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Approach to
vesiculobullous disorders
Medical Student Core Curriculum
in Dermatology
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Goals and Objectives
 The purpose of this module is to help medical
students develop a clinical approach to the
evaluation and initial management of patients
presenting with blistering conditions
 After completing this module, the learner will be
able to:
• List common causes of blisters by location
• Select appropriate tests to diagnose blisters
• Identify when to refer a patient with blisters to a
dermatologist
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Individual Quiz
 A 38-year-old man presents with one month of small
blisters on his feet. They do not itch, and he reports no
trauma or ill-fitting shoes. He is not using anything for
it.
 Past Medical History: none
 Allergies: none
 Medications: none
 Family history: mother with type II diabetes
 Social history: computer technician, recreational
swimmer
 Review Of Systems: negative
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Individual Quiz
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Individual Quiz
 The skin exam shows vesicles on his toes as well
as interdigital scaling and scaling on the bottom of
his feet. Which of the following tests would confirm
the most likely diagnosis?
a.
b.
c.
d.
Direct fluorescent antibody (DFA) test
Gram stain and bacterial culture
Potassium hydroxide (KOH) exam
Tzanck prep
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Individual Quiz
 The exam shows vesicles on his toes as well as
interdigital scaling and scaling on the bottom of his
feet. Which of the following tests would confirm
the most likely diagnosis?
a.
b.
c.
d.
Direct fluorescent antibody (DFA) test
Gram stain and bacterial culture
Potassium hydroxide (KOH) exam
Tzanck prep
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Individual Quiz
KOH exam shows branched septated hyphae
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Tinea pedis (athlete’s foot)
 Tinea pedis may have
fine scales on the sole
and between toes
 Vesicles often appear on
bottom of foot
 Scrape the roof of a
vesicle to improve
sensitivity of KOH exam
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Individual Quiz
 A 30-year-old woman 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.
 Past Medical History: childhood atopic dermatitis
 Allergies: peanuts
 Medications: none
 Family history: noncontributory
 Social history: mother of two
 Review Of Systems: negative
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Individual Quiz
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Individual Quiz
 The skin 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. Tinea manum
d. Herpes simplex
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Individual Quiz
 The skin 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 eczema
c. Tinea Manum (KOH exam negative)
d. Herpes simplex (no erythematous base;
Tzanck negative)
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Dyshidrotic eczema (pompholyx)
 Dyshidrotic eczema presents as very pruritic
vesiculopapules on the palms, soles, and sides of
the fingers.
• The vesicle fluid has been compared to tapioca pudding.
• After healing, they 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 steroids
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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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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
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Localized blisters: 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
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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 to dermatology
 With the exception of varicella (chicken
pox), most generalized vesicles and
bullae represent severe and potentially
fatal disease
 Patients with generalized vesicles and
bullae should be referred urgently to a
dermatologist
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LESS COMMON BULLOUS
DISORDERS (AUTOIMMUNE,
PORPHYRIA)
Pemphigus vulgaris
 Autoantibodies to
desmogleins resulting
in superficial bullae
and erosions (intra
epidermal)
 Usually in elderly (40
– 60 year olds)
 Nikolsky sign positive
 Diagnose with direct
immunofluorescence
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(skin biopsy)
 Consult dermatology
Nikolsky sign
• Apply tangential pressure with a finger or thumb to affected
skin, apparently normal skin.
• Positive if there is extension of the blister or removal of
epidermis
• Underlying pathophysiology is acantholysis occuring in areas
of erosions and bullae as well as in normal appearing skin.
Pemphigus Vulgaris
• Can first present with mucosal erosions in
the mouth; can be severe and increase
risk of mortality
• Can be drug induced
• Flaccid blisters can occur on skin of upper
trunk and back.
• May be a paraneoplastic phenomenon
• Managed with high dose corticosteroids or
immunosuppressants / intravenous
immunoglobulin
Bullous pemphigoid
 Autoantibodies to
hemidesmosome
resulting in deep,
tense bullae
(subepidermal)
 Chronic autoimmune
bullous disorder
 Usually in elderly >
65 years of age
 Diagnose with direct
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immunofluorescence
 Consult dermatology
Bullous pemphigoid
• Widespread itchy urticarial lesions,
developing into tense bullae
• Trunk (especially flexures and limbs)
• Affects mucosal surfaces only in 10 – 25%
• Mostly managed with high dose systemic
corticosteroids or immunosuppressants
• Tend to remit within 5 years
Dermatitis herpetiformis
•
•
•
•
•
Autoimmune bullous disorder
90% has coeliac disease; relatively younger
Extremely itchy, involving extensor surfaces
Remove gluten from diet
Use dapsone
Linear Ig A bullous disease
•
•
•
•
•
Self limiting autoimmune bullous disorder
Occurs in all age groups
Medications have been implicated
Mucosal involvement of eye and mouth is common
Treatment is with steroids, dapsone, colchicine or IV
immunoglobulins
Epidermolysis bullosa acquisita
• Chronic blistering disease involving skin and mucous
membranes
• Associated with inflammatory bowel disease, rheumatoid
arthritis, multiple myeloma and lymphoma.
• Can be resistant to immunosuppression
Erythema Multiforme
• Triggered by infections(HSV,
mycoplasma), medications
(penicillins and sulphonamides),
malignancy
• Can present as urticarial lesions
with central blistering (target
lesions) involving skin and
mucous membranes
• Supportive treatment with simple
dressings, prevention of infection
and hemodynamic support.
• Intravenous immunoglobulin
indicated for severe cases
Porphyria cutanea tarda
• Most common porphyria,
which are rare haem
biosynthetic pathway
disorders
• Onset in adulthood
• Due to alcohol, iron
overload, hepatitis C and
HIV infection
• Blistering, erosions on sun
exposed areas such as the
backs of hands.
Take Home Points
 The history of itch versus pain differentiates many
causes of blisters
 Grouped vesicles on an erythematous base, or
erosions with a rim of erythema, are herpes family of
viruses until proven otherwise
 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.)
 Tinea pedis may be vesicular; KOH confirms diagnosis
 Dyshidrotic eczema is diagnosed clinically and treated
with steroids
 Appearance of generalized vesicles, bullae, or erosions
warrants immediate consultation to dermatology
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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. Last
revised March 2011.
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References
 Berger T, Hong J, Saeed S, Colaco S, Tsang M, Kasper R. The WebBased Illustrated Clinical Dermatology Glossary. MedEdPORTAL; 2007.
Available from: www.mededportal.org/publication/462.
 Habif TP. Clinical Dermatology: a color guide to diagnosis and therapy,
4th ed. New York, NY: Mosby; 2004.
 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.
 Wolverton SE. Topical Antifungal Agents (Chapter 29), in
Comprehensive Dermatologic Drug Therapy, 2nd ed. China: Saunders
Elsevier; 2007: 547-59.
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