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Candidiasis, Mucocutaneous

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Candidiasis, Mucocutaneous

para>Vaginal antifungal creams and suppositories can weaken condoms and diaphragms.

Unknown-mucocutaneous candidiasis is common in immunocompetent patients. Complication rates are low.

Candida species are normal flora of oral cavity, pharynx, esophagus, and GI tract that are present in >70% of the U.S. population.

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.

Chronic mucocutaneous candidiasis is a heterogeneous, genetic syndrome with infection of skin, nails, hair, and mucous membranes; typically presents in infancy.

Initial Tests (lab, imaging)

Biopsy: epithelial parakeratosis with polymorphonuclear leukocytes in superficial layers; periodic acid-Schiff staining reveals presence of candidal hyphae.

- 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.

Probiotics: Lactobacillus and Bifidobacterium may inhibit Candida spp.

Proper oral hygiene. Protocols for brushing, denture care, and oral cavity moistening reduce oral candidiasis.

Immunocompromised persons benefit from regular evaluation and screening.

Active-culture yogurt or other live lactobacillus may decrease colonization; indeterminate evidence.

In HIV patients, moderate immunosuppression (e.g., CD4 200 to 500 cells/mm3) may be associated with chronic candidiasis. With more severe immunosuppression (e.g., CD4 <100 cells/mm3), esophagitis or systemic infection are possible.

11 Yang IA, Clarke MS, Sim EH, et al. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;(7):CD002991.22 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):1399-1412.33 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, 2015.44 Coughlin CC, Eichenfield LF, Frieden IJ. Diaper dermatitis: clinical characteristics and differential diagnosis. Pediatr Dermatol. 2014;31(Suppl 1):19-24.55 Williams DW, Jordan RP, Wei XQ, et al. Interactions of Candida albicans with host epithelial surfaces. J Oral Microbiol. 2013;5.66 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):503-535.77 Martins N, Ferreira IC, Barros L, et al. Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment. Mycopathologia. 2014;177(5-6):223-240.88 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.

  • 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.

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 considerationsInfants and seniors: thrush and cutaneous infections (infant diaper rash)Women of childbearing age: vaginitisPrepubertal or postmenopausal: yeast vaginitisPredominant sex: female > male
  • Infants and seniors: thrush and cutaneous infections (infant diaper rash)
  • Women of childbearing age: vaginitis
  • Prepubertal or postmenopausal: yeast vaginitis
  • Predominant sex: female > male

ETIOLOGY AND PATHOPHYSIOLOGY

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

DIAGNOSIS

HISTORY

  • Infants/childrenOral: adherent white patches on oral mucosae or on the tongue that do not wipe away easilyPerineal: erythematous rash with characteristic satellite lesions; painful if skin layer eroded. 40-75% of diaper rashes lasting >3 days are C. albicans (4,5)[A].Angular cheilitis: painful fissures in corners of mouth
  • AdultsVulvovaginal lesions; whitish "curd-like" discharge; pruritus; burning
  • Immunocompromised hostsOral: white, raised, painless, distinct patches; red, slightly raised patchesEsophagitis: dysphagia, odynophagia, retrosternal pain; usually concomitant thrushGI symptoms: abdominal painBalanitis: erythema, erosions, scaling; dysuriaFolliculitis: follicular pustulesInterdigital: redness, itchiness at base and webspaces of fingers and/or toes, possible maceration
  • Oral: adherent white patches on oral mucosae or on the tongue that do not wipe away easily
  • Perineal: erythematous rash with characteristic satellite lesions; painful if skin layer eroded. 40-75% of diaper rashes lasting >3 days are C. albicans (4,5)[A].
  • Angular cheilitis: painful fissures in corners of mouth
  • Vulvovaginal lesions; whitish "curd-like" discharge; pruritus; burning
  • Oral: white, raised, painless, distinct patches; red, slightly raised patches
  • Esophagitis: dysphagia, odynophagia, retrosternal pain; usually concomitant thrush
  • GI symptoms: abdominal pain
  • Balanitis: erythema, erosions, scaling; dysuria
  • Folliculitis: follicular pustules
  • Interdigital: redness, itchiness at base and webspaces of fingers and/or toes, possible maceration

PHYSICAL EXAM

  • Infants/childrenOral: white, raised, distinct patches within the mouth; when wiped off reveals red basePerineal: erythematous maculopapular rash with satellite pustules or papulesAngular cheilitis: tender fissures in mouth corners, often cracked and bleeding
  • AdultsVulvovaginal: thick, whitish, cottage cheese-like discharge; vagina or perineum erythema
  • Immunocompromised hostsOral: white, raised, nontender, distinct patches; red, slightly raised patches; thick, dark-brownish coating; deep fissuresEsophagitis: often, oral thrush is visible.Balanitis: erythema, linear erosions, scalingFolliculitis: follicular pustulesInterdigital: redness, excoriations at base of fingers and/or toes, often maceration
  • 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
  • Vulvovaginal: thick, whitish, cottage cheese-like discharge; vagina or perineum erythema
  • 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 candidiasisLeukoplakia; lichen planus; geographic tongueHerpes simplex; erythema multiformePemphigus
  • 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.
  • Leukoplakia; lichen planus; geographic tongue
  • Herpes simplex; erythema multiforme
  • Pemphigus

DIAGNOSTIC TESTS & INTERPRETATION

  • 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)
  • 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.

