Rheumatology Flashcards
What is rheumatoid arthritis?
Long term autoimmune disorder primarily affecting joints that is more common in females. Most commonly diagnosed in those aged 40-50 but affects people of all ages.
What are the two biggest risk factors for rheumatoid arthritis?
Genetics
Smoking
What causes rheumatoid arthritis?
Autoimmune disease involving immune complexes
Rheumatoid arthritis pathogenesis is basically an imbalance of immune proteins and cells.
Rheumatoid factor is a circulating factor that reacts with the Fc portion of a patients IgG
What are the clinical features of rheumatoid arthritis?
Insidious onset over a few months
Bilateral and symmetrically painful joints, usually the MCP and PIP joints
Joints will be warm, swollen, and stiff
Pain following rest i.e. when waking up in the morning
Stiffness following rest that is slowly improves with use (slower than osteoarthritis)
If picked up late the joints will become immobile and deformed – swan neck and boutonniere deformities
Positive squeeze test – discomfort on squeezing across MC or MT joints
Non-Joint manifestations
Rheumatoid nodules are the most common non joint manifestation
Respiratory – fibrosis, effusion, nodules, bronchiolitis obliterans, pneumonitis and pleurisy
Ocular – keratoconjunctivitis sicca, episcleritis, scleritis, corneal ulceration, keratitis, steroid induced cataracts, and chloroquine retinopathy
Osteoporosis
Cardiac – IHD (similar risk as T2DM),
Increased risk of infections
Depression
Anaemia (of chronic disease)
How should suspected rheumatoid arthritis be investigated?
Clinical diagnosis is most important
X-ray
Early signs – loss of joint space, juxta-articular osteoporosis and soft tissue swelling
Late signs – periarticular erosions and subluxation
Blood test for Rheumatoid factor (Rosa-waaler test or Latex agglutination test) (only positive in 70-80% of cases), high levels indicate severe progressive disease but are not a marker for disease activity.
Anti-cyclic citrullinated peptide antibodies (ACPA) – may be detectable 10 years before RA develops – sensitivity of 70% and specificity of 90-95%. Test if RF negative but high clinical suspicion
What other conditions are positive for rheumatoid factor?
Other conditions with raised RF include: Sjogren’s syndrome – 50% Infective endocarditis – 50% SLE – 20-30% Systemic sclerosis – 30% General population – 5%
Describe the American college of rheumatology criteria for diagnosis of rheumatoid arthritis?
Used in patients who have at least 1 joint with definite clinical synovitis that is not better explained by another disease. Scored on:
- Type and number of joints involved
- Serology – RF and ACPA
- Acute phase reactants – CRP and ESR
- Duration of symptoms – > or < 6 weeks
How is rheumatoid arthritis managed?
First line – DMARD monotherapy +/- short course of bridging prednisolone. Monitor efficacy with CRP and disease activity such as using the composite score DAS28
Pain control using paracetamol, codeine but avoid NSAIDs if possible.
Flares – corticosteroid either oral or IM
Anti-TNF agents – indicated if inadequate response to at least two DMARDs including methotrexate. Examples include etanercepts, infliximab and adalimumab. Most important SE of these are the possibility to reactivate TB.
Other monoclonal antibodies to consider are Rituximab and Abatacept
Give some examples of the DMARDs used in Rheumatoid Arthritis and their side effects?
DMARDs include:
Methotrexate – SE: myelosuppression, liver cirrhosis and pneumonitis
Sulphasalazine – SE: rashes, oligospermia, Heinz body anaemia and interstitial lung disease
Leflunomide – SE: liver impairment, interstitial lung disease and hypertension
Hydroxychloroquine – SE: retinopathy and corneal deposits
What is hydroxychloroquine and what are its side effects?
Hydroxychloroquine – very similar to chloroquine which is used to treat malaria. SE – bull’s eye retinopathy (severe and permanent visual loss) so baseline ophthalmological examination and annual screening is recommended. Safe in pregnancy.
What is methotrexate and what are its side effects?
Methotrexate – inhibits dihydrofolate reductase. SE mucositis, myelosuppression, pneumonitis, pulmonary fibrosis, and liver fibrosis. Avoid in pregnancy and must be on effective contraception for at least 6 months following treatment. Prescribed weekly and monitored through FBC, U&E and LFT every 2-3 months once stabilised (weekly before this). Should be co-prescribed with folic acid. Interacts with trimethoprim, co-trimoxazole and high dose aspirin.
What is penicillamine?
Penicillamine – mechanism of action unknown – SE rashes, disturbance of taste and proteinuria
What are the poor prognostic factors for rheumatoid arthritis?
Poor Prognostic Factors RF positive Poor functional status HLA DR4 X-ray showing early erosions after < 2 years Extra articular features e.g. nodules Insidious onset ACPA positive
What is SLE?
