Immune related toxicities (Anaphylaxis, Pseudoallergy, Autoimmune) IC9

Question 1

Difference between Nonimmune Hypersensitivity and Immune Hypersensitivity (cause)

Answer 1

Immune: allergy, caused by igE, igM, IgG, T cells
Involve innate and adaptive immune system

Nonimmune: aka Pseudoallergy, caused by release of mediators eg. histamine, prostaglandins.
Drugs will cause the release or inhibit breakdown of these chemical mediators, causing hypersensitivity reaction

Question 2

Examples of drugs and the corresponding Pseudoallergy reaction (3 points)

Answer 2

1) Vancomycin → Red man syndrome
Direct release of histamine

2) ACE / Sacubitril → Angioedema
Inhibition of breakdown of Bradykinin → vasodilation and increased vascular permeability

3) NSAID → induced asthma
Alter metabolism of Prostaglandins in lungs

Question 3

5 types of clinical manifestations in Anaphylaxis

Answer 3

Serum sickness / Drug fever

Drug induced autoimmunity (SLE)

Vasculitis

Respiratory (Asthma)

Hematologic (Eosinophilia , Hemolytic anaemia, Agranulocytosis)

Question 4

3 types of drug induced autoimmunity

Answer 4

Systemic Lupus Erythematosus (SLE)

Hemolytic anaemia (caused by Methyldopa)

Hepatitis (caused by Phenytoin)

Question 5

Treatment of Anaphylaxis (immediate and hospital)

Answer 5

Epinephrine / Adrenaline
Counteracts bronchoconstriction and vasodilation

Ambulance / Hospital setting
IV fluids to restore volume, BP
Intubation to save airway
Norepinephrine / Noradrenaline if shock
Steroids
Glucagon (Counter inotropic effect of Beta Blockers)
Antihistamines (Diphenhydramine H1 + Ranitidine H2)

Question 6

What is SCAR?

Answer 6

Serious Cutaneous Adverse Reaction
- serious anaphylactic reaction involving the skin

Involves DRESS, SJS, TEN

Question 7

What is DRESS?

Answer 7

Drug Rash with Eosinophilia and Systemic Symptoms

Caused by Allopurinol and Anticonvulsants

Question 8

What is TEN?

Answer 8

Toxic Epidermal Necrolysis

Caused by antibiotics (sulfamethoxazole)

Question 9

Treatment for SCAR

Answer 9

Similar to burn patients
Supportive care, Wound care
Nutritional support, fluids

Question 10

Difference between SJS and TEN

Answer 10

SJS < 10% detachment of skin
TEN > 30% detachment of skin

Question 11

Cause of autoimmune diseases

Answer 11

Genetics + Environment (injury, smoking)

Genetics: produce self-reactive lymphocytes

Environment: Antigen from tissue injury and inflammation → Present to self-reactive lymphocytes

Question 12

Why are autoimmune diseases difficult to treat (4 points)

Answer 12

Do not respond to treatment / Adverse reactions

Treatment for autoimmune diseases are off-label → great variability of treatment

Costly

People view autoimmune diseases as a weakness, unlikely to seek help

Question 13

Risk factors for SLE (3 points)

Answer 13

Females > Males
African highest, Non white > White
Genetic + Environment (Smoking, infection, Drugs)

Question 14

4 drugs approved for SLE

Which one should all patients receive?

Answer 14

Aspirin, Prednisolone, Hydroxychloroquine, Belimumab

All patients should receive Hydroxychloroquine

Question 15

Which medications are teratogenic? (4 points)

Which one also reduces fertility (getting pregnant)?

Answer 15

Methotrexate
Azathioprine
Mycophenolate
Cyclophosphamide

Cyclophosphamide

Question 16

Adverse effect of Hydroxychloroquine?

Answer 16

Retinal toxicity

Question 17

Adverse effects of Cyclophosphamide (3 points)

Answer 17

Hemorrhagic cystitis
Bladder malignancy
Infertility

Question 18

What does Antiphospholipid Syndrome (APS) result in?

General treatment for APS? (primary, secondary, pregnancy)

Answer 18

Increased clotting risk

Thromboprophylaxis
Primary: Aspirin
Secondary: Warfarin
Pregnancy: IV anticoagulant

Hydroxychloroquine has protective effect on phospholipids (from antibodies)

Question 19

What does immunosuppression therapy consist of?

Answer 19

Induction and Maintenance phase

Induction: high potency, short course to reduce existing damage and prevent worsening of autoimmune condition.

Maintenance: Use Calcineurin inhibitors, Antimetabolites, Corticosteroids, mTOR inhibitors, Biologics

Question 20

Examples of Calcineurin inhibitors

Answer 20

Cyclosporine
Tacrolimus

Question 21

Examples of mTOR inhibitors

Answer 21

Sirolimus
Everolimus

Question 22

Example of antimetabolites

Answer 22

Mycophenolate
Azathioprine

Question 23

Transplant therapy (4 steps)

Answer 23

1) Match HLA and blood type

2) Use intensive induction therapy to avoid initial rejection eg. Biologics

3) Use multiple maintenance agents eg. Calcineurin inhibitors + Glucocorticoids + Mycophenolate

4) Reduce dosage or withdraw drug if toxicity > benefit

Question 24

Complications of Immunosuppression

Answer 24

Immune related:
Opportunistic infections
Cancers

Nonimmune related:
Bone marrow suppression
Hepatotoxicity
Renal toxicity (with Calcineurin inhibitors, mTOR inhibitors)
Hypertension, Hyperlipidemia, Hyperglycemia (with steroids, Calcineurin inhibitors)

Question 25

How is cortisol released in the body?

Effect of chronic corticosteroid therapy on body

Answer 25

Via HPA axis
Hypothalamus secrete CRH, Anterior pituitary release ACTH, Adrenal cortex release cortisol

Chronic corticosteroid therapy causes adrenal suppression.
Long term steroids cause negative feedback on Hypothalamus and Anterior Pituitary, cause decreased secretion of CRH and ACTH