Cutaneous Drug Eruptions Flashcards
Describe the 4 types of immunologically mediated drug reactions (‘allergic’)
- Type I: anaphylactic reaction, urticaria
- Type II: cytotoxic reaction, pemphigus and pemphigoid
- Type III: immune complex mediated reaction, purpura/rash
- Type IV: T cell mediated delayed hypersensitivity reaction, erythema/rash
List some examples of non immunological (‘non allergic’) mediated drug reactions
- Eczema
- Drug-induced alopecia
- Phototoxicity
- Skin erosion due to topical 5-flurouracil
- Atrophy due to topical corticosteroids
- Psoriasis
- Pigmentation
- Cheilitis, xerosis
Are immunological drug reactions dose dependant
No - they will happen regardless of the dose
Are non immunological drug reactions dose dependant
Yes - they can be dose dependant
Cutaneous drug eruptions risk factors
- Elderly patients
- Females
- Concomitant diseases e.g. HIV, EBV, CF
- Previous drug reaction or positive skin test
- Topical drug use
- Higher dose of drug/ longer half life
- High molecular weight drugs
- β-lactam compounds, NSAIDS
How can drug eruptions present on the skin
Exanthematous/morbilliform/maculopapular
Urticaria
Purpuric or vasculitic
Pustular or bullous
What type of reaction causes an exanthematous drug eruption?
Type IV reaction
What drugs are most commonly associated with an exanthematous drug eruption
antibiotics (beta-lactams, sulfonamides),
NSAIDs,
anti-epileptics (carbamazepine, phenytoin),
allopurinol
chloramphenicol
When does an exanthematous drug eruption present after first taking the drug & what does it look like? What associated symptoms are common?
- Onset 4-21 days after first taking drug
- Widespread symmetrically distributed rash
- Usually no involvement of mucous membranes
- Pruritus common
- Mild fever common
What would you indicate a a more severe exanthematous drug reaction
- Involvement of mucous membrane and face
- Facial erythema and oedema
- Widespread confluent erythema
- Fever >38.5℃
- Blisters, purpura, necrosis
- Skin pain
- Lymphadenopathy, arthralgia
- Dysnpnoea, wheezing
What type of reaction is an urticarial drug reactions
Usually an immediate IgE-mediated (type I) hypersensitivity reaction after rechallenge with drug
What drugs are associated with a urticarial IgE mediated drug reaction
β-lactam antibiotics, carbamazepine, many others
Urticarial drug reactions can also be caused by direct release of inflammatory mediates from mast cells on first exposure. What drugs are commonly associated with this
aspirin, opiates, NSAIDs, muscle relaxants, vancomycin, quinolones
What drugs can cause drug induced acneiform
glucocorticoids (steriod acne), androgens, lithium, isoniazid, phenytoin
How can you distinguish drug induced aceniform from acne vulgaris
Drug induced acneiform does not cause comedones whereas acne vulgaris does
What drug is most commonly associated with acute generalised exanthematous pustulosis (AGEP) (a rare drug eruption)
calcium channel blockers
What drugs are associated with drug induced bullous pemphigoid
ACE inhibitors, penicillin, furosemide
What are fixed drug eruptions
Well demarcated round/ovoid plaques which recur at the same site each time a drug is taken and resolves with persistent pigmentation when drug stops
How & where do fixed drug eruptions initially present
Can present as eczematous lesions, papules, vesicles or urticaria. Can be red and painful. Can occur on hands, genitalia, lips & occasionally oral mucosa
What drugs are commonly associated with fixed drug eruptions
antibiotics (tetrecycline, doxycycline), paracetamol, NSAIDs and carbamazepine
What are the 4 main sever cutaneous adverse drug reactions
Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
Acute generalised exanthematous pustulosis (AGEP)
Drug reaction with eosinophilia and systemic symptoms (DRESS)
How are SJS & TEN characterised
They are characterised by varying extents of blistering/epidermal detachment and mucosal ulceration
What drugs are commonly associated with SJS & TEN
(Antibiotics) Sulfonamides, cephalosporins,
(Anti seizure meds) Carbamazepine, phenytoin,
(Pain meds) NSAIDs, tramadol
(HIV meds) Nevirapine, lamotrigine,
(Other) sertraline, pantoprazole,
How & when does DRESS present
Widespread erythema, facial oedema, fever, lymphadenopathy and hepatosplenomegaly which usually starts 2-6 weeks after initial exposure
What drugs are commonly associated with DRESS
(HIV meds) abacavir, nevirapine,
(Antibiotics) vancomycin, sulfonamides, minocycline, dapsone
(Other) allopurinol, anticonvulsants, NSAIDs,
How, where & when does AGEP present
Widespread rash with numerous small, non-follicular, sterile pustules around the neck, axillae and groin.
Usually starts a few days after drug exposure and resolves with peeling
What are phototoxic cutaneous drug reactions
Non-immunological skin reaction arising in an individual exposed to enough photo-reactive drug and light of the appropriate wavelength
Phototoxic cutaneous drug reactions pathophysiology
Drug metabolites interact with UV light (usually triggered by UVA) → free radical release → direct tissue or cell injury → severe rash
What phototoxic drugs present with immediate prickling with delayed erythema and pigmentation
Chlorpromazine
Amoidarone
What phototoxic drugs present with exaggerated sunburn
quinine, thiazides, demeclocycline
What phototoxic drugs present with exposed telangiectasia
calcium channel blockers
What phototoxic drug presents with delayed 3-5 days erythema and pigmentation
psoralens
What phototoxic drugs present with increased skin fragility
nalidixic acid, tetracyclines, naproxen, amiodarone
How do you diagnose cutaneous drug eruptions
History and physical examination usually sufficient to spot likely drug
What test can be used if you are not certain of the cause of a phototoxic drug reaction
Phototesting OR photopatch testing
What test can be used if you are not certain of the cause of an allergic contact dermatitis (type IV) drug reaction
Patch testing
What test can be used if you are not certain of the cause of a suspected allergic (Type I) drug reaction
Skin prick/intradermal test
When is skin prick testing not indicated
serum sickness reactions (Type III),
type IV reactions,
severe cutaneous adverse drug reactions
Cutaneous drug eruptions management
- Discontinue the drug (if possible), use an alternative
- Topical corticosteroids may be useful
- Antihistamines may help if type I or with symptoms of itch
- Allergy bracelets are useful for some drugs
What group of patients are more likely to suffer from a severe cutaneous drug reaction
Immunocompromised patients
