> Table of Contents > Candidiasis, Mucocutaneous
Candidiasis, Mucocutaneous
Hugh Silk, MD, MPH, FAAFP
Sheila O. Stille, DMD
Azra Borogovac, MD
image BASICS
DESCRIPTION
  • Heterogeneous mucocutaneous disorder caused by infection with Candida species
  • Characterized by superficial infection of the skin, mucous membranes, and nails
  • >20 Candida species cause infection in humans. Candida albicans is most common.
  • Candidiasis affects:
    • Aerodigestive system
      • Oropharyngeal candidiasis (thrush): mouth, pharynx
      • Angular cheilitis: corner of the mouth
      • Esophageal candidiasis
      • Gastritis and/or ulcers, associated with thrush; alimental or perianal
    • Other systems
      • Candida vulvovaginitis: vaginal mucosa and/or vulvar skin
      • Candidal balanitis: glans of the penis
      • Candidal paronychia: nail bed or nail folds
      • Folliculitis
      • Interdigital candidiasis: webs of the digits
      • Candidal diaper dermatitis and intertrigo (within skin folds)
  • Synonym(s): monilia; thrush; yeast; intertrigo
Pregnancy Considerations
  • Vaginal candidiasis is common during pregnancy.
  • Topical treatment during pregnancy should be extended by several days.
  • Vaginal yeast infection at birth increases the risk of newborn thrush but is of no overall harm to baby.
EPIDEMIOLOGY
  • Common in the United States; particularly with immunodeficiency and/or uncontrolled diabetes
  • Age considerations
    • Infants and seniors: thrush and cutaneous infections (infant diaper rash)
    • Women of childbearing age: vaginitis
    • Prepubertal or postmenopausal: yeast vaginitis
    • Predominant sex: female > male
Incidence
Unknown—mucocutaneous candidiasis is common in immunocompetent patients. Complication rates are low.
Prevalence
Candida species are normal flora of oral cavity, pharynx, esophagus, and GI tract that are present in >70% of the U.S. population.
ETIOLOGY AND PATHOPHYSIOLOGY
C. albicans (responsible for 80-92% vulvovaginal and 70-80% oral isolates). Altered cell-mediated immunity against Candida species (either transient or chronic) increases susceptibility to infection.
Genetics
Chronic mucocutaneous candidiasis is a heterogeneous, genetic syndrome with infection of skin, nails, hair, and mucous membranes; typically presents in infancy.
RISK FACTORS
  • Immunosuppression
  • Antibacterial therapy (broad-spectrum antibiotics)
  • Douches, chemical irritants, and concurrent vaginitides alter vaginal pH predisposing to candidal vaginitis.
  • Denture wear
  • Birth control pills; intrauterine devices
  • Hyperglycemia; diabetes
  • Uncircumcised men at higher risk for balanitis
GENERAL PREVENTION
  • Use antibiotics and steroids judiciously; rinse mouth after inhaled steroid use (1)[A].
  • Avoid douching. Treat other vaginal infections.
  • Minimize perineal moisture (wear cotton underwear; frequent diaper changes).
  • Clean dentures often; use well-fitting dentures, and remove during sleep.
  • Optimize glycemic control in diabetics.
  • Use preventive regimens during cancer treatments (2)[A].
  • Treat with HAART in HIV-infected patients
  • Antifungal prophylaxis against oral candidiasis is not recommended in HIV-infected adults unless patients have frequent or severe recurrences (3)[A].
COMMONLY ASSOCIATED CONDITIONS
  • HIV
  • Leukopenia
  • Diabetes mellitus
  • Cancer and other immunosuppressive conditions
image DIAGNOSIS
PHYSICAL EXAM
  • Infants/children
    • Oral: white, raised, distinct patches within the mouth; when wiped off reveals red base
    • Perineal: erythematous maculopapular rash with satellite pustules or papules
    • Angular cheilitis: tender fissures in mouth corners, often cracked and bleeding
  • Adults
    • Vulvovaginal: thick, whitish, cottage cheese-like discharge; vagina or perineum erythema
  • Immunocompromised hosts
    • Oral: white, raised, nontender, distinct patches; red, slightly raised patches; thick, dark-brownish coating; deep fissures
    • Esophagitis: often, oral thrush is visible.
