Melkersson Rosenthal Sindrome Ingles

34 Disorders of the Mucous Membranes
Bonus images for this chapter can be found online at

expertconsult.inkling.com
Allergic Contact Cheilitis
The vermilion border of the lips is much more likely to develop
Lesions on the mucous membranes may be more difficult to allergic contact sensitivity reactions than is the oral mucosa. Allergic
diagnose than lesions on the skin, and not merely because they cheilitis is characterized by dryness, fissuring, edema, crusting,
are less easily and less often seen. There is less contrast of color and angular cheilitis. Over 90% of patients are women and over
and greater likelihood of alterations in the original appearance half of the reactions are caused by lipsticks. Although patch testing
because of secondary factors, such as maceration from moisture, with standard allergens will reveal a relevant positive in approxi-
abrasion from food and teeth, and infection. Vesicles and bullae mately 25%–30% of patients, about one in five will only react to
rapidly rupture to form grayish erosions, and the epithelium their own product. It may result from use of topical medications
covering papules becomes a soggy, lactescent membrane, easily (Fig. 34.1), dentifrices and other dental preparations, antichap
rubbed off to form an erosion. Grouping and distribution are less agents, lipsticks, and sunscreen-containing lip balms; from contact
distinctive in the mouth than on the skin, and in some cases it with cosmetics, nail polish, rubber, and metals; or from eating
is necessary to establish the diagnosis by observing the character foods such as mangoes. Fragrance and nickel are the most com-
of any associated cutaneous lesions or by noting subsequent monly identified individual sensitizers.
developments. Treatment includes discontinuation of exposure to the offending
agent and administration of topical tacrolimus, pimecrolimus, or
corticosteroid preparations.
CHEILITIS
Aerts O, et al: Contact dermatitis caused by pharmaceutical
Cheilitis Exfoliativa ointments containing “ozonated” olive oil. Contact Dermatitis
The term cheilitis exfoliativa has been used to designate a primarily 2016; 75: 123.
desquamative, mildly inflammatory condition of the lips, of Alrowaishdi F, et al: Allergic contact cheilitis caused by carnauba
unknown cause, and also a clinically similar reaction secondary wax in a lip balm. Contact Dermatitis 2013; 69: 311.
to other disease states. The former is a persistently recurring Barrientos N, et al: Contact cheilitis caused by candelilla wax
lesion that produces scaling and sometimes crusting; it most often contained in lipstick. Contact Dermatitis 2013; 69: 126.
affects the upper lip. The recurrent exfoliation leaves a temporarily Bourgeois P, Goossens A: Allergic contact cheilitis caused by
erythematous and tender surface. menthol in toothpaste and throat medication. Contact Der-
In the latter form, the lips are chronically inflamed and covered matitis 2016; 75: 113.
with crusts that from time to time tend to desquamate, leaving a Budimir V, et  al: Allergic contact cheilitis and perioral dermatitis
glazed surface on which new crusts form. Fissures may be present, caused by propolis. Acta Dermatovenerol Croat 2012; 20: 187.
and there may be burning, tenderness, and some pain. The lower de Groot A: Contact allergy to (ingredients of) toothpastes.
lip is more often involved, with the inflammation limited to the Dermatitis 2017; 28: 95.
vermilion part. The cheilitis may be secondary to seborrheic O’Gorman S, Torgerson RR: Contact allergy in cheilitis. Int J
dermatitis, atopic dermatitis (AD), psoriasis, retinoid therapy, Dermatol 2016; 55: e386.
pyorrhea, long-term actinic exposure, or the habit of lip licking. Panasoff J: Cheilitis caused by to mint-containing toothpastes.
Infrequently, the initial or only manifestation of AD may be a Contact Dermatitis 2016; 75: 260.
chronic cheilitis. Irritating or allergenic substances in lipsticks, Sarre ME, et al: Allergic contact cheilitis caused by polysilicone-15
dentifrices, and mouthwashes may be causative factors. Dyes in (Parsol SLX) in a lip care balm. Contact Dermatitis 2014; 70:
lipsticks may photosensitize. Candidiasis may be present. Cheilitis 119.
may be part of Plummer-Vinson or Sjögren syndrome. Cheilitis Tan S, et al: Allergic contact dermatitis to Myroxylon pereirae
is seen in patients with acquired immunodeficiency syndrome (balsam of Peru) in papaw ointment causing cheilitis. Australas
(AIDS), and it is a known common complication of protease J Dermatol 2011; 52: 222.
inhibitor therapy. These and other, uncommon causes of cheilitis
are discussed in more detail within the specific entities.
The only uniformly effective treatment of cheilitis exfoliativa
Actinic Cheilitis
is the elimination of causes when they can be found. Topical Actinic cheilitis is an inflammatory reaction of the lips to chronic
tacrolimus ointment, pimecrolimus cream, or low-strength cor- excessive sunlight exposure over many years. The lower lip, which
ticosteroid ointments and creams are usually helpful. Excimer is usually the only one involved, becomes scaly, fissured, atrophic
laser therapy or the handheld ultraviolet B (UVB) unit may be (Fig. 34.2), and at times eroded and swollen; leukoplakia and
useful. If the underlying etiology is determined, specific therapy squamous cell carcinoma (SCC) may develop. Painful erosions
may be instituted. When there are fissures, petrolatum or zinc may occur; actual ulceration is very rare unless carcinoma has
oxide ointment applied liberally and often may heal them. developed. Hereditary polymorphous light eruption can resemble
chronic actinic cheilitis, but it has no malignant potential.
Almazrooa SA, et al: Characterization and management of Avoiding sun exposure and the use of sunscreen containing lip
exfoliative cheilitis. Oral Surg Oral Med Oral Pathol Oral pomades suffice to minimize further damage. A biopsy should be
Radiol Endod 2013; 116: e485. performed on any suspicious, thickened areas that persist; preferably,
Bhatia BK, et al: Excimer laser therapy and narrowband ultraviolet a shave technique should be used to avoid scarring.
B therapy for exfoliative cheilitis. Int J Womens Dermatol Cryosurgical treatment may be effective, particularly for local-
2015; 1: 95. ized lesions. In cases with diffuse involvement, application of topical
794
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CHAPTER 34 Disorders of the Mucous Membranes 795
34
Fig. 34.3 Cheilitis glandularis. (Courtesy Dr. Shyam Verma.)
Fig. 34.1 Allergic contact cheilitis to topical steroids. (Courtesy Glen

Crawford, MD.) Vieira RA, et al: Actinic cheilitis and squamous cell carcinoma
of the lip. An Bras Dermatol 2012; 87: 105.
Yazdani Abyaneh MA, et al: Photodynamic therapy for actinic
cheilitis. Dermatol Surg 2015; 41: 189.
Cheilitis Glandularis
Cheilitis glandularis is characterized by swelling and eversion
of the lower lip, patulous openings of the ducts of the mucous
glands, cysts, and at times, abscess formation. There is general
enlargement of the lips (Fig. 34.3). Mucus exudes freely to form a
gluey film that dries over the lips and causes them to stick together
during the night. When the lip is palpated between the thumb
and index finger, the enlarged mucous glands feel like pebbles
beneath the surface. The lower lip is the site of predilection.
Middle-aged men are most often affected. Cheilitis glandularis
is a chronic inflammatory reaction that is caused by an exuberant
response to chronic irritation, or to atopic, factitious, or actinic
damage.
On biopsy, there is a moderate histiocytic, lymphocytic, and
plasmacytic infiltration in and around the glands. Cheilitis glan-
dularis has been reported to eventuate in SCC, but these cases
Fig. 34.2 Actinic cheilitis. (Courtesy Joseph Sobanko, MD.) may be attributed to chronic sun exposure, which frequently
precedes cheilitis glandularis.
Treatment depends on the nature of the antecedent irritation;
in most cases, treatment as described for actinic cheilitis is appropri-
5-fluorouracil (5-FU), imiquimod, ingenol, or photodynamic ate. Surgical debulking may be necessary. Intralesional triamcinolone
therapy (PDT) may be curative. Treatment with a thulium fraction- may be beneficial in some patients, as may the combination of
ated or ablative erbium laser, dermabrasion, or electrodesiccation minocycline and tacrolimus ointment.
may be required for severe disease and provides excellent results.
Long-term follow-up is necessary. Should treatment fail, vermil- Kumar P, Mandal RK: Cheilitis glandularis. Indian J Dermatol
ionectomy of the lower lip may be necessary. Excision of the Venereol Leprol 2015; 81: 430.
exposed vermilion mucous membrane with advancement of the Nico MM, et al: Cheilitis glandularis. J Am Acad Dermatol 2010;
labial mucosa to the skin edge of the outer lip is effective, but 62: 233.
this is performed less frequently since the advent of laser therapy.
Refer to Chapter 29 for more information on actinic cheilitis.
Angular Cheilitis
Cohen JL: Erbium laser resurfacing for actinic cheilitis. J Drugs Angular cheilitis is synonymous with perlèche. Fissures radiate
Dermatol 2013; 12: 1290. downward and outward from the labial commissures. It is an
Dufresne RG Jr, et al: Dermabrasion for actinic cheilitis. Dermatol intertriginous dermatitis caused by excessive wetness or dryness.
Surg 2008; 34: 848. It is often complicated by secondary infection with Candida albicans
Flórez Á, et al: Management of actinic cheilitis using ingenol or Staphylococcus aureus.
mebutate gel. J Dermatolog Treat 2017; 28: 149. The disease usually occurs in elderly people who wear dentures,
Ghasri P, et al: Treatment of actinic cheilitis using a 1,927-nm but it may develop simply from an overhanging of the upper lip
thulium fractional laser. Dermatol Surg 2012; 38: 504. and cheek, and recession and atrophy of the alveolar ridges in old
Muthukrishnan A, Bijai Kumar L: Actinic cheilosis. BMJ Case age. Measuring the facial dimensions with a ruler and tongue
Rep 2017 Mar 20; 2017. blade will help with objective assessment of the importance of
796 Andrews’ Diseases of the Skin
decreased vertical facial dimension in the development of perlèche.

If the distance from the base of the nose to the lower edge of the
mandible is greater than or equal to 6 mm less than the distance
from the center of the pupil to the parting line of the lips, the
vertical dimension is decreased. In these circumstances, drooling
is usually a factor. In children, angular cheilitis occurs frequently
in thumb suckers, gum chewers, and lollipop eaters. Other inciting
factors include riboflavin deficiency, anorexia nervosa, Down
syndrome, intraoral candidiasis, especially in patients with diabetes,
AIDS, chronic mucocutaneous candidiasis, Sjögren syndrome,
orthodontic treatment, drug-induced xerostomia, and AD.
Opening the “bite” by improving denture fit, capping teeth,
replacing lost teeth, or increasing denture height, combined with
topical use of nystatin and iodochlorhydroxyquin in hydrocortisone
ointment, is usually effective when the condition is associated
with anatomically predisposing factors. Stubborn cases typically
respond to a slightly stronger corticosteroid, such as desonide, in Fig. 34.4 Fixed drug eruption.
combination with a topical anticandidal agent. Injection of collagen
or insertion of Softform implants to obliterate the angular creases
may be beneficial. Therapy for underlying diseases should be Senol M, et al: Intertriginous plasmacytosis with plasmoacanthoma.
maximized. If S. aureus is present, mupirocin ointment may be Int J Dermatol 2008; 47: 265.
needed. Excision of the region, followed by a rotating flap graft, Yoshimura K, et al: Successful treatment with 308-nm mono-
is another therapeutic option, but surgery should be reserved for chromatic excimer light and subsequent tacrolimus 0.03%
resistant cases. ointment in refractory plasma cell cheilitis. J Dermatol 2013;
40: 471.
Adedigba MA, et al: Patterns of oral manifestations of HIV/
AIDS among 225 Nigerian patients. Oral Dis 2008; 14: 341.
Lu DP: Prosthodontic management of angular cheilitis and
Drug-Induced Ulcer of the Lip
persistent drooling. Compend Contin Educ Dent 2007; 28: Painful or tender, well-defined ulcerations without induration on
572. the lower lip may heal after withdrawal of oral medications. The
Park KK, et al: Angular cheilitis. Part 1. Cutis 2011; 87: 289. causative drugs may be phenylbutazone, chlorpromazine, pheno-
Park KK, et al: Angular cheilitis. Part 2. Cutis 2011; 88: 27. barbital, methyldopa, or thiazide diuretics. Solar exposure appears
Sharifzadeh A, et al: Oral microflora and their relation to risk to be a predisposing causative influence; in some cases, this reaction
factors in HIV+ patients with oropharyngeal candidiasis. J may represent a fixed drug photoeruption. On rare occasions,
Mycol Med 2013; 23: 105. fixed drug eruptions may also involve the lip, usually caused by
Sharon V, et al: Oral candidiasis and angular cheilitis. Dermatol naproxen, one of the oxicams, or trimethoprim-sulfamethoxazole
Ther 2010; 23: 230. (Fig. 34.4).
Abdollahi M, et al: A review of drug-induced oral reactions. J

