Paediatrics Immunology Flashcards
What is allergy?
Umbrella term for hypersensitivy of the immune system to allergens (proteins that the immune sysem recognises as foreign and potentially harmful)
What is atopy?
Term for predisposition to having hypersensitivity reactions to allergens
What conditions does atopy encompass?
Eczema
Asthma
Hayfever
Allergic rhinitis
Food allergies
What is the skin sensitisation theory of allergy?
- Break in the infants skin (from eczema or a skin infection) allowing allergens e.g. peanut proteins into body and react with immune system
- Child does not have contact with allergen from GI tract and absence of GI exposure next time its encountered its recognised as foreign
What classification system is used for hypersensitivity reactions?
Coombs and Gell classification
What is a type 1 hypersensitivity reaction?
Immediate reaction with IgE antibodies a specific allergen triggers mast cells and basophils to release histamines and other cytokines
Typical food allergy reaction (= itching, facial swelling, urticaria, anaphylaxis)
What is a type 2 hypersensitivity reaction?
IgG and IgM antibodes react to an allergen and activate the complement system causing direct damage to local cells e.g. haemolytic disease of the newborn and transfusion reactions
What is a type 3 hypersensitivity reaction?
Immune complexes accumulate and cause damage to local tissues e.g. systemic lupus erythematosus (SLE) rheumatoid arthritis and Henoch-Schonlein purpura (HSP)
What is a type 4 hypersensitivity reaction?
Cell mediated hypersensitivity reaction caused by T lymphocytes - inappropriately activated - causing inflammation and damage to local tissues e.g. organ transplant rejection and contact dermatitis
How are allergies diagnosed?
History
What to cover in allergy history?
Timing after exposure to allergen
Previous and subsequent exposure and reaction to allergen
Symptoms of rash, swelling, breathing difficulty, wheezeand cough
Previous personal / FH of atopy
What are the 3 ways to test for allergy?
Skin prick testing
RAST testing - blood tests for total and specific immunoglobulin E (IgE)
Food challenge testing
What are skin prick testing and RAST testing assessing?
Sensitisation and not allergy (makes these tests notoriously unreliable and misleading)
What is the gold standard for diagnosing allergy?
Food challenge testing (requires lots of time and resources)
How is skin prick testing performed?
Allergens e.g. peanuts, house dust mite and pollen are dropped onto marked points on forearm along with water control and histamine control fresh needle is used to make a tiny break in the skin at each site - after 15 mins the size of the wheals to each allergen are assessed and compared
What testing is used to assess allergic contact dermatitis?
Patch testing
How is patch testing performed?
Patch containing allergen is placed on patients skin (either a specific allergen or grid of lots of allergens)
After 2-3 days the skin reaction to the patch is assessed
What is RAST testing?
Measures total and allergen specific IgE quantities in patients blood
In patients with atopic conditions e.g. eczema and asthma - results will often come back positive for everything you test
How is a food challenge performed?
In specialised unit with close monitoring
Child is given increasing quantities of an allergen to assess the reaction
Can be helpful in excluding allergies for reassurance
What is the management of allergy?
Establishing correct allergen
Avoidance of allergen
If allergic to dust mites then regular hoovering and changing sheets
Staying in doors when pollen count is high
Prophylactic antihistamines when contact is inveitable e.g. hayfever and allergic rhinitis
Given adrenalin auto-injector
What is immunotherapy?
Gradually exposing patient to allergens over months with aim of reducing their reaction
What is the treatment of allergic reactions?
Antihistamines (e.g. cetirizine)
Steroids (e.g. oral prednisolone, topical hydrocotrisone or IV hydrocortisone)
IM adrenalin in anaphylaxis
How do antihistamines and steroids work?
Dampening the immune response to allergens
What is anaphylaxis?
Life-threatening emergency
Severe type 1 hypersensitivity reaction
IgE stimulates mast cells to rapidly release histamine (mast cell degranulation) causing airway, breathing and/or circulation compromise
How to differentiate anaphylaxis from non-anaphylactic allergic reaction?
Compromise of the airway, breathing or circulation
How does anaphylaxis present?
Urticaria
Itching
Angio-oedema with swelling around the lips and eyes
Abdo pain
Which additional symptoms indicate anaphylaxis?
SoB
Wheeze
Swelling of larynx causing stridor
Tachycardia
Lightheadedness
Collapse
What is the initial management of anaphylaxis?
