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Blisters

Basic Dermatology Curriculum

Last updated September 20, 2013

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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.

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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

Question

What is the difference between a vesicle and a bulla?

a. Depth (epidermis versus dermis)

b. Diameter

c. Etiology

d. Location

e. Presence of hemorrhage

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Question

Answer: b What is the difference between a vesicle and

a bulla?a. Depth (distinguishes erosion and ulcer)b. Diameter (bullae are >1cm)c. Etiology (morphologic terms, not etiologic)d. Location (both can occur anywhere)e. Presence of hemorrhage (either vesicles or

bullae may be filled with blood)5

Vesicle: small blister (<1cm)

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Bulla: large blister (>1cm)

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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 disease: loss or disruption of adhesion molecules between cells or at the dermoepidermal junction (eg autoimmune blistering diseases like pemphigus vulgaris)

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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 seen an erosion or ulceration, consider causes of vesicles and bulla while building your differential diagnosis!

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Erosions: loss of the epidermis – occurs after blisters break

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Crust: dried transudate – can also occur after blisters break

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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)

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Case One

John Bennett

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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

Case One: Skin Exam

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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

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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. Acral (on distal extremities: hands and feet)b. Arcuate (in an arc or curve)c. Dermatomald. Intertriginous (in the body’s folds)e. Linear (straight lines)

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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. Allergic contact dermatitis to poison ivy

b. Bullous fixed drug eruption

c. Dyshidrotic eczema

d. Herpes simplex type 2

e. Shingles

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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

Herpes zoster (shingles)

Herpes zoster (shingles) is caused by an eruption of latent varicella zoster virus (VZV)

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

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Case Two

Mark Powers

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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

Case Two: Skin Exam

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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 ivyb. Bullous impetigoc. Chicken poxd. Herpes simplexe. Shingles

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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 simplexe. Shingles (not typically recurrent; dermatomal)

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

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Some examples of herpes simplex

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Herpes simplex

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Herpes simplex

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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

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Herpes simplex on lateral thigh

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Herpes simplex: genital, perianal

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Case Two, Question 2

You suspect this is recurrent herpes simplex. Which of the following tests would differentiate herpes simplex from shingles?

a. Biopsy for direct immunofluorescence test

b. Direct fluorescent antibody test

c. Gram stain

d. Herpes-specific IgG antibody (HerpSelect) test

e. Tzanck prep

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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 testc. 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)

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.

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.

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Case Two, Question 3

Which of the following is the most effective and cheapest initial therapy for this patient?

a. Acyclovir ointment

b. Oral acyclovir

c. Oral famciclovir

d. Oral gancyclovir

e. Oral valacyclovir

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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 acyclovirc. Oral famciclovir (for HSV but more expensive)d. Oral gancyclovir (for CMV)e. Oral valacyclovir (for HSV but more expensive)

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 dosing38

HSV treatment for recurrent episodes

Mounting evidence shows that patient-initiated, oral antiviral therapy works best

Patients start taking at earliest sign of outbreak (burning, pain, itching, etc.)

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

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Case Three

Dr. Richardson

Case Three: History

HPI: Dr. Richardson is a 43-year-old 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 with his 3-year-old daughter. Clobetasol ointment and oral diphenhydramine have been ineffective in controlling his symptoms.

PMH: none Allergies: none Medications: topical steroid, diphenhydramine Family History: noncontributory Social History: neonatologist, married, has a daughter ROS: difficulty sleeping due to itching

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Case Three: Skin Exam

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Case Three, Question 1

Dr. Richardson’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. Allergic contact dermatitis

b. Bullous insect bites

c. Cellulitis

d. Herpes zoster

e. Urticaria

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Case Three, Question 1

Answer: a Dr. Richardson’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 dermatitisb. 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)

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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 exposures45

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

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Case Three, Question 2

Dr. Richardson 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

b. Oral cephalexin

c. Silver sulfadiazine cream

d. Six days of methylprednisolone (Medrol dose pack)

e. 14-21 day taper of oral prednisone

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Case Three, Question 2

Answer: e Dr. Richardson 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

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

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Case Four

Sharon Neilson

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Case Four: History

HPI: Sharon Nielson is a 30-year-old woman who presents with ten years of recurrent itchy vesicles on her fingers, palms, and sides of her feet. She thinks they appear when she is stressed or anxious.

PMH: childhood atopic dermatitis Allergies: peanuts Medications: none Family history: noncontributory Social history: mother of two ROS: negative

Case Four: Skin Exam

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Case Four, Question 1

Mrs. Nielson’s exam shows small vesicles on the sides of her feet and fingers, and small crusts on her palms. KOH and Tzanck preps have been negative. What is the most likely diagnosis?

a. Bullous impetigo

b. Dyshidrotic eczema

c. Erythema multiforme

d. Herpes simplex

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Case Four, Question 1

Answer: b Mrs. Nielson’s exam shows small vesicles on the sides

of her feet and fingers, and small crusts on her palms. KOH and Tzanck preps have been negative. What is the most likely diagnosis?

a. Bullous impetigo (does not present with pruritus)b. Dyshidrotic eczemac. Erythema multiforme (targetoid, often on palms but

involving other parts of the body, may be recurrent)d. Herpes simplex (no erythematous base; Tzanck

negative)

Dyshidrotic eczema (pompholyx)

Dyshidrotic eczema presents with very pruritic vesiculopapules on the palms, soles, and sides of the fingers. • The vesicle fluid has been compared to tapioca pudding.

• After healing, the vesicles often leave behind a mark with a mahogany color, called post-inflammatory hyperpigmentation.

Many patients have a history of atopic dermatitis, and many have coexisting tinea pedis

The mainstay of treatment is potent topical steroids55

Location clues to vesicles on the feet

Dorsal foot: contact dermatitis, insect bites

Sides of feet and toes: dyshidrotic eczema

Soles: tinea pedis (often with scaling and interdigital maceration)

Balls, heels: friction blisters

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Case Five

Maggie Buford

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Case Five: 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

Case Five: Skin Exam

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Case Five, Question 1

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

d. Potassium hydroxide (KOH) exam

e. Tzanck prep

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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 cultureb. Biopsy for direct immunofluorescence testc. 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)

Bullous Impetigo

• 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 exotoxin-mediated disease (see next slide)

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Impetigo is a bacterial infection caused by gram positive bacteria, usually Staphylococcus aureus

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

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Review of

Localized vs. Extensive

Blistering

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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 dermatitis65

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…

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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

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Pemphigus vulgaris Autoantibodies to

desmogleins resulting in superficial bullae and erosions

Rarely see intact bullae

Usually in adults Diagnose with direct

immunofluorescence Consult dermatology

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Bullous pemphigoid

Autoantibodies to hemidesmosome resulting in deep, tense bullae

Usually in elderly Diagnose with direct

immunofluorescence Consult dermatology

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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

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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: Pemphigus, Pemphigoid Inflammation:

Drug: Stevens-Johnson syndome/Toxic Epidermal Necrolysis

Infection: Staph-Scalded Skin Syndrome Trauma: Burn

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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, 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

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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

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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. Last revised July 2013.

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End of the Module Berger T, Hong J, Saeed S, Colaco S, Tsang M, Kasper R. The Web-

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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.