Plasma Cell Cheilitis Contemp Dent Pract 2003; 4: 10.
This is also referred to as plasma cell orificial mucositis or, when Pemberton MN, et al: Fixed drug eruption to oxybutynin. Oral
the gingival is the site of involvement, plasma cell gingivitis. It is Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 106:
characterized by a sharply outlined, infiltrated, dark red plaque e19.
with a lacquer-like glazing of the surface of the involved area.
This lesion has the same microscopic features as Zoon balanitis
plasmacellularis. There is plasma cell infiltration in a bandlike
Other Forms of Cheilitis
pattern. Plasma cell cheilitis is not a response that is specific for Several diseases discussed elsewhere may affect the lips, includ-
any stimulus but rather represents a reaction pattern to any one ing lichen planus, lupus erythematosus, erythema multiforme,
of a variety of stimuli. Successful therapies include application of AD, and psoriasis. A high percentage of patients with Down
topical tacrolimus ointment or clobetasol propionate ointment syndrome have cheilitis of one or both lips. Lip biting may be a
twice daily, or use of the 308 nm excimer light. factor.
Plasmoacanthoma ORAL AND CUTANEOUS CROHN DISEASE

Plasma cell cheilitis and plasmoacanthoma have been reported in Crohn disease is a chronic granulomatous disease of any part or
the same patient and are believed to represent a spectrum of the parts of the bowel. Patients with Crohn disease may develop
same disease. Plasmoacanthoma is a verrucous tumor with a plasma inflammatory hyperplasia of the oral mucosa, with metallic dysgeusia
cell infiltrate involving the oral mucosa, particularly along the and gingival bleeding. Reported typical changes include diffuse
angles. Other locations may occur, such as the perianal, periumbili- oral swelling, focal mucosal hypertrophy and fissuring (cobbleston-
cal, or inguinal areas and toe webs. C. albicans has been found ing), persistent ulceration, polypoid lesions, indurated fissuring
within the tissue, suggesting that it may be implicated as a cause of the lower lip, angular cheilitis, granulomatous cheilitis, or
of this disease. Excision, destruction, anticandidal preparations, pyostomatitis vegetans. Oral involvement occurs in 10%–20% of
and intralesional steroids are all options for treatment. patients with Crohn disease, and 90% have granulomas on biopsy.
Males with early-onset disease are most often affected. Concomitant
Abhishek K, Rashmi J: Plasma cell gingivitis associated with involvement of the anal and esophageal mucosa is common. Direct
inflammatory cheilitis. Ethiop J Health Sci 2013; 23: 183. extension to perianal skin may occur.
da Cunha Filho RR, et al: “Angular” plasma cell cheilitis. Dermatol Many cases of Crohn disease with other cutaneous manifesta-
Online J 2014; 20. tions have been reported, notably pyoderma gangrenosum (more
closely associated with ulcerative colitis) and erythema nodosum,

Sweet syndrome, polyarteritis nodosa, pellagra, pernicious 34
anemia, an acrodermatitis-like eruption, urticaria, and necrotizing
vasculitis.
Metastatic Crohn disease denotes noncaseating granulomatous
skin lesions in patients with Crohn disease. In the absence of
bowel involvement, the diagnosis cannot be made. The morphologic
appearances seen include genital swelling or condyloma-like lesions,
leg ulceration, pyogenic granuloma–like lesions of the retroauricular
skin, and erythematous nodules, plaques, or ulcers in other locations.
At times step sectioning or multiple biopsies may be necessary to
reveal the granulomas.
Treatment of the gastrointestinal (GI) manifestations with
sulfasalazine, metronidazole, systemic corticosteroids, infliximab
or other anti–tumor necrosis factor (TNF) agents, or immunosup-
pressive medications such as cyclosporine, azathioprine, myco-
phenolate mofetil, and methotrexate can improve the cutaneous Fig. 34.5 Pyostomatitis vegetans. (Courtesy Scott Norton, MD.)
findings. Several delivery systems use only the active ingredient
of sulfasalazine, mesalamine, including Asacol, Pentasa, Rowasa,
and olsalazine, and may be useful in treating the skin involve- Clark LG, et al: Pyostomatitis vegetans (PSV)–pyodermatitis
ment of Crohn disease. A mouthwash containing triamcinolone vegetans (PDV). J Am Acad Dermatol 2016; 75: 578.
acetonide, tetracycline, and lidocaine may provide symptomatic Crippa R, et al: Oral manifestations of gastrointestinal diseases
and objective improvement. Cutaneous ulcerated granulomas in children. Part 2. Eur J Paediatr Dent 2016; 17: 164.
and erythematous plaques caused by Crohn disease may respond Dupuis EC, et al: Pyoblepharitis vegetans in association with
to high-potency topical corticosteroids or tacrolimus ointment. pyodermatitis-pyostomatitis vegetans. J Cutan Med Surg 2016;
Curettage and zinc by mouth have resulted in healing in several 20: 163.
reported patients. Dietary manipulation is another measure that can Fantus SA, et al: Vegetating plaques on the lips. Am J Derma-
be helpful in select individuals. The course is often prolonged over topathol 2015; 37: 699.
several years. Muhvic-Urek M, et al: Oral pathology in inflammatory bowel
disease. World J Gastroenterol 2016; 22: 5655.
Alemanno G, et al: Rare cutaneous manifestations associ- Wu YH, et al: Pyostomatitis vegetans. J Formos Med Assoc 2015;
ated with Crohn’s disease. Int J Colorectal Dis 2014; 29: 114: 672.
765.
Kurtzman DJ, et al: Metastatic Crohn’s disease. J Am Acad
Dermatol 2014; 71: 804.
CHEILITIS GRANULOMATOSA
Laftah Z, et al: Vulval Crohn’s disease. J Crohns Colitis 2015; Cheilitis granulomatosa is characterized by a sudden onset and
9: 318. progressive course, terminating in chronic enlargement of the
Marzano AV, et al: Cutaneous manifestations in patients with lips. Usually, the upper lip becomes swollen first; several months
inflammatory bowel diseases. Inflamm Bowel Dis 2014; 20: may elapse before the lower lip becomes swollen. Usually, only
213. enlargement is present, without ulceration, fissuring, or scaling.
Shah NP, et al: Treatment of a Crohn’s disease-related facial The swelling remains permanently. It may be a part of the
lesion with topical tacrolimus. Oral Surg Oral Med Oral Pathol Melkersson-Rosenthal syndrome when associated with facial
Oral Radiol 2014; 118: e71. paralysis and plicated tongue.
Thrash B, et al: Cutaneous manifestations of gastrointestinal The cause is unknown. Histologically, cheilitis granulomatosa
disease. J Am Acad Dermatol 2013; 68: 211. is characterized by an inflammatory reaction of lymphocytes,
Yuksel I, et al: Mucocutaneous manifestations of inflammatory histiocytes, and plasma cells and by tuberculoid granulomas
bowel disease. Inflamm Bowel Dis 2009; 15: 546. consisting of epithelioid and Langerhans giant cells. At times,
intralymphatic granulomas are found and may account for the
clinical swelling. In the differential diagnosis, solid edema, angio-
PYOSTOMATITIS VEGETANS edema, cheilitis glandularis, sarcoidosis, oral Crohn disease,
Pyostomatitis vegetans, an inflammatory stomatitis, is most often lymphangioma, hemangioma, and neurofibroma, infectious
seen in association with ulcerative colitis but may also occur in granulomas, contact allergy, reaction to silicone fillers, and Ascher
other inflammatory bowel diseases, such as Crohn disease. Edema syndrome must be considered. Ascher syndrome consists of swelling
and erythema with deep folding of the buccal mucosa characterize of the lips with edema of the eyelids (blepharochalasis) and is
pyostomatitis vegetans, together with pustules, small vegetating inherited.
projections, erosions, ulcers, and fibrinopurulent exudates (Fig. Cheilitis granulomatosa may be the presenting sign in a patient
34.5). Eroded pustules fuse into shallow ulcers, resulting in who will develop Crohn disease or sarcoidosis at a later time.
characteristic “snail-track” ulcers. It has also been associated with Treatment with intralesional injections of corticosteroids is
sclerosing cholangitis. Several cases have been reported with no usually successful but temporary. Combining this modality with
underlying systemic disorder. At times, crusted erythematous oral antiinflammatory agents for long-term control, such as doxy-
papulopustules that coalesce into asymmetric annular plaques may cycline, dapsone, colchicine, sulfasalazine, hydroxychloroquine,
occur with or after the oral lesions. These associated skin lesions anti-TNF agents, or topical tacrolimus ointment, is an excellent
favor the axillae, groin, and scalp and are termed pyodermatitis strategy. In the firmly established case, surgical repair of the involved
vegetans. Topical corticosteroids or tacrolimus ointment may be lip through a mucosal approach and, in some cases, concomitant
effective; systemic corticosteroids or infliximab, however, are usually intralesional corticosteroid treatment provide the best results.
necessary.
Histologically, there are dense aggregates of neutrophils and Alvarez-Garrido H, et al: Crohn’s disease and cheilitis granu-
eosinophils. lomatosa. J Am Acad Dermatol 2011; 65: 239.
Gonzalez-Garcia C, et al: Intralymphatic granulomas as a combined with intralesional corticosteroid injections and oral
pathogenic factor in cheilitis granulomatosa/Melkersson- medications may be more successful than any of the three alone.
Rosenthal syndrome. Am J Dermatopathol 2011; 33: 594. Compression therapy is another adjuvant intervention that may
Lynde CB, et al: Cheilitis granulomatosa treated with intralesional add improvement without side effects. Decompression of the facial
corticosteroids and anti-inflammatory agents. J Am Acad nerve may be indicated in patients with recurrent attacks of facial
Dermatol 2011; 65: e101. palsy. Odontogenic infection has been reported to initiate this
condition, and antibiotic therapy for this may lead to remission.
MELKERSSON-ROSENTHAL SYNDROME Al-Hamad A, et al: Orofacial granulomatosis. Dermatol Clin
Melkersson in 1928 and Rosenthal in 1930 described a triad 2015; 33: 433.
consisting of recurring facial paralysis or paresis, soft nonpitting Belliveau MJ, et al: Melkersson-Rosenthal syndrome presenting
edema of the lips, and scrotal tongue. Attacks usually start during with isolated bilateral eyelid swelling. Can J Ophthalmol 2011;
adolescence, with permanent or transitory paralysis of one or both 46: 286.
facial nerves, repeated migraines, and recurring edema of the upper Bohra S, et al: Clinicopathological significance of Melkersson-
lip, cheeks, and occasionally the lower lip and circumoral tissues. Rosenthal syndrome. BMJ Case Rep 2015 Jul 31; 2015.
Swelling of the skin and mucous membranes of the face and mouth Feng S, et al: Melkersson-Rosenthal syndrome. Acta Otolaryngol
is the dominant finding and most important diagnostic feature 2014; 134: 977.
(Fig. 34.6). In order of frequency, the swelling occurs first on the Li Z et al: Compression therapy. Eur J Dermatol 2011; 21: 1003.
upper lip, then the lower lip, and then other regions. Chronic Miest R, et al: Orofacial granulomatosis. Clin Dermatol 2016;
eyelid swelling may occur. 34: 505.
Extrafacial swellings appear on the dorsal aspect of the hands
and feet and in the lumbar region. The pharynx and respiratory
tract may be involved, with thickening of the mucous membrane.
FORDYCE DISEASE (FORDYCE SPOTS)
The relapsing condition produces an overgrowth of connective Fordyce spots are ectopically located sebaceous glands, clinically
tissue, edema, and atrophy of the muscle fibers, with permanent characterized by minute, orange or yellowish, pinhead-sized macules
deformities of the lips, cheeks, and tongue. or papules in the mucosa of the lips, cheeks, and less often the
The cause of Melkersson-Rosenthal syndrome is unknown. gums. Similar lesions may occur on the areolae, glans penis, and
The association at times with megacolon, otosclerosis, and cra- labia minora. Prominent lip involvement may result in a lipstick-
niopharyngioma supports the theory of a neurotrophic origin. It like mark left on the rim of a glass mug after consuming a hot
may be familial. Histopathologic evaluation shows a tuberculoid beverage (Meffert sign). Involvement of the labial mucosa with
type of granuloma with lymphedema and a banal perivascular pseudoxanthoma elasticum may simulate Fordyce spots. Because
infiltrate. Intralymphatic granulomas may account for the the anomaly is asymptomatic and inconsequential, treatment should
swelling. be undertaken only if there is a significant cosmetic problem.
Melkersson-Rosenthal syndrome is frequently seen in an The carbon dioxide (CO2) laser, electrodesiccation and curet-
incomplete form, and other granulomatous diseases may present tage, bichloracetic acid, PDT, and isotretinoin are therapeutic
as swellings of the lips or orofacial tissues. It is worthwhile calling options.
these, as a group, “orofacial granulomatosis” so that various
underlying disease states or etiologic factors will not be missed Chen PL, et al: Fordyce spots of the lip responding to electrodesic-
when evaluating such patients. The differential diagnosis is the cation and curettage. Dermatol Surg 2008; 34: 960.
same as cheilitis granulomatosa (discussed earlier). Errichetti E, et al: Areolar sebaceous hyperplasia associated with
Intralesional injections of corticosteroids may be beneficial oral and genital Fordyce spots. J Dermatol 2013; 40: 670.
therapy. Again, combining this with oral antiinflammatory agents
for long-term control, such as doxycycline, dapsone, colchicine,
sulfasalazine, hydroxychloroquine, anti-TNF agents, or topical
STOMATITIS NICOTINA
tacrolimus ointment, is an excellent strategy. Clofazimine and Also known as smoker’s keratosis and smoker’s patches, stomatitis
thalidomide are reported to be useful, but availability and side nicotina is characterized by distinct, umbilicated papules on the
effects limit their use. Surgery alone may be used, or surgery palate. The ostia of the mucous ducts appear as red pinpoints
surrounded by milky-white, slightly umbilicated, asymptomatic
papules. The intervening mucosa becomes white and thick and
tends to desquamate in places, leaving raw, beefy-red areas.
Ulceration and the formation of aphthous ulcers may occur.
Stomatitis nicotina is attributed to heavy smoking in middle-aged
men, although it has also been reported in nonsmokers who
habitually drink hot beverages. Heat may be the causative event.
Indeed, the most severe cases are associated with the type of
tobacco use that produces intense heat—pipe and reverse smoking.
Treatment consists of abstaining from the use of tobacco or the
ingestion of hot liquids.
Samatha Y, et al: Clinicopathologic evaluation of lesions associated

