Candida infections in children

INTRODUCTION — The clinical manifestations of infection with Candida species range from local mucous membrane infection to widespread dissemination with multisystem organ failure. Candida are considered normal flora in the gastrointestinal and genitourinary tracts of humans but invade and cause disease when there is an imbalance in their ecologic niche.

This topic will provide an overview of Candida infections in children. Many of these infections are discussed in detail in other topic reviews; they are briefly summarized here. The clinical features, diagnosis, and treatment of candidemia in children and Candida infections in neonates are discussed separately.

●(See "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis".)

●(See "Candidemia and invasive candidiasis in children: Management".)

●(See "Epidemiology and risk factors for Candida infection in neonates".)

●(See "Clinical manifestations and diagnosis of Candida infection in neonates".)

●(See "Treatment of Candida infection in neonates".)

PATHOGENESIS — The immune response of the host is an important determinant of the type of infection caused by Candida.

●The most benign infections are characterized by local overgrowth on skin or mucous membranes as a result of changes in the normal microbiota. More extensive and/or persistent mucous membrane infections occur in individuals with deficiencies in cell-mediated immunity.

●Candidemia results when Candida species gain access to the bloodstream, typically in immune-compromised individuals or patients in the intensive care unit or with vascular devices. Widespread dissemination may occur in neonates, neutropenic hosts, or severely ill patients in the intensive care unit.

●Invasive focal infections, such as endocarditis and meningitis, most often occur after hematogenous spread in patients with anatomic abnormalities or devices (eg, prosthetic heart valves, central nervous system shunts).

MICROBIOLOGY — The different Candida species generally are capable of producing all of the clinical syndromes, although infection with Candida albicans is the most common. The major reason to identify the infecting Candida species is that they have different susceptibility profiles (eg, Candida glabrata and Candida krusei are less susceptible to azole antifungal agents than are other species, Candida lusitaniae may be resistant to amphotericin B, and Candida auris are often resistant to both fluconazole and amphotericin B).

OROPHARYNGEAL CANDIDIASIS

Clinical manifestations — Oropharyngeal candidiasis (thrush) is common in young infants. It also may be seen in older children treated with antibiotics, inhaled glucocorticoids (for asthma or rhinitis), chemotherapy, or radiation therapy and in children with cellular immune deficiency, such as acquired immunodeficiency syndrome. (See "Major side effects of inhaled glucocorticoids", section on 'Topical candidiasis'.)

Pseudomembranous oropharyngeal candidiasis is the most common form of oropharyngeal candidiasis. It is characterized by white plaques on the buccal mucosa, palate, tongue, or the oropharynx (picture 1). Infants with thrush may be asymptomatic or may refuse to eat and swallow because of pain. Older children may be asymptomatic or may complain of a "cottony" feeling in the mouth, loss of taste, and sometimes pain on eating and swallowing.

Other forms of oropharyngeal candidiasis include angular cheilitis (perlèche) and acute atrophic candidiasis (glossitis).

●Angular cheilitis is characterized by painful fissuring at the corners of the mouth (picture 2). It may occur in immunocompromised children and children who habitually lick the corners of the mouth, creating an environment in which Candida can establish an infection. (See "Cheilitis", section on 'Angular cheilitis'.)

●Acute atrophic candidiasis is characterized by erosion of the papillae on the tongue accompanied by erythema and pain (picture 3). It is caused by alteration of the bacterial microbiota of the oral mucosa.

Evaluation and diagnosis — Oropharyngeal candidiasis is usually diagnosed clinically, based upon the characteristic white plaques (picture 1). If necessary, it can be confirmed by scraping the lesions with a tongue depressor and performing a Gram stain or potassium hydroxide (KOH) preparation on the scrapings. Demonstration of budding yeasts with or without hyphae confirms the diagnosis (picture 4). (See "Office-based dermatologic diagnostic procedures", section on 'Potassium hydroxide preparation'.)

We do not routinely obtain cultures in children with oropharyngeal candidiasis. However, for children with recalcitrant or recurrent oropharyngeal candidiasis, and children who have received antifungal prophylaxis with an azole agent (eg, fluconazole) and therefore are at greater risk for infection with an azole-resistant species, we obtain cultures to evaluate the possibility of an unusual or azole-resistant species (eg, C. glabrata, C. krusei).

