Angular cheilitis (AC) is a descriptive diagnosis for an inflammatory skin process of varied etiology occurring at the labial commissure – the angle of the mouth. "Angular," or commissural, refers to a localized lip inflammation (i.e., “cheilitis,” from the Greek chilos or “lips”) that is distinguishable from the more generalized cheilitides that have different causes. The angles of the mouth are points of interface for squamous epithelium of the face and oral mucosa. They are also a mechanically dynamic hinge for the oral aperture that endures more motion and tensile forces than the rest of the lips. Thus, the commissures are especially susceptible to certain stresses.
Diffuse cheilitides may be a function of environmental, chemical, or infectious exposures. They may also reflect internal condition, deficiency, or derangement. They include eczematous cheilitis, contact cheilitis, drug-induced cheilitis, infective cheilitis, actinic cheilitis, glandular cheilitis, granulomatous cheilitis, exfoliative cheilitis, plasma cell cheilitis, and nutritional cheilitis. Diffuse cheilitides will not be discussed here.
Angular cheilitis is also called angular cheilosis, angular stomatitis, commissural stomatitis, rhagades, or perleche (from the French for “through licking”). Rhagades is a general term for fissuring of the skin in areas of motion, especially the labial commissures and nose.
The following are alterations in mouth structure leading to changes in lip approximation and increased salivary pooling and maceration at the labial commissures:
Allergic or irritant contact dermatitis causes up to 22% of cases of AC and 25% to 34% of generalized cheilitis. Common causes include nickel (in individuals with orthodontic braces), foods (due to flavorings and preservatives), toothpaste, mouthwash, the sunscreen component of expired lip balm, lip cosmetics (due to preservatives, sodium laurel sulfate, emollients, colophony, Cocamidopropyl betaine), acne products, and chewing gum. It may be impossible to distinguish irritant and allergic contact dermatitis without a patch test.
Immune deficiency causes AC, often via the development of oral candidiasis (thrush) with extension to the labial commissures. Chronic steroid use (inhaled or oral), HIV/AIDS, thymic aplasia, severe combined immunodeficiency syndrome (SCID), DiGeorge syndrome, hereditary myeloperoxidase deficiency, and Chediak-Higashi syndrome. Blood dyscrasias and malignancies probably also imbue some immune suppression as seen in acute leukemia and agranulocytosis.
Nutritional deficiencies are less common in developed countries but exist in susceptible populations such as the elderly, celiac disease patients, the impoverished, the mentally ill, vegans and their solely breastfed infants not receiving vitamin supplementation, bariatric surgery and ileal resection patients, chronic gastritis and chronic pancreatitis sufferers, Crohn disease patients, and those with pernicious anemia. Up to 25% of AC has iron or vitamin B deficiency. The following are associated with angular cheilitis.
Manifestations of systemic disease (Sjogren syndrome, Inflammatory Bowel disease)
The most common cause of AC, with the organisms below isolated in over 50-80% of lesions.
Recurrent mechanical, chemical, or thermal injury to labial commissures or conditions that make the angles of the mouth susceptible to insults:
Idiopathic AC with No Identifiable Cause
Since infection is the most common cause and maceration from saliva exposure the most common risk factor, empiric treatment with antifungal and/or antibiotic creams are reasonable but, long-term emollient therapy may be necessary in unresponsive or recurrent cases. Any case of idiopathic AC, after it has undergone adequate investigation, should raise a red flag for nutritional deficiencies or malignancy (the latter, especially in unilateral cases that fail to respond to any therapy.) A rare cause of AC is glucagonoma – a pancreatic endocrine tumor that causes a syndrome of dermatitis, diabetes, weight loss, anemia, and AC.
Angular cheilitis (AC) occurs with a prevalence of 0.7% in the general American population, although it can occur more frequently in select groups. It is the most common bacterial/fungal infection of the lips. It has a bimodal distribution, occurring most frequently in children, and then again in adults (age 30 to 60). The elderly have about an 11% prevalence of AC, but there is a 3-fold incidence in denture-wearers, a prevalence of up to 28%, and is twice as frequent in men (but this risk seems more associated with denture use and comorbidities than chronological age.) Predisposing factors include immunodeficiency, and up to 10% of HIV-positive individuals have oral thrush, with or without concomitant AC. Patients with inflammatory bowel disease more frequently get AC, with 7.8% of Crohn’s patients and 5% of ulcerative colitis patients developing AC during some time in their disease course. In rare conditions such as orofacial granulomatosis, the incidence is as high as 20%.
Most cases of angular cheilitis (AC) are ultimately due to physical maceration at the angular commissures due to overexposure to saliva. The digestive enzymes in saliva can act even on body tissues in left if allowed prolonged contact. Continued saliva exposure induces a contact dermatitis and eczematous reaction at the commissures. The compromised integrity of the stratum corneum epithelium allows local commensal organisms to infect the area. Frequently, colonizing Candida albicans establishes and invades the susceptible tissue. This may then allow bacterial superinfection with staph and strep species. Thus, risk factors are those that increase saliva retention at the commissures, increase exposure to culprit microbes, cause direct tissue inflammation, or inhibit wound healing and immunity. Non-infectious causes of AC are further discussed in the etiology section.
The diagnosis of angular cheilitis (AC) is often purely clinical. Therefore, laboratory investigation is usually only performed after treatment failure. However, because an infection is the most common cause, testing for Candida or bacterial culture can be performed at diagnosis.
Investigation of underlying medical conditions that may contribute (nutritional deficiencies, immunocompromised states, systemic diseases) is at the discretion of the medical provider. If first-line antifungal/antibiotic combination yields no clinical improvement in 2 to 3 weeks, testing should include Hgb level with MCV, iron profile with ferritin, folate, and vitamin B2/B6/B12 levels, and fasting blood glucose.