    • Balanitis: erythema, linear erosions, scaling
    • Folliculitis: follicular pustules
    • Interdigital: redness, excoriations at base of fingers and/or toes, often maceration
DIFFERENTIAL DIAGNOSIS
  • For oral candidiasis
    • Leukoplakia; lichen planus; geographic tongue
    • Herpes simplex; erythema multiforme
    • Pemphigus
  • Baby formula or breast milk can mimic thrush— easier to remove than thrush (no red base when wiped away)
  • Hairy leukoplakia: does not rub off; dorsum and lateral margins of tongue
  • Angular cheilitis from vitamin B or iron deficiency, staphylococcal infection, or edentulous overclosure
  • Bacterial vaginosis and Trichomonas vaginalis tend to have more odor, itch, and a different discharge.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • 10% KOH slide preparation: mycelia (hyphae) or pseudo-mycelia (pseudohyphae) yeast forms; few WBC
  • Associated with normal vaginal pH (<4.5)
  • Barium swallow: cobblestone appearance, fistulas, or dilatation (denervation)
Diagnostic Procedures/Other
  • If 1st-line treatment fails, obtain samples for culture
  • Esophagitis may require endoscopy with biopsy (if suspicious for cancer).
  • HIV seropositive patients with thrush and dysphagia relieved by antifungal have Candida esophagitis.
Test Interpretation
Biopsy: epithelial parakeratosis with polymorphonuclear leukocytes in superficial layers; periodic acid-Schiff staining reveals presence of candidal hyphae.
image TREATMENT
GENERAL MEASURES
Screen for immunodeficiency.
MEDICATION
First Line
  • Vaginal (choose 1)
    • Miconazole (Monistat) 2% cream: one applicator or 200 mg (one suppository), intravaginally qhs for 7 days
    • Clotrimazole (Gyne-Lotrimin, Mycelex): intravaginal tablets (100 mg qhs for 7 days; 200 mg qhs for 3 days; 500 mg daily for 1 day) or 2% cream (one applicator qhs for 3 days)
    • Fluconazole 150 mg PO single dose
  • P.157

  • Oropharyngeal
    • Mild disease
      • Clotrimazole (Mycelex): oral 10 mg troche; 20 minutes 5 times daily for 7 to 14 days
      • Nystatin suspension: 100,000 U/mL swish and swallow 400,000 to 600,000 U 4 times per day
      • Nystatin pastilles: 200,000 U each, QID daily for 7 to 14 days (6)[B],(7)[A]
      • Denture wearers
        • Nystatin ointment: 100,000 U/g under denture and corners of mouth for 3 weeks
        • Remove dentures at night; clean 2× weekly with diluted (1:20) bleach.
    • Moderate to severe disease
      • Fluconazole: 200 mg load then 100 to 200 mg (>14 days of age: 6 mg/kg × 1 dose, then 3 mg/kg q24h × 7-14 days [max 100 mg/day])
  • Esophagitis
    • Fluconazole: PO 400 mg load then 200 to 400 mg/day for 14 to 21 days or IV 400 mg (6 mg/kg) daily if oral therapy not tolerated
Pregnancy Considerations
2% miconazole cream, intravaginally, for 7 days in uncomplicated candidiasis. Systemic amphotericin B for invasive candidiasis in pregnancy.
Second Line
  • Vaginal
    • Terconazole (Terazol): 0.4% cream (one applicator qhs for 7 days of induction therapy); 0.8% cream/80-mg suppositories (one applicator or one suppository qhs for 3 days)
    • For recurrent cases (≥4 symptomatic episodes in 1 year): induction therapy with 10 to 14 days of topical or oral azole, then, fluconazole, 150 mg once per week for 6 months (6)[A]
      • In HIV patients: Concerns with this regimen include emergence of drug resistance (8)[A].
  • Oropharyngeal
    • Miconazole oral gel (20 mg/mL): QID, swish and swallow
    • Itraconazole (Sporanox) suspension: 200 mg (20 mL) daily; swish-swallow for 7 to 14 days
    • Posaconazole (Noxafil) oral suspension: 400 mg BID for 3 days, then 400 mg daily for up to 28 days
    • Amphotericin B (Fungizone) oral suspension (100 mg/mL): 1 mL QID daily, swish and swallow; use between meals
  • Esophagitis
    • Amphotericin B (variable dosing) IV dose of 0.3 to 0.7 mg/kg daily; or an echinocandin should be used for patients who cannot tolerate oral therapy.
