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ANGULAR CHEILITIS (PERLECHE, ANGULAR STOMATITIS, CHEILOSIS)

Shari B. Marchbein;Raegan Hunt
|
March 13, 2019


ARE YOU CONFIDENT OF THE DIAGNOSIS?

WHAT YOU SHOULD BE ALERT FOR IN THE HISTORY





Angular cheilitis, also known as perlèche, is diagnosed clinically by the
presence of inflammation, maceration and fissuring of the oral commissures.
Affected patients may complain of a burning sensation or tenderness at the
corners of the mouth. The discomfort associated with this eruption may limit
range of motion of the mouth and impair eating.

CHARACTERISTIC FINDINGS ON PHYSICAL EXAMINATION





Both oral commissures are typically affected. Early lesions are small,
grey-white thickened areas bordered by mild mucosal erythema. More established
lesions exhibit a blue-white hue and are associated with scaling, erythematous
patches on surrounding skin (Figure 1, Figure 2). Maceration, fissuring and
crusting of the oral commissures are common late findings. Physical examination
may also reveal evidence of lip licking, drooling, or an anatomical
predisposition to the condition, such as dental malocclusion or poorly-fitting
dentures, which result in overlap of the upper and lower lips.

FIGURE 1.

Angular cheilitis (perleche) is characterized by maceration, erythema and
fissuring at the oral commissures. Skin adjacent to the angles of the mouth may
exhibit scale and erythema.

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FIGURE 2.

Skin adjacent to the angles of the mouth may exhibit scale and erythema.

EXPECTED RESULTS OF DIAGNOSTIC STUDIES



Lesional fungal and bacterial cultures, along with KOH and gram stain, may be
helpful in directing therapy, as angular cheilitis has been associated with
infectious organisms including Candida albicans, Staphylococcus and
Streptococcus spp, and, less frequently, gram negative rods. Skin biopsy is not
necessary or helpful for this diagnosis.

DIAGNOSIS CONFIRMATION





Although angular cheilitis is encountered relatively frequently (especially
among the aging population), it is important to consider that it can be a
presenting sign of nutritional deficiency of iron, riboflavin (B2), folate (B9),
cobalamin (B12), or zinc. Angular cheilitis may also be seen in anemia of
chronic disease and in the Plummer-Vinson syndrome, which manifests with the
triad of dysphagia, esophageal webs and iron deficiency anemia. In addition,
hypervitaminosis A or oral retinoid use can result in angular cheilitis.



A careful dietary and medication history and review of symptoms should be
obtained. If indicated, laboratory testing should be performed to evaluate the
complete blood cell count, reticulocyte count, appropriate vitamin levels, and
serum zinc level



The differential diagnosis of angular cheilitis also includes physical trauma,
chemical injury, and allergic contact dermatitis (classically to toothpaste or
metals used in dental or orthodontic appliances). Individuals with impaired
immunity, including those with HIV, primary immunodeficiency or diabetes
mellitus (DM), are at increased risk for angular cheilitis. Laboratory screening
to rule out undiagnosed underlying systemic disorders and patch testing to rule
out allergic contact dermatitis should be considered on an individual patient
basis.

WHO IS AT RISK FOR DEVELOPING THIS DISEASE?



Angular cheilitis can occur at any age. Risk factors for development of this
condition include lip licking, drooling, hyposalivation (such as occurs in
Sjögren’s syndrome and terminal malignancy), malocclusion, Down syndrome,
orthodontic treatment, denture use, anatomical volume loss in the aging face
resulting in lip overlap, nutritional deficiency, hypervitaminosis A, atopic
dermatitis, HIV, primary immunodeficiency syndromes, conditions requiring
pharmaceutical immunosuppression, and diabetes mellitus.



Isolated case reports describe angular cheilitis in association with pancreatic
glucagonoma and occurring as an adverse event after laser hair removal with
long-pulsed alexandrite laser. Additionally, angular cheilitis can occur acutely
in the post-operative period after tonsillectomy.



Large cross-sectional studies in the United States and Sweden have measured the
overall prevalence of angular cheilitis in the adult population to be 0.71-
3.76% respectively. However, a higher prevalence of 11% has been observed in
sequential patients receiving orthodontic treatment, and a prevalence of 28% was
reported in elderly denture wearers based on a cross-sectional study of elderly
patients (mean subject age 83 years).

WHAT IS THE CAUSE OF THE DISEASE?

