Allergies and Immunology Flashcards
Define sensitivity and hypersensitivity
Sensitivity: normal response to a stimulus
Hypersensitivity: reproducible symptoms or signs following exposure to a stimulus at a dose which is tolerated by normal people
Define allergen
any substance stimulating the production of IgE or a cellular immune response
Define sensitisation
production of IgE antibodies (detected by serum IgE assay) after repeated exposure to an allergen
Define atopy
A personal/ familial tendency to produce IgE antibodies in response to ordinary exposures to potential allergens, Strongly associated with asthma, rhinitis, conjunctivitis, eczema and food allergy
Describe the pathophys of a IgE mediated immune response
- allergen binds to TH2 cell, which stimulated B cell to become plasma cell and produce IgE antibodies to that antigen
- on second exposure antigen binds to specific IgE
- leads to mast cell activation and degranulation
- this leads to release of:
- histamine (vasodilates, increases permeability, bronchoconstricts, mucus production)
- prostaglandins (bronchoconstricts)
- trypase
- leukotrienes
- IL-3,4,5 (cytokines)
State the common IgE mediated allergens
- wheat
- sesame
- eggs
- milk
- soya milk
- kiwi
- seafood
- shellfish
- tree nuts
- peanuts
State the 4 common non IgE mediated allergens
- wheat
- eggs
- soya
- milk
Define anaphylaxis
A serious allergic reaction that is rapid in onset and may cause death
What is the course of an IgE mediated allergic reaction?
Early phase following exposure to allergens - caused by release of histamine and other mediators from mast cells
Causes urticaria, angioedema, sneezing and bronchospasm.
Late phase occurs after 4-6 hours, causes nasal congestion in upper airway, cough and bronchospasm in lower airway
How do allergies develop?
Allergic diseases occur when individuals make an abnormal immune response to harmless environmental stimuli, usually proteins.
Developing immune system may be ‘sensitised’ before an allergic immune response develops.
Sensitisation may be occult - e.g. sensitisation to egg from exposure to trace quantities in maternal breast milk
What is released from mast cells?
Histamines causing vasodilation, vasopermeability, bronchoconstriction, mucus production.
PGs - bronchoconstriction
Tryptase
Leukotrienes - bronchoconstriction, mucus
IL-4 and IL-3 switch B lymphocytes to IgE production
IL5 attract and prime eosinophils
What do B cells and T cells release?
B cells - antigen recognition, presents peptide to T cell, differentiations into a plasma cell and generates a specific antibody
T cell express specific antigen receptors in response to peptides presented to MHC cII
Activated T cells release. Th2 cytokines in allergy - IL4, IL5 IL10
What is it important to note on examination which may identify an allergy?
Mouth breathing - obstructed airway due to rhinitis
History of snoring or obstructive sleep apnoea
Allergic salute - from rubbing an itchy nose - line on the nose
Pale and swollen inferior nasal turbinates
Hyperinflated chest/Harrison sulci from chronic undertreated asthma
Atopic eczema affecting limb flexures
Allergic conjunctivities
What are the types of hypersensitivity reactions?
1 - IgE antibodies trigger mast cells and basophils, causes immediate reaction e.g. food allergy
2 - IgG and IgM antibodies react to allergen, activate complement system e.g. HDN, transfusion reactions
3 - immune complexes accumulate and damage local tissues e.g. SLE, RA, HSP
4 - cell-mediated hypersensitivity reactions caused by T lymphocytes; inappropriately activated causing inflammation and damage e.g. organ transplant rejection, contact dermatitis
What is it important to ask in the history of an allergy?
Timing after exposure to allergen
Previous and subsequent exposure and reaction
Symptoms of rash, swelling, breathing difficulty, wheeze, cough
Previous personal and family history of atopic conditions and allergies
What are the three main ways of testing for allergy?
Skin prick testing
RAST testing - blood test for total and specific immunoglobulin E
Food challenge testing
Skin prick and RAST assesses for sensitisation not allergy
What occurs in skin prick testing?
