Immunology Lecture

Question 1

What is a Type 1 Antibody Mediated Adverse Drug Reaction

Answer 1

IgE
Soluble antigen
Mast cell activation

Question 2

Example of Type 1 Antibody Mediated Adverse Drug Reaction

Answer 2

Penicillin (Beta-lactams)

urticaria
angioedema
bronchospasm
anaphylaxis

Question 3

what is a type 2 antibody mediated ADR

Answer 3

IgG
Cell or matrix associated antigen
FcR+ cells (phagocytes, NK cells)

Question 4

Example of Type 2 ADR

Answer 4

Beta lactams, Rifampicin, Sulfa antibiotics

Haem. anaemia
thrombocytopaenia

Question 5

What is a Type 3 ADR (antibody mediated)

Answer 5

IgG
Soluble antigen
FcR+ cells, complement

Question 6

Type 3 ADR (antibody mediated) example?

Answer 6

Vaccination: serum sickness (fever, vasculitic rash, joint inflam.)

Beta-lactams, sulfa antibiotics, minocycline: Arthus reaction

Hypersensitivity vasculitis

Question 7

Is Type 4 ADR antibody mediated or cell-mediated?

Answer 7

Cell

Question 8

what is a Type 4a ADR

Answer 8

IFN-y, TNF-a (Th1 cells)

antigen presenting cell or direct T. cell activation

Macrophage activation

Question 9

example of Type 4a ADR

Answer 9

Tuberculin reaction, contact dermatitis

Question 10

What is a Type 4b ADR?

Answer 10

IL-4, IL-5, IL-13 (Th2 cells)

apc/direct T cell stim

Eosinophils

Question 11

Example of Type 4b ADR

Answer 11

DRESS
Macpap exanthema with eosinophilia

Question 12

What is a Type 4c ADR

Answer 12

Perforin/Granzyme B

Cell-associated antigen/direct T cell stim.

T cells

Question 13

Eg of Type 4c ADR?

Answer 13

SLS/TEN, bullous exanthema, Fixed Drug Eruption, Hepatitis

Question 14

What is a Type 4d ADR

Answer 14

CXCL8, GM-CSF (T cell)

APC or direct T-cell activ.

Neutrophils

Question 15

Eg of Type 4d ADR

Answer 15

AGEP
Behcets disease

Question 16

ADR associated with carbamazapine

Answer 16

macpap eruption/DRESS/ SJS/TEN

Question 17

What is the most common class of drugs causing hypersensitivity reactions?

Answer 17

NSAIDS

Question 18

ADR associated with ACE-inhibitors

Answer 18

Angioedema (vasodilatory effect, not immune-mediated)

Question 19

What are some examples of Type 4 ADRs?

Answer 19

Severe cutaneous adverse drug reactions (SCAR) can either be confined to skin or multisystem

Mobilliform eruptions (mild common)

Stevens-Johnson syndrome and Toxic epidermal necrolysis

Drug rash with eosinophilia and systemic symptoms

Lichenoid drug eruptions

Acute generalised exanthematous pustulosis (AGEP)

Question 20

Examples of drugs causing SCAR

Answer 20

Rifampicin: DRESS commonest, LDE, SJS/TEN
Pyrazinamide: SJS/TEN, but also DRESS
Isoniazid: DRESS, LDE, SJS/TEN
Ethambutol: DRESS, SJS/TEN
Ethionamide: DRESS AND SJS/TEN
Cotrimoxazole: DRESS, SJS/TEN

Question 21

Drugs that cause DILI

Answer 21

TB drugs: Isoniazid +/- Rifampicin, Pyrazinamide
Sulfonamides
Azoles
Amox/Clavulanate
Anti-convulsants
NSAIDS
Herbal medicines

Question 22

Genes associated with DILI susceptibility to anti-TB therapy, Diclofenac, and Co-amoxyclav

Answer 22

anti- TB: N-acetyletransferase 2 and CYP2E
Diclofenac - cytokine polymorphisms
Co-amoxyclav - HLA

Question 23

Drugs causing acute interstitial nephritis

Answer 23

Antibiotics (penicillins, cephalosporins, quinolones, sulfa drugs [Bactrim])
Rifampicin
NB - Herbal remedies
NSAIDS
Diuretics (thiazides and furosemide)
Allopurinol
Phenytoin

Question 24

Biopsy findings in insterstitial nephritis

Answer 24

Interstitial oedema
Diffuse interstitial infiltrate’s of inflammatory cells - especially T-cells and eosinophils

Question 25

The pathogenesis of acute interstitial nephritis

Answer 25

Immunologically mediated hypersensitivity reaction to a antigen, classically from a drug or infectious antigen - not dose dependent - often associated with extra-renal manifestations

Question 26

Extra-renal manifestations of Drug induced AIN

Answer 26

Rash Joint Pain Eosinophilia Eosinophiliuria

Question 27

Time onset of drug AIN after starting the drug

Answer 27

Usually within 3 weeks, can vary up to 2 months or later with an NSAIDS

Question 28

Rifampicin induced AIN

Answer 28

Generally occurs after abx is reintroduced after an interval NOT normally associated with eosinophilia Flu-like symptoms, flank pain, HPT, oliguria, ARF are common Can see acute tubular necrosis

Question 29

Management of drug induced AIN

Answer 29

Cessation of causative drug results in quick recovery and complete resolution of renal disorder If there is no improvement with a few days: consider renal biopsy and give High dose prednisone