Introduction
Oral candidiasis, a common infection of the oral cavity caused by Candida albicans, was first identified in 1838. Predominantly occurring due to immune system compromise, it affects individuals across all age groups, particularly newborns, the elderly, and those with conditions like HIV/AIDS or undergoing prolonged steroid or antibiotic therapies. Local immunosuppression, such as from inhaled corticosteroids used for asthma and COPD, also increases susceptibility. While acute pseudomembranous candidiasis, commonly known as thrush, is the most recognized form, oral candidiasis presents in diverse ways, manifesting as both white and red lesions. White lesions include thrush and chronic hyperplastic candidiasis, whereas red lesions encompass acute and chronic erythematous candidiasis, angular cheilitis, median rhomboid glossitis, and linear gingival erythema. Accurate diagnosis is crucial, especially when considering the Thrush Differential Diagnosis, as various oral conditions can mimic its symptoms. This article delves into the evaluation, differential diagnosis of thrush, and treatment of oral candidiasis, emphasizing the essential role of a multidisciplinary healthcare approach. We will explore the disease’s origins, epidemiology, pathophysiology, and guide clinicians in approaching patients with suspected oral candidiasis, focusing on history, physical examination, evaluation, thrush differential diagnosis, and effective treatment strategies.
Etiology
Oral candidiasis is primarily caused by Candida species, with Candida albicans being the most prevalent, accounting for over 80% of cases. Candida albicans is a dimorphic fungus capable of existing in both hyphal and yeast forms, adapting to its environment. While less frequent, other Candida species such as Candida glabrata, Candida tropicalis, and others can also be responsible. Notably, non-albicans Candida species are observed more often in elderly patients over 80 years old.
It’s important to recognize that Candida is a natural inhabitant of the oral microbiome in healthy individuals. Approximately 30% to 60% of adults and 45% to 65% of infants carry Candida in their mouths, typically as a commensal organism. However, various risk factors can disrupt this balance, leading to pathogenic colonization. These factors include malnutrition, age extremes (infants and the elderly), metabolic disorders, immunocompromising conditions, concurrent infections, radiation therapy, organ transplantation, prolonged steroid use, antibiotic treatment, and reduced salivary gland function.
Epidemiology
Oral candidiasis affects both immunocompetent and immunocompromised individuals, but it is significantly more common in those with weakened immune systems. Alarmingly, over 90% of HIV-positive individuals will develop oral candidiasis at some point during their illness.
The incidence of oral candidiasis is equal across genders. It is frequently observed in newborns and infants, with rarity in the first week of life, peaking around the fourth week, and decreasing after six months, likely due to the maturation of the infant’s immune system. In infants, signs of underlying immunosuppression may include diarrhea, skin rashes, recurrent infections, and hepatosplenomegaly.
Pathophysiology
Oral candidiasis develops when the host’s immune defenses are compromised, allowing Candida species to proliferate. This immune disruption can be localized, such as from topical oral corticosteroid use. The fungal overgrowth results in the formation of a pseudomembrane, characteristic of thrush. Neonates can acquire Candida during vaginal delivery from an infected mother or through breastfeeding from colonized breasts. Oral Candida infections in infants can also spread to the gastrointestinal tract, leading to candidal diaper dermatitis. Candida thrives in moist environments, which explains the susceptibility to vaginal candidiasis in females.
In healthy individuals, the immune system and normal oral flora maintain control over Candida growth. Conditions causing immunosuppression, such as diabetes, denture use (creating a micro-environment), steroid therapy, malnutrition, vitamin deficiencies, and recent antibiotic use (disrupting normal flora), are significant predisposing factors for oral candidiasis.
Histopathology
Clinical examination is typically sufficient for diagnosing oral candidiasis. However, histopathological evaluation becomes necessary when the diagnosis is uncertain, particularly for thrush differential diagnosis, or in cases resistant to antifungal treatments. Biopsy is especially recommended for chronic hyperplastic candidiasis due to its potential for malignant transformation. Common diagnostic methods include 10% potassium hydroxide (KOH) stain and culturing on Sabouraud dextrose agar to identify Candida. Specialized media like Chromagar Candida can differentiate specific Candida species. ELISA and PCR tests are utilized for suspected invasive candidiasis and to distinguish Candida dubliniensis from Candida albicans.
