1. Basic Dermatology Curriculum
Blisters
Basic Dermatology Curriculum
Would take out the tinea case.
Combine some of the first slides together.
Last updated September 20, 2013

2. 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.

3. 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

4. Question What is the difference between a vesicle and a bulla?
Depth (epidermis versus dermis)
Diameter
Etiology
Location
Presence of hemorrhage

5. Question
Answer: b
What is the difference between a vesicle and a bulla?
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)

6. Vesicle: small blister (<1cm)

7. Bulla: large blister (>1cm)

8. 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)

9. 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!

10. Erosions: loss of the epidermis – occurs after blisters break

11. Crust: dried transudate – can also occur after blisters break

12. 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)

13. Case One
John Bennett

14. 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

15. Case One: Skin Exam

16. Case One, Question 1
Mr. Bennett’s exam shows grouped vesicles only on his left upper chest. How would you describe this eruption?
Acral
Arcuate
Dermatomal
Intertriginous
Linear

17. Case One, Question 1 Answer: c
Mr. Bennett’s exam shows grouped vesicles only on his left chest. How would you describe this eruption?
Acral (on distal extremities: hands and feet)
Arcuate (in an arc or curve)
Dermatomal
Intertriginous (in the body’s folds)
Linear (straight lines)

18. 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?
Allergic contact dermatitis to poison ivy
Bullous fixed drug eruption
Dyshidrotic eczema
Herpes simplex type 2
Shingles

19. 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?
Allergic contact dermatitis to poison ivy (not dermatomal; usually linear rather than grouped)
Bullous fixed drug eruption (not dermatomal)
Dyshidrotic eczema (affects the hands, feet)
Herpes simplex type 2 (not dermatomal)
Shingles

20. 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

21. Case Two
Mark Powers

22. 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

23. Case Two: Skin Exam

24. 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?
Allergic contact dermatitis to poison ivy
Bullous impetigo
Chicken pox
Herpes simplex
Shingles

25. 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?
Allergic contact dermatitis to poison ivy (unlikely location)
Bullous impetigo (not typically recurrent)
Chicken pox (generalized; various stages of healing)
Herpes simplex
Shingles (not typically recurrent; dermatomal)

26. 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

27. Some examples of herpes simplex

28. Herpes simplex

29. Herpes simplex

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?
Biopsy for direct immunofluorescence test
Direct fluorescent antibody test
Gram stain
Herpes-specific IgG antibody (HerpSelect) test
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?
Biopsy for direct immunofluorescence test (for autoimmune bullous diseases)
Direct fluorescent antibody test
Gram stain (for bacteria)
Herpes-specific IgG antibody (HerpSelect) test (this test reveals previous exposure to HSV, not current lesion)
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.
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.

36. Case Two, Question 3
Which of the following is the most effective and cheapest initial therapy for this patient?
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?
Acyclovir ointment (topical antivirals are relatively ineffective compared to oral antivirals)
Oral acyclovir
Oral famciclovir (for HSV but more expensive)
Oral gancyclovir (for CMV)
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
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

40. Case Three
Dr. Richardson

41. 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

42. Case Three: Skin Exam

43. 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?
Allergic contact dermatitis
Bullous insect bites
Cellulitis
Herpes zoster
Urticaria

44. 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?
Allergic contact dermatitis
Bullous insect bites (usually scattered, not linear or grouped)
Cellulitis (presents as a spreading erythematous, non-fluctuant tender plaque, often with fever)
Herpes Zoster (presents as a painful eruption of grouped vesicles in a dermatomal distribution)
Urticaria (presents as edematous plaques, not vesicles. In early phase of allergic contact dermatitis, these lesions could be mistaken for urticaria)

45. 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 hours after exposures

46. 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

47. 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?
1% hydrocortisone lotion
Oral cephalexin
Silver sulfadiazine cream
Six days of methylprednisolone (Medrol dose pack)
14-21 day taper of oral prednisone

48. 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?
1% hydrocortisone lotion (not strong enough)
Oral cephalexin (for gram positive bacterial infections)
Silver sulfadiazine cream (for burns)
Six days of methylprednisolone (Medrol dose pack) (will likely get worse rebound after withdrawal)
14-21 day taper of oral prednisone

49. 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

50. Case Four
Sharon Neilson

51. 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

52. Case Four: Skin Exam

53. 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?
Bullous impetigo
Dyshidrotic eczema
Erythema multiforme
Herpes simplex

54. 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?
Bullous impetigo (does not present with pruritus)
Dyshidrotic eczema
Erythema multiforme (targetoid, often on palms but involving other parts of the body, may be recurrent)
Herpes simplex (no erythematous base; Tzanck negative)

55. 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 steroids

56. 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

57. Case Five
Maggie Buford

58. 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

59. Case Five: Skin Exam

60. 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?
Bacterial culture
Biopsy for direct immunofluorescence test
Direct fluorescence antibody (DFA) test
Potassium hydroxide (KOH) exam
Tzanck prep

61. 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?
Bacterial culture
Biopsy for direct immunofluorescence test
Direct fluorescence antibody (DFA) test (this would rule out HSV/VZV, less likely given lack of grouped vesicles on erythematous base)
Potassium hydroxide (KOH) exam (tinea corporis is not vesicular and is rare in infancy)
Tzanck prep (same as C)

62. 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 exotoxin- mediated disease (see next slide)

63. 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

64. Review of Localized vs. Extensive Blistering

65. 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

66. History clues Pain precedes onset: Itch 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…

67. 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

68. Pemphigus vulgaris
Autoantibodies to desmogleins resulting in superficial bullae and erosions
Rarely see intact bullae
Usually in adults
Diagnose with direct immunofluorescence
Consult dermatology

69. Bullous pemphigoid
Autoantibodies to hemidesmosome resulting in deep, tense bullae
Usually in elderly
Diagnose with direct immunofluorescence
Consult dermatology

70. 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

71. 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

72. 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

73. 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

74. Acknowledgements
This module was developed by the American Academy of Dermatology Medical Student Core Curriculum Workgroup from
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.

75. End of the Module
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