Mucous Membrane Disorders KCOM/Texas Dermatology Residency Consortium

Cheilitis Exfoliativa Desquamative, recurrent, fissures if severe. MC upper lip if cause is unknown. MC lower lip if it is a reaction to other disease states, ie SD, AD, PV, Plummer-Vinson syndrome. Irritation: lipsticks, dentrifices, mouthwashes, shaving/aftershave, nail enamel, lip licking, UV Tx: Remove cause, topical steroids, ointments

Allergic Contact Cheilitis Vermillion border MC, dryness, fissuring, edema, crusting, angular cheilitis. Topicals - meds, dental, lipsticks, sunscreen lip balms, cosmetics, nail polish, cigarette holders, rubber, metals, toothpaste. Foods – oranges, lemons, artichokes, mangoes Saxophone or Clarinet cane reeds Tx: avoid antigen, topical steroids

Actinic Cheilitis Lower lip MC, UV induced Ulceration is rare unless SCC is present Hereditary PMLE may resemble Treatment: Biopsy if thickened or ulcerated Cyro, 5-FU, CO2 laser, Vermilionectomy, Photodynamic Therapy with 5-ALA H&E same as AK

Cheilitis Glandularis Swelling and eversion of lower lip with patulous openings of the ducts of the mucous glands - Chronic, inflammatory. Mucous exudes freely to form a glue-like film, lips stick together, palpation feels like pebbles beneath the surface. Apostematosa variant has abcess formation. Etiology: irritation, atopic, factitious, actinic

H&E – infiltration of lymphocytes, histiocytes and plasma cells in and around the ectatic glands.

Cheilitis Glandularis “STICKY LIPS” TX SAME AS ACTINIC CHEILITIS

Angular Cheilitis (Perleche) MC Candida albicans Labial commisures, moist fissures Elderly – facial and dental architecture Youth – thumbsucking, lollipops, Thrush in DM II or HIV, Tumoral calcinosis, Deficiency of Iron, Riboflavin, Vitamin A, E, etc.

Treatment: Dental consultation - dentures Topical nystatin with iodochlorhydroxyquin (Vioform) in hydrocortisone ointment. Injection of dermal filler substances, excision, flap.

Plasma Cell Cheilitis Sharply outlined, infiltrated, dark red plaque with a laquer-like glazing of the surface of the lower lip Similar to Zoon’s balanitis plasmacellularis Band-like infiltrate of plasma cells Reaction pattern to any number of stimuli Clobetasol propionate bid, Griseofulvin 500mg qd.

BAND-LIKE INFILTRATE OF PLASMA CELLS CHARACTERISTIC KERATINOCYTES ARE DIAMOND-SHAPED OR LOZENGE SHAPED

Plasmoacanthoma Advanced version of Plasma Cell Cheilitis Verrucous tumor with plasma cell infiltrate Candida albicans may be found in the lesions Usually grows along the angles of the mouth

Drug-Induced Ulcer of the Lip May be confused with ulcers of DLE or SCC Phenylbutazone Chlorpromazine Phenobarbital Methyldopa Thiazide diuretics Fixed-Drug/Photo?

Other forms of Cheilitis Lichen Planus SLE Psoriasis Lip Biting

Oral Crohn’s Disease 10-20% of Crohn’s patients 90% have granulomas on biopsy Inflammatory hyperplasia of oral mucosa, cobblestoning, fissuring, Metallic dysgeusia Gingival bleeding Metastatic Crohn’s – non-caseating granulomatous skin lesions in patients with Crohn’s.

Treatment – oral budesonide, mouthwash containing triamcinolone, tetracycline and lidocaine, oral metronidazole, Curettage & Zinc by mouth. Sulfasalazine, Asacol, Pentasa.

Pyostomatitis Vegetans Inflammatory stomatitis in setting of UC. Edema and erythema with deep folding of the buccal mucosa as well as pustules, small vegetating projections, erosions, ulcers and fibrinopurulent exudate. Pustules fuse into shallow ulcers resulting in characteristic “SNAIL TRACK” ulcers Skin lesions favor axilla, groin, scalp, crusted erythematous papulopustules that coalesce into asymmetrical annular plaques.