with tobacco usage. J Contemp Dent Pract 2014; 15: 466.
Vellappally S, et al: Smoking related system and oral diseases.
Acta Medica 2007; 50: 161.
TORUS PALATINUS
Torus palatinus is a bony protuberance in the midline of the hard
Fig. 34.6 Melkersson-Rosenthal syndrome. palate, marking the point of junction of the two halves of the
palate. It is asymptomatic. Exostoses also frequently occur in the

floor of the mouth, involving the inner surface of the mandible. 34
Bennett WM: Torus palatinus. N Engl J Med 2013; 368: 1434.
Ladizinski B, Lee KC: A nodular protuberance on the hard
palate. JAMA 2014; 311: 1558.
FISSURED TONGUE
Also known as furrowed tongue, scrotal tongue, or lingua plicata,
fissured tongue is a congenital and sometimes familial condition
in which the tongue is generally larger than normal, and plicate
superficial or deep grooves are usually arranged so that there is
a longitudinal furrow along the median raphe, reminiscent of
scrotal rugae (Fig. 34.7).
Fissured tongue is seen in Melkersson-Rosenthal syndrome
and in many patients with Down syndrome. Individual case reports
have been seen in association with pachyonychia congenita,
pemphigus vegetans, and Cowden syndrome. Geographic tongue Fig. 34.7 Fissured tongue.
occurs together with fissured tongue in 50% of patients, and both
are more often present in psoriasis patients than nonpsoriatic
patients.
The condition gives rise to no difficulty, and treatment is not
necessary, except that the deep furrows should be kept clean by
use of mouthwashes. Herpetic geometric glossitis may mimic
fissured tongue, but it is painful, affects predominantly immuno-
compromised individuals, and is centered on the back of the dorsal
tongue.
Dafar A, et al: Factors associated with geographic tongue and

fissured tongue. Acta Odontol Scand 2016; 74: 210.
Madani FM, et al: Normal variations of oral anatomy and common
oral soft tissue lesions. Med Clin North Am 2014; 98:
1281.
Pedersen AML, et al: Oral mucosal lesions in older people. Oral
Dis 2015: 21: 721.
Pereira CM, et al: Herpetic geometric glossitis. Indian J Pathol Fig. 34.8 Annulus migrans.
Microbiol 2010; 53: 133.
Picciani BL, et al: Geographic tongue and fissured tongue in
348 patients with psoriasis. ScientificWorldJournal 2015; 2015: identical; when the tongue lesions occur with psoriasis or reactive
564326. arthritis, the name annulus migrans has been suggested for this
entity (Fig. 34.8).
Histologically, the main features are marked transepidermal
GEOGRAPHIC TONGUE neutrophil migration with the formation of spongiform pustules
Geographic tongue, also known as benign migratory glossitis, it in the epidermis and an upper dermal mononuclear infiltrate.
is a manifestation of atopy, and in others, of psoriasis. It has been Although treatment is not usually necessary, a 0.1% solution of
reported as being acquired in patients with AIDS or as a result tretinoin applied topically has produced clearing within 4–6 days,
of lithium therapy. In most, however, it is an isolated finding. and tacrolimus ointment may improve it.
The dorsal surface of the tongue is the site usually affected.
Geographic tongue begins with a small depression on the lateral Mangold AR, et al: Diseases of the tongue. Clin Dermatol 2016;
border or the tip of the tongue, smoother and redder than the 34: 458.
rest of the surface. This spreads peripherally, with the formation Picciani BL, et al: Geographic tongue and psoriasis. An Bras
of sharply circumscribed, ringed or gyrate, red patches, each with Dermatol 2016; 91: 410.
a narrow, yellowish white border, making the tongue resemble Purani JM, Purani HJ: Treatment of geographic tongue with
a map. The appearance changes from day to day; patches may topical tacrolimus. BMJ Case Rep 2014 Aug 1; 2014.
disappear in one place and manifest in another. The disease is Varoni E, Decani S: Geographic tongue. N Engl J Med 2016;
characterized by periods of exacerbation and quiescence. The 374: 670.
appearance may also remain unchanged in the same site for long
periods. The condition is frequently unrecognized because it
produces no symptoms except for the occasional complaint of
BLACK HAIRY TONGUE
glossodynia. Black or brown hairy tongue occurs on the dorsum of the tongue
There are two clinical variants of geographic tongue. In one anterior to the circumvallate papillae, where black, yellowish, or
type, discrete, annular “bald” patches of glistening, erythematous brown patches form, consisting of hairlike intertwining filaments
mucosa with absent or atrophic filiform papillae are noted. Another several millimeters long (Fig. 34.9). The “hairs” result from a
type shows prominent circinate or annular, white raised lines that benign hyperplasia of the filiform papillae of the anterior two
vary in width up to 2 mm. The clinical appearance and histo- thirds of the tongue, resulting in retention of long, conical filaments
pathologic findings of the tongue lesions in pustular psoriasis, of orthokeratotic and parakeratotic cells. It occurs much more
reactive arthritis (Reiter syndrome), and geographic tongue are frequently in men than in women.
Fig. 34.9 Black hairy tongue. (Courtesy Steven Binnick, MD.)

Fig. 34.10 Smooth tongue in Plummer-Vinson syndrome.
Black hairy tongue may be associated with several conditions and a leukoplakia may result. Treatment of pernicious anemia
that may be predisposing factors in its causation: smoking, use with vitamin B12 therapy will result in improvements in the
of oral antibiotics, interferon treatment, xerostomia, psycho- appearance and sensitivity of the tongue.
tropic drugs, and presence of Candida on the surface of the Atrophic glossitis is also a distinctive sign of pellagra; it results
tongue. from a deficiency of niacin or its precursor, tryptophan. The sides
This lesion may be differentiated both clinically and histologi- and tip of the tongue are erythematous and edematous, with
cally from oral hairy leukoplakia, which is seen in human immu- imprints of the teeth. Eventually, the entire tongue assumes a
nodeficiency virus (HIV)–infected patients. Hairy leukoplakia is beefy-red appearance. Small ulcers appear, and all the mucous
usually seen on the lateral surface of the tongue, at first in cor- membranes of the mouth may be involved. Later, the papillae
rugated patches, then with time, as solid white plaques that are become atrophied to produce a smooth, glazed tongue, as seen
adherent. Microscopic examination reveals acanthosis, parakeratosis, in pernicious anemia. Burning or pain in the ulcers may be present.
irregular projections of keratin, and vacuolated keratinocytes with Increased salivary flow early in the disease may lead to drooling
Epstein-Barr virus (EBV) present within them. and angular cheilitis. In malabsorption syndrome, riboflavin
A toothbrush may be used to scrub off the projections, either deficiency, anorexia nervosa, alcoholism, and sprue, similar changes
alone, with 1%–2% hydrogen peroxide, or after application of may be noted. Vitamin B complex is curative.
tretinoin gel, 40% aqueous solution of urea, or papain (meat Patients with iron deficiency anemia, alone or with esophageal
tenderizer). Such predisposing local factors as smoking, antibiotics, webs (Plummer-Vinson syndrome), and those with folic acid
and oxidizing agents should be eliminated, if possible, and scru- deficiency, syphilis, amyloidosis, celiac disease, Sjögren syndrome,
pulous oral hygiene maintained. or Riley-Day syndrome, may all manifest smooth tongue. Can-
didiasis may result in tongue pain and a partial or total atrophic
Arab JP, et al: Black hairy tongue during interferon therapy for appearance, along with a red or magenta color, on the dorsum of
hepatitis C. Ann Hepatol 2015; 14: 414. the tongue. In such patients, anticandidal therapy results in rapid
Balaji G, et al: Linezolid induced black hairy tongue. Indian J improvement.
Pharmacol 2014; 46: 653.
Gurvits GE, Tan A: Black hairy tongue syndrome. World J Cunha SF, et al: Papillary atrophy of the tongue and nutritional
Gastroenterol 2014; 20: 10845. status of hospitalized alcoholics. An Bras Dermatol 2012; 87:
Thompson DF, et al: Drug-induced black hairy tongue. Phar- 84.
macotherapy 2010; 30: 585. Demir N, et al: Dermatological findings of vitamin B12 deficiency
and resolving time of these symptoms. Cutan Ocul Toxicol
2014; 33: 70.
SMOOTH TONGUE Lee HJ, et al: A smooth, shiny tongue. N Engl J Med 2009; 360:
Also known as atrophic glossitis, the smooth glossy tongue is often e8.
painful and results from atrophy of the filiform and eventually Mangold AR, et al: Diseases of the tongue. Clin Dermatol 2016;
the fungiform papillae (Fig. 34.10). It begins with the tip and 34: 458.
lateral surfaces of the tongue becoming intensely red, well-defined
irregular patches in which the filiform papillae are absent or thinned
and the fungiform papillae are swollen. The disease is chronic,
ERUPTIVE LINGUAL PAPILLITIS
and the patches are painful and sensitive, so eating may be difficult Lacour and Perrin first described this acute, self-limiting inflam-
and taste impaired. With time, the entire tongue becomes smooth, matory stomatitis in 1997. It affects children of both genders
34
Fig. 34.11 Eruptive lingual papillitis.
Fig. 34.12 Median rhomboid glossitis. (Courtesy Steven Binnick, MD.)

