Allergy and hypersensitvity Flashcards
what is hypersensitivity?
when the immune system over-responds to harmless antigens that result in harm to the body.
what are the four types of hypersensitivity?
type I: (A's) Allergic Anaphalaixs Atopy type II (B): antiBody type III (C): immune Comlpex type IV (D): Delayed
Type I: Classical allergy, mediated by the inappropriate production of specific IgE antibodies to harmless antigens
Type II: Caused by IgG and IgM antibodies that bind to antigens cells or tissues leading to cell or tissue damage
Type III: Caused by antibody-antigen complexes being deposited in tissues, where they activate the complement system and cause inflammation
Type IV: A delayed type hypersensitivity reaction caused by T helper cells traveling to the site of antigens, recruiting macrophages and causing inflammation (cell mediated)
*hypersensitivty can be antibody mediated (IgE, antibodies to self antigens, circulating antibody-antigen immune complex) or it can be t cell mediated (reaction to self antigens)
type I hypersensivity
(allergy)
allergens (antigens) produce allergic reactions
e.g. peanut, penicillin, pollen, house dust mite.
IgE mediated allergy is responsible for a number of atopic conditions e.g. food / drug allergy, asthma, allergic rhinitis, hayfever, eczema
sensitisation (type I)
he initial event that lead to the specific IgE being developed for that allergen
CD4 cells recognise the allergen
They proliferate and differentiate into T Helper 2 cells
These Th2 cells release IL-4, that stimulates the production of IgE by B Cells specific to that allergen
The IgE then circulates the blood and binds to mast cells
the allergic response
*activation of mast cells
- rexposure of allergen bidns to IgE
- this causes mast cell degranulation, releasing cytokines including histamine and TNF-alpha.
- histamine: vasodilation, icnreased vascular permeability, broncho-constriction and symptoms of allergy (itchy, flushing, rash, angiodema, wheeze)
-TNFalpha causes localised inflammatory process at the site of exposure (late phase)
mild-anaphalxis (shock from severe vasodilation)
can measure mast cell tryptase
type II hypersensivity
IgG and IgM bind to the antigen on cells or tissue which result in a reaction that is damaging
1) blood transfusion reaction. antibodies in the recipient’s blood attack the donor’s blood (e.g. antibody against an antigen attacks A antigens)
this causes haemolysis of the donor RBC
2) haemolytic disease of the newborn. rhesus negative mother has a rhesus positive baby. (mother makes rhesus antibodies IgG against the rhesus antigens)
3) Goodpastures syndrome. antibodies to a specific type of collagen in the GBM of the kidneys and lungs leads to inflammation and desturction= pulmonary haemorrhage and kidney failure
Grave’s (anti TSH receptor)
Myasthenia gravis (anti acetyl choline receptor antibodies)
transfusion reaction
type III hypersensitivity
antibodies (IgG, IgM) binds to antigens and forms complexes which become deposited in tissues and activate the complement system, causing inflammation
(type II antibodies bind to the target where as type III they bind and form a compelx which travels to the target organs and then causes the inflammation and damage)
1) rheumatoid arthritis. rheumatoid factor is an IgM antibody which recognises IgG antibodies as an antigen. for example the Fc portion is seen as ‘IgG’. there is an antibody-antigen complex in the blood which becomes deposited in the joints, skin, lungs, organs… chronic infection
2) farmers lung
mould and hay spores are breathed into the lungs. antibodies against the mould or hay antigens form a complex and are deposited in the lung tissues/alveoli where they activate the complement system which leads to inflammation of the lung tissue.
(extrinsic allergic alveolitis)
infections (post streptococcal glomerulonephritis, infective endocarditis)
innocuous environmental antigens (farmers lung)
autoantigens (DNA antibody in SLE)
type IV hypersensitivty
‘delayed type hypersensivity’
takes24-72hrs for a reaction to occur
‘cell-mediated’
- antigen enters the tissue and picked up by dendritic cells which deliver the antigen to CD4 cells
- CD4 proliferate and differentiate into T helper cells which travels to the tissue where the original antigen presented
- T helper cells release cytokines that recruit macrophages and both cells release cytokines which results in localised inflammation
e.g. contact dermatiits
poison ivy, nickel and gold (proteins turn into antigens), Mantoux test (a test for TB)
Mantoux test: TB (antigen) injected superficially into the skin. if the person has had a previous TB contact the antigen stimulates an immune response which leads to a localised inflammation around the infection site.
