Thrush

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Background

First described by the French pediatrician Francois Valleix in 1838, thrush is an infection of the buccal cavity by Candida albicans. The disease is typically limited to infants and neonates, patients on antibiotics or steroids, and patients with polyendocrine disorders or underlying immune dysfunction. Thrush may be the first sign of human immunodeficiency virus (HIV) infection; its appearance in advanced HIV indicates poor prognosis. Children on inhaled steroids also have increased incidence of oral candidiasis.

Pathophysiology

C albicans causes thrush when normal host immunity or normal host flora is disrupted. Overgrowth of yeast on the oral mucosa leads to desquamation of epithelial cells and accumulation of bacteria, keratin, and necrotic tissue. This debris combines to form a pseudomembrane, which may closely adhere to the mucosa. This membrane is usually not large but may rarely involve extensive areas of edema, ulceration, and necrosis of the underlying mucosa.

Affected neonates are typically colonized by C albicans during passage through the birth canal. Hence, the risk for thrush is increased when the mother has an active vaginal yeast infection. Other sources of transmission to neonates include colonized breasts (for breastfed infants), hands, and/or improperly cleaned bottle nipples. Kissing has also been implicated.

C albicans frequently and asymptomatically inhabits the GI tract of many children and adults, and the GI tract has been implicated as a reservoir for yeast contamination of the perineum. Thus, candidal diaper rash frequently occurs in conjunction with thrush.

A systematic review and meta-analysis reported that the prevalence of oral candidiases caused by non-albicans Candida species in sub-Saharan African HIV patients was 33.5% [95% confidence interval (CI) 30.9-36.39%]. Non-albicans Candida species found included C. glabrata (23.8%; 109/458), C. tropicalis (22%; 101/458) and C. krusei (10.7%; 49/458).[1]  

Epidemiology

Frequency

United States

As many as 37% of newborns may develop thrush during the first months of life.

International

Thrush is universal and is more common in poorly nourished populations.

Mortality/Morbidity

Thrush is usually a mild and self-limited illness, although it may cause discomfort sufficient to disrupt feeding in a newborn. Consider the possibility of an underlying immunodeficiency when thrush occurs after early infancy or without a reasonable explanation.

Sex

Thrush occurs equally in males and females.

Age

Thrush is rare during the first week of life. Incidence peaks around the fourth week of life; thrush is uncommon in infants older than 6-9 months. Thrush can occur, however, at any age in predisposed patients.

History

Parents of children with thrush usually notice a white coating in the child's mouth.

Infants may have trouble feeding in severe cases.

Medical history may include the following:

A study found that the adverse effects of antibiotics such as amoxicillin were underreported as treatment with amoxicillin or amoxicillin-clavulanic acid commonly results in candidiasis. The study concluded that clinicians need information about both harms and benefits when prescribing antibiotics.[2, 3]

Maternal history may include the following:

Physical

Lesions often start as tiny focal areas that enlarge to white patches on oral mucosae (see the image below).



View Image

White plaques are present on the buccal mucosa and the undersurface of the tongue and represent thrush. When wiped off, the plaques leave red erosive ....

When scraped with a tongue blade, lesions are difficult to remove and leave behind an inflamed base that may be painful and may bleed.

Candidal infection in the diaper area may accompany thrush. Examine an infant with diaper dermatitis for oral lesions.[5]

Differentiate thrush from a coated tongue.

Thorough physical examination is critical, especially for patients with recurrent thrush and for older children. Pay attention to the child's growth, rash distribution, lymphadenopathy, hepatosplenomegaly, and other potential sites of infection (eg, mucocutaneous candidiasis[6, 7, 8] ).

Causes

Consider an underlying immune deficiency such as AIDS, especially in recurrent cases and in older infants. For chronic infection, chronic mucocutaneous candidiasis should be considered.

Systemic antibiotic use may disrupt the normal flora, promoting candidal overgrowth.

Use of systemic and inhaled steroids is associated with increased incidence of oral thrush.

Laboratory Studies

A relatively simple way to confirm the suspected diagnosis of thrush is to scrape the plaques with a tongue blade to reveal an inflamed and/or bleeding base.

Plaques can be cultured, although cultures are rarely indicated. A simple Gram stain demonstrates large, ovoid, gram-positive yeast.

A study by Tooyama et al looked to establish a reliable laboratory test for diagnosing oral candidiasis. The study found that concentrated rinse sampling is suitable for evaluating oral candidiasis.[9]

Other Tests

Diagnosis can be confirmed by simple histologic findings.

Histologic Findings

Pseudohyphae and gram-positive yeast can be seen on Gram stain or with potassium hydroxide stain.

Medical Care

Although some anecdotal reports indicate no treatment is necessary for otherwise healthy neonates, no published studies support this assertion.[10]

Consultations

In cases in which underlying immune dysfunction is suspected, consultation with an immunologist and infectious diseases specialist may be warranted for further evaluation.

Diet

No special diet is indicated.

