Management of Immune Mediated Toxicities

Question 1

What is the allele associated with Abacavir hypersensitivity?

Answer 1

HLA-B*5701: Hypersensitivity rxns

Question 2

What is the allele associated with allopurinol hypersensitivity?

Answer 2

HLA-B*5801: SJS/TEN

Question 3

What is the allele associated with phenytoin hypersensitivity?

Answer 3

HLA-B*1502: SJS/TEN

Question 4

What are the alleles associated with carbamazepine hypersensitivity?

Answer 4

HLA-B1502: SJS/TEN
HLA-A3101: DRESS

Question 5

How do we manage anaphylaxis?

Answer 5

Aim: Restore respi& CV fn
Epinephrine (adrenaline): counteract bronchoconstr (relax) & vasodilation (vasoconstriction)

If able to reach the hospital:
- Supplement w IV fluids
- Norepinephrine (noradrenaline) if in shock
- Other meds
Glucagon: if pt is on BB, to help w ionotropic and chronotropic effect
Steroids: suppressed delayed rxn
Diphenhydramine: H1 antagonist
Ranitidine: H2 antagonist

Question 6

How do we manage SCAR?

Answer 6

Aim: Discontinue drug, symptom control
Treatment sim to burn pts
- Wound care
- Fluids
- Pain management
- Infection prevention
- Nut support
- T reg

Steroid use controversial
Use IV Ig or cyclosporine (cyclosporine more mortality assoc)

Question 7

What is the pathophysiology of Systemic Lupus Erythematosus?

Answer 7

Auto Ig to nucleic acids released from cells after apoptosis
Auto Ig disseminated throughout body
Deposition in smaller vessels
Occlusions in brain, kidney, joints, hands, CV

Drug induced
- Procainamide
- Hydralazine
- Quinidine
- Minocycline
- Isoniazid
- Methyldopa
- Carbamazepine

Question 8

What are the risk factors of SLE?

Answer 8

Infections
First degree relative w SLE
Drugs
Smoking
Pollution
UV light
Epstein-Barr virus

Question 9

Describe the epidemiology of SLE.

Answer 9

Females (10:1)
African > Non-white > white
First deg relatives 20x more likely

Question 10

Describe the presentations of SLE.

Answer 10

Various stages: Lupus nephritis, Cardiac, Neuropsychiatric

FBC
- Hemolytic anemia (decreased rbc)
- Decreased wbc
- Decreased platelets

Ig
- Antinuclear antibody (ANA)
- Anti-Smith Ig (anti-SM)
- Antinuclear ribonucleoprotein (anti-RNP)
- Low complement (C3,4, CH50)
- Anti-ds DNA

Question 11

What are the prinicples of management for SLE?

Answer 11

EULAR Guidelines
1st line: Hydroxychloroquine (for all mild-severe, even in pregnancy)

For acute flares:
- NSAIDs
- Corticosteroids

Non-response:
- Biologics

Question 12

What are the classes of drugs/agents available for SLE treatment?

Answer 12

Hydroxychloroquine
NSAIDs
Corticosteroids
Biologics
Immunosuppressants

Question 13

What is the MOA of hydroxychloroquine?

Answer 13

Inhibition of APC
Inhib toll like rece on T cell, var factors that suppress T cell activation
Decreased activation of CD4+ T cells , B cells and therefore the formation of auto Ig

Question 14

What is the onset of hydroxychloroquine?

Answer 14

4-8 weeks

Question 14

What are the clinical benefits of hydroxychloroquine?

Answer 14

Prevent flare
Improve long term survival
Anti inflamm, immunomodulatory
Antithrombotic

Question 15

What are the S/E of hydroxychloroquine?

Answer 15

Renal toxicity >10% prevalence after 20y use
GI intolerance
Rash
Skin hyperpigmentation

Question 16

When are NSAIDs indicated for SLE?

Answer 16

First line for acute symptoms

Question 17

What are the considerations to be made for NSAIDs in its use in SLE?

Answer 17

Asthma, increased CV risks, GI bleed, worsening lupus nephritis

Question 18

When are corticosteroids indicated for SLE?

Answer 18

Monotherapy or adjunctive to control flares
Maintain low disease activity

Question 19

What are the S/E of corticosteroids?

Answer 19

Cataract, glaucoma, osteoporosis, hyperglycemia, HTN, dyslipidemia, skin thinning, wt gain, fat redistr, sleep/mood disturbances

Topical: skin atrophy, dermatitis, telangiectasia,

Question 20

Name the biologics used in SLE

Answer 20

Belimumab and rituximab

Question 21

When are the biologics indicated for SLE?

Answer 21

Non-response to other drugs

Question 22

What is the MOA of biologics (belimumab and rituximab)?

Answer 22

Disrupts fning of B cells

Question 23

What are the S/E of Belimumab?

Answer 23

Infusion site rxns
Hypersensitivity
NV
Diarrhoea
Fever
Insomnia
Depression
Migraine
Nasopharyngitis
Bronchitis
Pain in extremity

Question 24

Name the immunosuppressants for SLE.

Answer 24

Cyclophosphamide
Mycophenolate
Azathioprine
Methotrexate

Question 25

What are the S/E for cyclophosphamide?

Answer 25

Myelosuppression, opportunistic reactions, haemorrhagic cystitis, bladder malignancy, infertility

Question 26

What are the S/E of mycophenolate?

Answer 26

Myelosuppression, NV, diarrhoea

Question 27

When is cyclophosphamide indicated in SLE?

Answer 27

Severe SLE w organ involvement, induction therapy

Question 28

When is mycophenolate indicated in SLE?

Answer 28

Induction and maintenance thera

Question 29

What considerations must be made for azathioprine use?

Answer 29

Test thiopurine methyltransferase (TPMT) before initiating
Risk of toxicity greatly increased in TPMT deficiency

Question 30

What are the S/E of azathioprine?

Answer 30

Myelosuppression, hepatotoxicity

Question 31

When is azathioprine indicated in SLE?

Answer 31

Alt to mycophenolate for maintenance

Question 31

How do we monitor SLE?

Answer 31

Regular labs Q1-3mo w active disease, 6-12mo if stable
- Urinalysis/renal fn, Anti-dsDNA Ig, Complement C3, C4 levels, CRP, FBC, LFT
- ANA, anti-SM, anti-RNP Ig do NOT need to be repeated at each visit as levels do not fluctuate w disease activity

Question 31

What is the lowest dose of hydroxychloroquine for effective treatment?

Answer 31

5 mg/kg/day

Question 32

What are the adjunctive therapy for non-renal SLE treatment?

Answer 32

Sun protection
Vacc
Exercise
Smoking cessation
Body wt control
Control of 3 highs

Antiplatelets
Anticoagulants