Vesic. Diseases chi ✅ QT PDF

QT Vesiculobullous Diseases Angela C. Chi, D.M.D. Professor [email protected] taking photos or video recording during this live class session is not permitted  Learnin...

QT Vesiculobullous Diseases Angela C. Chi, D.M.D. Professor [email protected] taking photos or video recording during this live class session is not permitted  Learning Objectives Define vesiculobullous disease. Discuss the classification, etiopathogenesis, demographics, clinical features, differential diagnosis, treatment, and prognosis of vesiculobullous diseases.  Vesiculobullous Diseases Diseases characterized by fluid-filled blisters on skin and/or mucosa  TERMINOLOGY: Vesicle vs. Bulla  Vesicle: Bulla: small fluid-filled blister ( symptomatic Acute herpetic gingivostomatitis – Fever, chills, nausea, LAD, irritability Leão, Jair & Gomes, Valder & Porter, Stephen. (2008). Ulcerative lesions of the mouth: An update for the general medical practitioner. Clinics (São Paulo, Brazil). 62. 769-80. 10.1590/S1807-59322007000600018. https://creativecommons.org/licenses/by-nc/4.0/  Primary HSV Acute herpetic gingivostomatitis O  Recurrent HSV Infection Possible stimuli for reactivation: – UV light, trauma, other infections Prodrome (6-24 hrs prior): – Pain, burning, itching, tingling, warmth  Recurrent Herpes Labialis https://phil.cdc.gov/details.aspx?pid=1573 clustered vesicles https://commons.wikimedia.org/wiki/File:Herpes_labialis_Ulcus.jpeg; Speifensender, CC BY-SA 3.0 , via Wikimedia Commons rupture, crust, heal in 7 – 10 days  Recurrent Intraoral HSV Infection Intraoral lesions: – Keratinized mucosa (immunocompetent pts.) – Symptoms often mild Giovanna Mosaico et al. Palate herpes simplex virus infection. Pan African Medical Journal. 2020;35:123. [doi: 10.11604/pamj.2020.35.123.18748]  HSV: Cytologic Features Dr. Roshan Nasimudeen, CC BY-SA 3.0 , via Wikimedia Commons, https://commons.wikimedia.org/wiki/File:Herpes_simplex_cytopathy.jpg HSV: Histopathologic Features Courtesy of Pathology Outlines. https://www.pathologyoutlines.com/topic/skinnontumorherpeszoster.html?mobile=off  Treatment Primary herpetic gingivostomatitis: days – Antivirals effective if administered EARLYwithin Zovirax (acyclovir) suspension or capsules - For pain: - NSAIDs, tetracaine lollipops, dyclonine HCl spray - Avoid viscous lidocaine and topical benzocaine in pediatric patients Recurrent herpes labialis: – Antiviral medications: initiate during prodrome – Mild cases in immunocompetent pts. do not require tx  Treatment Intraoral recurrent herpes: – Often mild, requires no tx – Chlorhexidine alone or in combination w/acyclovir peridex Immunocompromised pts. – systemic tx Antiviral – prophylactic tx VARICELLA ZOSTER VIRUS  ULCERATIVE and VESICULOBULLOUS CONDITIONS SOLITARY or MULTIFOCAL small cluster ACUTE CHRONIC/ ACUT CHRONIC/ PERSISTENT E PERSISTENT Primary HSV VZV Erythema multiforme  Varicella Zoster Virus Primary infection: – Varicella (chickenpox) Latency in dorsal root ganglia Reactivation – Zoster (shingles)  Varicella Clinical features (unvaccinated) – Malaise, pharyngitis, rhinitis – Pruritic rash itchy Source: PHIL Photo ID# 4493; https://www.cdc.govechickenpox/images/people_varic Thomas Netsch, Public domain, via Wikimedia ella5-lg.jpg Commonshttps://commons.wikimedia.org/wiki/File:Windpocken.jpg  Varicella Early (red macule) VESICULAR STAGE (dew drop on rose petal) Ulceration & scabbed “healing” stage F malan, CC BY-SA 3.0 , https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcode’ https://dermnetnz.org/topics/chickenpox/ via Wikimedia Commons  Varicella Breakthrough infection (vaccinated pts.): – Atypical rash (mild, smaller # lesions, shorter duration, less vesicular) https://www.cdc.gov/chickenpox/downloads/varicella-and-breakthrough- varicella.pdf  Varicella Oral lesions: – Esp. palate, buccal mucosa, lip – 3-4 mm white opaque vesicles / ulcers https://renumadan.files.wordpress.com/2017/04/chickenpox- sore.jpg  Varicella Tx: – Symptomatic : baking soda baths, calamine lotion, Benadryl tablets, acetaminophen – If increased risk for complications: Systemic antivirals Postexposure vaccination/VariZIG Prevention – Vaccination (12-15 mos & 4-6 yrs)  Herpes Zoster (Shingles) Predisposing factors for reactivation: – Old age, immunosuppression, EtOH abuse, dental manipulation Clinical: – Prodrome: intense pain (90%) – Acute phase: vesicles on an erythematous base – Chronic phase: postherpetic neuralgia (15%)  Herpes Zoster nerve distribution (dermatome), stops at midline leadto lossof vision eyeinventcan refertooptnamologist https://commons.wikimedia.org/wiki/File:Herps_zoster_ophthalmicus.jpg; Mohammad2018, CC BY-SA 4.0 , via Wikimedia Commons  Herpes Zoster CDC; https://www.sciencephoto.com/media/620945/view/herpes-zoster-of-the-tongue Plviino D et al. Oral herpes zoster. JETem. https://jetem.org/oral_herpes_zoster/ ; (Creative Commons Attribution 4.0 International)  Herpes Zoster Early: Dermatomal vesicular distribution https://dermnetnz.org/topics/herpes-zoster/; https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcode  Herpes Zoster Tx: – Non-aspirin antipyretics, diphenhydramine for itching, antibiotics for secondary skin infection – Antivirals most effective if initiated < 72 hrs after onset of rash – Neuralgia: TCAs, gabapentin, pregabalin, opioids, Prevention: Shingrix (>50yo) Vab M be I s NS ERYTHEMA MULTIFORME  Erythema Multiforme Uncertain etiopathogenesis ACUTE – Probably immune- mediated – Preceding infection (e.g., HSV, Mycoplasma pneumoniae) or exposure to drugs (antibiotics or analgesics) identified in ~50% of cases  Erythema Multiforme Clinical Features Acute onset Young adults, M>F Prodromal symptoms 1wk prior to onset Self limiting – 2-6 weeks – Recurrent episodes in 20% of patients (esp. autumn and spring  Erythema Multiforme n Mockenhaupt, Maja. (2020). Bullous Drug Reactions. https://commons.wikimedia.org/wiki/File:Erythema_multiforme_minor_of_the_hand.jpg; Acta Dermato Venereologica. 100. 10.2340/00015555- James Heilman, MD, CC BY-SA 3.0 , 3408.via CC BY-NC Wikimedia Commons https://dermnetnz.org/topics/erythema-multiforme/ https://creativecommons.org/licenses/by-nc- nd/3.0/nz/legalcode, ERYTHEM CENTRAL TARGET A BULLAE LESIONS  Erythema Multiforme Oral Lesions ulcers w/ irregular borders diffuse hemorrhagic crusting of lip vermilion Joseph, T & Vargheese, Geetha & Mathew, Deepu & Sathyan, Pradeesh. (2012). Drug induced oral erythema multiforme: A rare and less recognized variant of erythema multiforme. Journal of oral and maxillofacial pathology : JOMFP. 16. 145-8. 10.4103/0973-029X.92995. Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported  Erythema Multiforme CLINICAL SUBTYPES 1)MINOR 2)MAJOR Widespread skin lesions plus 2 or more mucosal sites involved (e.g., oral, ocular, genital) https://dermnetnz.org/topics/erythema-multiforme/, https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcode  Erythema Multiforme TX: Corticosteroids –systemic or topical Hydration, topical anesthetic agents Eliminate any causative drugs Acyclovir to prevent recurrences in herpes-induced lesions AUTOIMMUNE VESICULOBULLOUS DISEASES Dx is based upon – clinical features – histologic findings – immunologic findings (immunofluorescence, ELISA)  fromhere talyx itkenfromhere wontbegoodsample busitlikelyWONI haveepithelialcells Rastogi V, Sharma R, Misra SR, Yadav L. Diagnostic procedures for autoimmune vesiculobullous diseases: A review. J Oral Maxillofac Pathol. 2014;18(3):390-397. doi:10.4103/0973-029X.151324Creative Commons Attribution-Noncommercial-Share Alike 3.0 Fig 16-47. Oral and Maxillofacial Pathology. Available from: VitalSource Bookshelf, (4th Edition). Elsevier Health Sciences (US), [Insert Year of Publication].  ULCERATIVE and VESICULOBULLOUS CONDITIONS SOLITARY or MULTIFOCAL small cluster ACUTE CHRONIC ACUT CHRONIC E Pemphigus Pemphigoid Erosive lichen planus FIG 16-48 Oral and Maxillofacial Pathology. Available from: VitalSource Bookshelf, (4th Edition). Elsevier Health Sciences (US), [Insert Year of Publication].  Pemphigus Vulgaris 1-5 cases per million Pathogenesis: – autoantibodies against desmosomal glycoproteins (desmogleins 3 and 1) Saschenbrecker S et al. Serological Diagnosis of Autoimmune Bullous Skin Diseases. Front Immunol 20 Aug 2019 https://doi.org/10.3389/fimmu.2019.01974 Creative Commons Attribution licence (CC-BY)  Pemphigus Vulgaris Clinical Features mean age 50 yo slight F predilection esp. Mediterranean, South Asian, Jewish heritage Oral lesions 50% pts: oral lesions precede cutaneous 1st to show, last to go https://www.ijnpnd.com/viewimage.asp?img=IntJNutrPharmacolNeurolDis_2013_3_2_146_112842_f1.jpg; Kapoor S, Sikka P, et al. Pemphigus vlagris of oral caivity: a case report with it streatmen strategies. Int J Nutr Pharmacol neurol Dis 2013:3:146-9. Creative commons attribution noncommericial sharelike license CC BY-NA-SA  Pemphigus Vulgaris https://dermnetnz.org/topics/pemphigus-vulgaris-image. https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcodes/  Pemphigus Vulgaris Hiroyasu Endo, Terry D. Rees, Hideo Niwa, Kayo Kuyama, Maya Oshima, Tae Serizawa, Shigeo Tanaka, Morio Iijima, Masamichi Komiya and Takanori Ito (December 18th 2018). Gingival Nikolsky’s Sign: A Valuable Tool in Identifying Oral Manifestations of Mucous Membrane Pemphigoid and Pemphigus Vulgaris, Gingival Disease - A Professional Approach for Treatment and Prevention, Alaa Eddin Omar Al Ostwani, IntechOpen, DOI: 10.5772/intechopen.82582. Available from: https://www.intechopen.com/chapters/64825 (CC BY-NC 4.0) “DESQUAMATIVE GINGIVITIS” (DDx also includes pemphigoid and erosive lichen planus)  Pemphigus Vulgaris Ocular Involvement Cutaneous Lesions Infrequent conjunctivitis https://dermnetnz.org/topics/pemphigus-vulgaris-imagehttps://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcodes/ Pemphigus Vulgaris https://dermnetnz.org/topics/pemphigus-vulgaris-imagehttps://creativecommons.org/licenses/by-nc- nd/3.0/nz/legalcodes/  Pemphigus Vulgaris can be Positive Nikolsky Sign even airpressure to induce enough bullae induced on normal-appearing a blister skin/mucosa upon firm lateral pressure  Pemphigus Vulgaris Histopathology: Suprabasilar, intraepithelial separation – “Row of tombstones” Acantholysis Inflammation Suliman, Nada & Astrøm, Anne & Ali, Raouf & Salman, Hussein & Johannessen, Anne. (2013). Clinical and histological characterization of oral pemphigus lesions in patients with skin diseases: A cross sectional study from Sudan. BMC oral health. 