Candidiasis, Mucocutaneous

Basics

Superficial infections caused by >20 Candida species; C. albicans causes 70% worldwide infections
Common sites: oral thrush, angular cheilitis, esophageal candidiasis, vulvovaginal candidiasis, balanitis, paronychia, interdigital candidiasis, diaper dermatitis, intertrigo
Candida auris: emerging drug-resistant global pathogen

Epidemiology

Common in immunodeficiency and uncontrolled diabetes
Infants and elderly: thrush, cutaneous infections
Women (prepubertal to postmenopausal): yeast vaginitis
Candida spp. colonize oral and GI tract in >70% U.S. population

Etiology and Pathophysiology

Altered cell-mediated immunity increases susceptibility
Chronic mucocutaneous candidiasis: genetic syndrome presenting in infancy

Risk Factors

Immunosuppression (HIV/AIDS, cancer, transplant, steroids)
Smoking, alcoholism
Hyposalivation (Sjögren, drug-induced)
Broad-spectrum antibiotics
Birth control, douching, chemical irritants
Poor oral hygiene, dentures
Diabetes, pregnancy, renal failure, hypothyroidism
Uncircumcised men (higher balanitis risk)

General Prevention

Judicious antibiotic and steroid use; rinse mouth after inhaled steroids
Minimize perineal moisture (cotton underwear, diaper changes)
Clean and remove dentures nightly
Optimize diabetes control
HAART for HIV patients; antifungal prophylaxis only for frequent/severe recurrences

Diagnosis

History

Infants/children: adherent white oral patches, erythematous perineal rash with satellite lesions, angular cheilitis
Adults: vulvovaginal pruritus, burning, curd-like discharge; balanitis with erythema and scaling
Immunocompromised: white oral plaques, esophagitis symptoms, folliculitis

Physical Exam

Oral white plaques removable, red base beneath
Perineal erythema with satellite lesions
Angular cheilitis: fissures and bleeding
Vulvovaginal: thick white discharge, erythema
Balanitis: erythema, erosions
Interdigital redness and maceration
Immunocompromised: oral thrush with thick dark plaques, deep fissures

Differential Diagnosis

Oral candidiasis: leukoplakia, lichen planus, geographic tongue, herpes simplex, pemphigus, burning mouth syndrome
Angular cheilitis: vitamin deficiencies, staph infection
Vaginitis: bacterial vaginosis, trichomoniasis (different discharge and odor)

Diagnostic Tests

10% KOH prep: hyphae or pseudohyphae identification
Vaginal pH usually <4.5
Culture if first-line treatment fails
Esophageal candidiasis: endoscopy and biopsy if suspicious for malignancy

Test Interpretation

Biopsy shows epithelial parakeratosis, polymorphonuclear leukocytes, PAS-positive hyphae

Treatment

General Measures

Screen for immunodeficiency
Optimize underlying conditions

Medications

First Line

Vaginal:
Miconazole 2% cream QHS 7 days or suppositories (200 mg QHS 7 days)
Clotrimazole suppositories or cream, various regimens
Fluconazole 150 mg PO single dose
Oropharyngeal (mild):
Clotrimazole troches 10 mg 5x/day for 7-14 days
Nystatin suspension or pastilles
Denture wearers: nystatin ointment under dentures 3 weeks
Oropharyngeal (moderate/severe):
Fluconazole 200 mg load then 100-200 mg daily for 7-14 days
Esophagitis:
Fluconazole 400 mg load then 200-400 mg daily for 14-21 days or IV if oral not tolerated

Pregnancy

Vaginal candidiasis: 2% miconazole cream intravaginally for 7 days
Systemic amphotericin B for invasive disease

Second Line

Vaginal: various topical azoles or fluconazole 150 mg single dose
Recurrent vulvovaginitis: induction therapy + weekly fluconazole for 6 months
Oropharyngeal: miconazole gel, itraconazole suspension, posaconazole, amphotericin B oral suspension
Esophagitis: amphotericin B IV or echinocandins in oral intolerance or severe cases
Refractory: amphotericin B, itraconazole, posaconazole, voriconazole, isavuconazole, echinocandins

Contraindications and Precautions

Ketoconazole, itraconazole, nystatin (swallowed): hepatotoxicity
Amphotericin B: nephrotoxicity
Miconazole: potentiates warfarin; preferred in pregnancy
Fluconazole: renal excretion, rare hepatotoxicity, resistance frequent
Posaconazole: GI symptoms, QT prolongation risk
Voriconazole: visual disturbances, hepatitis, rare liver failure
Drug interactions: fluconazole affected by rifampin, warfarin, phenytoin; itraconazole inhibits CYP3A4

Issues for Referral

Recurrent infections: evaluate for immunodeficiency
GI candidiasis

Additional Therapies

Infants: boil pacifiers, check maternal nipples for infection
Denture-related: remove dentures nightly, disinfect with vinegar, chlorhexidine, or hypochlorite

Complementary and Alternative Medicine

Probiotics (Lactobacillus, Bifidobacterium) may inhibit Candida colonization

Admission/Inpatient

Oral hygiene protocols and denture care reduce oral candidiasis

Ongoing Care

Follow-up

Immunocompromised need regular evaluation and screening

Diet

Active culture yogurt or lactobacillus may reduce colonization (evidence indeterminate)

Patient Education

Warn about overgrowth risk with antibacterial therapy
Avoid oral azoles in 1st trimester unless benefits outweigh risks

Prognosis

Generally benign in immunocompetent; morbidity significant in immunosuppressed

Complications

HIV: risk of chronic candidiasis (CD4 200-500), esophagitis, systemic infection (CD4 <100)

References

Hendrickson JA, Hu C, Aitken SL, et al. Antifungal resistance: current concerns and future trends. Curr Infect Dis Rep. 2019;21(12):47.
Quindós G, Gil-Alonso S, Marcos-Arias C, et al. Therapeutic tools for oral candidiasis: current and new antifungal drugs. Med Oral Patol Oral Cir Bucal. 2019;24(2):e172-e180.
Denison HJ, Worswick J, Bond CM, et al. Oral vs intra-vaginal azole treatment for vulvovaginal candidiasis. Cochrane Database Syst Rev. 2020;8(8):CD002845.

Clinical Pearls

Candidiasis is usually diagnosed clinically; KOH prep is a simple office confirmatory test
Culture and biopsy are rarely needed unless malignancy is suspected
Person-to-person transmission is rare
Oral azoles are hepatically metabolized and may have serious side effects; monitor accordingly