Haematology and Oncology 2 Flashcards
What is Henoch-Schönlein purpura (HSP)?
Is it common?
IgA-mediated autoimmune hypersensitivity vasculitis of childhood
Unknown cause
Most common systemic vasculitis in children (but still rare - 10/20 per 100,000 per year)
What are the 5 main clinical features of HSP?
1) Skin purpura
2) Arthritis
3) Abdo pain
4) GI bleeding
5) Nephritis
At what age does HSP occur?
90% under 10 years
Peak 4-6 years
What is the pathophysiology of HSP?
IgA immune complexes deposit in small blood vessels of skin, joints, kidneys and GIT causing inflammatory reactions
How does HSP present?
Child comes in with limp!
Most often in autumn / winter, sometimes following an URTI or GI infection
1) Mildly ill + low grade fever
2) Symmetrical, erythematous macular rash on backs of legs, buttocks, ulnar side of arms
2) Within 24hrs maculses evolve into purpuric lesions which can coalesce to resemble bruises. Raised and palpable
4) Abdo pain and bloody diarrhoea may precede rash
5) +/- n&v
6) Joint pain esp knees and ankles
7) Renal involvement in 40%
- microscopic haematuria
- proteinuria
- nephritic syndrome
- (rarely oliguria and HTN)
8) Scrotal involvement
- Can mimic testicular torsion
Ddx of purpuric rash
Thrombocytopenia
Meningococcal meningitis
Trauma
Coughing / sneezing gives pinpoint petechia by ears / above nipples
Ddx of HSP
Intussusception
Connective tissue disease eg SLE
Other causes of purpuric rashes
Other causes of glomerulopnetphritis
Other causes of GI symptoms eg IBD
Acute haemorrhage oedema of infancy
What is acute haemorrhage oedema of infancy?
Self-limiting condition presenting with fever, oedema and targeted-shaped purpura affecting face, ears and extremities
How is HSP diagnosed?
Clinically
Tests include:
1) Urinalysis
- Haeamtuira and/or proteinuria (present in 20-40%)
2) FBC
- Raised WCC with eosinophilia
- Normal or inc platelets
- Helps exclude other causes eg thrombocytopenia
3) Raised ESR
4) Raised creatinine if renal involvement
5) Raised serum IgA
6) Testicular USS
- assess possible torsion
7) Renal biopsy
- Persistent nephrotic sundrome
What should be performed to confirm intussusception?
Barium enema
What is the management of HSP?
Usually self-limiting (resolves within 4 weeks)
Supportive treatment
NSAIDs for joints
- Caution if renal insufficiency or GI symptoms
Monitor BP and urinalysis for those with proteinuria
What are some complicaitons HSP?
Renal involvement usually mild (less than 1% progress to CKD)
Rarely MI, intussusception, GI bleeding, testicular haemorrhage
Recurrence in 1/3rd within 4-6 months of initial presentation
What are the 4 main types of leukaemia?
1) Acute lymphoblastic leukaemia (ALL)
2) Chronic lymphoblastic leukaemia (CLL)
3) Acute myeloid leukaemia (AML)
4) Chronic myeloid leukaemia (CML)
What is the most common leukaemia?
ALL
Chronic rare in childhood
Leukaemia is the most common malignancy of childhood (30%)
What is the pathophysiology of leukaemia?
Malignant proliferation of white cell precursors (B or T cells) within bone marrow
These ‘blast’ cells escape into circulation and are deposited in lymphoid or other tissue
What is the peak age of presentation of ALL?
What age of presentation has a worse prognosis of ALL?
Between 2-5yrs
<2 yr or >10yr
How may ALL present? (8)
Insidious
1) Malaise
2) Anorexia
3) Pallor
4) Bruising
5) Bleeding
6) Lymphadenopathy
7) Splenomegaly
8) Bone pain
What may FBC show in ALL?
1) Anaemia
2) Thrombocytopenia
3) Raised WCC
Extremely high WCC = worse prognosis
What may be seen on a peripheral blood film in ALL?
Blast cells
How is a diagnosis of ALL confirmed?
