Management of Immune Mediated Toxicities Flashcards
What is the allele associated with Abacavir hypersensitivity?
HLA-B*5701: Hypersensitivity rxns
What is the allele associated with allopurinol hypersensitivity?
HLA-B*5801: SJS/TEN
What is the allele associated with phenytoin hypersensitivity?
HLA-B*1502: SJS/TEN
What are the alleles associated with carbamazepine hypersensitivity?
HLA-B1502: SJS/TEN
HLA-A3101: DRESS
How do we manage anaphylaxis?
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
How do we manage SCAR?
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)
What is the pathophysiology of Systemic Lupus Erythematosus?
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
What are the risk factors of SLE?
Infections
First degree relative w SLE
Drugs
Smoking
Pollution
UV light
Epstein-Barr virus
Describe the epidemiology of SLE.
Females (10:1)
African > Non-white > white
First deg relatives 20x more likely
Describe the presentations of SLE.
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
What are the prinicples of management for SLE?
EULAR Guidelines
1st line: Hydroxychloroquine (for all mild-severe, even in pregnancy)
For acute flares:
- NSAIDs
- Corticosteroids
Non-response:
- Biologics
What are the classes of drugs/agents available for SLE treatment?
Hydroxychloroquine
NSAIDs
Corticosteroids
Biologics
Immunosuppressants
What is the MOA of hydroxychloroquine?
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
What is the onset of hydroxychloroquine?
4-8 weeks
What are the clinical benefits of hydroxychloroquine?
Prevent flare
Improve long term survival
Anti inflamm, immunomodulatory
Antithrombotic
What are the S/E of hydroxychloroquine?
Renal toxicity >10% prevalence after 20y use
GI intolerance
Rash
Skin hyperpigmentation
When are NSAIDs indicated for SLE?
First line for acute symptoms
What are the considerations to be made for NSAIDs in its use in SLE?
Asthma, increased CV risks, GI bleed, worsening lupus nephritis
When are corticosteroids indicated for SLE?
Monotherapy or adjunctive to control flares
Maintain low disease activity
What are the S/E of corticosteroids?
Cataract, glaucoma, osteoporosis, hyperglycemia, HTN, dyslipidemia, skin thinning, wt gain, fat redistr, sleep/mood disturbances
Topical: skin atrophy, dermatitis, telangiectasia,
Name the biologics used in SLE
Belimumab and rituximab
When are the biologics indicated for SLE?
Non-response to other drugs
What is the MOA of biologics (belimumab and rituximab)?
Disrupts fning of B cells
What are the S/E of Belimumab?
Infusion site rxns
Hypersensitivity
NV
Diarrhoea
Fever
Insomnia
Depression
Migraine
Nasopharyngitis
Bronchitis
Pain in extremity
Name the immunosuppressants for SLE.
Cyclophosphamide
Mycophenolate
Azathioprine
Methotrexate
What are the S/E for cyclophosphamide?
Myelosuppression, opportunistic reactions, haemorrhagic cystitis, bladder malignancy, infertility
What are the S/E of mycophenolate?
Myelosuppression, NV, diarrhoea
When is cyclophosphamide indicated in SLE?
Severe SLE w organ involvement, induction therapy
When is mycophenolate indicated in SLE?
Induction and maintenance thera
What considerations must be made for azathioprine use?
Test thiopurine methyltransferase (TPMT) before initiating
Risk of toxicity greatly increased in TPMT deficiency
What are the S/E of azathioprine?
Myelosuppression, hepatotoxicity
When is azathioprine indicated in SLE?
Alt to mycophenolate for maintenance
How do we monitor SLE?
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
What is the lowest dose of hydroxychloroquine for effective treatment?
5 mg/kg/day
What are the adjunctive therapy for non-renal SLE treatment?
Sun protection
Vacc
Exercise
Smoking cessation
Body wt control
Control of 3 highs
Antiplatelets
Anticoagulants