History and Physical Examination: Types of Oral Candidiasis
While pseudomembranous candidiasis, or oral thrush, is the classic and most common presentation, oral candidiasis manifests in several forms, presenting as either white or erythematous lesions within the oral cavity. Understanding these varied presentations is crucial for accurate diagnosis and effective thrush differential diagnosis. White lesions are categorized as pseudomembranous or hyperplastic, while erythematous lesions include acute and chronic atrophic forms, angular cheilitis, median rhomboid glossitis, and linear gingival erythema. Rarer forms not discussed in detail here include cheilocandidiasis, chronic mucocutaneous candidiasis, and chronic multifocal candidiasis.
Acute Pseudomembranous Candidiasis (Thrush)
Alt text: Dorsum of tongue exhibiting acute pseudomembranous candidiasis, showing characteristic white, curd-like plaques.
Pseudomembranous candidiasis, or thrush, is the most prevalent type of oral candidiasis, representing about one-third of all cases. It is most frequently observed in newborns and immunocompromised individuals, but also affects the elderly. Risk factors include topical steroid use (inhalers, gels, rinses) and reduced saliva production.
Thrush typically presents with extensive white patches that are easily removable, revealing an underlying erythematous mucosal surface. These pseudomembranes are composed of desquamated epithelial cells, fibrin, and fungal hyphae. Lesions are generally asymptomatic and can appear on the tongue, labial and buccal mucosa, gingiva, hard and soft palate, and oropharynx. Symptomatic patients may report a burning sensation, oral bleeding, and altered taste perception.
Hyperplastic Candidiasis
Hyperplastic candidiasis manifests as slightly raised, well-defined white plaques, typically on the buccal mucosa and potentially extending to the labial commissures. These lesions may also be nodular or speckled. Unlike thrush, hyperplastic candidiasis lesions are not easily wiped away. Smoking is strongly associated with its development, and smoking cessation is often necessary for complete resolution.
Hyperplastic candidiasis carries a risk of progressing to severe dysplasia or malignancy. The presence of Candida in leukoplakia lesions has been shown to increase the risk of malignant transformation compared to non-candidal leukoplakias. Therefore, careful monitoring and differentiation from other leukoplakic lesions are vital in the thrush differential diagnosis.
Acute Atrophic Candidiasis
Acute atrophic candidiasis presents as generalized or localized erythema of the oral mucosa, most commonly affecting the palate, but can also occur on the buccal mucosa and tongue dorsum. Atrophy of the tongue papillae may accompany the erythema. Patients often seek medical attention due to a burning sensation in the mouth or on the tongue, making it an important consideration in the thrush differential diagnosis of a sore tongue.
This form is frequently triggered by broad-spectrum antibiotic use. Other risk factors include corticosteroids, HIV infection, iron deficiency anemia, vitamin B12 deficiency, and uncontrolled diabetes mellitus.
Chronic Atrophic Candidiasis (Denture Stomatitis)
Chronic atrophic candidiasis, also known as denture stomatitis, is characterized by localized erythema of the oral mucosa directly beneath dentures. It’s a common condition, affecting up to 65% of denture wearers. Similar lesions can also occur under orthodontic appliances. Risk factors primarily include ill-fitting dentures, continuous denture wear (24 hours/day), and poor oral hygiene.
Lesions are typically edematous and erythematous, confined to the denture-contacting area. Angular cheilitis often co-occurs with denture stomatitis. Denture stomatitis is clinically classified into three types: Type I (petechial hemorrhage and localized inflammation), Type II (erythema of the mucosa under the denture), and Type III (erythema of the central hard palate or papillary hyperplasia under the denture). While often asymptomatic, patients may report oral soreness or burning.
Median Rhomboid Glossitis
Alt text: Clinical presentation of median rhomboid glossitis, showing a central, rhomboid-shaped, smooth, red patch on the posterior dorsum of the tongue.
Median rhomboid glossitis is a less common form of oral candidiasis, affecting less than 1% of the population. It appears as a rhomboid-shaped erythematous patch in the center of the tongue’s dorsum, anterior to the circumvallate papillae. This lesion arises from the atrophy of the filiform papillae. Smoking and inhaled steroid use are associated risk factors.
A “kissing lesion,” an erythematous lesion on the palate directly opposite the tongue lesion, can develop concurrently, often indicating immunosuppression. The kissing lesion is a potential marker for HIV, warranting further investigation.
Angular Cheilitis
Alt text: Angular cheilitis in an elderly patient, showing bilateral fissuring, redness, and crusting at the corners of the mouth, associated with dentures and iron deficiency.
