Revision - Non-blanching Rashes, Sickle Cell Flashcards
What are the 6 most common causes of non-blanching rashes?
1) Meningococcal septicaemia
2) HSP
3) HUS
4) Non accidental injury
5) ITP
6) Forceful coughing/vomiting
What is ITP?
Development of a purpuric rash in those with low circulating platelets (<100) in the absence of any clear cause.
What is ITP caused by?
Type II hypersensitivity reaction –> production of antibodies that target and destroy platelets.
What does ITP typically follow in children?
Viral illness
What is the most typical presentation of ITP?
An otherwise well child with a petechial rash alone.
Usually there is a history of a recent viral illness, in approximately 60% of children (e.g. URTI).
Usually, what the the only blood abnormality in ITP?
Isolated thrombocytopenia (<100)
Normally no treatment is required in ITP.
What are some cases where treatment may be required?
1) pt is actively bleeding
2) severe thrombocytopenia (<10)
In these specific cases, what mx is indicated in ITP?
1) Stopping any medications which may affect platelets (e.g. NSAIDs)
2) Oral prednisolone (1st line)
3) IV immunoglobulins (IVIG)
4) Monoclonal antibodies such as rituximab
5) Splenectomy: can be considered once all medical treatment options have been exhausted
What is generally considered 1st line for ITP when treatment is indicated?
Oral pred
What is some key education and advice to give in ITP?
1) Avoid contact sports
2) Avoid IM injections and procedures such as lumbar punctures
3) Avoid NSAIDs, aspirin and blood thinning medications
4) Advice on managing nosebleeds
5) Seek help after any injury that may cause internal bleeding, for example car accidents or head injuries
Inheritance of sickle cell?
Autosomal recessive
What mutation is present in sickle cell?
Single point mutation in the beta globin gene on chromosome 11.
This results in amino acid replacement in the beta globin gene, from glutamic acid to valine.
This results in HbS.
Sickle cell trait vs sickle cell disease?
One abnormal copy of the gene results in sickle-cell trait - usually asymptomatic as they are carriers of the condition.
Two abnormal copies result in sickle-cell disease.
What is the problem with having sickle shaped RBCs?
1) cells are fragile and haemolyse
2) can block small blood vessels, causing infarction
Under physiological stress, sickled haemoglobin (HbS) polymerises and causes erythrocytes to deform into a sickled shape.
What are some physiological stressors?
1) Hypoxia
2) Infection
3) Dehydration
4) Cold temperatures
5) Acidosis e.g. lactic acid following exertion
Note - The above stressors do not usually induce sickling in patients with sickle cell trait (HbAS).
Clinical features of sickle-cell anaemia may be divided up into acute events and chronic complications.
Name some acute complications
1) Vaso-occlusive crisis
2) Acute chest syndrome
3) Priapism
4) Aplastic crisis
5) Haemolytic crisis
6) Splenic sequestration
Why is acidosis a favourable condition for sickling?
As it decreases Hb’s affinity for O2
RBCs change shape when DEoxygenated
Why do low flow vessels induce sickling?
As RBCs have lots of time to get rid of O2 molecules (more deoxygenated = more sickling)
What is free Hb in the plasma bound by?
Haptoglobin (Hb then gets recycled)
What is a low haptoglobin a sign of?
Intravascular haemolysis
Why is low haptoglobin a marker of haemolysis?
Because haptoglobin levels become depleted in the presence of large amounts of free Hb.
When do clinical features of sickle cell typically begin?
Around 3-6m of age
This is when HbF levels fall and HbS levels start to rise.
What is the most common reason for hospital admission among sickle cell patients?
Vaso-occlusive crisis
Commonly affected sites in a vaso-occlusive crisis?
1) Bones (long bones and vertebrae): bone pain & avascular necrosis
2) Joints: painful swollen joints & dactylitis
3) Lungs: SOB, chest pain, tachypnoea (up to 30% mortality in adult patients)
4) Brain: headaches & stroke
What is acute chest syndrome?
A life-threatening complication of sickle cell.
This may result from vaso-occlusion in pulmonary vasculature or infection leading to pneumonia.
Features of acute chest syndrome?
1) fever
2) SOB
3) tachypnoea
4) cough
5) sputum production
6) new onset hypoxia
How will acute chest syndrome present on a CXR?
New pulmonary infiltrates
What is aplastic crisis in sickle cell?
Temporary cessation of erythropoesis, resulting in severe anaemia.
Pts may present with high output HF 2ary to anaemia.
What are aplastic crises usually precipitated by?
Parvovirus B19 infection
What is usually required for management of aplastic crisis?
A transfusion is usually required but recovery may also occur spontaneously.
How does bone marrow respond to anaemia in sickle cell?
Produces increased number of reticulocytes
What is the result of increased production of reticulocytes in sickle cell?
New bone formation –> expansion of medullary cavities in skull –> enlarged cheeks.
Skull XR results in sickle cell if there has been an expansion in the medullary cavities?
Hair on end appearance
What is a ‘hair on end’ skull appearance a sign of?
