Rheumatology: Kawasaki Disease & Rheumatic Fever Flashcards
What is Kawasaki disease?
An acute self-limiting systemic vasculitis of unknown cause that mainly affects children <5 (but can affect children of any age, including infants and teenagers).
It is a medium-sized artery vasculitis, particularly affecting the coronary arteries.
Which ethnicity does Kawasaki disease affect most?
Children of East Asian origin.
What arteries does Kawasaki disease particularly affect?
Coronary arteries
What are 3 risk factors for Kawasaki disease?
1) Asian ethnicity, especially Japanese
2) Aged <5 years (80% of cases occur in those under the age of five)
3) Male sex (male to female ratio 1.5:1)
Who should Kawasaki disease be considered in?
Any child with a fever lasting ≥5 days.
How is Kawasaki disease diagnosed?
It is a clinical diagnosis, and there is no diagnostic test.
What is the diagnosis of Kawasaki disease based on?
The American Heart Association diagnostic criteria.
What is the American Heart Association diagnostic criteria for Kawasaki disease?
Presence of fever (usually ≥39°C) for at least 5 days, plus at least 4 out of 5 key features:
1) Mucositis: erythema and cracking of the lips, strawberry tongue and/or oral erythema
2) Conjunctivitis: bilateral conjunctivitis without exudate
3) Rash: maculopapular, erythroderma or erythema multiforme
4) Peripheral changes: erythema, oedema and/or desquamation of the hands and feet
5) Cervical lymphadenopathy
What are the clinical features of Kawasaki disease?
1) High-grade fever which lasts for > 5 days –> characteristically resistant to antipyretics
2) Conjunctival injection
3) Bright red, cracked lips
4) Strawberry rongue
5) Cervical lymphadenopathy
6) Red palms of the hands and the soles of the feet which later peel
What 3 phases does Kawasaki disease usually follow?
1) Acute phase (1-2 weeks from fever onset)
2) Subacute phase (2-4 weeks from fever onset)
3) Convalescent phase (8 weeks from fever onset)
Describe the acute phase of Kawasaki disease
1-2 weeks from fever onset.
Symptoms –> High fever, irritability, rash, mucositis, peripheral erythema and oedema.
Describe the subacute phase of Kawasaki disease
2-4 weeks from fever onset.
Symptoms –> afebrile, most clinical features begin to resolve, desquamation of the hands and feet.
Which phase of Kawasaki disease is the highest risk period for developing cardiac complications?
Subacute phase (2-4 weeks from fever onset)
Which phase of Kawasaki disease can you see desquamation of the hands and feet?
Subacute phase (2-4 weeks from fever onset)
Describe the convalescent phase of Kawasaki disease
4-8 weeks from fever onset.
Asymptomatic period, clinical features have resolved.
Coronary artery aneurysms often improve but may get worse.
Give 5 differentials for Kawasaki disease
Fever is a common paediatric presentation.
1) Scarlet fever or acute rheumatic fever (Group A streptococcus)
2) Toxic shock syndrome or staphylococcal scalded skin syndrome (Staph aureus)
3) Measles
4) Steven-Johnson syndrome / toxic epidermal necrolysis
5) Systemic-onset juvenile idiopathic arthritis
What investigations may be relevant in Kawasaki disease?
1) ECG: may show arrhythmias or ST-T changes if myocarditis or myocardial infarction occurs
2) Urinalysis: may show sterile pyuria
3) Baseline blood tests (FBC, U&E, LFTs): there may be anaemia, raised white cells and raised platelets. LFTs may be deranged if hepatitis occurs.
4) ESR and/or CRP: often significantly raised
5) Anti-streptolysin O titre (ASOT): to exclude group A streptococcal infection
What investigation is ESSENTIAL in Kawasaki disease?
Echocardiogram
What is a key complication of Kawasaki disease?
Coronary artery aneurysm –> get an echo !
When should an echo be performed in Kawasaki disease?
It should be performed as soon as Kawasaki disease is suspected but should not delay treatment (e.g. if the child presents out-of-hours or to a hospital without a suitably qualified sonographer).
What may be some findings on an echo in Kawasaki disease?
1) Coronary artery aneurysms
2) Valvular disease (e.g. mitral regurgitation)
3) Coronary artery thrombosis
4) Poor ventricular function/evidence of myocarditis
5) Pericardial effusion/evidence of pericarditis
Does a normal echo rule out Kawasaki disease?
No - the echocardiogram can be normal in the first week of the disease
Management of Kawasaki disease?
Admit to hospital
Mainstay of treatment –> oral aspirin (high dose) and IV immunoglobulin.