Strategic allergic solutions selected for patch of skin, usually on forearm
Drop of each allergic placed as marked points, along with water control and histamine control
Fresh needle makes tiny break at site of each allergen
After 15 mins, size of wheals to each allergen assessed
What is a food challenge?
Child gradually given increasing quantities of an allergen to assess reaction
What is the management of allergies?
Establish correct allergen
Avoidance of allergen
Avoid foods that trigger reactions
Regular hoovering and changing sheets if allergic to house dust mites
Stay indoors when high pollen count
Prophylactic antihistamines when contact is inevitable
Risk of anaphylaxis - carry adrenaline auto-injector
Specialist centres may initiate lengthy process of gradually exposing patient to allergens - immunotherapy. Administer allergen until sensitised.
What is given follow exposure for the treatment of allergic reactions?
Antihistamines e.g. cetirizine
Steroids e.g. oral prednisolone, topical hydrocortisone or IV hydrocortisone
Intramuscular adrenaline in anaphylaxis
Describe the diagnostic criteria for anaphylaxis
Acute onset of an illness with involvement of the skin, mucosals tissue or both
AND AT LEAST 1 OF;
• Resp compromise (e.g. dyspnoea, wheeze bronchospasm, stridor, hypoxaemia)
• Reduced BP or associated symptoms of end organ dysfunction (e.g. syncope)
Give 5 symptoms of anaphylaxis
- Skin/ mucosal: itching lips/ tongue, lip/ tongue/ uvula swelling, skin flushing, itching, urticaria, angiodema
- Resp: stridor, SOB, tight chest, wheeze, cough, nasal itching and congestion, throat itching, hoarseness, cyanosis and resp arrest
- GI: abdo pain, nausea, vomiting, diarrhoea
- cardio: chest pain, tachy, brady, palpitations, hypotension, feeling faint, arrest
- CNS: altered behaviours, headache, dizzy, confused, feeling of impending doom
Give 3 unusual but possible presentations of anaphylaxis
- biphasic anaphylaxis: second reaction 4-12 hrs after initial reaction
- idiopathic anaphylaxis: diagnosed where no triggers can be found on hx and allergy tests are negative
- post prandial exercise induced: reaction requires food contact followed by exercise
What occurs in a food allergy?
Pathological immune response is mounted against a specific food protein
Usually IgE mediated
May be non-IgE mediated
What is an example of a non-immunological hypersensitivity reaction to a specific food?
Food intolerance
Cow’s milk
What is the difference between an intolerance and an allergy?
Allergy usually primary, where children have failed to ever develop immune tolerance
Infants commonly milk, egg, peanut
In older children, peanut, tree nuts, fish, shellfish
Can also be secondary, where children initially are intolerant and later become allergic
What is the cause of a secondary food allergy?
Cross-reactivity between proteins present in fresh fruits/veg/nuts and those present in pollens
e.g. child who can eat applies may develop an allergy because they develop an allergy to birch tree pollen
Share a very similar protein
This is an oral allergy syndrome/pollen fruit syndrome, common but leads to milder reactions e.g. itchy mouth
What are the clinical features of an IgE mediated food allergy?
e.g. immediate cow’s milk allergy
Mild - urticaria and itchy skin, facial swelling
Severe reaction - wheeze, stridor, abdominal pain, vomiting, diarrhoea, shock, collapse
What are the clinical features of a non-IgE mediated food allergies?
Diarrhoea, vomiting, abdominal pain, failure to thrive
Colic or eczema may also be present
Blood in stools in first few. weeks from life due to proctitis
How can IgE mediated food allergies be diagnosed?
Skin prick
RAST - measurement of specific IgE antibodies
Can yield false positives
How can non-IgE mediated food allergies be diagnosed?
Relies on clinical history and examination
If indicated, endoscopy and intestinal biopsy can be obtained, presence of eosinophil infiltrated
Gold standard in both IgE and non-IgE - exclusion of the relevant food, then double blind placebo controlled food challenge
What is the management of food allergies?