    • For refractory disease:
      • Itraconazole (Sporanox) oral solution: 200 mg daily
      • Posaconazole (Noxafil) oral suspension: 400 mg BID
      • Voriconazole (Vfend) 100 to 200 mg q12h PO or IV for 14 to 21 days (6)[A]
  • Continue treatments for 2 days after infection gone:
    • Contraindications
      • Ketoconazole, itraconazole, or nystatin (if swallowed): severe hepatotoxicity
      • Amphotericin B: can cause nephrotoxicity
    • Precautions
      • Miconazole: can potentiate the effect of warfarin but drug of choice in pregnancy
      • Fluconazole: renal excretion: rare; hepatotoxicity: resistance frequent
      • Itraconazole: Doubling the dosage results in ˜3-fold increase in itraconazole plasma concentrations.
  • Possible interactions (rarely seen with creams, lotions, or suppositories)
    • Fluconazole
      • Rifampin: decreased fluconazole concentrations
      • Tolbutamide: decreased concentrations
      • Warfarin, phenytoin, cyclosporine: altered metabolism; check levels.
    • Itraconazole: potent CYP 3A4 inhibitor. Carefully assess all coadministered medications.
ISSUES FOR REFERRAL
  • Patients without obvious reasons for recurrent superficial candidal infections should be evaluated for concurrent immunodeficiency.
  • GI candidiasis
ADDITIONAL THERAPIES
  • For infants with thrush: Boil pacifiers and bottle nipples; assess mother's breasts/nipples for concurrent candida infection.
  • For denture-related candidiasis: disinfect dentures (using soak solution of benzoic acid, 0.12% chlorhexidine gluconate, 1:20 NaOCl or alkalize proteases), and treat orally
COMPLEMENTARY & ALTERNATIVE MEDICINE
Probiotics: Lactobacillus and Bifidobacterium may inhibit Candida spp.
INPATIENT CONSIDERATIONS
Nursing
Proper oral hygiene. Protocols for brushing, denture care, and oral cavity moistening reduce oral candidiasis.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Immunocompromised persons benefit from regular evaluation and screening.
DIET
Active-culture yogurt or other live lactobacillus may decrease colonization; indeterminate evidence.
PATIENT EDUCATION
  • Advise patients at risk for recurrence about overgrowth with antibacterial therapy.
  • “Azole” medications are pregnancy Category C.
PROGNOSIS
  • Benign prognosis in immunocompetent patients
  • For immunosuppressed persons, Candida may become an AIDS-defining illness with significant morbidity.
REFERENCES
1. Yang IA, Clarke MS, Sim EH, et al. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;(7):CD002991.
2. Glenny AM, Gibson F, Auld E, et al. The development of evidence-based guidelines on mouth care for children, teenagers and young adults treated for cancer. Eur J Cancer. 2010;46(8):1399-1412.
3. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed June 10, 2015.
4. Coughlin CC, Eichenfield LF, Frieden IJ. Diaper dermatitis: clinical characteristics and differential diagnosis. Pediatr Dermatol. 2014;31(Suppl 1):19-24.
5. Williams DW, Jordan RP, Wei XQ, et al. Interactions of Candida albicans with host epithelial surfaces. J Oral Microbiol. 2013;5.
6. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(5):503-535.
7. Martins N, Ferreira IC, Barros L, et al. Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment. Mycopathologia. 2014;177(5-6):223-240.
8. Ray A, Ray S, George AT, et al. Interventions for prevention and treatment of vulvovaginal candidiasis in women with HIV infection. Cochrane Database Syst Rev. 2011;(8):CD008739.
Additional Reading
  • Kumar S, Bansal A, Chakrabarti A, et al. Evaluation of efficacy of probiotics in prevention of candida colonization in a PICU—a randomized controlled trial. Crit Care Med. 2013; 41(2):565-572.
  • Nyirjesy P, Sobel JD. Genital mycotic infections in patients with diabetes. Postgrad Med. 2013;125(3):33-46.
  • Terai H, Shimahara M. Tongue pain: burning mouth syndrome vs Candida-associated lesion. Oral Dis. 2007;13(4):440-442.
See Also
Candidiasis, Invasive; Candidiasis, Mucocutaneous; HIV/AIDS
Codes
ICD10
  • B37.9 Candidiasis, unspecified
  • B37.0 Candidal stomatitis
  • B37.49 Other urogenital candidiasis
Clinical Pearls
  • Candidiasis is generally a clinical diagnosis. KOH preparations are a simple confirmatory test in the office setting. Culture and biopsy are rarely needed to identify resistant strains.
  • Person-to-person transmission is rare.
  • If tongue pain continues after treatment, consider burning mouth syndrome. Obtain a biopsy if there is concern for oral cancer.
  • Oral antifungal medications are hepatically metabolized and may have serious side effects.