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MSK/Derm > Drug Reactions and Blistering Disorders > Flashcards

Drug Reactions and Blistering Disorders Flashcards

1
Q

What are the characteristics of most cutaneous drug reactions?

A

inflammatory

generalized

symmetric

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2
Q

What are the most common and important types of adverse drug reactions?

A

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)

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3
Q

immediate drug-induced skin reactions

A

occur less than 1 hour of the last adminstered dose

  • urticaria
  • angioedema
  • anaphylaxis
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4
Q

delayed drug-induced reactions

A

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)
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5
Q

What is the use of allergy testing for drug reactions?

A

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)

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6
Q

What are the important questions in a drug history?

A

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)

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7
Q

What are the uses of a drug timeline?

A

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)

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8
Q

What are some risk factors for drug reactions?

A

female

prior history of drug reaction

recurrent drug exposure

HLA type

certain disease state (EBC - aminopenicillins, HIV - sulfonamides)

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9
Q

exanthem

A

a rapidly erupting rash that may have specific diagnostic features of an infectious disease

usually referring to the rashes seen with viral/coccal infections

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10
Q

What are the classic diseases with exanthematous rashes?

A

chickenpox

measles

roseola infantum

rubella

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11
Q

What is the classic progression of measles?

A

starting on head, spreading down the body “like a can of pain would”

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12
Q

What is the exanthem characteristic of roseola infantum?

A

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

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13
Q

exanthematous drug eruption

A

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

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14
Q

What is the clinical course and treatment of exthematous reactions?

A

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

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15
Q

What is Drug-Induced Hypersensitiviety Syndrome?

A

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

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16
Q

What are the typical signs and symptoms of Drug-Induced Hypersensitivity Syndrome?

A

macular exanthem

erythematous centrofacial swelling

fever

malaise

lymphadenopathy

involvement of other organs such as liver or kidney

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17
Q

What is the clinical course of DRESS?

A

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%

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18
Q

medications implicated in DRESS

A

allopurinol

antibiotics

anti-TB drugs

anticonvulsants

NSAIDs

Anti-HIV drugs

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19
Q

What is the approach to the patient with suspected DRESS?

A

stop (or substitute) all suspect medications and discontinue non-essential medications

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20
Q

What is the treatment for DRESS?

A

stop medication if severe

also use systemic sterids if severe - gradually taper

if not, use topical steroids and systemic antihistamines

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21
Q

What is erythema multiforme?

A

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

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22
Q

erythema multiforme minor

A

papular target lesions with little or no mucosal involvement and no systemic symptoms

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23
Q

erythema multiforme major

A

papular target lesions with severe mucosal involvement and systemic features

24
Q

What are the most common precipitating factors of erythema multiforme?

A

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

25
Q

What reactions are included in the Epidermal Necrolysis Spectrum?

A

Stevens-Johnson Syndrome (SJS)

Toxic Epidermal Necrolysis (TEN)

26
Q

What is Stevens-Johnson Syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN)

A

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

27
Q

What is the major distinction between SJS and TEN?

A

SJS < 10% body surface covered

SJS-TEN overlap 10-30%

TEN >30% body surface covered

28
Q

What is the mortality rate for SJS/TEN?

A

1-5% for SJS

>20% for TEN

for TEN, increasing age, signficant comorbid conditions, and greater extent of skin invovlement correlate with poor prognosis

29
Q

What are the medications most frequently associated with SJS/TEN?

A

up to 20% remain idiopathic

over 100 different drugs:

Sulfa antibiotics, Sulfasalazine

Anticonvulsants (carbamazepine, lamotrigine, phenobarbital, phenytoin)

Tetracyclines/Thiacetazone

Allopurinol

NSAIDs/Nevirapine

30
Q

What is the pathophysiology of SJS-TEN?

A

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

31
Q

What is involved in the management of SJS and TEN?

A

early diagnosis

immediate discontinuation of the causative drug

supportive care (IV-Ig may have the potential to selectively block keratinocyte apoptosis)

32
Q

What are the clinical findings of SJS/TEN?

A

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

33
Q

What are the characteristics of the initial skin lesions in SJS/TEN?

A

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

34
Q

What are specific skin findings for SJS?

A

atypical target lesions

dusky apperance

mucous membrane involvement

35
Q

What are characteristic skin findings of TEN?

A

tender/painful skin

extensive sloughing

36
Q

What are SJS/TEN complications?

A

corneal damage (consult ophthalmologist)

fluid and electrolyte problems

nutrition problems

secondary infection (bacteremia, spesis)

37
Q

What is the treatment for SJS/TEN?

A

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

38
Q

What are systemic features that warn of a potentially severe drug reaction?

A

fever and/or other symptoms of internal organ involvement such as pharyngitis, malaise, arthralgia, etc.

lymphadenopathy

39
Q

What are the cutaneous clinical features that warn of potentially severe drug reaction?

A

evolution to erythroderma

prominent facial involvement +/- edema or swelling

mucous membrane involvement (particularly if erosive or involving conjunctiva)

skin tenderness, blistering, or shedding

purpura

40
Q

Why do cells separate from one another?

A

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

41
Q

What are the key features of intraepidermal vs. subepidermal blisters?

A

intraepidermal - flaccid and easily broken

subepidermal - tense and usually intact

42
Q

“nikolsky sign”

A

epidermal separation by lateral pressure to edge of blister or to normal appearing skin = characteristic for intraepidermal blisters

43
Q

What is dermatitis herpetiformis?

A

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

44
Q

What diseases are associated with dermatitis herpetiformis?

A

gastric atrophy, thyroid disease, small bowel lymphoma

45
Q

What is the treatment for dermatitis herpetiformis?

A

gluten-free diet, dapsone

46
Q

What is the difference between pemphigus and pemphigoid?

A

pemphigoid is under the epidermis

pemphigus is within the epidermis

47
Q

What is pemphigus vulgaris?

A

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

48
Q

What is the pathophysiology of pemphigus vulgaris?

A

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%

49
Q

What are drugs that can induce pemphigus vulgaris?

A

penicillamine and captopril

50
Q

What is the treatment for pemphigus vulgaris?

A

immunosuppression - Prednisone, Imuran, Rituximab

51
Q

What is bullous pemphigoid?

A

autoantibodies to hemidesmosomes, resultin gin deep, tense bullae

usually found in the elderly

52
Q

What is the pathophysiology of bullos pemphigooid?

A

onset is 60s-70s

large, tense bullae, flexural, oral 20%

subepidermal split

presence of IgG and C3 on the basement membrane with staining

53
Q

What is the treatment for bullous pemphigoid?

A

predinisone

azathioprine

tetracycline

dapsone

54
Q

What is prophyria cutanea tarda (PCT)?

A

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
55
Q

What is the pathophysiology of PCT?

A

results from a decreased catalytic activity of uroporphyrinogen

underling liver disease includes alcoholism and hep C

check porphyrins to diagnose

MSK/Derm (54 decks)

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