Musculoskeletal Flashcards
Definition of ankylosing spondylitis:
Ankylosing spondylitis is a seronegative inflammatory arthritis, primarily involving the axial skeleton. It is a type of axial spondyloarthritis known as radiographic axial spondyloarthritis, meaning that there are X-ray changes such as sacroiliitis (versus non-radiographic axial spondyloarthritis, where there may be changes visualised on MRI but not on X-ray.
What is the most important genetic factor for ankylosing spondylitis?
HLA-B27
What is an important modifiable risk factor for ankylosing spondylitis?
Smoking is an important modifiable risk factor
What are the musculoskeletal symptoms of ankylosing spondylitis
Lower back and buttock pain - alternating buttock pain
Pain elsewhere in the spine may also occur
Stiffness that is worse in the morning and with rest, and improves with activity
Patients may wake in the second half of the night with pain
Pain and stiffness respond to NSAIDs
Peripheral enthesitis (pain, stiffness and/or swelling of the Achilles, quadriceps or patellar tendons, as well as plantar fasciitis)
Peripheral arthritis occurs in up to a third of patients, commonly affecting the ankles, knees and hips
What are the extra-articular involvements of ankylosing spondylitis?
Anterior uveitis (eye pain, redness and blurred vision)
Inflammatory bowel disease (e.g. diarrhoea, abdominal pain, rectal bleeding)
Osteoporosis (increased risk of fragility fractures)
Aortitis which may lead to aortic regurgitation (shortness of breath, fatigue, chest pain)
Upper lobe pulmonary fibrosis (shortness of breath, exercise intolerance, dry cough)
IgA nephropathy (haematuria, fatigue)
Systemic symptoms of weight loss and fatigue
Triple A: anterior uveitis (most common), aortic insuffiencies and apical pulmonary fibrosis.
Signs on examination of ankylosing spondylitis
Restricted movement in the lumbar spine
Schober’s test can be used to assess this as follows:
Mark two points on the back (one at the level of the L5 spinous process and one 10 cm above this)
On forward flexion, the distance between the two points should increase by 5cm or more
If the increase in distance is <5 cm, this indicates restricted forward flexion
Hyperkyphosis of the thoracic spine may develop as the disease progresses
Reduced C-spine movements and fixed flexion deformities may be seen
This can be measured by asking the patient to stand with their back to the wall
A distance of > 2 cm between their occiput and the wall is abnormal
“Question mark posture” refers to the combination of thoracic hyperkyphosis, loss of the lumbar lordosis and flexion deformities of the neck and hips (seen in advanced disease)
Reduced chest expansion may be seen
Affected joints may be tender and swollen
Affected tendons may be tender, stiff or swollen
What would you expect to see on a blood test of ankylosing spondylitis?
FBC which may show anaemia of chronic disease
ESR and CRP are often raised due to inflammation
HLA-B27 positivity supports a diagnosis but a negative result shoudl not rule out ankylosing spondylitis
What are the image investigations for ankylosing spondylitis?
Pelvic X-rays looking for sacroiliitis
This is usually bilateral and symmetrical
In early disease, sclerosis or erosion of the sacroiliac joints may be difficult to visualise
In advanced disease, there is ankylosis or fusion of the joint
Lumbar X-rays may show squaring of the vertebral bodies
In late disease, there is ossification of spinal ligaments (“dagger sign”)
Fusion of the vertebral column by syndesmophytes may be seen (“bamboo spine”)
MRI may be required if X-rays are normal - MRI is the gold standard
Sensitivity for sacroiliitis is higher especially in early disease
Ultrasound or X-rays of other sites of pain may be indicated e.g. for enthesitis or peripheral arthritis
DEXA scans may be used to assess bone density
Signs of osteopenia or osteoporosis may be seen on other imaging also
DEXA imaging of the spine may be inaccurate due to syndesmophytes and calcification of ligaments (hip measurements tend to be more reliable)
Conservative management for ankylosing spondylitis?
Referral to rheumatology for confirmation of the diagnosis and ongoing management
Involvement of other specialties may be required for extra-articular manifestations e.g. emergency ophthalmology assessment for suspected anterior uveitis
Smoking cessation counselling
Physiotherapy referral for a structured exercise programme to optimise mobility
Occupational therapy, orthotics or podiatry input may be required to help maximise function
Monitor bone density and consider bone protection for osteoporosis
Assess cardiovascular risk and consider initiating treatment (e.g. statins)
What is the medical management for ankylosing spondylitis?
NSAIDs as the first-line treatment
These should be used at the lowest effective dose
Symptoms should improve in 2-4 weeks
Switching to a different NSAID should be considered before escalating treatment
Consider co-prescribing a PPI to prevent peptic ulceration
Paracetamol +/- codeine may be trialled if NSAIDs are contraindicated
Adjuncts for analgesia include local steroid injections
Biological DMARDs are the next step in treatment of severe disease if response to NSAIDs is inadequate
Anti-TNF agents such as infliximab or adalimumab are the treatment of choice
Secukinumab (an anti-IL17A biologic) is another option
Regular monitoring is required for patients on these medications
They are usually highly effective
Conventional disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine and methotrexate are not effective for axial arthritis but may be used for peripheral involvement
Topical cyclopentolate for the anterior uveitis
What is the surgical management for ankylosing spondylitis?
Referral to spinal surgery for patients with complications such as suspected spinal fractures or cauda equina syndrome
Surgery to correct spinal deformities may be indicated in some patients with severe disease significantly affecting quality of life
Total hip replacement may be considered in patients with structural damage leading to refractory hip pain and/or difficulty mobilising
What are the complications for ankylosing spondylitis?
Spinal deformities including fusion of the axial skeleton in severe cases
Limited mobility
Deterioration in mental health due to chronic pain and limitations in function
Sleep difficulties due to pain and stiffness
Osteoporosis and spinal fractures
Increased cardiovascular risk
Heart failure
Aortic regurgitation and other valvular disorders
Restrictive lung disease
Apical pulmonary fibrosis
IgA nephropathy
Anterior uveitis
Side effects from treatment e.g. immunosuppression with DMARDs, peptic ulcers with NSAIDs
What is the prognosis for ankylosing spondylitis?
Ankylosing spondylitis tends to be a progressive disease involving irreversible damage - however the course of the disease is variable and effective and prompt treatment minimises disability.
Good prognostic factors include:
Low functional impairment at diagnosis
Young age at disease onset
Short disease duration
High inflammatory markers at diagnosis
Key signs and symptoms of crystal arthropathies?
joint pain and swelling, often affecting one joint at a time
What is the most important investigation to confirm a crystal arthropathy?
Joint aspiration with subsequent polarised-light microscopy, culture and sensitivity is the gold standard:
The fluid may appear milky
On microscopy, a raised white cell count may be seen (typically <50 × 109/l – values above this are more indicative of septic arthritis)
Crucially, the presence of crystals on polarised light microscopy confirms the diagnosis
Note: It is important to send the fluid for Gram stain and culture to exclude the diagnosis of septic arthritis.
What is gout caused by?
Caused by monosodium urate crystals
What do you see on light microscopy of gout?
negatively birefringent and needle-shaped on light microscopy
Gout has Negatively birefringent, Needle-shaped crystals
What is pseudogout caused by?
Caused by calcium pyrophosphate dihydrate crystals
What do you see on light microscopy of pseudogout?
Pseudogout has Positively birefringent, rhomboid-shaped crystals
What blood tests do we do for gout?
Uric acid (gout only) – It is important to monitor uric acid levels in recurrent gout (A serum urate of 360 micromol/L or more confirms the diagnosis) and urate-lowering therapies reduce the risk of further attacks note: urate levels often fall during an acute episode of gout so are not often useful in the diagnosis of acute gout
There is no equivalent test for pseudogout
Renal function (gout only) – Renal impairment is a risk factor for gout
Inflammatory markers – These may be raised as in any inflammatory arthritis
What would you see in an X-ray for gout?
Gout – may be useful as a baseline
X-ray changes (aside from soft-tissue swelling) are usually not seen until multiple attacks of gout have occurred, and can then include:
Tophi
“rat bite” Erosions
Subchondral sclerosis
What would you see in an x-ray for pseudogout?
Chondrocalcinosis (calcification of cartilage)
The changes that are seen in osteoarthritis include:
Loss of joint space
Osteophytes
Subarticular sclerosis
Subchondral cysts
What would you see in a ultrasound of gout?
The double-contour sign is the most sensitive ultrasound finding of gout
A hyperechoic irregular band over the superficial margin of the articular cartilage
Gouty tophi and erosions may be seen
Define gout:
Gout is a form of arthritis that occurs when monosodium urate crystals deposit in joints. This causes both acute inflammation (gout flares) and in the longer-term, a chronic gouty arthritis with tophi (hard deposits of monosodium urate crystals in soft tissues).
What is the main risk factor for gout?
Hyperuricaemia (high urate) is the main risk factor (although most patients with a high urate do not develop gout, and some patients develop gout with a normal urate)
What are some factors that contribute to gout?
Older age - typically patients are above the age of 40
Male sex (post-menopausal women are also at increased risk)
Comorbidities including chronic kidney disease (CKD), diabetes, osteoarthritis, hypertension
Excess alcohol consumption
Dietary excess of meat, seafood and sugary drinks
Overweight or obesity
Medications such as thiazide diuretics and ciclosporin (diuretics (furosemide) and salicylates (aspirin) are risk factors)
Anti-tuberculosis medications such as pyrazinamide and ethambutol can significantly decrease uric acid excretion, increasing the risk of acute gout attacks.
