Continuing Education Activity

Angular cheilitis represents an inflammatory condition localized to the labial commissures, arising from multifactorial causes that include infectious, mechanical, allergic, nutritional, and systemic factors. This course reviews the manifestations of this condition, which include erythematous, fissured, or macerated lesions at the corners of the mouth, often accompanied by discomfort and functional impairment, as well as underlying etiologies including Candida albicans and Staphylococcus aureus, the most common pathogens, nutritional deficiencies, xerostomia, ill-fitting dentures, and immune compromise, which can predispose patients to this condition. Participants will gain an understanding of the clinical diagnosis,  laboratory confirmation, red flags such as unilateral persistent lesions, recurrent infections, and associated systemic signs that require further investigation or referral. 

This course explores the complex etiology, diagnostic approach, and evidence-based management of angular cheilitis, including differentiating infectious from noninfectious causes, recognizing systemic and nutritional associations, and implementing targeted therapeutic strategies. This activity for healthcare professionals is designed to enhance the learner's competence in recognizing angular cheilitis, performing the recommended evaluation, and implementing an appropriate interprofessional approach when managing this condition, thereby reducing recurrence and improving outcomes.

Objectives:

• Identify underlying etiologies contributing to angular cheilitis.
• Implement effective management strategies for angular cheilitis.
• Assess risk factors that predispose patients to recurrent or persistent lesions of angular cheilitis.
• Collaborate with interprofessional team members to coordinate care, including medication management, nutritional supplementation, and patient education to prevent recurrence of angular cheilitis.

Introduction

Angular cheilitis refers to an inflammatory skin condition of varied etiology that develops at the labial commissure, or angle of the mouth. The term “angular” or “commissural” describes localized lip inflammation—cheilitis, derived from the Greek chilos meaning “lips”—that differs from more diffuse forms of cheilitis with distinct underlying causes. Alternative names for angular cheilitis include angular cheilosis, angular stomatitis, commissural stomatitis, rhagades, and perleche—a French term meaning “through licking.” The word rhagades denotes fissuring of the skin in areas subject to frequent movement, most commonly at the labial commissures and nasal region.

The angles of the mouth serve as transition points between the squamous epithelium of the face and the oral mucosa, functioning as mechanically active hinges for the oral aperture. These regions experience greater motion and tensile stress than other parts of the lips, making the commissures particularly vulnerable to mechanical strain and inflammatory changes (see Image. Angular Cheilitis). Diffuse cheilitides often develop in response to environmental, chemical, or infectious factors, or may indicate an internal disorder, deficiency, or systemic imbalance. Conditions in this group include eczematous, contact, drug-induced, infective, actinic, glandular, granulomatous, exfoliative, plasma cell, and nutritional cheilitis. Discussion of diffuse cheilitides falls outside the scope of this activity.

Etiology

Maceration in the Labial Commissures

Alterations in oral and perioral structure may promote salivary pooling and subsequent maceration at the labial commissures, predisposing to angular cheilitis. Several factors can contribute to this process, including:

• Normal loss of skin turgor with aging, smoking, or rapid weight loss
• Reduction in the vertical dimension of the lower face due to severe tooth wear, edentulism, or ill-fitting dentures, which increases the overhang of the upper lip over the lower (ie, overclosure)
• Retrognathic malocclusion
• Deepening of furrows at the commissures (ie, marionette lines) [1] 

Conditions associated with lip enlargement, eg, orofacial granulomatosis, may also lead to commissural maceration, with approximately 20% of patients developing angular cheilitis, though Candida is not typically isolated from these lesions. Similarly, in individuals with Down syndrome, angular cheilitis affects about 25% of patients, primarily as a consequence of macroglossia with tongue protrusion and drooling.[2]

Atopic Dermatitis

Allergic and irritant contact dermatitis causes up to 22% of cases of angular cheilitis and 25% to 34% of generalized cheilitis. Common allergic etiologies 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, or cocamidopropyl betaine), acne products, and chewing gum.[3][4][3] A patch test may be performed to distinguish irritant and allergic contact dermatitis.[5]

Immune Deficiencies

Immune deficiency is also associated with angular cheilitis, often secondary to the development of oral candidiasis that extends to the labial commissures. Conditions affecting the immune system that may cause angular cheilitis include chronic inhaled or oral steroid use, HIV/AIDS, thymic aplasia, severe combined immunodeficiency syndrome (SCID), DiGeorge syndrome, hereditary myeloperoxidase deficiency, and Chediak-Higashi syndrome. Furthermore, blood dyscrasias and malignancies probably also imbue some immune suppression, as seen in acute leukemia and agranulocytosis.

