9. Adverse Drug Reactions: The Skin Flashcards
What can go wrong with the skin?
- Irritation
- (Corrosion)
- Heat rash (miliaria)
- Photosensation
- Contact sensitisation
- Clinical manifestation of systemic allergic reactions
- (Cancer)
CDR vs Skin Disease
- CDR (cutaneous drug reaction) can mimic skin diseases which is problematic
Management of CDR
- Immediate withdrawal of all potential offending agents
- Patient with extensive involvement should be cared for as a “burn-patient”
CDR considerations
- Most likely topical exposure but also possibly due to systemic exposure
- Time of onset: Acute (<60 min), Sub-acute (1-24 hours), Latent (> 2 days)
Criteria (timeframes) for CDR:
- Eruptions:
- Acute generalised pustulosis
- Mild CDR
- Reactions
- Drug hypersensitivity syndrome
- Eruptions (urticaria & anaphylaxis): Minutes - hours
- Acute generalised pustulosis/fixed drug eruption: 1 - 3 days
- Mild CDR: 9 ± 5 days
- Reactions such as Steven-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN): 2 - 3 weeks
- Drug hypersensitivity syndrome (DRESS): 4 - 6 weeks
Serious or Severe CDR?
- “Severe” describes the intensity (severity) of a specific event: Mild, moderate, severe
- “Serious” is based on patient/event outcome or action criteria usually associated with events that pose a threat to a patient’s life
Skin irritation
- Acute (single exposure)
- Cumulative (usually frequent exposure to mild irritants)
- Delayed (results in hyper proliferation & hyperkeratosis)
- May be due to drug or vehicle
Mechanisms for irritation
Damage to the barrier function of stratum corner:
- Removal of lipids by solvents & detergents
- Protein denaturation by acids & alkalis
- Reactive oxygen formation by bleaches
Results in greater water loss & may allow penetration of irritants to deeper layers
Drug-induced photosensitivity - phototoxic reactions
- Direct damage to tissue caused by light activation of the photosensitising agent
- Redness & swelling & (itchy?)
- Vesicles, blisters & bulle (severe reactions)
- Reaction occurs minutes to hours after exposure to agent
From toxicology to pharmacology:
Photodynamic Therapy
- Treatment used mainly for superficial types of skin cancer (actinic keratosis & superficial basal cell carcinoma)
- Photosensitising agents are administered into the body via topical, oral or IV
Off-targets pharmacological effects:
EGFR inhibitors
- Acneiform eruption (resembles acne)
- Can gradually develop dry skin over weeks resembling atopic eczema
- Nail fold inflammation, hair changes & hyperpigmentation can arise
Hand foot reactions:
Mild - moderate: Redness, swelling, burning/tingling sensation, tenderness, tightness of skin, blisters on palms & soles
Severe: Cracked/flaking/peeling skin, Blisters/ulcers/sores on skin, severe pain, difficulty walking or using hands
Grading:
1 - No symptoms or only slight dysesthesia, with mild redness
2. Dysesthesia but no pain, severe redness and/or swelling
3 – Dysesthesia with pain, severe redness and/or swelling
4 – Pain, desquamation, blistering & ulceration
Dysesthesia (abnormal sensation)
Heat rash (miliaria)
- Due to obstruction of the sweat gland
- Associated with antiperspirant use
- Chemotherapy-associated neutrophilic eccrine hidraenitis (drugs cause apoptosis affecting the major sweat glands)
Non-pharmacological Mechanisms: Allergic contact dermatitis (4)
Reactions:
- Anaphylactic (Type I):
- IgE binds to mast cells, degranulation & release of histamine occur
- Urticaria etc - Cytotoxic (Type II):
- IgG/IgM react with antigens & activate complement or bind to Fcg receptors and activate cyt K cells (cell damage)
- Pemphigus (blisters & erosions on skin) - Immune complex (Type III)
- Deposition of immune complexes in vascular beds activate complement & neutrophils damage tissues
- Red-purple spots on skin - Delayed type (Type IV):
- T cell mediated (CD4+ or CD8+)
- Involves skin
Acute Generalised Exanthematous Pustulosis (AGEP)
- Skin symptoms are accompanied by fever & leukocytosis
- Clinical course characterised by acute onset of skin symptoms & spontaneous resolution
- AGEP can occur at any age