Family history of hyperuricaemia and gout
Genetic disorders associated with hyperuricaemia such as Lesch-Nyhan or glycogen storage disorders
Organ transplant recipients
Acute attacks may be triggered by stressors including:
Trauma and surgery
Intercurrent illness
Alcohol excess
Sudden excess of protein in the diet
Chemotherapy (due to cell breakdown)
Urate-lowering medications can cause a flare (as crystals are shed into the joint space)
Signs and symptoms of acute gout?
Commonly presents with a monoarthritis
Pain is severe and rapid in onset, reaching a peak within 24 hours
Affected joints become swollen, erythematous and tender
The first metatarsophalangeal (MTP) joint is the most commonly affected (70% of first attacks)
Other common sites include the knees, ankles, midtarsal joints, wrists, elbows and small joints of the hands
Systemic features such as fever and malaise may be seen
Patients may be tachycardic due to pain
For the medication for gout which screening tests need to be done first?
Liver function tests are needed prior to starting febuxostat
Patients from Han Chinese, Thai and Korean backgrounds should be screened for HLA-B5801 prior to starting allopurinol (as this increases the risk of severe cutaneous adverse reactions if present)
What are the first three treatments for gout?
NSAIDs e.g. naproxen
Give at maximum dose
Continue until 1-2 days after resolution of symptoms
Consider giving with a PPI for gastric protection
Avoid in peptic ulcer
Avoid in heart failure, patients at high risk of gastrointestinal bleeding and severe renal failure
Colchicine
Dosing is 500 mcg 2-4 times per day
Continue until pain resolves
Dose-dependent side effects include diarrhoea, nausea and vomiting
Oral corticosteroids
e.g. prednisolone 30mg once a day for 3-5 days
Useful in patients with contraindications to both NSAIDs and colchicine
An injection of intramuscular, intravenous or intra-articular steroids can also be considered
Alongside this, consider other analgesia (e.g. paracetamol) and other non-pharmacological pain relief such as ice packs
A combination of the above may be tried if a single agent is ineffective
Patients should be advised to keep the affected joint cool and exposed and to rest and elevate the affected limb
Patients already on urate lowering treatment should continue this throughout the acute flare
In patients with chronic kidney disease on haemodialysis and an eGFR less than 10ml/minute/1.73m2, low dose steroids may be appropriate for managing gout attacks due to the need to avoid NSAIDs and Colchicine.
What is the prevention of acute gout?
Reducing alcohol consumption
Maintaining a balanced diet and healthy weight
Investigate and treat for comorbidities such as hypertension or CKD
Review medications and consider switching medications such as thiazides that cause hyperuricaemia
Where possible, switch antihypertensive medications to losartan or amlodipine, which have modest urate-lowering effects
Initiating urate-lowering therapy (see below)
When should someone with acute gout be sent to prompt referral to or discussion?
Patients with complications of gout
Atypical presentations (e.g. aged under 30) or uncertain diagnosis
Pregnant patients
Stage 3b to 5 CKD
Organ transplant recipients
Those at risk of adverse effects with standard medical treatment, or if treatment is ineffective or not tolerated
Indications for urate - lowering therapy?
Multiple or troublesome gout flares
Chronic gouty arthritis or tophi
Patients taking diuretics
CKD stage 3 to 5
How do you monitor urate levels?
ULT should be started at least 2-4 weeks after an acute flare if possible as medications can precipitate further attacks
Colchicine should be given whilst starting ULT to reduce the risk of a flare (NSAIDs or steroids are second-line)
Doses should be uptitrated with monthly monitoring of serum urate levels, aiming for a target of 360 micromol/L
A target urate level of 300 micromol/L may be helpful in patients with tophi or chronic arthritis due to gout, or those who continue to have flares despite ULT
First-line options are either allopurinol or febuxostat which are both xanthine oxidase inhibitors (so reduce uric acid production)
It is advised to start allopurinol after an acute flare of gout has completely settled. If started before this it can paradoxically cause symptoms to worsen.
Allopurinol is preferred in patients with significant cardiovascular disease
Allopurinol can cause serious side effect of Steven Johnson Syndrome
Second line options include uricosuric medications (e.g. probenecid) - these can promote stone formation so should be avoided if there is nephrolithiasis
Complications of gout:
Chronic gouty arthritis and permanent joint damage
Tophi, which may become inflamed or infected
Nephrolithiasis due to uric acid precipitation - these are responsible for 8% of renal calculi and are radiolucent
Chronic urate nephropathy - urate deposition in the renal interstitium causes inflammation and fibrosis
Both allopurinol and febuxostat can cause rashes, which in rare cases may be severe (e.g. Stevens Johnson syndrome or toxic epidermal necrolysis)
Increased risk of cardiovascular disease and mortality
Define pseudogout:
Articular and periarticular calcium pyrophosphate deposition (CPPD) causes a spectrum of disease, ranging from asymptomatic radiographic changes, to acute arthritis (also known as “pseudogout”) as well as a chronic inflammatory arthritis.
What are the risk factors for psuedogout?
Previous joint injury or surgery
Hyperparathyroidism and Haemochromatosis are specific for pseudogout!
Hypomagnesaemia
Hypothyroidism
Family history (ANK human gene mutations may be present)
What are the acute symptoms of CPP crystal arthritis?
Typically presents with an acute monoarthritis (rarely, an oligoarthritis)
The knee, wrist, shoulder and elbow are the most commonly affected joints
The affected joint is swollen, erythematous, warm and tender with an effusion on examination
Systemic symptoms include fever and malaise
What are the chronic CPP crystal inflammatory arthritis symptoms?
Usually a polyarticular arthritis affecting the small joints of the upper and lower limbs
May present similarly to osteoarthritis with knee involvement, but inflammatory flares and severe articular damage can differentiate
May resemble rheumatoid arthritis with wrists and metacarpophalangeal joint involvement
Symptoms and signs are of chronic intermittent swelling and pain of affected joints
What is the management for CPPD arthritis?
There are no treatments that eliminate CPP crystals or reduce articular deposition and so management is symptomatic
Non-pharmacological treatment includes resting the joint and using ice packs for pain
Joint aspiration may help to relieve symptoms as well as being important for diagnosis
As for an acute gout flare, options include a short course of NSAIDs, colchicine or steroids (either systemic or an intra-articular injection)
Long-term low dose colchicine may be used in chronic CPP arthritis to reduce flares
Long-term NSAIDs or steroids may also be considered however have a higher burden of adverse effects
Causes of secondary CPPD (as above) should be investigated for and treated e.g. with magnesium supplementation for hypomagnesaemia
What is the prognosis for CPP arthritis?
Acute CPP arthritis usually resolves within days to short weeks, although some flares may last months
Chronic CPP arthritis can cause significant joint damage with subsequent disability
In some cases of refractory chronic disease, biologic agents have been trialled (e.g. anakinra)
A diagnosis of pseudogout in a patient with diabetes and signs of bronzed skin pigmentation and gynaecomastia should raise suspicion for ???, characterised by excessive iron deposition leading to potential joint complications, thus, checking serum iron levels is crucial.
hereditary haemochromatosis
expect elevated serum iron in a blood test
What are the side effects of colchicine?
the most common side effects are diarrhoea, nausea and vomiting
Define osteoarthritis?
Osteoarthritis (OA) is the commonest form of arthritis, which is characterised by degenerative changes affecting the entirety of joints affected. Cartilage is lost, the subchondral bone becomes sclerosed with formation of osteophytes and subchondral cysts and there is inflammation of the synovial membrane lining the joint capsule (synovitis).
Risk factors for osteoarthritis:
Older age
Female sex
Overweight or obesity
Family history of OA
Previous joint injury
Joint damage due to inflammation (e.g. in patients with inflammatory arthritis)
Physical inactivity and reduced muscle strength
Low bone density
Deformities such as development dysplasia of the hip or leg length discrepancy
Stresses on joints due to occupational factors (e.g. repetitive squatting or kneeling) or exercise
Key symptoms of osteoarthritis:
Pain in the affected joint exacerbated by use
Pain may radiate e.g to the thigh, knee and ankle in hip OA, or to the wrist in hand OA
Joints may feel stiff (although prolonged morning stiffness is suggestive of inflammatory arthritis)
Worse after activity related exercise
Functional limitations such as difficulty opening jars (hand OA) or mobilising (knee or hip OA)
Locking or giving way of the knee
Examination findings of osteoarthritis:
Restricted and painful range of motion (e.g. in hip OA internal rotation with the hip flexed is particularly painful)
Crepitus (friction between bone and cartilage)
Affected joints may appear swollen or enlarged
A small effusion may form, especially when the knee is affected
Synovitis may present with mild soft tissue swelling, tenderness and warmth
Muscle wasting and weakness can result from disuse atrophy
Joint instability
An antalgic gait (“limping”) in knee OA
Trendelenburg gait in hip OA (due to weak abductors patients lurch towards the affected hip)
Deformities, including:
DIP and thumb CMC
Heberden’s nodes (bony nodules over the distal interphalangeal joints)
Bouchard’s nodes (bony nodules over the proximal interphalangeal joints)
Fixed flexion of the first carpometacarpal joint with hyperextension of the distal joints
This may lead to squaring of the joint with subluxation and remodelling
Ulnar or radial deviation of joints in the hand may occur
In severe hip OA the leg may be shortened due to fixed flexion and external rotation
Varus (most commonly) or valgus deformities of the knees
When can diagnosis of osteoarthritis be made on clinical history alone?
