Rheumatology Flashcards
What is ankylosing spondylitis?
• Seronegative arthritis that predominantly affects the spine and sacro-iliac joints
• It is a chronic inflammatory condition that can eventually lead to fusion (ankylosis) of the intervertebral joints and SI joints
What group tend to get ankylosing spondylitis?
More common in males and age of onset is typically between 20-40 year
Symptoms in ankylosing spondylitis?
• Typically, patients complain of back pain which can be cervical, thoracic or lumbar
• Pain is inflammatory in nature – i.e. it gets worse with rest and better with movement
• There is significant early morning stiffness
Examination in someone with suspected ankylosing spondylitis?
• On examination of spine schobers test would be done to show objectively that there is reduced lumbar spine flexion
• Schobers test involves measuring 5cm below PSIS and 10cm above whilst patient is upright and then get patient to bend forwards and you measure the distance, in normal situations the distance should extend beyond 20cm (so 5cm increase)
• In examination should also measure chest expansion as the costo-vertebral joints can sometimes be affected
• Will also see exaggerated lumbar lordosis and thoracic kyphosis on examination
Question mark spine or bamboo spine?
Ankylosing spondylitis
Investigations for ankylosing spondylitis?
• Bloods looking for increased inflammatory markers
• HLA testing (can be done by blood test) – ankylosing spondylitis and other seronegative arthritis are associated with HLA-B27
• X-rays of late disease may show sacroiliitis, syndesmophytes (bony growth inside ligaments), fusion of joints
• MRI is better for showing early disease changes
Non-articular manifestations of ankylosing spondylitis?
• Uveitis
• Occasionally respiratory disease, aortic valve incompetence and renal impairment
Management of ankylosing spondylitis?
• Key to management is early identification so preventative physiotherapy can be started before syndesmophyte formation and spinal mobility can be maintained
• NSAIDs can improve symptoms and signs of the disease
• DMARDs should only be given if peripheral joint involvement- they do not work in spinal disease
• Anti-TNF treatment (e.g. infliximab, certolizumab) are the only biologics that work and are only to be used in severe disease, they have been shown to reduce symptoms of spinal and peripheral joint inflammation and improve function
Explain the difference between inflammatory and mechanical pain?
inflammatory pain - worse with rest, better with movement, significant morning stiffness i.e. lasts more than 30 minutes
mechanical pain - worse with movement, better with rest, little bit of morning stiffness but not for long
What is the most prevalent seropositive polyarthropathy?
rheumatoid arthritis
Pathogenesis of rheumatoid arthritis?
1) Presence of susceptibility genes
2) Environmental triggers cause changes to the way DNA is transcribed leading to conversion of amino acid arginine into citrulline
3) This results in protein unfolding and this unfolded protein can now act as an antigen
4) Antibodies to citrullinated peptides (i.e. this unfolded protein) are distributed throughout the circulation and form immune complexes with citrullinated proteins produced in an inflamed synovium
5) There is infiltration and activation of neutrophils
What groups most commonly get rheumatoid arthritis?
• More common in women than men
• Most common age of onset is between 30 to 50yo
Presentation of rheumatoid arthritis?
• There is a progressive, symmetrical, peripheral polyarthritis evolving over a period of a few weeks or months
• Pain is inflammatory in nature i.e. It gets worse with rest and better with movement
• There is prolonged morning stiffness (lasting more than 30 minutes)
• There is involvement of the small joints of the hands and feet – the MCPs, PIPs and MTPs – not the DIPs (DIPs are in osteoarthritis)
• Symmetric distribution
• Inflamed joints are soft and squishy and on examination there will be a positive compression test of MCPs and/ or MTPs (when you squeeze over the joints it causes pain)
What are some deformities you can get later on in rheumatoid arthritis if it is not managed properly?
There can be ulnar deviation (fingers bend abnormally towards little finger), boutonniere deformity (fixed flexion of PIP and hyperextended DIP), swan-neck deformity (fixed flexion of the DIP, hyperextended PIP)
Antibodies for rheumatoid arthritis?
Anti-CCP - very specific, sensitivity 66% (so about 34% of people with RA will not be picked up by this test)
rheumatoid factor - very sensitive, but not very specific (so almost everyone with RA will be picked up by this test but so will lots of people without RA)
Imaging in rheumatoid arthritis?