Nutritional Deficiencies

Although nutritional deficiencies are relatively uncommon in developed countries, they remain an important predisposing factor for angular cheilitis in specific susceptible populations, including older adults, individuals with celiac disease, the socioeconomically disadvantaged, patients with mental illness, and strict vegans, as well as their exclusively breastfed infants who do not receive vitamin supplementation. Patients who undergo bariatric surgery or ileal resection are particularly vulnerable due to impaired nutrient absorption.

Other systemic conditions, eg, chronic gastritis, chronic pancreatitis, Crohn disease, and pernicious anemia, further increase the risk of developing angular cheilitis.[6] Additionally, up to 25% of cases of angular cheilitis are associated with iron or vitamin B deficiencies. Specific nutritional risk factors include vitamin B deficiencies (particularly cyanocobalamin, folate, and riboflavin), trace mineral deficiencies (eg, zinc and iron), and general protein malnutrition.[7][8][7]

Manifestations of Systemic Diseases

Angular cheilitis is the most common oral lesion found in Sjögren syndrome, followed by atrophic glossitis and oral candidiasis. This is according to a systematic review by Serrano et al, which incorporated the data of 2426 patients with Sjögren syndrome. The prevalence of angular cheilitis ranged from 2% to 81%, with the largest population reporting a frequency of 20% to 40%. Sjögren syndrome is a rheumatologic disease characterized by xerostomia (dry mouth) and hyposialia (decreased salivation). This results from lymphocytic infiltration and destruction of salivary glands. In this patient group, an inverse correlation between salivary flow and the presence of candidiasis has been noted, contrasting with patterns observed in non-Sjögren-related angular cheilitis. Adequate salivary levels promote mucosal lubrication, facilitate tissue healing, and support local immune defense, which likely accounts for this difference.

Secretory IgA in saliva prevents Candida species from adhering to mucosal surfaces and assists in their removal from the oral cavity. Denture use continues to predispose patients with Sjögren syndrome to angular cheilitis, as dental orthotics serve as reservoirs for Candida and increase the risk of oral candidiasis.[9] Inflammatory bowel disease, particularly Crohn disease, also contributes to angular cheilitis through mechanisms, eg, nutritional deficiency that impair wound healing.

Infection

Infection accounts for the majority of angular cheilitis cases, with microbial organisms isolated in 50% to 80% of lesions.[10]

Infection risk factors

Factors that increase exposure to infectious agents or raise the microbial burden of skin flora contribute significantly to disease development. Poor hygiene, oral thrush, gingival disease, and poor dentition promote colonization. Diabetes mellitus encourages Candida overgrowth through elevated salivary glucose levels and enhanced adherence of fungi to mucous membranes.[11] Immunosuppression resulting from chronic steroid therapy, chemotherapy, or HIV/AIDS reduces local immunity and heightens susceptibility. Prolonged antibiotic use depletes normal oral flora, enabling Candida proliferation.

Specific organisms of infection

Candida species, particularly Candida albicans, represent the most common cause of angular cheilitis. As a commensal yeast, C albicans resides in the oral cavity of 40% to 60% of healthy individuals, which explains its presence in 93% of angular cheilitis cases, though it serves as the sole pathogen in only 20% to 50% of these cases. Poor oral hygiene and denture use increase colony burden. The hyphal form of this dimorphic yeast represents the pathogenic variant, and potassium iodide staining helps distinguish pathogenic invasion from commensal colonization.

Uncontrolled diabetes mellitus heightens risk by producing relative immunodeficiency and providing excess glucose for fungal growth. Candida often initiates infection in macerated labial commissures, facilitating secondary bacterial colonization. Infantile angular cheilitis almost always accompanies oral candidiasis (thrush) and requires treatment to prevent recurrence.

