Rheumatology Flashcards
What is JIA?
Juvenile idiopathic arthritis (JIA) refers to a condition affecting children and adolescents where autoimmune inflammation occurs in the joints.
It is diagnosed where there is arthritis without any other cause, lasting more than 6 weeks in a patient under the age of 16.
It has also been known as juvenile chronic arthritis and juvenile rheumatoid arthritis.
When is JIA diagnosed?
Arthritis without any other cause
Lasting more than 6 weeks
In a patient under the age of 16
Key features of JIA
Inflammatory arthritis
Joint pain
Swelling
Stiffness
Five key subtypes of JIA
Systemic JIA
Polyarticular JIA
Oligoarticular JIA
Enthesitis related arthritis
Juvenile psoriatic arthritis
What condition is commonly known as Still’s disease?
Systemic juvenile idiopathic arthritis
Clinical features of systemic JIA
Subtle salmon-pink rash
High swinging fevers
Enlarged lymph nodes
Weight loss
Joint inflammation and pain
Splenomegaly
Muscle pain
Pleuritis and pericarditis
Blood abnormalities in systemic JIA?
Antinuclear antibodies and rheumatoid factors are typically negative.
There will be raised
- inflammatory markers, with raised CRP, ESR
- platelets and serum ferritin.
Key complication of Systemic JIA, and its presentation?
A key complication is macrophage activation syndrome (MAS), where there is severe activation of the immune system with a massive inflammatory response.
It presents with an acutely unwell child with disseminated intravascular coagulation (DIC), anaemia, thrombocytopenia, bleeding and a non-blanching rash. It is life threatening.
A key investigation finding is a low ESR.
What is polyarticular JIA and what pattern does it follow?
Polyarticular JIA involves idiopathic inflammatory arthritis in 5 joints or more.
The inflammatory arthritis tends to be symmetrical and can affect the small joints of the hands and feet, as well as the large joints such as the hips and knees.
Polyarticular JIA - systemic symptoms
There are minimal systemic symptoms, but there can be mild fever, anaemia and reduced growth. Systemic symptoms are mild, unlike systemic onset JIA.
Polyarticular JIA vs RA
Polyarticular JIA is the equivalent of rheumatoid arthritis in adults.
Most children are negative for rheumatoid factor and are described as “seronegative”.
When rheumatoid factor is positive they are described as “seropositive”. Seropositive patients tend to be older children and adolescents and the disease pattern is more similar to rheumatoid arthritis in adults.
What is oligoarticular JIA and what pattern does it follow?
This is also knowns as pauciarticular JIA. It involves 4 joints or less. Usually it only affects a single joint, which is described as a monoarthritis. It tends to affect the larger joints, often the knee or ankle.
In which patients does oligoarticular JIA occur more frequently?
Girls under 6 years
Blood abnormalities in oligoarticular JIA?
Patients tend not to have any systemic symptoms and inflammatory makers will be normal or mildly elevated.
Antinuclear antibodies are often positive
Rheumatoid factor is usually negative
What is a classic associated feature with oligoarticular JIA and who should patients with this be seen by?
Anterior uveitis
Patients should be referred to an ophthalmologist for management and follow up of uveitis.
Which patients are affected by enthesitis related arthritis?
Enthesitis-related arthritis is more common in male children over 6 years. It can be thought of as the paediatric version of the seronegative spondyloarthropathy group of conditions that affect adults
What is enthesitis-related arthritis?
An enthesis is the point at which the tendon of a muscle inserts into a bone. Enthesitis is inflammation of this insertion point.
Patients have inflammatory arthritis in the joints as well as enthesitis.
Why might enthesitis occur?
Traumatic stress e.g. repetitive strain during sports
Autoimmune inflammatory process
Investigating enthesitis-related arthritis?
MRI scan of the affected joint can demonstrate enthesitis (but cannot distinguish between an enthesitis due to stress or an autoimmune process)
GENETIC TESTING: The majority of patients with enthesitis-related arthritis have the HLA B27 gene.
OPTHAMOLOGY SCREENING: Patients with enthesitis-related arthritis are prone to anterior uveitis, and should see an ophthalmologist for screening, even if they are asymptomatic.
CONSIDER: When assessing patients for enthesitis-related arthritis, consider signs and symptoms of psoriasis (psoriatic plaques and nail pitting) and inflammatory bowel disease (intermitted diarrhoea and rectal bleeding)
When assessing patients for enthesitis-related arthritis, consider signs and symptoms of what other conditions?
Psoriasis
IBD
Anterior uveitis
Patients with enthesitis will be tender to localised palpation of the entheses. Therefore it is worth palpating key areas to elicit tenderness of the entheses at which points?