We suggest evaluation for cellular immune deficiency, including human immunodeficiency virus (HIV) testing, for children with recalcitrant, recurrent, or extensive oropharyngeal candidiasis. Evaluation for cellular immune deficiency also may be warranted for children ≥12 months of age who develop oropharyngeal candidiasis in the absence of a predisposing factor (eg, recent antibiotics, inhaled glucocorticoids, cancer, etc). (See "Laboratory evaluation of the immune system", section on 'Defects in cellular immunity' and "Screening and diagnostic testing for HIV infection" and "Diagnostic testing for HIV infection in infants and children younger than 18 months", section on 'Diagnostic tests'.)

Management — Management of oral candidiasis varies with age, severity of infection, and the immune competence of the host (algorithm 1 and algorithm 2).

The treatment recommendations provided below are consistent with those in the 2016 Infectious Diseases Society of America (IDSA) guidelines for the management of candidiasis [1].

Infants <1 month — The management of oropharyngeal candidiasis in neonates is discussed separately. (See "Treatment of Candida infection in neonates", section on 'Mucocutaneous candidiasis'.)

Infants 1 through 11 months — The successful treatment of oropharyngeal candidiasis in infants involves measures to prevent reinfection and antifungal therapy (algorithm 1).

●Prevention of reinfection – Measures to prevent reinfection include sterilization or decolonization of items and body sites that are placed in the infant's mouth [2]. Bottle nipples and pacifiers that are to be reused should be boiled after each use.

The treatment of Candida breast colonization and/or infection in lactating women is discussed separately. (See "Common problems of breastfeeding and weaning", section on 'Candidal infection'.)

●Antifungal therapy

•Immunocompetent infants – For immunocompetent infants 1 through 11 months of age, we suggest treatment with topical rather than systemic antifungal therapy (algorithm 1). (See "Common problems of breastfeeding and weaning", section on 'Candidal infection'.)

We initiate treatment for oral candidiasis in immunocompetent infants age one through 11 months with nystatin suspension 200,000 units (100,000 units to each cheek) four times daily for 7 to 14 days [2,3]. We prefer nystatin to oral fluconazole because nystatin is less expensive and to gentian violet because gentian violet may increase the risk of cancer and can stain the infant's lips and clothing [4].

Nystatin suspension may be squirted into the mouth or applied with gauze or cotton swab. Treatment is continued until two to three days after resolution of lesions, which typically occurs within two weeks. Failure to improve or resolve within two weeks may be related to persistent reexposure (eg, from pacifiers or bottle nipples) or infection with an unusual species.

Gentian violet (0.5 or 1 percent) applied to the buccal mucosa once or twice daily is also effective [3]. However, gentian violet is associated with increased risk of cancer, can stain the infant's lips and clothing, and may cause irritation and ulceration [4-7]. Given the availability of other effective agents, we generally do not suggest gentian violet.

In randomized trials, 10 to 21 days of treatment with nystatin suspension was associated with clinical cure rates of 29 to 80 percent [8-10]. Oral fluconazole may be used as an alternative to nystatin. In a randomized trial, compared with nystatin, oral fluconazole was associated with faster clearance of lesions, increased clinical cure rates (100 percent versus 29 percent), and increased mycologic cure rates (73 versus 6 percent); the rates of side effects were similar [9]. However, given the typically benign clinical course of oropharyngeal candidiasis in immunocompetent infants, we suggest nystatin as the initial treatment.

Our suggestion to treat immune-competent infants with thrush whether or not they have symptoms is consistent with the recommendations of the IDSA, which are endorsed by the American Academy of Pediatrics [1]. For infants <8 weeks of age, the National Institute for Health and Care Excellence guidelines suggest antifungal therapy if the infant has symptoms (eg, pain, poor feeding) or the infant is breastfed and the mother has symptoms or signs of Candida infection (eg, breast pain, shiny or flaky skin of the nipple) [11].

•Refractory thrush in immunocompetent infants and initial treatment of thrush in immunocompromised infants – For thrush that is refractory to nystatin, appropriate decolonization/sterilization measures in immunocompetent infants, and initial treatment of thrush in immunocompromised infants, we recommend systemic rather than topical antifungal therapy (algorithm 1). Systemic therapy is well tolerated and more effective [12,13]. We use fluconazole 3 to 6 mg/kg orally once per day (maximum dose 200 mg) for a total of 7 to 14 days.

For infants with oral thrush that does not respond to oral fluconazole, we obtain fungal culture and susceptibility testing. We also perform evaluation for immune deficiency (if not previously performed). (See "Laboratory evaluation of the immune system", section on 'Evaluation for specific types of disorders'.)

