Hypersensitivity Disorders Flashcards
immediate response (within 2 hours) provoked by re-exposure to an allergen. IgE mediated, resulting in mast cell degranulation which affects at least 2 organ systems.
Type I hypersensitivity
most prevalent allergic disorder in the UK
Asthma
Delayed, T-cell mediated reaction.
Type IV
defects in B-defensin and fillagrin. allergens can include irritants, foods and envrionmental factors. can predispose to S.Aureus superinfection. clinical diagnosis, usually <1yo.
Atopic dermatitis
gold standard test for IgE food allergy
Food challenge in hospital
exposure to allergens causes peri-oral tingling. Allergens usually include: birch pollen and rosacea fruit, mugwort and celery. 2% anaphylaxis
oral allergy syndrome. Diagnose by SPT
Rx: wash out mouth and oral antihistamine
Type 1 hypersens to chestnut, avocado, banana, kiwi, aubergine, melon, wheat.
Latex food syndrome
wheals which resolve within 6 weeks. 50% idiopathic. can be related to drugs, latex, viral infections.
Acute urticaria
Criteria for diagnosis of anaphylaxis (5)
- sudden onset and rapid progress,
- life-threatening compromise of A +/- B +/- C,
- skin changes - urticaria, angioedema,
- D, V, cramps, sense of doom
- Hx of exposure to allergen
IgE-mediated mast cell degranulation
peanut, penicillin, stings, latex
Non-IgE mediated mast cell degran
NSAIDS, IV contrast, opiods, exercise
Management of anaphylaxis in order (8)
1) Help 2) elevate legs 3) 100% O2 4) IM adrenaline 500mcg 5) inhaled bronchodilators 6) IV hydrocortisone 100mg 7) chloramphenamine 10mg IV 8) IV fluids
definition of positive SPT
wheal which is >= 2mm greater than the negative control
Gold standard to support diagnosis of allergy (not food)
SPT. remember to stop antihistamines 48hr before test
Indications for RAST
cant stop antihistamines, anaphylaxis hx, extensive eczema making test interpretation difficult
Component resolved diagnostics
measuring the IgE response to a SPECIFIC allergen protein
i.e: Ara-h-2 high risk allergen in peanuts, anaphylaxis
What to measure during an acute episode to determine if allergic/anaphylactic reaction:
Mast cell tryptase - evidence of mast cell degran
measure at 1hr, 3hr and 24hr - rise proportional to drop in BP
epipen dose for adults
300ug
epipen dose for children
150ug
presents in neonates with IgG-mediated reticulocytosis and anameia. Diagnosis made via positive DAT test
HDN. Rx with maternal plasma exchange, exchange transfusion in utero. prevent with anti-D. Type 2 HS
destruction of red blood cells by auto-antigens. Positive DAT.
AIHA. Type II
Evans syndrome
AIHA + ITP. Type II
anti-platelet antibodies against glp IIb/IIIa. presents with purpura, bruising, bleeding.
Autoimmunhe thrombocytopenic purpura
glomerulopnephritis, pulmonary haemorrhage. linear smooth immunoflurescence staining shows IgG deposits on the BM.
Goodpastures. anti-GBM
IgG/IgM which react with self antigens, resulting in tissue damage or receptor activation/blockade
Type II Hypersensitivity
antibodies against epidermal cadherin.
direct immunofluorescence shows IgG deposition.
Pemphigus Vulgaris. non-tense blistering of the skin and bullae
anti-TSHR abs
Grave’s disease
Treatment of Grave’s disease
Carbimazole and propylthiouracil
anti-AChR abs. fatiguable muscle weakness, double vision. Tensilon test shows improvement in fatiguability
MG
Rx of MG
Neostigmine, pyridostigmone
antibodies to the M proteins on GAS, can cross react with cardiac Myosin protein. Dx using Jones criteria
Acute rheumatic fever
Major criteria of Jones criteria for RF
Sydenhams chorea Transient arthritis Rheumatoid nodules Erythema marginatum Pancarditis
anti-intrinsic factor abs (50% specific), anti-gastric parietal cell ab (90% specific). causes megaloblastic anaemia
Pernicious anaemia
medium and small vessel vasculitis with an allergic prodrome and eosinophilia. Granulomas.
eGPA (Churg strauss)
p-ANCA against MYELOPEROXIDASE
medium and small vessel vasculitis that presents with sinusitis, pulmonary cavitations and haemorrhage, crescenteric glomerulonephritis.
GPA (Wegeners)
c-ANCA against PROTEINASE 3
Rx for condition with p-ANCA against MYELOPEROXIDASE
P-ANCA Rx = PA ‘n’ C
Pred
Azathioprine
Cyclophosphamide
Rx for condition with c-ANCA against PROTEINASE 3
c-ANCA Rx = CCC
Corticosteroids
cyclophosphamide
co-trimoxazole
pauci-immune necrotising small vessel vasculitis, presents with livedo, purpura. many organs affected.
microscopic polyangiitis
p-ANCA +ve
itchy wheals lasting >6 weeks. can be assoc with NSAIDS, cold, food, perssure, sun. associated with angioedema in 50% of cases.