• In early disease the XR may be normal however there may be some signs of soft tissue swelling or periarticular osteopenia
• In late disease may see erosions and subluxations
• Ultrasound can be good for showing synovitis in early disease and can detect MCP erosions
• MRI is occasionally used to show early disease
List some non-articular manifestations of rheumatoid arthritis?
• Subcutaneous rheumatoid nodules- these are firm subcutaneous nodules that generally occur over pressure points, they can be removed surgically but tend to recur
• Lung Disease- range of conditions can occur, can get airways disease, pleural disease, pulmonary fibrosis, intrapulmonary nodules
• Heart Disease- raynauds, pericarditis, myocarditis, and endocarditis
• Nervous System Involvement- peripheral neuropathies
• Eye Disease- Scleritis and episcleritis
• Kidneys- amyloidosis causing proteinuria, nephrotic syndrome and CKD
• Anaemia
Management of rheumatoid arthritis?
• First line treatment is DMARDs (disease modifying anti rheumatic drug) and first line DMARD is usually methotrexate (other examples include leflunomide or sulfasalazine)
• These should be started as soon as possible and ideally within 3 months of onset of persistent symptoms
• Offer additional DMARD in combination if remission/ low disease activity has not been reached
• If tried 2 DMARDs and still high disease activity biologics are offered, examples include infliximab, entanercept and rituximab
• Steroids can be used for managing flares
Drug side effects in rheumatoid arthritis?
• Methotrexate is teratogenic and must be stopped in females at least 3 months before conception
• Side effects of DMARDS include bone marrow suppression, infection, LFT derangement, pneumonitis and nausea (blood tests need to be done regularly on these drugs)
• Side effects of biologics include increased risk of infection particularly tuberculosis and patients need to be screened for latent infections before they go on these drugs
What type of crystals are there in gout?
monosodium urate crystals
Explain what gout is and what causes it?
• An inflammatory arthritis that is associated with hyperuricaemia and presence of intra-articular urate crystals
• Uric acid is the final compound in the breakdown of purines in DNA metabolism
• Hyperuricaemia can be caused by increased urate production or decreased urate excretion
• Increased urate production may be due to inherited enzyme defects, malignancy, psoriasis, haemolytic disorders or high purine intake e.g. in alcohol, red meat or sea food
• 2 common causes of reduced urate excretion are diuretics and chronic renal impairment
What groups is gout more common in?
• More common in men than women
• Generally, in older/ middle aged people
• (in young people it suggests some sort of genetic cause)
Presentation of acute gout?
• 1st presentation is typically in the MTP joint in the foot
• Sudden onset of agonizing pain, swelling and redness
• The attack settles in 10 days without treatment and 3 days with treatment
• May have normal uric acid during the attack
Presentation of chronic gout?
• Individuals with persistently high levels of uric acid can present with chronic tophaceous gout, as sodium urate forms smooth white deposits (termed tophi) in the skin and round joints, on the ear, fingers or the Achilles tendon
• There is chronic joint pain and sometimes acute attacks on top of the chronic pain
• It is often associated with renal impairment and/ or the long-term use of diuretics
What is polymyalgia rheumatica?
• This is a chronic inflammatory condition of muscles
• It is relatively common
What groups of patients tend to get polymyalgia rheumatica?
• It almost exclusively occurs in the elderly
• Thought to be associated with HLA-DR4, parvovirus and adenovirus
Presentation of polymyalgia rheumatica?
• Symmetrical myalgia of the proximal muscles (may start unilateral but becomes bilateral)
• Morning stiffness
• Reduced range of movement due to pain but the actual muscle strength is normal (this is in contrast to polymyositis where the muscle is weak)
• Fatigue anorexia, weight loss and low grade fever may occur
• PMR is associated with temporal/ giant cell arteritis and it is very important to ask about symptoms of GCA as it can result in loss of sight if untreated
What is polymyalgia rheumatica associated with?
giant cell arteritis - important to ask about symptoms as can result in loss of sight!!!
Diagnosis of polymyalgia rheumatica?
• No specific diagnostic test but most people have raised inflammatory markers
• Diagnosis is basically done by exclusion and response to steroids confirms the diagnosis
Treatment for polymyalgia rheumatica?
• Tends to respond very well to low dose steroids
• The condition generally lasts 18 months to 2 years before resolving
• If just PMR then start prednisolone 15 mg daily and gradually reduce the dose
• If GCA need to start at higher dose of steroids 40-60 mg daily and then reduce
Pathogenesis theory for SLE?