Osteoarthritis can be diagnosed clinically if the following apply:
The patient is aged over 45 years AND
The patient has activity-related joint pain AND
The patient has no morning stiffness or the morning stiffness lasts less than 30 minutes
Typical findings of osteoarthritis on x-ray can be remembered using:
Loss or narrowing of joint space due to thinning of cartilage
Osteophytes i.e. formation of new bony spurs at the joint margins
Subchondral sclerosis i.e. increased bone density beneath the cartilage
Subchondral cysts which are fluid-filled sacs in the subchondral bone
What is the conservative management for osteoarthritis?
Patient education and advice on self-care e.g. appropriate footwear
Weight loss advice and signposting to services in patients with excess body weight
Exercise has many benefits including strengthening muscles, improving fitness, reducing pain and improving function
Options include online fitness programmes designed for people with arthritis, physiotherapy and supervised exercise sessions
Physiotherapy services may also be able to offer manual therapies and joint supports such as braces or splints to reduce load and improve instability
Occupational health input may be needed in patients with functional impairment to assess their working environment and suggest adaptations
Patients should be asked about psychosocial stressors and support offered e.g. for associated depression and anxiety
Occupational therapy input may be helpful to advise on aids and devices to assist with activities of daily living (e.g. walking sticks, sock aids, grab rails, tap turners)
Podiatry input may be useful to assess the biomechanics of joint pain and advise on orthotic devices such as insoles
Referral to a pain management service may be appropriate for patients who have not responded to maximal medical (and if appropriate, surgical) management of OA
Assess falls risk and consider referral to specialist services for patients at risk (e.g. those with abnormal gait or balance, or who have had a fall in the last year)
What is the medical management for osteoarthritis?
First-line analgesia is with topical NSAIDs (such as ibuprofen gel) - patients should be made aware that some systemic absorption may occur
If this is ineffective or unsuitable, oral NSAIDs should be considered (with a PPI for gastroprotection if there are risk factors for gastrointestinal side effects)
Paracetamol or weak opioids (e.g. codeine) may also be used in the short-term
Topical capsaicin is another option, especially for knee OA
Intra-articular steroid injections may be considered if other treatments are not effective, and/or to enable therapeutic exercise
What is the surgical management for osteoarthritis?
Patients with OA of the hip, knee or shoulder who have symptoms significantly impacting quality of life despite optimal medical management should be considered for orthopaedic referral
The usual operation offered is an arthroplasty (joint replacement)
Rehabilitation before and after surgery is key to optimising outcomes
Complications of osteoarthritis:
Joint deformities (as above)
Increased risk of falls
Functional limitations, e.g. hand OA may making writing, turning keys or fasting buttons challenging
Reduced mobility
Sleep difficulties
Low mood and anxiety
Chronic pain
What is the prognosis of osteoarthritis?
Not all cases of OA are progressive and the disease course is variable
OA of the hands generally has a good prognosis, especially interphalangeal joint involvement
Hip OA has a poorer prognosis with many patients requiring arthroplasty
Knee arthroplasties for OA are also common however many patients’ symptoms improve or remain stable with time
Intermittent flares of OA may occur, where symptoms increase in intensity suddenly
Flares tend to last for a few days before improving
Define osteomalacia?
Osteomalacia is a metabolic bone disease that occurs in adults (i.e. after growth plate fusion) and is characterised by insufficient osteoid mineralisation.
Known as rickets in children
Risk factors for vitamin D deficiency?
Older age (aged over 65)
Darker skin pigmentation (e.g. South Asian or African-Caribbean patients)
Obesity
Patients who cover their skin for cultural, religious or health reasons
Housebound patients or those living in care homes
Malabsorption due to a gastrointestinal disorder or previous weight-loss surgery
End-stage chronic kidney disease
Severe liver cirrhosis
Vegetarian or vegan diets
Medications increasing risk of vitamin D deficiency (e.g. orlistat, carbamazepine, antacids)
What causes Vit D deficiency in osteomalacia?
The commonest cause of osteomalacia is vitamin D deficiency, which may occur due to:
Inadequate dietary intake
Lack of exposure to sunlight
Decreased absorption e.g. in coeliac disease, post-gastrectomy or pancreatic insufficiency
Medications e.g. antiepileptic medications, corticosteroids, rifampicin and thiazide diuretics
Vitamin D metabolism may be defective, for example in chronic kidney disease or cirrhosis
Phosphate deficiency may also cause osteomalacia
Dietary deficiency or decreased absorption may be responsible
Renal phosphate wasting may occur in Fanconi syndrome or rarely due to malignancy
The pathophysiology of osteomalacia involves chronic vitamin D (or rarely phosphate) deficiency leads to osteoclastic destruction of bone to maintain serum calcium levels
Resorbed bone is replaced with unmineralised osteoid and bone mineral density declines as a result (causing or worsening osteopenia or osteoporosis)
Symptoms of osteomalacia?
Bony pain (e.g. lower back, pelvis, shoulders, legs or ribs)
Muscular weakness and pain
Difficulty walking
Malaise and lethargy
Persistent fatigue
Paraesthesias (late sign)
Signs of osteomalacia?
A waddling gait
Proximal muscle weakness
Generalised bone and joint tenderness
Signs of hypocalcaemia (e.g. tetany, carpopedal spasm)
Spinal deformities e.g. kyphoscoliosis
Bedside tests for osteomalacia?
Urinalysis may show proteinuria in chronic kidney disease
Urinary calcium will be reduced
24 hour urinary phosphate to screen for renal phosphate wasting
Blood tests for osteomalacia?
Vitamin D - deficiency and osteomalacia occur at levels of under 25 nmol/L (levels of 25-50 may be insufficient; over 50 nmol/L is sufficient for most people)
Bone profile to check calcium and phosphate (which may be low or normal) and ALP (which will be raised)
Parathyroid hormone will be raised
U&Es to look for chronic kidney disease which may have associated renal osteodystrophy
LFTs looking for liver failure
Full blood count may show anaemia in patients with malabsorption
Ferritin, B12 and folate to identify other deficiencies
Thyroid function tests to rule out derangement as a cause of symptoms
Coliac serology if this is suspected as an underlying cause
Imaging for osteomalacia?
DEXA scanning shows low bone density
Bone X-rays may show insufficiency fractures
Looser zones (or pseudofractures) are transverse lucencies with sclerotic borders
These are often bilateral and symmetrical
Demineralisation of the bone may cause an “erased” or “fuzzy” appearance
Management for osteomalacia?
Underlying causes should be investigated for and managed (e.g. malabsorption)
Provide lifestyle advice on safe sun exposure and dietary intake of vitamin D and calcium
Loading dose vitamin D should be prescribed with approximately 300,000 IU given in total over 6-10 weeks (either weekly or daily)
After this is completed, maintenance vitamin D (800-2000 IU per day) should be continued
If calcium intake is insufficient and dietary measures are not possible, calcium supplements should be prescribed
Patients should be followed up to ensure symptoms resolve and vitamin D and calcium levels normalise
Patients with chronic kidney disease may require alfacalcidol rather than calciferol (due to reduced activity of 1-alpha hydroxylase which activates vitamin D)
Define osteomyelitis
Osteomyelitis is an infection of the bone that can manifest in both acute and chronic forms, caused by bacterial or fungal pathogens.
Acute infections of osteomyelitis are usually caused by a single or polymicrobial?
Single where as chronic are caused by polymicrobial
What are the most common causes of osteomyelitis?
The most common causative pathogens are Staphylococcus aureus and coagulase-negative staphylococci
What is the pathophysiology of osteomyelitis?
The pathophysiology of osteomyelitis involves:
Haematogenous seeding of the infection, which commonly occurs in children.
Spread from adjacent soft tissues or joints.
Direct inoculation of infection into the bone due to wound contamination during trauma or surgery.
What are the risk factors for osteomyelitis?
Diabetes mellitus
Peripheral vascular disease
Malnutrition
Immunosuppression
Malignancy
Extremes of age
Local factors such as chronic lymphedema, vasculitis, neuropathy etc.
Signs and symptoms of acute osteomyelitis?
Acute osteomyelitis is characterised by:
Fever
Pain at rest, worsening with weight-bearing
Swelling
Erythema of the affected site
Signs and symptoms of chronic osteomyelitis?
A lengthy history of pain
Persistently draining sinus tract or wound
Soft tissue damage
The presence of risk factors such as diabetes and peripheral vascular disease further supports the likelihood of chronic osteomyelitis
Investigations for osteomyelitis?
Blood inflammatory markers such as CRP, as well as routine markers checking for systemic upset
Blood cultures, which should always be obtained regardless of fever status.
Imaging:
X-ray: While it may initially present as negative, periosteal reactions become visible after around seven days, with bone necrosis detectable after ten. X-rays are useful for diagnosing chronic osteomyelitis, but cannot exclude the possibility of the condition.
MRI: This is the gold standard imaging for visualising both bone and soft tissue. Typical findings include bone marrow oedema secondary to inflammation.
CT: Effective in identifying necrotic bone and guiding a needle for biopsy.
Other tests:
Cultures from expressed pus. However, samples from sinus tracts are deemed unreliable.
What is the gold standard investigation for osteomyelitis?
MRI: This is the gold standard imaging for visualising both bone and soft tissue. Typical findings include bone marrow oedema secondary to inflammation.
What is the management for osteomyelitis?