A – Airway: Secure the airway
B – Breathing: Provide oxygen if required. Salbutamol can help with wheezing.
C – Circulation: Provide an IV bolus of fluids
D – Disability: Lie the patient flat to improve cerebral perfusion
E – Exposure: Look for flushing, urticaria and angio-oedema
What medications to give during anaphylaxis?
IM adrenalin (repeated after 5 minutes if required)
Antihistamines e.g. chlorphenamine or cetirizine
Steroids usually IV hydrocortisone
What is the management after anaphylaxis?
Period of assessment and observation as biphasic reactions can occur (admission to paediatric unit)
Confirm anaphylaxis with serum mast cell tryptase within 6 hours of the event (tryptase is released during mast cell degranulation)
Education and follow-up of family and child - educated about allergy, how to avoid and how to spot signs of anaphylaxis
Train patients in BLS
Train patients in using adrenalin auto-injector
What are the adrenalin auto-injector trade names?
Epipen
Jext
Emerade
When are adrenalin auto-injectors indicated?
Asthma requiring inhaled steroids
Poor access to medical treatment (e.g. rural locations)
Adolescents who are at higher risk
Nut or insect sting allergies are higher risk
Co-morbidities e.g. CVD
How is the adrenlin auto-injector used?
Confirm the diagnosis of anaphylaxis
Remove cap on non-needle end
Grip device with needle end pointing downwards
Administer injection (hold in place)
Remove device and gently massage area for 10 seconds
Phone an ambulance
Second dose may be given after 5 mins if required
What is allergic rhinitis?
Condition caused by an IgE-mediated type 1 hypersensitivity reaction
Environmental allergens cause an allergic inflammatory response in the nasal mucosa - very common and can significantly affect sleep, mood, hobbies, work and school performance and quality of life
What may the pattern of allergic rhinitis be?
Seasonal e.g. hay fever
Perennial (year round) e.g. house dust mite allergy
Occupational associated with school / work environment
How may allergic rhinitis present?
Runny, blocked and itchy nose
Sneezing
Itchy, red and swollen eyes
How is allergic rhinitis diagnosed?
Made on the history
Skin prick testing can be useful particularly testing for pollen, animals and house dust mite allergy
What are the triggers for allergic rhinitis?
Tree pollen or grass leads to seasonal symptoms (hay fever)
House dust mites and pets can cause persistent symptoms, often worse in dusty rooms at night - pillows can be full of house dust mites
Pets can lead to persistent symptoms when the pet or their hair, skin or saliva is present
What is the management of allergic rhinitis?
Avoid trigger
Hovering / changing pillows / allowing good ventilation of the home
Stay indoors during high pollen count
Minimise contact with pets known to trigger allergies
What is the medication for allergic rhinitis?
Oral antihistamines taken prior to exposure to reduce allergic symptoms
- non-sedating antihistamines e.g. cetirizine, loratadine and fexofenadine
- sedating antihistamines including chlorphenamine (Piriton) and promethazine
Nasal corticosteroid sprays e.g. fluticasone and mometasone used regularly to suppress local allergic symptoms
Nasal antihistamines could be a good option for rapid onset symptoms in response to a trigger
What is good nasal spray technique?
Aim to coat the nasal passage
Hold spray in left hand when spraying into right nostril and vice versa
Spray outwards - away from septum
DON’T sniff at the same time (should not taste spray at back of mouth)
What is cow’s milk protein allergy?
Hypersensitivity to protein in cow’s milk
If IgE mediated then rapid reaction to cows milk (within 2 hours)
Non-IgE mediated where reactions are slow over several days
Who does cow’s milk protein allergy affect?
Condition affecting infants and young children under 3 years
How is cow’s milk protein intolerance different to lactose intolerance or cow’s milk intolerance?
There is no allergy to lactose in cow’s milk protein intolerance (lactose is a sugar)
Cow’s milk intolerance is not an allergic process - doesn’t involve the immune system
When is cow’s milk protein allergy more common?
Formula fed babies
FH or atopy
When does cow’s milk protein intolerance become apparant?
When weaned from breast milk or breast fed babies when mother is consuming dairy products
What are the GI symptoms of cow’s milk protein intolerance?
Bloating and wind
Abdo pain
Diarrhoea
Vomiting
What are the allergic symptoms in response to cow’s milk protein?