Interphalangeal joints in the hand
Wrist
Over the greater trochanter on the lateral aspect of the hip
Quadriceps insertion at the anterior superior iliac spine
Quadriceps and patella tendon insertion around the patella
Base of achilles, at the calcaneus
Metatarsal heads on the base of the foot
Juvenile psoriatic arthritis is associated with what signs on examination?
Plaques of psoriasis on the skin
Pitting of the nails (nail pitting)
Onycholysis, separation of the nail from the nail bed
Dactylitis, inflammation of the full finger
Enthesitis, inflammation of the entheses, which are the points of insertion of tendons into bone
Patten of join involvement in Juvenile Psoriatic Arthritis?
The pattern of joint involvement varies. Patients can have a symmetrical polyarthritis affecting the small joints similar to rheumatoid, or an asymmetrical arthritis affecting the large joints in the lower limb.
What is Psoriatic arthritis?
Psoriatic arthritis is an seronegative inflammatory arthritis associated with psoriasis, the skin condition.
Management of Juvenile Idiopathic Arthritis
The management should be coordinated by a specialist in paediatric rheumatology, with a specialist multi-disciplinary team. The aim of treatment is to reduce inflammation within the joints, minimise symptoms and maximise function.
Medical treatment depends on the severity and response, and involves:
NSAIDs, such as ibuprofen
Steroids, either oral, intramuscular or intra-artricular in oligoarthritis
Disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate, sulfasalazine and leflunomide
Biologic therapy, such as the tumour necrosis factor inhibitors etanercept, infliximab and adalimumab
What is EDS?
Ehlers-Danlos syndrome (EDS) is an umbrella term that encompasses a group of genetic conditions that cause defects in collagen, resulting in hypermobility of the patient’s joints and abnormalities in connective tissue such as the skin, bones, blood vessels and organs. There are several types of Ehlers-Danlos syndrome.
Types of Ehlers-Danlos syndrome?
Hypermobile
Classical Ehlers-Danlos syndrome
Vascular Ehlers-Danlos syndrome
Kyphoscoliotic Ehlers-Danlos syndrome
Hypermobile EDS - features and inheritance
Hypermobile Ehlers-Danlos syndrome represents most cases of EDS
It is the most common and least severe type of Ehlers-Danlos syndrome.
The key feature is joint hypermobility, but patients also have soft and stretchy skin.
The gene for hypermobile EDS has not been identified and there is no single mode of inheritance.
Classical Ehlers-Danlos syndrome features and inheritance
Classical Ehlers-Danlos syndrome features remarkably stretchy skin that feels smooth and velvety to touch.
They also have severe joint hypermobility, joint pain and abnormal wound healing.
They often develop lumps over pressure points, such as the elbows.
They are prone to hernias, prolapses, mitral regurgitation and aortic root dilatation.
Inheritance is autosomal dominant.
Vascular Ehlers-Danlos syndrome - features and inheritance?
Vascular Ehlers-Danlos syndrome is the most dangerous form of EDS, where the blood vessels are particularly fragile as a result of defective collagen.
Patients have characterise thin, translucent skin that you can almost see through.
The skin, internal organs and arteries are fragile and prone to rupturing.
Patients are monitored for vascular abnormalities and told to seek urgent medical attention for sudden unexplained pain or bleeding.
Inheritance is autosomal dominant.
Kyphoscoliotic Ehlers-Danlos syndrome features and inheritance
Kyphoscoliotic Ehlers-Danlos syndrome is characterised initially by poor tone (hypotonia) as a neonate and infant, followed by kyphoscoliosis as they grow.
There is significant joint hypermobility.
Patients tend to be tall and slim.
There is a risk of rupture in the medium sized arteries.
Inheritance is autosomal dominant.
Which types of Ehlers-Danlos syndrome are inherited by an autosomal dominant pattern?
Classical Ehlers-Danlos syndrome
Vascular Ehlers-Danlos syndrome
Kyphoscoliotic Ehlers-Danlos syndrome
What is the most dangerous form of EDS?
Vascular - skin, internal organs and arteries are fragile and prone to rupture
Thin, translucent skin is a characteristic of which type of EDS?
Vascular
Abnormal wound healing is a charecteristic of which type of EDS?
Classical EDS
Which type of EDS is initially characterised by hypotonia?
Kyphoscoliosis EDS
The most common presenting complaint for hypermobile EDS is joint pain and hypermobility, however abnormalities in collagen make it a multi-system disorder leading to symptoms across multiple areas of the body, such as what?
