Cheilitis Glandularis

Cheilitis glandularis (CG) is a clinically descriptive diagnosis that refers to an uncommon, poorly understood inflammatory disorder of the lower lip. Its etiology remains obscure. ^[1] Cheilitis glandularis is characterized by progressive enlargement and eversion of the lower labial mucosa that results in obliteration of the mucosal-vermilion interface. With externalization and chronic exposure, the delicate lower labial mucous membrane is secondarily altered by environmental influences, leading to erosion, ulceration, crusting, and, occasionally, infection. Most significantly, susceptibility to actinic damage is increased. Therefore, cheilitis glandularis can be considered a potential predisposing factor for the development of actinic cheilitis and squamous cell carcinoma.

Historically, cheilitis glandularis has been subclassified into 3 types: simple, superficial suppurative, and deep suppurative. The deep suppurative type has also been variously referred to as myxadenitis labialis or cheilitis apostematosa, and the superficial suppurative type has been termed Baelz disease. Many believe these subtypes represent a continuum of disease, where the simple type, if not treated, could become secondarily infected and progress to become the superficial or eventually, the deeply suppurative type.

Note the images below.

A 56-year-old woman with an 18-month history of chronic swelling and a dry, burning sensation in her lower lip. She reports intermittent increases and decreases in size of the lip with painful episodes of erosion, crusting, and rare instances of drainage. History reveals medication-induced xerostomia plus a tendency to compulsively lick the lip to maintain hydration. Note eversion of the mucosal surface, which appears erythematous and dry, and narrowing of the vermilion border. The lower labial mucosa appears nodular; however, on palpation, it is diffusely soft. The composite features are consistent with a clinical impression of cheilitis glandularis. A lip biopsy sample was obtained.

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Note the fullness of the lower portion of the lip and the indistinct junction between the vermilion border and the skin.

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In 1870, von Volkmann introduced the term cheilitis glandularis. ^[2] He described a clinically distinct, deeply suppurative chronic inflammatory condition of the lower lip characterized by mucopurulent exudates from the ductal orifices of the labial minor salivary glands. In 1914, Sutton proposed that the characteristic lip swelling was attributable to a congenital adenomatous enlargement of the labial salivary glands. ^{[3, 4]} This remained the prevailing hypothesis until 1984 when Swerlick and Cooper reported 5 new cases and a retrospective analysis of all cases of cheilitis glandularis reported up to that time. ^[5] Their studies revealed no evidence to support the assertion that submucosal salivary gland acinar hyperplasia is either responsible for or a consistent feature of established cheilitis glandularis.

Since then, other authors have corroborated this observation. Salivary ductal ectasia, hyperplasia, and squamous metaplasia likely occur secondary to an unspecified chronic insult to the lip.

Stoopler et al reported a papillary cystadenoma-like ductal growth pattern in one patient with cheilitis glandularis. ^[6] Periductal chronic inflammation (dochitis), scarring, and chronic sclerosing sialadenitis in otherwise unremarkable minor salivary glands have also been noted. Musa and coauthors reported a case with a more generalized presentation of cheilitis glandularis, which they termed suppurative stomatitis glandularis. ^[7] In their patient, suppurative labial minor salivary gland involvement extended to also involve the buccal mucosa. Reichart and coauthors reported a retention cyst in the upper lip of an elderly patient with the "simplex" form of cheilitis glandularis; they interpreted the retention cyst as a consequence of cheilitis glandularis. However, this was mere conjecture on the authors' part. ^[8]

In a case reported by Leao and coauthors, cheilitis glandularis was the presenting clinical finding in a patient later discovered to have undiagnosed HIV-infection. ^[9] The lip findings could have resulted from (undiagnosed but HIV-related) minor salivary gland dysfunction leading to exfoliative cheilitis, a well-documented and frequently encountered manifestation of HIV-infection. Butt and coauthors reported a case of cheilitis glandularis that progressed to squamous cell carcinoma in an HIV-infected patient. ^[10]

Although some have speculated that cheilitis glandularis represents a hereditary autosomal dominant condition, composite findings in most cases appear to indicate cheilitis glandularis represents a clinical reaction pattern to chronic irritation of the lip from a spectrum of highly diverse external causes. These include actinic damage, factitial injury, atopy, infection, and tobacco irritation. Carrington and Horn reported a case in which an elderly man developed cheilitis glandularis related to actinic damage following vermilionectomy for squamous cell carcinoma of the lower lip. ^[11] These authors advocate clinical investigation in cases of cheilitis glandularis to rule out neoplastic, immune suppressive, or inflammatory changes due to local factors. This illustrates the concept that cheilitis glandularis is not a separate and distinct disease. Instead, it appears to be a descriptive phenomenon that could represent any one of a host of diverse clinicopathological entities.

