Cortex rheumatology - Inflammatory arthropathies 3 Flashcards
Connective tissues diseases are seropositive inflammatory arthropathies - what are the most common ones ?
- Systemic lupus erythematosus (SLE)
- Sjogrens syndrome
- Systemic sclerosis
- Mixed connective tissue disease
- Anti-phospholipid syndrome.
These tend to be multisystem disorders and cause organ pathology
What is SLE?
- A chronic autoimmune disease in which the presentation and disease course can be highly variable
- It mainly involves the skin, joints, kidneys, blood cells, and nervous system but can affect almost any organ
Who is at most risk of developing SLE?
Women 11:1 during child-bearing years (20s and 30s)
What are the key diagnostic features seen on history and examination of SLE?
- Malar (butterfly) rash
- Photosensitive rash
- Discoid rash
Describe the pathogenesis of SLE
- Defective apoptosis causes increased cell death.
- The defective clearance of the apoptotic cell debris allows for the persistence of antigen and immune complex production.
- Many of the clinical manifestations result from the circulating immune complexes forming with antigens in various tissues
- Leading to complement activation and inflammation
- Antibody-antigen complexes are deposited on the basement membranes of skin and kidneys.
What are some of the symptoms of SLE?
(Note SLE pretty much affects everything so try to look out for the presence of antibiody specific to it and also key features of it)
- General - fever, fatigue, mouth ulcers & lymphadenopathy
- Musculoskeletal: arthralgia, myalgia and inflammatory arthritis (non-erosive)
- Skin - malar (butterfly) rash: spares nasolabial folds, discoid rash (scaly, erythematous, well demarcated rash in sun-exposed areas.), photosensitivity, Raynaud’s phenomenon, livedo reticularis, non-scarring alopecia
- Renal: proteinuria, glomerulonephritis (diffuse proliferative glomerulonephritis is the most common type)
- Respiratory: pleurisy & interstitial lung disease (fibrosing alveolitis)
- Haematological: leukopenia, lymphopenia, anaemia (may be haemolytic), and thrombocytopenia
- Neuropsychiatric: seizures, psychosis, headache, aseptic meningitis
- Cardiac: pericarditis, myocarditis
What are some of the key investigations for SLE ? (note there is not one diagnostic test)
1st investigations to order:
- FBC and differential
- activated PTT
- urea and electrolytes
- ESR and CRP
- antinuclear antibodies, dsDNA, Smith antigen
- urinalysis
- chest x-ray
- ECG
What are the tests done to monitor SLE?
- Urinanalysis - to look for blood and protein in the urine indicating glomerulonephritis
- Monitoring cardiac risk factors - BP, chiolestrol etc
- Check anti-dsDNA antibodies and complement levels regularly
What are the auto-antibodies associated with 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 is the best auto-antibody test for SLE?
Anti-dsDNA
What is the main overall treatment of SLE?
- 1st line: NSAID + lifestyle changes
- adjunct: hydroxychloroquine
- adjunct: corticosteroids - prednisolone
What is sjorgens syndrome ?
An auto-immune disorder characterised by the presence of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) as a consequence of lymphocytic infiltration into the lacrimal and salivary glands.
What are the key signs/symptoms of sjogrens syndrome?
- Fatigue
- Dry eyes
- Dry mouth
What are some of the other (possibly less common) signs of sjorgens syndrome ?
(add in pic of parotid gland swelling)
Other symptoms include:
- Arthralgia,
- Fatigue
- Vaginal dryness
- Parotid gland swelling
(try think its the disease which causes dryness and swelling in the neck)
What are thinvestigations used to diagnose sjorgens syndrome ?
1st investigatiojns to order:
- Schirmer’s test
- anti-60 kD (SS-A) Ro and anti-La (SS-B)
What is the treatment of sjorgens syndrome ?
- Lubricating eyedrops are used and saliva replacement products may be tried
- Tx for arthralgia = NSAID’s + hydroxychloroquine
What does sjorgens increase the risk of ?