Staphylococcus aureus functions as the sole pathogen in approximately 20% of cases. Because the anterior nares commonly harbor S aureus, decolonization therapy with topical anti-staphylococcal ointments should target the nares when this organism is identified. Beta-hemolytic streptococci appear in 8% to 15% of cases and less often act as solitary pathogens, though they, like S aureus, may colonize the anterior nares. Most angular cheilitis cases involve polymicrobial infection, with C albicans and S aureus identified together in 60% to 75% of patients.

Recurrent Mechanical, Chemical, or Thermal Injury

Repeated mechanical, chemical, and thermal insults to labial commissures or conditions make the angles of the mouth more susceptible to injury.

Xerostomia contributes to 5% of cases of angular cheilitis, with the causes including:

• Radiation treatment
• Sjögren syndrome
• Medications causing xerostomia and xeroderma, eg, isotretinoin, acitretin, indinavir, sorafenib, anticholinergic medications, and anticancer drugs
• Hypervitaminosis A
• Environmental exposures (dry heat, cold)

Repetitive behaviors lead to salivary overexposure and commissural maceration. Habit-induced cheilitis is sometimes considered a distinct entity from angular cheilitis and is termed either “factitious cheilitis” or perleche. These behaviors can include:

• Nervous tics such as over-licking of lips
• Thumb-sucking or lollipops
• Sialorrhea, drooling, or hypersialia
• Aggressive dental flossing [12]
• Smoking

Acute mechanical stress at the labial commissures, eg, posttonsillectomy, can also lead to the development of angular cheilitis.

Idiopathic Angular Cheilitis

Since infection is the most common cause and maceration from saliva exposure is the most common risk factor, empiric treatment with antifungal or antibiotic creams is reasonable; however, long-term emollient therapy may be necessary in cases that are unresponsive or recurrent. Any case of idiopathic angular cheilitis, 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 angular cheilitis is glucagonoma, a pancreatic endocrine tumor that causes a syndrome of dermatitis, diabetes, weight loss, anemia, and angular cheilitis.

Epidemiology

Angular cheilitis affects approximately 0.7% of the general American population but occurs more frequently in specific groups. As the most common bacterial and fungal infection of the lips, angular cheilitis demonstrates a bimodal distribution, appearing most often in children and again in adults between ages 30 and 60. Older adults experience an approximate 11% prevalence, while denture wearers face a 3-fold higher incidence of angular cheilitis, reaching up to 28%. Men are affected about twice as often as women, though this difference primarily reflects denture use and comorbidities rather than age alone.

Immunodeficiency significantly increases susceptibility to developing angular cheilitis. Up to 10% of individuals with HIV develop oral thrush, with or without associated angular cheilitis. Patients with inflammatory bowel disease also show elevated rates, as 7.8% of those with Crohn disease and 5% with ulcerative colitis develop angular cheilitis during some stage of illness. In rare disorders, eg, orofacial granulomatosis, incidence may rise to 20%.[13]

Pathophysiology

Most cases of angular cheilitis 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 if prolonged contact is allowed. Continued saliva exposure induces 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, which may then allow bacterial superinfection with Staphylococcus and Streptococcus 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. (Please refer to the Etiology section for more information on noninfectious causes of angular cheilitis.)

History and Physical

Clinical History

Evaluation of angular cheilitis begins with a detailed history, including prior dental procedures and denture use. Pain may not be a prominent symptom, but when present, it usually manifests as mild discomfort described as dry, itchy, sore, irritated, or burning. Sensations generally remain localized to the lesion and worsen with mouth opening.

In severe cases, angular cheilitis can interfere with eating and contribute to malnutrition, although this condition rarely serves as the primary cause. Clinicians should inquire about symptoms of systemic disease, including diarrhea, hematochezia, or abdominal pain suggestive of Crohn disease, and dryness of eyes or mouth indicative of Sjögren syndrome. Presence of oral thrush warrants assessment of risk factors, eg, diabetes, proton pump inhibitor or steroid use, and HIV status.

