Cortex 3 - Rheumatology Flashcards
what conditions is connective tissue disease an umbrella term for ?
Conditions including:
- systemic lupus erythematosus (SLE),
- Sjogrens syndrome,
- systemic sclerosis,
- mixed connective tissue disease
- anti-phospholipid syndrome.
tend to be multisystem disorders which can cause organ pathology
what is SLE (systemic lupus erythematosus) and what does it affect in the body?
chronic autoimmune disease
Mainly involves the skin, joints, kidneys, blood cells, and nervous system but can affect almost any organ system.
what is the SLICC - classification criteria for SLE?
what is the pathogenesis of SLE?
Development of autoantibodies involves a defect in apoptosis that causes increased cell death and a disturbance in immune tolerance. The defective clearance of the apoptotic cell debris allows for the persistence of antigen and immune complex production.
Many clinical manifestations of SLE are mediated by circulating immune complexes that form with antigens in various tissues. Immune complexes form in the small blood vessels, leading to complement activation and inflammation. Moreover, antibody-antigen complexes are deposited on the basement membranes of skin and kidneys.
who is SLE more common in and what age does it usually present ?
SLE is high in black persons in the UK and US
90% cases occur in women and usually in there 20s and 30s
what is the survival rates in SLE ?
90% after 10 years
what are some of the clinical features of SLE?
Constitutional: fever, fatigue and weight loss
Musculoskeletal: arthralgia, myalgia and inflammatory arthritis. Arthropathy is rarely erosive or deforming. There is an increased prevalence of avascular necrosis, usually of the femoral head, which may relate to steroid use
Muco-cutaneous: malar rash (sometimes described as butterfly rash), photosensitivity, discoid lupus, subacute cutaneous lupus, oral/nasal ulceration and Raynauds phenomenon.
Renal: lupus nephritis
Respiratory: pleurisy, pleural effusion, pneumonitis, pulmonary embolism, pulmonary hypertension, and interstitial lung disease.
Haematological: leukopenia, lymphopenia, anaemia (may be haemolytic), and thrombocytopenia
Neuropsychiatric: seizures, psychosis, headache, aseptic meningitis
Cardiac: pericarditis, pericardial effusion, pulmonary hypertension, sterile endocarditis and accelerated iscahemic heart disease.
Gastrointestinal: less common but include autoimmune hepatitis, pancreatitis and mesenteric vasculitis
what is this a specific feature of ?
SLE - it is alopecia
what is this clincial feature and what is it a sign off?
butterfly rash (malar rash) - good sign of SLE
what is this clinical feature and what condition is it a sign off?
Reynolds - good sign of SLE
what are some of the immunological tests used to diagnose SLE?
Immunology:
- Anti-nuclear antibody - positive in >95% of patients, not specific
- Anti-dsDNA antibody - specific and varies with disease activity
- Anti-Sm - specific but low sensitivity
- Anti Ro, anti-La and anti-RNP - may be seen in SLE but may also be seen in other conditions
- C3/4 levels - low when disease active, especially renal disease
what are some of the other tests used to diagnose SLE besides immunological tests?
FBC may show anaemia, leucopenia and thrombocytopenia
Urinalysis to look for evidence of glomerulonephritis
imaging used to look for evidence of organ involvement - eg CT chest for interstitial lung disease, MRI brain for cerebral vasculitis, echo for pericardial effusion.
what is the management of SLE?
management depends on manifestations:
For skin disease and arthralgia (joint pain) hydroxychloroquine, topical steroids and NSAIDs are commonly used.
If inflam arthritis or organ involvement e.g. pericardial disease or interstitial lung disease then - immunosuppression like azathioprine or mycophenolate mofetil may be required. Corticosteroids at moderate doses may also be used, ideally for short periods.
In severe organ disease e.g. lupus nephritis or CNS lupus then treatment tend to involve IV steroids and cyclophosphamide.
In unresponsive cases other therapies such as IV immunoglobulin and rituximab may be necessary.
what should be monitored for patients with SLE?
check anti-dsDNA antibodies and complement levels regularly, as these vary with disease activity and may give some warning of a disease flare.
check urinalysis for blood or protein, which may indicate glomerulonephritis.