Long-term antibiotic therapy, typically for a minimum of 4-6 weeks (12 weeks to 3-6 months for chronic osteomyelitis). Empirical treatment usually involves IV flucloxacillin plus fusidic acid/rifampicin, with vancomycin used if MRSA is suspected.
Clindamycin is the preferred choice for those allergic to penicillin.
Initial treatment is intravenous, transitioning to oral antibiotics once the patient stabilises or post two weeks of surgery.
Treatment for chronic osteomyelitis is typically delayed until culture and sensitivity results are available.
Surgical debridement, primarily for chronic osteomyelitis and for draining collections associated with acute osteomyelitis. Acute infections can be addressed with extensive surgical cleaning early on, along with antibiotics.
What investigation gives a definitive investigation for osteomyelitis?
a bone biopsy
What is seen on an x-ray of osteomyelitis?
regional osteopenia, focal cortical loss and periosteal changes
Define osteoporosis?
Osteoporosis refers to a state of low bone density with structural deterioration of bones. This causes bones to weaken, increasing the risk of fragility fractures (defined as a fracture sustained due to a fall from standing or without any trauma).
Patients are defined as having osteoporosis if their bone mineral density (BMD) is at least 2.5 standard deviations below the mean peak mass of young healthy adults. This is measured with a dual-energy X-ray absorptiometry (DEXA) scan which gives BMD for the lumbar vertebrae and the femur.
Risk factors for osteoporosis?
Low body weight, menopause, immobility, older age, smoking, alcohol excess, long term use of corticosteroids, history of fragility exercise, parental hip fracture, chronic disease e.g CKD, COPD, malabsorption e.g coeliac disease IBD, endocrine disorders e.g hyperparathyroidism, hyperthyroidism, certain medications e.g PPI, SSRI, carbamazepine, inflammatory arthritis
When is osteoporosis mostly diagnosed?
Osteoporosis itself is asymptomatic and so is usually diagnosed either with screening of people at high risk (e.g. those on long-term corticosteroids) or when someone presents with a fragility fracture.
The most common fragility fracture in osteoporosis is?
Vertebral body
Neck of femur (hip)
Distal radius
Proximal humerus
Pelvis
Some osteoporotic fractures (e.g. vertebral fractures) may also be asymptomatic acutely. Loss of height and kyphosis may occur due to multiple vertebral fractures, with severe kyphosis leading to reduced mobility and function.
Other common symptoms of fragility fractures include acute severe pain, difficulty weight-bearing (e.g. for a hip fracture) and mobilising.
Signs include deformities, such as a shortened and externally rotated leg due to a hip fracture or a “dinner fork” deformity in a Colles’ wrist fracture.
The area around the fracture may be bruised, swollen and tender to touch.
What is the diagnostic investigation for osteoporosis?
The diagnostic investigation for osteoporosis is a dual-energy X-ray absorptiometry scan (DEXA)
This measures bone mineral density (BMD)
Explain the T score and Z score in a DEXA scan for osteoporosis?
A T-score of -2.5 or less is considered diagnostic of osteoporosis
If the T-score is between -1 and -2.5 this is referred to as osteopenia
Z-score is also reported (this compares bone density to a age, sex and ethnicity matched population rather than healthy young adults) - below -2 is low for their age
Which patients should be offered a DEXA scan?
Aged over 50 presenting with a fragility fracture
Aged under 40 with a major risk factor for fragility fracture (e.g. long-term steroids)
Those about to start treatment that will rapidly decrease bone density (e.g. hormone deprivation in breast cancer) - consider
All other patients with risk factors should have their fracture risk assessed as the initial step
Explain QFracture and FRAX
QFracture and FRAX are the two online assessment tools used
These both predict a patient’s 10-year risk of hip and major osteoporotic fractures
QFracture is interpreted based on whether the risk score is greater or less than 10%
FRAX plots fracture risk versus age on a graph that stratifies people into low/intermediate/high risk
With QFracture, those at approximately 10% risk or more at 10 years should have a DEXA scan
With FRAX, patients at intermediate or high risk of fracture should have a DEXA
In women over the age of 75 with a history of fragility fractures, a clinical diagnosis of osteoporosis may be appropriate (if a DEXA is unfeasible)
What other investigations should be done in osteoporosis?
Vitamin D to check for deficiency; this is needed prior to starting bisphosphonate treatment
Bone profile to check serum calcium as this may also require supplementation
X-rays or other imaging modalities (e.g. CT or MRI) may be required to diagnose and assess fragility fractures
If an underlying cause is suspected of osteoporosis what should also be investigated?
Full blood count which may show anaemia in malabsorption or malignancy, and leukocytosis in malignancy or inflammatory disease
Liver function tests for chronic liver disease
U&Es for chronic kidney disease
ESR or CRP which may be raised in inflammatory disease or malignancy
Thyroid function tests if hyperthyroidism is suspected
Testosterone and sex hormone-binding globulin if hypogonadism is suspected in men
Anti-TTG antibodies for coeliac disease if there is evidence of malabsorption
What is the conservative management for osteoporosis?
Identification and treatment of any underlying condition contributing to osteoporosis
Optimisation of risk factors e.g. smoking cessation, alcohol reduction
Advise patients to take regular weight-bearing exercise to improve muscle strength, including walking, strength training and balance and flexibility training
Advise patients to eat a balanced diet and assess their calcium intake
Assess falls risk and consider measures to reduce this, including referral to multidisciplinary falls teams
Referral to specialist services for patients with very high fracture risk (e.g. T score less than -3.5, multiple vertebral fractures)
What is the medical management for osteoporosis?
Prescribing vitamin D supplementation for patients not exposed to adequate sunlight
Prescribing calcium supplements to patients with an inadequate dietary calcium intake
For patients at high risk of fragility fracture, prescribe bone-sparing treatment
Treatment should be started promptly after a fragility fracture to reduce the risk of another fracture
Oral bisphosphonates are the first-line treatment in the majority of patients - works by inhibiting the activity of osteoclasts
Options include alendronate and risedronate, which can be given either daily or weekly
These must be taken on an empty stomach, at least 30 minutes before food or other medications
Explain how oral biphosphonates need to be taken and what their side effects are?
Options include alendronate and risedronate, which can be given either daily or weekly
These must be taken on an empty stomach, at least 30 minutes before food or other medications
Common side effects include nausea, dyspepsia, gastritis, abdominal pain and musculoskeletal pains
Rarer side effects include oesophagitis or ulceration, stricturing or erosions, osteonecrosis of the jaw or external auditory canal and atypical stress fractures
To minimise risk of osteonecrosis of the jaw, patients with poor dentition or malignancy should have a dental check-up (and any work required performed) before starting bisphosphonates
They should also continue to have routine dental checks and maintain good oral hygiene during treatment
Contraindications include severe chronic kidney disease, hypocalcaemia or vitamin D deficiency, and oesophageal abnormalities such as stricture or achalasia
Patients with recent peptic ulceration, upper gastrointestinal bleeding or surgery, dysphagia, gastritis or duodenitis should be prescribed bisphosphonates with caution
If oral bisphosphonates are not tolerated or unsuitable, options for bone-sparing treatment include:
Parenteral bisphosphonates (e.g. zoledronate)
Denosumab - inhibiting RANKL, which is responsible for the activation and development of osteoclasts that lead to the breakdown of bone.
Raloxifene hydrochloride
Strontium ranelate
For younger women experiencing menopausal symptoms at risk of osteoporosis what do we offer?
Hormone replacement therapy should be considered for younger women experiencing menopausal symptoms as this will also reduce their fragility fracture risk
Teriparatide and romosozumab are other bone-sparing treatments that may be recommended first-line in women with severe osteoporosis - these are then followed by bisphosphonate treatment
What is the surgical management for osteoporosis?
Fragility fractures may require surgical fixation or joint replacement (e.g. hip arthroplasty for a fractured neck of femur)
Complications of osteoporosis?
Hip fractures are high-consequence injuries and lead to permanent disability in 50% and death in 20% of patients
Vertebral fractures may lead to disabling and painful kyphosis which may in turn cause difficulty breathing and gastrointestinal problems such as dyspepsia
Wrist fractures can significantly affect independence and functional ability
Many patients experience a “fracture cascade” where further fractures occur in the years following the initial one
Pain from fractures can lead to poor sleep, low mood and reduced quality of life
Complications of treatment may be significant (e.g. osteonecrosis of the jaw or oesophageal ulceration with bisphosphonates)
Prognosis of osteoporosis?
There is no cure for osteoporosis
In general however, prognosis is good with effective treatment
Bisphosphonate treatment should be reviewed after 3-5 years
If patients remain at high risk of fracture it may be continued for up to 7-10 years
Patients with previous hip or vertebral fractures, those aged 70 or older or those who sustain another fragility fracture whilst on bone protection often require longer durations of treatment
Repeat DEXA may be appropriate to aid decision making
If bone protection is stopped, fracture risk should be reassessed 18 months to 3 years later
Define polymyalgia rheumatica
Polymyalgia rheumatica (PMR) is a chronic inflammatory condition which presents with stiffness and pain of the proximal large joints.
