Society of Dermatology Physicians Assistants Orocutaneous Disease: Review and Update June 29, 2018

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Job Neal Barrett
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1 Society of Dermatology Physicians Assistants Orocutaneous Disease: Review and Update June 29, 2018 John M Wright DDS, MS Regents Professor and Chair Diagnostic Sciences Texas A&M College of Dentistry Dallas, TX jwright@tamhsc.edu

2 Infectious Stomatitis I. Viral Herpes family: DNA viruses characterized by dormancy or latency. HSV, VZV, EBV, CMV A. Herpes Simplex Virus HSV Ubiquitous, most exposed early, 90-95% asymptomatic or subclinical Type 1 (Oral), Type 2 (genital), 20% cross over 1. Primary Herpetic Gingivostomatitis Mostly children (not uncommon in adults) Acute onset vesiculobullous oral eruption, panoral distribution Multiple sharply marginated ulcers, tend to coalesce, very painful gingiva swollen and erythematous Cervical adenopathy, fever ( o F) Diagnosis: Clinical features + cytologic smear (cytopathic effect of multinucleation and ballooning degeneration) + culture Treatment: Supportive Nonsteroidal anti-inflammatories for pain and fever (avoid aspirin).5% dyclonine HCl rinse Tetracycline oral suspension as rinse Hydration (dehydration most serious medical risk in kids) Popsicles Antivirals 2. Secondary or recurrent herpetic infections HSV neurotrophic and remains latent in sensory ganglia (trigeminal) reactivation produces recurrent attacks, localized and milder Recurrent herpes labialis (cold sores, fever blisters) most common, junction of vermilion and skin, prodrome of burning, itching, tingling (most active viral replication) Vesiculation, burst, crust, heal (7-10 days) Treatment: Antivirals at prodrome (apply with covered finger) LLLT- Low level laser therapy Patient education Recurrent intraoral herpetic infection clusters of 1-3mm sharp, painful ulcers on keratinized mucosa (gingiva, palate) immunocompromised - any mucosal surface precipitating factor often dental work Herpetic whitlow/conjunctivitis

3 infection in fingers or conjunctiva / occupational risk Approximately 70% of patients excrete HSV asymptomatically in saliva. At any point in time about 5% have HSV detectable in saliva. B. Varicella-Zoster (VZV) Primary infection, Chickenpox. Recurrence, Shingles Neurotropic, Vth CN - second most common site Post-herpetic neuralgia C. Epstein-Barr (EBV) Burkitt's (African) lymphoma, Infectious Mononucleosis Oral Hairy Leukoplakia D. Cytomegalovirus (CMV) Cytomegalic inclusion disease - multisystem infection (salivary glands) Oro-pharyngeal and esophageal ulcers in HIV II. Fungal A. Candidosis Infection by yeast-like fungus of candida species (albicans usually) C albicans a commensal in normal flora in %, low virulence, opportunistic infection, exist as yeast and hyphae (disease) Clinical Presentations Acute pseudomembranous candidosis Multiple, whitish, curd-like plaques lying on surface with variable erythema. Plaques rub off leaving normal or erythematous base, burning or pain. Acute atrophic candidosis (antibiotic sore mouth) acute discomfort following antibiotics erythema, commonly of gingiva Chronic atrophic candidosis (denture sore mouth) common, erythema confined to denture bearing areas of maxilla constant wear, may be asymptomatic median rhomboid glossitis - mid-dorsal tongue. Predisposing factors Immunological immaturity of infancy Corticosteroid therapy Antibiotic therapy Diabetes mellitis Iron deficiency Xerostomia Advanced malignancy Other immunosuppresive states eg. HIV, transplants, chemotherapy

4 Chronic hyperplastic candidosis (candidal leukoplakia) white or red and white, doesn't rub off clinically identical to leukoplakia, diagnosis by biopsy tongue & commissures malignant transformation Angular cheilitis cracks, fissures, erythema at commissures alone or with intraoral infection 80-90% due to candidosis Diagnosis: Clinical features + cytologic smear Treatment: Antifungals (Nystatin, Mycelex, Ketoconazole, Fluconazole) B. Deep fungal Opportunistic in HIV eg. Histoplamosis