ETIOLOGY

PATHOPHYSIOLOGY



The etiology of angular cheilitis is multifactorial and may involve interplay of
physical conditions promoting a moist environment at the oral commissures and
infectious agents. Although C albicans can exist harmoniously in the oral
cavity, it is thought to contribute to the pathophysiology of angular cheilitis.
A higher incidence of C albicans in affected individuals versus unaffected
control patients and observed improvement of the condition with anti-candidal
treatment supports this supposition. Other pathogens implicated in angular
cheilitis include methicillin-sensitive S aureus, Streptococcus spp and gram
negative bacteria.

SYSTEMIC IMPLICATIONS AND COMPLICATIONS



Awareness that angular cheilitis may be associated with nutritional deficiency
(B2, B12, folate, iron, zinc), vitamin overdose (hypervitaminosis A), anemia of
chronic disease, or undiagnosed immunosuppressing systemic disorders (HIV, DM,
primary immunodeficiency) will enable the physician to perform appropriate
testing to diagnose any associated systemic disorders as directed by patient
history. Recurrent angular cheilitis in a patient without dentures should prompt
suspicion for HIV or DM. In addition, patients with severe or chronic angular
cheilitis should be monitored for weight loss or secondary nutritional
deficiencies, which may develop as a consequence of decreased food intake due to
pain from the condition.


TREATMENT OPTIONS



Treatment options are summarized in Table I.

TABLE I.

Medical Treatment Surgical Treatment Physical Modalities Identify and treat any
nutritional deficiencies Injection of fillers to restore anatomy/repair sulcus
at oral commissure Behavioral modification (limit lip licking, thumb sucking,
and/or aggressive dental floss use) Topical anti-candidal agent (clotrimazole,
miconazole, ketoconazole, nystatin)+ barrier paste (zinc oxide)+ topical
corticosteroid (low to mid-potency) Reconstructive dental or orofacial repair  
Topical antibiotic (mupirocin, erythromycin, clindamycin) if bacterial culture
positive or high index of suspicion for bacterial overgrowth     Frequent
barrier paste (zinc oxide) or emollient (petrolatum, lip balm) application for
barrier protection alone     Topical corticosteroids alone (low to mid-potency)
    Intralesional corticosteroids    


OPTIMAL THERAPEUTIC APPROACH FOR THIS DISEASE



Treatment of angular cheilitis should be customized to address the suspected
cause/causes of this multifactorial condition in the individual patient. For
each case, it is helpful to determine if the condition is likely due to
mechanical factors alone or due to a combination of local factors and yeast
and/or bacterial overgrowth.



Perform a careful dietary history and review of symptoms. If concerned about the
possibility of nutritional deficiency, check complete blood count (CBC),
reticulocyte count, iron, B2, B9, B12 and zinc levels. Angular cheilitis that is
secondary to nutritional deficiency will improve with appropriate nutritional
supplementation.



Although limited randomized control trial data exists for the treatment of
angular cheilitis, the available evidence suggests an important role for
antifungal medications. In one small study of Candida culture-positive angular
cheilitis (n=8), treatment with topical nystatin resulted in statistically
significant shortened time to healing when compared to placebo ointment
application in a split-lip treatment study design. Another study that randomized
52 patients with red palate, angular cheilitis, or both conditions to treatment
with nystatin, amphotericin B or placebo oral lozenges found that use of either
nystatin or amphotericin B lozenges resulted in a statistically significant cure
rate of angular cheilitis at 1 month when compared to placebo lozenge use.



Anecdotal evidence supports empiric treatment of angular cheilitis with a
topical anti-candidal agent (clotrimazole, miconazole, ketoconazole, nystatin)
and barrier paste (zinc oxide) layered with low-to-mid potency topical
corticosteroid as needed to control inflammation. Clotrimazole and miconazole
may be advantageous over the other anti-candidal choices as they demonstrate
both anti-candidal and anti-staphylococcal activity. If the patient is also
affected by thrush, the oral cavity should be simultaneously treated with
nystatin solution or systemic fluconazole.



If honey-colored crusts are present or the patient has active atopic dermatitis,
consider bacterial culture at the first visit and empiric treatment with
antibiotic ointment (mupirocin, clindamycin, erythromycin).



Obtain fungal and bacterial cultures to identify contributing infections if poor
response to empiric therapy (topical anti-candidal agent, zinc oxide and
corticosteroid) after 2-3 weeks.



