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Blisters
Basic Dermatology Curriculum
Last updated January 15, 2016
1
Module Instructions
 The following module contains a number
of blue, underlined terms which are
hyperlinked to the dermatology glossary,
an illustrated interactive guide to clinical
dermatology and dermatopathology.
 We encourage the learner to read all the
hyperlinked information.
2
Goals and Objectives
 Goal: To help learners develop a clinical
approach to the evaluation and initial
management of patients presenting with
blisters.
 After completing this module, the learner will be
able to:
• List common causes of blisters by location
• Select appropriate tests to determine the cause
of blisters
• Identify when to refer a patient with blisters to a
dermatologist
3
Question
What is the difference between a vesicle
and a bulla?
a.
b.
c.
d.
e.
Depth (epidermis versus dermis)
Diameter
Etiology
Location
Presence of hemorrhage
4
Question
Answer: b
What is the difference between a vesicle
and a bulla?
a.
b.
c.
d.
e.
Depth (distinguishes erosion and ulcer)
Diameter (bullae are >1cm)
Etiology (morphologic terms, not etiologic)
Location (both can occur anywhere)
Presence of hemorrhage (either vesicles or
bullae may be filled with blood)
5
Vesicle: small blister (<1cm)
6
Bulla: large blister (>1cm)
7
Understanding blisters
 There are various causes of blisters including:




