Hypersensitivity Disorders

Question 1

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.

Answer 1

Type I hypersensitivity

Question 2

most prevalent allergic disorder in the UK

Answer 2

Asthma

Question 3

Delayed, T-cell mediated reaction.

Answer 3

Type IV

Question 4

defects in B-defensin and fillagrin. allergens can include irritants, foods and envrionmental factors. can predispose to S.Aureus superinfection. clinical diagnosis, usually <1yo.

Answer 4

Atopic dermatitis

Question 5

gold standard test for IgE food allergy

Answer 5

Food challenge in hospital

Question 6

exposure to allergens causes peri-oral tingling. Allergens usually include: birch pollen and rosacea fruit, mugwort and celery. 2% anaphylaxis

Answer 6

oral allergy syndrome. Diagnose by SPT

Rx: wash out mouth and oral antihistamine

Question 7

Type 1 hypersens to chestnut, avocado, banana, kiwi, aubergine, melon, wheat.

Answer 7

Latex food syndrome

Question 8

wheals which resolve within 6 weeks. 50% idiopathic. can be related to drugs, latex, viral infections.

Answer 8

Acute urticaria

Question 9

Criteria for diagnosis of anaphylaxis (5)

Answer 9

1. sudden onset and rapid progress,
2. life-threatening compromise of A +/- B +/- C,
3. skin changes - urticaria, angioedema,
4. D, V, cramps, sense of doom
5. Hx of exposure to allergen

Question 10

IgE-mediated mast cell degranulation

Answer 10

peanut, penicillin, stings, latex

Question 11

Non-IgE mediated mast cell degran

Answer 11

NSAIDS, IV contrast, opiods, exercise

Question 12

Management of anaphylaxis in order (8)

Answer 12

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

Question 13

definition of positive SPT

Answer 13

wheal which is >= 2mm greater than the negative control

Question 14

Gold standard to support diagnosis of allergy (not food)

Answer 14

SPT. remember to stop antihistamines 48hr before test

Question 15

Indications for RAST

Answer 15

cant stop antihistamines, anaphylaxis hx, extensive eczema making test interpretation difficult

Question 16

Component resolved diagnostics

Answer 16

measuring the IgE response to a SPECIFIC allergen protein

i.e: Ara-h-2 high risk allergen in peanuts, anaphylaxis

Question 17

What to measure during an acute episode to determine if allergic/anaphylactic reaction:

Answer 17

Mast cell tryptase - evidence of mast cell degran

measure at 1hr, 3hr and 24hr - rise proportional to drop in BP

Question 18

epipen dose for adults

Answer 18

300ug

Question 19

epipen dose for children

Answer 19

150ug

Question 20

presents in neonates with IgG-mediated reticulocytosis and anameia. Diagnosis made via positive DAT test

Answer 20

HDN. Rx with maternal plasma exchange, exchange transfusion in utero. prevent with anti-D. Type 2 HS

Question 21

destruction of red blood cells by auto-antigens. Positive DAT.

Answer 21

AIHA. Type II

Question 22

Evans syndrome

Answer 22

AIHA + ITP. Type II

Question 23

anti-platelet antibodies against glp IIb/IIIa. presents with purpura, bruising, bleeding.

Answer 23

Autoimmunhe thrombocytopenic purpura

Question 24

glomerulopnephritis, pulmonary haemorrhage. linear smooth immunoflurescence staining shows IgG deposits on the BM.

Answer 24

Goodpastures. anti-GBM

Question 25

IgG/IgM which react with self antigens, resulting in tissue damage or receptor activation/blockade

Answer 25

Type II Hypersensitivity

Question 26

antibodies against epidermal cadherin. | direct immunofluorescence shows IgG deposition.

Answer 26

Pemphigus Vulgaris. non-tense blistering of the skin and bullae

Question 27

anti-TSHR abs

Answer 27

Grave's disease

Question 28

Treatment of Grave's disease

Answer 28

Carbimazole and propylthiouracil

Question 29

anti-AChR abs. fatiguable muscle weakness, double vision. Tensilon test shows improvement in fatiguability

Answer 29

MG

Question 30

Rx of MG

Answer 30

Neostigmine, pyridostigmone

Question 31

antibodies to the M proteins on GAS, can cross react with cardiac Myosin protein. Dx using Jones criteria