infection- tuberculoid leprosy
contact dermatitis
what is an allergy?
allos ergos - altered reactivity
the immune system responds to harmless molecules and causes tissue inflammation and organ dysfunction
an allergen is an antigen which causes an allergy
- contains epitopes (short sequence of amino acid)
- predominante type
- water soluable
risk factors for allergy
atopy
predisposition towards developing an allergic disease (eczema, hayfever, asthma)
chromosomes 5,6,11
filaggrin gene (Severe form of dry skin, eczema)
environmental factors- hygine hypothesis
examples of allergens
skin contact: latex, animal scratches
inhalation: pollens, moulds, dust mite
injections: venom, vaccination
ingestion: meds
food: nuts, milk, egg, soybean, wheat, fish, shellfish
primary and secondary food allergy
primary (class 1) first manifestation of atopy, early childhood. the higher prevalence in milk and egg allergy. normallly outgrow
secondary class 2- mainly effects adolecents and adult with established respiratory allergy. cross-reactivity.
IgG IgA IgM IgD IgE
IgG: blood/placenta IgA: mucosa/milk IgM: first immunoglobulin. B cell receptor IgD: B cell receptor IgE: allergy
early and late phase of type I hypersensivity
early phase: immediate release in response to allergy. degranulatio of mast cells and basophils. release of histamine, leukotriene, platelet activating factor, bradykinin
late phase: 8-12 hrs. TH2 helper t cells and mas cells produce chemokine IL-5 which attracts eosinophils and T lymphocytes. eosinophils degranulate and release ECGP, EPX, MBP, leukotriene and prostaglandins
histamine effect
affects nerve cells- itching
smooth muscle cells- contraction
goblet cells- mucus production
endothelial cells- vasodilation and edema
leukotriene
platelt activating factor
bradykinin
leukotriene - triggers smooth muscle contraction
platelet-activating factor- triggers platelet aggregation and degranulation
bradykinin- causes vasodilation and vascular permeability.
initial allergen encounter
inhale/inject/ingest the allergen binds to APC TH2 B cell Plasma cell makes IgE IgE binds to mast cell
next time: allergen binds to IgE on mast cell= degranulates…
how do we investigate for an allergy?
- skin prick testing. indirect assay of IgE, can do multiple allergen test, quick, convenient and safe
- operator dependent
- sensitivity/specficity
- depends on quality ofallegen extract
- immunoCAP specific IgE blood test. use fluorscent label anti-IgE more invasive but greater specificty.
- respiratory allergy- spirometry (FEV1, peak flow) bronchiol provocation
- food allergy - food challenges
asthma
chronic inflammatory disease of airway. hyper responsiveness, variable airflow obstruction, inflammation, reverisble.
symptoms- breathless, tight chest, wheezing, coughing
risk factors- fhx, bronchiolitis as a child, tobacco, premature birth/low birth weight.
types of asthma: alergy, work exposure, exertion, infection, drugs.
asthma attack
immediate phase: spasm of bronchial smooth muscle. release of histamine from mast cells.
late phase: eosinophils and t lymphocytes. inflammatory cells act on smooth muscle causing hypertrophy and hyperplasia
asthma treatment
bronchodilators:
- b2 adrenoceptor agonist) salbutamol. relax bronchiol smooth muscle. inhibits mast cell mediator release. increases mucus clearance
- methylxanthinese (theophylline) relaxes bronchiol smooth msucle
- antimuscarinin (tiotropium) relaxes bronchiol smooth muslce.
