Candidiasis is an acute, subacute, or chronic inflammatory condition of the skin, mucous membranes, and organs caused by Candida species. In rare cases, it can lead to candidemia. It is predominantly considered an opportunistic infection and is the most common fungal disease in children.
Etiology and Pathogenesis
Candida, previously known as monilia, represents one of the primary fungal pathogens affecting humans. The major species responsible for human infections are Candida albicans, Candida tropicalis, Candida krusei, and Candida glabrata. Candida albicans is oval or round in shape, primarily reproduces by budding, and generates blastospores and pseudohyphae. It is Gram-positive. As an opportunistic pathogen, it is normally found on the skin, oral cavity, upper respiratory tract, intestinal tract, and vaginal mucosa of healthy individuals, with colonization rates ranging between 5% and 30% in healthy children. Under conditions of immunosuppression, Candida can transition from a commensal organism to a pathogenic agent, resulting in endogenous infections. High-risk populations include young infants, particularly preterm or low-birth-weight infants, as well as immunocompromised individuals.
Candida adheres to the host's epithelial cells, invades intracellularly, and transforms into its pathogenic yeast form in tissues. It releases toxins and proteases that increase vascular permeability and cause inflammatory necrosis. Additional secreted factors, such as phosphatases and lecithinases, can accelerate tissue damage.
Clinical Manifestations
Candidiasis can be classified based on clinical presentation into mucocutaneous candidiasis, cutaneous candidiasis, candidiasis-related hypersensitivity, and systemic candidiasis. Broadly, it can also be categorized into mucocutaneous types and visceral types. The disease can present as acute, subacute, or chronic, with visceral forms demonstrating a variety of clinical manifestations.
Mucocutaneous Candidiasis
Mucocutaneous candidiasis is most commonly observed in newborns and young infants, particularly in individuals with obesity or excessive sweating. During the neonatal period, diaper-covered areas such as the perianal region, buttocks, genital area, and groin are most frequently affected, followed by the axillae, anterior neck, and submandibular areas.
The most common presentation is excoriation. Redness and erosion are observed in skin folds, with well-demarcated margins, grayish-white scaling, and surrounding red papules, vesicles, or pustules. Immunocompromised patients may exhibit granulomatous changes on the skin, and disseminated forms may show generalized miliaria-like lesions.
Mucosal involvement most frequently manifests as oral thrush. White, curd-like plaques appear on the mucosal surfaces of the cheeks, gums, and hard and soft palates. These plaques are difficult to remove, and forced removal may reveal reddened, eroded surfaces that can bleed. In cases of immunosuppression, mucosal lesions may spread from the tongue and buccal mucosa to the throat, trachea, and esophagus.
Visceral Candidiasis
Gastrointestinal Candidiasis
Gastrointestinal involvement most commonly presents as Candida enteritis, often accompanied by low-grade fever and occurring in the context of diarrhea. Stool may be loose, watery, or curd-like, containing bubbles and having a fermented odor, with bowel movements ranging from three to over ten times per day. Severe cases may develop intestinal mucosal ulceration, presenting with bloody stools.
Candida esophagitis is characterized by symptoms such as nausea, vomiting, refusal to eat, dysphagia, and drooling. Older children may report substernal pain, burning sensations, or pain on swallowing. X-ray imaging reveals esophageal narrowing and altered peristalsis, and endoscopy shows thick white plaques.
Respiratory Candidiasis
Respiratory candidiasis, typically presenting as candidal pneumonia, demonstrates clinical signs consistent with bronchopneumonia. Symptoms include a cough with gelatinous, colorless sputum, sometimes containing streaks of blood, and medium to fine crackles on auscultation. Pulmonary consolidation signs may develop when lesions coalesce. Radiographic findings resemble bronchopneumonia. The condition often persists despite antibiotic therapy.
Urinary Tract Candidiasis
In mild cases, clinical symptoms may be minimal, while severe cases may exhibit frequent urination, urgency, dysuria, and renal dysfunction.