Urticarial rash (hives)
Angio-oedema (facial swelling)
Cough / wheeze
Sneezing
Watery eyes
Eczema
How is cow’s milk protein intolerance diagnosed?
Full history and examination
Skin prick testing can help support diagnosis
What is the management of cow’s milk protein intolerance?
Avoid cow’s milk
If breast feeding then avoid dairy products
Replace formula with special hydrolysed formulas designed for cow’s milk allergy
What are hydrolysed formulas?
Contain cow’s milk, however proteins have been broken down so they no longer trigger an immune response (severe causes require elemental formulas made from basic amino acids e.g. neocate)
How does cow’s milk protein intolerance progress?
Most outgrow allergy by age 3
Every 6 months or so tried on the milk ladder (e.g. malted milk biscuits) then slowly progress up the ladder
How does cow’s milk intolerance present?
Same GI symptoms as cow’s milk allergy:
- Bloating
- Wind
- Diarrhoea
- Vomiting
No allergic features (e.g. rash, angio-oedema, sneezing and coughing)
How is cow’s milk intolerence managed?
Grow out of it by 2-3 years
Fed with breast milk, hydrolysed formulas and weaned to foods not containing cow’s milk
After one year can be started on milk ladder
How many respiratory infections are normal for a child in a year?
4-8
When should children with recurrent infection be investigated?
Chronic diarrhoea since infancy
Failure to thrive
Appearing unusually well with a severe infection e.g. afebrile with a large pneumonia
Significantly more infections than expected e.g. bacterial lower respiratory tract infections
Unusual or persistent infections e.g. cytomegalovirus, candida and pneumocystis jiroveci
What are the choice of investigations for recurrent infection in childhood?
FBC: low neutrophils = phagocytic disorder
low lymphcytes = T cell disorder
Immunoglobulins: abnormalities suggest B cell disorders
Complement proteins: abnormalities suggest complement disorder
Antibody responses to vaccines, specifically pneumococcal and haemophilus vaccines
HIV test if clinically relevant
Chest X-ray for scarring from previous chest infections
Sweat test for cystic fibrosis
CT test for bronchiectasis
What is severe combined immunodeficiency (SCID)?
Immunodeficiency (most severe condition)
Almost no immunity to infection
Caused by genetic disorder causing absent / dysfunctioning T and B cells
How does SCID present?
First few months of life:
- Persistent severe diarrhoea
- Failure to thrive
- Opportunistic infection e.g. severe / fatal chickenpox
- Pneumocystic jiroveci pneumonia and cytomegalovirus
- Unwell after live vaccinations such as the BCG, MMR and nasal flu vaccine
- Omenn syndrome
What genetic mutations can cause SCID?
- Mutation in common gamma chain on the X-chromosome which codes for interleukin receptors on T and B cells (X-linked recessive)
- JAC3 gene mutation
- Mutation leading to adenosine deaminase deficiency
What is the genetic abnormality in Omenn syndrome?
Mutation in the recombination-activating gene (RAG1 or RAG2) which codes for important proteins in T and B cells (autosomal recessive inheritance)
What are the features of Omenn syndrome?
Red, scaly, dry rash (erythroderma)
Hair loss (alopecia)
Diarrhoea
Failure to thrive
Lymphadenopathy
Hepatosplenomegaly
What is the management of SCID?
At specialist immunology centre
- Treat infections
- Immunoglobulin therapy
- Sterile environment
- Avoid live vaccines
- Haematopoietic stem cell transplantation
Fatal unless successfully treated
What do B cells do?
Produce immunoglobulins (antibodies)
What is a deficiency in immunoglobulins called?
Hypogammaglobulinemia (causing susceptibility to recurrent infections especially LRTI)
What is the most common immunoglobulin deficiency?
Selective immunoglobulin A deficiency (low IgA and normal IgG and IgM)
Where is IgA?
Secretions of mucous membranes e.g. saliva, respiratory tract secretions, GI tract secretions, tears and sweat - protecting against opportunistic infections
How does selective IgA deficiency present?
Often aasymptomatic and never diagnosed - tendency to recurrent mucous membrane infections
If testing for coeliacs with IgA anti-TTG and anti-EMA need to test total IgA to rule out deficiency
What is common variable immunodeficiency?