equally, with a mean age at onset of 3 1 2 years. It has a seasonal
distribution, with the majority of cases occurring in the spring.
Fever (40%), difficulties in feeding (100%), and intense salivation
(60%) are common symptoms. The tongue examination reveals
EOSINOPHILIC ULCER OF THE ORAL MUCOSA
inflammatory hypertrophy of the fungiform papillae on the tip Eosinophilic ulcer occurs most frequently on the tongue but may
and dorsolateral sites (Fig. 34.11). Additional signs include sub- occur anywhere in the oral mucosa. It is characterized by an ulcer
mandibular or cervical adenopathy (40%) and angular cheilitis with indurated and elevated borders that is usually covered by a
(10%). Associated skin eruptions have not been described. Spontane- pseudomembrane. It develops rapidly, most often on the posterior
ous involution occurs in a mean of 7 days (range 2–15 days). aspect of the tongue, and spontaneously resolves in a few weeks.
Recurrence is noted in 13%. Eruptive lingual papillitis is thought A traumatic cause has been postulated for this benign, self-limited
to result from a viral infection, and the 50% transmission among disorder. The histopathologic findings show a predominantly
family members further supports this eosinophilic infiltrate with some histiocytes and neutrophils.
theory. In some multifocal, recurrent cases, CD30+ cells have been
reported. These patients may have the oral counterpart of primary
Mondal A, et al: Eruptive lingual papillitis. Indian Pediatr 2014; cutaneous CD30+ lymphoproliferative disease, or may simply be
51: 243. a simulator of this disorder. In one positive case, EBV staining
Roux O, et al: Eruptive lingual papillitis with household transmis- was positive; the lesion resolved in 4 weeks. HIV-infected patients
sion. Br J Dermatol 2004; 150: 299. may develop ulcerations of the oral mucosa, resulting from a
variety of infectious agents, such as herpes simplex virus (HSV),
candidiasis, and histoplasmosis. However, 5 of the 16 patients
MEDIAN RHOMBOID GLOSSITIS reported had no evidence of infection and simply showed eosino-
Median rhomboid glossitis is characterized by a shiny, oval or philic infiltrates below the ulcer.
diamond-shaped elevation, invariably situated on the dorsum in
the midline immediately in front of the circumvallate papillae Abdel-Naser MB, et al: Oral eosinophilic ulcer, an Epstein-Barr
(Fig. 34.12). The surface is abnormally red and smooth. In some virus–associated CD30+ lymphoproliferation? Dermatology
cases, a few pale-yellow papules surmount the elevation. On palpa- 2011; 222: 113.
tion, the lesion feels slightly firm, but it usually causes no symptoms. Damevska K, et al: Eosinophilic ulcer of the oral mucosa. Am J
It persists indefinitely, with minimal or no increase in size. There Dermatopathol 2014; 36: 594.
is no relationship to cancer. Didona D, et al: Eosinophilic ulcer of the tongue. An Bras
Median rhomboid glossitis may result from abnormal fusion Dermatol 2015; 90: 88.
of the posterior portion of the tongue, but it is almost always Lee EY, et al: Clinical characteristics of odontogenic cutaneous
chronically infected with Candida. If there is palatal inflammation fistulas. Ann Dermatol 2016; 28: 417.
above the inflamed part of the tongue, AIDS should be suspected
and an HIV test obtained. Histologically, the changes are those
of a simple, chronic inflammation with fibrosis, and usually with
CAVIAR TONGUE
fungal hyphae in the parakeratin layer. Treatment with clotrimazole This is a purplish venous ectasias commonly found on the under-
troches or oral antifungals, such as itraconazole, may lead to surface of the tongue after age 50. They are attributed to elastic
improvement. tissue deterioration with aging and may be associated with Fordyce
angiokeratomas of the scrotum. Phleboliths or thrombophlebitis
Basak P, et al: A smooth patch on the tongue. N Engl J Med may occasionally complicate this condition.
2010; 363: 1949.
Panta P, Erugula SR: Median rhomboid glossitis—developmental Viswanath V, et al: Caviar tongue. Indian J Dermatol Venereol
or candidal? Pan Afr Med J 2015; 21: 221. Leprol 2011; 77: 78.
NEOPLASMS
Many tumors may involve the oral cavity. Most are discussed
elsewhere in this book, and several are uncommon entities that
affect specialized oral structures, such as the many subtypes of
benign and malignant proliferations that occur in the major and
minor salivary glands. These are not covered further here, and
only a few select neoplasms are presented.
Leukoplakia
Clinical Features
Leukoplakia presents as a whitish thickening of the epithelium of
the mucous membranes, occurring as lactescent superficial patches
A of various shapes and sizes that may coalesce to form diffuse
sheets. The surface is generally glistening and opalescent, often
reticulated, and may even be somewhat pigmented. The white
pellicle is adherent to the underlying mucosa, and attempts to
remove it forcibly cause bleeding. At times, it is a thick, rough,
elevated plaque. The lips, gums, cheeks, and edges of the tongue
are the most common sites, but the lesion may arise on the anus
and genitalia. Leukoplakia is found chiefly in men over age 40.
Biopsy of these white lesions may reveal orthokeratosis or
parakeratosis with minimal inflammation, or there may be evidence
of varying degrees of dysplasia. A benign form is usually a response
to chronic irritation and has very little chance of conversion into
the precancerous dysplastic form. Premalignant leukoplakia, with
atypical cells histologically, is present in only about 10%–20% of
leukoplakia. Unfortunately, it is not possible to predict clinically
which lesions will be worrisome histologically, except that if
ulceration, red areas, or erosions are scattered throughout, the
lesion is most likely precancerous. Therefore biopsy is indicated.
B When the lesion occurs on the lip, leukoplakia is closely related
to chronic actinic cheilitis, which consists of a circumscribed or
Fig. 34.13 (A) Cutaneous dental sinus. (B) Poor oral hygiene in the diffuse keratosis, almost invariably on the lower lip. It is preceded
patient shown in (A). by an abnormal dryness of the lip and may be caused by smoking
(especially pipe smoking) or chronic sun exposure. This type of
leukoplakia is distinguished from SCC of the lip by the absence
of infiltration, from lichen planus and psoriasis of the lips and
mouth by the absence of lesions elsewhere, and from lupus ery-
CUTANEOUS SINUS OF DENTAL ORIGIN thematosus by the absence of telangiectases. Biopsy is necessary,
however, to differentiate these conditions fully.
(DENTAL SINUS) Intraoral leukoplakia appears to progress to SCC in no more
In dental (or odontogenous) sinus, chronic periapical infection than 1% of lesions per year. In time, an extensive, thick, white
around a tooth produces a burrowing, practically asymptomatic, pellicle may cover the tongue or oral mucosa. In old lesions, the
occasionally palpable, cordlike sinus tract that eventually appears epithelium may be desquamated, and there may be fissures or
beneath the surface of the gum, palate, or periorificial skin. It ulcerations. Such changes are associated with more or less hyper-
forms a fistulous opening with an inflamed red nodule at the emia and tenderness, and with a tendency to bleed after slight
orifice. It may appear anywhere from the inner ocular canthus to trauma. If transformation to carcinoma occurs, it generally follows
the neck, but is most often seen on the chin or along the jawline a lag time of 1–20 years, although immunosuppressed transplant
(Fig. 34.13). Bilateral involvement has been reported. Dental patients may have a rapid course of transformation.
radiography is diagnostic. Pyogenic granuloma, actinomycosis, Oral hairy leukoplakia is a term used to describe white, corrugated
SCC, osteomyelitis of the mandible, congenital fistulas, the deep plaques that occur primarily on the sides of the tongue. It was
mycoses, bisphosphonate-related osteonecrosis of the jaw, and initially described as a manifestation of AIDS. Its appearance in
foreign body reactions must be considered in the differential these patients has decreased. It may be seen in patients with local
diagnosis. Treatment requires the removal of the offending tooth or systemic immunosuppression such as those on steroid inhalers,
or root canal therapy of the periapical abscess. on immunosuppressant or chemotherapy, therapy, or with leukemia.
(Fig. 34.14). This is a virally induced lesion, discussed in Chapter
Bodner L, et al: Cutaneous sinus tract of dental origin in children. 19, which has a characteristic histology.
Pediatr Dermatol 2012; 29: 421. Leukoplakia of the vulva usually occurs in obese women after
Gupta, et al: A clinical predicament—diagnosis and differential menopause as grayish white, thickened, pruritic patches that may
diagnosis of cutaneous facial sinus tracts of dental origin. Oral become fissured and edematous from constant rubbing and
Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 112: scratching. Secondary infection with edema, tenderness, and pain
e132. may occur. It is differentiated from lichen planus by the absence
Truong SV, et al: Bisphosphonate-related osteonecrosis of the of discrete, rectangular, or annular flat papules of violaceous hue
jaw presenting as a cutaneous dental sinus track. J Am Acad in the mucosa outside the thickened patches, about the anus, on
Dermatol 2010; 62: 672. the buccal mucosa, or on the skin. Leukoplakia of the vulva is
34
Fig. 34.14 Oral hairy leukoplakia of HIV. Fig. 34.15 Erythroplakia.
most frequently confused with lichen sclerosus et atrophicus and

other vulval atrophies. On the penis, although leukoplakia may
Epidermization of the Lip
occur, a similar precancerous process called erythroplasia (of Relatively smooth leukokeratosis of the lower vermilion, blending
Queyrat) is usually seen instead. evenly into the skin surface distally and having a steep, sharp,
irregular proximal margin, may easily be mistaken clinically for
precancerous leukoplakia. Histologically, it shows only hyperkera-
Etiology tosis, without parakeratosis or cellular atypia. A shallow shave
Numerous factors are involved in the cause of leukoplakia. It may excision suffices to cure it and to rule out precancerous leukoplakia;
develop as a result of tobacco smoking; use of smokeless tobacco; no fulguration is required.
areca, qat, or betel nut chewing; reverse smoking; alcohol; poorly
fitting dentures; sharp and chipped teeth; treatment with BRAF
inhibitors; or improper oral hygiene. Extensive involvement of
Erythroplakia
the lips and oral cavity with leukoplakia may exist for years with The term erythroplakia is applied to leukoplakia that has lost (or
no indication of carcinoma. On the other hand, small, inflamed has not developed) the thick keratin layer that makes leukoplakia
patches may be the site of a rapidly growing tumor, which, with white; it is the usual pattern in mucocutaneous junctions. A focal
relatively insignificant local infiltration, may involve the cervical red patch with no apparent cause should be suspected of being
lymphatics. Carcinoma in leukoplakia usually begins as a localized precancerous when found on the floor of the mouth, soft palate,
induration, often around a fissure, or as a warty excrescence or a or buccal mucosa or under the tongue (Fig. 34.15). Histologically,
small ulcer. There is a 6%–10% transformation rate of intraoral there is cellular atypia, pleomorphism, hyperchromatism, and
leukoplakia into SCC. Predictors of a higher risk of SCC develop- increased mitotic figures. Carcinoma in situ or invasive carcinoma
ment include older age; female gender; nonsmokers; large size; is found in 90% of lesions.
presence on the lateral or ventral tongue, floor of the mouth, or
retromolar/soft palate complex; erythroleukoplakia; and a non-
homogeneous morphology.
Oral Florid Papillomatosis
The degree of epithelial atypia may be considered in staging Oral florid papillomatosis is a confluent papillomatosis covering
the risk of developing malignancy. Aneuploid leukoplakia has a the mucous membranes of the oral cavity. The distinctive picture
high rate of transformation into aggressive SCC, and the cancers is that of a white mass resembling a cauliflower, covering the
derived from it are more likely to be lethal. tongue and extending on to the other portions of the mucous
membranes, including the oropharynx, larynx, and trachea. Usually,
there is no lymphadenopathy.
Treatment The course of the disease is progressive. Many lesions
It must be remembered that cancer develops frequently on histologi- eventuate in SCC, whereas others continue for many years,
cally dysplastic leukoplakia, and thus its complete removal should with the patient dying of some intercurrent disease. Oral florid
be the goal in each case—first by conservative measures, then by papillomatosis should be regarded as a verrucous carcinoma,
surgery or destruction, if necessary. The use of tobacco should which has been defined as a distinctive, slowly growing, fun-
be stopped and proper dental care obtained. Fulguration, simple gating tumor representing a well-differentiated SCC in which
excision, cryotherapy, PDT, and CO2 laser ablation are effective metastases occur very late or not at all. The histologic features
methods of treatment. Medical therapies that have been the subject are those of papillomatosis, acanthosis, and varying degrees of
of randomized clinical trials may lead to temporary resolution of dysplasia of the epithelium, without disruption of the basement
the lesions, but relapses and adverse effects are common, and there membrane. It is reasonable to expect the eventual development
is no evidence that they prevent the transformation to malignancy. of epidermoid carcinoma in most patients. Esophageal involve-
ment and keratotic papules of the extremities may occur. In
Leukoplakia With Tylosis and Esophageal the differential diagnosis, leukoplakia, proliferative verrucous
leukoplakia, candidiasis, acanthosis nigricans, and condyloma
Carcinoma acuminatum should be considered. The recommended treatment
Leukoplakia associated with tylosis and esophageal carcinoma is is surgical excision; however, it is often followed by recurrence and
extremely rare but may occur. spread.
Fig. 34.16 Proliferative verrucous leukoplakia; three sites of