13. 66. 10.1186/1472-6831- 13-66. https://creativecommons.org/licenses/by/4.0/legalcode  Pemphigus Vulgaris DX: BE fishnet Perilesional tissue for pattern light microscopy & DIF; serum for IIF Direct Immunofluorescence – Antibodies (IgG and IgM) and complement components (C3) Indirect Immunofluorescence – Positive in 80-90% of cases Emmanuelm at English Wikipedia, CC BY 3.0 , via Wikimedia Commonshttps://commons.wikimedia.org/wiki/File:Pemphigus_immunofluorescence.jpg  Pemphigus Vulgaris “FISH NET PATTERN” https://commons.wikimedia.org/wiki/File:Lake_Erie_Sunset_with_ fish_net.JPG CC BY-SA 3.0 Emmanuelm at English Wikipedia, CC BY 3.0 , via Wikimedia , via Wikimedia Commonshttps://commons.wikimedia.org/wiki/File:Pemphigus_immunofluorescence.jpg Commons  Pemphigus Vulgaris Treatment Systemic immunosuppressive therapy (e.g., rituximab, prednisone) Prognosis Remission rate ~30% Mortality rate 5-10% due to complications of long term systemic corticosteroids  scarring Wilesions associated Mucous Membrane Pemphigoid “Cicatricial Pemphigoid” morelikely to be scar intact than pemphigus Pathogenesis: autoantibodies against one or more components of the basement membrane Mucous Membrane Pemphigoid twice as prevalent as pemphigus vulgaris similar clinical appearance to pemphigus  Mucous Membrane Pemphigoid Clinical Features Average age of onset: 50-60 yo F>M, 2:1 Sites of involvement: oral, skin, ocular, nasal, esophageal, laryngeal, vaginal  Mucous Membrane Pemphigoid Oral Lesions Painful vesicles, bullae, ulcers Desquamative gingivitis Hiroyasu Endo, Terry D. Rees, Hideo Niwa, Kayo Kuyama, Maya Oshima, Tae Serizawa, Shigeo Tanaka, Morio Iijima, Masamichi Komiya and Takanori Ito (December https://dermnetnz.org/topics/mucous-membrane-pemphigoid/, 18th 2018). Gingival Nikolsky’s Sign: A Valuable Tool in Identifying Oral Manifestations of Mucous Membrane Pemphigoid and Pemphigus Vulgaris, Gingival Disease - A https://creativecommons.org/licenses/by-nc-nd/3.0/nz/ Professional Approach for Treatment and Prevention, Alaa Eddin Omar Al Ostwani, IntechOpen, DOI: 10.5772/intechopen.82582. Available from: https://www.intechopen.com/chapters/64825 (CC BY-NC 4.0) Mucous Membrane Pemphigoid https://dermnetnz.org/topics/mucous-membrane-pemphigoid/, https://creativecommons.org/licenses/by-nc-nd/3.0/nz/  Mucous Membrane Pemphigoid Ocular Involvement Symbleturon Fibrous connection ineye 0 https://dermnetnz.org/topics/mucous-membrane-pemphigoid/, https://creativecommons.org/licenses/by-nc-nd/3.0/nz/  Mucous Membrane Pemphigoid Histopathologic Features Direct Immunofluorescence Subepithelial clefting 90% of cases: linear BMZ deposition of immunoreactants ( IgG and C3 > IgA Chronic inflammation and IgM) Hiroyasu Endo, Terry D. Rees, Hideo Niwa, Kayo Kuyama, Maya Oshima, Tae Serizawa, Shigeo Tanaka, Morio Iijima, Masamichi Komiya and Takanori Ito (December 18th 2018). Gingival Nikolsky’s Sign: A Valuable Tool in Identifying Oral Manifestations of Mucous Membrane Pemphigoid and Pemphigus Vulgaris, Gingival Disease - A Professional Approach for Treatment and