anti-inflammatories
- inhaled corticosteroids (beclomethasone) suppress PGE and leukotriene
- leukotriene receptor antagonist (montelukast) relax airway in mild asthma, reduce eosinophilia
- anti-IgE antibody (omalizumab)
- cromones (mast cell stabilisers)
- self-injectable adrenaline EpiPen
acute anaphylaxis management
call for help
airway
breathing
circulation
adrenaline 0.5mg IM oxygen high flow IV access 200mg hydrocortisone IV 10mg IV chlorpheniramine (slowly) IV fluid if BP remains low repeat adrenaline 0.5m IM if no improvement in 5-10 in
measure tryptase
monitor 6-8hrs
differentials for allergy
Less severe allergic reactions C-1-Esterase Inhibitor Deficiency (hereditary angioedema) Panic Attack Vasovagal reaction Dystonic reaction Side effect of drug “Idiopathic Urticaria and Angioedema”
what is anaphalaxis
a severe life threatening type I hypersensitivity reaction, classed as a medical emergency
non IgE mediated anaphalaxis are clinically indistinguishable and managed the same sway
anaphylaxis signs and symptoms
urticaria/hives/wheals angiodema/swelling decreased BP increased HR stomach pain clammy skin wheezing/SOB hoarse voice/stridor dizzy/light headed/LOC/confusion/collapse difficulty swalowing anxiety - impending doom
*exacerbated by alcohol, exercise, inflammation, infection, extremes of temps, stress, asthma
differentials for anaphalaxis
Less severe Type 1 hypersenstivity reaction (same as above but without cardiorespiratory compromise Acute asthma attacks Vasovagal syncope Panic/anxiety attack Angioedema – e.g. HAE Cardiovascular events (myocardial infarction, pulmonary embolus)
mast cell tryptase
Mast Cell Tryptase at presenation, 2 hours after symptom onset and at 24 hours to establish baseline. See NICE guidance on Anaphylax
chronic spontaenous urticaria and agniodema
symptoms for over 6 weeks (chronic) with no discernible underyling cause (spontaenous). fleeting wheals lasting 1-24 hrs and/or angiodema lasting 72 hours.
25% of adults will have one episode
signs and symptoms of urticarial lesions and angiodema.
Urticarial lesions: erythematous, well-defined and variable size. May have evidence of excoriations Angioedema: Episodic, submucosal or subcutaneous swellings. Asymmetric, non-pitting in non-dependent parts of the body eg arms, legs, genitals, lips, cheeks. May be tingling or numb
differentials for urticaria.
Urticarial vasculitis: painful rather than itchy, lesions scar and non-migratory SLE: Prominent systemic features e.g. arthralgia, weight loss, fever, lymph N’s Cryoglobulinaemia: Cold induced lesions over buttocks/lower limbs- Hep B,C Acute illness & H pylori infection
investigations for urticaria
Bedside
Routine observations should be normal
Dermographism
Bloods
Usually nil
May do FBC, U&Es, TFTs, ANA or MCT to exclude systemic disorder
Imaging
Nil Special Skin prick testing if D/D drug allergy- rarely Skin biopsy if excluding urticarial vasculitis H. pylori testing
management of urticaria
Support Groups Allergy UK
Lifestyle Modification Avoidance of triggers Exercise, heat, alcohol & stress typically worsen symptoms Epipen training and awareness (rare)
Education Epipen training-(rare). Managing expectations Disease Activity Scale: Urticarial & angioedema Activity Score (UAS7)
Medical Acute Management (attack/complication) Avoidance of precipitant non-sedating antihistamine Long term
Management First Line: Non-sedating antihistamine (Fexofenadine, cetirizine, loratadine). Can increase to QDS/day if not pregnant/on interacting medications Second line: Add in leukotriene receptor antagonist (Montelukast) or ranitidine Third line: Consideration of omalizumab or cyclosporin
allergic rhinitis
IgE mediated Inflammation of the nasopharynx as a response to aeroallergens. Causes release of preformed mediators histamine and chemotactic factors
types of rhinitis
Perennial Rhinitis:
House Dust Mite/Pets/moulds – throughout year
Seasonal Rhinitis:
Grass Pollen – late spring to early summer ·
Tree Pollen – early to late spring ·
Weed Pollen – spring to late autumn
Occupational Rhinitis – latex, flour, wood dust Individuals can have more than one allergen causing symptoms
signs and symptoms of allergic rhinitis
Eyes- watering, gritty, redness, dryness, discharge, localised swelling/puffiness Nasal – congestion, discharge, sinusitis Respiratory – sneezing, wheeze, itchy palate and ears
O/E conjunctiva, nasal mucosa, swollen/greyish, mouth breathing, cough, halitosis
Allergic rhinitis in childhood is a risk factor for development of Asthma and can contribute to poor asthma control. Hx of Atopy Fam Hx Rhinitis or Atopy Exposure to common allergens Air pollution
differential diagnosis for allergy
Non-allergic rhinitis – common in older age group, symptoms less responsive to AH
Infective Rhinitis – Viral (rhinovirus, RSV, parainfluenza, influenza) Bacterial (S. pneumonia, Group A Beta-haemolytic streptococci, Haemophilus influenzae.)