1) There is defect in the apoptosis mechanism meaning that when cells die their contents float around longer than normal so this causes the immune system to develop auto-antigens from the cells
2) Cells expressing these antigens are attacked by the immune system
3) There is formation of nucleosome/ anti-nucleosome complexes
4) These complexes are mainly deposited in the skin and kidneys (hence these are the areas most frequently affected by lupus)
What group of patients is SLE more common in?
• Lupus is 9x more common in females than males and commonly presents in childbearing years
• It is more common and there are more severe presentations in those of Afro-Caribbean, Hispanic American, Asian and Chinese ethnicity
Common presentations of SLE?
fatigue, skin problems (usually relating to sun exposure) and arthralgia
classic skin problems: malar butterfly rash, discoid lesions, photosensitivity, alopecia
also aphthous mouth ulcers and pleuritic chest pain can be complications
List some organ system manifestations of SLE?
• Renal- lupus nephritis, it should be noted that renal involvement is often asymptomatic until it is very serious so it is very important to do urine analysis in anyone suspected of SLE to check for proteinuria
• Haematological- leukopenia, lymphopenia, anaemia, thrombocytopenia
• Neuropsychiatric- seizures, psychosis, headache, aseptic meningitis
• Cardiac- pericarditis, pericardial effusion, pulmonary hypertension, endocarditis, accelerated ischaemic heart disease
• Respiratory- pleural effusions, rarely pulmonary fibrosis
• GI- less common but include autoimmune hepatitis, pancreatitis and mesenteric vasculitis
Describe antibody tests for lupus?
• Best antibody test is Anti-double stranded DNA (anti-ds-DNA), this is specific for lupus and the titre correlates with disease activity and is associated with lupus nephritis (however only present in 70% of people with SLE so if someone doesn’t have it that doesn’t rule out lupus)
• Anti-nuclear antibody – this is the “gateway” to connective tissue disease, i.e. will be positive in most people with any connective tissue disease which could be SLE or something else e.g. scleroderma or sjogrens. It has low specificity so doesn’t confirm SLE but if someone is negative they are unlikely to have SLE
• Anti-Ro and Anti-La is present in some with lupus and can be associated with neonatal lupus, these antibodies aren’t present in everyone with lupus and are also present in Sjogrens
• Anti-Sm is very specific for SLE but only 2/3 of people with SLE will be positive
What is antiphospholipid syndrome and what other condition is it related to?
• This condition can occur on its own but it is often secondary to SLE
• It is associated with recurrent venous and arterial thrombosis and recurrent miscarriages
Antibodies for antiphospholipid syndrome?
lupus anti-coagulant, anti-cardiolipin and anti-beta2glycoprotein
Management of antiphospholipid syndrome?
• If someone with this condition has had an episode of thrombosis they should be treated with anti-coagulation, those who have recurrent pregnancy loss can be put on LMWH during pregnancy, if someone is positive for the antibodies but never had an episode of thrombosis they do not require anti-coagulation
- note that DOACs have questions over if they are as effective as warfarin and LMWH in preventing thrombosis and are generally not used in APS
What do all patients with SLE need screened for?
Renal involvement:
All patients with SLE need a urine analysis done and if positive for protein then a kidney biopsy should be done to check for lupus nephritis
General measures for those with SLE?
• Education on fatigue
• Sun protection and advice on avoiding excessive exposure to sunlight
• Patients should be encouraged to reduce cardiovascular risk factors
Symptomatic treatment for SLE?
• Most patients don’t need oral corticosteroids or immunosuppressive agents
• Arthralgia, arthritis, fever and serositis all respond well to standard doses of NSAIDS
• Topical corticosteroids are effective for treating skin disease
• Antimalarial drugs such as hydroxychloroquinine also help mild skin disease, fatigue and arthralgias although patients require regular eye checks due to retinal toxicity
Treatment for SLE patients with Organ involvement?
• Corticosteroids and immunosuppressive drugs are given in organ involvement
• Examples of immunosuppressive agents include methotrexate or azathioprine (in moderate disease) or cyclophosphamide (in severe disease as very potent), cyclophosphamide is being increasingly replaced by mycophenolate mofetil
Monitoring for patients with SLE?
• It is important to monitor patients over time as new manifestations can develop
• Anti ds-DNA and complement levels are checked regularly (low levels of complement correspond to high disease activity because complement is consumed by the autoimmune disease process)
Management of gout?