Explain the epidemiology of polymyalgia rheumatica:
PMR has a prevalence of approximately 1% in the UK
Incidence increases with age, peaking in those aged 70-80 years old
PMR is very rare in the under 50s
Women make up the majority of cases
Incidence is significantly higher in patients with Northern European ancestry
Approximately 15-20% of patients with PMR develop giant cell arteritis (see separate topic), and PMR affects up to 60% of patients with giant cell arteritis
Signs and symptoms of polymyalgia rheumatica:
The key symptom is bilateral shoulder, neck and pelvic girdle pain
Joints feel stiff, especially after rest or sleep, and movement worsens pain
Pain may radiate to the elbows or knees
Systemic symptoms are common, including:
Low-grade fevers
Loss of appetite
Weight loss
Malaise
Depression
On examination, muscle power is usually preserved (unless there is disuse atrophy from prolonged symptoms)
Active range of motion may be limited by pain and stiffness
Some patients may have associated swelling and pain in peripheral joints (e.g. wrists and ankles) - this is usually asymmetrical
Hands and feet may be swollen with pitting oedema
Carpal tunnel syndrome may be present
What investigations do we do for polymyalgia rheumatica?
Urine dipstick may be positive for blood due to myoglobin released in myositis
ESR and/or CRP are usually moderately raised in PMR
FBC - raised white cells may indicate infection, anaemia may be seen in malignancy or due to chronic disease
U&Es may show renal impairment in myeloma or infection
LFTs may be deranged e.g. due to metastatic cancer or a high ALP in osteomalacia
Bone profile may show high calcium in myeloma, or low calcium in osteomalacia
Creatine kinase will be raised in myositis
Thyroid function tests for hypo or hyperthyroidism
Protein electrophoresis to screen for myeloma; urine Bence Jones protein should be considered
Rheumatoid factor as a screen for rheumatoid arthritis, ANA and anti-CCP antibodies should also be sent if there is clinical suspicion
HbA1c prior to starting steroids due to their impact on blood glucose control
Chest X-ray may be indicated if there is suspicion of tuberculosis or lung cancer
Management for polymyalgia rheumatica?
Patients with core symptoms of PMR, no atypical features and no suspicion of differentials after initial investigations should be started on steroids in primary care
15mg of oral prednisolone once a day is the usual regimen
Patients should be reassessed after a week to assess treatment response, and ESR/CRP should be rechecked at 3-4 weeks
Consider weaning steroids at 3 weeks - this should be done slowly with close monitoring
Usually patients require steroids for 1-2 years
Safety-net patients for the risk of giant cell arteritis and advise them to seek urgent medical attention if symptoms develop
Secondary care management options for PMR include methotrexate and azathioprine, and physiotherapy may also be of benefit.
What are the important management considerations when starting long term steroid use?
Give patients a steroid card
Advise never to stop steroids suddenly due to the risk of adrenal insufficiency
If they are unable to take tablets (e.g. due to vomiting) they need to seek urgent medical advice
Explain the risk of immunosuppression and check vaccination status - advise seeking urgent medical advice in patients not immunised if they are exposed to chickenpox, shingles or measles
Consider starting bone protection with bisphosphonates +/- vitamin D and calcium supplementation; this should be continued for the duration of steroid treatment before reassessing fragility fracture risk
Assess the risk of peptic ulceration and consider starting a proton pump inhibitor for gastric protection
Monitor blood pressure and glucose (as hypertension and hyperglycaemia are common side effects)
a DEXA scan should be considered to assess fracture risk
Which patients with suspected polymyalgia rheumatica should be referred to rheumatology?
Atypical clinical features:
Aged under 60
No shoulder/pelvic girdle pain
No stiffness lasting > 45 minutes on waking/after rest
Chronic onset of symptoms
Red flag signs or symptoms e.g. weight loss or night pain
Atypical inflammatory markers i.e. normal or very high (ESR > 100 mm/hour)
Limited or no response to steroid treatment
Steroids required for over 2 years
Unable to wean steroids without relapses
Significant adverse effects (or high risk of these) with steroids
Suspected giant cell arteritis (ideally requires same day assessment with same day ophthalmology assessment also if there is visual loss)
Define reactive arthritis?
Reactive arthritis (ReA) is a type of inflammatory arthritis that occurs secondary to a recent infection, usually genitourinary or gastrointestinal in nature. It is described as “sterile”, meaning that the affected joints are not themselves infected.
What is the classic triad of reactive arthritis?
Reactive arthritis was originally referred to as Reiter’s syndrome, which refers to the classic triad of conjunctivitis, urethritis and arthritis (remembered with the mnemonic “can’t see, can’t pee, can’t climb a tree).
What causes reactive arthritis?
The triggering infection occurs up to a month before the onset of arthritis
Most infections are sexually transmitted (postvenereal ReA) or gastrointestinal (postenteric ReA)
Common causative organisms include:
Chlamydia trachomatis - most common - negative Gram stain and sterile pyuria
Campylobacter jejuni
Salmonella
Shigella
Yersinia
Less common causes include E coli, HIV, Neisseria gonorrhoea and Mycoplasma pneumoniae
Postvenereal ReA is mainly seen in men aged 20-30
Postenteric ReA affects both sexes equally
There may not be an identifiable triggering infection in all cases
Patients who are HLA-B27 positive have a 50x increased risk of ReA and are more likely to have severe and persistent symptoms
Signs and symptoms of reactive arthritis:
Arthritis
Typically this is asymmetrical and primarily affects the large joints of the lower limbs
Usually oligoarticular (affecting few joints)
A small joint polyarthritis in the upper limbs may also occur
Axial involvement and sacroiliitis are more common with urogenital rather than enteric ReA
Dactylitis refers to swelling of an entire digit (finger or toe)
Enthesitis causes pain and swelling at sites of tendon or ligament insertions into bone
Achilles tendonitis and plantar fasciitis are common and cause pain on walking
Keratoderma blennorhagicum is the classic rash of ReA
Pustular lesions form on the palms and soles of the feet
These become hyperkeratotic and scaly and form plaques
Circinate balanitis refers to red or grey plaques with an irregular white margin that form on the penis (the shaft or the glans)
Oral ulceration
Nail dystrophy
Eye involvement may be the first presenting feature, with manifestations including:
Conjunctivitis
Anterior uveitis
Keratitis
Episcleritis
Genitourinary features may occur in both postvenereal and postenteric ReA, including:
Urethritis or cervicitis
Cystitis
Prostatitis
Salpingo-oophoritis
dysuria
Constitutional symptoms are often present and include:
Fevers
Malaise
Fatigue
What bedside investigations do we do for reactive arthritis?
Chlamydia trachomatis and gonorrhoea testing should be done with nucleic acid amplification tests (NAAT) on urine or a urethral/vulvovaginal swab
In patients with a history of oral or anal sexual intercourse, pharyngeal and/or rectal swabs should also be tested
Antibiotic sensitivity testing is required for positive samples
Stool MC&S, viral PCR and Clostridium difficile testing should be done in patients with ongoing diarrhoea (although usually this has resolved by the time ReA develops)
Aspiration of synovial fluid should usually be carried out to rule out septic arthritis or crystal arthropathies - in ReA cultures will be negative but white cell count is high
What blood tests do we do for reactive arthritis?
FBC is usually indicative of inflammation with a normocytic anaemia, mildly raised white cell count and thrombocytosis
CRP and ESR are raised acutely and normalise with time
HIV testing should be offered as people with HIV have an increased risk of ReA
Testing for other sexually transmitted infections including syphilis, hepatitis B and C should be considered
HLA-B27 is often positive in patients with ReA and is a poor prognostic marker
Serology for other infections may be indicated e.g. salmonella or shigella
What would you see on imaging of reactive arthritis?
X-rays of affected joints which may be normal early on in the disease course
Imaging features include erosions, enthesopathy with bony spur formation, loss of joint space and soft tissue swelling
Sacroiliitis may be seen on X-ray however MRI is more sensitive for joint erosions in the acute phase
What is the management for reactive arthritis?
Patients diagnosed with a sexually transmitted disease (usually Chlamydia trachomatis) should be referred to a sexual health specialist to be assessed for other infections and for contact tracing
Patients with chlamydia and their partners should be treated with antibiotics (usually 7 days of oral doxycycline)
Otherwise, management of joint symptoms is usually symptomatic with NSAIDs being first-line
If NSAIDs are contraindicated or ineffective, local steroid injections for affected joints (or systemic steroids if many joints are affected) may be used
Bone and stomach protection should be considered for all patients who require oral steroid treatment
In patients with persistent disease, conventional DMARDs should be initiated with sulfasalazine being the preferred medication
Biologics can be initiated if conventional DMARDs are ineffective, with anti-TNF agents such as etanercept being first-line options
Additional treatment may be required for significant skin involvement, with topical treatments including steroids, salicylic acid and vitamin D analogues
What is the prognosis of reactive arthritis?
In most patients, disease is self-limiting with a duration of around 3 to 5 months
However in 25% of patients symptoms persist for longer than 6 months (referred to as chronic ReA)
Recurrence of disease may also occur, which may be in response to another infective trigger
Secondary osteoarthritis may complicate reactive arthritis due to inflammatory joint damage
Define rheumatoid arthritis?
Rheumatoid arthritis (RA) is a chronic inflammatory disease which primarily affects the joints, causing an erosive polyarthritis. It may progress to affect many other organ systems with a variety of extra-articular manifestations.
Epidemiology for rheumatoid arthritis?
RA is the commonest inflammatory arthritis, with a 1% prevalence in the UK
The majority of patients are female (3:1 ratio)
Onset peaks between 30-50 years old
First-degree relatives of a person with RA have a 2-4x increased risk of developing it themselves
Smoking is an important modifiable risk factor for development of RA and worsening of symptoms in those with the disease
What criteria is used to diagnose rheumatoid arthritis? And what score is diagnostic?
The ACR/EULAR 2010 criteria are used for diagnosis of RA in patients with synovitis.
A total score of 6 points or more is diagnostic of RA.
