Oral+candidiasis

ORAL CANDIDIASIS
http://www.dentalcare.com/soap/intermed/oralcan.htm **Synonyms**: Candidosis Thrush Moniliasis

Overview
Candidiasis is an opportunistic infectious condition caused by a ubiquitous, saprophytic fungi of the genus //Candida//, which includes eight species of fungi, the most common of which is //Candida albicans//. Candidiasis is usually limited to the skin and mucous membranes. Common clinical types of mucocutaneous candidiasis include: **oropharyngeal** (affecting the oral cavity and/or pharynx), **vulvovaginal** (affecting the vaginal and vulvar mucosa), **paronychial** (affecting the nail beds and folds), **interdigital** (usually affecting the skin in between the fingers), **intertriginous** (affecting the skin of the submammary areas or the groin and/or scrotum). Systemic, invasive, infections of candidiasis can occur, especially in those patients with severe immunosuppression. The gastrointestinal tract, trachea, lungs, liver, kidneys and central nervous system are all potential sites for infection in disseminated systemic candidiasis and may result in septicemia, meningitis, hepatosplenic disease, and endocarditis.

Epidemiology
Oral candidiasis is predominately caused by //Candida albicans//, although other related //Candida// species may be involved. //Candida// is commensal organism and part of the normal oral flora in about 30% - 50% of the population, and is capable of producing opportunistic infections within the oral cavity when appropriate predisposing factors exist.

Etiology and Pathogenesis
Neville, //et. al.// have identified three general factors that may lead to clinically evident oral candidiasis. These factors are: (1) the immune status of the host, (2) the oral mucosal environment, (3) the particular strain of //C. albicans// (the hyphal form is usually associated with pathogenic infection). The following is a list of specific conditions that may predispose a patient to develop oral candidiasis.
 * 1) Factors that alter the immune status of the host:
 * Blood dyscrasias or advanced malignancy
 * Old age/Infancy
 * Radiation therapy/Chemotherapy
 * HIV infection or other immunodeficiency disorders
 * Endocrine abnormalities:
 * Diabetes mellitus
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Hypothyroidism or Hypoparathyroidism
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Pregnancy
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Corticosteroid therapy/Hypoadrenalism
 * 1) <span style="font-size: 16pt; font-family: Norasi, serif;">Factors that alter the oral mucosal environment:
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Xerostomia
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Antibiotic therapy
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Poor oral or denture hygiene
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Malnutrition/Gastrointestinal malabsorption
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Iron, folic acid, or vitamin deficiencies
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Acidic saliva/Carbohydrate-rich diets
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Heavy smoking
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Oral epithelial dysplasia

<span style="font-size: 16pt; font-family: Norasi, serif;">Diagnosis
<span style="font-size: 16pt; font-family: Norasi, serif;">The diagnosis of oral candidiasis is most frequently made on the basis of clinical appearance along with exfoliative cytology examination. This involves the histologic examination of intraoral scrapings which have been smeared microscope glass slides. A 10% - 20% potassium hydroxide preparation ("KOH prep") can be used for immediate microscopic identification of yeast cell forms. Alternatively, the slide containing the cytologic smear can be sprayed with a cytologic fixative and stained using PAS (Periodic acid - Schiff) stain prior to microscopic examination. A biopsy of affected tissue may be indicated, especially when candidiasis is suspected in conjunction with some concurrent pathology, such as epithelial dysplasia, squamous cell carcinoma, or lichen planus. It is also possible to culture //Candida// using a Sabouraud's agar slant to aid in the definitive identification of the fungal organism.

<span style="font-size: 16pt; font-family: Norasi, serif;">Clinical Presentation and Treatment
<span style="font-size: 16pt; font-family: Norasi, serif;">**I. (Acute) Pseudomembranous Candidiasis** <span style="font-size: 16pt; font-family: Norasi, serif;">**Rationale for Treatment: Topical vs. Systemic Drugs**
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Pseudomembranous candidiasis is the most common form of oral candidiasis.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">The most common sites include buccal mucosa, dorsal tongue, and palate.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Most frequent etiologies include antibiotic therapy or immunosuppression.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">It appears as soft, creamy white to yellow, elevated plaques, that are easily wiped off affected oral tissues and leave an erythematous, eroded, or ulcerated surface which may be tender.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Topical antifungals are usually the drug of choice for uncomplicated, localized candidiasis in patients with normal immune function.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Systemic antifungals are usually indicated in cases of disseminated disease and/or in immunocompromised patients.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Duration of therapy: Medication should be continued for at least 48 hours after the disappearance of clinical signs of candidiasis along with complete healing and the absence of mucosal erythema. Some sources recommend drug therapy should be continued for 10-14 days regardless of the disappearance of clinical signs of candidiasis.

