Cutaneous Drug Eruptions Flashcards
Skin eruption is one of the most common adverse drug reactions - T/F?
True - About 30% of adverse drug reactions are cutaneous
What is the range of severity of cutaneous drug reactions?
Wide range which mimic a wide variety of skni conditions from a mild rash to life threatening toxic epidermal necrolysis
What are the two main types of adverse cutaneous drug reactions ?
- Immunologically-mediated reactions (“allergic”)
- Non immunologically mediated reactions (“non-allergic”)
Give some examples of Immunologically-mediated reactions (“allergic”)
- 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
Give some examples of Non immunologically mediated reactions (“non-allergic”)
- Eczema
- Drug-induced alopecia
- Phototoxicity
- Skin erosion or atrophy from topically applied 5-fluorouracil or steroids
- Psoriasis
- Pigmentation
- Cheilitis, xerosis
Which of the two main types of adverse drug reactions are affected by the dose of drug given ?
Immunologically mediated - is not affected by dosage
Non-immunologically mediated - can be affected by the dosage
In what patients should you consider an cutaneous drug reaction ?
Any patient who is taking medication and develops a symmetric skin eruption of sudden appearance.
What are some of the risk factors for the development of drug eruptions ?
•Age
Young adults>infants/elderly
•Gender
–Females>males
- Genetics
- Concomitant disease
–Viral infections (HIV/EBV/CMV); cystic fibrosis
Previous drug reaction or positive skin test
•Chemistry
–Β-lactam compounds, NSAIDs
–High molecular weight/hapten-forming drugs
What is the most common drug eruption?
Exanthematous Drug Eruptions (90%)
What specific type of drug eruption is an exanthematous drug eruption?
T-cell mediated delayed type hypersensitivity (Type IV) reaction.
What are the signs and symptoms of Exanthematous Drug Eruptions?
- Usually mild & self limiting but can priogress to life-threatening reaction
- Widespread symmetrically distributed rash which usually appears on the trunk & the spreads to the limbs & neck
- Rash consists of pink-red flat macules or papules
- Lesions mostly blanch with pressure
- Mucous membranes, hair & nails are not affected
- Pruritus (itch) is common.
- Mild fever is common.
- Onset is 4-21 days after first taking drug.
What is shown in the pic ?
Exanthematous drug reaction
What are the clinical indicators for a severe exanthematous drug reaction?
- Involvement of mucous membrane and face.
- Facial oedema & erythema.
- Widespread confluent erythema.
- Fever (>38.5⁰C).
- Blisters, purpura, necrosis.
- Lymphadenopathy, arthalgia.
- Shortness of breath, wheezing.
Give some examples of the drugs associated with exanthematous drug eruptions
Most common drugs:
- Beta-lactam antibiotics (penicillins, cephalosporins)
- Sulfonamides
- Allopurinol
- Anti-epileptic drugs
- NSAID’s
Note many others can cause it
What is the 2nd most common adverse drug reaction ?
Drug-induced acute urticaria
What is drug-induced acute urticaria ?
Drug-induced urticaria is the term used when urticaria is caused by a drug, most often penicillin, a non-steroidal anti-inflammatory agent (NSAID), or sulfamethoxasole in combination with trimethoprim
What are the clinical features of drug-induced acute urticaria ?
The clinical features and treatment for drug-induced urticaria are identical to those for urticaria not related to drugs:
- Red patches & weals on the surface of the skin
- Usually very itchy & may have a burning sensation
- Pain & tenderness uncommon
- Can affect any skin site & tends to be distributed widely, weals shape is variable - may be round, form rings, map-like, target like lesion or form giant patches
How quickly does drug-induced urticaria usually come on ?
Usually occurs within 36hr but may develop within minutes on re-challenge
What are Pustular/Bullous drug eruptions?
Adverse drug reactions that result in fluid-filled blisters or bullae
What are the different Pustular/Bullous drug eruptions? and give examples of drugs which cause them
Acne - Glucocorticoids, Androgens (therapeutic), lithium, isoniazid, phenytoin
Acute generalised exanthematous pustulosis (AGEP) - Antibiotics, calcium channel blockers, antimalarials
Drug-induced bullous pemphigoid - ACE inhibitors, penicillin, furosemide
Linear IgA disease - Vancomycin
What is meant by fixed drug eruptions ?
Fixed drug eruptions (FDEs) characteristically recur in the same site or sites each time a particular drug is taken; with each exposure however, the number of involved sites may increase. Fixed drug eruption is a type of allergic reaction
Describe the presentation of fixed drug eruptions
- Well demarcated round/ovoid plaques of redness & swelling which are painful.
- Sometimes plaques are surmounted by a blister
- Hands, genitalia, lips common sites. Occasionally oral mucosa.
- Resolves with persistent pigmentation when the drug is stopped.
- Can re-occur on the same site on re-exposure to the drug.
- Usually mild when restricted to a single lesion.
- Can present as eczematous lesions, papules, vesicles or urticaria.
What are some of the drug associated with fixed drug eruptions ?
- NSAIDS
- Paracetamol
- Carbamazepine
- Tetracycline, doxycycline
How quickly do fixed drug eruptions occur ?
- lesions develop 1 to 2 weeks after a first exposure.
- May persist for years and only re-appear after drug exposure at exact same area within 24 hours
What is shown in this pic ?
A fixed drug eruption
What is Stevens-Johnson syndrome and what is it caused by?
A form of toxic epidermal necrolysis, is a life-threatening skin condition, in which cell death causes the epidermis to separate from the dermis.
Usually caused by an unpredictable adverse reaction to certain medications e.g:
- allopurinol
- carbamazepine
- NSAIDS
What is Drug reaction with eosinophilia and systemic symptoms (DRESS)?
Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) is caused by exposure to certain medications that may result in a rash, fever, inflammation of internal organs, lymphadenopathy, and characteristic hematologic abnormalities such as eosinophilia, thrombocytopenia, and atypical lymphocytosis
What is acute generalized exanthematous pustulosis AGEP?
Acute generalized exanthematous pustulosis (AGEP) (also known as “Pustulardrug eruption,” and “Toxic pustuloderma”) is a rare cutaneous reaction pattern that in 90% of cases is related to medication administration, characterized by a sudden eruption that appears on average five days after the medication is started
What is drug-induced photosensitivity ?
Drug-induced photosensitivity occurs when certain photosensitising medications cause unexpected sunburn or dermatitis (a dry, bumpy or blistering rash) on sun-exposed skin (face, neck, arms, backs of hands and often lower legs and feet). The rash may or may not be itchy
What are the common causes of drug-induced photosensitivity?
- quinine, thiazide
- Abx’s
- Retinoids
- Diuretics
- NSAID’s
- Hypogylcaemics
- Anti-psychotics
What is erythema nodosum ?
An inflammatory disorder affecting subcutaneous fat. It presents as tender red nodules on the anterior shins.
Who is erythema nodosum most common in ?
Can affect anyone but most common in women aged 25-40
What are the causes of erythema nodosum ?
- Infection - throat (streptococcal or viral), TB, leprosy etc
- Systemic disease - sarcoidosis, IBD, Behcet’s
- Malignancy/lymphoma
- Drugs - penicillins, sulphonamides, COCP
- Pregnancy
- Idiopathic
What are the clinical features of erythema nodosum ?
- Discrete tender nodules which may become confluent
- Lesions continue to appear for 1-2 weeks and leave bruise like discolouration as they resolve
- Lesions are warm, oval, round or bow shaped
- Lesions do not ulcerate & resolve without atrophy or scarring
- The shins are the most common site
What is shown in this pic ?
Erythema nodosum
What is the clinical course of erythema nodosum?
Usually resolves spontaneously
What is shown in this pic ?
Drug-induced erythema multiforme - pic shows characteristic target lesions
Define what vasculitis is & specifically what small vessel vasculitis is
- Vasculitis is a disorder in which there are inflamed blood vessels. These may include capillaries, arterioles, venules and lymphatics.
- Small vessel vasculitis is the most common form of vasculitis affecting arterioles and venules.
Define what cutaneous vasculitis is
- Cutaneous vasculitis is a group of disorders in which there are inflamed blood vessels in the skin. Presenting as purpura.
- It may be due to - idiopathic/primary, or secondary to infection, drug or disease
- In a minority of patients cutaneous vasculitis is associated with systemic (small, medium & large vessel vasculitis) However, n most cases, an underlying cause is not found and the disease is self-limiting.
What is cutaneous vasculitis due to a known drug or infection called?
Hypersensitivity vasculitis
What are the clinical features of cutaneous vasculitis ?
- Prominent involvement of lower legs with fewer lesions on proximal sites
- Palpable purpura (purple, non-blanching papules and plaques)
- Sometimes, petechiae and ecchymoses
- Haemorrhagic bullae, necrosis and superficial ulceration
- Local pruritus, burning pain and swelling
List some of the common drug causes of hypersensitivity vasculitis
Allopurinol, amiodarone, NSAIDs, thiazide, penicillins, sulphonamides, hydralazine
What is key to exclude when someone presents with cutaneous vasculitis ?
Systemic vasculitis
What is shown in this pic?
Drug induced erythroderma - widespread erythema (>90%) associated with exfoliation (skin peeling off in scales or layers) seen
What is shown in this pic?
Lichenoid drug eruption
What is the main different between typical bullous phemphigoid and drug-induced bullous phemphigoid ?
Patients tend to be younger than in typical bullous pemphigoid.
List some of the common causes of drug-induced bullous phemphigoid
- Furosemide, penicillamine, penicillin, sulphasalzine
- Captopril, gold
Note - clinical features are the same as typical bullous phemphigoid
What is shown in this pic and list the common causes
Drug-induced hyperpigmentation = blue-grey or dark brown pigmentation affecting the skin
common causes include:
- Minocycline
- Chlorpromazine
- NSAID’s
- Heavy metals
- Anti-psychotics
- Tetracyclines
- Amidoarone
What are the investigations carried out when suspecting a drug eruption?
Usualy physcial examination and history is enough but in less clear situations:
Phototesting done for suspected phototoxic drug reactions
Biopsies may be useful for identifying the type of drug reaction and exclusion of other diseases.
Patch and photopatch tests - Eg. for suspected allergic contact dermatitis (Type IV)
Skin prick/intradermal tests for specific drugs - Eg. for suspected allergic reactions (Type I)
Why is skin testing not indicated for serum sickness reactions (Type III) or for T-cell mediated reactions (Type IV)?
As they can cause SJS, TEN & DRESS, also not indicated for those with severe cutaneous adverse drug reactions
What is the management for drup eruptions?
- Discontinue the drug (if possible). Use an alternative.
- Topical steroids may be useful.
- Antihistamines may be useful.
- Allergy bracelets are useful for some drugs.
- Drug eruptions should be reported via the Yellow Card scheme (Medicines and Healthcare products Regulatory Agency).
Appreciate the summary of this lecture
- Cutaneous drug eruptions are common.
- Presentation can mimic other diseases.
- They affect quality of life, can trigger unnecessary investigations and can be life-threatening (SJS/TEN).
- Some infections/diseases increase the risk of drug eruptions.
- A detailed history is critical, especially if investigations are to be performed