Role of aspirin in Kawasaki disease?
Aspirin is thought to reduce the risk of coronary artery aneurysms and thrombosis through its antiplatelet and anti-inflammatory effects.
How long is aspirin given for in Kawasaki disease?
Typically, high-dose aspirin is given until the fever has resolved for 48 hours, then low-dose aspirin for approximately 6 weeks (duration will be guided by cardiology).
Why is aspirin usually contraindicated in children <16?
Due to risk of Reye’s syndrome.
However, in Kawasaki disease, the benefits are felt to outweigh this risk.
What is Reye’s syndrome?
A rare acute encephalopathy associated with liver failure.
Role of IV immunoglobulin in Kawasaki disease?
An infusion of IVIG within the first 10 days of illness can reduce the incidence of coronary artery aneurysms.
When should improvement be seen after intiating treatment in Kawasaki disease?
Within 36 hours.
Note - A second dose of IVIG may be given if an improvement is not seen.
What can be used in refratory cases of Kawasaki disease?
Other treatments, including corticosteroids or infliximab (an anti-TNF agent), may be used in refractory cases or in those with risk factors for IVIG resistance.
What are some complications of Kawasaki disease?
1) Coronary artery aneurysms
2) Myocarditis/pericarditis
3) Arrhythmias
4) Valvular disease (e.g. mitral regurgitation)
5) Coronary artery thrombosis/myocardial infarction
6) Sudden cardiac death
What is the danger of a coronary artery aneurysm in Kawasaki disease?
Giant aneurysms may rupture, causing cardiac tamponade.
What % of children with Kawasaki disease develop a coronary artery aneurysm?
15-25% of untreated children develop aneurysms, but the risk is much lower with early treatment.
What is rheumatic fever?
A systemic inflammatory disorder that arises as a complication following infection with group A Strep (S. pyogenes).
How soon after Strep infection can rheumatic fever develop?
2-6 weeks
Is rheumatic fever contagious?
No, unlike the initial infection.
What age does rheumatic fever typically affect?
Rheumatic fever typically affects children between the ages of 5 and 15, with girls being affected slightly more commonly than boys.
How does initial Strep. pyogenes infection typically present?
- Pharyngitis (sore throat)
- Can also present as cellulitis
Pathophysiology of rheumatic fever?
1) Initial Streptococcus pyogenes infection
2) Rheumatic fever develops in susceptible hosts (roughly 2% of the population) due to a hypersensitivity reaction against the bacteria –> involves both the humoral and cell-mediated immune responses (type 2 hypersensitivity).
3) Similarities in the molecular makeup of the cell walls of streptococcal bacteria and human heart valve tissue may result in the body’s antibodies attacking the host instead of the pathogen, leading to permanent damage to the valves –> this phenomenon is termed antigen mimicry.
What are some biological risk factors associated with an increased risk of developing rheumatic fever?
1) Age: rare in children under 4 years.
2) Sex: more common in females.
3) Ethnicity: for example, there is a higher prevalence of rheumatic fever among indigenous groups in Australia and New Zealand.
4) Immune status: immunocompetent vs immunocompromised.
5) Genetic susceptibility: as indicated by findings from twin studies.
6) Prior or untreated infection with Group A Streptococcus.
7) Virulence of the infective organism.
What are some social risk factors associated with an increased risk of developing rheumatic fever?
1) Low socioeconomic status: due to poor access to healthcare and antibiotics.
2) Overcrowding and poor housing: associated with poor hygiene and sanitation.
3) Climate: higher incidence over the winter months. In hot countries, streptococcal infection is more likely to present as a skin infection versus pharyngitis.
How is strep infection more likely to present in hot countries?
As skin infection instead of pharyngitis
What criteria is used for diagnosing rheumatic fever?
Jones criteria
What does the Jones criteria state about the diagnosis of rheumatic fever?
There must be:
- Evidence of recent group A Streptococcus infection
Plus either:
- two major criteria
- or one major criterion and two minor criteria
Give some evidence of a recent group A strep infection
- Positive throat swab
- Positive rapid streptococcal antigen test
- Raised streptococcal antibody titre (ASO or DNAse B titres)
- Recent episode of scarlet fever
Give the 5 major criteria for rheumatic fever
1) Polyarthritis (i.e. joint involvement)
2) Carditis & valvulitis (heart involvement)
3) Sydenham’s chorea (nervous system involvement)
4) Erythema marginatum (skin involvement)
5) Subcutaneous nodules (skin involvement)
typical symptoms of rheumatic fever?
1) Fever
2) Joint pain
3) Rash
4) Shortness of breath
5) Chorea
6) Nodules
How can rheumatic fever affect the joints?