Explain the ACR/EULAR 2010 criteria
What are the classic signs and symptoms of rheumatoid arthritis?
A symmetrical, polyarticular inflammatory arthritis involving the small joints of the hands (metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints), wrists, and metatarsophalangeal joints in the feet (MTP)
As the disease progresses, larger joints may become affected
Symptoms include:
Pain which improves with movement
Prolonged early morning stiffness (over an hour)
Systemic features e.g. lethargy and malaise are common in active disease
Signs include:
Joint swelling, erythema and warmth
Joint tenderness
Positive metacarpophalangeal squeeze test (pain on squeezing metacarpophalangeal or metatarsophalangeal joints together)
Muscle wasting (e.g. of the interosseous muscles of the hands)
Reduced range of movement e.g. unable to make a fist
Deformities - see below for details
Name some of the deformities of RA one gets in the hands and fingers?
Swan-neck deformity - PIPJ hyperextension and DIPJ flexion
Boutonniere (or “buttonhole”) deformity - PIPJ flexion and DIPJ hyperextension
Ulnar deviation of the MCP joints
Z-thumb (or “hitchhiker’s thumb”) - hyperextension of the interphalangeal joint with flexion of the MCP joint
Name the feet deformities in RA?
Hallux valgus - fixed abduction of first metatarsophalangeal joint (MTPJ)
Hammer toe deformity - PIPJ hyperflexion, usually with DIPJ hyperextension
Name the spinal deformities in RA?
Erosion of the dens
Erosion of spinal processes
Cervical spine involvement is involved in 50% of patients with RA
Thoracic and lumbar spinal involvement is rare
Atlantoaxial subluxation is an important complication where the C1 and C2 vertebrae become malaligned (see Complications section for more details)
Name the peri-articular deformities in RA?
Carpal tunnel syndrome - causes pain, weakness and paraesthesia in the median nerve distribution of the hand
Tenosynovitis - typically of the flexor tendons in the hands, causes pain and swelling
Bursitis - typically of the olecranon (elbow) and subacromial (shoulder) bursae, causing pain and swelling
Name the systemic symptoms and signs in RA?
Malaise
Low-grade fevers
Sweats
Fatigue
Weight loss
Generalised lymphadenopathy
Name the respiratory features in RA?
Pleural thickening
Pleural effusions - usually unilateral, exudative, characteristically have a low pH and glucose
Pulmonary fibrosis - lower zone predominant; usual interstitial pneumonia is the commonest pattern seen
Rheumatoid lung nodules - usually peripheral, often asymptomatic, may cavitate and cause pneumothoraces
Caplan syndrome refers to pneumoconiosis (lung disease secondary to inhalation of inorganic dusts) with rheumatoid arthritis; multiple nodules are seen throughout the lungs
General signs and symptoms of respiratory involvement include cough, shortness of breath and pleuritic chest pain
Name the cutaneous features in RA?
Rheumatoid nodules - common in seropositive patients; non-tender firm nodules that are movable in the subcutaneous tissues
Vasculitis - can cause ulceration of the legs, nailfold infarcts and a vasculitic rash
Name the ophthalmic features of RA?
Keratoconjunctivitis sicca - dry eyes, can occur on its own or as part of a secondary Sjogren’s syndrome
Episcleritis - eyes are erythematous and painful, usually self-limiting
Scleritis - severe eye pain, photophobia and visual loss, can become necrotising (scleromalacia perforans) which often causes long-term visual impairment
Name the cardiac features of RA?
Pericardial disease - e.g. pericarditis, pericardial effusions
Accelerated atherosclerosis of the coronary arteries with an increased risk of myocardial ischaemia and infarction
Myocarditis
Valvular heart disease (e.g. mitral or aortic valve insufficiency)
Symptoms include chest pain, palpitations, syncope, dizziness or shortness of breath
Name the neurological features of RA?
Peripheral neuropathy is very common and may be subclinical or present with sensory or motor symptoms
There is an increased risk of entrapment neuropathies such as carpal tunnel syndrome
Symptoms include numbness in the hands and feet, paraesthesias or neuropathic pain, and weakness
Name the bedside investigations for RA?
Urinalysis as haematuria or proteinuria may suggest a differential such as SLE; proteinuria may indicate amyloidosis
What are the blood tests for RA?
Full blood count often shows anaemia of chronic disease; neutropenia may be present in Felty’s syndrome
U&Es for baseline renal function and liver function tests prior to starting treatment
CRP and ESR are often raised and correlate with disease activity
Rheumatoid factor is positive in 60-70% of people with RA
Anti-cyclic citrullinated peptide (anti-CCP) antibodies are positive in 80% of people with RA, and are more specific than rheumatoid factor
Urate if gout is suspected
What is the imaging for RA?
X-rays of affected joints helps differentiate rheumatoid from osteoarthritis; findings include soft tissue swelling, joint space narrowing, erosions and periarticular osteoporosis
Ultrasound is useful to assess soft tissue inflammation such as synovitis, tenosynovitis and bursitis
MRI is especially sensitive to early changes in RA
What target is used for regular monitoring of RA disease severity and efficacy of treatment
The disease activity (DAS28) score is used
This gives a composite score based on ESR or CRP, the number of tender or swollen joints and a patient-reported measure of global health
Results are interpreted as follows:
< 2.6 - disease remission
2.6-3.2 - low disease activity
3.2-5.1 - moderate disease activity
5.1 - high disease activity
This is used to guide treatment decisions, with a treat to target approach used aiming for disease remission (or low disease activity if remission is not achievable)
The DAS28 should be repeated monthly in active RA until the target is achieved
What is the conservative management for RA?
Non-pharmacological management includes physiotherapy to maintain muscle strength and range of movement
Occupational therapy may involve activity modifications and physical aids to maximise functional ability and preserve independence
Podiatry input may be required for patients with foot problems, to assess needs and provide therapeutic footwear and insoles if required
The Health Assessment Questionnaire (HAQ) may be used to monitor self-reported functional ability
Psychological interventions should be available to help patients with psychological difficulties associated with RA
What is the medical management for RA?
Symptomatic management with analgesia
Simple analgesics such as paracetamol or NSAIDs (with consideration of proton pump inhibitor cover with NSAIDs)
Flares may be treated with a short course of oral or intramuscular corticosteroids
Intra-articular steroids may also be used if the flare is localised to an accessible joint
Septic arthritis should be ruled out if there is a single inflamed joint
Conventional disease-modifying anti-rheumatic drugs (cDMARDs) are the first-line treatment
These should be initiated without delay, ideally within 3 months of disease onset
Methotrexate (avoid in pregnancy and give a three month washout period), leflunomide and sulfasalazine are all first-line options
Hydroxychloroquine may be used first-line in mild or palindromic RA (where the joints return to normal in between attacks of inflammation) - The use of chloroquine or hydroxychloroquine can result in maculopathy, causing visual acuity loss and disturbances in colour vision.
Monotherapy is first-line, with dose escalation as tolerated
If the treatment target is not achieved with monotherapy, an additional cDMARD may be added such as Leflunomide
Steroids may be used to bridge treatment when starting a new cDMARD
Patients who do not achieve their treatment target with cDMARDs should have a biological DMARD (bDMARD) added or substituted
First-line bDMARDs are tumour necrosis factor (TNF) inhibitors e.g. adalimumab, etanercept or infliximab
If this is not successful, other options include rituximab (anti-CD20) and tocilizumab (anti-IL6)
These are expensive medications that are immunosuppressive, and so should be discontinued if patients are not responsive
Other new options for patients who have not adequately responded to other DMARDs include targeted synthetic DMARDs such as filgotinib (a JAK inhibitor)
Ciclosporin lowers the activity of T lymphocytes by inhibiting calcineurin, which is normally responsible for activating the transcription of interleukin 2. It is used as an immunosuppressant in autoimmune conditions and following organ transplants, to prevent rejection. Diarrhoea is a common side effect.
What is the surgical management for RA?
Patients with progressive deformity, persistent localised synovitis, worsening joint function or persistent pain should be referred for surgical assessment
Other complications that may require surgical intervention include tendon rupture, nerve compression, stress fractures and suspected cervical myelopathy
Treatments include joint replacements, synovectomy and arthrodesis
What are the complications of RA?
AA amyloidosis due to chronic uncontrolled inflammation
Occurs due to high levels of serum amyloid A protein in the blood which is converted into amyloid
On average amyloidosis manifests 20 years after the onset of RA
Deposits are mainly in the spleen and kidneys, causing nephrotic syndrome and renal failure
Felty syndrome is a variant of RA that is seen in less than 1% of cases
There is a triad of RA, splenomegaly and persistent neutropenia
Usually occurs in patients with longstanding seropositive RA
There is an increased risk of infection due to neutropenia
RA in these cases is usually severe with significant extra-articular disease
Atlanto-axial instability refers to hypermobility between the C1 and C2 cervical vertebrae
Neck pain radiating to the occiput may be seen
There is a risk of atlanto-axial subluxation with subsequent cord compression
Cervical myelopathy may present with weakness and sensory loss in the upper limbs
Minor neck trauma may exacerbate a subluxation and can result in spinal cord compression, vertebral artery compression and sudden death
X-ray screening of the cervical spine should be performed in all RA patients prior to neck manipulation during anaesthesia
Anaemia of chronic disease is common in RA
Anaemia may also be a side effect of DMARDs such as methotrexate
Cardiovascular disease with accelerated atherosclerosis is the leading cause of death in RA
Increased risk of lymphoma independent of medication side effects
Increased infection risk due to steroids and immunosuppressant DMARDs; septic arthritis is a particular risk
Disability with restricted mobility, chronic pain and difficulties at work
Depression
Increased risk of osteoporosis secondary to RA itself and steroid use
What is the prognosis of RA?