Angular cheilitis presents as erythematous, fissured patches at one or both corners of the mouth, commonly bilaterally. The lesions are typically painful and sore. A moist environment, due to saliva accumulation in the mouth corners, promotes Candida growth. However, bacteria such as Staphylococcus aureus and streptococcal species are also frequently involved. Factors contributing to saliva accumulation include denture wear, lip licking, corner biting, and facial wrinkles. Nutritional deficiencies, particularly iron, folic acid, thiamine, riboflavin, and vitamin B12 deficiencies, are also linked to angular cheilitis.
Linear Gingival Erythema
Linear gingival erythema is frequently observed in HIV-positive individuals and can be an indicator of disease progression. However, it can also occur in healthy children. Clinically, it presents as a distinct erythematous line or band along the gingival margins of one or more teeth. Both Candida and bacterial infections contribute to its development.
Evaluation
The diagnosis of oral candidiasis is primarily clinical, based on physical examination, patient history, and risk factor assessment. Diagnosis relies on identifying characteristic lesion features, excluding other conditions in the thrush differential diagnosis, and assessing the lesion’s response to antifungal treatment. Biopsy is recommended for acute atrophic and chronic hyperplastic candidiasis, in addition to empirical treatment, as these forms can mimic premalignant or malignant lesions.
Culture and sensitivity testing are indicated when antifungal treatment is ineffective. Various methods exist for sampling the oral cavity to identify Candida species. For visible lesions, a swab or imprint using a sterile foam pad is recommended. If no specific lesion is apparent but Candida infection is suspected, collecting a whole saliva sample or using an oral rinse technique is advised. In suspected denture stomatitis, samples should be taken from both the denture’s internal surface and the palatal mucosa, as sampling only the oral mucosa might yield false negatives.
Beyond confirming candidiasis, evaluating for underlying immunocompromising conditions is crucial. Patients may require testing for HIV, adrenal insufficiency, malnutrition, steroid use, and diabetes mellitus.
Treatment / Management
Treatment strategies for oral candidiasis focus on targeting Candida species, tailored to the extent of the infection and the patient’s immune status. Topical antifungal therapy is the first-line approach for uncomplicated cases and should be continued even when systemic treatment is necessary. Systemic antifungals are reserved for patients unresponsive to topical treatments, those intolerant to topical therapy, or those at high risk of systemic infection.
Topical antifungal medications and good oral hygiene are usually sufficient for mild oral candidiasis. Available topical antifungals include nystatin, miconazole, clotrimazole, and ketoconazole. While miconazole use in the mouth can cause nausea and diarrhea, it is effective for angular cheilitis and denture stomatitis. Nystatin, available as pastilles, mouthwash, and oral suspension, is a commonly used topical treatment. Patients typically rinse with nystatin mouthwash four times daily for two weeks. Common side effects are nausea, vomiting, and diarrhea.
Nystatin oral rinse and clotrimazole troches are high in sucrose. For diabetic patients or those at high risk of dental caries, triazoles like fluconazole or itraconazole, taken once daily, are suitable alternatives.
Topical treatment is recommended for mild or first-time presentations. Options include clotrimazole troches 10 mg orally five times daily (dissolved slowly) or nystatin oral suspension (100,000 units/mL) 5 mL orally four times daily (swished and swallowed). Miconazole oral gel may also be considered.
For moderate to severe disease, fluconazole 200 mg orally initially, then 100 mg orally once daily for 7 to 14 days is recommended. Fluconazole is generally considered safe during breastfeeding.
For refractory cases, options include itraconazole oral solution 200 mg once daily (empty stomach, 28 days), posaconazole suspension 400 mg orally twice daily for three days, then 400 mg orally daily (28 days total), and voriconazole 200 mg orally twice daily for 28 days.
Single-dose oral fluconazole 150 mg has shown efficacy in advanced cancer patients, reducing medication burden.
Oral azoles are teratogenic and should be avoided in the first trimester for mucosal candidiasis. Clotrimazole troches, nystatin topical therapies, and miconazole buccal tablets are alternative treatment options during pregnancy. Pediatric dosages should be weight-adjusted.
Patient counseling should include managing immunosuppressing conditions like uncontrolled diabetes, smoking cessation, and addressing malnutrition.
Denture Management
Denture hygiene is critical in treating denture stomatitis and should be emphasized in all forms of oral candidiasis to eliminate Candida reservoirs on dentures.
Specific Treatment Considerations
Acute Pseudomembranous Candidiasis in Infants: Treatment for breastfed infants involves topical antifungals for both the infant and mother’s nipples, even if asymptomatic. If nipples show thrush symptoms, systemic fluconazole may be added for the mother. Nystatin oral suspension is applied to the infant’s lesions, and miconazole 2% cream to the mother’s nipples (off-label use for breastfeeding thrush).