Avoidance of relevant foods
Management of an allergic attack
Drug management for mild reactions is antihistamines, more severe with adrenaline
What is the management of anaphylaxis?
Initial assessment ABCE
A secure airway
B provide oxygen, salbutamol for wheezing
C provide IV bolus fluids
D lie flat, improves cerebral perfusion
E look for flushing, urticaria, angio-oedema
Intramuscular adrenaline, repeat after 5 mins if needed
Antihistamines e.g. oral chlorphenamine, cetirizine
Steroids, IV hydrocortisone
What are the emergency drug doses for anaphylaxis?
500 micrograms 1:1000 IM for adults, 300 for kids 6-12
Chlorphenamine 10mg
5 for 6-12, 6 months 2.5mg
Hydrocortisone
200mg adults
100mg 6-12
50mg 6 months - 6 years
Nebulised salbutamol
5mg adults, kids
2.5 6 months - 6 years
What is the mnemonic for food allergy histories?
EATERS
Exposure - what type of contact was there; eaten, touched, inhaled, environmental
Allergen - what was it
Timing - after exposure and symptoms, immediate or delayed, 2-24 hours
Environment - first exposure during weaning, eating away from home in older child
Reproducible symptoms - occurs on each exposure to suspected allergen/food
Symptoms - multisystem, typical for an allergy, spread from site of exposure, does not persist if allergen removed
What is the management following an anaphylactic shock?
Period of assessment and observation, as biphasic reactions can occur - second anaphylaxis
Confirmed by measuring serum mast cell tryptase within 6 hours - released during mast cell degranulation and stays in blood for 6 hours
Education and follow up, recognise signs, basic life support, use of epipen
When might an adrenaline auto-injector be prescribed?
All with anaphylactic reactions
Generalised allergic reactions without anaphylaxis with certain risk factors:
Asthma requiring inhaled steroids
Poor access to medical treatment e.g. rural
Adolescents who are at higher risk
Nut or insect sting allergies are higher risk
Significant co-morbidities such as CVD
What is allergic rhinitis?
IgE mediated type 1 hypersensitivity reaction
Environmental allergens cause an allergic inflammatory response in nasal mucosa
Can be seasonal e.g. hay fever
Perennial (year round) e.g. dust mite allergy
Occupational - school or work environment
What is the presentation of allergic rhinitis?
Runny blocked itchy nose
Sneezing
Itchy, red, swollen eyes
Family history of other allergic conditions, atopy
Diagnosis made based on history, skin prick for pollen, animals, house dust mite
What can be the triggers for allergic rhinitis?
Tree pollen or grass - hayfever
House dust mites, pets
Persistent symptoms with pets
Symptoms after exposure with e.g. mould
What is the management of allergic rhinitis?
Avoid trigger
Regular hoovering, changing bedding, good ventilation
Staying indoors with high pollen counts
Minimise contact with pets
Oral antihistamines prior to exposure
Non-sedating antihistamines e.g. cetirizine, loratadine, fexofenadine
Sedating sprays - fluticasone, mometasone taken regularly to suppress local allergic symptoms
Nasal antihistamines good option for rapid onset symptoms
Leukotriene receptor antagonists e.g. montelukast
What is the presentation of cow’s milk protein allergy?
May become apparent when weaned from breast milk to formula or food containing milk.
Can present in breastfed babies when mum is consuming diary
GI symptoms - bloating, wind, abdo pain, diarrhoea, vomiting
General allergic symptoms: urticarial rash, angio-oedema, cough or wheeze, sneezing, watery eyes, eczema
Regurgitation and vomiting
Colic symptoms - irritability and crying
What is the management of cow’s milk allergy if formula-fed?
Extensive hydrolysed formula as a replacement formula
Amino acid based formula is severe allergy
What is the management of cow’s milk allergy if breastfed?