Soft stretchy skin
Easy bruising
Poor wound healing
Bleeding
Headaches
Autonomic dysfunction causing dizziness and syncope
GORD
Abdo pain
IBS
Menorrhagia and dysmenorrhea
PROM in pregnancy
Urinary incontience
Pelvic organ prolapse
TMJ dysfunction
Myopia
Joint features in hypermobile EDS?
Hypermobility
Joint pain after exercise or inactivity
Joint dislocations (e.g. shoulders of hips)
What tool is used to assess patients with hypermobility and how is it calculated?
The Beighton score is used to assess the extent of hypermobility and support the diagnosis of hypermobility syndrome. One point is scored for each side of the body, with a maximum score of 9:
Palms flat on floor with straight legs (score 1)
Elbows hyperextend
Knees hyperextend
Thumb can bend to touch the forearm
Little finger hyperextends past 90 degrees
Diagnosing hypermobile EDS
Diagnosis is made using the Beighton score
What should be excluded when diagnosing EDS?
It is important to exclude Marfan syndrome, which also features hypermobility, by examining for features such as high arch palate, arachnodactyly and arm span.
There is no cure for Ehlers-Danlos syndrome. Management focuses on maintaining health joints, monitoring for complications and minimising symptoms. Management involves what?
Follow up with relevant specialties depending on the associated complications
Physiotherapy to strengthen and stabilise the joints
Occupational therapy to maximise function
Maintaining good posture in the joints
Moderating the intensity of activity to minimise flares
Psychology may be required to a help manage the chronic condition and pain
Postural orthostatic tachycardia syndrome (POTS) can occur with hypermobile Ehlers-Danlos syndrome - what is it?
POTS is a result of autonomic dysfunction.
This causes inappropriate tachycardia on sitting or standing up, resulting in distressing symptoms such as presyncope, syncope, headaches, disorientation, nausea and tremor.
What common condition associated with aging are patients with EDS more likely to develop at an earlier age?
Hypermobility in the joints leads to additional wear and tear on the joint. This means patients with hypermobility often develop generalised osteoarthritis at an earlier age.
What is Henoch-Schonlein Purpura?
Henoch-Schonlein Purpura (HSP) is an IgA vasculitis that presents with a purpuric rash affecting the lower limbs and buttocks in children.
Inflammation occurs in the affected organs due to IgA deposits in the blood vessels.
What causes inflammation in HSP?
Inflammation occurs in the affected organs due to IgA deposits in the blood vessels.
Which organs are affected by Henoch-Schonlein Purpura?
Skin (purpuric rash)
Kidneys (IgA nephritis)
GI tract (abdominal pain)
What is Henoch-Scholein Purpura often triggered by?
The condition is often triggered by an upper airway infection or gastroenteritis.
In what ages is HSP most common?
It is most common in children under the age of 10 years.
What are the four classic features of HSP?
Purpura (100%),
Joint pain (75%),
Abdominal pain (50%)
Renal involvement (50%)
What causes the rash in HSP?
The rash is caused by inflammation and leaking of blood from small blood vessels under the skin (due to IgA deposits in the blood vessels) forming purpura.
What are purpura?
Purpura are red-purple lumps under the skin containing blood.
The majority of patients with HSP have purpura - what is purpura, where do patients get affected by this, and what complication can occur?
They are red-purple in colour and are palpable under the skin. Typically they start on the legs and spread to the buttocks. They can also affect the trunk and arms. In severe cases, skin ulceration and necrosis can develop.
HSP - joint manifestations?
75% of patients with HSP develop arthralgia or arthritis, mostly affecting the knees and ankles. The joints can become swollen and painful, with a reduced range of movement.
HSP - GI manifestations?
Abdominal pain is indicative of gastrointestinal involvement.
This affects around 50% of patients with HSP.
In severe cases, it can lead to gastrointestinal haemorrhage, intussusception and bowel infarction.
HSP - renal manifestations?
HSP affects the kidneys in around 50% of patients, causing an IgA nephritis.
This is sometimes referred to as HSP nephritis.
This can lead to microscopic or macroscopic haematuria and proteinuria.
If there is more than 2+ of protein on the urine dipstick the child has developed nephrotic syndrome and will have a degree of oedema.
The most important initial step in ?Henoch-Schonlein Purpura is to exclude other serious pathology, such as what?
- Meningococcal septicaemia and leukaemia
- Idiopathic thrombocytopenic purpura and haemolytic uraemic syndrome are also differentials for a non-blanching rash
HSP - investigations to exclude other pathology nd to assess for organ involvement?
