Candidiasis

Overview

Microbiology & Pathogenesis

• Adhesion to human epithelial cells
• Morphologic switching between yeast and pseudohyphal/hyphal forms — hyphae are more invasive
• Biofilm formation — particularly on indwelling catheters and prosthetic devices
• Immune evasion — escape from phagocytosis

• Innate immunity: Neutrophils and macrophages are critical (especially in the first 48 hours). Leukopenia — especially from chemotherapy — dramatically increases invasive risk.
• Adaptive immunity: T-cell (Th17) immunity protects mucosal surfaces. Defects in the IL-17 pathway (STAT1, STAT3, IL17F, IL17RA mutations) predispose to chronic mucocutaneous candidiasis. CARD9 mutations specifically impair neutrophil killing of Candida.
• Notably, anti-IL-17 biologics (brodalumab, secukinumab, ixekizumab) increase mucosal candidiasis risk.

• Neutropenia → risk of invasive/disseminated candidiasis
• T-cell deficiency (HIV/AIDS) → risk of persistent mucocutaneous candidiasis; invasive disease is rare

Clinical Classifications

1. Mucocutaneous / Superficial Forms

Oropharyngeal Candidiasis (Thrush)

• White, curd-like plaques on buccal mucosa, palate, tongue — scraped off to reveal erythematous non-ulcerated mucosa
• Erythematous (atrophic) form: shiny, depapillated tongue (median rhomboid glossitis), common in denture wearers
• Angular cheilitis (perlèche): painful fissuring/crusting at oral commissures
• Thrush in an otherwise healthy individual without risk factors warrants HIV testing

Oral candidiasis — white-yellow plaques on soft/hard palate, uvula, and tongue (Sleisenger & Fordtran's Gastrointestinal and Liver Disease)

Esophageal Candidiasis

• Almost always requires immune dysfunction (low CD4 in HIV, leukemia, immunosuppressants)
• Classic symptom: odynophagia localized to a discrete substernal area
• Concurrent thrush may or may not be present
• Endoscopy: plaque-like lesions/ulcerations; biopsy shows budding yeasts and pseudohyphae invading mucosa

Cutaneous Candidiasis

• Intertriginous (axillae, inframammary, groin, infrapannus): beefy-red patches/plaques with satellite papules and pustules at the periphery; maceration common
• Diaper dermatitis: same appearance in the diaper area
• Interdigital: macerated whitish plaque on erythematous base (erosio interdigitalis blastomycetica) — especially in chronic wet-work exposure
• Paronychia and onychomycosis: nail fold inflammation, nail dystrophy

Vulvovaginitis

• Most frequent mucocutaneous manifestation of candidiasis in women of childbearing age
• Thick, white, curd-like ("cottage cheese") discharge; pruritus and burning; vulvar erythema and edema
• Risk factors: antibiotic use, diabetes, pregnancy, OCP use, immunosuppression

Balanitis / Balanoposthitis

• Erythema, pustules on glans and prepuce; more pustular than vulvitis

Chronic Mucocutaneous Candidiasis (CMC)

• Diffuse skin, mucosal, and nail involvement due to underlying primary immunodeficiency (IL-17 pathway defects)

2. Invasive / Disseminated Candidiasis

Candidemia

• Candida is the most common cause of fatal fungal sepsis
• Risk factors: indwelling central venous catheters, TPN, broad-spectrum antibiotics, abdominal surgery, ICU stay, neutropenia, renal replacement therapy
• Mortality: ~35% at 12 weeks; can exceed 80% in some series
• Skin findings: erythematous papules and nodules, sometimes with central pustulation — hematogenous emboli

Disseminated candidiasis with candidemia — erythematous papules and nodules on the hand (Fitzpatrick's Dermatology)

Other Sites of Invasive Disease

Risk Factors

Diagnosis

Mucocutaneous Disease

• Often clinical
• KOH preparation of skin scrapings: budding yeasts and pseudohyphae
• Gram stain: gram-positive budding yeasts
• Culture if recurrent/unresponsive — to identify resistant species (C. glabrata, C. krusei)
• Esophageal disease: endoscopy + biopsy

Invasive Candidiasis

• Blood cultures — sensitivity is only ~50%; negative culture does not exclude invasive disease
• Beta-D-glucan (BDG) assay: serum marker of fungal infection; useful for early detection and monitoring
• CT/MRI: hepatosplenic candidiasis shows punched-out lesions in liver and spleen
• Dilated fundoscopy: mandatory for all patients with candidemia to exclude endophthalmitis
• Species identification matters — determines azole susceptibility and guides treatment

Management

Cutaneous / Mucocutaneous

Invasive / Disseminated Candidiasis

• First-line (all invasive): Echinocandin (caspofungin, micafungin, or anidulafungin) IV
• Fluconazole is an acceptable alternative in hemodynamically stable, non-neutropenic patients with susceptible species
• Step-down: transition to oral fluconazole once clinically improved, blood cultures negative, species confirmed susceptible
• Neutropenic patients: echinocandin preferred over fluconazole; may add G-CSF/GM-CSF
• Candida endocarditis: antifungal therapy + surgical valve replacement usually required
• Remove all intravascular catheters when feasible — central venous catheters are a critical source
• Duration: at least 14 days after last positive blood culture and resolution of symptoms

Important Species Notes

• C. auris: Emerging, multidrug-resistant species; difficult to identify by standard laboratory methods; prone to nosocomial outbreaks; requires MALDI-TOF with updated databases or molecular methods for identification
• C. glabrata / C. krusei: Intrinsically reduced azole susceptibility; echinocandin preferred
• C. parapsilosis: May have reduced echinocandin susceptibility; commonly associated with catheter infections and neonatal candidemia