Drug Reactions and Blistering Disorders Flashcards
What are the characteristics of most cutaneous drug reactions?
inflammatory
generalized
symmetric
What are the most common and important types of adverse drug reactions?
exanthematous
drug-induced hypersensitivity syndrome (DIHS), also called Drug-related eosinophilia with systemic symptoms (DRESS)
epidermal necrolysis - Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis (TEN)
immediate drug-induced skin reactions
occur less than 1 hour of the last adminstered dose
- urticaria
- angioedema
- anaphylaxis
delayed drug-induced reactions
occurs after one hour, but usually more than 6 hours (and occasionally weeks to months after the start of administration)
- exanthematous eruptions
- fixed drug eruption
- systemic reactions (DRESS, SJS, TEN)
- vasculitis (may also be systemic)
What is the use of allergy testing for drug reactions?
limited value in evaluating adverse cutaneous rections to medications
penicillin is the exception - skin testing is the preferred method of evaluation of possible type I, IgE-mediated penicillen allergy (urticaria)
What are the important questions in a drug history?
seven I’s:
1) instilled (eye drops, ear drops)
2) inhaled (steroids, beta adrenergic)
3) ingested (capsules, tablets, syrup)
4) inserted (suppositories)
5) injected (IM, IV)
6) incognito (herbs, non-traditional medicine, homeopathic, vitamins, over-the-counter)
7) intermittent (patients may not reveal medications they take on an intermittent basis unless specifically asked)
What are the uses of a drug timeline?
most important data in determining if a rash is meidcation-related
start with onset of the rash as Day 0, and work backwards and forwards
for exanthematous drug eruptions, the initiation of the medication is often 7-10 days before the rash (may be much shorter for repeate exposrues)
What are some risk factors for drug reactions?
female
prior history of drug reaction
recurrent drug exposure
HLA type
certain disease state (EBC - aminopenicillins, HIV - sulfonamides)
exanthem
a rapidly erupting rash that may have specific diagnostic features of an infectious disease
usually referring to the rashes seen with viral/coccal infections
What are the classic diseases with exanthematous rashes?
chickenpox
measles
roseola infantum
rubella
What is the classic progression of measles?
starting on head, spreading down the body “like a can of pain would”
What is the exanthem characteristic of roseola infantum?
caused by HHV 6
starts with high fever and often ends abruptly
happens about the same time as a pinkish-red flat or raised rash that appears on the trunk and spreads over the body
exanthematous drug eruption
most common of all cutaneous drug eruptions
limited to the skin
lesions intially appear on the trunk and spread centrifugally to the extremities in a systemic fashion
erythematous macules and papules
pruritis and mild fever may be present
skin lesions usually appear more than 2 days after the drug has been started, mainly around 7-10, and occasionally persists 2-3 dys after havving stopped the drug
What is the clinical course and treatment of exthematous reactions?
resolves in a few days to a week after the medication is stopped
can continue the medication if the eruption is not too severe, but use with caution
resolves without sequelae (though scaling/desquamation can occur)
treatment consists of topical steroids, oral antihistamines, and reassurance
What is Drug-Induced Hypersensitiviety Syndrome?
also known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
skin eruption with systemic symptoms (ex. fever) and internal organ involvement
more than 70% of patients have an eosinophilia
What are the typical signs and symptoms of Drug-Induced Hypersensitivity Syndrome?
macular exanthem
erythematous centrofacial swelling
fever
malaise
lymphadenopathy
involvement of other organs such as liver or kidney
What is the clinical course of DRESS?
signs and symptoms typically begin in the 3rd week after starting the mediction or increasing dose
signs and symptoms may persist and recur for many weeks even after cessation of drug treatment
fatality rate may be up to 10%
medications implicated in DRESS
allopurinol
antibiotics
anti-TB drugs
anticonvulsants
NSAIDs
Anti-HIV drugs
What is the approach to the patient with suspected DRESS?
stop (or substitute) all suspect medications and discontinue non-essential medications
What is the treatment for DRESS?
stop medication if severe
also use systemic sterids if severe - gradually taper
if not, use topical steroids and systemic antihistamines
What is erythema multiforme?
self-limited but potentially recurrent disease
abrupt onset of papular “target” lesions, with vast majority of lesions appearing within 24 hours
target lesions favor acrofacial sites
erythema multiforme minor
papular target lesions with little or no mucosal involvement and no systemic symptoms
erythema multiforme major
papular target lesions with severe mucosal involvement and systemic features
What are the most common precipitating factors of erythema multiforme?
preceding HSV or mycoplasma pneumoniae infections are the most common precipitating factors
NOT usually a drug reaction
erythema multiforme does not carry the risk of progression to toxic epidermal necrolysis
What reactions are included in the Epidermal Necrolysis Spectrum?
Stevens-Johnson Syndrome (SJS)
Toxic Epidermal Necrolysis (TEN)
What is Stevens-Johnson Syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN)
differing levels of severity
characterized by mucocutaneous tenderness and erythema as well as extensive skin erosion
acute life-treatening mucocutaneous reactions
extensive necrosis and detachment of the epidermis and mucosal surfaces
these two conditions represent an identical process but differ in severity based on body surfce area (BSA) that is involved
What is the major distinction between SJS and TEN?
SJS < 10% body surface covered
SJS-TEN overlap 10-30%
TEN >30% body surface covered
What is the mortality rate for SJS/TEN?