Chronic rhinosinusitis – structural abnormalities, chronic infection, ?Immune deficiency if Hx of other infections.
Nasal Polyps – complication of and cause of chronic inflammation; Samtar’s triad.
Foreign Body in nose (most common age 6 months to 5 years) Nasal septum abnormalities (congenital, trauma, perforation), Tumour, Vasculitis
investigations for allergic rhinitis
bedside: Listen – nasal voice, sniffing! Chest exam if suspecting asthma Sputum/Nasal discharge for MS&C or respiratory virus PCR if infection suspected
bloods: Serum Specific IgE – (choices depend on history and potential for desensitization
imaging: *Polyps – X-ray, CT-Scan – uncommon in allergy clinic, more common in ENT if surgery or malignancy is suspected. Nasendoscopy and biopsy – as above
special:
1) Skin Prick Testing (SPT) – PPV 97-99% (results can be suppressed by antihistamines, topical corticosteroids, and tricyclic antidepressants).
Allergen-specific IgE concentrations determined by ELISA (only if SPT inconclusive or if desensitization therapy being considered) ·
(RAST is the old technique for Specific IgE rarely done now but well known in Primary care)
*** Total IgE rarely useful in routine investigation of allergy unless strong atopic tendency and you are concerned that high total IgE is making interpretation of Specific IgE difficult
management of allergic rhinitis
Most cases manageable by GP. Specialist Allergy nurse or immunologist if; · To optimise treatment if the GP has tried a few things · Severe symptoms despite optimised managed and desensitization is possible · Possible occupational link · Uncertainty about the diagnosis
support groups
life style modifications
- limit exposure
air filters, close windows, cange clothes, nasal barreirs,
occupational allergy
- latex free gloves, dust mask
medical management for allergic rhinitis
Allergen avoidance where possible · Start regular treatment 2-4 weeks before seasonal symptoms start · Regular long-acting, non-sedating antihistamine at licensed dose (up to BD for breakthroughs) · Regular topical nasal steroid (with good admin technique) · Sodium cromoglycate eye drops regularly Other options Intra-nasal antihistamine Intra-nasal steroid + intra-nasal antihistamine combined device
Immunotherapy (desensitisation- inducing immunological tolerance) Sublingual and subcutaneous therapies. Only available for some allergens and only funded by the NHS for a smaller list. Best in mono-sensitized people. Add on therapy to support existing medication regimen.
Pregnancy/ Breast feeding: Topical nasal steroids may be considered CKS recommends loratidine (or other non-sedating Antihistamine at licensed dose). Can use additional chlorphenamine as well until third trimester. 2nd line intranasal Sodium cromoglicate (more effective than placebo) Nasal Douche with normal saline
drug allergy
increased chance of having a drug allergy in conditions like HSV-1, HIV and CF
having atopy inccreases changes of having a more severe reaction
20% of deaths in UK are attributable to penicillin allergy
extrinsic allergic alevolitis
extrinsic allergic alveolitis
immune complex-mediated reaction (type III hypersensitivity)
bird fanciers lung / hypersensitivity pneumonitis caused by exposure to bird droppings
signs and symptoms: breathless, dry cough, fevers are exposure, progressive interstitial fibrosis and chronic restrictive lung disease after long term exposure
CXR: CT classical ground glass apperances
non IgE mediated e.g. cows milk protein allergy non IgE mediated
cutaenous and GI symptoms
eczeetaous rash
not an immediate reaction suggess non IgE mediated (urticarial rash would be expected if IgE mediated)
patch test
used to diagnose delayed type IV hypersensitivity (Cell-mediated) reactions
apply various test substances to the skin under adhesive tape.
the skin is examined upon application and at an interval of 48hrs for any inflammatory response
skin prick testing
used to diagnose type I hypersensitivity reactions which are mediated by IgE. results in an immediate degranulatoin of mast cells and histamine.
e.g allergic rhinits, systemic annaphaylaxis, allergic asthma