BP and cholesterol should be monitored. as patients can often die due to cardio complications
what is sjorgens syndrome ?
An autoimmune condition characterized by lymphocytic infiltrates in exocrine organs. can be a primary condition or occur secondary to e.g. RA and SLE
what are the symptoms of sjorgens syndrome ?
This typically causes dryness of the eyes and mouth (sicca symptoms). Other symptoms include arthralgia, fatigue and vaginal dryness and parotid gland swelling.
Peripheral neuropathy (numbness or weakness) and interstitial lung disease may occur.
what does sjorgens increase the risk off ?
lymphoma
how is sjorgens syndrome diagnosed?
Based on the confirmation of ocular dryness (Schirmers test), positive anti-Ro and anti-La antibodies and typical features on a lip gland biopsy.
what is this clinical feature and what is it typically seen in ?
oral dryness seen in sjorgens syndrome
what is this clinical feature and what condition is it typically seen in ?
parotid gland swelling seen in sjorgens syndrome
what is the treatment of sjorgens syndrome ?
mainly symptomatic - Lubricating eyedrops are used and saliva replacement products may be tried. Regular dental care is important due to the high risk of caries. Pilocarpine can stimulate saliva production but often causes side effects such a flushing.
Hydroxychloroquine can sometimes help with arthralgia and fatigue.
immunosuppression would usually only be used in the context of organ involvement e.g. interstitial lung disease.
what is systemic sclerosis and what is the pathogenesis of it?
it is a systemic connective tissue disorder in which excessive collagen deposition causes skin and internal organ changes
what is the common presentation of systemic sclerosis ?
Raynauds phenomenon
Thickening and tightening of the skin - this can be classed into major and minor features.
Major - includes centrally located skin sclerosis that affects the arms, face, and/or neck
Minor - includes sclerodactyly (localized thickening and tightness of the skin of the fingers or toes - can lead to ulceration) and atrophy of the fingertips and bilateral lung fibrosis.
what do patients with systemic sclerosis usually die off ?
renal and lung changes with pulmonary hypertension causing 12 % of deaths
how is a diagnosis of systemic sclerosis made ?
when the patient has 1 major and 2 minor features
note:
Major: includes centrally located skin sclerosis that affects the arms, face, and/or neck
Minor: includes sclerodactyly and atrophy of the fingertips and bilateral lung fibrosis.
what is this clinical sign and what condition is it a feature off ?
facial changes seen in systemic sclerosis
Note:
When the skin of the face is affected this can cause pinching of the skin of nose (‘beaking’) and tightening of the skin around the mouth. Telangiectasia (a condition characterized by dilatation of the capillaries causing them to appear as small red or purple clusters, often spidery in appearance, on the skin or the surface of an organ.) are also seen
what is this clincial sign and what condition is it a feature off?
sclerodactyly and is a feauture of systemic sclerosis
Note:
calcinosis may also be seen (calcium deposits in the digits)
what are some of the organ involvement in systemic sclerosis ?
Pulmonary hypertension, pulmonary fibrosis and accelerated hypertension leading to renal crisis are important organ manifestations.
Gut involvement may lead to dysphagia, malabsorption and bacterial overgrowth of the small bowel.
how is systemic sclerosis classed ?
into diffuse and limited forms:
diffuse - skin changes develop more rapidly and can involve the trunk. Early significant organ involvement. Anti-Scl-70 antibody association.
limited - skin involved tends to be confined to face, hands and forearms and feet. Organ involvement tends to occur later. Anti-centromere antibody association.
what is the management of systemic sclerosis?
Raynauds/digital ulcers: calcium channel blockers (first line), Iloprost (second), bosentan
Renal involvement: ACE inhibitors
GI involvement: proton pump inhibitors for reflux
Interstitial lung disease: immunosuppression, usually with cyclophosphamide.
what is a useful mnemonic when thinking about the features of systemic sclerosis ?
CREST (calcinosis, reynolds, esphageal dysmotility, sclerodactyly, telangiectasia)
what is mixed connective tissue disease ?
Is a defined condition which features symptoms also seen in other connective tissue diseases such as:
Raynauds phenomenon
Arthralgia/arthritis
Myositis
Sclerodactyly
Pulmonary hypertension
Interstitial lung disease (ILD)
what monitoring is required in patients with systemic sclerosis ?
