Immunology Lecture Flashcards
What is a Type 1 Antibody Mediated Adverse Drug Reaction
IgE
Soluble antigen
Mast cell activation
Example of Type 1 Antibody Mediated Adverse Drug Reaction
Penicillin (Beta-lactams)
urticaria
angioedema
bronchospasm
anaphylaxis
what is a type 2 antibody mediated ADR
IgG
Cell or matrix associated antigen
FcR+ cells (phagocytes, NK cells)
Example of Type 2 ADR
Beta lactams, Rifampicin, Sulfa antibiotics
Haem. anaemia
thrombocytopaenia
What is a Type 3 ADR (antibody mediated)
IgG
Soluble antigen
FcR+ cells, complement
Type 3 ADR (antibody mediated) example?
Vaccination: serum sickness (fever, vasculitic rash, joint inflam.)
Beta-lactams, sulfa antibiotics, minocycline: Arthus reaction
Hypersensitivity vasculitis
Is Type 4 ADR antibody mediated or cell-mediated?
Cell
what is a Type 4a ADR
IFN-y, TNF-a (Th1 cells)
antigen presenting cell or direct T. cell activation
Macrophage activation
example of Type 4a ADR
Tuberculin reaction, contact dermatitis
What is a Type 4b ADR?
IL-4, IL-5, IL-13 (Th2 cells)
apc/direct T cell stim
Eosinophils
Example of Type 4b ADR
DRESS
Macpap exanthema with eosinophilia
What is a Type 4c ADR
Perforin/Granzyme B
Cell-associated antigen/direct T cell stim.
T cells
Eg of Type 4c ADR?
SLS/TEN, bullous exanthema, Fixed Drug Eruption, Hepatitis
What is a Type 4d ADR
CXCL8, GM-CSF (T cell)
APC or direct T-cell activ.
Neutrophils
Eg of Type 4d ADR
AGEP
Behcets disease
ADR associated with carbamazapine
macpap eruption/DRESS/ SJS/TEN
What is the most common class of drugs causing hypersensitivity reactions?
NSAIDS
ADR associated with ACE-inhibitors
Angioedema (vasodilatory effect, not immune-mediated)
What are some examples of Type 4 ADRs?
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)
Examples of drugs causing SCAR
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
Drugs that cause DILI
TB drugs: Isoniazid +/- Rifampicin, Pyrazinamide
Sulfonamides
Azoles
Amox/Clavulanate
Anti-convulsants
NSAIDS
Herbal medicines
Genes associated with DILI susceptibility to anti-TB therapy, Diclofenac, and Co-amoxyclav
anti- TB: N-acetyletransferase 2 and CYP2E
Diclofenac - cytokine polymorphisms
Co-amoxyclav - HLA
Drugs causing acute interstitial nephritis
Antibiotics (penicillins, cephalosporins, quinolones, sulfa drugs [Bactrim])
Rifampicin
NB - Herbal remedies
NSAIDS
Diuretics (thiazides and furosemide)
Allopurinol
Phenytoin
Biopsy findings in insterstitial nephritis
Interstitial oedema
Diffuse interstitial infiltrate’s of inflammatory cells - especially T-cells and eosinophils
The pathogenesis of acute interstitial nephritis
Immunologically mediated hypersensitivity reaction to a antigen, classically from a drug or infectious antigen
- not dose dependent
- often associated with extra-renal manifestations
Extra-renal manifestations of Drug induced AIN
Rash
Joint Pain
Eosinophilia
Eosinophiliuria
Time onset of drug AIN after starting the drug
Usually within 3 weeks, can vary up to 2 months or later with an NSAIDS
Rifampicin induced AIN
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
Management of drug induced AIN
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