Acute Erythematous Candidiasis: Often antibiotic-induced, stopping antibiotics may resolve it. If symptoms are severe, systemic fluconazole 50 mg daily for one week may be indicated.
Angular Cheilitis: Treatment includes antifungal and steroid creams. Miconazole cream is recommended for ten days post-resolution. Combined miconazole/hydrocortisone cream can be used. Treat concurrent oral lesions. Address nutritional deficiencies. Mupirocin cream in anterior nares can eliminate Staphylococcus aureus reservoirs.
Chronic Hyperplastic Candidiasis: Fluconazole 50 mg daily for 7-14 days and smoking cessation are key. Patients need to be aware of malignant transformation risk. Systemic antifungal treatment for seven days before biopsy can differentiate true dysplasia from Candida-related dysplasia.
Linear Gingival Erythema: Management includes debridement, chlorhexidine mouthwash, antiretroviral therapy for HIV patients, and antifungal treatment.
Differential Diagnosis
The differential diagnosis of thrush and other erythematous forms of oral candidiasis includes several conditions that can mimic its presentation. For erythematous forms, consider oral mucositis, erythroplakia, thermal burns, erythema migrans (geographic tongue), and anemia. Chronic hyperplastic candidiasis can be mistaken for leukoplakia, lichen planus, pemphigoid, pemphigus, and oral squamous cell carcinoma (OSCC).
Other conditions to differentiate from oral candidiasis include oral hairy leukoplakia (Epstein-Barr virus related), angioedema, aphthous stomatitis, herpes gingivostomatitis, herpes labialis, measles (Koplik spots), perioral dermatitis, Stevens-Johnson syndrome, histiocytosis, blastomycosis, lymphohistiocytosis, diphtheria, esophagitis, syphilis, and streptococcal pharyngitis. A thorough clinical examination and history are crucial to narrow down the thrush differential diagnosis.
Alt text: Oral pseudomembranous candidiasis infection, showing extensive white plaques on the oral mucosa, a classic presentation of thrush.
Prognosis
The prognosis for oral candidiasis is generally favorable with appropriate and timely treatment. Recurrence is often linked to poor treatment adherence, inadequate denture hygiene, or unresolved underlying predisposing factors.
Complications
While uncommon in immunocompetent individuals, oral candidiasis can spread to the pharynx, causing dysphagia and respiratory distress. In immunocompromised patients, systemic dissemination is a significant concern. Candidal esophagitis is a common complication of oral candidiasis in HIV/AIDS patients.
Deterrence and Patient Education
Patient education is crucial in preventing and managing oral candidiasis. Key points include:
- Advise patients using steroid inhalers to rinse their mouths with water after each use.
- Counsel patients on the link between oral candidiasis and nutritional deficiencies, emphasizing balanced nutrition.
- Provide thorough instructions on denture care and oral hygiene practices to prevent denture stomatitis and other forms of oral candidiasis.
- Advise reducing high sugar intake, which can promote Candida overgrowth.
Enhancing Healthcare Team Outcomes
Oral candidiasis, while often viewed as a straightforward condition, presents in diverse clinical forms beyond just oral thrush. Effective management requires a collaborative interprofessional healthcare team. Patients may present with varied symptoms, from asymptomatic infections to oral burning and taste changes. Accurate diagnosis relies on history, risk factor assessment, and clinical examination, with further evaluation for refractory cases. General practitioners, dentists, and pediatricians are often the first to diagnose and manage oral candidiasis. Pediatricians are crucial in managing neonatal and infant thrush. Nurses play a vital role in identifying thrush in breastfeeding infants and educating mothers. All team members, including dental nurses and pharmacists, are essential for reinforcing oral and denture hygiene instructions. Pharmacists ensure medication compliance, verify dosing, check for drug interactions, and communicate concerns to the team. Nurses administer medications, provide patient counseling, and reinforce key educational points. Effective interprofessional collaboration, with clear communication and shared patient records, is essential for achieving optimal outcomes in oral candidiasis management and addressing the thrush differential diagnosis effectively.
Review Questions
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Disclosures:
Disclosure: Michael Taylor declares no relevant financial relationships with ineligible companies.
Disclosure: Melina Brizuela declares no relevant financial relationships with ineligible companies.
Disclosure: Avais Raja declares no relevant financial relationships with ineligible companies.