squamous cell carcinoma: lip and twice in palate.
Proliferative Verrucous Leukoplakia Fig. 34.17 Squamous cell carcinoma secondary to chewing betel nut.
Proliferative verrucous leukoplakia is a slowly progressive condition (Courtesy Shyam Verma, MBBS, DVD.)
that begins as multifocal sites of hyperplasia of the oral mucous
membranes and proceeds to thicken and enlarge until SCC results
(Fig. 34.16). Women outnumber men 4 : 1. Initially flat, usually Abadie WM, et al: Optimal management of proliferative ver-
white patches are present, but the lesions relentlessly become rucous leukoplakia. Otolaryngol Head Neck Surg 2015; 153:
warty, exophytic masses. About 70% of patients develop SCC, 504.
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patients dying of it. There has been an irregular association with proliferative verrucous leukoplakia compared with conventional
human papillomavirus (HPV)–16 infection, and risk factors for squamous cell carcinoma. Oral Surg Oral Med Oral Pathol
SCC of the oral cavity are usually not present. Treatment is difficult Oral Radiol 2015; 119: 318.
because of the multifocal nature of the lesions. Aggressive early Bagan JV, et al: Malignant transformation of proliferative verrucous
surgical therapy is best. Many patients develop recurrence after leukoplakia to oral squamous cell carcinoma. Oral Oncol 2011;
only a short interval. 47: 732.
Carrard VC, et al: Proliferative verrucous leukoplakia. Med Oral
Patol Oral Cir Bucal 2013; 18: e411.
Squamous Cell Carcinoma Chambers AE, et al: Twenty-first-century oral hairy leukoplakia.
SCC is the most common oral malignancy and constitutes 2%–3% Oral Surg Oral Med Oral Pathol Oral Radiol 2015; 119:
of all new cancers. With almost 30,000 yearly cases in the United 326.
States, SCC is the tenth most common malignancy. It occurs Gillenwater AM, et al: Proliferative verrucous leukoplakia. Head
primarily in older men. The most frequent sites are the lower lip, Neck 2014; 36: 1662.
tongue, soft palate, and floor of the mouth. SCC of the lip develops Hall LD, et al: Epstein-Barr virus. J Am Acad Dermatol 2015;
from actinic damage, with 95% of the cases involving the lower 72: 1.
lip. Intraoral lesions frequently develop from leukoplakia or Liu W, et al: Oral cancer development in patients with leukoplakia.
erythroplakia, at sites of frequent irritation, or from long-standing PLoS One 2012; 7: e34773.
mucosal inflammatory disease such as ulcerative lichen planus. Lodi G, et al: Interventions for treating oral leukoplakia to
About 20% of oral squamous cell cancers have an associated focus prevent oral cancer. Cochrane Database Syst Rev 2016; 7:
of leukoplakia; these tend to be diagnosed at a less advanced stage CD001829.
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of intraoral SCC. Alcohol has not been shown to be an independent 315.
risk factor. Many are positive for HPV-16 or HPV-18. The risk Vale DA, et al: Retrospective analysis of the clinical behavior of
factors may also include xeroderma pigmentosa (tip of tongue), oral hairy leukoplakia in 215 HIV-seropositive patients. Braz
dyskeratosis congenita, dystrophic epidermolysis bullosa, erosive Oral Res 2016; 30: e118.
lichen planus, and oral submucous fibrosis. Unfortunately, the Vigarios E, et al: Oral squamous cell carcinoma and hyperkera-
survival rate has remained at 50% for many years because disease totic lesions with BRAF inhibitors. Br J Dermatol 2015; 172:
is often discovered late, after it has metastasized to the cervical 1680.
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to oral cancer screening. Surgical excision is the treatment of algorithm. J Oral Maxillofac Surg 2017; 75: 723.
choice; the roles of sentinel lymph node dissection and adjuvant Yang SW, et al: Outcome of excision of oral erythroplakia. Br J
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approach to oral SCC treatment. 857.
34
Fig. 34.18 Acquired dyskeratotic leukoplakia. Fig. 34.19 Oral melanosis.
lentigo, blue nevus, Spitz nevus, and labial melanotic macules are
Acquired Dyskeratotic Leukoplakia other types of focal hyperpigmentation. Ephelides darken on sun
James and Lupton reported a patient with acquired dyskeratotic exposure and are usually limited to the lower lip. The blue nevus
leukoplakia that manifested as distinctive white plaques on the has dendritic cells in the submucosa. Lentigines show acanthosis
palate, gingivae, and lips (Fig. 34.18). There were similar lesions of rete ridges on biopsy. Oral melanotic macules are solitary, sharply
of the genitalia. Histologically, there was a unique finding of clusters demarcated, flat, pigmented lesions that occur chiefly in young
of dyskeratotic cells in the prickle cell layer in all affected sites. women, do not change on sun exposure, and show only acanthosis
Aggressive laser treatment was followed by recurrence. Use of and basal-layer melanin on biopsy.
etretinate afforded some improvement, but the condition continued Oral melanoacanthoma is a simultaneous proliferation of
unabated more than 20 years. keratinocytes and melanocytes. It is most frequently observed in
young black patients (average age 23) on the buccal mucosa. It
James WD, et al: Acquired dyskeratotic leukoplakia. Acta Dermatol seems to be a reactive process, usually after trauma and resolving
1988; 124: 117. spontaneously in 40% of patients. It has been reported to be
Kim JH, et al: Acquired dyskeratotic leukoplakia of the lip and multifocal, as was likely the case with a patient reported by James
conjunctiva. Int J Dermatol 2015; 54: 332. et al. A 30-year-old woman developed numerous distinct pigmented
oral macules. The condition progressed rapidly to a diffuse oral
hyperpigmentation (Fig. 34.19). This appeared to be caused by
White Sponge Nevus an undefined inflammation, and slow partial resolution occurred
The mouth, vagina, or rectum may be the site of this spongy, after several years of observation.
white overgrowth of the mucous membrane, with acanthosis, Melanoma occurs infrequently, mostly in older patients. It is
vacuolated prickle cells, and acidophilic condensations in the recognized by being larger than the usual benign pigmented lesion
cytoplasm of keratinocytes, which electron microscopy has shown and more irregular in shape, with a tendency to ulcerate and bleed.
to be aggregated tonofilaments. The buccal mucosa is the most A peripheral areola of erythema and satellite pigmented spots may
common site of involvement. There are no extramucosal lesions. be present. There is a striking predilection for palatal (or less
Progression of the disorder generally stops at puberty. The disease often gingival) involvement. The overall prognosis is poor (<5%
is inherited as an autosomal dominant disorder. A mutation in survival at 5 years) because the lesions are usually deeply invasive
the mucosal keratin pair K4 and K13 has been identified as the by the time they are discovered. Whereas oral nevi are uncommon,
inherited defect. HPV-16 DNA has been present in some patients, biopsy of solitary pigmented oral lesions is indicated when the
the significance of which remains to be determined. Antibiot- clinical diagnosis is uncertain. Biopsy of a pigmented tumor will
ics, particularly tetracycline, may give significant improvement. occasionally reveal an SCC.
A 0.25% aqueous preparation of tetracycline as a mouth rinse,
5 mL swished in the mouth for 1 min twice daily, has been Cardoso LB, et al: Oral compound nevus. Dermatol Online J
successful. 2014; 20.
Feller L, et al: A review of the aetiopathogenesis and clinical and
Bumbǎcea RS, et al: Familial case of white sponge nevus. Acta histopathological features of oral mucosal melanoma. Scientific
Dermatovenerol Croat 2015; 23: 228. World Journal 2017; 2017: 9189812.
Cai W, et al: Current approaches to the diagnosis and treat- Fernandes D, et al: Pigmented lesions on the mucosa. Oral Surg
ment of white sponge nevus. Expert Rev Mol Med 2015; Oral Med Oral Pathol Oral Radiol 2015; 119: 374.
17: e9. Gondak RO, et al: Oral pigmented lesions. Med Oral Patol Oral
Kimura M, et al: Mutation of keratin 4 gene causing white sponge Cir Bucal 2012; 17: e919.
nevus in a Japanese family. Int J Oral Maxillofac Surg 2013; Gupta AA, et al: Oral melanoacanthoma. J Oral Maxillofac Pathol
42: 615. 2012; 16: 441.
James WD, et al: Inflammatory acquired oral hyperpigmentation.
J Am Acad Dermatol 1987; 16: 220.
Melanocytic Oral Lesions Kauzman A, et al: The blue nevus. Gen Dent 2014; 62: e22.
A wide variety of melanocytic lesions appear on the mucous Lambertini M, et al: Oral melanoma and other pigmentations.
membranes. Nevi of the oral mucosa in general are extremely J Eur Acad Dermatol Venereol 2017 Sep 1; ePub ahead of
uncommon. Among the melanocytic nevi of the cellular type, the print.
intramucosal type occurs most frequently, with the compound Matsumoto N, et al: Pigmented oral carcinoma in situ. Oral
nevus next and the junction nevus occurring only rarely. Ephelis, Surg Oral Med Oral Pathol Oral Radiol 2014; 118: e79.
Ojha J, et al: Intraoral cellular blue nevus. Cutis 2007; 80: 189.
Shen ZY, et al: Oral melanotic macule and primary oral malignant
Osseous Choristoma of the Tongue
melanoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod Osseous choristoma of the tongue presents as a nodule on the
2011; 112: e21. dorsum of the tongue containing mature lamellar bone without
Vaccaro M, et al: Spitz nevus. Pediatr Dermatol 2016; 33: e154. osteoblastic or osteoclastic activity. This does not recur after simple
excision.
Melanosis Adhikari BR, et al: Osseous choristoma of the tongue. J Med
Pigmentation of the oral cavity tends to occur most frequently in Case Rep 2016; 10: 59.
black persons. In other races, the darker the skin, the more mucosal Ginat DT, Portugal L: Lingual osseous choristoma. Ear Nose
pigmentation may be expected. Oral melanosis may occur with Throat J 2016; 95: 260.
Albright syndrome, Peutz-Jeghers syndrome, Carney complex,
Laugier-Hunziker disease, and Addison disease or, rarely, as an
idiopathic process with no associated disease.
Peripheral Ameloblastoma
The differential diagnosis of oral hyperpigmentation should This is a neoplasm of the gingivae, which appears most often on
include the amalgam tattoo, a focal, brownish blue macule arising the lower jaw. The mean age at onset is the early fifties and men
from fragments of dental silver or amalgam implanting into the outnumber women. Peripheral ameloblastoma presents as a
buccal mucosa or gingiva (Fig. 34.20). Heavy-metal poisoning growing, pink to red, sessile or pedunculated mass. Excision is
may also induce such lesions. Bismuth, lead, and cisplatin may followed by recurrence in 19% of the cases, but the lesion is
produce a pigmented line along the gums near their margin. A benign. It can simulate basal cell carcinoma histologically.
multitude of drugs will cause pigmentation; the most common
include amodiaquine, chloroquine, imatinib, oral contraceptives, Chhina S, Rathore AS: Peripheral ameloblastoma of gingiva
phenothiazines, phenolphthalein, quinacrine, quinidine, thallium, with cytokeratin 19 analysis. BMJ Case Rep 2015 Jun 4; 2015.
nicotine (tobacco), and zidovudine.
Alawi F: Pigmented lesions of the oral cavity. Dent Clin North