Typically, RA follows a relapsing clinical course with flares followed by periods of remission
Some patients have mild and self-limiting disease
Other patients follow a more severe and progressive chronic course
Prognosis is improved with prompt diagnosis and early initiation of effective treatment
Poor prognostic factors include:
High disease activity
Positive autoantibodies (RF and/or anti-CCP)
Early joint damage with erosions
Rheumatoid nodules
Extra-articular disease
Greater number of joints affected
Approximately one third of people stop work due to RA within 2 years of onset; this increases with time
Life expectancy is on average reduced by 10 years, however this is improving with newer treatments and improved management
What factors are associated with a poor prognosis of RA?
Rheumatoid nodules, positive rheumatoid factor and anti-CCP antibodies, insidious disease onset, smoking history, HLA-DR4 and poor functional status at presentation.
Compare osteoarthritis and rheumatoid arthritis?
What serological marker is the most specific for RA?
Anti-CCP is a sensitive (70%) and specific (95%) marker for the diagnosis of rheumatoid arthritis (RA). A positive anti-CCP result means RA is likely (although positive anti-CCP can precede clinical signs), but a negative result does not rule out RA as it is present in only a quarter to half of the patients before or at diagnosis. Anti-CCP occurs in approximately 1.5% healthy population and 10% of patients with other rheumatology conditions.
Before being started on a biologic therapy such as infliximab, what important screening test needs to be done first?
This patient with rheumatoid arthritis is likely to be started on biologic therapy, such as infliximab, given her persistently high disease activity despite treatment with traditional DMARDs like methotrexate and sulfasalazine. Infliximab, a TNF-α inhibitor, can lead to reactivation of latent tuberculosis (TB), hence the need for screening. A chest X-ray (CXR) is essential to rule out any previous TB infection or lung pathology before initiating treatment, as infliximab increases the risk of TB reactivation, especially in those with previous exposure.
Which antibiotic when given with methotrexate increases the risk of haematological side-effects?
Trimethoprim
Mouth sores, fatigue and dyspnoea
Which additional investigation would be most appropriate when considering the anaesthetic approach to a patient with RA?
In patients with rheumatoid arthritis, particular care is needed when assessing the cervical spine (C1-C2) due to an increased risk of instability and subluxation at the atlanto-axial joint.
Exudative pleural effusions are a well recognised complication of rheumatoid arthritis, and are usually positive for ???
rheumatoid factor
What are the recommended treatments for women with Rheumatoid Arthritis who are planning a pregnancy.
Hydroxychloroquine and Sulfasalazine, alongside Folic Acid
In individuals with rheumatoid arthritis, exposure to dust particles such as coal, asbestos, or silica can result in ???, characterized by intrapulmonary nodules leading to shortness of breath.
Caplan syndrome
Define septic arthritis?
Septic arthritis is an infection of the joint, specifically the synovial fluid. It is typically caused by a bacterial or viral pathogen and necessitates prompt medical intervention due to the high risk of joint damage and other severe complications.
What is the most common organism in septic arthritis?
The most prevalent organism implicated in septic arthritis is Staphylococcus aureus. Other responsible organisms include:
Gonococcus: primarily in sexually active individuals
Streptococcus spp.
Gram-negative bacilli
Name some risk factors for septic arthritis?
Risk factors contributing to septic arthritis include:
Pre-existing joint diseases such as rheumatoid arthritis
Chronic kidney disease
Immunosuppressive states
Presence of prosthetic joints
What are the signs and symptoms of septic arthritis?
The clinical presentation of septic arthritis usually involves:
Acute onset of tender, swollen joint
Reduced range of joint movement
Systemic symptoms such as fever, malaise, or chills
What are the investigations for septic arthritis?
Diagnostic investigations for septic arthritis include:
Joint aspiration for Microscopy, Culture, and Sensitivity: The aspirate usually appears turbid and yellow, resembling pus.
Blood tests: elevated white cell count, high ESR/CRP
Blood cultures: to identify causative organisms
Imaging: X-ray of the joint may be performed to evaluate for osteomyelitis or other complications.
What is the treatment for septic arthritis?
The treatment of septic arthritis involves:
IV antibiotics guided by local antibiograms and susceptibilities - immediate initiation of intravenous antibiotics for at least two weeks, followed by an additional four to six weeks of oral antibiotics
Consideration of joint washout under general anaesthesia to remove infected material
Physiotherapy following the resolution of acute infection to restore joint function
Intravenous Flucloxacilin 1 to 2g every 6 hours
What are the complications of septic arthritis?
Complications of septic arthritis can include:
Osteomyelitis: infection of the bone
Chronic arthritis: persistent joint inflammation
Ankylosis: joint fusion resulting in immobility
If the patient’s has a history of intravenous drug use and presents with a high fever, and a swollen, erythematous knee because of septic arthritis what would be the most likely causative agent?
Pseudomonas aeruginosa
How does management change if the septic arthritis is in a prosthetic joint?
In patients with recent prosthetic joint surgery and suspected septic arthritis, it is essential to arrange for urgent orthopaedic review rather than performing joint aspiration in a non-sterile setting.
Define systemic lupus erythematous?
Systemic lupus erythematosus (SLE) is a complex autoimmune disease that may affect a wide variety of organs. The clinical course is commonly a relapsing-remitting one, with intermittent flares of disease activity.
Causes of systemic lupus erythematous?
The pathogenesis of SLE is complex, involving multiple autoantibodies leading to immune complex formation and deposition
There is a genetic contribution with many genetic risk factors identified
Proposed environmental risk factors include:
Smoking
Ultraviolet light
Silica exposure
Epstein-Barr virus
Flares of SLE may be triggered by:
Oestrogen exposure (e.g. pregnancy, the combined oral contraceptive pill)
Infections
Emotional stress
Physical stress e.g. surgery, injury
Excessive ultraviolet light exposure
How does one classify systemic lupus erythematous?
patients need to have positive antinuclear antibodies (ANA) and score 10 or more with at least one clinical criterion:
What are the systemic manifestations of systemic lupus erythematous?
Fevers
Fatigue
Weight loss
Myalgia
Malaise
What are the dermatological manifestations of systemic lupus erythematous?
80% of patients have skin involvement
Photosensitivity is common
The classic malar rash appears as butterfly-shaped erythema across the cheeks, sparing the naso-labial folds
A discoid rash consists of indurated hyperpigmented plaques in sun-exposed areas, that may occur without systemic features
Livedo reticularis
A variety of other rashes may occur e.g. maculopapular, bullous, annular, urticarial or hypertrophic rashes
Nonscarring diffuse alopecia
Raynaud’s phenomenon
Cutaneous vasculitis may manifest as splinter haemorrhages and/or purpura
What are the musculoskeletal manifestations of systemic lupus erythematous?
Generalised arthralgia, often with early morning stiffness, is common
A non-erosive symmetrical polyarthritis often affects the knees, wrists, shoulders and hands
A minority of patients develop a non-erosive arthropathy (Jaccoud’s arthropathy) that may mimic rheumatoid arthritis deformities
Complications of chronic steroid treatment may be seen, including osteonecrosis, insufficiency fractures and tendinopathies
What are the renal manifestations of systemic lupus erythematous?
The majority of patients develop renal disease, with approximately 4% progressing to end-stage renal disease
Lupus nephritis varies in severity and may be asymptomatic, or present with nephritic or nephrotic syndrome
Presenting features include hypertension, frothy urine and peripheral oedema
Renal involvement is classified based on histology as below:
What are the cardiovascular manifestations of systemic lupus erythematous?
Pericarditis is the most common cardiac feature of SLE, presenting with chest pain, dyspnoea, tachycardia and a pericardial rub may be heard on auscultation
Pericardial effusions are also common although the risk of tamponade is low
Myocarditis is rare and may present with arrhythmias and heart failure
Libman-Sacks endocarditis refers to the formation of non-infective vegetations that usually form on the mitral and aortic valves
There is a significantly increased risk of adverse cardiovascular events such as myocardial infarction
What are the respiratory manifestations of systemic lupus erythematous?
Pleurisy is very common (where there is inflammation of the pleura, typically presenting with sharp chest pain exacerbated by vigorous inhalation or expiration)
Pleural effusion
Patients with antiphospholipid antibodies are at increased risk of pulmonary emboli
Rarer pulmonary manifestations include:
Acute lupus pneumonitis
Pulmonary hypertension
Chronic interstitial pneumonitis
Obliterative bronchiolitis
Pulmonary vasculitis
Alveolar haemorrhage
Patients on immunosuppressive treatments are at increased risk of opportunistic infections
What are the neurological manifestations of systemic lupus erythematous?
Up to 80% of patients develop neuropsychiatric involvement
Seizures are the most common features (either generalised or local)
There is a significantly increased risk of stroke, which is contributed to by:
Antiphospholipid syndrome
Hypertension
Accelerated atherosclerosis
Embolisms from Libman-Sacks endocarditis
Thrombocytopaenia
Cerebral vasculitis
Psychosis
Delirium
Cognitive impairment (although usually not severe enough to result in dementia)
Increased rates of depression and anxiety
Headaches
Peripheral neuropathy (most commonly a sensorimotor polyneuropathy)
What are the haematological manifestations of systemic lupus erythematous?
