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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 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. 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