TRUMPETER’S WART
Am 2013; 57: 699. Trumpeter’s wart is a firm, fibrous, hyperkeratotic, pseudoepithe-
Meleti M, et al: Oral pigmented lesions of the oral mucosa and liomatous nodule on the upper lip of a trumpet player. A similar
perioral tissues. Oral Surg Oral Med Oral Pathol Oral Radiol callus may grow on the lower lip of trombone players.
Endod 2008; 105: 606.
Moraes RM, et al: Graphite oral tattoo. Dermatol Online J 2015; Gambichler T, et  al: Skin conditions in instrumental musicians.
21. Contact Dermatitis 2008; 58: 217.
EPULIS
The term epulis means any benign lesion situated on the gingiva.
The majority of these are reactive processes that display varying
degrees of fibrosis, inflammation, and vascular proliferation on
biopsy. Giant cell epulis (peripheral giant cell granuloma) is a
solitary, bluish red, 10–20 mm tumor occurring on the gingiva
between or around deciduous bicuspids and incisors. Lesions
may be induced by dental implants. Similar lesions may occur
in the autosomal dominant inherited syndrome, cherubism.
Histologically, epulides resemble giant cell tumor of the tendon
sheath.
Banthia R, et al: Peripheral giant cell granuloma. Gen Dent

2013; 61: e12.
Roginsky VV, et al: Familial cherubism. Int J Oral Maxillofac
Surg 2009; 38: 218.
Yee J: Congenital epulis in a newborn. Minn Med 2014; 97: 39.
Pyogenic Granuloma
Pyogenic granuloma is an exuberant overgrowth of granulation
tissue, frequently occurring in the oral cavity, most often involving
the gingiva. It may also occur on the buccal mucosa, lips, tongue,
or palate. It is a red to reddish purple, soft, nodular mass that
bleeds easily and grows rapidly, but is usually not painful. It often
develops during pregnancy. Surgical excision, pulsed dye,
erbium:yttrium-aluminum-garnet (Er:YAG) or neodymium:YAG
laser, and cryosurgery offer effective methods of treatment.
Cardoso JA, et al: Oral granuloma gravidarum. J Appl Oral Sci

2013; 21: 215.
Cheney-Peters D, Lund TC: Oral pyogenic granuloma after
bone marrow transplant in the pediatric/adolescent population.
Fig. 34.20 Amalgam tattoo. J Pediatr Hematol Oncol 2016; 38: 570.
Daif ET: Correlation of age, sex, and location with recurrence infrequently involved. It presents as a soft, rounded, translucent
of oral giant pyogenic granuloma after surgical excision. J projection and usually has a bluish tint. The lesion varies from 34
Craniofac Surg 2016; 27: e433. 2–10 mm in diameter. It is painless, fluctuant, and tense. Incision,
Kaya A, et al: Oral pyogenic granuloma associated with a dental or sometimes merely compression, releases sticky, straw-colored
implant treated with an Er:YAG laser. J Oral Implantol 2015; fluid (or bluish fluid if hemorrhage has occurred into it). Usually,
41: 720. the lesions are solitary; however, multiple superficial mucoceles
Kocaman G, et al: The use of surgical Nd:YAG laser in an oral have been reported to occur with graft-versus-host disease and
pyogenic granuloma. J Cosmet Laser Ther 2014; 16: 197. lichenoid inflammation. In these patients, topical corticosteroids
Thompson LD: Lobular capillary hemangioma (pyogenic granu- may help prevent recurrences.
loma) of the oral cavity. Ear Nose Throat J 2017; 96: 240. The cause of mucocele is rupture of the mucous duct, with
extravasation of sialomucin into the submucosa to produce cystic
spaces with inflammation. Granulation tissue formation is followed
GRANULOMA FISSURATUM by fibrosis. Excisional biopsy will document the diagnosis and
Granuloma fissuratum is a circumscribed, firm, whitish, fissured, eliminate the problem. Cryotherapy and laser ablation have also
fibrous granuloma occurring in the labioalveolar fold. The lesion been reported to be successful.
is discoid, smooth, and slightly raised, about 1 cm in diameter. There are mucous retention cysts in which true obstruction
The growth is folded like a bent coin, so that the fissure in the of the duct leads to an epithelial-lined cavity. These are seen more
bend is continuous on both sides with the labioalveolar sulcus. in the posterior portions of the oral mucosa. A ranula (from Rana,
Symptoms are slight. It is an inflammatory fibrous hyperplasia the frog genus) is a mucocele of the floor of the mouth.
that usually results from chronic irritation caused by poorly fitting Two other cysts may be present in the mouth. The parotid
dentures. In the dental literature, it is called epulis fissuratum, duct cyst occurs in musicians who use wind instruments; it develops
particularly when there is a deep cleft traversing the lesion. Treat- opposite the upper second molar on the buccal mucosa. The
ment is by surgical extirpation, CO2 laser ablation, or electrodesic- dermoid cyst may occur on the floor of the mouth, especially in
cation after biopsy. the sublingual area.
Mohan RP, et al: Epulis fissuratum. BMJ Case Rep 2013 Jul 17; Carlson ER: Diagnosis and management of salivary lesions of
2013. the neck. Atlas Oral Maxillofac Surg Clin North Am 2015; 23:
49.
Carlson ER, Ord RA: Benign pediatric salivary gland lesions.
ANGINA BULLOSA HEMORRHAGICA Oral Maxillofac Surg Clin North Am 2016; 28: 67.
The sudden appearance of one or more blood blisters of the oral Vieira EM, et al: Unusual dermoid cyst in oral cavity. Case Rep
mucosa characterizes angina bullosa hemorrhagica. There is no Pathol 2014; 2014: 389752.
associated skin or systemic disease. The blisters may be recurrent,
occur most often in the soft palate, and usually present in middle- ACUTE NECROTIZING ULCERATIVE
aged or elderly patients. No treatment is necessary.
GINGIVOSTOMATITIS (TRENCH MOUTH,
Shoor H, et al: Angina bullosa haemorrhagica. BMJ Case Rep VINCENT DISEASE)
2013 Dec 11; 2013. Acute necrotizing ulcerative gingivitis (ANUG) is characterized
Singh D, et al: Angina bullosa haemorrhagica. BMJ Case Rep by a rapid onset of characteristic punched-out ulcerations appearing
2013 Feb 8; 2013. on the interdental papillae and marginal gingivae. A dirty-white
pseudomembrane may cover the ulcerations (Fig. 34.22). The
lesions may spread rapidly and involve the buccal mucosa, lips,
MUCOCELE and tongue, as well as the tonsils, pharynx, and entire respiratory
The term mucocele refers to a lesion resulting from trauma or tract. The slightest pressure causes pain and bleeding. There is a
obstruction of the minor salivary ducts. The most common type characteristic foul, fetid odor that is always present. ANUG may
is the mucous extravasation phenomenon, which is usually seen
inside the lower lip because it is caused by trauma from biting
(Fig. 34.21). The inside of the upper lip and buccal mucosa are
Fig. 34.22 Acute necrotizing ulcerative gingivostomatitis. (Courtesy

Department of Oral Medicine, University of Pennsylvania School of
Fig. 34.21 Mucocele. Dentistry.)
lead to loss of attachment of the gingiva and alveolar bone (necrotiz-

ing ulcerative periodontitis).
CYCLIC NEUTROPENIA
Trench mouth begins in a nidus of necrotic tissue, which Cyclic, or periodic, neutropenia is characterized by a decrease of
provides an anaerobic environment for the infection by fuso- circulating neutrophils and dermatologic manifestations. At regular
spirochetal organisms (Bacteroides fusiformis) in association with intervals (21 days), neutropenia and mouth ulcerations develop,
Borrelia vincentii and other organisms. Poor dental hygiene, smoking, usually accompanied by fever, malaise, and arthralgia. Ulcerations
poor nutrition, ingestion of methylenedioxymethamphetamine of the lips, tongue, palate, gums, and buccal mucosa may be
(ecstasy), and immunosuppression are predisposing factors. It extensive. The ulcers are irregularly outlined and are covered by
may be seen as a component of the oral infections and inflam- a grayish white necrotic slough. The anterior teeth may show a
matory lesions that occur in immunocompromised HIV-infected grayish brown discoloration. Premature alveolar bone loss and
patients. periodontitis occur. In addition, opportunistic cutaneous infections,
Acute herpetic gingivostomatitis, or primary HSV infection, such as abscesses, furuncles, noma, pyomyositis, and cellulitis, may
may be confused with ANUG. Young children are susceptible to develop during the neutropenic stage. Urticaria and erythema
this severe febrile stomatitis with lymphadenitis. It is not primarily multiforme have been reported.
gingival in location and does not cause necrosis of the interdental There is a cyclic depression of neutrophils occurring at
papillae. Noma is a form of fusospirillary gangrenous stomatitis intervals of 12–30 days (average 21 days) and lasting 5–8 days.
occurring in children with low resistance and poor nutrition. The The neutrophils in the peripheral blood regularly fall to low
onset is often triggered by measles. At the onset, there is ulceration levels or completely disappear. Some cases have been associated
of the buccal mucosa; this rapidly assumes a gangrenous character with agammaglobulinemia. The cause of cyclic neutropenia is
and extends to involve the skin and bones, with resultant necrosis. a germline mutation of the gene encoding neutrophil elastase
It may end in the patient’s death. (ELANE). This is thought to produce apoptosis of bone marrow
Treatment of ANUG consists of thorough dental hygienic progenitor cells. Both autosomal dominant disease and sporadic
measures under the supervision of a dentist. Penicillin with cases have this abnormality. Severe congenital neutropenia is
debridement is the treatment of choice. Use of a 3% hydrogen caused by a mutation in the same gene but at a different site. The
peroxide mouthwash is also helpful. latter condition predisposes to the development of myelodysplasia
and acute myelogenous leukemia, whereas cyclic neutropenia
Atout RN, Todescan S: Managing patients with necrotizing does not.
ulcerative gingivitis. J Can Dent Assoc 2013; 79: d46. The differential diagnosis includes other periodic fever syn-
Feller L, et al: Necrotizing periodontal diseases in HIV-seropositive dromes, such as the periodic fever, aphthous stomatitis, pharyngitis,
subjects. J Int Acad Periodontol 2008; 10: 10. and adenopathy (PFAPA) syndrome; Mediterranean fever; Hibernian
Hu J, et al: Acute necrotising ulcerative gingivitis in an fever and hyperimmunoglobulin D syndrome; TNF receptor–
immunocompromised young adult. BMJ Case Rep 2015 Sep associated periodic syndrome (TRAPS); and pyogenic sterile
16; 2015. arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. All
Tonna JE, et al: A case and review of noma. PLoS Negl Trop share a predisposition to the development of aphthous-like oral
Dis 2010; 4: e869. ulcerations. The autoinflammatory syndromes are discussed in
detail in Chapter 7.
Use of recombinant human granulocyte colony-stimulating
ACATALASEMIA factor (G-CSF) has been successful in the treatment of cyclic
Acatalasemia (Takahara disease) is a rare disease in which the neutropenia patients. If side effects limit use of this therapy,
enzyme catalase is deficient in the liver, muscles, bone marrow, cyclosporine has been reported to be effective as well. Admin-
erythrocytes, and skin. There are several forms. The absence of istering antibiotics during infections seems to expedite recovery.
catalase leads to progressive gangrene of the mouth, with recurrent Careful attention to oral hygiene, including plaque control, helps
ulcerations resulting from increased susceptibility to infection by improve mouth lesions and reduces the risk of infections. Death
anaerobic organisms. may occur from pneumonia, sepsis, gangrenous pyoderma, or
Almost 60% of patients with acatalasemia develop alveolar granulocytopenia.
ulcerations, beginning in childhood. The mild type of the disease
is characterized by rapidly recurring ulcers. In the moderate Ashok N, et al: A review on noma. Glob J Health Sci 2015; 8:
type, alveolar gangrene develops, with atrophy and recession 53.
of the alveolar bone, so that the teeth fall out spontaneously. Boo YJ, et al: Cyclic neutropenia with a novel gene mutation
In the severe type, widespread destruction of the jaw occurs. presenting with a necrotizing soft tissue infection and severe
After puberty, all lesions heal, even in individuals who have the sepsis. BMC Pediatr 2015; 15: 34.
severe type. Chen Y, et al: Cyclic neutropenia presenting as recurrent oral
There is no gross difference in appearance between the blood ulcers and periodontitis. J Clin Pediatr Dent 2013; 37: 307.
of an acatalasic patient and that of a normal individual, but when Cush JJ: Autoinflammatory syndromes. Dermatol Clin 2013; 31:
hydrogen peroxide is added to a sample of blood, acatalasic blood 471.
immediately turns blackish brown, and the peroxide does not Horwitz MS, et al: ELANE mutations in cyclic and severe
foam. Normal blood remains bright and causes the peroxide congenital neutropenia. Hematol Oncol Clin North Am 2013;
to foam exuberantly because of the presence of erythrocyte 27: 19.
catalase. Nguyen TV, et  al: Autoinflammation. J Am Acad Dermatol 2013;
Acatalasia is a rare peroxisomal disorder and is inherited as an 68: 834.
autosomal recessive trait. Treatment consists of extraction of the Tripathi SV, et al: Autoinflammatory diseases in dermatology.
diseased teeth and the use of antibiotics to control the harmful Dermatol Clin 2013; 31: 387.
effects of the causative bacteria.
RECURRENT INTRAORAL HERPES
Goth L, et al: Inherited catalase deficiency. Mutat Res 2013; 753:
147. SIMPLEX INFECTION
Wang Q, et al: Long-term follow-up evaluation of an acatalasemia Recurrent intraoral infection with HSV is characterized by
boy with severe periodontitis. Clin Chim Acta 2014; 433: 93. numerous small, discrete vesicles occurring in one or a few
34
Fig. 34.23 Chronic herpes in patient receiving cancer chemotherapy.
Fig. 34.24 Aphthous stomatitis. (Courtesy Steven Binnick, MD.)