Systemic Lupus Erythematous
Definition – multisystemic autoimmune disease with a type 3 hypersensitivity reaction mostly to nuclear antigens and DNA itself causing immune complex formation and deposition resulting in inflammation and damage to tissue. 9:1 F:M ratio typically women of child bearing age with a strong genetic link for some forms of the disease. Most common in afro Caribbean and Asian populations. Associated with HLA B8, DR2 and DR3.
What causes SLE?
95% are ANA positive (antinuclear antibodies)
60% are anti-double stranded DNA positive
40% are Rheumatoid factor positive
SLE can also be associated with antiphospholipid antibodies, autoimmune thyroid disease and Sjogren’s.
What is drug induced lupus?
Features – renal and nervous system involvement is unusual. Arthralgia, myalgia, malar rash and pulmonary involvement, ANA positive in 100% but dsDNA negative, anti-histone antibodies in 80-90%.
Most common causes are procainamide and hydralazine with isoniazid, minocycline and phenytoin being less common.
What are the clinical features of SLE?
Skin
Malar – butterfly rash that spares the nasolabial folds
Discoid rash – scaly, erythematous and well demarcated in sun exposed areas – may progress to pigmented and hyperkeratotic before becoming atrophic
Photosensitivity
Raynaud’s phenomenon
Livedo reticularis
Non-scarring alopecia
Other
MSK – Arthralgia and non-erosive arthritis
Cardiac – pericarditis and non-infective endocarditis (Libman-Sacks syndrome)
Respiratory – pleurisy and fibrosing alveolitis
Renal – proteinuria and glomerulonephritis – diffuse proliferative most commonly
Neuropsychiatric – anxiety and depression, psychosis and seizures
How should suspected SLE be investigated?
Clinical diagnosis + antibodies
ANA – 99% of people with SLE are positive
RF – 20% of people with SLE are positive
Anti-dsDNA – highly specific (>99%) but less sensitive (70%)
Anti-Smith – highly specific (>99%) but less sensitive (30%)
How is SLE monitored?
Inflammatory markers – ESR used more commonly, CRP may be normal in active disease
Complement levels C3 and C4 are low during active disease
Anti-dsDNA titres can be used for disease monitoring
How is this diagnosis of SLE made?
Diagnosis based on >4 criteria with at least 1 laboratory, and 1 clinical (or biopsy proven lupus nephritis with positive ANA or anti-DNA.
Clinical Criteria
Acute cutaneous lupus rash – butterfly rash (over cheeks sparing nasolabial folds)
Non-scarring alopecia
Oral/nasal ulcers
Synovitis – 2 or more joints with >30mins of morning stiffness
Serositis – pleurisy or pericarditis
Urinalysis – proteinuria or red cell casts
Neurological features – seizures, psychosis, neuropathies and confusion
Haemolytic anaemia
Leukopenia
Thrombocytopenia
How is SLE managed?
High factor sun block
Hydroxychloroquine – reduces disease activity and improves survival
For skin flares use topical steroids
Maintenance
NSAIDs unless renal involvement
Hydroxychloroquine for skin and joint symptoms
Azathioprine, methotrexate or mycophenolate mofetil as steroid sparing agents
Flares
Mild (no serious organ damage): low dose steroids or hydroxychloroquine
Moderate (organ involvement): DMARDs or mycophenolate Mofetil
Severe (life or organ threatening): Urgent high dose steroids, Mycophenolate, rituximab or cyclophosphamide
What is azathioprine and what are its side effects?
Azathioprine – inhibits purine synthesis and patients should be tested for thiopurine methyltransferase (TPMT) prior to starting as this makes individuals prone to toxicity.
SE – bone marrow depression, nausea and vomiting, pancreatitis and increased risk of non-melanoma skin cancer. Significant interaction with allopurinol. Safe in pregnancy
What are the complications of SLE?
80% 15 years survival Lupus nephritis – intensive immunosuppression with steroids and cyclophosphamide or Mycophenolate Haemolytic anaemia Pericarditis CNS involvement Osteoporosis Stroke
What is antiphospholipid syndrome?
Acquired disorder characterised by a predisposition to venous and arterial thrombosis, recurrent foetal loss and thrombocytopaenia. Can occur as a primary disorder or secondary to others, most commonly SLE, but also autoimmune disorders, lymphoproliferative disorders and phenothiazines.
What are the clinical features of antiphospholipid syndrome?
Paradoxical rise in APTT – reaction of lupus anticoagulant antibodies with phospholipids involve in coagulation cascade Venous/arterial thrombosis Recurrent foetal loss Livedo reticularis Thrombocytopenia Pre-eclampsia Pulmonary hypertension
How is antiphospholipid syndrome managed?
Primary thromboprophylaxis – low dose aspirin
Secondary thromboprophylaxis
• Initial venous event or any arterial events = warfarin with target INR of 2-3
• Recurrent venous events = warfarin with target INR of 3-4
What is gout?