Organ screening, includes pulmonary function testing, echo and monitoring of renal function.
what autoantibody is mixed connective tissue disease associated with ?
anti-RNP antibodies.
what monitoring should occur in patients with mixed connective tissue disease?
echo and pulmonary function test
what is the management of mixed connective tissue disease?
it is according to presentation:
CCB may help for reynaulds, immunosuppression may be required if significant lung or muscle disease
what is antiphospholipid syndrome ?
(APS) is a disorder that manifests clinically as recurrent venous or arterial thrombosis and/or fetal loss.
It can sometimes occur in association with SLE or another rheumatic or autoimmune disorder.
what can APS cause an increased frequency off ?
Increased frequency of stroke or MI, especially in younger individuals.
Strokes may develop secondary to in situ thrombosis or embolization that originates from the valvular lesions of Libman-Sacks (sterile) endocarditis, which may be seen in patients with APS.
what are some of the other features of APS?
migraines
livedo reticularis. (seen in the pic)
what immunological tests may be positive in APS?
Lupus anticoagulant,
anti-cardiolipin antibodies
and anti-beta 2 glycoprotein
what blood problems may be present due to APS?
prolonged activated partial thromboplastin time (APTT) and thrombocytopenia (deficiency of platelets in the blood. This causes bleeding into the tissues, bruising, and slow blood clotting after injury).
what is the treatment of APS?
anti-coagulation for those with an episode of thrombosis
In patients with recurrent pregnancy loss low molecular weight heparin is used during pregnancy (warfarin is teratogenic i.e. can cause birth defects).
Patients with positive antibodies but no episodes of thrombosis don’t require anti-coagulation.
what is gout ?
A crystal arthropathy caused by deposition of urate crystals within a joint
what is the pathogenesis of gout ?
Usually due to high serum uric acid levels (hyperuricaemia). Uric acid is the final compound in the breakdown of purines in DNA metabolism (adenine & guanine).
what are some causes of hyperuricaemia ?
Renal underexcretion (which can be exacerbated by diuretics or renal failure) or due to excessive intake of alcohol, red meat and seafood.
what are some triggers of uric acid crystals ?
Uric acid crystals precipitate in joints and this can be triggered by dehydration, trauma or surgery.
what is the classical joint affected by gout?
first metatarsalphalangeal joint (MTP) known as podagra
what are some of the other most common joints affected by gout ?
ankle and knee
what are the presenting features of gout ?
Intensely painful red, hot swollen joint which may mimic a septic arthritis. Symptoms usually last for 7-10 days if untreated then resolve.
what can chronic gout result in ?
destructive erosive arthritis
what is this clinical feature and what is it a sign of ?
Inflammation of first MTP joint
classic feature of gout
what is this clinical feature and what is it a sign of ?
Gouty trophi - painless white accumulations of uric acid which can occur in the soft tissues and occasionally erupt through the skin.
how is a definitive diagnosis of gout made ?
analysing a sample of synovial fluid with polarised microscopy (it is also analysed with gram stain and culture to exclude infection).
Uric acid crystals are needle shaped and display negative birefringence (change from yellow to blue when lined across the direction of polarization).
what is the treatment of gout for acute and recurrent attacks/destruction or trophi ?
acute - NSAIDs, corticosteroids, opioid analgesics and colchicine for patients who cannot tolerate NSAIDs.
recurrent - treat it acutely then give allopurinol
what is the difference of pseudogout to gout?
pseudogout is caused by calcium pyrophosphate crystals.
which pic is pseudogout crystals and which is gout crystals?
A = pseudogout - positive birefringent
B = gout - negative birefringent
what is the term used to describe when calcium pyrophosphate deposition occurs in cartilage and other soft tissues in the absence of acute inflammation?
chondrocalcinosis - comes under the umbrella term Calcium Pyrophosphate Deposition disease (CPPD).
what do calcium pyrophospahte deposition disease commonly affect? (CPPD)
the knee, wrist and ankle
what is the treatment of CPPD?
NSAIDs,
corticosteroids (systemic and intra‐articular)
and occasionally colchicine