Red – edema Black – perivascular infiltrate Blue – abcess formation with eosinophils TX – Systemic Steroids

Cheilitis Granulomatosa Sudden onset of lip swelling that progresses to permanent lip enlargment Upper lip usually swells first Cause unknown Histology shows tuberculoid granulomas and an inflammatory reaction pattern TX- IL steroids.

Pathology – tuberculoid granulomas with epithelioid and Langerhan’s giant cells

Melkersson-Rosenthal Syndrome Classic Triad starts in adolescence Lip enlargement (other areas may swell too) Scrotal Tongue Recurring facial paralysis Pathology similar to Cheilitis Granulomatosa R/O Ascher Syndrome – lip swelling, edema of eyelids (blepharochalasis) IL Steroids, Surgical nerve decompression, cosmetic surgery for lip reduction, Clofazimine, Thalidomide

Fordyce’s Disease (Spots) Ectopically located sebaceous glands Minute orange or yellowish pinhead sized macules in mucosa of lips Tx: Isotretinoin

Stomatitis Nicotina “Smokers keratosis” “Smokers patches” Ostia of the mucous ducts appear as red pinpoints surrounded by milky white, slightly umbilicated papules on the palate Maceration, ulceration and aphthae. Heat may be causative event. Tx: Stop smoking, stop drinking hot liquids.

Torus Palatinus Bony protuberance in the midline of the hard palate, asymtomatic

Scrotal Tongue May be congenital or familial. Large tongue with plicate superficial or deep grooves, longitudinal along the median raphe Associations: Melkersson-Rosenthal Syndrome, Down’s Syndrome, Pachyonychia Congenita, Pemphigus Vegetans, Cowden’s Syndrome

Geographic Tongue Isolated finding or associated with Atopic Dermatitis or Psoriasis Annular atrophic areas looks like outlines of countries on a map, locations of lesions change weekly. Asymptomatic usually Topical 0.1% Tretinoin solution may clear in 4-6 days

Histology: epidermal hyperkeratosis and marked transepidermal migration of neutrophils (aka munro’s microabcesses). Cannot be differentiated histologically from pustular psoriasis or Reiter’s syndrome.

Black Hairy Tongue Benign hyperplasia of the filiform papillae of the anterior 2/3 of the tongue Etio: smoking, oral antibiotics, Candida Histo: elongated and stratified filaments composed of ortho and parakeratotic cells. TX: toothbrush, tretinoin, 40% urea, stop predisposing factors.

Moller’s Glossitis Painful, chronic, makes eating difficult Tip and lateral tongue Intensely red, well defined irregular patches in which the filiform papillae are absent and thinned and the fungiform papillae are swollen. Check for macrocytic anemia, if present Pernicious Anemia is likely Hypersegmented neutrophil

Glossitis of Pellagra Sides & tip of tongue are erythematous and edematous with imprints of teeth, “Beefy red” with smooth “glazed” appearance. Niacin, Tryptophan (Niacin precursor), Alcoholism.

4 D’s of Pellagra: diarrhea, dermatitis, dementia, death.

Median Rhomboid Glossitis Shiny oval or diamond shaped elevation, midline, directly in front of the circumvallate papillae. Candida species may be present Histo: Chronic inflammation with fibrosis with occas. hyphae in areas of parakeratosis Itraconazole helpful.

Eosinophilic Ulcer of the Tongue Ulcer with elevated borders usually covered by a pseudomembrane. MC posterior aspect of tongue Rapid onset, spontaneously resolves in a few weeks. Benign, self-limited. Histo: Predominantly eosinophilic infiltrate with histiocytes and neutrophils If multifocal and recurrent CD30 positive lymphoproliferative disease may be present.