Children ≥12 months

●Assessment of severity – Standardized severity assessments for oropharyngeal candidiasis in children are lacking. We define severity clinically as follows:

•Mild thrush – Involves <50 percent of the oral mucosa and absence of deep, erosive lesions

•Moderate/severe thrush – Involves ≥50 percent of the oral mucosa or deep, erosive lesions (picture 5)

●Approach to initial antifungal therapy — Our approach to antifungal therapy varies with severity and immune competence of the child (algorithm 2).

•Mild thrush in immunocompetent children – For mild oropharyngeal candidiasis in immunocompetent children ≥12 months, we suggest topical rather than systemic antifungal therapy (algorithm 2). We use topical nystatin or clotrimazole:

-Nystatin suspension 400,000 to 600,000 units four times per day for 7 to 14 days. Nystatin suspension should be swished and held in the mouth as long as possible before swallowing; the suspension can be squirted into the mouth for children who are unable to swish and swallow.

-Nystatin lozenge 200,000 units to 400,000 units (one to two lozenges) four times per day for 7 to 14 days.

-Clotrimazole 10 mg (one lozenge) five or six times per day for 7 to 14 days.

Nystatin and clotrimazole lozenges are a choking hazard and should not be used in children younger than four years.

•Mild thrush in immunocompromised children and moderate/severe thrush in all children – For mild thrush in immunocompromised children ≥12 months and moderate/severe thrush (picture 5) in all children ≥12 months, we recommend systemic rather than topical antifungal therapy (algorithm 2). Systemic therapy is well tolerated and more effective [12,13].

We generally use oral fluconazole:

-Fluconazole 6 mg/kg orally once on the first day (maximum dose 200 mg for non-HIV-exposed/positive children, 400 mg for HIV-exposed/positive), followed by 3 mg/kg once per day (maximum dose 100 mg for non-HIV-exposed/positive children, 400 mg for HIV-exposed/positive children) for a total of 7 to 14 days

Immunocompromised patients with thrush and significant oropharyngeal pain (ie, pain that interferes with eating) may require intravenous antifungal therapy (eg, fluconazole 6 mg/kg intravenously once on the first day, followed by 3 mg/kg once per day for at least 14 days).

In a randomized trial in immunocompromised children (including those with malignancy, immune disorder, HIV, and those receiving immunosuppressive therapy) with oropharyngeal candidiasis, more patients treated with fluconazole achieved clinical cure (91 versus 51 percent) and mycologic cure (76 versus 11 percent) [13]. In a meta-analysis of 22 studies assessing treatment for oropharyngeal candidiasis in patients with HIV infection, treatment with fluconazole was superior to nystatin for clinical cure in adults [12]. Clinical cure rates were similar among patients treated with fluconazole, ketoconazole, itraconazole solution, clotrimazole troches, and posaconazole solution, but fluconazole and itraconazole solution were superior to clotrimazole troches for mycologic cure.

Given the potential for serious adverse effects, oral ketoconazole tablets should not be used in the treatment of mucocutaneous candidiasis [14]. For additional information, refer to the drug interactions program included within UpToDate.

●Refractory thrush in children ≥12 months – For immunocompetent children with mild thrush that persists despite topical antifungal therapy, we suggest oral fluconazole (algorithm 2).

For immunocompetent or immunocompromised children, moderate to severe oropharyngeal candidiasis that is refractory to oral or intravenous fluconazole generally is treated intravenously with amphotericin (deoxycholate or lipid formulation) or an echinocandin (eg, caspofungin, anidulafungin, micafungin), given the possibility of fluconazole resistance (algorithm 2).

In addition to a change in empiric antifungal therapy, culture of the lesions and evaluation for cellular immune deficiency may be warranted. (See 'Evaluation and diagnosis' above and "Laboratory evaluation of the immune system", section on 'Defects in cellular immunity' and "Screening and diagnostic testing for HIV infection" and "Diagnostic testing for HIV infection in infants and children younger than 18 months", section on 'Diagnostic tests'.)

DIAPER DERMATITIS — Candida diaper dermatitis is common in young infants. It is typically caused by C. albicans. The rash of Candida diaper dermatitis classically occurs in the inguinal region and has areas of confluent erythema with discrete erythematous papules and plaques, superficial scale, and satellite lesions (picture 6A-C).

Candida diaper dermatitis is usually diagnosed clinically, based upon the location and appearance of the rash. If necessary, the diagnosis can be confirmed by scraping the lesions and performing a Gram stain or potassium hydroxide (KOH) preparation on the scrapings. Budding yeasts with or without hyphae establish the diagnosis. (See "Office-based dermatologic diagnostic procedures", section on 'Potassium hydroxide preparation'.)

