Connective Tissue Disorders Flashcards
what is SLE
chronic autoimmune disease which mainly involves the skin, joints, kidneys, blood cells and NS but can affect almost any organ system
what is the pathogenesis of SLE
defect in apoptosis that causes increased cell death the defective clearance of apoptotic cell debris allows for persistence of antigen and immune complex production
how do the clinical manifestations occur in SLE
because the circulating immune complexes are deposited on blood vessels and on basement membrane of skin and kidneys
what is the prevalence of SLE
based on environmental genetics (if mother has SLE, her daughters risk is 1:40 and son risk 1:250)
what is typical SLE patient
asian, afro-americans or afro-caribbean women frequently starting at childbearing age
what causes SLE
genetics - high concordance in monozygous twins hormonal factors - those with high oestrogen exposure
what are general symptoms of SLE
fever, fatigue and weight loss
what are MSK symptoms of SLE
non-deforming polyarthritis deforming arthropathy - Jaccoud’s arthritis myopathy - weakness, myalgia, myositis inflammatory arthritis increased prevalence of AVN, usually of femoral head which may relate to steroid use
what are muco-cutaneous symptoms of SLE
malar rash photosensitivity discoid lupus subacute cutaneous lupus oral / nasal ulceration alopecia raynauds phenomenon
what are renal symptoms of SLE
lupus nephritis proteinuria of >500mg in 24 hours
what are respiratory symptoms of SLE
pleurisy pleural effusion pneumonitis PE pulmonary hypertension ILD
what are haematological symptoms of SLE
leukopenia lymphadenopathy leucopenia lymphopenia anaemia (may be haemolytic) thrombocytopenia
what are neuropsychiatric symptoms of SLE
seizures psychosis / depression headache aseptic meningitis
what are cardiac symptoms of SLE
pericarditis pleural effusion pulmonary hypertension sterile endocarditis accelerated ischaemic HD
what are GI symptoms of SLE
less common but include autoimmune hepatitis, pancreatitis and mesenteric vasculitis
what is diagnostic criteria of SLE
>4 criteria (at least 1 clinical and 1 laboratory criteria) OR biopsy proven lupus nephritis with positive ANA or anti-DNA
what is list of clinical criteria in diagnosis of SLE
acute cutaneous lupus chronic cutaneous lupus oral or nasal ulcers non scarring alopecia arthritis serositis renal neurologic haemolytic anaemia leukopenia thrombocytopenia
what is list of immunologic criteria in diagnosis of SLE
ANA anti-DNA anti-SM anti phospholipid Ab low complement (C3, C4, CH50) direct coombs test - do not count in presence of haemolytic anaemia
how is SLE treated
depends on manifestation avoid sun exposure
how is skin disease and arthralgia in SLE treated
hydroxychloroquine topical steroids NSAIDs
how is inflammatory arthritis or organ involvement in SLE treated
immunosuppression (azathioprine mycophenolate mofetil) corticosteroids for short period
how is severe organ disease (eg lupus nephritis or CNS lupus) in SLE treated
IV steroids cyclophosphamide
how is unresponsive cases of SLE treated
IV immunoglobulin and rituximab
how is SLE monitored
check anti-dsDNA antibodies and complement levels regularly also important to check urinalysis for blood or protein which may indicate glomerulonephritis
what is Sjorgens syndrome
autoimmune condition characterised by lymphocytic infiltrates in exocrine organs
Sjorgens can be primary, or secondary to what
other autoimmune conditions eg RA and SLE
what diseases are associated with sjorgens
peripheral neuropathy and ILD. Also risk of lymphoma
what are symptoms of sjorgens
dryness of eyes and mouth (sicca symptoms) - keratoconjunctivitis sicca arthralgia belpharitis (eyes swollen and red) tooth decay dry cough fatigue vaginal dryness parotid gland swelling
how is ocular dryness confirmed for patients with sjorgens
schirmers test
what antibodies are positive in sjorgens
anti-SSA (Ro) anti-SSB (La) Raised IgG
sjorgens must have 4 of the american european consensus group to be diagnosed; what are these
occular symptoms - dry eyes for 3 months, use of tear substitutes, schirmers test performed without anaesthesia (<5mm in 5 mins) oral symptoms - dry mouth, swollen salivary glands, abnormal salivary scintigraphy or parotid sialography findings (unstimulated salivary flow <1.5mm in 15 mins) positive minor salivary gland biopsy findings positive antibodies
how is sjorgens treated