5 Non-Infectious Stomatitis Chronic course I. Benign Migratory Glossitis (Geographic Tongue) (Erythema Migrans) Common, inflammatory condition, unknown etiology, Clinical features: 2:1 females, dorsal and/or lateral tongue, depapillated erythematous areas surrounded by yellowish-white border, single or multiple lesions, usually migrate, asymptomatic, may burn. R/O: Reiters syndrome (urethritis, arthritis, conjunctivitis) Psoriasis Treatment: Topical corticosteroids Zinc supplementation 220 mg daily II. Lichen planus Common, immune mediated (T-cell) mucocutaneous disorder, unknown etiology Clinical features: Middle age, more common in females, bilateral, predilection for cheeks and gingiva, + stress. About 10% with skin disease (purple, pruritic, papules). Reticular: Wickham's striae, most common and most characteristic form, asymptomatic. Erosive: Atrophic, erythematous, ulceration, painful. on gingiva: Desquamative gingivitis Uncommon variants: Bullous, pigmented, plaque R/O lichenoid reactions, especially to drugs. Histology: Hyperkeratotic epithelium, often with angular (saw tooth) rete ridges. Basal cell degeneration, band-like infiltrate of lymphocytes, + colloid bodies (degenerating keratinocytes) Direct IF: Non-specific fibrinogen at BMZ Treatment: Corticosteroids for symptomatic lesions, patients not curable. Complications: Candidosis Malignancy, controversial, low risk. III. Pemphigus vulgaris

6 Pemphigus vegetans very rare Chronic blistering condition affecting skin and mouth, may be fatal. Autoimmune: Antibodies produced against desmoglein 3, a 130KDa extracellular glycoprotein that forms part of extracellular desmosome. Its destruction results in loss of cellular adhesion with desquamation. Clinical features: M=F, 4-5th decade, Jewish and Mediterranean descent. Chronic painful vesiculobullous lesions, desquamative gingivitis, erosions, + Nikolsky sign Oral lesions first in 50% Rare to see vesicles Histology: Direct IF: Intraepithelial, suprabasilar epithelial separation. Epithelial cells lose adhesion (acantholysis) and round (Tzanck cells). IgG, C3 in intercellular spaces. "Chicken coop wire" Indirect IF: + in up to 90%. Treatment: Variant: Moderate to high dose corticosteroids + steroid sparing agents (azathioprine) + topical corticosteroids. Paraneoplastic pemphigus - condition that is clinically, histologically and immunologically similar to pemphigus and pemphigoid. Occurs in patients with malignancies, especially lymphoreticular, (lymphoma, leukemia.) IV. Mucous Membrane Pemphigoid (MMP) (Cicatricial Pemphigoid) Chronic blistering condition affecting primarily mucous membranes that may lead to scarring. Autoimmune: Antibodies against basement membrane constituents (Bullous pemphigoid antigen 2, 180 KDa and others) Clinical features: ages 50-70, females 2:1 desquamative gingivitis, vesiculobullous lesions, ulcers gingiva most common site, painful; + Nikolsky sign ocular involvement about 20-25% (scar, blindness) Histology: Direct IF: Chronic mucositis with epithelial separation at BMZ IgG and/or C3 at BMZ (IgA, IgM Occasionally) Indirect IF: + in about 5%