The possibility of a genetic predisposition for cheilitis glandularis has been raised by some authors. Parmar and Muranjan, among others, described a genetic syndrome involving "double lip" of both lips in conjunction with ptosis and other physical abnormalities. ^{[12, 13]} Dhanapal and coworkers reported a case in which a 14-year-old girl with double lip developed cheilitis glandularis. ^[14] None of these cases offers support for the conjecture that cheilitis glandularis is primarily a minor salivary gland disease.

Cheilitis glandularis is an unusual clinical manifestation of cheilitis that evolves in response to one or more diverse sources of chronic irritation.

Lip enlargement is attributable to inflammation, hyperemia, edema, and fibrosis.

Surface keratosis, erosion, and crusting develop consequent to longstanding actinic exposure or unusual repeated manipulations that include self-inflicted biting or other factitial trauma, excessive wetting from compulsive licking, drying (sometimes associated with mouth breathing, atopy, eczema, and asthma), and any other repeated stimulus that could serve as a chronic aggravating factor.

Frequency

United States

Cheilitis glandularis is an uncommon condition in the United States. However, factitial injury to the lower lip vermilion border and mucosa due to chronic lip biting, lip drying, or habitual lip licking, combined with sun-induced lip damage, are extremely commonplace. Any of the latter influences could result in lip eversion, ulceration, and secondary infection.

International

Similar to its prevalence in the United States, cheilitis glandularis is uncommon worldwide

Race

Cheilitis glandularis has no apparent racial predilection. However, actinic damage is more common in whites than in darker-skinned individuals. The case for a relationship to sun sensitivity in cheilitis glandularis is supported by a 2010 study of 22 cheilitis glandularis patients by Nico and coauthors. ^[15] All of the patients were fair skinned and, among them, were 6 albino patients. Signs of photodamage were evident, and, in 3 cases, in situ and invasive squamous cell carcinoma was detected.

Yanagawa et al reported 2 cases of cheilitis glandularis in Asian-Japanese men. One of the patients had involvement of both lips with the superficial suppurative type, while the second patient had involvement of the lower lip alone. The latter patient's cheilitis glandularis was of the deep suppurative type. ^[16]

Sex

Cheilitis glandularis appears to favor adult males; however, cases have been reported in women and in children. One possibility is that some purported childhood cases actually represent exfoliative cheilitis, frequently attributable to factitial injury. Actinic cheilitis favors adults in midlife or older, and a male predilection is reported for the latter condition.

Age

Cheilitis glandularis most frequently occurs between the fourth and seventh decades of life; however, the age range is wide. One report exists of cheilitis glandularis in a child, and several cases have arisen in teenagers and young adults.

The risk of dysplasia and carcinoma increases with age, especially in fair-skinned individuals with sun-damaged skin. This is because the characteristic eversion of the lower lip results in long-term chronic exposure of the thinner, more vulnerable labial mucosa to actinic influence.

Cheilitis glandularis has been associated with a heightened risk for the development of squamous cell carcinoma. In many cases, dysplastic (premalignant) surface epithelial change is evident histopathologically, and frank carcinomas have been reported in 18-35% of cases. Rarely, cases of chronic persistent or recurrent suppurative infection may result from inappropriate antibiotic treatment.

A case of persistent suppurative cheilitis glandularis, confirmed by punch biopsy, in a 52-year-old African American woman with a 15-pack year smoking history responded to a 4-week course of oral penicillin at 1 g/d combined with oral fluoroquinolone at 1 g/d. Two weeks into the therapy, the swelling was significantly reduced. The antibiotic regimen was continued for 2 additional weeks, with resolution of the lip lesions and continued normality at 1-year follow-up. ^[17]

Reinforce instruction in measures for sun protection.