If physical and behavioral factors (thumb sucking, lip licking, aggressive
dental floss use) are suspected as the etiology, consider frequent emollient or
barrier paste application and behavioral modification as initial therapy.



Refer any patients with malocclusion or ill-fitting dentures to a dental
specialist. With time, ill-fitting dentures can promote bone remodeling which
will eventually exacerbate overlapping of lips and create a more favorable
environment for angular cheilitis. In some cases, reconstructive oral surgery
can be performed to correct anatomical abnormalities which promote angular
cheilitis.



If depressions at the oral commissures are likely promoting angular cheilitis,
injection of dermal filler (such as hyaluronic acid) can be considered as a
minimally invasive method to achieve improvement in the local anatomy.



Topical corticosteroids or intralesional corticosteroid injections may be used
as single agent therapy, but if an element of yeast or bacterial overgrowth is
present, may not result in significant improvement.



Obtain history about dental hygiene practices, history of dental procedures
and/or orthodontic work, and dental appliances. Determine how any changes in
these factors may relate to timing of onset of angular cheilitis. If angular
cheilitis symptoms do not respond to empiric therapy (topical anti-candidal
agent, barrier paste and a low-to-mid corticosteroid) or historical timing
suggests allergic contact dermatitis, consider patch testing to toothpastes, as
well as chemicals and metals used in orthodontics and dental appliances.



If recurrent angular cheilitis occurs in an individual without dentures, inquire
about risk factors and consider HIV testing and blood sugar screening to rule
out HIV and DM as underlying predisposing conditions.


PATIENT MANAGEMENT



Although the various treatment options for angular cheilitis have not been
rigorously studied in large randomized placebo controlled trials, the proposed
treatments (topical anti-candidal agents, zinc oxide barrier paste, low-to-mid
potency topical corticosteroids, antibiotic ointments, and emollients) are
supported by anecdotal evidence and offer minimal risk to the patient.



Given the multifactorial nature of this eruption, patients should have a
follow-up visit in 2-3 weeks after initiation of therapy to determine if their
treatment regimen should be adjusted. Given that chronic local factors often
contribute to the development of angular cheilitis, it is likely that the
condition will recur. In one study of 48 patients who were successful treated
with antimicrobial therapy and followed for 5 years, 80% experienced recurrence
of symptoms on one or more occasion. Neither the type of microbe (ie, Candida vs
bacterial species) cultured at diagnosis nor the presence of associated denture
stomatitis was predicative of number of flares of angular cheilitis.



No maintenance or preventative regimens have been well studied to date. A double
blind, randomized control trial of patients aged 60 or greater living in
residential homes demonstrated reduction of angular cheilitis with chewing of
placebo gum and chlorhexidine acetate containing gum twice daily for 15 minutes.
While the study did not analyze its results with intention-to-treat methodology,
the reduction of angular cheilitis and microbial colonization in the
chlorhexidine gum group was significantly greater than that of the control gum
(xylitol) and no gum control groups. Future studies may indicate that
chlorhexidine containing mouthwashes or gums are effective for prevention of
angular cheilitis in specific populations.



In patients with dentures or anatomical changes predisposing them to recurrent
episodes of angular cheilitis, optimization of dental hygiene (including denture
fit and cleaning) and frequent application of barrier paste or emollient (zinc
oxide, petrolatum, lip balm) seem to be reasonable but unproven prevention
strategies. In patients with significant impairment from recurrent angular
cheilitis flares in the context of anatomical distortion, injection of filler
material or oral surgery to restore anatomy should be considered.



Physicians should monitor patients who are chronically affected by angular
cheilitis for weight loss and nutritional deficiencies that may develop from
decreased food intake secondary to pain from the condition.

UNUSUAL CLINICAL SCENARIOS TO CONSIDER IN PATIENT MANAGEMENT



Recurrent angular cheilitis in patients without dentures who lack obvious
predisposing behaviors or anatomical changes should prompt testing to rule out
HIV, DM and other immunodeficiency syndromes.


WHAT IS THE EVIDENCE?

Axell, T. “A prevalence study of oral mucosal lesions in an adult Swedish
population”. Odontol Revy Suppl. vol. 36. 1976. pp. 1-103. (This cross-sectional
study helps to define the prevalence of angular cheilitis and other oral lesions
in adults.)