Full blood count and blood film for thrombocytopenia, sepsis and leukaemia
Renal profile for kidney involvement
Serum albumin for nephrotic syndrome
CRP for sepsis
Blood cultures for sepsis
Urine dipstick for proteinuria
Urine protein:creatinine ratio to quantify the proteinuria
Blood pressure for hypertension
EULAR/PRINTO/PRES criteria for diagnosis of Henoch-Schonlein Purpura?
Palpable purpura (not petichiae) + at least one of:
Diffuse abdominal pain
Arthritis or arthralgia
IgA deposits on histology (biopsy)
Proteinuria or haematuria
Henoch-Schonlein Purpura - management and monitoring?
Management is supportive, with simple analgesia, rest and proper hydration.
The use of steroids is debatable, with evidence suggesting they may shorten the duration of the illness but not affect long term outcomes or rate of recurrence. Steroids may be considered by specialist doctors in patients with severe gastrointestinal pain or renal involvement.
It is important that patients with HSP are monitored closely whilst the illness is active. They need close monitoring with repeated:
Urine dipstick monitoring for renal involvement
Blood pressure monitoring for hypertension
HSP prognosis
Abdominal pain usually settles within a few days.
Patients without kidney involvement can expect to fully recover within 4 to 6 weeks.
A third of patients have a recurrence of the disease within 6 months.
A very small proportion of patients will develop end stage renal failure.
What is Kawasaki disease also known as?
Mucocutaneous lymph node syndrome.
What type of vasculitis is mucocutaneous lymph node syndrome (Kawasaki disease)?
It is a systemic, medium-sized vessel vasculitis.
In which patients is Kawasaki disease/mucocutaneous lymph node syndrome more common?
It affects young children, typically under 5 years.
There is no clear cause or trigger.
It is more common in Asian children, particularly Japanese and Korean children.
It is also more common in boys
Clinical features of Kawasaki disease (mucocutaneous lymph node syndrome)
Persistent high fever (above 39ºC) for more than 5 days
Widespread erythematous maculopapular rash and desquamation (skin peeling) on the palms and soles
Strawberry tongue (red tongue with large papillae)
Cracked lips
Cervical lymphadenopathy
Bilateral conjunctivitis
A rash, strawberry tongue, lymphadenopathy, conjunctivitis and a fever persisting more than 5 days in a child suggest what?
Kawasaki disease?
What investigations should be performed in suspected Kawasaki disease and what might they show?
Full blood count can show anaemia, leukocytosis and thrombocytosis
Liver function tests can show hypoalbuminemia and elevated liver enzymes
Inflammatory markers (particularly ESR) are raised
Urinalysis can show raised white blood cells without infection
Echocardiogram can demonstrate coronary artery pathology
Key complications of Kawasaki disease?
coronary artery aneurysm
Kawasaki disease: acute phase
The child is most unwell with the fever, rash and lymphadenopathy.
This lasts 1 – 2 weeks.
Kawasaki disease: subacute phase
The acute symptoms settle (fever, maculopapular rash, lymphadenopathy), the desquamation and arthralgia occur and there is a risk of coronary artery aneurysms forming.
This lasts 2 – 4 weeks
Kawasaki disease - convalescent stage
The remaining symptoms settle, the blood tests slowly return to normal and the coronary aneurysms may regress.
This last 2 – 4 weeks
Management of Kawasaki disease?
There are two first line medical treatments given to patients with Kawasaki disease:
High dose aspirin to reduce the risk of thrombosis
IV immunoglobulins to reduce the risk of coronary artery aneurysms
Patients will need close follow up with echocardiograms to monitor for evidence of coronary artery aneurysms.
Kawasaki disease is one of the few scenarios where aspirin is used in children - why?
Aspirin is usually avoided due to the risk of Reye’s syndrome.
What is Rheumatic fever and why does it occur?
Acute rheumatic fever is an autoimmune condition triggered by streptococcus bacteria. It is caused by antibodies created against the streptococcus bacteria that also target tissues in the body.
It is a multi-system disorder that affects the joints, heart, skin and nervous system. It is rare in the UK due to early treatment of streptococcus with antibiotics.
Rheumatic fever - pathophysiology
Rheumatic fever is caused by group A beta-haemolytic streptococcal, typically streptococcus pyogenes causing tonsillitis.
The immune system creates antibodies to fight the infection.
These antibodies not only target the bacteria, but also match antigens on the cells of the person’s body, for example the muscle cells in the myocardium in the heart.
This results in a type 2 hypersensitivity reaction, where the immune system begins attacking cells throughout the body.