Genetic mutation in gene coding for components of B cells cauing deficiency in IgG and IgA (with maybe deficiency in IgM)
Causes recurrent resp tract infections (leading to chronic lung disease over time)
Unable to develop immunity to infections or vaccinations
What are patients with common variable immunodeficiency also prone to?
Rheumatoid arthritis and cancers e.g. non-Hodgkins lymphoma
What is the management of common variable immunodeficiency?
Immunoglobulin infusion
Treating infections and complications as occur
What is X-linked Agammaglobinaemia?
X-linked recessive condition causing abnormal B cell development - deficiency in all classes of immunoglobulins (causes issues similar to common variable immunodeficiency)
What is X-linked agammaglobulinaemia also known as?
Bruton’s agammaglobulinaemia
What is DiGeorge syndrome also known as?
22q11.2 deletion syndrome
What is the genetic abnormality in DiGeorge syndrome?
Microdeletion in a portion of chromosome 22 causing a developmental defect in the third pharyngeal pouch and third brachial cleft
What is an immune complication of DiGeorge syndrome?
Incomplete development of the thymus gland - inability to create functional T cells
What are the features of DiGeorge syndrome?
C – Congenital heart disease
A – Abnormal faces (characteristic facial appearance)
T – Thymus gland incompletely developed
C – Cleft palate
H – Hypoparathyroidism and resulting Hypocalcaemia
22nd chromosome affected
What is purine nucleoside phosphorylase deficiency (PNP)?
Autosomal recessive condition (PNPase is an enzyme that helps break down purines_
What is a result of PNP deficiency?
PNPase is an enzyme which helps break down purines
Without this - metabolite called dGTP builds up
dGTP is toxic to T cells
There are normal levels of B cells and immunoglobulins
How do patients with PNP deficiency progress?
Immunity to infection gets worse becoming increasingly susceptible to infections particularly viruses and live vaccines
What is Wiskott-Aldrich syndrome?
X-linked recessive causing a mutation on the WAS gene causing abnormal functioning of T cells
What are the other features of Wiskott-Aldrich syndrome?
Thrombocytopenia
Immunodeficiency
Neutropenia
Eczema
Recurrent infections
Chronic bloody diarrhoea
What is ataxic telangiectasia?
Autosomal recessive condition affecting the gene coding for the ATM serine/threonine kinase protein on chromosome 11
Protein is important in functions of DNA coding
What are the features of ataxic telangiectasia?
Low numbers of T-cells and immunoglobulins
Ataxia: problems with coordination due to cerebellar impairment
Telangiectasia: particularly in the sclera and damaged area of skin
Predisposition to cancers particularly haematological cancers
Slow growth and delayed puberty
Accelerated ageing
Liver failure
What is acquired immunodeficiency syndrome?
Caused by infection with HIV which reduces the number of CD4 T-cells
What are complement proteins?
Make up complement system which help destroy pathogenic cells - most important in dealing with encapsulated organisms e.g.:
- Haemophilus influenza B
- Streptococcus pneumonia
- Neisseria meningitidis
What do deficiencies in complement proteins result in?
Vulnerability to certain infective organisms (in respiratory tract, ears and throat)
What are complement deficiencies associated with?
Immune complex disorders e.g. systemic lupus erythematous
Incomplete complement cascade leads to immune complexes being deposited in tissues
What is the most common complement deficiency?
C2 deficiency
What is an important part of the management of complement deficiencies?
Vaccination against encapsulted organisms
What is C1 esterase inhibitor deficiency also known as?
Hereditary angioedema
What is bradykinin?
Part of inflammatory response - causes blood vessel dilatation and increased vascular permeability causing angioedema
What is the action of C1 esterase?
Inhibits bradykinin
What does an absence of C1 esterase cause?
Intermittent angioedema in response to minor triggers such as viral infections or stress without any clear triggers at all
Where can angioedema effect? What happens?
Lips / face / GI tract / larynx
Can last several days
What is the prophylaxis against dental / surgical procedures for acute attacks of angiooedema?
IV C-1 esterase inhibitor
What is the test for C1 esterase inhibitor deficiency (hereditary angioedema)?
Check levels of C4 (compliment 4) - levels will be low in the condition
How common is mannose-binding lectin deficiency?
Relatively common in general population
What does mannose-binding lectin deficiency cause?
Inhibition of the alternative pathway of the complement system - relatively unimportant in healthy individuals
In patients who are susceptible to infection e.g. CF can cause more severe variant of existing disease