TREATMENT

GENERAL MEASURES

MEDICATION

  • Vaginal (choose 1)Miconazole (Monistat) 2% cream: one applicator or 200 mg (one suppository), intravaginally qhs for 7 daysClotrimazole (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
  • OropharyngealMild diseaseClotrimazole (Mycelex): oral 10 mg troche; 20 minutes 5 times daily for 7 to 14 daysNystatin suspension: 100,000 U/mL swish and swallow 400,000 to 600,000 U 4 times per dayNystatin pastilles: 200,000 U each, QID daily for 7 to 14 days (6)[B],(7)[A]Denture wearersNystatin ointment: 100,000 U/g under denture and corners of mouth for 3 weeksRemove dentures at night; clean 2 — weekly with diluted (1:20) bleach.Moderate to severe diseaseFluconazole: 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])
  • EsophagitisFluconazole: 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
  • 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
  • Mild diseaseClotrimazole (Mycelex): oral 10 mg troche; 20 minutes 5 times daily for 7 to 14 daysNystatin suspension: 100,000 U/mL swish and swallow 400,000 to 600,000 U 4 times per dayNystatin pastilles: 200,000 U each, QID daily for 7 to 14 days (6)[B],(7)[A]Denture wearersNystatin ointment: 100,000 U/g under denture and corners of mouth for 3 weeksRemove dentures at night; clean 2 — weekly with diluted (1:20) bleach.
  • Moderate to severe diseaseFluconazole: 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])
  • 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 wearersNystatin ointment: 100,000 U/g under denture and corners of mouth for 3 weeksRemove dentures at night; clean 2 — weekly with diluted (1:20) bleach.
  • 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.
  • 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])
  • 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

2% Miconazole cream, intravaginally, for 7 days in uncomplicated candidiasis. Systemic amphotericin B for invasive candidiasis in pregnancy.

  • VaginalTerconazole (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].
  • OropharyngealMiconazole oral gel (20 mg/mL): QID, swish and swallowItraconazole (Sporanox) suspension: 200 mg (20 mL) daily; swish-swallow for 7 to 14 daysPosaconazole (Noxafil) oral suspension: 400 mg BID for 3 days, then 400 mg daily for up to 28 daysAmphotericin B (Fungizone) oral suspension (100 mg/mL): 1 mL QID daily, swish and swallow; use between meals
  • EsophagitisAmphotericin 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 dailyPosaconazole (Noxafil) oral suspension: 400 mg BIDVoriconazole (Vfend) 100 to 200 mg q12h PO or IV for 14 to 21 days (6)[A]
  • Continue treatments for 2 days after infection gone:ContraindicationsKetoconazole, itraconazole, or nystatin (if swallowed): severe hepatotoxicityAmphotericin B: can cause nephrotoxicityPrecautionsMiconazole: can potentiate the effect of warfarin but drug of choice in pregnancyFluconazole: renal excretion: rare; hepatotoxicity: resistance frequentItraconazole: doubling the dosage results in ~3-fold increase in itraconazole plasma concentrations.
  • Possible interactions (rarely seen with creams, lotions, or suppositories)FluconazoleRifampin: decreased fluconazole concentrationsTolbutamide: decreased concentrationsWarfarin, phenytoin, cyclosporine: altered metabolism; check levels.Itraconazole: potent CYP 3A4 inhibitor. Carefully assess all coadministered medications.
  • 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].
  • In HIV patients: concerns with this regimen include emergence of drug resistance (8)[A].
  • 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
  • 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 dailyPosaconazole (Noxafil) oral suspension: 400 mg BIDVoriconazole (Vfend) 100 to 200 mg q12h PO or IV for 14 to 21 days (6)[A]
  • 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]
  • ContraindicationsKetoconazole, itraconazole, or nystatin (if swallowed): severe hepatotoxicityAmphotericin B: can cause nephrotoxicity
  • PrecautionsMiconazole: can potentiate the effect of warfarin but drug of choice in pregnancyFluconazole: renal excretion: rare; hepatotoxicity: resistance frequentItraconazole: doubling the dosage results in ~3-fold increase in itraconazole plasma concentrations.
  • Ketoconazole, itraconazole, or nystatin (if swallowed): severe hepatotoxicity
  • Amphotericin B: can cause nephrotoxicity
  • 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.
  • FluconazoleRifampin: decreased fluconazole concentrationsTolbutamide: decreased concentrationsWarfarin, phenytoin, cyclosporine: altered metabolism; check levels.
  • Itraconazole: potent CYP 3A4 inhibitor. Carefully assess all coadministered medications.
  • Rifampin: decreased fluconazole concentrations
  • Tolbutamide: decreased concentrations
  • Warfarin, phenytoin, cyclosporine: altered metabolism; check levels.

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

INPATIENT CONSIDERATIONS

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

DIET

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.

COMPLICATIONS

REFERENCES

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

CODES

ICD10

  • B37.9 Candidiasis, unspecified
  • B37.0 Candidal stomatitis
  • B37.49 Other urogenital candidiasis
  • B37.3 Candidiasis of vulva and vagina
  • B37.81 Candidal esophagitis
  • B37.89 Other sites of candidiasis
  • B37.2 Candidiasis of skin and nail

ICD9

  • 112.9 Candidiasis of unspecified site
  • 112.0 Candidiasis of mouth
  • 112.2 Candidiasis of other urogenital sites
  • 112.1 Candidiasis of vulva and vagina
  • 112.89 Other candidiasis of other specified sites
  • 112.3 Candidiasis of skin and nails

SNOMED

  • 29147005 Mucocutaneous candidiasis (disorder)
  • 79740000 Candidiasis of mouth (disorder)
  • 84679006 Gastrointestinal candidiasis (disorder)
  • 111904009 candidiasis of urogenital site (disorder)
  • 72605008 Candidal vulvovaginitis (disorder)
  • 187014000 Candidiasis of skin and nails

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.