1-5% for SJS
>20% for TEN
for TEN, increasing age, signficant comorbid conditions, and greater extent of skin invovlement correlate with poor prognosis
What are the medications most frequently associated with SJS/TEN?
up to 20% remain idiopathic
over 100 different drugs:
Sulfa antibiotics, Sulfasalazine
Anticonvulsants (carbamazepine, lamotrigine, phenobarbital, phenytoin)
Tetracyclines/Thiacetazone
Allopurinol
NSAIDs/Nevirapine
What is the pathophysiology of SJS-TEN?
usually occurs 7-21 days after initiation of responsible drug
erosion due to extensive death of keratinocytes via apoptosis
mediated by interaction of the death receptor-ligand pair Fas-FasL
What is involved in the management of SJS and TEN?
early diagnosis
immediate discontinuation of the causative drug
supportive care (IV-Ig may have the potential to selectively block keratinocyte apoptosis)
What are the clinical findings of SJS/TEN?
findings begin 8 weeks post drug exposure - systemic findings preceed mucocutaneous lesions by 1-3 days
eruption is initially symmetric and distribution on the face, upper trunk, and proximal extremities, can rapidly extend ot the rest of the body
What are the characteristics of the initial skin lesions in SJS/TEN?
initial skin lesions characterized by erythematous, irregularly shapedd, dusky red to purpuric macules (atypical targets), which progressively coalesce
dark center of atypical target lesions may blister
mucous membrane involvement can precede skin eruption
What are specific skin findings for SJS?
atypical target lesions
dusky apperance
mucous membrane involvement
What are characteristic skin findings of TEN?
tender/painful skin
extensive sloughing
What are SJS/TEN complications?
corneal damage (consult ophthalmologist)
fluid and electrolyte problems
nutrition problems
secondary infection (bacteremia, spesis)
What is the treatment for SJS/TEN?
early recognition and withdrawal of the offending drug(s) and supportive care
consult dermatology at earliest moment of concern for SJS or TEN
care should proceed in a burn unit for patients with >25-30% BSA involvement
immediately consult opthalmology if there is ocular involvement
What are systemic features that warn of a potentially severe drug reaction?
fever and/or other symptoms of internal organ involvement such as pharyngitis, malaise, arthralgia, etc.
lymphadenopathy
What are the cutaneous clinical features that warn of potentially severe drug reaction?
evolution to erythroderma
prominent facial involvement +/- edema or swelling
mucous membrane involvement (particularly if erosive or involving conjunctiva)
skin tenderness, blistering, or shedding
purpura
Why do cells separate from one another?
edema/spongiosis/hydrostatic pressure - acute eczema, stasis pressure
acantholysis - pemphigus
cellular degeneration - viral infections (HSV), EM/SJS/TEN, sunburns
cytolysis - friction blister, hereditary mechanobullous disorders
keratinocyte-keratinocyte or basement membrane disruption - immunobullous disorders
What are the key features of intraepidermal vs. subepidermal blisters?
intraepidermal - flaccid and easily broken
subepidermal - tense and usually intact
“nikolsky sign”
epidermal separation by lateral pressure to edge of blister or to normal appearing skin = characteristic for intraepidermal blisters
What is dermatitis herpetiformis?
puritic papulovesicles or excoriated papules on extensor surfaces, buttocks, and back
caused by neutrophilic infiltration of the dermal papillae with vesicle formation at the dermal-epidermal junction
there is granular deposition of IgA in the dermal papillae of clinically normal-appearing skin adjacent ot a lesion
What diseases are associated with dermatitis herpetiformis?
gastric atrophy, thyroid disease, small bowel lymphoma
What is the treatment for dermatitis herpetiformis?
gluten-free diet, dapsone
What is the difference between pemphigus and pemphigoid?
pemphigoid is under the epidermis
pemphigus is within the epidermis
What is pemphigus vulgaris?
autoantibodies to desmogleins resulting in deep bullae and erosions
pemphigus foliaceous is more superficial than p vulgaris
usually found in the elderly
diagnose with direct immunofluorescence
What is the pathophysiology of pemphigus vulgaris?
5th/6th decade
flaccid, easily rupture bullae on the skin and mucous membranes (oral lesions appear first in 60% of cases
immunofluorscence shows IgG to Dsg3 (+/-) Dsg1
death from sepsis in 10%
What are drugs that can induce pemphigus vulgaris?
penicillamine and captopril
What is the treatment for pemphigus vulgaris?
immunosuppression - Prednisone, Imuran, Rituximab
What is bullous pemphigoid?
autoantibodies to hemidesmosomes, resultin gin deep, tense bullae
usually found in the elderly
What is the pathophysiology of bullos pemphigooid?
onset is 60s-70s
large, tense bullae, flexural, oral 20%
subepidermal split
presence of IgG and C3 on the basement membrane with staining
What is the treatment for bullous pemphigoid?
predinisone
azathioprine
tetracycline
dapsone
What is prophyria cutanea tarda (PCT)?
porphyrins absorb UV lightly intensely in the Soret band (400-410nm)
cutaneous manifestation include:
- photosensitivity
- skin fragility
- possible blistering
- erosions
- crust
- milia and scar in sun-exposed sites
What is the pathophysiology of PCT?
results from a decreased catalytic activity of uroporphyrinogen
underling liver disease includes alcoholism and hep C
check porphyrins to diagnose