clusters. The site of involvement is a key feature in suspecting
the diagnosis. The keratinized or masticatory mucosa—the palate,
gingiva, and tongue—is affected. The grouped vesicles rupture
rapidly to form punctate erosions with a red base. Smears from palate. There is a marked predilection for the nonkeratinized
the base prepared with Wright stain will show giant multinucleated mucosa (any not bound to underlying periosteum). This fact, and
epithelial cells. Immunofluorescent tests and viral cultures are also because they are rarely confluent, even when they occur as small
confirmatory. crops of 1- or 2-mm lesions (herpetiform aphthae), help to dis-
The differential diagnosis of this uncommon manifestation of tinguish them from the uncommon, recurrent intraoral HSV
HSV includes oral herpes zoster, herpangina, and oral aphthosis. infection. Aphthae may also occur on the vagina, vulva, penis,
The latter two involve nonattached mucosa, whereas recurrent anus, and even the conjunctiva. When they involve the oral and
HSV involves mucosa fixed to bone. Differentiation from zoster genital mucosa and number three or more, the term complex aphthosis
is made on clinical grounds or by culture and immunofluorescent is applied.
testing. The lesions tend to involute in 1–2 weeks, but recurrences are
Chronic progressive ulcerative and nodular intraoral herpes common. These recurrences may be induced by trauma (e.g.,
are seen occasionally in HIV-infected patients or those with self-biting, toothbrush injury, dental procedures), spicy foods, citrus,
leukemia or neutropenia (Fig. 34.23). The presentation may mimic fresh pineapple, walnuts, allergy, emotional stress, or hormonal
mucosal toxicity to chemotherapy. Solitary painful erosions of the changes in women, as in menstruation, pregnancy, menarche, and
tongue or attached mucosa should be tested for HSV in such menopause. A familial predisposition has also been described as
patients. Additionally, herpetic geometric glossitis may occur, with familial epidemic aphthosis.
linear longitudinal, cross-hatched, or branching fissures of the Recurrent aphthous stomatitis is the most common lesion of
dorsal tongue, usually along the central area. This condition may the oral mucosa, affecting 10%–20% of the population. It typically
be quite painful and may limit oral intake. Although the glossitis starts in the second or third decade, and patients may experience
usually affects only immunocompromised patients, at least one recurrent bouts of lesions several times yearly for many decades.
immunocompetent patient has been affected. When present in neonates or young children, autoinflammatory
syndromes should be considered. In PFAPA syndrome, the high
Mirowski GW, et al: Herpetic geometric glossitis in an immu- fevers and associated findings occur with striking periodicity every
nocompetent patient with pneumonia. J Am Acad Dermatol 4 weeks, last 4–6 days, and resolve only to recur the following
2009; 61: 139. month. The children are otherwise well. One or two doses of
Stoopler ET, et al: Recurrent intraoral herpes. J Emerg Med prednisone (2 mg/kg) abort the attack, and tonsillectomy may
2016; 51: 324. cure it. Aphthous oral ulcerations may also be seen in the auto-
inflammatory syndromes, such as familial Mediterranean fever,
RECURRENT APHTHOUS STOMATITIS (CANKER TRAPS, hyperimmunoglobulinemia D and periodic fever, PAPA
syndrome, and deficiency of the interleukin-1 receptor antagonist
SORES, APHTHOSIS) (DIRA) syndrome.
Ulcerations such as these may also be the presenting sign in
Clinical Features Behçet syndrome, HIV infection, malabsorption syndromes,
Aphthous stomatitis is a painful, recurrent disease of the oral gluten-sensitive enteropathy, pernicious anemia, cyclic neutropenia,
mucous membrane. It begins as small, red, discrete, or grouped neutropenia, ulcerative colitis, and Crohn disease. History, physical
papules, which in a few hours become necrotizing ulcerations. examination, complete blood count, and long-term follow-up
They are small, round, shallow, white ulcers (aphthae), generally documenting the recurrent course, in the absence of other
surrounded by a ring of hyperemia (Fig. 34.24). As a rule, they symptoms, will secure the diagnosis. Some patients have aphthosis
are tender; they may become so painful that they interfere with associated with low folate, vitamin B12, or iron levels, so testing
speech and mastication. They are mostly about 5 mm in diameter should include this evaluation.
but may vary in size from 3–10 mm. When larger, they are called
major aphthae. A third subcategory, herpetiform aphthae, consists
of small, 1- to 3-mm lesions grouped into a coalescing larger
Etiologic Factors
plaque, which may take 1–4 weeks to resolve. Usually, one to five Although individual patients often suspect that one of the factors
lesions occur per attack; however, they may occur in any number. just mentioned is responsible for precipitating recurrence of the
They are located in decreasing frequency on the buccal and labial lesions, investigators favor infectious or immunologic causation.
mucosa, edges of the tongue, buccal and lingual sulci, and soft The true cause is unknown.
Histologically, the lesion consists of a lymphocytic inflammatory Brocklehurst P, et al: Systemic interventions for recurrent
infiltration with occasional plasma cells and eosinophils, which aphthous stomatitis (mouth ulcers). Cochrane Database Syst
suggests delayed hypersensitivity. Rev 2012; 9: CD005411.
Cui RZ, et al: Recurrent aphthous stomatitis. Clin Dermatol
2016; 34: 475.
Diagnosis Femiano F, et al: Guidelines for diagnosis and management of
Aphthous stomatitis must be differentiated from mucous patches aphthous stomatitis. Pediatr Infect Dis J 2007; 26: 728.
of early syphilis, candidiasis, Vincent angina, the avitaminoses Glucan E, et al: Cyanocobalamin may be beneficial in the treat-
(particularly pellagra and scurvy), erythema multiforme, pemphigus, ment of recurrent aphthous stomatitis even when vitamin B12
cicatricial pemphigoid, lichen planus, primary HSV infection of levels are normal. Am J Med Sci 2008; 336: 379.
the mouth, recurrent labial herpes, and recurrent intraoral HSV Kalampokis I, Rabinovich CE: Successful management of
infection. refractory pediatric-onset complex aphthosis with lenalidomide.
J Clin Rheumatol 2014; 20: 221.
Manthiram K, et al: Family history in periodic fever, aphthous
Treatment stomatitis, pharyngitis, adenitis (PFAPA) syndrome. Pediatrics
No permanent cure is available for aphthosis. Several topical agents 2016; 138,
will lessen the pain. A mixture of equal parts of elixir of Benadryl Mays JW, et al: Oral manifestations of systemic autoimmune and
and Maalox, held in the mouth for 5 minutes before meals, is inflammatory diseases. J Evid Based Dent Pract 2012; 12: 265.
soothing. Kaolin may also be added to the mixture. Lidocaine Montgomery-Cranny JA, et al: Management of recurrent
(Xylocaine Viscous) 2% solution, keeping 1 teaspoonful in the aphthous stomatitis in children. Dent Update 2015; 42: 564.
mouth for several minutes, is also helpful in allaying pain. Another Stoopler ET, Sollecito TP: Recurrent oral ulcers. JAMA 2015;
useful topical anesthetic is dyclonine hydrochloride (Dyclone) 313: 2373.
0.5% applied to the lesions. A large number of reasonably effective
over-the-counter remedies are also available. Triggers, such as
spicy foods, citrus, walnuts, pineapple, and other irritating sub-
MAJOR APHTHOUS ULCER
stances, should be avoided. In Sutton disease, a major aphthous ulcer begins as a small, shotlike
Other measures may be used to shorten the course and induce nodule on the inner lip, buccal mucosa, or tongue that breaks
healing of lesions. Chlorhexidine mouthwashes are used twice down into a painful, sharply circumscribed ulcer with a deeply
daily with any of the other treatments described. A mixture of punched-out and depressed crater. It may at times begin in the
equal parts of fluocinonide ointment and Orabase, applied to the faucial pillars or oropharynx (Fig. 34.25). It may persist for 2–12
ulcers three or four times daily, is effective in aiding the healing weeks before healing with a soft, pliable scar. There are seldom
of existing ulcers; however, it does not prevent new ulcers. Some more than one to three lesions present at one time. However,
patients object to the thick, sticky texture of Orabase and prefer remissions tend to be short, and new lesions may appear before
fluocinonide gel. Clobetasol ointment can also be very effective. old ones have healed.
Intralesional corticosteroids and short, 3- or 4-day courses of oral The cause is unknown, but evidence favors an immunologic
corticosteroids may help, particularly for indolent or large lesions. or infectious etiology. These painful lesions are frequently present
Nonsteroidal alternatives include 5 mL of an oral suspension in immunocompromised HIV-infected patients who may experience
containing 250 mg of tetracycline; this is held in the mouth for similar lesions in the esophagus, rectum, anus, and genitals. Treat-
2 minutes and then swallowed. This is done four times daily for ment is difficult, and the general measures discussed under recurrent
1 week. Amlexanox 5% oral paste (Aphthasol) is a useful topical aphthae should be employed. Intralesional or systemic corticosteroids
therapy both to induce healing and to relieve pain. Sucralfate in short courses may be effective and are often given. If recurrences
suspension, alone or compounded with a topical corticosteroid, are such that systemic steroids are prescribed for more than two
may be useful, as described in peptic ulcer disease and the ulcer- or three short courses per year, alternative oral medications, such
ations of Behçet disease. as colchicine, dapsone, or thalidomide, may be tried.
To try to prevent new lesions, known triggers for the individual
patient should be avoided as much as possible. Colchicine at 0.6 mg/ Boldo A: Major recurrent aphthous ulceration. Conn Med 2008;
day for 1 week, then increasing to 1.2 or even 1.8 mg/day, is recom- 72: 271.
mended. If this is ineffective or GI or other side effects limit dosage,
dapsone may be added to colchicine or substituted for it. It is given
in steadily increasing doses of 25 mg for 3 days, then 50 mg for 3
days, then 75 mg for 3 days, then 100 mg for 7 days. If the blood
count is normal, no side effects are present, and the disease is not
controlled, further increases to 125 mg or even 150 mg may be
given. Thalidomide and lenalidomide are other effective alternatives,
but caution regarding teratogenicity and neurotoxicity is necessary
if this is considered. One method is thalidomide, 300 mg/day to
start, 200 mg/day after 10 days, and 100 mg/day after 2 months.
Relapses are treated with 100 mg/day for 12 days.
Several investigators have reported finding low folate, iron, or
B12 levels in about 20% of aphthosis patients investigated, but
others do not see this with such high frequency. Still, it is worth
investigating, because correction of the abnormality clears or
improves the condition in most patients who have an abnormality.
Two studies document improvement with cyanocobalamin, even
in those without abnormality.
Akintoye SO, Greenberg MS: Recurrent aphthous stomatitis.