symptomatic lubricating eyedrops regular dental care pilocapine can stimulate saliva production (SE: flushing) hydroxychloroquine for arthralgia and fatigue other immunosuppression only useful in organ involvement eg ILD
what is systemic sclerosis
systemic connective tissue disease where there is vasomotor disturbances (raynauds), fibrosis and atrophy of skin and subcutaneous tissue
what is it that causes the skin and internal organ changes in systemic sclerosis
collagen deposition calcium deposits in skin
the limited symptoms of scleroderma are referred to as a CREST, what does this stand for
calcinosis - calcium deposits in skin raynauds - spasm of vessels in response to cold or stress eosophageal dysfunction - acid reflux sclerodactyly - thickening and tightening of skin on fingers and hands telangiectasis - dilation of capillaries causing red mark on surface of skin
what is the limited form (lsCC) of systemic sclerosis
skin involvement - face, hands, forearms, feet organ involvement tends to occur later anti-centromere antibody association (ACA)
what is the diffuse form (dsCC) of systemic sclerosis
skin changes more rapid and involve trunk early significant organ involvement anti-Scl-70 antibody association
what is the three phases of cutaneous involvement in systemic sclerosis
oedematous, indurative, atrophic
what are major features of cutaneous involvement in systemic sclerosis
centrally located skin sclerosis affects arm, face and/or neck
what are the minor features of cutaneous involvement in systemic sclerosis
sclerodactyly and atrophy of fingertips bilateral lung fibrosis
how is systemic sclerosis diagnosed
when patient has 1 major or 2 minor features anti-centromere and anti-scl-70
how is systemic sclerosis treated
no overall, needs to be tailored to specific issue
how would raynauds in systemic sclerosis be treated
CCB (amlodipine, nifedipine, verapamil) Iloprost Bosentan
how is renal involvement in systemic sclerosis treated
ACE inhibitors
how is GI involvement in systemic sclerosis treated
PPI
how is ILD in systemic sclerosis treated
immunosuppression usually with cyclophosphamide (chemo)
what organs can become involved in systemic sclerosis
lung - pulmonary hypertension, fibrosis accelerated hypertension leading to renal crisis gut - dysphagia, malabsorption, bacterial overgrowth inflammatory arthritis and myositis may be seen
what is generally responsible for death in systemic sclerosis patients
renal and lung changes pulmonary hypertension leads to 12% systemic sclerosis related deaths
what is mixed connective tissue disease (MCTD)
defined condition which features symptoms also seen in other connective tissue diseases
what symptoms may be seen in MCTD
raynauds arthralgia arthritis myositis sclerodactyly (thickening of skin on fingers and toes) pulmonary hypertension ILD
how is MCTD diagnosed
anti-RNP antibodies
what should take place after diagnosis of MCTD
annual echocardiograms suggested due to risk of pulmonary hypertension screening for ILD with PFTs should also take place
how is MCTD treated
as with other CTDs - symptomatic eg CCB for raynauds or immunosuppression for significant muscle or lung disease
what is anti phospholipid syndrome
disorder which manifests clinically as recurrent venous or arterial thrombosis and/or foetal loss
although some patients have no associated disease, what diseases can anti phospholipid syndrome be associated with
SLE or another rheumatic or autoimmune disorder
what are symptoms of anti phospholipid syndrome
migraine livedo reticularis (mottled skin) late, spontaneous foetal loss (2nd or 3rd trimester) common recurrent early foetal loss (<10 weeks) also possible
how does anti phospholipid syndrome contribute to increased frequency of stroke or MI especially in younger patients
stroke may develop in situ thrombosis or embolisation that originates from valvular lesions or Libman-Sacks endocarditis recurrent pulmonary emboli or thrombosis can lead to life threatening pulmonary hypertension
how is anti phospholipid syndrome diagnosed
may be thrombocytopenia and prolongation of APTT lupus anticoagulant anti-cardiolipin antibodies anti-beta 2 glycoprotein
how is antiphospholipid syndrome treated
anticoagulation with LMWH patients who are found to have positive antibody but who never had thrombosis do not require anticoagulation
why do you not give warfarin in antiphosphlipid syndrome
it is teratogenic
what is complication of antiphospholipid syndrome
catastrophic APS is a rare, serious and fatal manifestation characterised by multi organ infarction over a period of days to weeks