Physical Examination

Angular cheilitis presents with red, edematous, often tender patches at the labial commissures, typically triangular in shape. Mild lesions display pinkish erythema with adjacent lips appearing normal or slightly chapped. As lesions progress, moisture can cause superficial maceration and erosion, producing small gray-white areas bordered by reddened mucosa. Moderate lesions may appear papular, eczematous, and fissured, while established lesions can show bluish-white coloration with exfoliative scale and surrounding erythema. Severe fissuring may lead to bleeding, and chronic lesions can exude, crust, or develop granulation tissue.

Bacterial involvement often produces honey-colored exudates or pustules. Angular cheilitis usually remains confined to the mouth corners, but when it extends beyond the vermillion border, fissures (rhagades) follow natural salivary flow along marionette lines. Lesions tend to be bilateral and symmetrical unless asymmetric mechanical or salivary exposure factors exist; unilateral lesions without a clear cause warrant further investigation. Examination should include the oral cavity for candidiasis and other conditions, eg, acute or chronic pseudomembranous plaques, atrophic or erythematous patches, chronic hyperplastic nodules, denture stomatitis, median rhomboid glossitis, keratinized lesions superinfected with Candida, leukoplakia, lichen planus, or lupus erythematosus.[14]

Syndromic and Nutritional Presentations

Angular cheilitis can indicate underlying vitamin or mineral deficiencies. Ariboflavinosis (vitamin B2 deficiency) manifests with cheilosis, angular cheilitis, photosensitivity, magenta glossitis, stomatitis, pharyngitis, and pseudo-syphilis; iron absorption may also be impaired, causing normocytic anemia. Pellagra (vitamin B3 deficiency) presents with dermatitis, diarrhea, dementia, glossitis, and angular cheilitis.

Vitamin B5 deficiency, although rare, can cause angular cheilitis, glossitis, and seborrheic-like rash around the eyes, nose, and mouth. Moreover, vitamin B6 deficiency may present with sideroblastic anemia, cognitive or psychiatric depression, hypertension, hyperhomocysteinemia, neuropathy, conjunctivitis, oral ulcers, atrophic glossitis, angular cheilitis, and intertrigo. Folate and vitamin B12 deficiencies can produce megaloblastic anemia, neurological deficits including peripheral neuropathy, cognitive impairment, and glossitis with angular cheilitis.

Furthermore, iron deficiency manifests as microcytic anemia, glossitis, angular cheilitis, koilonychia, and alopecia areata; associated dysphagia may indicate Plummer-Vinson syndrome. Zinc deficiency can present with symptoms, eg, angular cheilitis, alopecia, diarrhea, dermatitis, and oral ulcers. These symptoms are frequently seen in conditions, eg, acrodermatitis enteropathica, that impair zinc absorption.

Evaluation

The diagnosis of angular cheilitis relies primarily on clinical evaluation, with laboratory investigations typically reserved for cases that fail to respond to initial therapy. Because infection represents the most common etiology, testing for Candida species or bacterial culture may be performed at the time of diagnosis.

Assessment of underlying medical conditions, such as nutritional deficiencies, immunocompromised states, or systemic diseases, depends on clinical judgment. When first-line antifungal or antibiotic therapy fails to produce improvement within 2 to 3 weeks, additional testing should include hemoglobin with mean corpuscular volume (MCV), iron profile with ferritin, folate, vitamin B2, B6, and B12 levels, and fasting blood glucose.

Candidal Angular Cheilitis

Confirmation can involve light microscopy of lesion scrapings stained with periodic acid-Schiff (PAS), which highlights hyphae (indicative of infection) or yeast (potential colonization). Gram staining shows these structures as dark blue, and KOH slides can also visualize hyphae and yeast. Additional methods include the germ tube test (Reynolds-Braude phenomenon) in sheep or human serum at 37 °C for 2 to 4 hours, chlamydospore formation on CMA or rice starch agar incubated at 25 °C for 2 to 3 days, sugar assimilation assays for glucose and maltose fermentation, fungal cultures using Sabouraud dextrose agar with antibiotics, cornmeal agar, or CHROM agar, Candida strain typing (serotyping, isoenzyme profiles, morphotyping, and resistance patterns), and immunodiagnostic testing (eg, enzyme-linked-immunosorbent assay, radioimmunoassay, counterimmunoelectrophoresis,  phytohemagglutinin-induced lymphocyte proliferation, or line probe assay).