Non-hodgkins lymphoma
What is systemic sclerosis ?
- A systemic autoimmune connective tissue disorder.
- Where excessive collagen deposition causes skin and internal organ changes
Describe the presentation of systemic sclerosis and how a diagnosis is reached from an examination
Raynaulds is a common early finding (uncommon to not have it)
Skin becomes thickened and tight
Features are divided into major and minor:
- Major: includes centrally located skin sclerosis that affects the arms, face (pinching of the skin of nose (‘beaking’)), and/or neck
- Minor: includes sclerodactyly (thickened and tight skin of the fingers and toes) and bilateral lung fibrosis.
Systemic sclerosis can affect organs what are some of the common complications occuring in systemic sclerosis due to organ involvement ?
Pulmonary hypertension, Pulmonary fibrosis and accelerated hypertension leading to renal crisis are important organ manifestations.
What are the two different classifications of systemic sclerosis and how do they differ in presentation ?
Diffuse and limited
- Diffuse - skin changes develop more rapidly and can involve the trunk. Early significant organ involvement
- Limited - skin involved tends to be confined to face, hands and forearms and feet. Organ involvement tends to occur later.
What are the investigations done to help diagnose systemic sclerosis ?
Autoantibody tests:
- Diffuse - anti-scl-70 antibody
- Limited - anti-centromere
Organ screening performed regularly also - pulmonary function testing, echo and monitoring of renal function.
Describe the main idea of the management of systemic sclerosis
Management tends to be tailored to the specific issues below:
- Raynauds/digital ulcers: calcium channel blockers (nifedipine), Iloprost, bosentan
- Renal involvement: ACE inhibitors
- GI involvement: proton pump inhibitors for reflux
- Interstitial lung disease: immunosuppression, usually with cyclophosphamide.
What is meant by mixed connective tissue disease?
It is a condition which features symptoms also seen in other connective tissue diseases, these include:
- Raynauds phenomenon
- Arthralgia/arthritis
- Myositis
- Sclerodactyly
- Pulmonary hypertension
- Interstitial lung disease (ILD)
What investigations should be taken in patients with mixed connective tissue disease ?
Associated with anti-RNP antibodies
- Risk of pulmonary hypertension so regular echocardiograms
- Screening for ILD with pulmonary function tests
What is the management of mixed connective tissue disease?
Management as with most connective tissue disease varies dependant on its presentation e.g. immunosuppression if significant muscle or lung disease, CCB for Reynolds etc
What is Anti-phospholipid syndrome?
A disorder that manifests clinically as recurrent venous or arterial thrombosis and/or fetal loss.
What are the common presenting features of antiphospholipid syndrome ?
- Increased frequency of stroke or MI, especially in younger individuals.
- Recurrent pulmonary emboli or thrombosis can lead to life-threatening pulmonary hypertension.
- Spontaneous fetal loss prior to 34 weeks due to eclampsia, pre-eclampsia or with evidence of placental insufficiency.
- A common cutaneous finding is of livedo reticularis (shown in the pic below)
What are the investigations and antibodies associated with antiphospholipid syndrome ?
Antibodies:
- Lupus anticoagulant
- Anti-cardiolipin antibodies
- Anti-beta 2 glycoprotein
There may be thrombocytopenia (low platelets) and prolongation of APTT (activated partial thromboplastin time - measures clotting time)
What is the treatment of antiphospholipid syndrome ?
Mainstay is anti-coagulation:
non-pregnant with acute thrombosis:
- 1st line:low molecular weight heparin
- plus: warfarin following low molecular weight heparin
- plus: management of risk factors
pregnant
with acute thrombosis
- 1st line: low molecular weight heparin
- plus: fetal monitoring + specialist multidisciplinary care
- plus: warfarin post-delivery
- plus: management of risk factors
(remember warfarin is teterogenic)
Long term Mx:
- Life long warfarin with a target INR of 2-3