Inflammation/Infection: fluid accumulates within the epidermis
causing it to lift (eg contact dermatitis)
Injury: physical disruption of the bonds between epidermal cells
or at the dermoepidermal junction (eg coma bulla)
Autoimmune: loss or disruption of adhesion molecules
between cells or at the dermoepidermal junction (eg
autoimmune blistering diseases like pemphigus vulgaris)
Genetic: changes or loss of proteins that contribute to cellular
adhesion (eg epidermolysis bullosa)
8
When blisters break
 When the top of a blister is disrupted, it
forms an erosion (loss of all or part of the
epidermis) or, less commonly, an
ulceration (loss of the epidermis and part
of the dermis). It then oozes serous fluid
to form a crust.
 So when you see an erosion or ulceration,
consider causes of vesicles and bulla
while building your differential diagnosis!
9
Erosions: loss of the epidermis –
occurs after blisters break
10
Crust: dried transudate – can also
occur after blisters break
11
Understanding blisters
This module will focus on common and dangerous
causes of blisters
 History is very helpful
•
•
•
•
•
Symptoms: pain, itch?
Triggers: trauma, injury?
Timing: first time or recurrent?
Distribution: localized or generalized?
Location: which part of the body? (Especially
consider mucous membrane involvement)
12
Case One
John Bennett
13
Case One: History
 HPI: John Bennett is a 28-year-old man who
presents with four days of pain and blisters on
his left chest.
 PMH: none
 Allergies: none
 Medications: none
 Family History: noncontributory
 Social History: single; works in construction
 ROS: negative
14
Case One: Skin Exam
15
Case One, Question 1
Mr. Bennett’s exam shows grouped vesicles only
on his left upper chest. How would you describe
this eruption?
a. Acral
b. Arcuate
c. Dermatomal
d. Intertriginous
e. Linear
16
Case One, Question 1
Answer: c
Mr. Bennett’s exam shows grouped vesicles only
on his left chest. How would you describe this
eruption?
a.
b.
c.
d.
e.
Acral (on distal extremities: hands and feet)
Arcuate (in an arc or curve)
Dermatomal
Intertriginous (in the body’s folds)
Linear (straight lines)
17
Case One, Question 2
Mr. Bennett has a dermatomal grouping of vesicles
on an erythematous base located on his trunk.
What is the most likely diagnosis?
a.
b.
c.
d.
e.
Allergic contact dermatitis to poison ivy
Bullous fixed drug eruption
Dyshidrotic eczema
Herpes simplex type 2
Shingles
18
Case One, Question 2
Answer: e
Mr. Bennett has a dermatomal grouping of vesicles
on an erythematous base located on his trunk.
What is the most likely diagnosis?
a. Allergic contact dermatitis to poison ivy (not
dermatomal; usually linear rather than grouped)
b. Bullous fixed drug eruption (not dermatomal)
c. Dyshidrotic eczema (affects the hands, feet)
d. Herpes simplex type 2 (not dermatomal)
e. Shingles
19
Herpes zoster (shingles)
 Herpes zoster (shingles) is caused by an eruption of latent varicella
zoster virus (VZV)
 It can occur in children, but is less frequent compared to adults
 The clues to the diagnosis of shingles are:
• Dermatomal (zosteriform) eruption on one side of the body
• Grouped vesicles on an erythematous base are typical of the
herpes family of viruses, including VZV
• Shingles appears most often on trunk but can be anywhere
• Usually preceded by pain or burning
• Generally shingles occurs only once in the immunocompetent,
in contrast to herpes simplex virus (HSV), which frequently
recurs
20
Case Two
Mark Powers
21
Case Two: History
 HPI: Mark Powers is an 18-year-old high school
senior. He presents with two days of painful blisters
around his mouth. He had a similar eruption about
a year ago in the same location.
 PMH: none
 Allergies: none
 Medications: ibuprofen as needed
 Family History: noncontributory
 Social History: senior in high school; lives with
parents and younger sister; state champion in
varsity wrestling
 ROS: negative
22
Case Two: Skin Exam
23
Case Two, Question 1
Mark’s exam shows grouped vesicles on an
erythematous base on his left chin and lip, and a
pustular vesicle on his left lip. What is the most
likely diagnosis?
a. Allergic contact dermatitis to poison ivy
b. Bullous impetigo
c. Chicken pox
d. Herpes simplex
e. Shingles
24
Case Two, Question 1
Answer: d
Mark’s exam shows grouped vesicles on an