Addition Etiology-Specific Studies

Assessment of other underlying medical conditions also includes the following studies:

• Bacterial causes: Bacterial culture with sensitivity testing guides targeted therapy.
• Oral candidiasis: Patients may require HIV testing and diabetes evaluation, including random or fasting blood glucose, glucose tolerance testing, or HgbA1c measurement.
• Nutritional deficiency: Testing should include serum folate, vitamin B12 (along with serum homocysteine or methylmalonic acid levels for greater reliability), urinary riboflavin excretion or erythrocyte glutathione reductase activity for vitamin B2, serum iron profile (eg, iron, saturation, ferritin, TIBC), and serum zinc.
• Allergic or irritant contact angular cheilitis: Patch testing can help distinguish allergic contact dermatitis.
• Suspected malignancy: Biopsy provides definitive evaluation.

Treatment / Management

Angular Cheilitis Management Approaches

Treatment selection depends on whether the underlying etiology of an angular cheilitis case is infectious or noninfectious. Empiric therapy targets infection as the predominant cause. Because saliva-induced eczema and resulting maceration represent the most frequent risk factors, protecting the labial commissures with a topical barrier, eg, petrolatum jelly, emollients, or lip balm, remains essential and often suffices for idiopathic angular cheilitis.[15]

Follow-up after 2 weeks helps assess treatment response and identify unresolved or recurrent disease.

Fungicidal Medications

Fungal infections require topical fungicidal agents applied to the labial commissures, typically 3 times daily for 2 weeks. Recommended treatments include:

• Nystatin 100,000 units/mL ointment topically twice per day
• Gentian violet solution, topically applied 2 to 3 times daily, is effective in children (provided the resulting purple discoloration is acceptable)
• Ketoconazole 2% cream topically
• Clotrimazole 1% cream topically
• Miconazole 2% cream topically with or without hydrocortisone 1% (mixed staphylococcal and candidal infections respond best to this treatment due to its inherent gram-positive bacteriostatic activity; used as first-line treatment by some clinicians)
• Iodoquinol 1% cream topically 2 to 3 times daily (usually combined with hydrocortisone 1% cream)

Topical Antiseptics or Antibiotics

Bacterial infections respond best to topical antiseptics or antibiotics. Applying the same preparation to the anterior nares 4 to 5 times daily can reduce recurrence in cases of nasal colonization. Treatment typically lasts 1 to 2 weeks. Mupirocin 2% ointment, applied 3 to 4 times daily, or fusidic acid 2% cream, used 4 times daily with or without hydrocortisone 1%, serve as standard antistaphylococcal regimens.

Oral (Systemic) Antifungals

Systemic antifungals are reserved for more extensive infections. Nystatin benefits mild thrush confined to the oral cavity, while triazoles treat moderate or severe oral candidiasis and cases extending into the esophagus. Triazoles eliminate the need for topical antifungals but inhibit hepatic cytochrome P450 enzymes, posing a risk for drug interactions. Fluconazole provides the strongest evidence of efficacy.[16] Recommended regimens include:

• Nystatin 5 mL of 100,000 units/mL suspension, swish and swallow 4 times daily for 7 to 14 days (no oral bioavailability).
• Clotrimazole 1 troche, dissolved 5 times daily for 7 to 14 days for mild oropharyngeal candidiasis refractory to nystatin.
• Fluconazole 200 mg orally for 1 day, followed by 100 mg daily for 7 to 14 days; dose may increase to 200 mg daily in severe or immunocompromised cases.
• Itraconazole 200 mg daily for 2 to 4 weeks or 200 mg, swish and swallow 4 times daily without food for 7 to 14 days.
• Posaconazole 100 mg orally twice on day 1, then 100 mg daily for 7 to 14 days, with dose escalation to 400 mg twice daily for fluconazole- or itraconazole-refractory cases.
• Voriconazole is reserved for failure of fluconazole and itraconazole or posaconazole.
• Caspofungin 70 mg once, then 50 mg daily until 2 days after symptom resolution.
• Amphotericin 30 to 40 g daily until 2 days after resolution (40–50 g daily for neutropenic patients).