Bone marrow aspirate
- Shows marrow infiltrated with blast cells
Cells examined by immunophenotyping and cytogenetic analysis
What % of ALL have specific genetic abnormalities in the leukaemic cell line? Example?
> 90%
eg TEL-AMLI fusion gene = 20% children with ALL
How can ALL be subdivide?
Common = 75% T-cell = 15% Null = 10% B-cell = 1%
What does treatment of ALL involve?
Chemo to induce remission - remove blast cells from circulation and restore normal marrow function
Then maintain remission
How is remission remained in ALL?
Intensification chemo
MTX or cranial irradiation protects CNS from involvement
Monthly cycles of maintenance chemo
What % of children achieve are successfully induced into remission in ALL?
What is the prognosis?
95%
Good prognosis - 80% 5yr survival
What are children who relapse in ALL offered?
High-dose chemo and bone marrow transplant
What may a CXR show in ALL?
Mediastinal mass
Lytic bone lesions
What are the cells in the myeloid cell line?
RBC
Platelets
Granulocytes
Monocytes
What are the cells in the lymphoid cell line?
Lymphocytes
What are WBC?
Lymphocyte (lymphoid)
Monocytes and granulocytes (myeloid)
What is lymphoma?
Malignancy of the lymphatic system
How common is lymphoma in children? It follows which other cancers?
3rd most common cancer
after leukaemia and brain tumours
What are the two main types of lymphoma?
Hodgkin and non-Hodgkin lymphoma (NHL)
How is Hodgkins lymphoma characterised?
Presence of multinucleate giant cell = Reed-Sternberg cells
What are the 4 types of NHL found in children?
1) Burkitt and Burkitt-like lymphoma
2) Diffuse large B-cell lymphoma
3) Anaplastic large cell lymphoma
4) Lymphoblastic lymphoma (of B or T cell origin)
What are some risk factors for NHL?
Male
Immunocompromised
DNA repair defects
How may NHL present?
Painless lymphadenopathy - neck, supraclavicular, axillary, groin
What investigations are done for NHL?
Bone marrow aspirate LP Pleural and peritoneal fluid asirate Exclusional biopsy CT and PET scans
What is the treatment of NHL?
Same as ALL
What is the prognosis of NHL?
> 70% survival in >90% localised disease
What are some risk factors for Hodgkin’s lymphoma?
Inc age (rare before 5yr) More common in pt with previous EBV
How may Hodgkin’s lymphoma present?
Progressive, painless LN enlargement
- Mostly cervical and mediastinal
B symptoms = common in advanced stages
- Fever
- Night sweats
- Weight loss
How is Hodgkin’s lymphoma staged?
Ann Arbour staging
What investigations are done for Hodgkin’s lymphoma?
CT - neck, chest, abdo, pelvis
FDT-PET scan
Bone marrow aspiration and trephine (remove 1/2cm core of bone marrow)
EBV serology
ESR
Isotope if bone involvement / b symptoms
What is the treatment of Hodgkin’s lymphoma?
What may be required in a relapse?
What is 5yr survival?
Chemo
Radiotherapy
Autologous stem cell transplant
90% 5yr survival
What is the commonest haemoglobinopathy?
Sickle cell anaemia
What population does sickle cell anaemia most commonly affect?
Black ethnicity
What is the cause of sickle cell anaemia?
Genetic defect where there is a substitution of one of the amino-acids in the global chain
Causes an unstable haemoglobin = HbS with shorter lifespan
Autosomal recessive
What is the pathophysiology of sickle cell anaemia?
When HbS is deoxygenated, it forms highly structured polymers which cause brittle, spiny red cells
These occlude blood vessels = ischaemic changes
Chronic haemolytic anaemia
How may children with sickle cell anaemia present?
Recurrent, acute, painful crises
Swelling of hands and feet
What may precipitate a crisis in sickle cell anaemia?
Dehydration
Hypoxia
Acidosis
Why may children with sickle cell anaemia be more susceptible to infections?
Repeated splenic infarction (esp in early years) can leave the child asplenic
What may lead to dehydration in children with sickle cell anaemia?
Renal damage leading to a reduced ability to concentrate urine
What is sickle cell trait?
Heterozygous HbS (as opposed to homozygous in sickle cell disease)
How may sickle cell trait present?