7 Treatment: Corticosteroids, other immunosuppressants, monitor for eye involvement. V. Lupus Erythematosus Autoimmune disorder, antinuclear antibodies Systemic (SLE), Discoid or Chronic Cutaneous LE (CCLE), Subacute SLE: Female 10:1, young adults - middle age Fever, weight loss, arthritis, pleuropulmonary symptoms, skin rash (butterfly) worsened by sunlight, renal involvement and failure. Clinical features: Erythema or central erythema + ulceration + whitish dots, often with short white striae radiating at margins, painful. Oral lesions 5-50% of patients, rarely alone. Diagnosis: Combination of clinical and laboratory findings as defined by Amer Rheumatism Assoc. Histology: Direct IF: Hyperkeratosis with atrophy and hyperplasia. Basal cell degeneration, papillary edema, lymphocytic infiltrate, often perivascular. Granular band IgG, IgM, C3 at BMZ Treatment: Systemic corticosteroids + other immunosuppressives Antimalarial drugs Oral lesions usually respond to systemic treatment VI. Allergic reactions Topical or systemic Type I Hypersensitivity: IgE - mast cell - histamine mediated painful erythema Type IV Hypersensitivity: Cell mediated immunity, T-cell-cytokine induced red and white or predominantly white lesions Allergens: Cinnamon (Tartar-control toothpaste, mints, gum) Nickel Involvement of cheek and tongue on same side very suggestive. Histology: Treatment: Chronic mucositis, often lichenoid pattern, with perivascular plasma cells Withdraw allergen

8 VII. Recurrent Aphthous Stomatitis Very common mucosal disorder of unknown etiology producing immune mediated, self-limiting ulcers in 4 distinct clinical patterns. Minor, Major, Herpetiform, Behcets Syndrome Precipitating factor: Allergy, genetic (HLA-B12, B51, Cw7), hematologic (B1, B2, B6, B12, Iron, Folate), hormonal, trauma, stress, malabsorption Clinical features: Affects 10% of world population, 50% of some, children and young adults Minor aphthae: 80-90% of cases, 1 + small < 1.5cm painful ulcers with erythematous border, lining mucosa (not overlying bone), heal 7-10 days without scar. Major aphthae: 10%, > 1.5cm ulcers, larger & deeper, soft palate, tonsilar pilars, pharyngeal wall. Last weeks, may heal with scar. Herpetiform aphthae: Behcets Syndrome: Immunopathogenesis: Diagnosis: Treatment: Clusters of small, 1-3mm ulcers. Multisystem disease (small vessel vasculitis) Aphthae, genital ulcers, uveitis, arthritis. Cytotoxic T-cells (CD8) produce cytokines (including tumor necrosis factor) which lyses epithelial cells, suggests antigen is within epithleium. By history and clinical features, biopsy - nonspecific. Topical high-potency corticosteroids Chlorhexidine Amlexanox 5% (Aphthasol) + other immune modulators

9 Acute Onset I. Allergy Usually Type I hypersensitivity. Systemic, skin rash, urticaria with widespread mucosal erythema, desquamation. II. Erythema Multiforme / Stevens Johnson Syndrome Immune mediated mucocutaneous reaction, often to drugs, viral or unknown antigens. Clinical features: Immunopathogenesis: Histology: Direct IF: Treatment: Young adults, slight predilection men, blacks Prodrome flu-like symptoms, acute vesiculobullous mucocutaneous eruption, generalized, symmetrical painful, hemorrhagic crusting of lips + skin, palms & soles, iris or target lesions, self-limiting 2-6 weeks, recurrence 20% Stevens Johnson Syndrome: skin, mouth, eyes, genital, + internal organs Circulating immune complexes localize in vessel walls and activate complement, producing vascular occlusion and ischemic necrosis. Also HSV antigens in epithelial cells. Characteristic but not diagnostic. Subacute inflammation with neutrophils, lymphocytes, eosinophils, exocytosis and keratinocyte necrosis, perivascular inflammation. IgG, IgM, C3 in vessel walls Moderate dose systemic corticosteroids

10 Antifungals Nystatin Oral Suspension disp: 180 ml sig: Rinse with 1 tsp for 3-4 min qid and swallow Clotrimazole (Mycelex) Troche 10mg Vaginal tabs 100mg disp: 50 disp: 20 sig: Dissolve one tab slowly in mouth 5 x daily sig: Dissolve 1 tab slowly bid Ketoconazole (Nizoral) 200mg tab disp: 10 sig: 1 tab daily Fluconazole (Diflucan) 100mg tab disp: 11 sig: 2 tab on day 1, then 1 tab daily Nystatin Ointment disp: 15gm sig: Apply sparingly to affected areas qid Nystatin/triaincinolone acetonide ointment (Mycolog II) disp: 15gm sig: Apply sparingly to affected areas qid Clotrimazole 1% and betamethasone cream (Lotrisone) disp: 15gm sig: Apply sparingly to affected area bid Hydrocortisone-iodoquinol cream 1% (Vytone) disp: 30gm sig: Apply to affected areas qid Anti-virals Acyclovir Caps 200mg (Zovirax) disp: 50 sig: 1 cap 5 x daily Famciclovir Tabs 125mg (Famvir) disp: 14 sig: 1 tab bid

