Cutaneous drug reactions Flashcards
How many adverse drug reactions are cutaneous?
About 30% (3% of hospitalisations)
What are the categories of immunologically-mediated reactions?
Type I (anaphylactic reactions e.g urticaria), type II (cytotoxic reactions e.g pemphigus), type III (cell-mediated (purpura/rash), type IV (T-cell mediated delayed reaction e.g erythema/rash), not dose dependent
What are some examples of non-immunological reactions?
Eczema, drug-induced alopecia, skin erosion due to topical 5-fluorouracil, atrophy due to topical corticosteroids, psoriasis, pigmentation, cheilitis, xerosis
How do drug reactions present?
Exanthematous/morbilliform/maculopapular (75-95%), urticarial (5-10%), papulosquamous/pustular/bullous, pigmentation, itch, pain, photosensitivity
When do drug reactions normally stop?
Once drug is removed = exceptions to this rule, half life and the ability if the drug to be retained in the tissue play a role, may cross-react with similar class of drugs
What are the risk factors for drug reaction?
Age (young adults > children/elderly), gender (females > males), genetics, concomitant disease (viral infection, cystic fibrosis), immune status (previous drug reaction or positive skin test)
What are some reasons relating to their chemistry and route why drugs cause reactions?
Chemistry = beta lactam, NSAIDs, high molecular weight/hapten-forming drugs Route = topical vs oral/systemic, dose, kinetics/ half life
What is the most common type of drug reaction?
Exanthematous (90%)
What type of hypersensitivity is a exanthematous drug reaction?
Type 4 delayed reaction (T-cell mediated), normally idiosyncratic
What are some features of exanthematous drug eruptions?
Usually mild and self-limiting, widespread symmetrically distributed rash, mucous membranes usually spared, pruritus and mild fever common, can progress to life threatening reaction
How long does it take for a exanthematous reaction to occur?
Onset is 4-21 days after first taking drug
What are the indicators of a potentially severe exanthematous reaction?
Involvement of mucous membranes and face, facial erythema and oedema, widespread confluent erythema, fever (>38.5), skin pain, blisters, purpura, necrosis, lymphadenopathy, arthralgia, SOB, wheezing
What are some drugs associated with exanthematous drug reactions?
Penicillins, sulphonamides, erythromycin, streptomycin, allupurinol, NSAIDs, chloramphenicol, anti-epileptics (carbamazepine, phenytoin)
How do urticarial drug reactions normally occur?
Immediate IgE-mediated reaction after rechallenge with drug (beta lactam antibiotics, carbamazepine)
How can urticarial reactions cause an eruption on first exposure to a drug?
Direct release of inflammatory mediators from mast cells (aspirin, opiates, NSAIDs, muscle relaxants, vancomycin, quinolones)
What symptoms are commonly associated with urticarial reactions?
Angioedema and anaphylaxis
What are some forms of pustular/bullous drug eruptions?
Acneiform (glucocorticoids, androgens, lithium, isoniazid, phenytoin)
Acute generalised exanthematous pustulosis (rare, antibiotics, calcium channel blockers, antimalarials)
Vesicular/bullous reactions (range from mild to severe)
Drug induced pemphigoid (ACE inhibitors, penicillins, furosemide)
Linear IgA disease (vancomycin)
What are some features of fixed drug reactions?
Well demarcated round/ovoid plaques, red, painful, on hands/genitalia/lips (occasionally oral mucosa)
What happens to a fixed drug reaction when the drug is stopped?
Resolves with persistent pigmentation, can re-occur at same site if drug re-introduced
How can fixed drug reactions present?
Eczematous lesions, papules, vesicles or urticaria
What are some drugs associated with fixed drug reactions?
Tetracycline, doxycycline, paracetamol, NSAIDs, carbamazepine
What are some conditions caused by severe cutaneous adverse reactions?
Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
Drug reactions with eosinophila and systemic syndrome (DRESS)
Acute generalised exanthematous pustulosis (AGEP)
What are some drugs associated with toxic epidermal necrolysis?
Sulphonamides, cephalosporins, phenytoin, carbamazepine, NSAIDs, nevirapine, lamotrigine, sertraline, pantoprazole, tramadol
What are some drugs associated with drug eruptions with eosinophila and systemic syndrome?
Sulphonamides, anticonvulsants, allopurinol, minocycline, dapsone, NSAIDs, abacavir, nevirapine, vancomycin
What are the features of acute phototoxic drug reactions?
Skin toxicity (photosensitivity), systemic toxicity, photodegration
What are the features of chronic phototoxic drug reactions?
Pigmentation, photoaging, photocarcinogenesis
What kind of reaction is a phototoxic drug reaction?
Non-immunological skin reaction arising in an individual exposed to enough photoreactive drug and light of appropriate wavelengths (usually UVA/visible light), sometimes idiosyncratic
What are two systemic reasons that photosensitivity could arise?
Lupus, immunosuppression
What are some patterns of skin phototoxicity?
Exaggerated sunburn (quinine, thiazides, democlocyline)
Increased skin fragility (naldixic acid, tetracycline naproxen, amiodarone)
Immediate prickling with delayed erythema and pigmentation (amiodarone, chloropromazine)
Exposed telangiectasia (calcium channel blockers)
Delayed 3-5 days erythema and pigmentation (psoralens)
What are some drugs associated with phototoxic drug reactions?
Antibiotics (fluoroquinolones, doxycycline, demeclocycline), thiazides, chloropromazine, NSAIDs, quinine, psoralens, amiodarone, porphyrins, BRAF inhibitors (vemurafenib), immunosuppressants, antifungals (voriconazole)
What is usually enough to diagnose a drug reaction?
A detailed history and physical examination
What are some investigations that can be done to diagnose drug reactions?
Phototesting for suspected phototoxic drug reaction
Biopsies to identify the type of drug reaction and exclusion of other diseases
Patch and photopatch testing for suspected allergic contact dermatitis
Skin prick/intradermal test for specific drugs
When is skin testing not indicated for diagnosing drug reactions?
In serum sickness reactions (type III) or for T-cell mediated reactions that could potentially trigger SJS, DRESS or TEN, or for those with severe cutaneous adverse drug reactions
What are some management options for cutaneous drug reactions?
Discontinue drug if possible/use an alternative, topical corticosteroids may be useful, antihistamines may help with itch or in type I reaction, allergy bracelets may be useful for some drugs
Where should severe adverse drug effects be reported to?
The Yellow card scheme
What patient group are most likely to suffer a severe cutaneous adverse drug reaction?
Immunocompromised