Asymptomatic other than in low oxygen situations eg high altitude or under GA
What may a physical examination of a child with sickle cell anaemia show?
Chronic anaemia Flow murmur Jaundice Chronic leg ulcers Dactylitis Splenomegaly (young child only) Haematuria
What are the four types of acute crisis in sickle cell anaemia?
1) Thrombotic
2) Sequestration
3) Aplastic
4) Haemolytic
What is a thrombotic sickle cell acute crisis?
Aka painful crisis / vaso-occlusive
Various organs including bones, eg:
- Avascular necrosis of the hip
- Hand-foot syndrome
- Lungs
- Spleen
- Brain
What is a sequestration sickle cell acute crisis?
Sickling within organs eg spleen/lungs causes pooling blood with worsening anaemia
Spleen becomes enlarged causing abdominal pain
More common in early childhood
What may result from a sequestration sickle cell crisis?
Severe anaemia
Marked pallor
CV collapse due to loss of effective circulating volume
What is an aplastic acute crisis of sickle cell caused by?
Infection with parvovirus B19 (86%)
Other causes include viral illness
Sudden fall in Hb
What is a haemolytic sickle cell acute crisis?
Rare
Fall in Hb due to an increased rate of haemolysis
Ddx of sickle cell anaemia
Leukaemia Arthritis Osteomyelitis Septic artritis Trauma
What investigations can be done for sickle cell anaemia?
Peripheral blood smear:
- Target cells
- Poikilocytes (abnormally shaped RBC)
- Irreversibly sickled cells
Electrophoresis:
- HbS
- Absent HbA
Abnormal LFTs
What is the management of sickle cell anaemia?
Treatment of crises is symptomatic
Severe cases (very high HbS) - exchange transfusion
Immunisations kept up date
Daily lifelong prophylactic PO penicillin V to reduce the risk of pneumococcal disease
Antenatal screening of affected individuals
Daily oral folic acid
Bone marrow transplantation can be curative
What are some complications of sickle cell anaemia?
Pneumococcal infection due to asplenism
Osteomyelitis
Renal damage
Gall stones
HF from chronic anaemia
What is the prognosis of aplastic anaemia?
High mortality from sepsis <3yr
What is priapism?
Persistent and painful erection of penis
Usually nocturnal with risk of long term impotence
Can occur in sickle cell crisis
What is a neuroblastoma?
Commonest extra cranial tumour in children
Malignancy that can affect any part of the sympathetic nervous system most commonly the adrenal medulla
How may a neuroblastoma present?
Depends on site of disease
Abdo mass +/- associated pain
Failure to thrive
Bleeding
Unwell child
Horner’s syndrome
Spinal cord, airway, bowel or vein compression
Increase in urinary catecholamine metabolites - symptoms related to excess catecholamines eg HTN, dizziness, headaches
What is the peak age of presentation of neuroblastoma?
What is the survival of neuroblastoma in:
1) Disseminated disease
2) Low risk cases
First 2 years of life
1) Disseminated disease = 20-30%
2) Low risk cases = >90%
What is tumour lysis syndrome?
Breakdown of large number of malignant cells either before/during chemo can lead to very high serum urate, phosphate and potassium levels
Urate precipitate in kidneys causing renal failure
How can tumour lysis syndrome be prevented?
Good hydration
Allopurinol (xanthine oxidase inhibitor) or uric acid oxidase
What investigations can be done for neuroblastoma?
Urine catecholamine metabolites - homovanillic acid and vanillymandelic acid
Imaging (US / MRI) - heterogenous mass with calcification
Confirm diagnosis with tumour biopsy + bone marrow biopsy of both iliac crest to check for mets (common at presentation)
What is the management of neuroblastoma?
Surgery
Chemo
Radiotherapy
What is a Wilm’s tumour? What is the mean age of onset?
= nephroblastoma
Commonest renal tumour in children
Mean age of onset = 3.5yrs
How does a Wilm’s tumour present?
Most commonly = abdo mass
May have:
- pain
- haematuria
+/- HTN (inc renin)
How may a Wilm’s tumour be investigated?