11 Valacyclovir Tabs 500mg (Valtrex) disp: 28 sig: 2 tabs bid Valtrex 500 mg (herpes labialis) disp: 8 sig: 4 tabs at prodrome and 4 tabs after 12 hrs Acyclovir Ointment 5% disp: 15gm sig: Apply 5 x daily with fingercot at first symptom Penciclovir Cream 1% (Denavir) disp: 2 gm sig: Apply q 2 h with fingercot at first symptom Docosanol (Abreva ) (OTC) disp: 2 gm sig: Apply 6 x daily with fingercot Anti-inflammatory / Immunosuppressants High Potency Topical Corticosteroids * Fluocinonide 0.05% (Lidex) * Fluocinolone 0.2% (Synalar HP) * Triamcinolone Acetonide 0.5% (Aristocort, Kenalog) * Desoximetasone 0.25% (Topicort) Highest Potency * Clobetasol propionate 0.05% (Temovate) * Betamethasone diproprionate 0.05% (Diprolene) * Halobetasol Proprionate Ointment 0.05% (Ultravate) Fluocinonide gel disp: 15gm sig: Apply sparingly to affected areas qid Betemathasone diproprionate gel disp: 15gm sig: Apply sparingly to affected areas bid Decadron Elixir 0.5mg/5ml disp: Two 100ml bottles

12 sig: Rinse with 1tsp for 3-4 min after meals and at bedtime and spit out Prednisone 10mg tab disp: 40 sig: 2 tabs bid x 7d, then 1 tab bid x 4d, then 1 tab daily til gone Amlexanox oral paste 5% (Aphthasol) disp: 5gm sig: Apply to affected area qid Symptomatic Relief Xylocaine Viscous 2% disp: 100ml sig: Rinse with 1 tsp as needed and spit out Tetracycline caps 250mg disp: 30 sig: Dissolve contents in 10ml water and swish and spit out q 2 h Mix Dimetapp Elixir 40 Kaopectate 80ml Distilled H2O 120ml sig: Rinse with 1tsp and spit out as needed. Benzocaine in Orabase OTC Paroex Chlorhexidine Gluconate Oral Rinse USP 0.12% (Aqueous)

13 DRUGS CAUSING LICHENOID REACTIONS Allopurinol Gabapentin Phenothiazines Amiphenazole Gold Practolol Atorvastatin (Lipitor) Hydroxychloroquine Propanolol Captopril Ketoconazole Pyrimethamine Carbamazepine Labetalol Quinidine Chloroquine Mercury Quinacrine Chlorpropamide Methyldopa Spironolactone Cyanamide Metopromazine Streptomycin Dapsone NSAID Tetracycline Enalapril Oxyprenolol Thiazides Erythromycin Palladium Tolbutamide Fenclofenac Para-amino salicylic acid Triprolidine Furosemide Penicillamine Zoloft

LESIONS OF THE ORAL CAVITY ORAL CAVITY. Oral Cavity Subsites 4/10/2013 LIPS TEETH GINGIVA ORAL MUCOUS MEMBRANES PALATE TONGUE ORAL LYMPHOID TISSUES

LESIONS OF THE ORAL CAVITY ORAL CAVITY. Oral Cavity Subsites 4/10/2013 LIPS TEETH GINGIVA ORAL MUCOUS MEMBRANES PALATE TONGUE ORAL LYMPHOID TISSUES LESIONS OF THE ORAL CAVITY David I. Kutler, MD, FACS Associate Professor Division of Head and Neck Surgery Department of Otolaryngology HNS Weill Cornell Medical Center ORAL CAVITY LIPS TEETH GINGIVA ORAL