Candidiasis

Candida albicans is the most common cause of candidiasis and appears almost universally in low numbers on healthy skin, in the oropharyngeal cavity, and in the gastrointestinal and genitourinary tracts. In immunocompetent individuals, C. albicans usually causes minor localized infections, including thrush (affecting the oral cavity), vaginal yeast infections (if there is an underlying pH imbalance), and infections of the intertriginous areas of skin (e.g., the axillae or gluteal folds). More widespread and systemic infections may occur in immunocompromised individuals (e.g., neonates, diabetics, and HIV patients), with the esophagus most commonly affected (candida esophagitis). Localized cutaneous candidiasis may be treated with topical antifungal agents (e.g., clotrimazole). More widespread and systemic infections require systemic therapy with fluconazole or caspofungin.

Pathogen

• Most common: Candida albicans (C. albicans)
  • A type of dimorphic fungi that can form:
    • Oval, budding yeast (see general mycology) and hyphae and long pseudohyphae at 20^oC
    • Germ tubes at 37^oC
  • Ubiquitous on healthy skin, as well as in the oropharyngeal cavity, gastrointestinal tract, genitourinary tract, and vagina
• Other candida species: C. krusei, C. glabrata, C. tropicalis, C. parapsilosis ^[1]

Risk factors

• Immunosuppression is the main risk factor for infection.
  • HIV
  • Diabetes mellitus
  • Neutropenia
  • Certain patient groups (e.g., ICU, transplant patients, surgical patients, and neonates)
• Imbalance in local flora
  • Medications: e.g., antibiotics, steroids, cytostatic agents, immunosuppressive therapy
  • ↑ Estrogen levels during pregnancy
• Compromised skin
  • Excessive moisture (e.g., diaper rash)
  • Local lesions (e.g., older patients with dentures, patients with burns)
• Hematologic malignancies (e.g., acute myeloid leukemia, multiple myeloma)
• Smoking cigarettes
• Congenital disorders, e.g., autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED): an inherited autoimmune disease caused by a mutation in the AIRE gene that manifests with chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency.

C. albicans appears almost universally in low numbers on healthy adults but can cause disease in certain high-risk patients, especially those that are immunocompromised.

References:^{[2][3][4][5][6][7]}

• Local infection: imbalance in local flora (e.g., triggered by antibiotic use) → local overgrowth of C. albicans → local mucocutaneous infection (e.g., oropharyngeal infection, vaginitis)
• Systemic infection: local mucocutaneous infection → breach of skin/mucosal barrier or translocation (IV catheterization, ascending infection in pyelonephritis, or resorption via GIT) → direct invasion of bloodstream (candidemia) → spread to visceral tissues → disseminated organ infection (e.g., pyelonephritis, endocarditis)

References:^{[2][8][9][10]}

Mucocutaneous candidiasis

• Skin and nail infections: erythematous patches and satellite lesions
  • Intertriginous areas; : warm and moist areas in which skin touches skin, e.g., the axillae, the groin, the gluteal folds, beneath the breasts, and the abdominal folds of obese patients
  • Digital web spaces (erosio interdigitalis blastomycetica)
  • Paronychia and onychomycosis
  • Diaper dermatitis: typically in infants
    • Peak incidence: 3–4 months of age
    • Develops as a result of prolonged wetness and diaper occlusion
    • Chronic candidal diaper dermatitis should raise suspicion of diabetes mellitus type 1
  • Chronic mucocutaneous candidiasis
• Oropharyngeal (oral thrush)
  • Pseudomembranous candidiasis
    • White plaque in the oral cavity that can be scraped off, giving way to red, inflamed, or bleeding areas.
    • Cottony feeling in the mouth, loss of taste, and in some cases pain while eating
    • Fissuring at the mouth corners
• Candida esophagitis
  • AIDS-defining illness and in patients with hematologic malignancies
  • Often presents together with oral thrush (but may occur on its own)
  • Retrosternal pain on swallowing (odynophagia)
  • Differential diagnosis:
    • CMV esophagitis
    • Herpes simplex virus esophagitis
    • Drug-induced esophagitis (e.g., doxycycline, tetracycline, clindamycin)
• Other
  • Vaginal yeast infection (vulvovaginitis)
  • Balanitis

Systemic candidiasis

• Candidemia: symptoms may vary from fever to sepsis (hard to distinguish from bacterial sepsis)
  • Fever, chills, fatigue
  • Skin rash
  • Abdominal and muscle pain
  • Headache
  • Neurological deficits, vision changes
• Infiltration of organs may occur either directly; (e.g., ventriculoperitoneal shunt in meningitis) or hematogenous (e.g., endocarditis with IV drug use)
• Infiltration of any organ
  • Endophthalmitis, chorioretinitis: Patients with candidemia, even without ocular symptoms, should undergo ophthalmologic evaluation to rule out endophthalmitis. ^[11]
  • Pneumonia (pulmonary candidiasis)
  • Meningitis
  • Endocarditis
  • Muscle abscesses
  • Possible signs of multiorgan failure

References:^{[2][8][12][13][14][15]}

A suspected diagnosis based on clinical appearance requires confirmation with additional tests.

• Best initial test: KOH test on a wet mount preparation of scrapings or smears
  • Also called potassium hydroxide smear
  • Shows budding yeasts, hyphae, and pseudohyphae
• Best confirmatory test: blood or tissue culture
  • Candida spp. form yeast cells and pseudohyphae at 20–25°C
  • Candida albicans forms germ tubes at 37°C
• Other tests
  • Endoscopy (with or without biopsy)
    • Indications
      • Immunocompetent individuals with odynophagia
      • Candida infection that is not responsive to oral fluconazole therapy
    • Findings: white mucosal plaque-like lesions
  • Tissue biopsy: can be stained with silver stain
  • Candida antigen detection

References:^[16]

Treatment of local mucocutaneous candidiasis

• Topical antifungal agents: e.g., clotrimazole, miconazole, ketoconazole, nystatin for 7–14 days
• Vaginal yeast infection: either topical antifungal agents (e.g., clotrimazole cream) 3–14 days or a single dose of oral fluconazole
• Oral candidiasis
  • First line
    • Newborns: topical nystatin (preferred due to easy administration)
    • Children and adults: topical nystatin or oral fluconazole
  • Alternatives if treatment fails: other azoles (e.g., itraconazole, voriconazole) or echinocandins (e.g., caspofungin)
• Esophageal candidiasis
  • First line: oral or IV fluconazole for 14–21 days
  • Alternatives if treatment fails: IV echinocandins (e.g., caspofungin or micafungin), topical or IV amphotericin B, or oral or IV voriconazole

Treatment of systemic candidiasis

• Indications: systemic treatment is preferred in the following
  • Immunocompromised patients
  • Hematological infiltration or organ involvement
• Drug of choice: IV caspofungin; or micafungin (echinocandins) for 2 weeks after resolution of symptoms and documented clearance of C. albicans
• Alternatives
  • Fluconazole: in patients that are not critically ill and in the case that resistance is unlikely
  • Amphotericin B: because of toxicity, only indicated if there is intolerance, limited availability, or resistance to alternatives

References:^{[2][15][16][17][18][19]}