erythematous base on his left chin and lip, and a
pustular vesicle on his left lip. What is the most likely
diagnosis?
a. Allergic contact dermatitis to poison ivy (unlikely
location)
b. Bullous impetigo (not typically recurrent)
c. Chicken pox (generalized; various stages of
healing)
d. Herpes simplex
e. Shingles (not typically recurrent; dermatomal)
25
Herpes simplex
 Herpes simplex viruses 1 and 2 cause painful,
grouped vesicles on an erythematous base
•
•
•
•
•
Vesicles may appear pustular (white to yellow)
Tends to recur in the same place
HSV 1 favors the mouth and nose
HSV 2 favors the genitalia, buttocks, thighs
Perianal erosions or ulcerations in immunosuppressed
patients are usually HSV
 Often don’t see vesicles, just see the erosions
• Look for bright red rim on erosion
• Pain and recurrence suggests HSV
26
Some examples of herpes
simplex
27
Herpes simplex
28
Herpes simplex
29
Painful blisters on the fingers
• Herpetic whitlow
– Multiple, red borders,
may be pustular
– Look for oral HSV
• Blistering dactylitis
– Often single bulla
caused by Strep
– Culture the aspirate
JAAD 2007;57(5):737-63.
30
Vesicles in bathing suit distribution
 Recurrent vesicles on genitalia, buttocks,
or thighs, are HSV until proven otherwise
 HSV usually has bright red borders and
may present as crusts or erosions
 Severe perianal HSV may occur in HIV or
other immunosuppression
 Single genital ulcers could be syphilis or
chancroid as well
31
Herpes simplex on lateral thigh
32
Herpes simplex: genital, perianal
33
Case Two, Question 2
You suspect this is recurrent herpes simplex.
Which of the following tests would differentiate
herpes simplex from shingles?
a.
b.
c.
d.
Biopsy for direct immunofluorescence test
Direct fluorescent antibody test
Gram stain
Herpes-specific IgG antibody (HerpSelect)
test
e. Tzanck prep
34
Case Two, Question 2
Answer: b
You suspect this is recurrent herpes simplex. Which
of the following tests would differentiate herpes
simplex from shingles?
a. Biopsy for direct immunofluorescence test (for
autoimmune bullous diseases)
b. Direct fluorescent antibody test
c. Gram stain (for bacteria)
d. Herpes-specific IgG antibody (HerpSelect) test (this
test reveals previous exposure to HSV, not current
lesion)
e. Tzanck prep (non-specific for herpes family of viruses)
35
Tests for herpes family viruses
 Tzanck prep can be used to confirm herpes family viruses, but it
does not differentiate them from one another. It requires
scraping the base of an active vesicle or erosion. Results are
immediate.
 Viral culture can be performed when there is fluid present, but it
is less helpful once crusts have formed. Results in 1-3 weeks.
Not as helpful for VZV. The gold standard for HSV.
 Polymerase chain reaction (PCR) may be used instead of viral
culture if favored at your institution. You often need to send
separate swabs to distinguish between HSV and VZV.
 Direct fluorescent antibody (DFA) test can differentiate HSV 1
and 2, as well as VZV. Like Tzanck prep, scrape the base of a
vesicle or erosion. Results in 48 hours.
 The HerpSelect test is a blood test, which uses IgG antibodies
to differentiate past exposures to HSV 1 and 2 but not VZV.
Results in days to weeks. It can only tell you about past
exposures, not if the current eruption is caused by HSV or VZV.
36
Case Two, Question 3
Which of the following is the most effective
and cheapest initial therapy for this patient?
a.
b.
c.
d.
e.
Acyclovir ointment
Oral acyclovir
Oral famciclovir
Oral gancyclovir
Oral valacyclovir
37
Case Two, Question 3
Answer: b
Which of the following is the most effective
and cheapest initial therapy for this patient?
a. Acyclovir ointment (topical antivirals are relatively
ineffective compared to oral antivirals)
b. Oral acyclovir
c. Oral famciclovir (for HSV but more expensive)
d. Oral gancyclovir (for CMV)
e. Oral valacyclovir (for HSV but more expensive)
38
HSV treatment
 Acyclovir is a safe, cheap, and reliable
treatment for HSV
• Should be started immediately at first sign of
recurrence
• Acyclovir can be used in pregnancy
• Intravenous acyclovir is available for
generalized HSV or VZV in the
immunocompromised
 Famciclovir and valacyclovir are more
expensive but have easier dosing
39
HSV treatment for recurrent episodes