Acute
• High dose NSAIDS e.g., diclofenac, naproxen
• Colchicine is an alternative medication for pain if the patient cannot tolerate NSAIDs
• Corticosteroids can be given if resistant pain
Chronic
• Xanthine oxidase inhibitors help lower urate levels (xanthine oxidase is an enzyme used in purine metabolism so inhibiting it lowers urate) the main one is allopurinol, another example would be febuxostat
• It is important that these are not given during an acute attack as they can make an acute attack worse
• They should be given after the attack has settled to prevent future attacks
• NSAIDs can potentially be used to try and stop attacks whilst hyperuricaemia is being corrected
What is pseudo gout?
• Inflammatory arthritis caused by deposition of calcium pyrophosphate crystals in the joint
Causes and groups of patients that tend to get pseudo gout?
• More common in the elderly (wouldn’t generally consider in someone < 70yo)
• Causes include hyperparathyroidism, previous cartilage problems, hypothyroidism, haemochromatosis, hypomagnaesia
Presentation of pseudo gout?
• Tends to affect larger joints like the knee
• May get attacks of pain, swelling and stiffness
Diagnosis of pseudo gout?
• The radiological appearances are known as chondrocalcinosis
• Joint fluid microscopy shows rhomboidal weakly positive birefringement crystals
Management of pseudo gout?
• Unlike gout there are no prophylactic medications
• NSAIDs, colchicine or steroids can be given in acute attacks like in gout
What is osteoarthritis?
commonest disorder of joints
basic pathology is degeneration of the articular cartilage
Difference between primary and secondary osteoarthritis?
• Primary osteoarthritis has no obvious predisposing cause
• In secondary osteoarthritis there is a clear association with some predisposing condition which can be virtually any abnormality of a joint e.g. previous injury, abnormal stress on joint, previous inflammation
Groups more likely to get osteoarthritis?
• Prevalence increases with age
• Obesity predisposes to OA as putting more weight and therefore stress through the joints
• To some extent it runs in families
Presentation of osteoarthritis?
• Tends to affect the larger weight bearing joints e.g. the knee, hip, lumbar and cervical spine
• It can also affect the DIPs and PIPs in the hand but NEVER the MCPs (MCP involvement BUZZWORD for rheumatoid arthritis/ autoimmune condition!!!)
• Pain is mechanical – this means it is worse on activity but relieved by rest (this contrasts to inflammatory pain present in RA etc.)
• Can get stiffness in the morning but only lasts for 5-10 mins (stiffness is nowhere near as bad as RA)
Examination of osteoarthritis?
• May not see anything abnormal
• May be able to palpate crepitus (grating sensation over joints)
• May be hard swelling over affected joints (this is due to osteophyte formation)
• There may be reduced range of movement
• Joints may be tender and may be presence of effusions
• In OA affecting the hands may see Heberden’s nodes (swelling over the DIPs) and/ or Bouchard’s (swelling over the PIPs)
Diagnosis of osteoarthritis?
• Usually, a clinical diagnosis and XR is not needed to confirm
• However, if done features on XR include:
(LOSS)
- Loss of joint space
- Osteophyte formation
- Subchondral cysts
- Subchondral sclerosis
It should be noted that some patients with severe symptoms may have only small changes on XR and some patients with no symptoms may have substantial changes on XR.
Management of osteoarthritis?
There is no cure, all about managing symptoms
Step wise management:
1) Offer education and reassurance
2) Give advice on self-management in exercise, weight loss (if overweight) and suitable pacing
3) Refer to physiotherapy (can also refer to OT or podiatrist)
4) Analgesia (update from guidance 2022)- first should try topical NSAIDs, then oral NSAIDS, no longer meant to routinely prescribe paracetamol or weak opioids - only prescribe these for short term relief
5) Surgical treatment with joint replacement is a definitive solution however this is a big surgery with risk of complications and joint replacements only last for approximately 10-20yrs so other options should be tried first
Pathology of osteoarthritis?
• Degradation and damage to cartilage causes remodelling of bone due to active response of chondrocytes in the cartilage and inflammatory cells in the surrounding tissues
• Release of enzymes results in further degradation
• Initially there is flaking and fibrillation of the cartilage
• Then exposure of subchondral bone which gets harder (sclerotic) known as eburnation
• Remodelling changes lead to formation of osteophytes and subchrondral bone cysts
Used to be thought that osteoarthritis was purely a degenerative disease, but it is an inflammatory cycle in response to joint wear and tear that some people are more prone to than others