Affects large joints - hot, swollen, painful joints.
‘Migratory polyarthritis’ - different joints become inflamed and improve at different times.
What is the most common symptom of rheumatic fever?
Polyarthritis (80%)
What may aspiration of synovial fluid in polyarthritis caused by rheumatic fever show?
Sterile inflammation without any organisms present
What is the most significant manifestation of rheumatic fever?
Carditis - due to its potential for causing long-term sequelae.
What does carditis caused by rheumatic fever involve?
Can involve all 3 layers of the heart - pericardium, myocardium & endocardium –> ‘pancarditis’
What clinical features can carditis caused by rheumatic fever cause?
1) Pericarditis:
- chest pain
- pericardial rub on auscultation
- possible pleural effusion
2) Myocarditis:
- congestive heart failure: SOB, orthopnoea, PND, cardiogenic shock
3) Endocarditis:
- valvular regurgitation murmurs (most commonly mitral and aortic): can lead to chronic valvular dysfunction
What is the most commonly affected valve in rheumatic fever?
Mitral valve
How does rheumatic fever typically affect valves?
In an attack of rheumatic fever, valve incompetence (i.e. regurgitation) is more likely to develop than valve stenosis.
Valve stenosis tends to develop as a feature of chronic disease many years later.
What is Sydenham’s chorea?
A rare and late-presenting sign of rheumatic fever.
It consists of involuntary, semi-purposeful movements of the body which may be unilateral or bilateral.
Occasionally the chorea is preceded by emotional lability or behaviour which is out of character for the patient.
How soon after initial streptococcal infection does Sydenham’s chorea appear?
2-6 months after
What is Sydenham’s chorea sometimes preceded by?
Emotional lability or behaviour which is out of character for the patient.
What is Sydenham’s chorea sometimes referred to as?
St Vitus’ dance
What are the 2 key skin findings in rheumatic fever?
1) Subcutaneous nodules
2) Erythema marginatum rash
What are subcutaneous nodules?
Hard, mobile, pea-sized nodules, typically found on the extensor surfaces (e.g. back of the elbows) or the spine. They are often painless and normally disappear within one month.
Are subcutaneous nodules a common finding in rheumatic fever?
No - usually only seen when severe carditis is present.
What is Erythema marginatum?
A rash found in rheumatic fever which may present early on in the disease process.
This is a pink macular rash predominantly affecting the trunk and limbs while sparing the face.
It expands outwards, leaving a pale centre and is described as a “geographical rash” because its borderlines resemble those drawn on a map.
Where are subcutaneous nodules typically found in rheumatic fever?
Extensor surfaces
Where is Erythema marginatum rash typically found in rheumatic fever?
predominantly affecting the trunk and limbs while sparing the face
What are the 4 minor criteria for rheumatic fever?
1) Raised ESR or CRP
2) Pyrexia (typically >39 degrees)
3) Polyarthralgia i.e. pain present in multiple joints (this is not included in the criteria if polyarthritis is already present)
4) Prolonged PR on ECG
5) History of rheumatic fever
Give some differentials for rheumatic fever
Joint:
- Systemic-onset juvenile idiopathic arthritis
- Reactive arthritis
- Henoch-Schönlein purpura (HSP)
Cardiac:
- Cardiomyopathy
- Kawasaki disease
- Infective endocarditis
Skin:
- Adverse drug reactions
- Erythema multiforme
Chorea:
- Wilson’s disease
- Adverse drug reactions
Mneumonic for rememebering major criteria for rheumatic fever: JONES
J - Joint arthritis
O - Organ inflammation such as carditis
N - Nodules
E - Erythema marginatum rash
S - Sydenham chorea
Mneumonic for rememebering minor criteria for rheumatic fever: FEAR
F - Fever
E - ECG changes (prolonged PR interval) without carditis
A - Arthralgia without arthritis
R - Raised inflammatory markers (CRP and ESR)
Investigations in rheumatic fever?
1) ECG: may show prolonged PR interval and tachycardia.
2) Vital signs: fever may be present.
3) Throat swabs: testing for cultures of group A Streptococcus
4) Rapid streptococcal antigen test (RAST)
5) Anti-streptococcal antibodies
6) Blood tests: FBC, ESR, CRP, troponin, rheumatoid factor, anti-CCP
What are the 2 most common antibody tests used for rheumatic fever?
1) anti-streptolysin O (ASO)
2) anti-DNAse B
When may troponin be raised in rheumatic fever?
Myocarditis
Role of doppler echo in rheumatic fever?
May be used to aid diagnosis of carditis in acute rheumatic fever.
Role of CXR in rheumatic fever?