Further systemic management of oral candidiasis extends beyond this activity.

Oral (Systemic) Antibiotics

Systemic antibiotics are rarely indicated unless lesions are extensive or resistant to topical therapy. Culture and sensitivity testing should guide alternative diagnoses and subsequent therapy.

Topical Glucocorticoids

Topical glucocorticoids serve as monotherapy for inflammatory causes or adjuncts to antimicrobial regimens to reduce inflammation, promote healing, and prevent recurrence. Desonide 0.05% ointment and hydrocortisone 1% ointment applied 2 to 3 times daily for 2 weeks, often combined with iodoquinol 1% or fusidic acid 2% cream, remain standard options.

Nutritional Replacement and Supplementation

Patients with avitaminosis, mineral deficiencies, or general malnutrition require nutritional correction, though detailed protocols extend beyond this review. Please see StatPearls' companion resource, "Nutritional Assessment" and "Severe Acute Malnutrition: Recognition and Management of Marasmus and Kwashiorkor," for further information on nutritional deficiencies. 

Dental Management

Dentists play a crucial role by refitting ill-fitting dentures or appliances to restore facial contour. Dentures, as Candida reservoirs, require antifungal treatment and frequent cleaning. In debilitated patients, a denture-incorporated cannula can redirect salivary flow into the oropharynx.

Occasionally, malocclusion persists despite dental realignment or is not a viable option for a patient. Additionally, in some cases, depressions at the commissures exist that are amenable to dermal filler therapy. When malocclusion persists or dental correction proves impractical, dermal filler therapy using collagen or hyaluronic acid, or surgical implants, can restore commissural anatomy and reduce saliva pooling. Practitioners skilled in filler application should perform these procedures, as the intent extends beyond cosmetic enhancement.

Improved Control of Chronic Medical Conditions

Optimal management of systemic diseases reduces the recurrence of angular cheilitis. Glycemic control in diabetes lowers the incidence of angular cheilitis, as HgbA1c levels correlate directly with disease frequency. In HIV/AIDS, antiretroviral therapy enhances immune function and indirectly decreases the incidence of angular cheilitis.

Elimination of Contributory Behaviors

Behavioral modification remains essential to reduce the occurrence of angular cheilitis. Patients should avoid lip licking and tobacco smoking, both of which exacerbate commissural irritation and delay healing.

Treatment Failures

Various factors can result in treatment failure. Persistent disease may result from unaddressed oral candidiasis, resistant Candida, Staphylococcus, or Streptococcus strains, or failure to manage modifiable factors, eg, hygiene and denture fit. Other contributors to therapeutic failure include unmodifiable risk factors and undiagnosed conditions, eg, nutritional deficiencies, systemic inflammatory diseases (eg, Sjögren’s syndrome, inflammatory bowel disease), immunosuppression, or malignancy.[17]

Treatment Monitoring

Follow-up after 2 weeks allows clinicians to assess therapeutic response, confirm resolution of lesions, and identify persistent or recurrent infection. Reevaluation should include inspection of the labial commissures, assessment of hygiene and denture fit, and review of medication adherence. Persistent symptoms warrant repeat culture, evaluation for resistant organisms, and investigation of underlying nutritional, systemic, or behavioral factors contributing to treatment failure.

Differential Diagnosis

Underlying differential diagnoses that should be considered when evaluating a patient with angular cheilitis include:

• Secondary syphilis/syphilitic papule localized to the labial commissure; more likely to be unilateral
• Erosive oral lichen planus or lichenoid oral lesions
• Impetigo
• Atopic dermatitis
• Seborrheic dermatitis
• Allergic contact cheilitis
• Irritant contact cheilitis
• Early or isolated diffuse cheilitis

  • Actinic cheilitis, especially if the commissures go unprotected with sun-protective lip balms
  • Cheilitis glandularis
  • Cheilitis granulomatosa
  • Exfoliative cheilitis

Toxicity and Adverse Effect Management

Nystatin therapy has been associated with mucositis and, in rare cases, Stevens-Johnson syndrome. Oral fluconazole and clotrimazole troches may lead to elevated liver function tests and, infrequently, hepatotoxicity. Proton pump inhibitors reduce systemic absorption of azole antifungals by increasing gastric pH.