Medication Summary

Antifungal therapy generally hastens resolution of infection.[11, 39] The treatment of choice for thrush is fluconazole or oral nystatin suspension, although numerous antifungal agents are effective. Resistance to nystatin is rare, although the drug's contact killing makes it somewhat more difficult to use because it must be applied to all of the affected mucosal surfaces to be effective (unlike systemic therapies). Failures with nystatin are more common than with fluconazole.[12]

In older children and adults, antifungal medications should be swished around in the oral cavity and swallowed. Failure to do so may provide ineffective treatment for lesions in the posterior pharynx and esophagus. In younger patients, instruct parents to apply 1-2 mL of the solution to the inside of each cheek during each administration. Medication can also be directly applied to the lesions with a nonabsorbent swab or applicator. The best time to administer medication is between meals because this allows longer contact time.

Gentian violet solution should not be swallowed. Lozenges (troches) may be used if suspension preparations are unavailable.

These antifungal preparations have minimal adverse effects and few contraindications because they involve little or no systemic absorption. Aside from itraconazole, against which candidal resistance is increasing, other readily available antifungals are effective. If inability to adequately apply nystatin (or the oral cavity's normal flushing mechanisms) results in treatment failure, oral fluconazole or gentian violet are second-line agents.

Nystatin (Mycostatin, Nilstat, Nystex)

Clinical Context:  DOC for oral thrush. No significant absorption from the intact skin, GI tract, or vagina. Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei; effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak.

Amphotericin B deoxycholate (Fungizone Oral Suspension)

Clinical Context:  Produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

Clotrimazole (Mycelex Troches)

Clinical Context:  Alters cell membrane. Very effective treatment in immunocompetent host. If susp not available (not available in the United States), troches (lozenges) can be used, but troche has been associated with elevated liver enzymes and GI adverse effects.

Miconazole oral (Daktar)

Clinical Context:  Not available in the United States. Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol; increases membrane permeability, causing nutrients to leak out, resulting in fungal cell death.

Gentian violet

Clinical Context:  Although inexpensive, efficacious for thrush refractory to other therapies. Solution stains clothing and mucosa intensely, causing undesirable cosmetic effects.

Fluconazole (Diflucan)

Clinical Context:  Azole antifungal with excellent bioavailability. Interferes with cell membrane and is eliminated via renal pathway.

Fungistatic activity. Synthetic PO antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.

Class Summary

The mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Complications

Very rarely, extensive tracheal and esophageal involvement in thrush may lead to dysphagia and respiratory distress in otherwise healthy hosts.

Bronchopulmonary candidiasis has been reported.

Systemic dissemination may occur in immunosuppressed patients.

Candidal esophagitis is a common complication of thrush in immunocompromised patients. In one study, it was the most common opportunistic infection in adults with acquired immunodeficiency syndrome (AIDS) (13.3 episodes per 100 person-years).

Prognosis

Thrush is considered a self-limited disease, but resolution is hastened by medical therapy.

Patient Education

Discuss thrush etiology and incidence as part of general reassurance to the parents of the healthy newborn or infant.

If indicated, offer information about the necessity of further evaluation for underlying immune dysfunction.

For excellent patient education resources, visit eMedicineHealth's Infections Center. Also, see eMedicineHealth's patient education article Candidiasis (Yeast Infection).

What is thrush?What is the pathophysiology of thrush?What is the prevalence of thrush?What is the morbidity associated with thrush?What are the sexual predilections of thrush?Which age groups have the highest prevalence of thrush?Which clinical history findings are characteristic of thrush?Which physical findings are characteristic of thrush?What causes thrush?What are the differential diagnoses for Thrush?What is the role of lab testing in the workup of thrush?How is a diagnosis of thrush confirmed?Which histologic findings are characteristic of thrush?How is thrush treated?Which specialist consultations are beneficial to patients with thrush?Which dietary modifications are used in the treatment of thrush?What is the role of medications in the treatment of thrush?Which medications in the drug class Antifungal agents are used in the treatment of Thrush?What are the possible complications of thrush?What is the prognosis of thrush?What is included in patient education about thrush?

Author

Mudra Kumar, MD, MRCP, FAAP, Professor of Pediatrics, Course Director, Course 6 MSII, Preclerkship Director, Clinical Integration, Department of Pediatrics, University of South Florida Morsani College of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD, Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Disclosure: Nothing to disclose.

Additional Contributors

Leonard R Krilov, MD, Chief of Pediatric Infectious Diseases and International Adoption, Vice Chair, Department of Pediatrics, Winthrop University Hospital; Professor of Pediatrics, Stony Brook University School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Leslie L Barton, MD Professor Emerita of Pediatrics, University of Arizona College of Medicine

Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

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White plaques are present on the buccal mucosa and the undersurface of the tongue and represent thrush. When wiped off, the plaques leave red erosive areas. Courtesy of Matthew C. Lambiase, DO.

White plaques are present on the buccal mucosa and the undersurface of the tongue and represent thrush. When wiped off, the plaques leave red erosive areas. Courtesy of Matthew C. Lambiase, DO.