Candidal AC Suspected
Bacterial AC Suspected: Bacterial culture with sensitivities
Oral candidiasis confirmed:
Nutritional Deficiency AC Suspected
Allergic or Irritant Contact AC Suspected: Patch testing to distinguish allergic contact dermatitis
Malignancy Suspected: Biopsy
Treatment depends on non-infectious or infectious etiology. Empiric treatment includes a focus on infection as the most common etiology. Since the most common risk factors involve saliva-induced eczema and the resultant maceration, an effort to protect the labial commissures topical barrier application (petrolatum jelly, emollients, or lip balm) is important, and often sufficient for idiopathic cases of AC.
Fungal infections require topical fungicidal medications applied to the labial commissures, usually 3 times daily for 2 weeks.
Topical Antiseptics or Antibiotics
Bacterial infections require topical antiseptics or antibiotics. Application of the same preparation to the anterior nares (usually 4 to 5 times daily) can prevent recurrent infection when colonization is present. Treatment course is for 1 to 2 weeks.
Oral (systemic) Antifungals
Nystatin is used in mild cases or thrush and those isolated to the oral cavity. Triazoles treat moderate and severe cases of oral candidiasis and any cases extending into the esophagus. When triazoles are used, they obviate the need for topical antifungals. However, they are inhibitors of hepatic cytochrome P450 system and may interact with other drugs. Fluconazole has the highest level of evidence. 
Oral (Systemic) Antibiotics
These rarely warranted unless lesions are extensive or treatment failure to topical antibiotics; should warrant culture, sensitivities, and consideration of an alternative diagnosis
Topical glucocorticoids are monotherapy in strictly inflammatory processes or add-on therapy to anti-candidal or antibacterial regimens to decrease inflammation, enhance healing of erosions, and prevent relapses.
Nutritional replacement/supplementation is necessary in cases of avitaminosis, mineral deficiencies, or general malnutrition. The specifics are beyond this review.
A dentist should refit ill-fitting dentures or other dental apparati to restore facial contour. As the functional reservoir of Candida, treat dentures with an antifungal and cleaned frequently. In chronically debilitated patients, a cannula incorporated into the dentures can channel salivary flow into the oropharynx.
Sometimes, malocclusion persists despite dental realignment or is not a viable option for a patient. Other times, depressions at the commissures exist and are amenable to dermal filler therapy. Injectable fillers (collagen, hyaluronic acid) or surgical implants can change mouth shape and restore commissural anatomy. This makes saliva less likely to accumulate at the fissures. A practitioner who is well-versed in the administration of fillers should apply these fillers since the purpose is beyond the normal cosmetic application.
Improved Control of Chronic Medical Conditions that Contribute to AC
Elimination of Behavioral Practices that Contribute to AC
Follow up in 2 weeks recommended.
As described in the seminal article from 1986 by Ohman, et al., staging is described in four categories. While this is largely used for academic purposes only, it can help clinicians categorize severity and response to treatment:.
Angular cheilitis (AC) is a highly manageable condition. AC is mostly curable and poses no inherent risk to life and rarely results in permanent disfigurement. AC improves within the first several days of successful treatment and typically resolves by 2two weeks, thus schedule a follow up then. Chronic cases can provoke atrophy or granulation formation at the angles of the mouth. In one study done over 5 years, AC had a recurrence rate of 80%. Identification and management of underlying risk factors is a necessity to prevent recurrence. When non-modifiable risk factors exist, when modifiable risk factors go unaddressed, or when the treatment course is incomplete, repeat bouts of AC are commonplace. Common reasons for recurrence are failure to identify and treat oral candidiasis, continued poor oral and denture hygiene. If relapses are frequent, prolong treatment past 2 weeks and use preventive measures with topical emollients or antifungals.
Longstanding angular cheilitis can cause tissue atrophy and permanent scarring or discoloration.
If asymptomatic, AC may go untreated and only recognized by a dental professional who should then be able to manage the AC if due to a correctable malocclusion or ill-fitting dentures. Symptomatic cases (itching, burning, aesthetic concerns) are often brought to primary care physicians’ attention. Empiric treatment with emollients and topical antifungals are reasonable for uncomplicated cases. The suspicion of AC must prompt an evaluation for oral candidiasis (thrush). If confirmed, thrush must be treated, and its cause investigated, for example, HIV, uncontrolled diabetes, steroid use, among others. Should symptoms suggest a systemic cause (Sjogren, IBD) or lesions extend beyond what is expected for common AC, then referral to rheumatology or dermatology is reasonable. Unilateral AC, without a definable explanation, should raise suspicion for malignancy. Cases that respond but recur to not necessarily warrant referral. Severe cases and those failing to respond to conservative empiric therapy should also be referred to dermatology or an oral pathologist. The suspicion that poorly fitting dentures play a role should prompt referral to a dentist or prosthodontist.
Angular cheilitis is a usually a symptom of some condition that leads to saliva-induced maceration of structurally susceptible epithelium at the labial commissures. Symptoms are often mild, and the condition can go untreated for years before being brought to the attention of a medical provider. The observation of angular cheilitis should prompt an evaluation for oral candidiasis. As the elderly as especially susceptible to angular cheilitis, practitioners should be more vigilant in this population. A thorough review of patient medication, behaviors, comorbidities, overall immune and nutritional status is imperative for effective treatment.
Due to the complexity of therapy and a variety of alternatives, a specialty trained pharmacist should work with the interprofessional team. The pharmacist should perform medication reconciliation and assure that there are no allergies to the initial medication choice. The pharmacist should assist in the education of the patient and family in regards to compliance.
The best outcomes are achieved with an interprofessional approach to the care of angular cheilitis. [Level V]
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