Cutaneous Drug Eruptions Flashcards
What is the commonest reason for drugs to cause a rash?
due to an allergic reaction
How can allergic reactions to drugs be grouped?
- Type 1 reactions which are immediate and IgE related
- Type 2-4 reactions which are cytotoxic, immune-complex or cell-mediated
What symptoms are Type 1 allergic reactions associated with?
urticaria and angioedema (soft tissue swelling)
What type of allergic reaction is more difficult to diagnose?
type 2-4 reactions
this is because they have a delayed onset
What are other reasons why drugs may cause a rash?
- predictable reactions explained by pharmacology or dose-related reactions
- pseudoallergy
What is an example of a dose related reaction involving warfarin?
This is due to the inherent effects of the drug
e.g. if you were to overdose anyone on warfarin, it would eventually lead to petechial skin changes due to bleeding within the skin
What is an example of pseudoallergy involving opiates?
opitates cause increased histamine release
this causes urticaria in patients who are prone to it
What are the 4As for drugs that commonly cause adverse skin reactions?
- Antibiotics
- Anti-epileptics
- Anti-inflammatories
- Allopurinol
(also antipsychotics, ART, immunotherapy, sulphonamides, ACEi)
What antibiotics commonly cause drug reactions?
- penicillins
- cephalosporins
- co-trimoxazole
What anti-epileptics commonly cause drug reactions?
- phenytoin
- carbamazepine
What anti-inflammatories commonly cause drug reactions?
- naproxen
- diclofenac
- ibuprofen
What are the 3 types of cutaneous drug reaction?
- morbilliform / exanthematous
- urticaria (sometimes accompanied by angioedema)
- fixed drug eruption
there are also serious cutaneous adverse reactions (SCAR)
What are the 3 main serious cutaenous adverse reactions (SCAR)?
- drug reaction with eosinophilia and systemic symptoms (DRESS)
this is also known as drug hypersensitivity syndrome
- acute exanthematous generalised pustulosis (AGEP)
- Steven Johnson syndrome (SJS) + toxic epidermal necrolysis (TEN)
What are some other potential less common types of cutaenous drug rashes?
- lichenoid
- vasculitic
- bullous
- lupus
- photosensitivity
What type of rash is shown here?
What causes this?
vasculitic rash
characterised by palpable purpura (non-blanching areas) with occasional central blistering and necrosis
this is often due to underlying infection or is idiopathic, but can also be part of a drug reaction
What type of rash is shown in this photo?
What are potential differentials?
morbilliform rash (typical drug rash)
this type of rash can also be secondary to infections (particularly viral)
How does a morbilliform rash present?
- looks like a viral rash
- erythematous macules and papules
- can be itchy, patient is normally well
- usually on the trunk and spreads to limbs but spares the face, palms, soles, axillae and groins
What % of drug rashes are morbilliform rashes?
around 95%
What type of reaction is a morbilliform rash?
How long does it take to develop after starting the drug?
it is a type 4 hypersensitivity reaction
onset of 1-3 weeks after starting the drug
What can a morbilliform rash potentially progress to?
a typically benign drug rash can progress to erythroderma and SJS/TEN
erythroderma is skin redness covering >90% of the body
What does an urticarial rash look like?
raised plaques with erythematous edges and central clearing
What is urticaria often accompanied by?
angioedema
this is swelling of the subcutaneous tissue
What often causes urticaria?
it is often idiopathic or due to other causes e.g. food allergy
seen in anaphylaxis
What is the onset of urticaria like?
rapid onset (<2 hours) and change
individual lesions last <24 hours but the actual rash may last for longer than this
What drugs typically cause an urticarial rash?
- penicillin
- NSAIDs
- aspirin
- opiates
- radio contrast agents (e.g. used in CT scans)
- ACEi
What is a fixed drug eruption?
a much rarer form of drug reaction in which every time someone is given a drug they get a localised rash that occurs at the same site each time
What is the onset of a fixed drug eruption like?
Is it stable?
the onset is usually within hours
it may become more severe or widespread with repeat exposure
Which parts of the body are usually affected in a fixed drug eruption?
- hands
- feet
- lips
- eye lids
- genitals
What drugs usually cause a fixed drug eruption?
- tetracyclines
- paracetamol
- NSAIDs
- sulphonamides
What is shown in these images?
a fixed drug eruption rash
the areas may sometimes blister
How does drug hypersensitivity syndrome/DRESS present?
