Drug Reactions Flashcards
Drug Reactions
Cutaneous reactions to drugs occur in up to 8% of hospitalized patients
The 2 most common cutaneous drug reactions are:
Morbilliform/exanthematous eruption
Urticaria
Vary in severity
Trivial to life threatening
Can be :
Expected: penicillin common
Sporadic
Epidemiology– Risk Factors
Women > men Elderly Immunosuppression Number of Drugs Genetic Predisposition
Primary drugs in hospitalized patients: penicillins, sulfonamides, NSAIDS
Mechanism of Drug Reactions
Type 1 IgE dependent drug reactions: • urticaria, angioedema, anaphylaxis
Type 2 Cytotoxic drug-induced
reactions• pemphigus and thrombocytopenia/purpura
Type 3 Immune complex • Vasculitis, serum sickness
Type 4 Delayed Hypersensivity –
most common
• exanthem, fixed and lichenoid drug
Non-immune • overdose, drug interactions
Idiosyncratic • DRESS, drug induced lupus (bad luck)
Basics of Cutaneous Drug
Reactions—Things to consider
Consider ALL drugs as a potential cause of a skin reaction
Prescribed medications, OTC, herbals, etc…
Other helpful clues:
Appearance (symmetric? bullous? Mucous membranes involved?)
Timing relative to drug initiation
Biopsy results
(Allergy testing is of very limited value and generally not recommended)
patch testing better for delay type 4 hypersens
Always document drug reactions in the patient’s chart with the medication and description of the reaction
Timing
Immediate reactions < 1 hour from the last administered dose Examples: urticaria, angioedema, anaphylaxis
Delayed reactions > 1 hour and usually > 6 hours from last administered dose •Occasionally weeks to months after the start of administration Examples: morbilliform eruptions, fixed drug eruption, SJS, TEN, vasculitis
drug historiy
7 I’s
Drug timeline:
Start with the onset as day 0, and work
backwards and forwards
recent hours to weeks
Instilled (eye drops, ear drops)
Inhaled (steroids, beta adrenergic)
Ingested (capsules, tablets, syrup
Intermittent (patients may not reveal medications they take on an intermittent basis unless specifically asked)
Inserted (suppositories)
Incognito (herbs, nontraditional medicine, homeopathic, vitamins, over-the-counter)
Injected (IM, IV)
Exanthematous Drug Eruptions
One of the most common cutaneous drug reaction presentations
Type 4 hypersensivity reaction
“Morbilliform” – refers to rashes that resembles measles
Usually develops 7-14 days after starting a new medication
Most often penicillins, sulfonamides, cephalosporins, anticonvulsants
Begins on trunk and upper extremities becomes confluent
“maculopapular rash”
Mucous membranes spared - no mucous mem involvement
Pruritus and low grade fever
Exanthematous Drug Eruptions
DDx
Viral exanthem - virus more common in peds
very similar morphologically
Often lack peripheral eosinophilia
Most commonly seen in the pediatric population
DRESS - severe facial edema
facial edema
TEN/SJS
mucous membranes involved, annular lesions
Treatment is supportive
Stop the offending agent!!
Topical steroids for symptom relief and vasoconstriction
Resolves within 2 weeks without any complications or sequelae
Drug-induced Urticaria
Type 1 hypersensivity reaction mediated by IgE antibodies
Erythematous and edematous papules and plaques with pruritus
Appear within minutes to days of drug administration
Antibiotics (penicillins, cephalosporins)
Duration of individual lesions is less than 24 hrs
(move around the body)
Urticarial vasculitis lesions last longer than 24 hrs
Acute urticaria <6 weeks
Chronic urticaria > 6 weeks
Angioedema – subcutaneous swelling of the skin or mucosa (eyelids, lips, oropharynx - more serious if airway)
Stop the culprit drug
Consider antihistamines
steroids if itchy
Vasculitis
inflammation and immune complex deposition and actual destruction of some of these
blood vessels under the surface of the skin
Small vessel vasculitis (type 3 reaction, due to immune deposition): Can involve medium sized vessels
Numerous underlying
causes for vasculitis: Idiopathic 50% ofases, Infections (URTI, strep…) 20%, Drugs 15%
Vasculitis
presentation
Clinically: Non blanchable palpable purpura typically on lower extremities Urticaria-like lesions Hemorrhagic blisters
Systemic symptoms: fever, myalgia, headache
Presents within: 7 to 21 days of drug administration
Common drugs: Allopurinol
NSAIDS (oral and topical),
OCPs Antibtiotics (Penicillins, Cephalopsorins, Sulfonamides)
Drug-induced vasculitis
treatment
Stop culprit drug
Topical steroids
Systemic corticosteroids for systemic involvement
Of minimal benefit for localized cutaneous disease
Rule out Kidney and GI involvement
Always do urine analysis and creatinine in anyone
suspected of having vasculitis
AGEP/
Acute Generalized Exanthematous Pustulosis
causes
tx
90% of cases are drug induced Antibiotics (penicillins, cephalosporins, clindamycin) calcium channel blockers, Antimalarials
tx:
Withdraw culprit drug
Topical steroids
Antipyretics
AGEP/
Acute Generalized Exanthematous Pustulosis
presentationton
Arises within 4 days of drug initiation
Small non-follicular sterile pustules within areas of
erythema
Lesions start on face or intertriginous zones
Can get purpura, vesicles, bullae
Mucous membrane involvement in 50% of cases
17% of patients get systemic involvement (liver
and kidney > lung, shown by high WBC count)
Marked leukocytosis
elevated neutrophils and eosinophils
Occasionally hypocalcemia and transient
renal dysfunction
Lesions typically last for 1-2 weeks followed by superficial desquamation
DRESS
Drug reaction with eosinophilia and
systemic symptoms
causes
Drug reaction with eosinophilia and systemic symptoms Common perpetrators: Anticonvulsants (phenytoin, carbamazepine, phenobarbital) Antibiotics (dapsone, sulfonamides, minocycline) Antiretrovirals Allopurinol NSAIDs
DRESS
presentation
There are diagnostic scoring systems for DRESS
RegiSCAR
J-SCAR
Clinically: Develops 2 to 6 weeks after the drug was started Edema of the face – hallmark of DRESS Fever, exanthem, +/- arthralgia Prominent eosinophilia Hepatitis is responsible for most deaths from DRESS (10% mortality) Can also develop: myocarditis, pneumonitis, nephritis, thyroiditis
DRESS Treatment
Stop the culprit drug
Most cases require prolonged treatment with systemic corticosteroids
Slow taper over several weeks or even months
Longterm sequelae: Thyroiditis Monitor TSH and T4 at 3mos, 1 yr, and 2 yrs post reaction Pancreatitis Type I diabetes mellitus Chronic exfoliative dermatitis
Fixed drug eruption (FDE)
causes
Common perpetrators:
Tetracyclines
Sulfonamides
NSAIDs
Pseudoephedrine – associated with non-pigmented fixed drug eruption
This is likely a localized type IV hypersensitivity
Fixed drug eruption (FDE)
pres
Peculiar and uncommon reaction
One or a few lesions occur in the same (fixed) site(s) with each subsequent exposure to a drug.