Prevention, Alaa Eddin Omar Al Ostwani, IntechOpen, DOI: 10.5772/intechopen.82582. Available from: https://www.intechopen.com/chapters/64825 (CC BY-NC 4.0)  Mucous Membrane Pemphigoid Treatment Ophthalmologist referral Topical corticosteroids Systemic corticosteroids plus immunosuppressive agents (cyclophosphamide) Alternatives: – Dapsone, Tetracycline, Minocycline, Niacinamide  EROSIVE LICHEN PLANUS More common than pemphigoid and pemphigus EROSIVE LICHEN PLANUS doesn't rlly cause blistering ulcers erythema https://dermnetnz.org/topics/oral-lichen-planus/, https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcode EROSIVE LICHEN PLANUS “DESQUAMATIVE GINGIVITIS” (DDx also includes pemphigoid and pemphigus) https://dermnetnz.org/topics/oral-lichen-planus/, https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcode  LICHEN PLANUS HISTOPATHOLOGY: superficial band-like lymphocytic infiltrate; basilar vacuolar change, Attili SK. “Interface” Dermatoses: Revisited. Indian J Dermatopathol Diagn Dermatol [serial online] 2019 [cited 2021 Aug 26];6:14-24. Available Hasan S, Attribution-NonCommercial-ShareAlike 4.0 License from: https://www.ijdpdd.com/text.asp? 2019/6/1/14/260182. Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License  LICHEN PLANUS HISTOPATHOLOGY: ragged subepithelial separation Attili SK. “Interface” Dermatoses: Revisited. Indian J Dermatopathol Diagn Dermatol [serial online] 2019 [cited 2021 Aug 26];6:14-24. Available from: https://www.ijdpdd.com/text.asp?2019/6/1/14/260182. Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License  LICHEN PLANUS DIRECT IMMUNOFLUORESCENCE: shaggy subepithelial deposition of fibrinogen NO AUTOANTIBODIES! soimmunofluorescencenot rlly used for this one Hasan S, Ahmed S, Kiran R, Panigrahi R, Thachil JM, Saeed S. Oral lichen planus and associated comorbidities: An approach to holistic health. J Family Med Prim Care. 2019;8(11):3504-3517. Published 2019 Nov 15. doi:10.4103/jfmpc.jfmpc_749_19. Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License  LICHEN PLANUS Treatment – 1st line: topical corticosteroids – Alternatives: topical calcineurin inhibitors (e.g., tacrolimus), steroid-sparing agents, biologics  ULCERATIVE and VESICULOBULLOUS CONDITIONS LOCALIZED (solitary or MULTIFOCAL small cluster ACUTE CHRONIC ACUTE CHRONIC – Primary HSV – Pemphigus – Recurrent HSV – Pemphigoid – VZV infection – Erosive lichen – Erythema multiforme planus  ETIOLOGY INTRAEPITHELIAL SPLIT SUBPITHELIAL SPLIT Viral HSV VZV – Pemphigus – Trauma-induced Friction, suction, burns, Immune- Pemphigus Vulgaris Pemphigoid liquid nitrogen, etc. (Paraneoplastic) mediated – Darier-White disease – LichenErosive planus lichen planus – BullousErythema pemphigoidmultiforme – Cicatricial pemphigoid bullosa acquisita Epidermolysis – Erythema multiforme Linear IgA disease – Epidermolysis bullosa – Epidermolysis bullosa Heritable Darier disease acquisita Epidermolysis bullosa Epidermolysis bullosa (simplex) (junctional, dystrophic, Kindler)  References Neville B, Damm D, Allen C, Chi A. Oral and Maxillofacial Pathology, 5th ed. Available from: VitalSource Bookshelf. Elsevier Health Sciences(2023): – Chapter 7 Viral infections pages 229-240 – Chapter 16 Dermatologic diseases pages 768-779 and 7870792 Kumar V, et al. Robbins Basic Pathology E-Book. Available from: VitalSource Bookshelf, (10th Edition). Elsevier Limited (UK), 2017, pages 895-897.