Chronic urticaria
IgG against FcER1
Tissue damage mediated by IgG or IgM immune complexes (abs against soluble antigens)
Type III
Hypersens condition in which antibodies directed at intracellular proteins such as nuclear ag (anti dsDNA - 95% specific, anti-histones) and cytoplasmic ag (anti-Ro, La and Sm).
ab-ag complexes activate complement cascade via classical pathway and lead to C4 (+/- C3) depletion.
SLE
anti-CCP antibodies (95% specific) form immune complexes with citrullinated proteins and deposit, trigger complement.
RA
joint pain, splenomeg and skin/nerve involvement. associated with Hep C.
Mixed Essential Cryoglobulinaemia. IgM against IgG +/- hepatitis C ags
Cryo = C = Hep C = Chronic
Exposure to anti-serum i.e penicllin, causes rash arthralgia itching LN fever malaise. occurs 7-12d post-exposure. Decreased C3 levels.
Serum sickness. Rx with steroids, antihistamines and stop the precipitant.
fever, fatigue, weakness, arthralgia, MI, pericarditis, kidney involvement. associated with Hep B. Rosary sign.
Polyarteritis Nodosa. ab against hep B viral antigens
anti-GAD abs. CD8+-mediated destruction
T1DM. also anti-ilset abs, anti-insulin abs
abs against antigens in the synovial membrane. RF+ve, (85%) anti-CCP (95%), raised CRP and ESR
RA
Itching, blisters and wheals, usually short lived. can be triggered by chemicals, poison ivy, nickel.
Contact demratitis - patch test to dx
Type IV hypersensitivity, used in testing for mycobacterium
Mantoux
Diarrhoea, bloating, blood in stool. Th1 mediated, associated with NOD2 gene mutation in 30%. Dx using biopsy.
Crohn’s. Chronic inflammation and skip lesions.
HLA association for Ank Spond
HLA-B27 - By the time youre 27 you’ll know you have Ank Spond
HLA-DR3
T1DM, Graves, SLE
T1DM
HLADR3/DR4 - present when youre 3-4
Goodpastures
HLADR-15/DR2 - kids get it - CPR = 15:2
HLA-DR1/DR4
RA
SLE
HLA-DR3 (SLE is 3 letters)
PTPN22 genetic polymorphism associated with:
RA, SLE, T1DM (P(Q)RST)
CTLA4 genetic polymorphism
receptor for CD80-86. assoc w AI thyroid disease, SLE,, T1DM
Calcinosis, Raynauds, Esophageal dysmotility, sclerodactyly, telangiectasia. skin involvement on the forearms and perioral ONLY. associated with anti-centromere abs.
Limited cutaneous systemic sclerosis
anti-Scl70, anti-RNA Pol, anti-fibrillarin. extensive skin disease, GI disease, interstitial pulmonary disease and sclerdermic kidney crises.
Diffuse cutaneous SS
Low back pain, enthesitis, large joint arthritis, uveitis, stiffness. young males.
Ank Spnod HLA B27
immune complex mediated vasculits. Perivascular CD4 cells. proximal muscle weakness and Gottron’s papules. ANA +ve, anti-Mi2, Jo-1 abs.
Dermatomyositis - muscles weakeneD
Type IV hypersens, CD8 cells surround and destroy HLA I muscle fibres via perforin. Loss of muscle mass, interstitial lung disease, cardiac disease. anti-SRP, anti-Mi2.
Polymyositis
periodic fevers lastimh 48-90 hours, chest pain (pleursy/pericarditis), abdo pain (peritonitis), arthritis and skin involvement. Can develop amyloidosis in long term.
MEFV gene defect
sephardic jews, arabs, turks
familial mediterranean fever
Rx for FMF
1) colchicine - binds to tubulin of neutrophils and disrupts chemokine action and migration.
2) TNF-a/IL-1 inhibitors - etanercept, anakira
CARD15 gene on chromosome 6
Crohns. also known as NOD2 gene
mutation within Fas pathway (Fas-ligand) leading to defects in cell apoptosis, lymphocytosis, LN and HSM.
Autoimmune lymphoproliferative syndrome
defect in AIRE gene, AR. leads to failure of central tolerance - auto-abs form against endocrine glands. hypoparathyroidism, addisons….
also have ab against IL-17 and IL-22 leading to candidiasis.
APECED Autosomal recessive Polyendocrinopathy Candidiasis Ectodermal Dystrophy Also called APS1
X-linked mutations in the FOXP3 genes needed to make CD4+ Treg cells. male infants, eczema, nail dystrophy, AI skin disease, multiple endocrinopathies, immune dysfunction and diarrhoea. usually die within first 2 years of life if no BMT.
IPEX Immune dysfunction Polyendcrinopathy Enteropathy X-linked recessive
Dry mouth, dry eyes, dry nose, dry skin. F, late 40s. Can also affect kidneys, blood vessels, lungs, liver, pancreas, peripheral nervous system. Anti-Ro and La positive.
Schirmers test
Parotid or salivary gland enlargement.
Sjogrens
associated with polymorphisms in PAD 2 and 4 enzymes, and infection with P.Gingivalis
RA
CD25+, Foxp3+, CD4+ T reg cells secrete:
TGF-B, IL-10. Deficiency of these T reg cells due to lack of any of the above genes (i.e FOXP3) leads to dysfunction in peripheral tolerance = IPEX.