Continue breastfeeding
Eliminate cow’s milk protein from maternal diet
Consider prescribing calcium supplements for breastfeeding mothers whose babies have or are suspected. to have it to prevent deficiency whilst excluding diary
Use extensive hydrolysed formula eHF milk when breastfeeding stops, until 12 months of age and at least for 6 months
Infants can be tried on the first step of the milk ladder e.g. malted milk biscuits and progress until develop symptoms, progress towards a normal diet containing milk
What features of recurrent infections may require further assessment?
Chronic diarrhoea since infancy
Failure to thrive
Appearing unusually well with quite a severe infection e.g. afebrile with large pneumonia
More infections than expected e.g. bacterial lower respiratory tract infections
Unusual or persistent infections e.g. cytomegalovirus, candida, pneumocystis jiroveci
What are the investigations for recurrent infections?
FBC - low neutrophils suggest phagocytic disorder
Low lymphocytes - T cell disorder
Immunoglobulins - abnormalities suggest B cell disorders
Complement proteins - abnormalities suggest complement disorder
Antibody responses to vaccines spec. pneumococcal and haemophilus vaccines
HIV test
CXR
Sweat test - CF
CT - bronchiectasis
What is urticaria?
Weals caused by chemical mediators e.g. histamines, cytokines released from inflammatory cells and mast cells.
Mediators cause vasodilation and leakage into surrounding fluid causing redness and swelling
What can be some of the triggers of acute spontaneous urticaria?
Viral infection e.g. URTI, viral hepatitis, glandular fever Bacterial infection Food allergy Drug induced e.g. antibiotics or NSAID Bee or wasp sting
What are the clinical features of urticaria?
Itchy
White or red, localised or widespread, weals change shape and size
Angiodema localised to single area e.g. hands, feet, genitalia
Swollen tongue, eyelids, lipids
Inducible urticaria due to physical stimulus comes on within minutes, resolves in less than an hour - localised to exposed site
What is the treatment for urticaria?
Non sedating antihistamine e.g. cetirizine
Controls itch and spread until settled on own
If unresponsive, oral prednisolone
When do you suspect a primary immunodeficiency disease in paediatrics?
SPUR
Serious
Persistent
Unusual
Recurrent
Four or more new ear infections in one year
Two or more serious sinus infections within one year
Two or more months on abx with little effect
Two or more pneumonias in one year
Failure to gain weight or grow normally
Recurrent, deep skin or organ abscesses
Persistent thrush in mouth, fungal infection on skin
Need for IV abx to clear infections
Two or more deep seated infections including septicaemia
Family history of persistent infections
What should be established in the history when investigating PID?
Infection history
Site, freq, need for admission, IV abx, microbiology
Immunisation status
FH - infections, autoimmunity, consanguinity, neonatal deaths
What are the types of PID?
Antibody - B cells Combined - T cells Complement Phagocyte disorders Those associated with symptoms
What are the types of antibody deficiency?
X linked agammaglobulinaemia
Common variable immunodeficiency
Specific antibody deficiency
Transient hypogammaglobulinaemia
IgG subclass deficiency/IgA deficiency
What is hypogammaglobulinaemia?
Deficiency in immunoglobulins
Leads to susceptibility to recurrent infections, particularly LRTIs
What is selective immunoglobulin A deficiency?
Most common
Low levels of IgA
Normal levels of IgG, IgM
IgA is in mucous membranes; saliva, resp tract, GI secretions so protects against opportunistic infections
Mild immunodeficiency
Often asymptomatic or have recurrent mucous membrane infections
When can you commonly come across IgA deficiency?
When testing for coeliac disease
Testing IgA levels of anti-TTG and anti-EMA antibodies
Test total immunoglobulin A
If IgA low due to deficiency, coeliac test negative even if they have coeliac disease
What is common variable immunodeficiency?
Caused by genetic mutation coding for components of B cells
Deficiency in IgG and IgA
With/without deficiency in IgM
Recurrent respiratory tract infections, chronic lung disease
Cannot develop immunity to infections or vaccinations
Prone to immune disorders e.g. rheumatoid arthritis, cancers e.g. non-Hodgkins
Management with regular immunoglobulin infusions and treating infections and complications as they occur
What is Bruton’s agammaglobulinaemia?