Oval erythematous or dusky red plaques
Classically a dusky, violaceous hue (non-pigmented fixed drug eruption exists)
Can be widespread (generalized fixed drug eruption).
Common areas of involvement: (unusal distribution comp other rashes)
Acral surfaces
Face/lips
Genitals
Bullous Pemphigoid
easy to burst
presentation
Most common autoimmune subepidermal blistering disease
Most commonly affects patients > 60 years old
If the patient is < 60 yo consider a drug induced variant!
Clinically:
Intensely pruritic eruption
Widespread TENSE blister formation (differentiates from pemphigus which typically has
flaccid blisters)
can become flaccid if pricked or pressured
Bullous Pemphigoid
Common perpetrators: Furosemide ACE-inhibitors NSAIDs Antibiotics Sitagliptin
BP Treatment
If suspected to be drug-induced, discontinue
offending agent
Call dermatology for more rapid assessment
Ultrapotent Topical Steroids
Systemic steroids very slow taper over 6 months!
0.5-1mg/kg
Steroid sparing agents
Methotrexate, azathioprine, mycophenolate mofetil
Stevens-Johnson Syndrome
and Toxic Epidermal Necrolysis
serious
presentation
Rare, potentially fatal drug reactions that exist on a
spectrum
Characterized by:
mucocutaneous tenderness
Positive Nikolsky sign
Skin fragility and erosion/necrosis
Skin lesions typically arise first on palms and soles
Involvement of oral, genital, ocular mucosa, esophageal, respiratory tract
TEN and SJS usually occur 7-21 days after
initiation of the responsible drug
Classified based on epidermal detachment:
SJS <10% body surface area (BSA) epidermal detachment
SJS-TEN overlap : 10-30% BSA involvement
TEN >30% BSA epidermal detachment
Stevens-Johnson Syndrome
and Toxic Epidermal Necrolysis
causes
Allopurinol Antibiotics (penicillins, cephalosporins, sulfonamides, quinolones) Antiretroviral medications Anticonvulsants
Stevens-Johnson Syndrome
and Toxic Epidermal Necrolysis
tx
Treatment:
Discontinue the offending medication
Reduces risk of death by 30% per day
Debated Cyclosporine(~7 days) Etanercept 50mc SC x 1 dose IVIg Systemic corticosteroids
current thinking that cyclo or etan can give best outcome
Involve ophtho, urology, wound care,
ICU
Quick note on erythema multiforme vs SJS/TEN
erythema multiforme: you can have somewhat again targetoid
appearing lesions you’re not going to get them so much on palms and souls and again you’re not going to get that mucosal membrane involvement and patients are generally going to be a lot more well
Phototoxic Reactions
exagg sun burn rxn due to meds and made wourse in sun (eg. tetracyc)
can be:
- Idiopathic
- Secondary to endogenous substances (porphyrins as in porphyrias)
- Secondary to exogenous substances (medications)
There are 2
major types of
photosensitivity
reactions:
- Phototoxic reactions - most common
- Appears identical to a sunburn
- Involves sun-exposed sites only
- Secondary to tetracyclines, NSAIDs, thiazide diuretics
•Photoallergic reactions
•Secondary to a cell-mediated hypersensitivity to an allergen activated or
produced by the effect of light on a drug
•Typically appears more eczematous
•Can result in a chronic dermatitis
•Involves both sun-exposed and non-sun exposed sites
•Secondary to quinolones, sulfonamides, antimalarias, TCAs
phototoxic tx
- Discontinue the offending agent
- Topical corticosteroids
- Sun protection
PEARLS
The most common cutaneous drug reactions are:
Morbilliform eruption
urticaria
Vasculitis
palpable purpura; rule out internal organ involvement
DRESS
edema of the face, systemic features
AGEP
hundreds of sterile pustules
Fixe drug eruption
recurrent violaceous oval plaque, same site on multiple occasions (everytime they take NSAID its same spot)
Bullous pemphigoid
pruritic, tense blisters in the elderly; if < 6o yo, consider drug-induced BP
SJS/TEN
atypical targets, painful skin, mucosal involvement, positive Nikolsky sign
Most drug reactions do not follow the textbooks, there can be overlap amongst them