<span style="font-size: 16pt; font-family: Norasi, serif;">Suggested Medications for the Treatment of Pseudomembranous Candidiasis:
<span style="font-size: 16pt; font-family: Norasi, serif;">Topical antifungal medications: > Nystatin oral suspension 100,000 units/ml > Disp: 300 ml (14+ day supply) > Sig: Rinse with 1 teaspoonful (5 ml) for two minutes, use q.i.d. (after meals, and at bedtime) and spit out. NPO 1/2 hour. (Patient can be directed to rinse and swallow if there is pharyngeal involvement). > Clotrimazole troches, 10 mg > Disp: 70 troches > Sig: Let 1 troche dissolve in mouth 5 times per day for 14 days. Do not chew. NPO 1/2 hour. <span style="font-size: 16pt; font-family: Norasi, serif;">Systemic antifungal medications: > Ketoconazole tablets, 200 mg > Disp: 14 tablets > Sig: Take 1 tab q.d. with a meal or orange juice for 14 days > Fluconazole tablets, 100 mg > Disp: 15 tablets > Sig: Take 2 tablets stat, then 1 tablet q.d. for 14 days > Itraconazole tablets, 100 mg > Disp: 28 tablets > Sig: Take 1 tablet b.i.d. with a meal or orange juice for 14 days
 * 1) <span style="font-size: 16pt; font-family: Norasi, serif;">Rx:
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<span style="font-size: 16pt; font-family: Norasi, serif;">II. Chronic Hyperplastic Candidiasis

 * <span style="font-size: 16pt; font-family: Norasi, serif;">The most common sites are the anterior buccal mucosa along the occlusal line, and laterodorsal surfaces of the tongue.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">The etiology may be idiopathic or associated with immunosuppression.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">The most common appearance is that of asymptomatic white plaques or papules (sometimes against an erythematous background) that are adherent and do not scrape off.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Some sources believe that hyperplastic candidiasis may have the ability to promote the development of oral epithelial carcinogenesis.

<span style="font-size: 16pt; font-family: Norasi, serif;">Treatment of hyperplastic candidiasis:

 * <span style="font-size: 16pt; font-family: Norasi, serif;">Use topical or systemic medications as was recommended for pseudomembranous candidiasis.

<span style="font-size: 16pt; font-family: Norasi, serif;">III. Chronic Atrophic (Erythematous) Candidiasis

 * <span style="font-size: 16pt; font-family: Norasi, serif;">The most common site is the hard palate under a denture, but atrophic candidiasis may also be found on the dorsal tongue and other mucosal surfaces.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">The most common etiology is poor denture hygiene, and/or continuous denture insertion, but it may also be caused by immunosuppression, xerostomia, or antibiotic therapy.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">The most common appearance is that of a red patch or velvet textured plaque. When atrophic candidiasis occurs on the hard palate in association with a denture, it is frequently associated with papillary hyperplasia.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Patients may complain of a burning sensation associated with this type of candidiasis.

<span style="font-size: 16pt; font-family: Norasi, serif;">Rationale for Treatment of Chronic Atrophic (Erythematous) Candidiasis

 * <span style="font-size: 16pt; font-family: Norasi, serif;">It is important to remember to treat both the denture (if present) and the oral tissues. (The denture will act as a reservoir for the //Candida// and reinfect the tissues if they are not treated concurrently).

<span style="font-size: 16pt; font-family: Norasi, serif;">Suggested Medications for the Treatment of Chronic Atrophic (Erythematous) Candidiasis
<span style="font-size: 16pt; font-family: Norasi, serif;">Rx: Nystatin ointment or Clotrimazole cream 1% or Miconazole cream 2% or Ketoconazole cream 2%

Disp: One tube (15 or 30 gm) Sig: Apply thin coat of medicine to entire inner surface of denture after each meal for 14 days.*
 * <span style="font-size: 16pt; font-family: Norasi, serif;">* || <span style="font-size: 16pt; font-family: Norasi, serif;">Instruct the patient to leave dentures out at night and to soak denture in a 1% sodium hypochlorite solution for 15 minutes with thorough rinsing under running water for at least 2 minutes, before bedtime. ||

<span style="font-size: 16pt; font-family: Norasi, serif;">IV. Median Rhomboid Glossitis

 * <span style="font-size: 16pt; font-family: Norasi, serif;">Median rhomboid glossitis is a form of chronic atrophic candidiasis characterized by an asymptomatic, elongated, erythematous patch of atrophic mucosa of the posterior mid-dorsal surface of the tongue due to a chronic //Candida// infection. (In the past, median rhomboid glossitis was thought to be a developmental defect resulting from a failure of the tuberculum impar to retract before fusion of the lateral processes of the tongue).
 * <span style="font-size: 16pt; font-family: Norasi, serif;">A concurrent "kissing lesion" of the palate is sometimes noted.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">Specific predisposing etiologic factor(s) for median rhomboid glossitis have not been clearly established.