X linked recessive
Defect in Bruton’s tyrosine kinase leads to severe block in B cell development
Recurrent bacterial infections, mostly respiratory tract
Humoral immunodeficiency
Most likely between 6-9 months old
What are examples of T cell disorders?
DiGeorge syndrome Purine nucleoside phosphorylase deficiency Wiskott-Aldrich syndrome Ataxic telangiectasia Acquired immunodeficiency syndrome
What is DiGeorge syndrome?
Microdeletion in portion of chromosome 22
Leads to developmental defect in third pharyngeal pouch and third branchial cleft
Means incomplete development of thymus so inability to create functional T cells
What are the features of DiGeorge syndrome?
CATCH-22
C - congenital heart disease
A - abnormal facies - characteristic facial appearance
T - thymus gland incompletely developed
C - cleft palate
H - hypoparathyroidism and resulting hypocalcaemia
22nd chromosome affected
What is severe combined immunodeficiency syndrome?
SCID
Most severe condition causing immunodeficiency
No immunity to infections
No of different genetic disorders results in absent or dysfunctioning T and B cells
What is the presentation of SCID?
In first few months of life
Persistent severe diarrhoea
Failure to thrive
Opportunistic infections - more frequent or severe than healthy children
e.g. severe and later fatal chickenpox, pneumocystis jiroveci
Unwell after live vaccinations e.g. BCG, MMR
Omenn syndrome
What are the causes of SCID?
Mutations in the common gamma chain on X chromosome
Which codes for interleukin receptors on T and B cells
X-linked recessive inheritance
JAC3 mutations
Adenosine deaminase def
What is Omenn syndrome?
Rare cause of SCID
Mutation in RAG1 or 2 gene
Codes for proteins in T and B cells
Autosomal recessive
Abnormally functioning and deregulated T cells, attack tissues in fetus or neonate
What are the features of Omenn syndrome?
Red scaly dry erythematous rash Hair loss - alopecia Diarrhoea Failure to thrive Lymphadenopathy Hepatosplenomegaly
What is the management of SCID?
Fatal unless treated
Management in specialist immunology centre
Treat underlying infections, immunoglobulin therapy, minimise risk of new infections, avoid live vaccines, perform haemopoietic stem cell transplantation
What is PNP deficiency?
Purine nucleoside phosphorylase deficiency
Autosomal recessive
Without this; dGTP builds up which is toxic to T cells and leads to low levels of t cells
Normal levels of B cells and immunoglobulins
Immunity to infection gradually becomes worse, increasingly susceptible to infections, viruses, live vaccines
What is Wiskott-Aldrich syndrome?
WAS X-linked recessive Abnormal functioning of T cells Thrombocytopenia Immunodeficiency Neutropenia Eczema Recurrent infections Chronic bloody diarrhoea
What is ataxic telangiectasia?
Autosomal recessive
Chromosome 11 protein
Low numbers of T cells and immunoglobulins causing immunodeficiency
Recurrent infections
Ataxia - cerebellar impairment leads to problems with coordination
Telangiectasia - broken capillaries - particularly in sclera and damaged skin
Slow growth
Delayed puberty
Accelerated ageing
Liver failure
When are complement proteins most important in dealing with infections?
Encapsulated organisms e.g. haemophilus influenza B
Streptococcus pneumonia
Neisseria meningitidis
What is seen in complement deficiencies and what are some examples?
Deficient in complement proteins, also associated with immune complex disorders e.g. SLE
C2 deficiency most common
Need vaccination against encapsulated organisms
C1 esterase inhibitor deficiency (hereditary angioedema)
Absence of C1 esterase means no inhibition of bradykinin causing intermittent angioedema to minor triggers
Check C4 levels which will be low in this condition
Mannose binding lectin deficiency leads to inhibition of an alternative pathway in complement