Caviar Tongue Small round purplish capillary telangiectasias Commonly found on underside of tongue after age 50 Etio: elastic tissue deterioration

Dental Sinus Tooth abcess forms a sinus tract that opens on the skin as an inflammed nodule MC chin or jawline May palpate a cord-like tract beneath the lesion Dental X-Ray diagnostic Other fistulas: SCC, Actinomycosis, osteomyelitis, deep fungal, foreign body

Leukoplakia Once regarded as precancerous Whitish patches or plaques of the mucous membranes. May or may not reveal cellular atypia Discussed in SCC lecture

Erythroplakia Leukoplakia that has lost the thick macerated keratin layer. MC in mucocutaneous junctions Histologically cellular atypia, pleomorphism, hyperchromatism, increased mitotic figures 90% are SCC in situ or invasive. Moral: biopsy red areas in the setting of leukoplakia

Proliferative Verrucous Leukoplakia 70% become SCC F>M 4 to 1. Flat white areas on mucous membranes that thicken and become exophytic Assoc with HPV 16 Aggressive early therapy is best.

SCC Lower lip has high metastatic rate. Intraoral lesions more likely in those who consume: Cigarettes, Chewing Tobacco, Betel Nuts, Alcohol. May complicate DEB, Erosive LP, XP, Dyskeratosis Congenita Intraoral SCC has only 30% survival rate.

Aquired Dyskeratotic Leukoplakia 1 patient White plaques on palate, gingiva, lips and genitalia Unique finding of clusters of dyskeratotic cells in the prickle cell layer Laser, Etretinate

Melanocytic Oral Lesions Intramucosal MC > Compound > Junctional Labial melanotic macule – solitary @ vermillion border of lower lip, sharply demarcated, young women Blue nevus – dendritic cells in submucosa Oral melanoacanthoma, young blacks, buccal mucosa after trauma, resolves in 40% Melanoma rare, mostly in elderly patients

LABIAL MELANOTIC MACULE

Melanoacanthoma, variant of pigmented SK, melanocytes not restricted to basal layer

Oral Melanosis MC African Americans Things to keep in mind: McCune Albright Syndrome (dimple over 4th knuckle, Coast of Maine border, unilateral café au lait macule with bony abnormalities below it) Peutz-Jeghers (polyposis, colon cancer) Addison’s Disease Tar, Heavy metal poisoning, dental amalgams Cis-platinum – gingival platinum line

Osseous Choristoma of the Tongue Nodule on dorsum of tongue. Contains mature lamellar bone or cartilage Does not recur after excision.

Peripheral Ameloblastoma Rare invasive neoplasm of gingiva MC lower jaw Probably BCC of oral mucosa per Lever

Trumpeter’s Wart Simply a callus Upper lip = trumpeter Lower lip = trombone

Epulis Benign lesion situated on the gingiva. Reactive, inflammatory Peripheral giant cell granuloma solitary bluish red, 10-20 mm tumor between or near bicuspids, incisors.

Pyogenic Granuloma Exuberant overgrowth of granulation tissue Bleeds easily Rapidly growing Asymptomatic

Low power shows a well circumscribed nodule with lobules of dilated and congested capillaries High power shows myxoid stroma and bland endothelial cells

Granuloma Fissuratum Discoid, folded “like a bent coin”, Chronic inflammatory fibrous hyperplasia

Angina Bullosa Haemorrhagica Sudden appearance of one or more blood blisters in the oral mucosa No associated skin or systemic disease May be recurrent MC on soft palate of middle-aged or elderly patients No treatment is necessary

Angina Bullosa Haemorrhagica Subepidermal bullae KEY: bulla is filled with red blood cells.

Mucocele Result of trauma or obstruction of salivary ducts, usually on the lower lip Soft rounded translucent projection often with a bluish tint.

Acute Necrotizing Ulcerative Gingivostomatitis (Trench Mouth, Vincent’s Disease) “Punched out” ulcerations, rapid onset, painful, foul, fetid odor Bacteroides fusiformis & Borrelia vincentii TX: PCN, 3% H2O2 mouthwash, debridement R/O herpes infection NOMA: severe variant in children with poor nutrition, gangrenous spread to bone may result in death.