Dent Clin North Am 2014; 58: 281. Fig. 34.25 Major aphthae.
Picciani BL, et al: Regression of major recurrent aphthous Unfortunately, the international criteria include nonspecific
ulcerations using a combination of intralesional corticosteroids common cutaneous lesions (pseudofolliculitis, papulopustular or 34
and levamisole. Clinics 2010; 65: 650. acneiform lesions). Demonstration of either leukocytoclastic
vasculitis or a neutrophilic vascular reaction on histologic examina-
BEHÇET SYNDROME (OCULO-ORAL-GENITAL tion of a lesion would make the cutaneous criteria more
specific.
SYNDROME) There is a relatively high prevalence of Behçet disease in the
Far East and Mediterranean countries, whereas in the United
Clinical Features States and Western Europe it is much less common. In large series
Behçet syndrome consists of recurrent oral aphthous ulcerations of patients from areas of high prevalence, men with an age of
that recur at least three times in one 12-month period in the onset in the thirties predominate. They tend to have a worse
presence of any two of the following: recurrent genital ulceration, prognosis than women. In the United States most reported patients
retinal vasculitis or anterior or posterior uveitis, cutaneous lesions are young women with a high frequency of mucocutaneous lesions
(erythema nodosum; pseudofolliculitis or papulopustular lesions; and a low prevalence of ocular involvement. This may reflect
or acneiform nodules in postadolescent patients who are not referral bias or could indicate that the disease is less severe and
receiving corticosteroid treatment), or a positive pathergy test. female predominant in the United States.
Oral lesions occur on the lips, tongue (Fig. 34.26), buccal On histologic examination, the early lesions show a leukocy-
mucosa, soft and hard palate, tonsils, and even in the pharynx and toclastic vasculitis. There is perivascular infiltration, which is chiefly
nasal cavity. The lesions are single or multiple, 2–10 mm or larger lymphocytic in older lesions, with endothelial proliferation that
in diameter, and sharply circumscribed, with a dirty-grayish base obliterates the lumen. The cause of Behçet disease has been
and a surrounding bright-red halo. Other patients show deep postulated to have an infectious, immunologic, and/or genetic
ulcerations that leave scars resembling those caused by Sutton basis, but the evidence is still inconclusive for any of these.
major aphthous ulcers. The lesions are so painful that eating may
be difficult. A foul mouth odor is in most cases very noticeable.
Genital lesions occur in men on the scrotum and penis or in
Diagnosis
the urethra and in women on the vulva, cervix, or vagina; lesions Usually, the disease starts with a single oral ulceration, which is
may be found in both genders on the genitocrural fold, anus, or followed by others. It may take years before additional lesions
perineum or in the rectum. These ulcerations are similar to those develop. Again, the diagnosis requires two classic signs in addition
seen in the mouth. In addition, macules, papules, and folliculitis to oral ulcerations. In women, anal and genital lesions predominate,
may develop on the scrotum. Lesions in women may lead to deep often with subsequent involvement of the eyes.
destruction of the vulva. Swellings of the regional nodes and fever Behçet disease must be differentiated from herpetic or aphthous
may accompany oral and genital attacks. stomatitis, pemphigus, oral cancer, and Stevens-Johnson syndrome
The ocular lesions start with intense periorbital pain and (erythema multiforme). A skin puncture or pathergy test may be
photophobia. Retinal vasculitis is the most classic eye sign and used to investigate patients further; however, it is not reliable in
the major cause of blindness. Conjunctivitis may be an early that it may be negative in otherwise well-documented cases. It is
accompaniment of uveitis, and hypopyon may be a late one. Iri- done by injecting 0.1 mL of normal saline solution into the skin
docyclitis is frequently seen. Both eyes are eventually involved. or by simply pricking the skin with a sterile needle. A pustule
Untreated disease leads to blindness from optic atrophy, glaucoma, appears at the site within 24 hours. If results are negative, the test
or cataracts. should be repeated at two to five points before results are accepted.
Neurologic manifestations are mostly in the central nervous Pathergy has been observed in patients with Behçet disease,
system and resemble most closely those of multiple sclerosis. pyoderma gangrenosum, Sweet syndrome, and bowel-associated
Remissions and exacerbations are the rule. Thrombophlebitis dermatosis–arthritis syndrome.
occurs with some frequency. Thrombosis of the superior vena
cava may also occur. Arthralgia is most often present in the form
of polyarthritis.
Treatment
Usually, the ulcerations heal spontaneously. Chlorhexidine
mouthwashes twice daily and toothpastes and restricted use of
the toothbrush should be prescribed when there are oral lesions.
For treating the symptoms and healing of the aphthae, local
treatments as described for aphthae may be used. Sucralfate suspen-
sion has been studied in Behçet oral and genital ulcers and was
found to decrease pain and healing time. On the whole, the
therapeutic problem of aphthosis is not the healing of the individual
lesions but the prevention of new attacks. For that purpose, several
options exist, none of which is optimal. Colchicine, 0.6 mg twice
daily, may be started for 2 weeks. In the absence of response and
GI side effects, the dose may be increased to three times daily.
Although this may not totally alleviate the mucocutaneous lesions,
it may decrease their recurrence rate by 50% or more. Dapsone
may be substituted or added to this for improvement of response.
The usual therapeutic final dose is 100 mg/day. Thalidomide has
been found to be effective in many patients. One dosing method
is thalidomide, 200 mg twice daily for 5 days, and 100 mg twice
daily for 15–60 days. It has no effect on iridocyclitis. Again, long-
term treatment will usually be complicated by neurotoxicity, and
the teratogenicity of thalidomide is well known.
Methotrexate, in a weekly oral dose of 7.5–20 mg, should be
Fig. 34.26 Behçet disease. (Courtesy Ken Greer, MD.) reserved for severe refractory cases, as should more aggressive
systemic treatments such as systemic corticosteroids, azathioprine, Scully C: Oral and maxillofacial medicine, 3rd ed. New York:
chlorambucil, cyclosporine, interferon alfa, TNF antagonists, Churchill Livingstone, 2013.
apremilast, anakinra, tocilizumab, rituximab, and cyclophosphamide. Sollecito TP, Stoopler ET (Eds.): Clinical approaches to oral
In general these more aggressive therapeutics have been tested mucosal disorders. Dent Clin North Am 2013; 57: 561.
in small trials or case series for treatment of ocular, neurologic, Vitale A, et al: New therapeutic solutions for Behçet’s syndrome.
pulmonary, digestive, or vascular manifestations. Expert Opin Investig Drugs 2016; 25: 827.
The long-term outlook is for intermittent recurrent flares that
may be lifelong. Blindness, neurologic impairment, and vascular Bonus images for this chapter can be found online at

thromboses are potential serious complications of Behçet syndrome. expertconsult.inkling.com
Alpsoy E: Behçet’s disease. J Dermatol 2016; 43: 620. eFig. 34.1 Melkersson-Rosenthal syndrome. (Courtesy Dr. Curt
Davari P, et al: Clinical features of Behçet’s disease. J Dermatolog Samlaska.)
Treat 2016; 27: 70. eFig. 34.2 Melkersson-Rosenthal syndrome. (Courtesy Dr. Shyam
Hatemi G, et al: One year in review 2017: Behçet’s syndrome. Verma.)
Clin Exp Rheumatol 2017; 35 Suppl 108: 3. eFig. 34.3 Odontogenic sinus.
Koné-Paut I: Behçet’s disease in children, an overview. Pediatr eFig. 34.4 Oral squamous cell carcinoma.
Rheumatol Online J 2016; 14: 10. eFig. 34.5 Oral squamous cell carcinoma. (Courtesy Dr. Shyam
Ozguler Y, Hatemi G: Management of Behçet’s syndrome. Curr Verma.)
Opin Rheumatol 2016; 28: 45. eFig. 34.6 Benign oral leukoplakia.
Pramod JR: Textbook of oral medicine, 3rd ed. New Delhi: Jaypee eFig. 34.7 Torus palatinus.
Brothers Medical Publishers, 2014. eFig. 34.8 Behçet disease.
Rotondo C, et al: Mucocutaneous involvement in Behçet’s disease.
Mediators Inflamm 2015; 2015: 451675.
CHAPTER 34 Disorders of the Mucous Membranes 812.e1
34
eFig. 34.1 Melkersson-Rosenthal syndrome. (Courtesy Dr. Curt

Samlaska.) eFig. 34.4 Oral squamous cell carcinoma.
eFig. 34.2 Melkersson-Rosenthal syndrome. (Courtesy Dr. Shyam

Verma.)
eFig. 34.5 Oral squamous cell carcinoma. (Courtesy Dr. Shyam

Verma.)
eFig. 34.3 Odontogenic sinus. eFig. 34.6 Benign oral leukoplakia.
812.e2 Andrews’ Diseases of the Skin
eFig. 34.8 Behçet disease.
eFig. 34.7 Torus palatinus.

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34 Disorders of the Mucous Membranes

Bonus images for this chapter can be found online at

Fig. 34.3 Cheilitis glandularis. (Courtesy Dr. Shyam Verma.)

Fig. 34.1 Allergic contact cheilitis to topical steroids. (Courtesy Glen

decreased vertical facial dimension in the development of perlèche.

Abdollahi M, et al: A review of drug-induced oral reactions. J

Plasmoacanthoma ORAL AND CUTANEOUS CROHN DISEASE

closely associated with ulcerative colitis) and erythema nodosum,

Samatha Y, et al: Clinicopathologic evaluation of lesions associated

palate. It is asymptomatic. Exostoses also frequently occur in the

Dafar A, et al: Factors associated with geographic tongue and

Fig. 34.9 Black hairy tongue. (Courtesy Steven Binnick, MD.)

Fig. 34.11 Eruptive lingual papillitis.

Fig. 34.12 Median rhomboid glossitis. (Courtesy Steven Binnick, MD.)

Fig. 34.14 Oral hairy leukoplakia of HIV. Fig. 34.15 Erythroplakia.

most frequently confused with lichen sclerosus et atrophicus and

Fig. 34.16 Proliferative verrucous leukoplakia; three sites of

Fig. 34.18 Acquired dyskeratotic leukoplakia. Fig. 34.19 Oral melanosis.

Alawi F: Pigmented lesions of the oral cavity. Dent Clin North

Banthia R, et al: Peripheral giant cell granuloma. Gen Dent

Cardoso JA, et al: Oral granuloma gravidarum. J Appl Oral Sci

Fig. 34.22 Acute necrotizing ulcerative gingivostomatitis. (Courtesy

lead to loss of attachment of the gingiva and alveolar bone (necrotiz-

Fig. 34.23 Chronic herpes in patient receiving cancer chemotherapy.

Fig. 34.24 Aphthous stomatitis. (Courtesy Steven Binnick, MD.)

Akintoye SO, Greenberg MS: Recurrent aphthous stomatitis.

thromboses are potential serious complications of Behçet syndrome. expertconsult.inkling.com

eFig. 34.1 Melkersson-Rosenthal syndrome. (Courtesy Dr. Curt

eFig. 34.2 Melkersson-Rosenthal syndrome. (Courtesy Dr. Shyam

eFig. 34.5 Oral squamous cell carcinoma. (Courtesy Dr. Shyam

eFig. 34.3 Odontogenic sinus. eFig. 34.6 Benign oral leukoplakia.

eFig. 34.8 Behçet disease.

eFig. 34.7 Torus palatinus.

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