Chronic hemolysis and is usually seen in patients with:
1) Thalassaemia
2) Sickle cell anemia
3) Hereditary spherocytosis
4) Iron deficiency anemia
5) Neuroblastoma metastasis
What is a sequestrian crisis in sickle cell?
The sudden enlargement of the spleen due to haemorrhage within it.
This is associated with an acute drop in Hb and a markedly raised reticulocyte count.
How can sequestration crisis present?
Sequestration may lead to circulatory collapse and hypovolaemic shock.
Occurs mainly in babies and young children.
what is recurrent splenic sequestration an indication for?
a splenectomy
What are some chronic complications of sickle cell?
1) anaemia
2) infections
3) leg ulcers
4) ocular complications
5) renal complications
6) CVS complications
What is functional asplenia?
Occurs when splenic tissue is present by doesn’t work well (e.g. sickle cell).
Such patients are managed as if asplenic.
Why are sickle cell patients more at risk of infections?
Functional asplenia occurs due to recurrent splenic infarctions.
This increases the susceptibility to encapsulated bacterial infections e.g. Streptococcus pneumoniae & Haemophilus influenzae.
What investigation is required for diagnosis of sickle cell?
Haemoglobin electrophoresis
How are infections prevented in sickle cell?
Vaccinations: regular childhood vaccinations plus vaccinations against meningococcus, pneumococcus, hepatitis B and influenza.
Oral penicillin prophylaxis is recommended until at least age five but is often continued life-long.
How is severe anaemia prevented in sickle cell?
Folic acid supplementation
How can sickle cell cause priapism?
Obstruction of venous outflow from the corpora cavernosa by sickled cells may cause persistent penile erection accompanied by pain.
What is hydroxyurea?
A once daily medication that increases HbF production (and thus reduces the proportion of HbS in the blood).
When is hydroxyurea given in sickle celkl?
It is offered to all patients with sickle cell anaemia from the age of 9 months old onwards (unless pregnant).
What will haemoglobin electrophoresis reveal in sickle cell?
Presence of HbS as well as absent or decreased HbA levels.
What are some complications of sickle cell to monitor for?
1) Stroke –> get head CT
2) Acute chest syndrome –> get CXR
3) Avascular necrosis of femoral head –> get XR or MRI of hips
4) Recurrent or severe infections due to functional asplenia
5) Dactylitis
6) Priapism
7) Gallstones
8) Retinopathy
9) Leg ulcers –> get a Doppler
What type of gallstones are seen in sickle cell?
Pigmented gallstones.
This is due to chronic red blood cell destruction leading to persistently elevated unconjugated bilirubin levels in sickle cell.
Why can hepatomegaly be seen in sickle cell?
Extramedullary haematopoiesis most commonly occurs in the liver.
What 4 bacteria are those with sickle cell particularly susceptible to?
Encapsulated bacteria:
1) strep. pneumoniae
2) h. influenzae
3) neisseria meningitidis
4) salmonella
What may be seen on a peripheral blood smear in sickle cell?
Howell Jolly bodies –> basophilic nuclear remnants of RBCs
How often should sickle cell patients receive the pneumonoccal vaccine?
Every 5 years
Mx of sickle cell?
1) O2 & fluids (mainstays of treatment)
2) Opioids
3) Abx
4) Occasionally blood transfusions (risk of iron overload)
5) Oral penicillin prophylaxis in children
6) Hydroxyurea
What is the mainstay of mx of a sickle cell crisis?
1) O2
2) Analgesia
3) IV fluids
How can a splenectomy affect HbA1c level?
Can cause a falsely high HbA1c level due to the increased lifespan of RBCs
How is a vaso-occlusive crisis diagnosed?
Clinically
What is HUS?
An IgA mediated small vessel vasculitis.
What does HUS typically follow?
Infection
Features of HSP?
1) Palpable purpuric rash (with localised oedema) over buttocks & extensor surfaces of arms & legs
2) Abdo pain
3) Polyarthritis
4) Features of IgA nephropathy e.g. haematuria, renal failure
Mx of HSP?
1) analgesia for arthralgia
2) supportive
Prognosis of HSP?
usually excellent, HSP is a self-limiting condition, especially in children without renal involvement
What shoold be monitored in HSP?
1) BP
2) Urinalysis
To detect progressive renal involvement
Mx of any child with sickle cell presenting with a fever (temp >38)?
Urgent hospital admission is mandatory regardless of how well they appear.
This is because these patients are functionally asplenic and are at high risk of overwhelming sepsis, particularly from encapsulated organisms such as Streptococcus pneumoniae.
What is anti-glomerular basement membrane (GBM) disease (previously known as Goodpasture’s syndrome)?
a rare type of small-vessel vasculitis
2 key features of anti-GBM disease?
1) pulmonary haemorrhage (haemoptysis)
2) rapidly progressive glomerulonephritis (AKI/proteinuria/haematuria)
What is the most common inherited bleeding disrder?
Von Willebrand’s disease
What is HUS classically caused by?
E. coli 0157
Mx of acute chest syndrome in sickle cell?
Same as vaso-occlusive crisis i.e. analgesia & O2
PLUS antibiotics & transfusion
In beta-thalassaemia major, what is required alongside repeated transfusions?
Desferrioxamine (to prevent complications of iron overload)