Cross, D, Eide, ML, Kotinas, A. “The clinical features of angular cheilitis
occurring during orthodontic treatment: a multi-centre observational study”. J
Orthod. vol. 37. 2010. pp. 80-6. (This multicenter European study reports the
incidence of angular cheilitis in patients undergoing orthodontic treatment.)

Dorocka-Bobkowska, B, Zozulinska-Ziolkiewicz, D, Wierusz-Wysocka, B, Hedzelek,
W, Szumala-Kakol, A, Budtz-Jorgensen, E. “Candida-associated denture stomatitis
in type 2 diabetes mellitus”. Diabetes Res Clin Pract. vol. 90. 2010. pp. 81-6.
(This cohort study of patients with type 2 diabetes mellitus examines the
relationship of denture stomatitis, angular cheilitis and glossitis with glucose
control in diabetes. As compared to the control group, patients with diabetes
mellitus demonstrated a significantly higher incidence of angular cheilitis. In
addition, oral complaints coincided with elevated hemoglobin A1c levels.)

Ohman, SC, Jontell, M. “Treatment of angular cheilitis. The significance of
microbial analysis, antimicrobial treatment, and interfering factors”. Acta
Odontol Scand. vol. 46. 1988. pp. 267-72. (This prospective, open trial
monitored patients diagnosed with C albicans and/or S aureus associated angular
cheilitis after treatment with nystatin and/or fusidic acid as guided by
culture. After 42 days of antimicrobial treatment, 96% of treated patients
demonstrated no signs of infection. In addition, 8 patients with C albicans
associated angular cheilitis were treated in a double-blind study. Angular
cheilitis lesions treated with nystatin healed within 28 days, whereas angular
cheilitis persisted past 1 month with placebo treatment.)

Ohman, SC, Jontell, M, Dahlen, G. “Recurrence of angular cheilitis”. Scand J
Dent Res. vol. 96. 1988. pp. 360-5. (This prospective, observational study
reports the incidence of recurrence of angular cheilitis following successful
antimicrobial treatment in 48 patients over a 5-year period. During the 5-year
observation period, 80% of patients experienced one of more repeat episodes of
angular cheilitis. Primary infection with C albicans or S aureus was not
correlated to the number of recurrent episodes.)

Peltola, P, Vehkalahti, MM, Wuolijoki-Saaristo, K. “Oral health and treatment
needs of the long-term hospitalised elderly”. Gerodontology. vol. 21. 2004. pp.
93-9. (This cross-sectional study of the long-term hospitalized elderly reports
that angular cheilitis occurred in 28% of denture wearers in this population.)

Sharon, V, Fazel, N. “Oral candidiasis and angular cheilitis”. Dermatol Ther.
vol. 23. 2010. pp. 230-42. (This review discusses risk factors and
manifestations of the spectrum of Candida associated oral lesions and their
treatment.)

Shulman, JD, Beach, MM, Rivera-Hidalgo, F. “The prevalence of oral mucosal
lesions in U.S. adults: data from the Third National Health and Nutrition
Examination Survey, 1988-1994”. J Am Dent Assoc. vol. 135. 2004. pp. 1279-86.
(This large cross-sectional study of the U.S. population reports the overall
prevalence of angular cheilitis and other oral lesions in U.S. adults.)

Simons, D, Brailsford, SR, Kidd, EA, Beighton, D. “The effect of medicated
chewing gums on oral health in frail older people: a 1-year clinical trial”. J
Am Geriatr Soc. vol. 50. 2002. pp. 1348-53. (This randomized, placebo-controlled
double-blind trial investigates the efficacy of chewing chlorhexidine medicated
gum versus control gum versus no gum in the institutionalized population over
age 60 years. Although intention-to-treat analysis was not done in this 1-year
study, a significant reduction of angular cheilitis is observed in the
-chlorhexidine gum treated population when compared to both the control gum- and
no gum- treated groups.)

Yesudian, PD, Memon, A. “Nickel-induced angular cheilitis due to orthodontic
braces”. Contact Dermatitis. vol. 48. 2003. pp. 287-8. (This single case report
describes the diagnosis of allergic contact dermatitis due to nickel sulfate
contained in orthodontic metal in a 12-year-old boy with treatment-resistant
angular cheilitis. Removal of braces after identification of the allergen by
patch testing resulted in rapid resolution of the angular cheilitis. This
article supports patch testing to relevant chemicals and metals in patients with
treatment resistant angular cheilitis beginning at the time that new
orthodonture or dental work is installed.)



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