Cool compresses, lubricants and topical or oral
analgesics can be helpful
Topical antiviral therapy is of little use for uncomplicated
cases
For older children, an oral therapy taken at the earliest
sign of outbreak (burning, pain, itching, etc.) can
shorten the outbreak
Short therapies work as well as longer ones
•
•
•
Acyclovir 800 mg TID x 2 days
Famciclovir 1 gram BID x 1 day
Valacyclovir 2 grams BID x 1 day
40
Neonatal Herpes Simplex Virus (HSV)
Neonatal HSV may be acquired in utero, perinatally, or
postnatally
•
perinatal or neonatal acquisition are most frequent
Classification:
•
•
•
Localized skin, eye, and mouth (SEM)
Central nervous system (CNS) with or without SEM
Disseminated disease involving multiple organs
Prognosis:
•
•
Early diagnosis and treatment is critical. If suspected testing should be
pursued.
Treatment can prevent progression from localized SEM to CNS and
disseminated infections. Untreated disseminated neonatal HSV has a
mortality rate exceeding 80%
41
Case Three
Trey Richardson
42
Case Three: History
 HPI: Trey is a 13-year-old young man who presents
with 3 days of intense itching and blisters on his
neck, arms and legs. He noticed the eruption 2
days after a hike. Hydrocortisone 1% ointment and
oral diphenhydramine have been ineffective in
controlling his symptoms.
 PMH: none
 Allergies: none
 Medications: topical steroid, diphenhydramine
 Family History: noncontributory
 Social History: lives with his parents and sister
 ROS: difficulty sleeping due to itching
43
Case Three: Skin Exam
44
Case Three, Question 1
Trey’s exam shows erythematous plaques, consisting
of confluent papules and weeping vesicles on his arms,
legs, and neck bilaterally. Some of them are linear.
What is the most likely diagnosis?
a.
b.
c.
d.
e.
Allergic contact dermatitis
Bullous insect bites
Cellulitis
Herpes zoster
Urticaria
45
Case Three, Question 1
Answer: a
Trey’s exam shows erythematous papules and extensive
weeping vesicles on his arms, legs, and neck bilaterally. Some
of them are linear. What is the most likely diagnosis?
a. Allergic contact dermatitis
b. Bullous insect bites (usually scattered, not linear or grouped)
c. Cellulitis (presents as a spreading erythematous, non-fluctuant
tender plaque, often with fever)
d. Herpes Zoster (presents as a painful eruption of grouped vesicles
in a dermatomal distribution)
e. Urticaria (presents as edematous plaques, not vesicles. In early
phase of allergic contact dermatitis, these lesions could be
mistaken for urticaria)
46
Allergic contact dermatitis
 Allergic contact dermatitis (ACD) is a common
source of vesicles
• The most common cause is rhus dermatitis, from
poison ivy, poison oak, or poison sumac
• Rhus dermatitis often shows linear streaks of vesicles
 The main symptom of ACD is itching
 ACD is bilateral if the exposure is bilateral (e.g.,
shoes, gloves, ingredients in creams, etc.)
 This is a delayed hypersensitivity reaction so
the rash appears 24-72 hours after exposures
47
Rhus dermatitis (poison ivy)
 Linear streaks aid in
diagnosis (from the
linear contact of the
plant)
 Fomites can be
contaminated by the
plant oil and lead to
recurrent eruptions
48
Case Three, Question 2
Trey can’t sleep due to itching and has had no
improvement with clobetasol ointment the past
three days. What treatment do you recommend?
a.
b.
c.
d.
e.
1% hydrocortisone lotion
Oral cephalexin
Silver sulfadiazine cream
Six days of methylprednisolone (Medrol dose pack)
14-21 day taper of oral prednisone
49
Case Three, Question 2
Answer: e
Trey can’t sleep due to itching and has had no
improvement with clobetasol ointment the past three
days. What treatment do you recommend?
a. 1% hydrocortisone lotion (not strong enough)
b. Oral cephalexin (for gram positive bacterial
infections)
c. Silver sulfadiazine cream (for burns)
d. Six days of methylprednisolone (Medrol dose pack)
(will likely get worse rebound after withdrawal)
e. 14-21 day taper of oral prednisone
50
Rhus dermatitis treatment
 Most patients need minor supportive care
• Topical steroids for localized involvement
• Topical or oral antihistamines may help
• Oatmeal soaks/calamine lotion may help soothe weeping
erosions
 Severe involvement may require oral steroids
•
•
•
•
Use in cases failing potent topical steroids, or widespread
If given for less than 2-3 weeks, patients may relapse
Do not give short bursts of steroids for this reason
Dosing in children is typically 0.5-1.0mg/kg/day
51
Case Four
Maggie Buford
52
Case Four: History
 HPI: Maggie Buford is an 18-month-old girl who
had blisters on her chest and abdomen one
week ago. The blisters started crusting a few
days ago.
 PMH: normal birth, no illnesses
 Allergies: none
 Medications: none
 Family history: noncontributory
 Social history: lives with both parents
 ROS: negative
53
Case Four : Skin Exam
54
Case Four, Question 1
Maggie is afebrile and her exam shows multiple
crusted plaques on her abdomen, chest, and back.
Which test would you order?
a.
b.
c.
d.
e.
Bacterial culture
Biopsy for direct immunofluorescence test
Direct fluorescence antibody (DFA) test
Potassium hydroxide (KOH) exam
Tzanck prep
55
Case Five, Question 1
Answer: a
Maggie is afebrile and her exam shows multiple
crusted plaques on her abdomen, chest, and back.
Which test would you order?
a. Bacterial culture
b. Biopsy for direct immunofluorescence test
c. Direct fluorescence antibody (DFA) test (this would rule
out HSV/VZV, less likely given lack of grouped vesicles
on erythematous base)
d. Potassium hydroxide (KOH) exam (tinea corporis is not
vesicular and is rare in infancy)
e. Tzanck prep (same as C)
56
Bullous Impetigo
• Impetigo is a bacterial infection
caused by gram positive bacteria,
usually Staphylococcus aureus
• It occurs more frequently in children
• Bullous impetigo is caused by an
exotoxin produced by the bacteria
• After rupture, the majority of
lesions are crusted papules or
erosions
• The infection is localized to the skin
• Staphylococcal scalded skin syndrome
is a generalized form of exotoxinmediated disease (see next slide)
57
Staphylococcal Scalded Skin
Syndrome
 A focus of infection secretes
toxin into the blood leading to
widespread superficial blisters
• Skin peels away in sheets
• Wound cultures from erosions
are negative
 At risk: kids < 2 years and
adults with renal disease
 It is important to distinguish
localized vs. extensive
blistering as the later should
be referred urgently to a
dermatologist
58
Review of
Localized vs. Extensive
Blistering
59
Location clues for localized vesicles
 Mouth/nose/eyes: HSV, bullous impetigo
 Chest, back (dermatomal): VZV
 Fingers: dyshidrotic eczema, contact
dermatitis, herpetic whitlow (HSV on fingers)
 Arms, legs: contact dermatitis
 Genitalia / Bathing suit distribution: HSV
 Feet: dyshidrotic eczema, tinea pedis,
allergic contact dermatitis
60
History clues
 Pain precedes onset:
• HSV, VZV
 Itch precedes onset:
• Allergic contact dermatitis, dyshidrotic eczema, VZV
 Trauma precedes onset:
• Friction blister, pressure ulcer, cryotherapy
 Recurrent blisters:
• HSV
 Now some more causes of diffuse blistering…
61
Chicken pox
 Varicella zoster virus
(VZV) infection
 Diffusely scattered
vesicles on an
erythematous base
 Can be extensive and
severe, especially in adult
 Confirm diagnosis with
Tzanck prep, or direct
fluorescent antibody (DFA)
test
62
Pemphigus vulgaris
 Autoantibodies to
desmogleins
resulting in
superficial bullae
and erosions
 Rarely see intact
bullae
 Usually in adults
 Diagnose with direct
immunofluorescence
 Consult dermatology
63
Linear IgA (Chronic Bullous Dermatosis of
Childhood), or Bullous Pemphigoid
 Autoantibodies to parts of the hemidesmosome
resulting in deep, tense bullae
 Diagnose with direct immunofluorescence
 Linear IgA in kids
 Bullous pemphigoid
 In older adults
 Consult dermatology
64
Drug eruptions
 Drug eruptions appear
acutely and can lead to
vesicles, bullae, and large
erosions
 These will be discussed in
the “Drug Reactions”
module
 Consult dermatology for
any acute widespread
blistering eruption in sick
patients
65
Generalized blisters:
When to Refer