Definition – Inflammatory arthritis occurring as a result of urate crystal deposits. It is more common in men until age of 60 and twice as common in men of African descent.
What causes gout?
Persistently elevated levels of uric acid due to diet and genetic factors. The uric acid crystallises and deposits itself within the join capsule making moving very painful.
Triggers – drugs, stress illness and dehydration as well as many drugs, food and drink
Decreased excretion of Urate
• Drugs – diuretics and high dose aspirin
• Chronic kidney disease
• Lead toxicity
Increased production of urate
• Myeloproliferative/lymphoproliferative disorders
• Cytotoxic drugs
• Psoriasis
What are the clinical features of gout?
Patient have episodes lasting several days during flares with:
• Erythema
• Pain with maximal intensity within 12 hours
• Hot
• Swollen – can form tophi which are large swelling of urate deposition
Usually affecting the 1st metatarsal-phalangeal joint
Other joints commonly affected: ankles, knees, wrists and fingers
Without treatment will resolve within a week but repeated episodes can damage the joints resulting in chronic problems
How should suspected gout be investigated?
Blood Urate levels
Aspiration of synovial fluid if there is any doubt
X-ray in chronic disease will show – joint effusion, punched out erosions with sclerotic margins, relative preservation of joint space, eccentric erosions, no periarticular osteopenia (on contrast to RA) and soft tissue tophi may be seen
How is gout managed acutely?
Acute management
NSAIDs at maximum dose until 1-2 days after the symptoms are settled and gastroprotection is usually required
Colchicine – slower onset of action and the main SE is diarrhoea
If NSAIDs and Colchicine are CI then oral steroids
Intraarticular steroid injection
Continue allopurinol if already on it
How is gout managed in the long term?
Ongoing management Everyone who has had their first attack of gout should be using urate lowering therapy Particularly if: • 2 attacks in 12 months • Tophi • Renal disease • Uric acid renal stones • Prophylaxis if on cytotoxic or diuretic drugs
Allopurinol is first line – do not start until 2 weeks post attack/after inflammation has settled as long-term drug decision are best made when not in pain
Titrate dose against serum uric acid levels aiming for < 300umol/l
Consider Colchicine cover when starting allopurinol and may be required for 6 months
Second line agent is Febuxostat (another xanthine oxidase inhibitor)
If refractory to treatment, then trial uricase or pegloticase (infusion every 2 weeks)
Note losartan has a specific uricosuric action and is particularly useful if hypertensive
What lifestyle modifications should people with gout be encouraged to make?
Lifestyle Modification
Reduce alcohol intake and avoid during an acute attack
Lose weight if obese
Avoid food high in purines – liver, kidneys, seafood, oily fish (mackerel and sardines) and yeast products
Increased vitamin C intake
What is pseudogout?
Pseudogout is an inflammatory arthritis caused by deposits of calcium pyrophosphate crystals within the joint so also known as Acute calcium pyrophosphate crystal deposition disease. The condition often mimics gout, however, is more likely to affect proximal joints, with the knee and wrist being most commonly affected.
What are the risk factors for pseudogout?
Advanced age
Hyperparathyroidism,
Hypophosphatemia and hypomanesaemia
Acromegaly and Wilson’s disease
What are the clinical features of pseudogout?
Knee, wrist and shoulders most commonly affected
Acute onset joint swelling
Subcutaneous deposits near the affected joint
How should suspected pseudogout be investigated?
Diagnosis of pseudogout is also made by joint aspiration and microscopy, which will show weakly-positively birefringent rhomboid-shaped crystals.
X-ray – chondrocalcinosis
Exclude septic arthritis
How is pseudogout managed?
Pseudo-gout is treated acutely with NSAIDs
Intra-articular or intra-muscular or oral steroids
What is chronic fatigue syndrome?
Diagnosed after at least 4 months of disabling fatigue affecting mental and physical function more than 50% of the time in the absence of other diseases which may explain the symptoms. It is more common in females.
What are the clinical features of chronic fatigue syndrome?
Sleep problems – insomnia, hypersomnia, unrefreshing and disturbed sleep-wake cycle Muscle and/or joint pains Headaches Painful lymph node enlargement Sore throat Cognitive dysfunction General malaise Dizziness Nausea Palpitations
Physical or mental exertion make symptoms worse
How is chronic fatigue syndrome investigated?
Mostly to exclude other pathology – FBC, U&E, LFT, Glucose, TFT, CRP, Calcium, CK, ferritin, Coeliac and urinalysis
How is chronic fatigue syndrome managed?
CBT – very effective
Graded exercise therapy – formal supervised program
Pacing – organising activities to avoid tiring
Low dose amitriptyline if poor sleep
Referral to pain management clinic if this is the main symptoms
Better prognosis in the young