Rule out HF
Management of rheumatic fever can be divided into acute management and prophylaxis.
What does acute management of rheumatic fever involve?
1) Supportive –> bed rest is 1st line
2) Abx –> single stat dose of IV benzylpenicillin followed by oral penicillin V (phenoxymethylpenicillin) for at least 10 days
3) High dose aspirin
4) Corticosteroids: if moderate to severe carditis is suspected (e.g. cardiomegaly on XR, complete heart block on ECG, evidence of HF)
What Abx are indicated in acute rheumatic fever?
Single stat dose of IV benzylpenicillin followed by 10 day course of oral penicillin V.
Purpose –> to kill GAS infection.
Alternative in pencillin allergy –> oral erythromycin, azithromycin, or first-generation cephalosporins.
Role of high dose aspirin or other NSAIDs in acute rheumatic fever?
To manage inflammation and reduce symptoms such as fever, joint pain, and swelling.
How can aspirin affect children?
1) Can cause a respiratory alkalosis (from hyperventilation), followed by metabolic acidosis.
2) Tinnitus
3) Reye’s syndrome
When are corticosteroids indicated in rheumatic fever?
Prednisolone may be used in cases of severe carditis or heart failure, as well as in patients who do not respond to NSAIDs.
What management may be indicated for patients with rheumatic fever to manage HF?
Diuretics, ACEi, beta-blockers, and other standard HF medications may be used as appropriate based on the severity of the carditis and heart failure.
Management of Sydenham chorea in rheumatic fever?
Anticonvulsant medications, such as valproic acid or carbamazepine, may be used to manage the symptoms of Sydenham chorea.
In severe cases, corticosteroids or intravenous immunoglobulin (IVIG) may be considered.
Importance of bed rest in rheumatic fever?
Rheumatic fever is one of the few conditions where bed rest is recommended as first-line treatment, even if the patient feels well.
This is even more important in cases of suspected active myocarditis (indicated by abnormalities seen on the echocardiogram and a raised ESR), where limitation of exercise is strongly advised.
After the initial attack, the child should be followed up regularly and prophylactic treatment started to reduce the chance of any future attacks.
What is the current recommended first-line prophylactic treatment for rheumatic fever?
Benzathine penicillin G, given every 4 weeks as an IM injection.
Alternatively, the patient can take oral penicillin instead of having the injections, but they must take these every day for the duration of prophylaxis and this may make compliance difficult.
Alternative to Benzathine penicillin G for prophylaxis of rheumatic fever?
Erythromycin or azithromycin may be used
How long should prophylaxis for rheumatic fever be considered?
If carditis is not a feature of the acute episode, and there is no evidence of valvular disease, then prophylaxis may be given for only 5 years, or until age 21 (whichever is sooner).
If carditis is present during the acute episode but there is no valvular disease, then prophylaxis should be given for 10 years.
Where there is both carditis and persistent valvular disease, prophylaxis should be continued for life, or at least up to the age of 40.
What are long-term complications of rheumatic fever related to?
Increased risk without adequate treatment of the acute episode and prophylaxis.
The severity of chronic disease is related to both the number and the severity of childhood attacks of rheumatic fever.
What are the majority of rheumatic fever complications related to?
The heart –> 60% of patients presenting acutely with carditis go on to develop chronic rheumatic heart disease.
What are some cardiac complications of rheumatic fever?
- Carditis (e.g. infective endocarditis)
- Heart failure
- Pericardial effusions
- Valvular disease (especially the mitral valve)
- AF (from severe untreated mitral stenosis)
- Pulmonary HTN
- Thromboembolic events, such as strokes (a consequence of atrial fibrillation)
What is the most common valve lesion in rheumatic fever overall?
Mitral regurgitation
Note - other valves may also be affected but this is less common (aortic 40%, tricuspid 10% and pulmonary 2% cases).
What is the most common long-term cardiac complication of rheumatic fever?
Mitral stenosis
Very occasionally, some individuals with rheumatic fever may develop refractory chorea, which may persist for years and is resistant to standard treatment.
In these patients, what management option may be considered?
Plasmapheresis, whereby plasma is removed from the blood and the cells are transfused back into the body with a plasma substitute.
What 3 factors can trigger a relapse of rheumatic fever?
1) re-infection with streptococcal bacteria
2) use of COCP
3) pregnancy
What long term monitoring do patients with rheumatic fever require?
long-term monitoring of cardiac function
What is the most common valvular abnormality in Kawasaki disease?
Mitral regurgitation
What is the most commonly affected valve in rheumatic heart disease?
Mitral valve (regurgitation in early stages then stenosis in later stages).
