1. Approach to vesiculobullous disorders Medical Student Core Curriculum in Dermatology 1

2. 2 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

3. 3 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

4. Individual Quiz 4

5. 5  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.Direct fluorescent antibody (DFA) test b.Gram stain and bacterial culture c.Potassium hydroxide (KOH) exam d.Tzanck prep

6. 6 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.Direct fluorescent antibody (DFA) test b.Gram stain and bacterial culture c.Potassium hydroxide (KOH) exam d.Tzanck prep

7. Individual Quiz KOH exam shows branched septated hyphae 7

8. Tinea pedis (athlete’s foot)  Tinea pedis may have fine scales on the sole and between toes Tinea pedis  Vesicles often appear on bottom of foot  Scrape the roof of a vesicle to improve sensitivity of KOH exam 8

9. 9 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

10. Individual Quiz 10

11. 11 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

12. 12 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)Herpes simplex

13. 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 13

14. 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 14

15. 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 15

16. 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 16

17. 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 17

18. 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 18

19. LESS COMMON BULLOUS DISORDERS (AUTOIMMUNE, PORPHYRIA)

20. 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 (skin biopsy)  Consult dermatology 20

21. 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.

22. 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

23. 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 immunofluorescence  Consult dermatology 23

24. 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

25. Dermatitis herpetiformis Autoimmune bullous disorder 90% has coeliac disease; relatively younger Extremely itchy, involving extensor surfaces Remove gluten from diet Use dapsone

26. 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

27. 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

28. 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

29. 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.

30. 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 30

31. 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 31

32. 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. 32

33. 33 References  Berger T, Hong J, Saeed S, Colaco S, Tsang M, Kasper R. The Web- Based Illustrated Clinical Dermatology Glossary. MedEdPORTAL; 2007. Available from: www.mededportal.org/publication/462.  Habif TP. Clinical Dermatology: a color guide to diagnosis and therapy, 4 th ed. New York, NY: Mosby; 2004.  Marks Jr JG, Miller JJ. Lookingbill and Marks’ Principles of Dermatology, 4 th 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, 2 nd ed. China: Saunders Elsevier; 2007: 547-59.