Patients with generalized (extensive) vesicles and bullae
should be seen urgently by a dermatologist

The cause may be a severe and potentially fatal disease:

Autoimmune: Linear IgA disease, Dermatitis
herpetiformis, Pemphigus, Pemphigoid

Inflammation:



Drug: Stevens-Johnson syndome/Toxic Epidermal Necrolysis

Infection: Staph-Scalded Skin Syndrome
Trauma: Burn
Genetic: Epidermolysis bullosa
66
Take Home Points
 Get a good history: itch versus pain differentiates many
causes of blisters
 Think about causes of blisters including inflammation,
infection, injury or autoimmune disease
 Grouped vesicles on an erythematous base – think Herpes
 Tzanck prep, viral culture, PCR, and direct fluorescent
antibody test help confirm the diagnosis, but clinical diagnosis
is sufficient for empiric therapy
 Acyclovir is a readily available, cheap, and safe medication
 Allergic contact dermatitis may be vesicular and starts with
itch
67
Take Home Points (cont.)
 Topical steroids, antihistamines, and oatmeal soaks help
relieve symptoms of allergic contact dermatitis
 When necessary, oral steroids should be used for 2-3 weeks
to treat allergic contact dermatitis
 Dyshidrotic eczema is diagnosed clinically and treated with
steroids
 Bullous impetigo can be diagnosed with bacterial culture
 Appearance of generalized vesicles, bullae, or erosions
warrants immediate consultation to dermatology
 See references (eg UpToDate review) for further information
68
Acknowledgements





This module was developed by the American Academy of
Dermatology Medical Student Core Curriculum Workgroup
from 2008-2012.
Primary Author: Patrick McCleskey, MD, FAAD.
Reviewers: Timothy G. Berger, MD, FAAD; Peter A. Lio, MD,
FAAD; Elizabeth A. Buzney, MD, FAAD; Sarah D. Cipriano,
MD, MPH.
Revisions: Patrick McCleskey, MD, FAAD. Jessica
Kaffenberger, MD, Joslyn Kirby, MD, Irene Lara-Corrales,
MD.
Thanks to the Society for Pediatric Dermatology for their help
with revisions. Last revised January 2016.
69
End of the Module
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 Habif TP. Clinical Dermatology: a color guide to diagnosis and therapy,
4th ed. New York, NY: Mosby; 2004.
 Hull C, Zone JJ. Approach to the patient with cutaneous blisters. In:
UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2013.
 James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin, 11th
ed. Elsevier; 2011:12-17.
 Marks Jr JG, Miller JJ. Lookingbill and Marks’ Principles of
Dermatology, 4th ed. Elsevier; 2006:187-197.
 Spruance S, Aoki FY, Tyring S, Stanberry L, Whitley R, Hamed K.
Short-course therapy for recurrent genital herpes and herpes labialis. J
Fam Pract. 2007 Jan;56(1):30-6.
 Usatine RP, Riojas M. Diagnosis and management of contact
dermatitis. Am Fam Physician. 2010 Aug;82(3):249-55.
70
To take the quiz, click on the following link:
https://www.aad.org/quiz/blisters--learners