Mucous Membrane Disorders

Andrews Chapter 34

Michael Hohnadel, D.O.

May 25th, 2004

KCOM/Texas Dermatology Residency Consortium

Cheilitis Exfoliativa

• Desquamative, mildly inflammatory, recurrent condition of the lips. Fissures if severe.

• Etiology: – upper lip: cause is often unknown. Primary disorder.

– lower lip: 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 is most common with

dryness, fissuring, edema, crusting, angular cheilitis.

• Etiology: – 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

Allergic Contact Cheilitis

Toothpaste

Actinic Cheilitis

• Lower lip, UV induced.• Ulceration is rare unless SCC is present• Hereditary PMLE may mimic.• Treatment:

– Biopsy if thickened or ulcerated.– Cyro, 5-FU, CO2 laser, Vermilionectomy,

Photodynamic Therapy with 5-ALA, H&E same as AK.

Cheilitis Glandularis

• Presentation: 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 abscess formation.• Etiology: irritation, atopic, factitious, actinic.

Cheilitis Glandularis “STICKY LIPS”

TX SAME AS ACTINIC CHEILITIS

Cheilitis Glandularis

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

Angular Cheilitis (Perleche)• Etiology: Labial commisures, moist fissures with

overlying Candida albicans infection.– Elderly – facial and dental architecture– Youth – thumbsucking, lollipops,

• Other Inciting factors: 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, Sealing agents.

Last resort is excision, flap.

Angular Cheilitis (Perleche)

Plasma Cell Cheilitis

• Sharply outlined, infiltrated, dark red plaque with a laquer-like glazing of the surface of the lower lip

• Reaction pattern to any number of stimuli

• Histology: – Similar to Zoon’s balanitis plasmacellularis– Band-like infiltrate of plasma cells

• Treatment: Clobetasol propionate bid, Griseofulvin 500mg qd.

BAND-LIKE INFILTRATE OF PLASMA CELLS

CHARACTERISTIC KERATINOCYTES ARE DIAMOND-SHAPED OR LOZENGE SHAPED

Plasma Cell Cheilitis

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

• Mackie reports 7 Patients with Ulcers of lower lip. Dc oral meds and resolved.

• May be confused with ulcers of DLE or SCC• Offending agents:

– Phenylbutazone, Chlorpromazine, Phenobarbital, Methyldopa, Thiazide diuretics.

• Fixed-Drug/Photoreaction ?

Other forms of Cheilitis

• Lichen Planus

• SLE

• Psoriasis

• Lip Biting

Oral Crohn’s Disease

• 10-20% of Crohn’s patients. Assoc with active esophageal and anal involvement.

• 90% have granulomas on biopsy• Presentation: 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.

Oral Crohn’s Disease

Pyostomatitis Vegetans• Inflammatory stomatitis in setting of UC or other

inflammatory bowel disease.• Presentation: 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 may occur and favor: axilla, groin, and scalp. – Appear as crusted erythematous papulopustules that coalesce

into asymmetrical annular plaques.

Red – edema

Black – perivascular infiltrate

Blue – abscess formation with eosinophils

TX – Systemic Steroids

Pyostomatitis Vegetans

Cheilitis Granulomatosa

• Sudden onset of lip swelling that progresses to permanent lip enlargement.

• Upper lip usually swells first.

• Cause unknown

• Histology shows tuberculoid granulomas and an inflammatory reaction pattern

• TX- IL steroids and surgical repair.

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

Melkersson-Rosenthal Syndrome• Classic Triad (starts in adolescence)

1. Edema with lip enlargement (other areas may swell too)

2. Scrotal Tongue

3. Recurring facial paralysis (transient or permanent)

• Pathology similar to Cheilitis Granulomatosa• R/O Ascher Syndrome – lip swelling, edema of

eyelids (blepharochalasis)• Treatment: IL Steroids, Surgical nerve

decompression, cosmetic surgery for lip reduction, Clofazimine, Thalidomide

Melkersson-Rosenthal Syndrome

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.

Stomatitis Nicotina

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 (very common), Pachyonychia Congenita, Pemphigus Vegetans, Cowden’s Syndrome.

• Treatment: None required. Keep clean.

Scrotal Tongue

Geographic Tongue

• Usually isolated finding. May be 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.

Geographic Tongue

Black Hairy Tongue

• Benign hyperplasia of the filiform papillae of the anterior 2/3 of the tongue

• Etiology: smoking, oral antibiotics, Candida

• Histology: elongated and stratified filaments composed of ortho and parakeratotic cells.

• TX: toothbrush, tretinoin, 40% urea, stop predisposing factors.

Black Hairy Tongue

Black Hairy Tongue

Benign hyperplasia of the filiform papillae

Moller’s Glossitis• Intensely red, well defined

irregular patches in which the filiform papillae are absent and thinned and the fungiform papillae are swollen.

• Tip and lateral tongue. Tongue may become smooth and glazed.

• Painful, chronic and makes eating difficult

• Check for macrocytic anemia, if present then 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• Presentation: Shiny, oval or diamond shaped

elevation, midline, directly in front of the circumvallate papillae.

• Candida species may be present. No assoc. with cancer.

• Histology: Chronic inflammation with fibrosis with occasional hyphae in areas of parakeratosis

• Itraconazole helpful.

Median Rhomboid Glossitis

Eosinophilic Ulcer of the Tongue

• Ulcer with elevated borders usually covered by a pseudomembrane.– Most common on posterior aspect of tongue– Rapid onset, spontaneously resolves in a few weeks.