Imaging (US then CT / MRI) shows heterogenous mass causing distortion of renal architecture
What is the most common site of metastases of a Wilm’s tumour?
Lungs = 20%
How is a Wilm’s tumour managed? What is the 5yr survival?
Nephrecctomy + chemo
(adjuvant and/or Neo-adjuvant)
5 yr survival = 90%
What is the genetic inheritance and pathophysiology of thalassaemia?
Autosomal recessive mutation leading to absence or dysfunction of the alpha or beta globing chains on haemoglobin A (HbA)
Cause haemolytic anaemia because of decreased or absent synthesis of a globin chain
What is alpha thalassaemia?
Leads to impaired impaired oxygen transport and extravascular haemolysis via splenic clearance
What are is the asymptomatic carrier state of alpha thalassaemia?
Alpha-thalassaemia silent carrier (minima) = one allele affected
Alpha-thalassaemia trait (minor) = two alleles affected
How many alleles are there for alpha and beta?
Alpha:
4 alleles = 2 genes on Chr 16
Beta:
2 alleles = 1 gene on Chr 11
What is the asymptomatic carrier state of beta thalassaemia?
Beta-thalassemia trait (minor) = one beta allele affected
What is the symptomatic state alpha thalassaemia?
3 affected alleles (HbH) or 4 affected alleles (Hb Bart)
What does Hb Bart cause?
Intrauterine haemolytic anaemia and hydros fettles = usually fatal
What is the symptomatic state of beta thalassaemia?
Homozygous for partly functioning alleles (thalassaemia intermedia) or non-functioning alleles (thalassaemia major)
What regions are alpha thalassaemia more common in?
Southeast Asia, Africa, India
What regions are beta thalassaemia more common in?
Mediterranean, Middle East, Central and South Asia, China
= In UK often Greek Cypriot or Bangladeshi origin
When does thalassaemia present?
Anytime from neonate to adulthood but later onset tends to be milder
Are presenting symptoms more severe in alpha or beta thalassamia?
Symptoms tend to be worse in beta-thalassaemia as the most severe alpha-thalassamia don’t survive pregnancy or early life
How may thalassaemia present?
1) Haemolytic anaemia
- Fatigue
- SOB
- Pallor
- Jaundice (beta)
- Cardiac flow murmur
2) Splenomegaly (alpha) or hepatosplenomegaly with abdo distension (beta)
3) FTT / growth restriction
4) Facial dysmorphia
5) Osteopenia (beta)
Why may there be a cardiac flow murmur in thalassamia?
High CO
What facial dysmorphia is seen in thalassaemia? Is it seen more in alpha or beta?
Fontal bossing
Maxillary hypertrophy
Large head
Commoner and more prominent in beta
What investigations are done for thlassaemia?
Preconception screening for both parents in risk populations
What would bloods show in thalassaemia?
Hypochromic microcytic anaemia
FBC - Low Hb, Low MCV, Low MCH
Inc reticulocytes
Blood film
Inc iron and inc ferritin in severe disease (either due to disease or due to treatment)
LFTS - increased unconjugated bilirubin (beta), inc liver enzymes if iron overload
How is thalassaemia diagnosed?
Hb electrophoresis
Gap-PCR detects common deletions to confirm
What is the management of thalassaemia?
Asymptomatic require no specific treatment (just avoid iron supplementation)
Transfusion if symptomatic
- Regular transfusions
Iron chelation if overload
Splenectomy / Bone marrow transplantation in severe cases
What causes low MCV (microcytic) anaemia and what would you check? (3)
Low ferritin = IDA
Abnormal electrophoresis = haemoglobinopathy eg thalassaemia
High lead levels = lead toxicity
What causes normal MCV anaemia?
High reticulocyte count:
1) Normal bilirubin = recent blood loss
2) Target cells + High bilirubin = haemolysis
Low reticulocyte count = chronic illness
What is the classic sign seen in thalassaemia in skull radiographs?
“hair-on-end” sign
What causes “hair-on-end” sign in thalassaemia?
Bone marrow hyperplasia due to insufficient erythropoiesis
What is seen on blood smear in thalassaemia?
Target cells
Tear drop cells
Anisopoikilycytosis (RBC vary in size + shape)