Disseminated Candidiasis and Candidemia
Disseminated candidiasis and candidemia often present with persistent fever superimposed on preexisting conditions such as leukemia or malignancies. Symptoms worsen, and systemic health deteriorates. Dissemination typically involves multiple organs, such as the heart, lungs, kidneys, and brain. Endocardial vegetations in candidal endocarditis are large and prone to embolism. Hematogenous spread may also lead to meningitis or cerebral abscesses, with a high associated mortality rate.
Diagnosis
Fungal Examination
Microscopic examination of lesion tissue, pseudomembranes, or exudates may reveal thick-walled spores and pseudohyphae. Repeated positive findings under microscopy hold diagnostic significance. Fungal cultures from specimens typically produce smooth, creamy white colonies within one week. A colony count exceeding 50% of the sample is diagnostically relevant.
Pathological Diagnosis
Confirmation of the disease is achieved by identifying fungi and corresponding pathological changes in tissue samples.
Fundoscopic Examination
In patients with candidemia, cloud-like or cotton-ball-shaped lesions can often be observed on the retina or choroid.
Serological Testing
Serum 1,3-β-D-glucan testing (also referred to as the G test) detects 1,3-β-D-glucan, an essential component of fungal cell walls. A positive result is an important indicator of invasive fungal infections. However, false positives may occur due to factors such as the infusion of albumin or globulin, specimen contact with gauze, or bacterial contamination.
Treatment
Nystatin
Topical Application
Nystatin can be formulated as ointments, creams, powders, or solutions at a concentration of 100,000 U/g or 100,000 U/mL in its base. Selection of the preparation depends on the patient’s condition, with application performed two to four times daily.
Oral Administration
Nystatin is effective for treating intestinal candidiasis. The dosage is 200,000–400,000 U daily for neonates, 400,000–800,000 U daily for children under 2 years old, and 1,000,000–2,000,000 U daily for children over 2 years old. The total dose is divided into three to four doses and taken before meals for a course of 7–10 days. Oral absorption is poor, and the drug is excreted entirely in the feces. Adverse effects include nausea, vomiting, and mild diarrhea.
Nebulized Inhalation
Respiratory candidiasis can be treated by dissolving 50,000 U of nystatin in 2 mL of 0.9% sodium chloride solution for inhalation.
Amphotericin B
Amphotericin B, a polyene antibiotic, is currently the first-line treatment for systemic candidiasis. Intravenous administration begins with a low dose of 0.1 mg/kg daily, gradually increasing to 1–1.5 mg/kg daily if no adverse reactions occur, for a treatment course lasting one to three months. The drug is diluted in 5% glucose solution at a concentration of no more than 0.05–0.1 mg/mL and administered via slow intravenous infusion over at least six hours per dose. High concentrations may lead to phlebitis, while rapid infusion can cause complications such as seizures, arrhythmias, sudden hypotension, or cardiac arrest. Amphotericin B has known toxicity to the liver, kidneys, and hematopoietic system, necessitating periodic monitoring every 3–7 days for blood counts, urinalysis, and liver and kidney functions. Dosage reductions are required if serum creatinine exceeds 221 μmol/L (2.5 mg/dL). Discontinuation is indicated if blood urea nitrogen exceeds 14.28 mmol/L (40 mg/dL).
5-Fluorocytosine (5-FC)
5-Fluorocytosine is an oral antifungal medication effective against Candida albicans. When co-administered with amphotericin B, it reduces the likelihood of resistance development, allows for reduced dosage and toxicity, and shortens the treatment course. The dosage ranges from 50 to 150 mg/kg daily, divided into four doses for 4–6 weeks. Dosage adjustments are required for infants. Adverse effects include nausea, vomiting, rash, neutropenia, thrombocytopenia, and liver or kidney damage.
Ketoconazole
Ketoconazole is a synthetic imidazole derivative with antifungal properties. Currently, it is only used topically for treating cutaneous candidiasis. A 2% ketoconazole cream is applied once or twice daily.
Fluconazole
Fluconazole, a triazole antifungal agent, is well absorbed orally and effective against Candida infections. For children over 3 years of age, the dosage is 3–12 mg/kg per day, administered as a single oral or intravenous dose. Adverse reactions may include gastrointestinal symptoms, rash, and, rarely, liver function abnormalities.