lymphadenopathy
Palmar erythema
strawberry tongue
May cause coronary artery aneurysm
what are examples of medium/small vessel vasculidities
wegeners vasculitis/Granulomatosis with polyangiitis
Churg-struass syndrome
microscopic polyangitis
henoch-schlonein purpura
cryoglobinaemia
what are some featues of wegeners vasculitis
Lung, kidney, ENT involvement with granuloma formation seen on biopsies
what are some features of churg-strauss syndrome
Late-onset asthma
Atopy
Cardio-pulmonary involvement
what are some features of microscopic polyangitis
Commonly causes pulmonary renal syndrome
Haemoptysis and haematuria
what are some features of cryoglobinaemia
Associated with hep C
Rash
Arthralgia
Neuropathy
what are some features of henoch-schlonein purpura
purpuric rash on back/buttocks/back legs
commonly in kids
some associated kidney/joint/bowel disease
what are some investigations done for a suspected vasculitis
BP + urine dip - for prognosis
bloods
FBC: leukocytosis in primary disease/infection, leukopenia in CTDs
LFTs: hepatitis is often a secondary marker of vasculitis
Inflammatory markers
Immunology
C-ANCA associated with wegeners
P-ANCA associated with Churg-Strauss syndrome
what specific test is associated with churg-strauss syndrome
P-ANCA
what specific test is associated with wegeners syndrome
C-ANCA
how is vasculitis typically treated
Depends on the size of the vessel involved
Corticosteroids are mainstay of treatment – prolonged dose reduction over 12 hours
Cyclophosphamide (low dose or pulse) is often used in ANCA positive disease to induce remission
IVIG is used in kawasakis
Plasma exchange may be done In life threatening conditions
what is done for life threatening vasculitis episodes
plasma exchange
whats an important side effect of cyclophosphamide
infertility
what treatment is done in kawasakis disease
IVIG