<span style="font-size: 16pt; font-family: Norasi, serif;">V. Angular Cheilitis (Perleche)

 * <span style="font-size: 16pt; font-family: Norasi, serif;">Clinical appearance is that of red, eroded, fissured lesions which occur bilaterally in the commissures of the lips and are frequently irritated and painful.
 * <span style="font-size: 16pt; font-family: Norasi, serif;">The most common etiology is loss of vertical occlusal dimension, but it may also be associated with immunosuppression.

<span style="font-size: 16pt; font-family: Norasi, serif;">Suggested Medications for the Treatment of Angular Cheilitis
<span style="font-size: 16pt; font-family: Norasi, serif;">Rx: Nystatin - triamcinolone acetonide ointment orClotrimazole cream 1% or Miconazole cream 2% or Ketoconazole cream 2%

Disp: One tube (15 gm) Sig: Apply to affected areas q.i.d. (after meals, and at bedtime) for 14 days.

<span style="font-size: 16pt; font-family: Norasi, serif;">Insurance coding: ICD-9-CM
<span style="font-size: 16pt; font-family: Norasi, serif;">112.0 Candidiasis, oral

<span style="font-size: 16pt; font-family: Norasi, serif;">Authored by F. John Firriolo, DDS, PhD
<span style="font-size: 16pt; font-family: Norasi, serif;">Dr. Firriolo is an Associate Professor in the Division of Oral Diagnosis and Oral Medicine at the University of Louisville, School of Dentistry.

<span style="font-size: 16pt; font-family: Norasi, serif;">Reference List
<span style="font-size: 16pt; background: #ffff00; font-family: Norasi, serif;">Oral Candidiasis
 * 1) <span style="font-size: 16pt; font-family: Norasi, serif;">Bunetel L, Bonnaure-Mallet M. Oral pathoses caused by Candida albicans during chemotherapy: update on development mechanisms. //Oral Surg Oral Med Oral Pathol Oral Radiol Endod// 1996;82:2,161-5.
 * 2) <span style="font-size: 16pt; font-family: Norasi, serif;">Greenspan D. Treatment of oral candidiasis in HIV infection. //Oral Surg Oral Med Oral Pathol// Oral 1994;78:2, 211-5.
 * 3) <span style="font-size: 16pt; font-family: Norasi, serif;">Lynch DP. Oral candidiasis. History, classification, and clinical presentation. //Oral Surg Oral Med Oral Pathol// 1994;78:2, 189-93.
 * 4) <span style="font-size: 16pt; font-family: Norasi, serif;">Neville BW, Damm DD, Allen CM, Bouquot JE. //Oral & Maxillofacial Pathology//. Philadelphia: W.B. Saunders, 1995, p. 163-9.
 * 5) <span style="font-size: 16pt; font-family: Norasi, serif;">Sapp JP, Eversole, LR, Wysocki GP. Contemporary Oral and Maxillofacial Pathology. St. Louis: Mosby, 1997, p228-31.
 * 6) <span style="font-size: 16pt; font-family: Norasi, serif;">Silverman S, Gallo JW, McKnight ML, et. al. Clinical characteristics and management responses in 85 HIV-infected patients with oral candidiasis. //Oral Surg Oral Med Oral Pathol Oral Radiol Endod// 1996;82:4, 402-7.
 * 7) <span style="font-size: 16pt; font-family: Norasi, serif;">Rosenberg SW, Arm RN, eds. Clinician's Guide to Treatment of Common Oral Conditions. Baltimore: The American Academy of Oral Medicine,1997, p. 5-7.

<span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">**Definition:** “<span style="font-size: 16pt; font-family: Norasi, serif;">Oral thrush,” a fungal disease of the oral mucosa and tongue, is caused most often by //Candida albicans//, although there have been reports of increased incidence of non-albicans species. In the absence of other known causes of immune suppression, oral thrush in an adult is highly suggestive of HIV infection. Three clinical presentations are common in people with HIV: pseudomembranous, erythematous, and angular cheilitis. As HIV disease progresses, candida infection may invade the esophagus (See //Esophageal Complaints// in Complaint-specific section, and //Esophageal Candidiasis// in Disease-Specific section), causing dysphagia or odynophagia.