This process is usually delayed 2 – 4 weeks after the initial infection.
What organism causes Rheumatic fever?
Rheumatic fever is caused by group A beta-haemolytic streptococcal, typically streptococcus pyogenes causing tonsillitis.
What type of hypersensitivity reaction occurs in rheumatic fever?
Type 2 hypersensitivity
How long after initial streptococcal infection does rheumatic fever occur?
2-4 weeks
Presentation of rheumatic fever?
The typical presentation of rheumatic fever occurs 2 – 4 weeks following a streptococcal infection, such as tonsillitis.
Symptoms affect multiple systems, causing:
Fever
Joint pain
Rash
Shortness of breath
Chorea
Nodules
Joint involvement in rheumatic fever?
Rheumatic fever causes a migratory arthritis affecting the large joints, with hot, swollen, painful joints.
It is migratory because different joints become inflamed and improve at different times, giving the appearance that the arthritis is moving from one joint to the next.
Heart involvement in rheumatic fever?
Carditis, or inflammation throughout the heart, with pericarditis, myocarditis and endocarditis, leads to:
Tachycardia or bradycardia
Murmurs from valvular heart disease, typically mitral valve disease
Pericardial rub on auscultation
Heart failure
Skin involvement in rheumatic fever?
There are two key skin findings with rheumatic fever:
Subcutaneous nodules
Erythema marginatum rash
Firm painless nodules occur over extensor surfaces of joints, such as the elbows. The erythema marginatum rash involves pink rings of varying sizes affecting the torso and proximal limbs.
CNS involvement in rheumatic fever
Chorea is the key nervous system symptom. This involves irregular, uncontrolled and rapid movements of the limbs. This is also known as Sydenham chorea and historically as St Vitus’ Dance.
?Rheumatic fever - investigations?
Throat swab for bacterial culture
ASO antibody titres
Echocardiogram, ECG and chest xray can assess the heart involvement
What antibody titres are used to help support a diagnosis of rheumatic fever?
Anti-streptococcal antibodies (ASO)
ASO levels following acute infection
Rise over 2 – 4 weeks
Peak around 3 – 6 weeks
Gradually falls over 3 – 12 months
ASO levels are usually repeated after 2 weeks to:
Confirm a negative test
Assess whether levels are rising or falling
Rheumatic fever - Jones Criteria for diagnosis
A diagnosis of rheumatic fever can be made when there is evidence of recent streptococcal infection, plus:
Two major criteria OR
One major criteria plus two minor criteria
The mnemonic for the Jones criteria is JONES – FEAR.
Major Criteria:
J – Joint arthritis
O – Organ inflammation, such as carditis
N – Nodules
E – Erythema marginatum rash
S – Sydenham chorea
Minor Criteria:
Fever
ECG Changes (prolonged PR interval) without carditis
Arthralgia without arthritis
Raised inflammatory markers (CRP and ESR)
Jones criteria for diagnosing rheumatic fever - major
J – Joint arthritis
O – Organ inflammation, such as carditis
N – Nodules
E – Erythema marginatum rash
S – Sydenham chorea
x2 minor + 1 major + evidence of recent streptococcal infection required for diagnosis of RF
Jones criteria for diagnosing rheumatic fever - minor?
Fever
ECG Changes (prolonged PR interval) without carditis
Arthralgia without arthritis
Raised inflammatory markers (CRP and ESR)
x2 minor + 1 major + evidence of recent streptococcal infection required for diagnosis of RF
Management of rheumatic fever?
Treatment of streptococcal infections with antibiotics helps prevent the development of rheumatic fever. Tonsillitis caused by streptococcus should be treated with phenoxymethylpenicillin (penicillin V) for 10 days.
Patients with clinical features of rheumatic fever should be referred immediately for specialist management. Management involves medications and follow up:
NSAIDs (e.g. ibuprofen) are helpful for treating joint pain
Aspirin and steroids are used to treat carditis
Prophylactic antibiotics (oral or intramuscular penicillin) are used to prevent further streptococcal infections and recurrence of the rheumatic fever. These are continued into adulthood.
Monitoring and management of complications
Complications of rheumatic fever?
Recurrence of rheumatic fever
Valvular heart disease, most notably mitral stenosis
Chronic heart failure
What kind of murmur is associated with rheumatic fever?
Mitral stenosis potential complication:
Mitral stenosis is associated with a low-pitched, rumbling, mid-diastolic murmur heard loudest over the apex.
Mitral stenosis (MS) involves narrowing of the mitral valve, which results in decreased filling of the left ventricle during systole and increased left atrial pressure (due to incomplete left atrial emptying).