NOMA, means “to devour” gangrenous, starts in the mouth as a benign oral lesion and rapidly destroys tissues of the mouth and face. MC under six years of age. Fatal in 70% and 90% of cases, survivors disfigured for life Flourishes where poverty is greatest, nutrition is poorest and hygiene is neglected. “Face of poverty”

Acatalasemia AKA “Takahara’s disease” AR, Rare, Japan Deficiency of Catalase enzyme in liver muscles, bone marrow, erythrocytes and skin. Recurrent alveolar ulcerations may progress to gangrene, tooth loss, resolves in puberty. Add H2O2 to blood: it turns blackish brown and the peroxide does not foam TX: Antibiotics and dental extractions.

Cyclic Neutropenia Decrease of circulating neutrophils Every 21 days neutropenia, mouth ulcerations, fever, malaise, arthralgias. Ulcers irregularly outlined and covered with grayish white slough TX: Recombinant Colony Stimulating Factor, Cyclosporine, Antibiotics for infections, good dental hygiene.

Recurrent Apthous Stomatitis

Approach to Recurrent Apthous Stomatitis CBC – Anemia, B-12, Folate, Iron, Neutropenia GI symptoms or surgeries ? – UC, Crohn’s, Celiac Dz, Malabsorption (B1, B2, B6) Genital or Ocular lesions? – think Behcet’s, or Reiter’s. Risk factors for HIV, AIDS ??? Tzanck to R/O Herpes, RPR to R/O Syphillis Biopsy to rule out pemphigus, LP

RAS - Treatment Viscous Lidocaine 2% solution Dyclonine HCl, 0.5% 50/50 mix of Benadryl and Maalox Fluocinonide or Triamcinolone in Orabase. Beconase nasal Spray TCN 250mg dissolved in 5ml solution gargled for 2 minutes then swallowed Apthasol paste (Amlexanox) Dapsone, Colchicine, Thalidomide

Recurrent Intraoral Herpes Simplex Infection Numerous small vesicles in clusters Rupture abruptly to form punctate erosions with a red base. Tzanck smear shows multinucleated epithelial cells. MC Palate (Pearl: Herpangina and Apthous ulcers occur on non-attached mucosa, whereas recurrent Herpes simplex occurs on mucosa fixed to bone)

Periadenitis Mucosa Necrotica Recurrens (Major Apthous Ulcer) Sutton’s Dz Sharply circumscribed ulcer with deeply punched out and depressed crater Heals with scar Tx: IL steroids

Behcet’s Syndrome (Oculo-Oral-Genital Syndrome) Oral ulcers that recur at least 3 times per year in the presence of any 2 of the following: 1) Recurrent genital ulceration 2) Retinal vasculitis, Ant./Post. Uveitis 3) EN, Folliculitis, Papulopustular, Acneiform 4) Positive pathergy test

Behcet’s Disease Ulcers are 2-10mm, sharply circumscribed, with a dirty grayish base and a surrounding bright red halo. Eating may be painful Genital lesions are similar Ocular lesions start with intense periorbital pain and photophobia, conjunctivitis CNS – multiple sclerosis-like GI symptoms due to intestinal ulcerations. Thrombophlebitis, Vasculitis, Arthralgia

Pathergy test – pustule forms 3-4 days after needle-stick Helpful for diagnosis, but usually negative even in the presence of Behcets’ Syndrome

HISTOLOGY OF BEHCET’S = LCV - A neutrophilic infiltrate surrounds the superficial capillary plexus in the papillary dermis, with destruction of small venules. There is fibrin deposition in the blood vessel walls, transmural migration of PMNs, extravasated RBCs and nuclear dust

FIBRIN C-3 IgM

Behcet’s Treatment Ulcerations usually heal spontaneously Oral hygiene – mild toothpastes Sucralfate suspension Colchicine 0.6mg bid Dapsone 100mg daily Thalidomide 200mg bid x 5 days then 100mg bid x 15-60 days Methotrexate for severe refractory cases

The End