<span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">**S: Patient complains of white patches on tongue and oral mucosa, smooth red areas on dorsal tongue, burning or painful mouth areas, changes in taste sensation, sensitivity to spicy foods, and decreased appetit**e. Erythematous candidiasis tends to be symptomatic with c/o oral burning, most often while eating salty or spicy foods or drinking acidic beverages. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">**O: PE:** Patients presenting with oral candidiasis may be totally asymptomatic, so it is important to inspect the oral cavity thoroughly. Lesions can occur anywhere on the hard and soft palates, under the tongue, on the buccal mucosa or gums, or extending back into the posterior pharynx. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">__Pseudomembranous candidiasis__ appears as creamy white curd-like plaques on the buccal mucosa, tongue, and other mucosal surfaces that will wipe away, leaving a red or bleeding underlying surface. Lesions may be as small as 1-2 mm. in size, or extensive plaques covering the entire hard palate. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">__Erythematous candidiasis__ presents as a flat red, subtle lesion or lesions either on the dorsal surface of the tongue and/or the hard/soft palates. The tongue may have depapillated red mucosal areas on its dorsal surface. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">__Angular cheilitis__ presents with fissuring and redness at either one or both corners of the mouth, and may appear alone or in conjunction with another form of oral candida infection. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">**A:** Partial Differential: For suspected pseudomembranous candidiasis, rule out oral hairy leukoplakia, coated tongue, and other fungal infections. For suspected erythematous candidiasis: R/O burn or trauma. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">**P: LABS:** Clinical exam alone is usually diagnostic. Organisms may be detected on smear or culture. 1. Do a KOH preparation of a smear collected by the gentle scraping of the affected area with a wooden tongue depressor. Visible hyphae or blastospheres on KOH mount indicate candida infection. 2. Culture is diagnostic. 3. Refractory cases of oral candidiasis may be caused by //Candida glabrata, C. tropicalis//, or //C. Krusei//, all of which are azole-resistant. Candidiasis which does not respond to therapy should be cultured to check the identity of the fungal species. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">**TX:** **Topical therapies are recommended for mild to moderate cases of intraoral candidiasis.** Treatment with fluconazole can result in selective growth of non-albicans species, and should only be implemented when necessitated by more severe disease. 1. Clotrimazole troches (Mycelex) dissolved in mouth 5 times/day x 2 weeks. 2. Alternative therapy: Nystatin vaginal pastilles dissolved in mouth are very effective, or may use nystatin oral suspension "swish and swallow", 4-6 ml. Swish, retain in mouth as long as possible, then swallow. Recommended therapy with either is QID x two weeks. Note that the oral suspension has a high sugar content, which may precipitate caries or xerostomia.

<span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">2. In refractory cases, check to ensure that the causal organism is not azole-resistant. If discovered to be of mycotic etiology, treat with IV Amphotericin B <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">3. In cases so severe as to interfere with adequate nutrition and hydration, patient may require hospitalization for hydration and nutritional support. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">4. In patients who wear partials or dentures, have them soak the prosthesis in chlorhexidine solution (such as PerioGard), then apply a thin coating of Nizoral cream on the acrylic portion of the appliance that will be in contact with the oral mucosa before reinserting into the mouth. This will prevent re-infection by the appliance. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">5. Maintenance therapy for future suppression may be necessary, and can range from one Mycelex lozenge per day to one lozenge TID. Fluconazole suppressive therapy is generally not recommended except for those patients with documented esophageal candidiasis due to the possibility of azole resistance with long term use. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">**Patient Education:**

2. Rinse mouth of all food before using either lozenges or suspension for treatment. Teach proper use of all medications. 3. Avoid mouth trauma: use a soft toothbrush, don't eat food or drink liquids that are too hot in temperature or too spicy. 4. For patients who have candidiasis under a denture or partial denture: Remove prosthesis before use of topical agents such as Mycelex or Nystatin. At bedtime, place the prosthesis in a chlorhexidine solution, then apply a thin coating of Nizoral cream on the acrylic portion of the appliance before reinserting into the mouth. 5. Women on azole drugs should avoid pregnancy due to possible skeletal and craniofacial abnormalities in infants. <span style="font-size: 16pt; color: #000000; font-family: Norasi, serif;">**References:** Magaldi S, Mata S, Hartung C, et al. In vitro susceptibility of 137 Candida sp. isolates from HIV positive patients to several antifungal drugs. //Mycopathologia// 2001; 149(2):63-68. <span style="font-size: 16pt; font-family: Norasi, serif;">Sande MA, Gilbert DN, Moellering RC Jr. //The Sanford// //Guide to HIV/AIDS Therapy, 10th edition.// 2001; Hyde Park, VT, Antimicrobial Therapy, Inc.

Bartlett JG, Gallant JE. //2001-2002 Medical Management of HIV Infection.// 2001, Baltimore, Johns Hopkins University Division of Infectious Diseases. <span style="font-size: 16pt; font-family: Norasi, serif;">CDC. USPHS/IDSA Guidelines for Preventing Opportunistic Infections Among HIV-Infected Persons. //MMWR// 2002; 51 (No. RR-8). <span style="font-size: 16pt; font-family: Norasi, serif;">New York State Department of Health AIDS Institute. //Oral health care for people with HIV infection.// Downloaded 11/1/02 from http://www.hivguidelines.org/public_html/CENTER/clinical-guidelines

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