• Benign, self-limited. • Etiology: Likely Trauma. • Histology: Predominantly eosinophilic infiltrate

with histiocytes and neutrophils• If multifocal and recurrent, CD30 +

lymphoproliferative disease may be present.

Eosinophilic Ulcer of the Tongue

Caviar Tongue

• Small round purplish capillary telangiectasias

• Commonly found on underside of tongue after age 50

• Etiology: elastic tissue deterioration

Dental Sinus• Tooth abscess forms a sinus

tract that opens on the skin as an inflamed nodule. May palpate a cord-like tract beneath the lesion

• Chin or jawline.• Dental X-Ray diagnostic• DDX: SCC, Actinomycosis,

osteomyelitis, deep fungal, foreign body

Dental Sinus

Leukoplakia

• Once regarded as pre-cancerous

• 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.

• Most common 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

Erythroplakia

Proliferative Verrucous Leukoplakia

• Flat white areas on mucous membranes that thicken and become exophytic

• 70% become SCC

• F > M is 4:1

• Assoc with HPV 16

• Aggressive early therapy is best.

Squamous Cell Carcinoma

• 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 due to late discovery.

Melanocytic Oral Lesions• Melanocytic nevi frequency by type: Intramucosal

> 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%.• Oral Melanoma - Rare, mostly in elderly patients.

Bleeds easily, irregular shape, periphery of erythema or satellite lesions may be present.

LABIAL MELANOTIC MACULE

Melanoacanthoma Variant of pigmented SK. Melanocytes not restricted to basal layer

Oral Melanosis

• Most common in African Americans• Oral melanosis is associated with:

1. McCune Albright Syndrome (dimple over 4th knuckle, Coast of Maine border, unilateral café au lait macule with bony abnormalities below it)

2. Peutz-Jeghers (polyposis, colon cancer)3. Addison’s Disease

• Other causes of oral melanosis: Tar, Heavy metal poisoning, dental amalgams. Cis-platinum can causes a 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• Assoc

Pregnancy.

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

• Most common 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 2nd to biting.

• Soft rounded translucent projection often with a bluish tint.

• TX: excision.

Acute Necrotizing Ulcerative Gingivostomatitis (Trench Mouth, Vincent’s Disease)

• “Punched out” ulcerations on interdental papillae and marginal gingivae. Rapid onset with pain and foul, fetid odor. Erodes gingivae.

• Bacteroides fusiformis & Borrelia vincentii.

• TX: PCN, 3% H2O2 mouthwash, debridement

• R/O herpes infection – not primarily gingivae, no necrosis.

• Means “to devour”• Gangrenous. Starts in the

mouth as a benign oral lesion and rapidly destroys tissues of the mouth and face. < 6 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”

NOMA

Acatalasemia• AKA “Takahara’s disease” • Rare -Autosomal Recessive. 1 in 100,000 in

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

• Pathology: Decrease of circulating neutrophils– Every 21 days neutropenia, mouth ulcerations,

fever, malaise, arthralgias.

• Ulcers irregularly outlined and covered with grayish white slough on mucosal surfaces.

• Cause is unknown.

• TX: Recombinant Colony Stimulating Factor, Cyclosporine, Antibiotics for infections, good dental hygiene.

Recurrent Aphthous Stomatitis

Approach to Recurrent Apthous Stomatitis

• GI symptoms or surgeries ? – UC, Crohn’s, Celiac Dz, Malabsorption (B1, B2, B6)

• Genital or Ocular lesions? – Behcet’s, or Reiter’s syndromes.

• Evaluate risk factors for HIV, AIDS.• Laboratory:

– CBC for anemia, B-12, Folate, Iron, Neutropenia.– Tzanck to R/O Herpes, RPR to R/O syphillis– Biopsy to rule out pemphigus, LP

Recurrent Aphthous Stomatitis Treatment

Symptomatic 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)

Prevention: – 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.• Palate is most common. (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 Aphthous Ulcer)

• Sutton’s Dz• Sharply circumscribed

ulcer with deeply punched out and depressed crater

• Heals with scar.• Freq.assoc with HIV.• Tx: IL steroids. If

frequent then colchicine or dapsone.

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• Oral:

– Ulcers are 2-10mm, sharply circumscribed, with a dirty grayish base and a surrounding bright red halo.

• Genital lesions: – Similar to oral lesions. Appear on genitals, perineum, anus

or rectum.

• Ocular lesions: – Start with intense periorbital pain and photophobia,

conjunctivitis. Retinal vasculitis may lead to blindness. Also glaucoma and cataracts.

• CNS:– Multiple sclerosis-like.

• GI symptoms: due to intestinal ulcerations.• Others: thrombophlebitis, vasculitis,Polyarthralgia

Behcet’s Disease

• Course: Starts with oral ulcerations and over time (often years) others symptoms develop.

• Incidence: Relatively high prev in Far East and Mediterranean. Less common in U.S.

• Pathology: LCV

Pathergy test – Inject 0.1 ml of NS or just prick the skin. Pustule forms 24 hours 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 vennules. There is fibrin deposition in the blood vessel walls, transmural migration of PMNs, extravasated RBCs and nuclear dust

FIBRIN

C-3

IgM

Behcet’s Disease

Behcet’s TreatmentTreatment of ulcers:• Ulcerations usually heal spontaneously• Oral hygiene – mild toothpastes, limited toothbrushing.

Prevention of attacks:• 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