Cutaneous drug reactions

Question 1

How many adverse drug reactions are cutaneous?

Answer 1

About 30% (3% of hospitalisations)

Question 2

What are the categories of immunologically-mediated reactions?

Answer 2

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

Question 3

What are some examples of non-immunological reactions?

Answer 3

Eczema, drug-induced alopecia, skin erosion due to topical 5-fluorouracil, atrophy due to topical corticosteroids, psoriasis, pigmentation, cheilitis, xerosis

Question 4

How do drug reactions present?

Answer 4

Exanthematous/morbilliform/maculopapular (75-95%), urticarial (5-10%), papulosquamous/pustular/bullous, pigmentation, itch, pain, photosensitivity

Question 5

When do drug reactions normally stop?

Answer 5

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

Question 6

What are the risk factors for drug reaction?

Answer 6

Age (young adults > children/elderly), gender (females > males), genetics, concomitant disease (viral infection, cystic fibrosis), immune status (previous drug reaction or positive skin test)

Question 7

What are some reasons relating to their chemistry and route why drugs cause reactions?

Answer 7

Chemistry = beta lactam, NSAIDs, high molecular weight/hapten-forming drugs
Route = topical vs oral/systemic, dose, kinetics/ half life

Question 8

What is the most common type of drug reaction?

Answer 8

Exanthematous (90%)

Question 9

What type of hypersensitivity is a exanthematous drug reaction?

Answer 9

Type 4 delayed reaction (T-cell mediated), normally idiosyncratic

Question 10

What are some features of exanthematous drug eruptions?

Answer 10

Usually mild and self-limiting, widespread symmetrically distributed rash, mucous membranes usually spared, pruritus and mild fever common, can progress to life threatening reaction

Question 11

How long does it take for a exanthematous reaction to occur?

Answer 11

Onset is 4-21 days after first taking drug

Question 12

What are the indicators of a potentially severe exanthematous reaction?

Answer 12

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

Question 13

What are some drugs associated with exanthematous drug reactions?

Answer 13

Penicillins, sulphonamides, erythromycin, streptomycin, allupurinol, NSAIDs, chloramphenicol, anti-epileptics (carbamazepine, phenytoin)

Question 14

How do urticarial drug reactions normally occur?

Answer 14

Immediate IgE-mediated reaction after rechallenge with drug (beta lactam antibiotics, carbamazepine)

Question 15

How can urticarial reactions cause an eruption on first exposure to a drug?

Answer 15

Direct release of inflammatory mediators from mast cells (aspirin, opiates, NSAIDs, muscle relaxants, vancomycin, quinolones)

Question 16

What symptoms are commonly associated with urticarial reactions?

Answer 16

Angioedema and anaphylaxis

Question 17

What are some forms of pustular/bullous drug eruptions?

Answer 17

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)

Question 18

What are some features of fixed drug reactions?

Answer 18

Well demarcated round/ovoid plaques, red, painful, on hands/genitalia/lips (occasionally oral mucosa)

Question 19

What happens to a fixed drug reaction when the drug is stopped?

Answer 19

Resolves with persistent pigmentation, can re-occur at same site if drug re-introduced

Question 20

How can fixed drug reactions present?

Answer 20

Eczematous lesions, papules, vesicles or urticaria

Question 21

What are some drugs associated with fixed drug reactions?

Answer 21

Tetracycline, doxycycline, paracetamol, NSAIDs, carbamazepine

Question 22

What are some conditions caused by severe cutaneous adverse reactions?

Answer 22

Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
Drug reactions with eosinophila and systemic syndrome (DRESS)
Acute generalised exanthematous pustulosis (AGEP)

Question 23

What are some drugs associated with toxic epidermal necrolysis?

Answer 23

Sulphonamides, cephalosporins, phenytoin, carbamazepine, NSAIDs, nevirapine, lamotrigine, sertraline, pantoprazole, tramadol

Question 24

What are some drugs associated with drug eruptions with eosinophila and systemic syndrome?

Answer 24

Sulphonamides, anticonvulsants, allopurinol, minocycline, dapsone, NSAIDs, abacavir, nevirapine, vancomycin

Question 25

What are the features of acute phototoxic drug reactions?

Answer 25

Skin toxicity (photosensitivity), systemic toxicity, photodegration

Question 26

What are the features of chronic phototoxic drug reactions?

Answer 26

Pigmentation, photoaging, photocarcinogenesis

Question 27

What kind of reaction is a phototoxic drug reaction?

Answer 27

Non-immunological skin reaction arising in an individual exposed to enough photoreactive drug and light of appropriate wavelengths (usually UVA/visible light), sometimes idiosyncratic

Question 28

What are two systemic reasons that photosensitivity could arise?

Answer 28

Lupus, immunosuppression

Question 29

What are some patterns of skin phototoxicity?

Answer 29

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)

Question 30

What are some drugs associated with phototoxic drug reactions?

Answer 30

Antibiotics (fluoroquinolones, doxycycline, demeclocycline), thiazides, chloropromazine, NSAIDs, quinine, psoralens, amiodarone, porphyrins, BRAF inhibitors (vemurafenib), immunosuppressants, antifungals (voriconazole)

Question 31

What is usually enough to diagnose a drug reaction?

Answer 31

A detailed history and physical examination

Question 32

What are some investigations that can be done to diagnose drug reactions?

Answer 32

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

Question 33

When is skin testing not indicated for diagnosing drug reactions?

Answer 33

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

Question 34

What are some management options for cutaneous drug reactions?

Answer 34

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

Question 35

Where should severe adverse drug effects be reported to?

Answer 35

The Yellow card scheme

Question 36

What patient group are most likely to suffer a severe cutaneous adverse drug reaction?

Answer 36

Immunocompromised