Anaemia may occur due to chronic disease, medications or haemolysis
Leukopaenia and thrombocytopaenia are also common
Reactive lymphadenopathy and splenomegaly may be present, particularly in active disease
Antiphospholipid syndrome occurs in around 20% of patients (although higher numbers have antibodies without complications)
What are the gastrointestinal manifestations of systemic lupus erythematous?
Mouth ulcers are common and may be painful
A protein-losing enteropathy may be seen
Ascites may occur secondary to peritonitis or hypoalbuminaemia due to enteropathy or nephrotic syndrome
Pancreatitis
Splenic infarction
Hypoadrenalism
Hepatomegaly, hepatitis or cirrhosis may be seen
Vasculitis affecting the GI tract may cause colitis, mucosal ulceration, mesenteric ischaemia or oesophageal dysmotility
Antiphospholipid syndrome may cause Budd-Chiari syndrome or thrombosis of intestinal vessels
What are the bedside tests for systemic lupus erythematous?
Blood pressure to monitor for hypertension
Urine dip for proteinuria or haematuria
Urinary protein:creatinine ratio may be useful to quantify proteinuria
Urine microscopy looking for casts
ECG in suspected cardiac involvement
What are the blood tests for systemic lupus erythematous?
Full blood count looking for anaemia, leukopenia and thrombocytopaenia
U&Es to screen for renal impairment due to lupus nephritis
Liver function tests are usually normal; hypoalbuminaemia may be seen due to GI or renal involvement
ESR is usually high; CRP may be normal or mildly raised
Clotting screen may show paradoxical prolongation of the APTT if there are anti-phospholipid antibodies present
Complement (C3 and C4) may be low in active disease
Antinuclear antibody (ANA) is almost always positive
Results may be given as a titre (i.e.how much serum can be diluted and still test positive)
A titre of 1:160 or higher is considered positive
The pattern of staining may also be described - classically this is speckled in SLE
Anti-double stranded DNA (anti-dsDNA) antibodies are highly specific for SLE
T hey correlate with disease activity, especially lupus nephritis
Anti-Smith (anti-Sm) antibodies are found in fewer patients but are also highly specific
Antiphospholipid antibodies should be tested for in all patients
Anti-histone antibodies are found in both SLE and drug-induced lupus and so should be sent in patients on causative medications
Anti-Ro and anti-La antibodies are not specific to SLE but may be positive
They are associated with neonatal lupus syndrome in babies born to mothers with these antibodies
Anti-RNP antibodies may be positive in SLE but are non-specific; if found alone positivity suggests mixed connective tissue disease
Creatine kinase to screen for associated myositis
Vitamin D as patients avoiding sun exposure are at increased risk of deficiency
Thyroid function as thyroid disease often coexists with SLE and symptoms may overlap (e.g. fatigue)
Immunoglobulins prior to starting immunosuppressive medications that may lead to immunoglobulin deficiency
Direct Coombs’ test to screen for autoimmune haemolytic anaemia
What is the imaging for systemic lupus erythematous?
Chest X-ray in all patients as a baseline and to screen for pulmonary involvement
CT chest may be required for more detailed assessment of lung involvement; CT pulmonary angiography is required in suspected pulmonary embolism
Ultrasound of the kidney, ureters and bladder (KUB) to exclude other causes of renal impairment e.g. obstruction
X-rays of affected joints looking for arthritis and fractures
Joint space narrowing is uncommon
Soft tissue swelling and periarticular osteoporosis may be seen
Ultrasound of affected joints may show signs of inflammation e.g. tenosynovitis
CT or (preferably) MRI brain if cerebral lupus is suspected
Echocardiogram may show pericarditis, heart failure, pericardial effusion or pulmonary hypertension
What are the special tests for systemic lupus erythematous?
Renal biopsy is the key diagnostic test for lupus nephritis and is important for classification
A ‘full house’ pattern refers to glomerular deposits that stain dominantly for IgG, IgA, IgM, C3 and C1q- five major stains on a renal biopsy are all positive.
Skin biopsy may be useful for the diagnosis of dermatological manifestations
Pulmonary function tests if there
Pleural tap if there is an effusion present - the majority of cases are exudative
Neurophysiology testing in suspected peripheral neuropathy
What is the conservative management for systemic lupus erythematous?
Patients with suspected SLE should all be referred to specialist services for confirmation of the diagnosis and ongoing management
All patients require regular follow up
1-3 monthly follow up is appropriate for patients with active disease
Stable patients can be followed up every 6-12 months
Patient counselling and education, with signposting to resources and support
Advise on sun protection e.g. using sunscreen, limiting exposure and covering skin
Avoid triggers such as oestrogen-containing contraceptives
Optimise cardiovascular health with regular exercise, smoking cessation and a balanced diet
Ensure patients are up to date with vaccinations
What is the medical management for systemic lupus erythematous?
All patients should be treated with hydroxychloroquine
Steroids are also commonly used e.g. oral prednisolone; high-dose IV methylprednisolone is often required for acute severe disease (e.g. renal or neuropsychiatric lupus)
Use of steroid-sparing agents is very important to minimise the long-term effects of prolonged steroid use - options include methotrexate and azathioprine
Patients with severe or refractory disease may be considered for biologic agents such as belimumab or rituximab
Topical agents may be used in addition to systemic treatment for skin disease e.g. topical glucocorticoids or calcineurin inhibitors
Mycophenolate mofetil (MMF) and cyclophosphamide are commonly used for lupus nephritis, with most patients continuing on either MMF or azathioprine
If anti-phospholipid syndrome is present, this may require additional management (see separate chapter)
Cardiovascular risk factors such as hypertension and hyperlipidaemia may require medical treatment
Vitamin D supplementation may be required as well as bone protection in patients on long-term steroids
What are the complications of systemic lupus erythematous?
Medication side effects are common
Retinal toxicity is the main issue with hydroxychloroquine and all patients should undergo regular eye screening
Patients on immunosuppressive treatments are at increased risk of opportunistic infections
Reactivation of latent infections (e.g. tuberculosis, hepatitis) is also a risk and so these should be screened for prior to initiating treatment
Other DMARDs (e.g. methotrexate) have their own extensive side effect profiles
End-stage renal failure develops in approximately 20% of patients with lupus nephritis
This may require renal replacement therapy either with dialysis or transplant
Accelerated atherosclerosis leads to an increased risk of myocardial infarction, ischaemic stroke and peripheral vascular disease
Overlap syndromes may develop in patients with SLE (where the criteria for multiple rheumatological diseases are met), for example
Sjogren’s syndrome
Antiphospholipid syndrome
Mixed connective tissue disease
Neonatal lupus is a complication that arises in babies born to mothers with anti-Ro and/or anti-La antibodies
These antibodies cross the placenta and cause a transient autoimmune syndrome
Manifestations include a red rash on the scalp and around the eyes, complete heart block, deranged liver function and cytopaenias
Other pregnancy complications include recurrent miscarriage, pre-eclampsia, intrauterine growth restriction and preterm delivery
What is the prognosis of systemic lupus erythematous?
Patients with SLE have a 2.6x increased mortality compared to the general population
Although death from active lupus is rare in the UK, life expectancy is shortened to an average of 54 years
A third of patients develop lupus nephritis and this is associated with a poorer prognosis, with a mean age of death of 40 years
Other poor prognostic factors include:
Black ethnicity
Male sex
Antiphospholipid antibodies
Central nervous system involvement
Explain the difference between ANA and anti-dsDNA in SLE?
Anti-double stranded DNA (anti-dsDNA) is more specific for SLE but less sensitive than ANA
What is the most appropriate treatment to control both the systemic inflammation and severe central nervous system involvement. in SLE?
Cerebral lupus can present with a wide range of neurological and psychiatric symptoms, including psychosis. The combination of high-dose corticosteroids and cyclophosphamide is the most appropriate treatment to control both the systemic inflammation and severe central nervous system involvement.
Which class is the most common and severe form of lupus nephritis?
Class IV lupus nephritis, diffuse proliferative glomerulonephritis, is the most common and severe form of lupus nephritis.
What are the features of drug induced SLE?
This patient describes the classic features of drug-induced lupus secondary to minocycline therapy for her acne vulgaris - symptoms of polyarthritis and oral ulceration. A positive anti-histone antibody result indicates that a patient may have a drug-induced lupus.
Explain drug induced lupus (DIL) secondary to isoniazid therapy
Isoniazid is a first line drug for TB treatment and is usually taken for 6 months. DIL typically presents as a less severe form of SLE which starts while taking an offending medication, and completely resolves after it is discontinued
Explain the difference between drug induced lupus and SLE?
Hydralazine-induced lupus is the most likely diagnosis. This is more common in patients of Afro-Caribbean descent and presents with equal frequency in males and females. This patient has systemic symptoms, arthralgia and pleurisy. Renal involvement and dermatological features of systemic lupus erythematosus (malar rash) are less common in drug-induced lupus. Anti-dsDNA and anti-Smith antibodies, which are specific for systemic lupus erythematosus are usually absent, but there might be positive anti-histone antibodies which are highly specific for drug-induced lupus.
Explain the relationship between C3 and C4 levels and SLE disease activity?
This is used to monitor disease activity. The lower the level of complements, the higher the disease activity
In SLE and Sjoren’s syndrome what should one monitor children for?
In SLE and Sjoren’s syndrome, transplacental passage of maternal anti-Ro and anti-La autoantibodies can result in Congenital Heart Block, manifesting as fetal bradycardia during the second trimester.