Triazole antifungals, including fluconazole, itraconazole, voriconazole, and posaconazole, act as inhibitors of hepatic cytochrome P450 enzymes. All triazoles inhibit CYP3A4 and can increase plasma concentrations of multiple medications. Fluconazole and ketoconazole also inhibit CYP2C8 and CYP2C9. Clinicians should exercise caution when prescribing triazoles alongside other drugs and consider substituting amphotericin or nystatin when appropriate. Specific drug interactions include: 

• Warfarin, monitor for a 2 to 3 times increase in INR
• Vinca alkaloids
• Steroids (methylprednisolone and dexamethasone)
• Statins
• Protease inhibitors
• Phosphodiesterase type-5 inhibitors
• Phenytoin (clinicians should decrease the dose and monitor serum levels with fluconazole and itraconazole)
• Felodipine cut the dose by 50%
• Digoxin: monitor serum digoxin levels
• Cyclosporine (decrease dosage by 50% and monitor serum cyclosporine levels)
• Carbamazepine (only in azole doses over 200 mg per day)
• Benzodiazepines reduce the dose
• Aripiprazole

Staging

As outlined in the seminal 1986 publication by Ohman et al, staging divides the condition into 4 distinct categories. Although primarily intended for academic application, this classification also assists clinicians in assessing disease severity and monitoring treatment response.[18][19][20] The stages of angular cheilitis include:

• Type I: Localized fissuring at the commissure with minimal extension to adjacent skin
• Type II: Deeper, more irregular lesions that extend further in length and depth than type I
• Type III: Multiple radiating fissures spreading from the corner of the mouth into the surrounding skin
• Type IV: Absence of fissures, but with erythema affecting the skin adjacent to the vermilion border

Prognosis

Angular cheilitis remains a highly manageable and generally curable condition that poses no direct threat to life and rarely leads to permanent disfigurement. Most patients with angular cheilitis experience improvement within the first few days of effective therapy, with complete resolution typically occurring by 2 weeks; therefore, a follow-up appointment should be scheduled at that time. Chronic disease can lead to atrophy or granulation tissue formation at the oral commissures.

A 5-year study reported an 80% recurrence rate in patients with angular cheilitis, emphasizing the necessity of identifying and managing underlying risk factors to prevent relapse. Recurrence becomes common when nonmodifiable factors persist, modifiable contributors remain uncorrected, or the treatment course ends prematurely. Frequent causes of relapse include undiagnosed or untreated oral candidiasis and inadequate oral or denture hygiene. For patients experiencing repeated episodes of angular cheilitis, treatment should extend beyond 2 weeks, accompanied by preventive measures, eg, regular application of topical emollients or antifungal agents.

Complications

Complications of angular cheilitis primarily arise from chronic or recurrent disease and inadequate management of underlying causes. Persistent inflammation can lead to atrophy, granulation tissue formation, discoloration, and scarring at the labial commissures, potentially resulting in mild distortion of the mouth contour. Secondary bacterial or fungal superinfection may occur, prolonging healing and increasing discomfort. Recurrent cases often reflect untreated oral candidiasis, resistant microbial strains, nutritional deficiencies, or poor oral hygiene. In individuals with diabetes or immunosuppression, delayed healing and more severe infections may develop. Although angular cheilitis rarely causes permanent disfigurement, ongoing irritation and relapse significantly affect comfort, function, and quality of life.

Consultations

Asymptomatic angular cheilitis often remains unnoticed until identified by a dental professional, who can manage the condition when related to correctable malocclusion or ill-fitting dentures. Symptomatic cases presenting with itching, burning, or cosmetic concerns typically reach the attention of primary care clinicians. Empiric therapy with emollients and topical antifungals offers an appropriate initial approach for uncomplicated presentations. Any suspicion of angular cheilitis should prompt evaluation for oral candidiasis (thrush).

When thrush is confirmed, treatment must address both the infection and its underlying cause, eg, HIV infection, uncontrolled diabetes, or corticosteroid use. Symptoms suggesting a systemic condition (eg, Sjögren syndrome or inflammatory bowel disease) or lesions extending beyond typical boundaries warrant referral to rheumatology or dermatology. Unilateral angular cheilitis without an identifiable cause should raise concern for possible malignancy. Cases that respond to treatment but recur do not necessarily require referral, while severe or treatment-resistant cases should be evaluated by a dermatologist or oral pathologist. When poorly fitting dentures contribute to disease persistence, consultation with a dentist or prosthodontist is appropriate.

