Drug eruptions

Question 1

prescription drug reaction rates

Answer 1

10 cases per 100 new users, higher with some classes of drugs- antimicrobials eastimated at 50 per 100 new users (PCN, cephalosporins, sulfonamides)

Question 2

pathogenesis of a drug eruption

Answer 2

eruption beginning within 2 weeks of a new drug, supplement, or herb should be worked up as a possible drug reaction. 2 main mechanisms- immunologic (with 4 subtypes) and non- immunologic

Question 3

non immunologic (predictable)

Answer 3

• pharmacologic side effect- dry mouth from antihistamine
• second pharmacologic- candidiadis from oral abx
• toxicity- hepatotoxicity from methotrexate
• drug interaction- seizure from theophylline from taking erythromycin
• nonimmunological activation of effector pathways- anyphylactiod reaction from radiocontrast
• overdose- excessive administration for person or condition, intentional or not inentional

Question 4

non immunologic (unpredictable)

Answer 4

intolerance- tinnitis from ASA

idiosyncrasy- hemolytic anemia from dapsone

Question 5

immunologic (unpredictable)

Answer 5

• IgE mediated- anaphylactic reaction to beta lactam abx
• cytotoxic- hemolytic anemia from PCN
• immune complex- serum sickness from tetanus antitoxin
• cell- mediated, delayed- contact dermatitis from nickel
• specific t-cell activation- exanthem from sulfonamides
• Fas/ Fas ligand induced- stevens johnsons syndrome, toxic epidermal necrolysis
• Misc- anticunvulsant hypersensitivity syndrome, Lupus- like syndrome

Question 6

vital to the diagnosis and treatment of a drug reaction

Answer 6

accurate history!

• relationship of eruption to any rx meds, OTCs, supplements, vitamins, herbals
• onset, duration, pattern of eruption
• drug hx- when it was started, dosage changes, any interruptions in therapy
• look up whether drug is associated with reactions

Question 7

most reliable way to determine the source of the eruption

Answer 7

Reintroduction- but this is dangerous and decision should not be made lightly. (Most drug eruptions will improve once the offending med is stopped)

Question 8

patterns seen in cutaneous drug eruptions

Answer 8

basically anything- acneiform, alopecia, eczema, EM, erythema nodosum, exanthems, fixed eruption, lichenoid, photosensitivity, pigmentation, PR- like, purpura seb derm- like, toxic epidermal nocrolysis, urticarial vasculitis, vesiculobullous, lupus erythematosus- like

Question 9

most common patterns seen in cutaneous drug eruptions

Answer 9

maculopapular (exanthemous eruptions, morbiliform)
urticarial
fixed drug eruptions

Question 10

Exanthems (maculopapular) drug eruption

Answer 10

• most frequent of all cutaneous reactions (often indistinguishable from viral exanthems)
• typical from ampicillin and amoxicillin but pretty much any drug
• immunocompromised pts at increased risk
• sever rxns associated with: mucous membrane involvement, blisters, facial edema, lymphadenopathy,, temp higher than 101.3

Question 11

Exanthems (maculopapular) clinical features

Answer 11

• red macules and papules that may come confluent
• distribution often symmetric, generalized (face often spared)
• can involve mucous membranes, palms, soles
• fever may be present at onset, labs can’t usually tell the diff between this and viral exanthum
• onset: 4- 21 days after start of drug
• duration: 1-3 weeks (sometimes fades even if drug isn’t stopped)
• rash clears quickly after med is stopped. May progress to generalized exfoliative dermatitis if med is continued

Question 12

urticarial drug eruption- most frequent causes

Answer 12

ASA, PCNs, blood products
(most commonly associated with penicillins and derivatives)
*caution- almost all drugs have been associated

Question 13

3 mechanisms of drug induced urticaria

Answer 13

1. immunologic histamine release:
   - IgE dependent- immediate (minutes) or accelerated (hours)
   - anaphylactic mast cell degranulation occurs within minutes of drug exposure
2. nonimmunologic histamine release
3. serum sickness

Question 14

clinical features of urticarial drug eruptions

Answer 14

itchy
erythematous plaques with edema
usually generalized and symmetrical
no scaling or vesiculation
vary in size from small papules to huge plaques
typically fade within 24 hrs, often recur in another area
angioedema- urticarial swelling of deep dermal and subq tissue and mucous membranes- life threatening

Question 15

fixed drug eruptions (FDE)

Answer 15

accounts for 25% of drug eruptions
reoccurs after each time the offending drug is administered
some reports of FDE on genitals associated with a drug taken by sexual partner

Question 16

most common causes of FDE in kids

Answer 16

sulfa drugs, tylenol and ibuprofen

Question 17

most common causes of FDE in adults

Answer 17

tetracylcines, quinone derivatives (hydrochloroquine), tartrazine (flavoring in mountain due)

Question 18

fixed drug eruptions clinical feature

Answer 18

localized or circumscribed round or oval dermatitis
start erythematous and edematous
change to dusky violaceous or brown color
numerous variants (morbilliform, EM- like, urticarial, nodular, eczematous, bullous, and scarlantinaform)
typically occurs within 2 weeks after initial exposure (expect recurrence within 24hrs of re- exposure)
most common on limb, less common on trunk
favors hands, feet, genital area

Question 19

testing for drug eruptions

Answer 19

pathology- limited usefulness, should be performed only if considering other differentials such as lupus, vasculitis, CTCL, GVHD
controlled rechallenge with offending agent- not done frequently r/t risks
other tests to consider: 1. patch testing for allergic contact dermatitis 2. radioallergosorbent test (RAST) “prick” test (difficult to determine what allergens to test) 3. serum tryptase levels 4. immunoassays for drug specific antibody isotypes