Answer 31

Acute rheumatic fever

Question 32

Major criteria of Jones criteria for RF

Answer 32

``` Sydenhams chorea Transient arthritis Rheumatoid nodules Erythema marginatum Pancarditis ```

Question 33

anti-intrinsic factor abs (50% specific), anti-gastric parietal cell ab (90% specific). causes megaloblastic anaemia

Answer 33

Pernicious anaemia

Question 34

medium and small vessel vasculitis with an allergic prodrome and eosinophilia. Granulomas.

Answer 34

eGPA (Churg strauss) | p-ANCA against MYELOPEROXIDASE

Question 35

medium and small vessel vasculitis that presents with sinusitis, pulmonary cavitations and haemorrhage, crescenteric glomerulonephritis.

Answer 35

GPA (Wegeners) | c-ANCA against PROTEINASE 3

Question 36

Rx for condition with p-ANCA against MYELOPEROXIDASE

Answer 36

P-ANCA Rx = PA 'n' C Pred Azathioprine Cyclophosphamide

Question 37

Rx for condition with c-ANCA against PROTEINASE 3

Answer 37

c-ANCA Rx = CCC Corticosteroids cyclophosphamide co-trimoxazole

Question 38

pauci-immune necrotising small vessel vasculitis, presents with livedo, purpura. many organs affected.

Answer 38

microscopic polyangiitis | p-ANCA +ve

Question 39

itchy wheals lasting >6 weeks. can be assoc with NSAIDS, cold, food, perssure, sun. associated with angioedema in 50% of cases.

Answer 39

Chronic urticaria | IgG against FcER1

Question 40

Tissue damage mediated by IgG or IgM immune complexes (abs against soluble antigens)

Answer 40

Type III

Question 41

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.

Answer 41

SLE

Question 42

anti-CCP antibodies (95% specific) form immune complexes with citrullinated proteins and deposit, trigger complement.

Answer 42

RA

Question 43

joint pain, splenomeg and skin/nerve involvement. associated with Hep C.

Answer 43

Mixed Essential Cryoglobulinaemia. IgM against IgG +/- hepatitis C ags Cryo = C = Hep C = Chronic

Question 44

Exposure to anti-serum i.e penicllin, causes rash arthralgia itching LN fever malaise. occurs 7-12d post-exposure. Decreased C3 levels.

Answer 44

Serum sickness. Rx with steroids, antihistamines and stop the precipitant.

Question 45

fever, fatigue, weakness, arthralgia, MI, pericarditis, kidney involvement. associated with Hep B. Rosary sign.

Answer 45

Polyarteritis Nodosa. ab against hep B viral antigens

Question 46

anti-GAD abs. CD8+-mediated destruction

Answer 46

T1DM. also anti-ilset abs, anti-insulin abs

Question 47

abs against antigens in the synovial membrane. RF+ve, (85%) anti-CCP (95%), raised CRP and ESR

Answer 47

RA

Question 48

Itching, blisters and wheals, usually short lived. can be triggered by chemicals, poison ivy, nickel.

Answer 48

Contact demratitis - patch test to dx

Question 49

Type IV hypersensitivity, used in testing for mycobacterium

Answer 49

Mantoux

Question 50

Diarrhoea, bloating, blood in stool. Th1 mediated, associated with NOD2 gene mutation in 30%. Dx using biopsy.

Answer 50

Crohn's. Chronic inflammation and skip lesions.

Question 51

HLA association for Ank Spond

Answer 51

HLA-B27 - By the time youre 27 you'll know you have Ank Spond

Question 52

HLA-DR3

Answer 52

T1DM, Graves, SLE

Question 53

T1DM

Answer 53

HLADR3/DR4 - present when youre 3-4

Question 54

Goodpastures

Answer 54

HLADR-15/DR2 - kids get it - CPR = 15:2

Question 55

HLA-DR1/DR4

Answer 55

RA

Question 56

SLE

Answer 56

HLA-DR3 (SLE is 3 letters)

Question 57

PTPN22 genetic polymorphism associated with:

Answer 57

RA, SLE, T1DM (P(Q)RST)

Question 58

CTLA4 genetic polymorphism

Answer 58

receptor for CD80-86. assoc w AI thyroid disease, SLE,, T1DM

Question 59

Calcinosis, Raynauds, Esophageal dysmotility, sclerodactyly, telangiectasia. skin involvement on the forearms and perioral ONLY. associated with anti-centromere abs.

Answer 59

Limited cutaneous systemic sclerosis

Question 60

anti-Scl70, anti-RNA Pol, anti-fibrillarin. extensive skin disease, GI disease, interstitial pulmonary disease and sclerdermic kidney crises.

Answer 60

Diffuse cutaneous SS

Question 61

Low back pain, enthesitis, large joint arthritis, uveitis, stiffness. young males.

Answer 61

Ank Spnod HLA B27

Question 62

immune complex mediated vasculits. Perivascular CD4 cells. proximal muscle weakness and Gottron's papules. ANA +ve, anti-Mi2, Jo-1 abs.

Answer 62

Dermatomyositis - muscles weakeneD

Question 63

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.

Answer 63

Polymyositis

Question 64

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

Answer 64

familial mediterranean fever

Question 65

Rx for FMF

Answer 65

1) colchicine - binds to tubulin of neutrophils and disrupts chemokine action and migration. 2) TNF-a/IL-1 inhibitors - etanercept, anakira

Question 66

CARD15 gene on chromosome 6

Answer 66

Crohns. also known as NOD2 gene

Question 67

mutation within Fas pathway (Fas-ligand) leading to defects in cell apoptosis, lymphocytosis, LN and HSM.

Answer 67

Autoimmune lymphoproliferative syndrome

Question 68

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.

Answer 68

``` APECED Autosomal recessive Polyendocrinopathy Candidiasis Ectodermal Dystrophy Also called APS1 ```

Question 69

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.

Answer 69

``` IPEX Immune dysfunction Polyendcrinopathy Enteropathy X-linked recessive ```

Question 70

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.

Answer 70

Sjogrens

Question 71

associated with polymorphisms in PAD 2 and 4 enzymes, and infection with P.Gingivalis

Answer 71

RA

Question 72

CD25+, Foxp3+, CD4+ T reg cells secrete:

Answer 72

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.