Deterrence and Patient Education

Preventative Measures 

A clinical trial by Simons et al demonstrated that xylitol or chlorhexidine acetate/xylitol gum reduced the incidence of angular cheilitis in patients aged 60 and older.[21] Avoidance of allergens remains essential for managing cases related to allergic contact dermatitis. Rinsing the mouth after inhaled corticosteroid use in patients with COPD or asthma decreases the risk of developing oral candidiasis. In individuals colonized with Staphylococcus or Streptococcus species, application of mupirocin or bacitracin to the anterior nares can eradicate bacterial reservoirs and prevent bacterial angular cheilitis.

Identifying and addressing infection reservoirs, eg, dentures, also plays a key preventive role; dentures should be cleaned thoroughly and may require overnight storage in hypochlorite or chlorhexidine solutions. Early referral to a prosthodontist becomes necessary when denture-related factors contribute to disease persistence. In edentulous or immunosuppressed patients, prophylactic use of barrier ointments such as petrolatum or zinc oxide, or daily application of an imidazole cream, helps prevent recurrence.

  Patient Education   Patient education for angular cheilitis should focus on hygiene, prevention, and adherence to treatment. Patients must maintain proper oral and denture hygiene, avoid lip licking and tobacco use, and apply prescribed topical agents as directed. Instruction on rinsing the mouth after inhaled corticosteroid use reduces oral candidiasis risk. Individuals with diabetes should monitor blood glucose closely, and those using dentures should ensure proper fit, frequent cleaning, and overnight disinfection when advised. Patients with recurrent episodes should understand the importance of addressing underlying risk factors and attending scheduled follow-up visits to monitor healing and prevent relapse.

Pearls and Other Issues

Key factors that should be kept in mind include:

• Every case of angular cheilitis should prompt an investigation for oral candidiasis. A finding of oral candidiasis should prompt an investigation for diabetes or immunosuppression, including, but not limited to, steroid use.
• Do not use topical steroid monotherapy without excluding infectious angular cheilitis.
• Unilateral angular cheilitis may be due to local trauma, herpetic lesions, or syphilitic papule. Cases that do not respond to treatment may also be a manifestation of malignancy.

Enhancing Healthcare Team Outcomes

Angular cheilitis is an inflammatory condition affecting the labial commissures, often resulting from a combination of infectious, mechanical, nutritional, or systemic factors. Candida species represent the most common infectious cause, frequently compounded by bacterial colonization from Staphylococcus aureus or beta-hemolytic streptococci. Mechanical stress, salivary maceration, and ill-fitting dental appliances predispose the labial angles to lesion formation. Nutritional deficiencies, particularly of iron, zinc, and B vitamins, along with immunocompromised states such as diabetes or HIV, further increase susceptibility. Clinical presentation ranges from mild erythema to fissuring, maceration, and crusting, often requiring antifungal or antibacterial therapy, topical barrier protection, and correction of underlying risk factors. Laboratory confirmation and systemic testing become essential when lesions fail to resolve with first-line therapy.

Effective management of angular cheilitis requires a coordinated, interprofessional approach. Physicians and advanced practitioners assess underlying causes and implement appropriate pharmacologic interventions, including triazole antifungals, while monitoring for drug interactions. Dentists and prosthodontists ensure proper fitting of dentures and dental appliances to minimize mechanical stress. Nurses provide patient education on hygiene, topical therapy application, and behavior modification to prevent recurrence. Pharmacists evaluate medication interactions, particularly with systemic azoles, and guide dose adjustments. Dietitians address nutritional deficiencies, while care coordination among team members ensures timely follow-up, monitoring of systemic conditions, and optimized patient-centered outcomes, improving overall safety and reducing recurrence.

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Disclosure: Melina Brizuela declares no relevant financial relationships with ineligible companies.

Disclosure: Joseph Daley declares no relevant financial relationships with ineligible companies.