- rash that is usually morbilliform but can develop erythrodema
- fever
- lymphadenopathy
- haematological abnormalities
- inflammation of internal organs
When does DRESS usually occur after taking a drug?
usually within 2-8 weeks after starting a drug
What are some characteristic features of DRESS/DHS that are usually present?
- morbilliform rash that can develop into erythroderma
- palpable lymph nodes in 75%
- facial swelling in 33%
- mucosal ulceration (mouth, eyes, genitals) in 25%
What characteristic feature is looked for on the bloods of someone with DRESS/DHS?
characterisitic eosinophila
What other blood test results are expected in DRESS/DHS?
- raised WCC particularly eosinophils
- may develop anaemia or thrombocytopenia
- hepatitis usually occurs meaning 80% will have deranged LFTs
- any other organ can also be involved (nephritis, meningitis, pneumonitis, percarditis)
What is the mortality like for DRESS/DHS?
mortality rate of 8%
this is due to fulminant hepatitis and multi-organ failure
What is shown in these images?
some features characteristic of drug hypersensitivity syndrome
- widespread erythematous papular rash
- angioedema / facial swelling
What is the onset of acute generalised erythematous pustulosis (AGEP) like?
What areas tend to be involved?
usual onset is within 2 days of starting the drug
it starts in the axillae / groin / face and then becomes generalised
What does the AGEP rash look like?
Are there any other symptoms?
erythroderma with sheets of small pustules
oral lesions in 20%
may have fever and malaise but generally not unwell, although 10% show organ dysfunction
What do blood tests show in someone with AGEP?
neutrophilia
(raised neutrophils)
What does a drug rash look like when it begins to resolve?
it is inflamed and oedematous at first
it then becomes dry (desquamation) and scaly, particularly on the arms
What 4 stages are involved in how to approach a suspected drug induced rash?
- history
- examination
- investigations
- initial management
What are the main questions that you want to ask in the history about the rash?
- onset - when did it start?
- evolution - where did the rash start and has it spread?
- symptomatic - itchy, painful?
What are the red flags when taking a history about a rash?
- mucosal ulceration
- blisters
- painful skin (sometimes seen in SJS/TEN)
What is useful to make when a taking a history of a patient with a drug-induced rash?
What questions should be asked with this?
a drug timeline should be made, including over the counter drugs
ask whether patient has had prior exposure to these drugs and if they have any known allergies
What other causes should be considered when taking a history for a drug-induced rash?
- are there any viral symptoms?
- is there a history of skin problems?
What 2 things are important to look for when examining a patient with a drug-induced rash?
Distribution:
- where on the body is the rash?
- is it erythrodermic (>90% of body surface area involved)?
Morphology of individual lesions:
- macules? targetoid lesions? blisters?
What are the red flags to look for when examining a patient with a drug induced rash?
- mucosal involvement - look at the eyes, mouth and genitals
- blisters/erosions - Nikolsky sign
What is Nikolsky sign?
the epidermis shears away from the dermis when gentle lateral force is applied to the skin
What 3 investigations should be performed in a patient with a drug-induced rash?
- bloods
- urine dip
- skin biopsy
What might be seen on the bloods in someone with a drug-induced rash?
- inflammatory markers are normally raised
- check for organ dysfunction through LFTs and U&Es
red skin + raised WCC/CRP is not always infection
When is it important to do a urine dip?
this is the most important investigation in the context of a drug-induced vasculitic rash
you are looking for protein and blood (to a lesser extent) in the urine as you are concerned about glomerulonephritis
When is a skin biopsy performed?
if the rash is very severe or there is diagnostic doubt
What are general measures for management of a drug-induced rash?
STOP THE DRUG !!!
- maintain skin barrier
- bland greasy emollients (act as a barrier to replace skin barrier) 4x daily
- non-adherent dressings for painful desquamated areas
- analgesia
- monitor fluid status, electrolytes & temperature
Why is it important to prevent skin barrier failure?
the skin barrier has important functions in:
- microbial defence
- thermoregulation
- fluid balance + electrolyte balance
What may be done to treat drug rashes that are more severe?
potent topical steroids may be given
such as betnovate or mometasone
these can be used for up to a few weeks
What additional treatment may be given if there is urticaria with a drug rash?
high dose anti-histamines
What additional treatment may be used in a drug rash caused by DRESS/DHS?
potentially oral or IV steroids can be used
especially if you are worried about organ dysfunction
When might allergy testing be performed?
this is usually done if someone has many drug allergies (usually to different antibiotics) and suffers from recurrent infections
this is done to find out what is specifically causing the drug allergy
How is allergy testing performed?
using skin prick or patch testing
