Dermatology: Drug Eruptions

Question 1

Types of drug reactions affecting the skin?

Answer 1

Immunologically-mediated reaction (allergic) - these are NOT DOSE-DEPENDENT

Non-immunologically mediated reaction (non-allergic) - these CAN be DOSE-DEPENDENT

Question 2

Types of immunologically mediated reactions and examples of each?

Answer 2

Type I - anaphylactic reactions:
Urticaria

Type II - cytotoxic reactions:
Pemphigus & pemphigoid

Type III - immune complex-mediated reactions:
Purpura/rash

Type IV - cell-mediated delayed hypersensitivity reactions:
T-cell mediated
Erythema/rash

Question 3

Examples of non-immunologically mediated reactions?

Answer 3

Eczema 
Drug-induced alopecia
Phototoxicity, e.g: doxycycline
Skin erosion or atrophy from topically applied steroids
Psoriasis
Pigmentation
Cheilitis, xerosis

Question 4

Morphologies/presentation of drug reactions?

Answer 4

Exanthematous/morbilliform/maculopapular

Urticarial

Papulosquamous/pustular/bullous

Can present with:
Pigmentation
Itch/pain
Photosensitivity

Question 5

Who may had a drug reaction?

Answer 5

Any patient who is taking mediation and develops a SYMMETRIC skin eruption of sudden appearance

Question 6

Exception to the rule “reactions normally resolve when the drug is withdrawn”?

Answer 6

Half-life of the drug plays a role
Ability of the drug to be retained/accumulated in tissues, e.g: highly lipid-soluble drugs
Cross-reaction with a similar class of drugs

Question 7

Risk factors for development of drug eruptions?

Answer 7

Age - young adults more so than infants/elderly (however, reactions occur in the elderly more, due to increased drug usage)

Gender - females more than males

Genetics

Concomitant disease, e.g: viral infection (HIV/EBV/CMV), cystic fibrosis

Immune status - previous drug reaction or positive skin test

Question 8

For a patient on multiple drugs, what should be considered?

Answer 8

Drug that is known to be most likely to cause an eruption

The time interval between exposure and development of skin reaction

History of previous exposure to the same drug (sometimes, they may develop a reaction on subsequent uses)

Question 9

What are exanthematous drug eruptions?

Answer 9

Most common type of drug eruption (90%)

Idiosyncratic, T-cell mediated delayed type hypersensitivity (Type IV) reaction

Question 10

Features of exanthematous drug eruptions?

Answer 10

Usually mild & self limiting but involves:
Widespread, symmetrically distributed rash
Mucous membranes usually being spared
Pruritus and mild fever are common

Onset is 4-21 days after first taking drug and may progress to a severe life-threatening reaction

Question 11

Red flag symptoms in exanthematous drug eruptions?

Answer 11

Involvement of mucous membrane and face

Facial oedema & erythema

Widespread confluent erythema; may see Nikolsky sign (gentle pressure lifts skin)

Fever (>38.5⁰C)

Blisters, purpura, necrosis

Lymphadenopathy, arthalgia

Shortness of breath, wheezing

Question 12

Drugs assoc. with exanthematous drug eruptions?

Answer 12

Penicillins

Sulphonamide antibiotics

Erythromycin

Streptomycin

Allopurinol

Anti-epileptics: carbamazepine

NSAIDs
Phenytoin

Chloramphenicol

Question 13

What is an urticarial reaction?

Answer 13

Usually an immediate IgE-mediated hypersensitivity reaction (Type I) after re-challenge with the drug, e.g: β-lactams

OR

Direct release of inflammatory mediators from mast cells on first exposure, e.g: aspirin, opiates, NSAIDs

Question 14

Drugs that can cause an acne-like reaction?

Answer 14

Glucocorticoids (steroid acne)

Androgens (therapeutic), lithium, phenytoin

Question 15

Drugs that cause acute generalised exanthematous pustulosis (AGEP)?

Answer 15

Sheets of sterile putsules (negative culture); these are reactions that can occur due to antibiotics, CCBs and anti-malarials

Question 16

Examples of pustular/bullous drug eruptions?

Answer 16

Vesicular/bullous reactions can range from mild-severe, e.g:
Drug-induced bullius pemphigoid (normally in the elderly) - ACE inhibitors penicillin and furosemide

Linear IgA disease can be triggered by drugs like vancomycin

Question 17

What are fixed drug eruptions?

Answer 17

Reaction that always re-occurs in the same area with the same drug

Question 18

Appearance of fixed drug eruptions?

Answer 18

Welll-demarcated round/ovoid plaques; they are red and painful and often occur at the hands, genitalia, lips and, sometimes, oral muscosa

Could present as eczematous lesions, papules, vesicles or urticaria

These resolve with persistence pigmentation when the drug is stopped

Question 19

Drugs assoc. with FDEs?

Answer 19

Tetracycline, doxycycline
Paracetamol
NSAIDS
Carbamazepine

Question 20

2 types of severe cutaneous adverse reactions and causes?

Answer 20

Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
E.g: caused by sulfonamide antibiotics, NSAIDs, phenytoin, cephalosporins and carbamazepine, etc

Drug reaction with eosinophilia and systemic symptoms (DRESS) is characterised by facial oedema and a very high eosinophil count:
Sulfonamides, anti-convulsants, allopurinol, NSAIDs, vancomycin, abacavir

Acute generalised exanthematous pustulosis (AGEP)

Question 21

Acute and chronic phototoxic drug reaction examples?

Answer 21

Acute:
Skin toxicity
Systemic toxicity
Photodegradation

Chronic:
Pigmentation
Photoageing
Photocarcinogenesis

Question 22

What are phototoxic cutaneous drug reactions?

Answer 22

Non-immunological mediated skin reaction which will arise in any individual providing there is enough photo-reactive drug and the appropriate wavelength of light (UVA is usually of concern and can occur through window glass)

Increased sensitivity to sunlight, caused by drugs, can also occur via other mechanisms, e.g: immunosuppression

Question 23

Major patterns of cutaenous phototoxicity?

Answer 23

Immediate prickling with delayed erythema and pigmentation, e.g: chlorpromazine, amiodarone

Exaggerated sunburn, e.g:
quinine, thiazides, DCMT

Exposed telangiectasia, e.g:
CCBs

Delayed 3-5 days erythema and pigmentation, e.g: psoralens

Increased skin fragility, e.g:
nalidixic acid, tetracycline naproxen, amiodarone

Question 24

Information to ask in history?

Answer 24

Detailed description of reaction

Timing of onset of symptoms in relation to drug administration:
Previous exposure to drug
When did the drug start (in relation to symptoms)
When was the drug stopped
Did stopping the drug affect the symptoms

Photograph of reaction?

Why was the drug being taken:
Underlying illness

Comprehensive drug history including prescribed/non prescribed and herbal/alternative remedies

Previous history of drug reaction, allergy or other illnesses

Question 25

Why is skin testing NOT INDICATED for serum sickness reactions (Type III) or for T-cell mediated reactions (Type IV)?

Answer 25

Can trigger SJS, TEN or DRESS

Question 26

Management of drug eruptions?

Answer 26

Discontinue the drug (if possible) and use an alternative (class if able to)
Topical steroids, anti-histamines may be useful may be useful.
Allergy bracelets are useful for some drugs