The treatment of Candida diaper dermatitis is discussed separately. (See "Diaper dermatitis".)

Persistent Candida diaper dermatitis in young children may be a sign of type 1 diabetes mellitus, chronic mucocutaneous candidiasis, or an underlying immunodeficiency. (See "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents", section on 'Young children' and "Chronic mucocutaneous candidiasis".)

INTERTRIGO — Candida intertrigo refers to Candida infection of closely opposed skin surfaces (eg, neck folds in infants, the axillae, intergluteal folds, etc). Clinical features include erythematous, macerated plaques and erosions with peripheral scale, and satellite papulopustules (picture 7). The lesions may be painful if skin breakdown accompanies the infection. The diagnosis and treatment of Candida intertrigo are discussed separately. (See "Intertrigo".)

VULVOVAGINITIS — Predisposing factors for vulvovaginal candidiasis in infants include diaper use, broad-spectrum antibiotics, and immunosuppression (including glucocorticoids and HIV infection). Additional risk factors in adolescents include certain contraceptive devices (vaginal sponges, diaphragms, intrauterine devices), estrogen therapy (including oral contraceptives), and pregnancy. (See "Candida vulvovaginitis: Clinical manifestations and diagnosis", section on 'Risk factors'.)

The primary clinical manifestations of Candida vulvovaginitis are itching and discharge. Dysuria and vaginal irritation also may be present. Dyspareunia may be a complaint in sexually active adolescents. Examination shows vulvar erythema and swelling and vaginal erythema and discharge, which is classically curd-like but may be watery. Some patients, primarily those with C. glabrata infection, have little discharge and often only erythema on vaginal examination [15].

The diagnosis of Candida vulvovaginitis is typically made clinically. If necessary, confirmation is easily obtained by observing budding yeast, with or without hyphae, on a wet mount or potassium hydroxide (KOH) preparation of vaginal secretions (picture 8). (See "Candida vulvovaginitis: Clinical manifestations and diagnosis", section on 'Clinical features'.)

The treatment of Candida vulvovaginitis is discussed separately. (See "Candida vulvovaginitis in adults: Treatment of acute infection".)

BALANITIS — Candida balanitis may occur as a component of diaper dermatitis in infants. It also may be acquired sexually in adolescents. Clinical features include white patches on the penis in association with severe burning and itching. The infection can spread to the thighs, gluteal folds, buttocks, and scrotum.

The diagnosis and treatment of Candida balanitis are discussed separately. (See "Balanitis and balanoposthitis in children and adolescents: Clinical manifestations, evaluation, and diagnosis".)

ESOPHAGITIS — Esophageal candidiasis occurs predominantly in individuals with hematologic malignancies and HIV. In patients with HIV infection, esophageal candidiasis is an acquired immunodeficiency syndrome (AIDS)-defining illness. (See "Pediatric HIV infection: Classification, clinical manifestations, and outcome", section on 'Esophageal candidiasis'.)

The hallmark of Candida esophagitis is pain with swallowing (odynophagia). Patients usually localize their pain to a discrete retrosternal area. Concomitant thrush may or may not be present.

Candida esophagitis usually is diagnosed endoscopically. White mucosal plaque-like lesions suggest the diagnosis. Confirmatory biopsy demonstrates yeasts and pseudohyphae invading mucosal cells. An alternative diagnostic approach in HIV/AIDS patients with suggestive clinical features is to treat with systemic antifungal agents (eg, fluconazole loading dose of 6 mg/kg orally on the first day, followed by 3 mg/kg orally once per day). Odynophagia due to candidiasis typically improves within several days; if symptoms do not improve within three to four days, endoscopy and biopsy should be performed [16]. If endoscopy reveals clinical features suggestive of candidiasis, treatment with an antifungal agent other than fluconazole may be warranted pending culture results. (See "Evaluation of the patient with HIV, odynophagia, and dysphagia", section on 'Management'.)

CHRONIC MUCOCUTANEOUS CANDIDIASIS — Chronic mucocutaneous candidiasis is a rare syndrome that usually has its onset in childhood. Some patients with chronic mucocutaneous candidiasis have autosomal recessive polyglandular autoimmune syndrome type I (which may be manifested by hypoparathyroidism, hypothyroidism, and adrenal insufficiency), whereas others have no associated diseases. (See "Chronic mucocutaneous candidiasis" and "Causes of primary adrenal insufficiency (Addison disease)", section on 'Type 1 (monogenic)'.)

An underlying T cell defect is thought to be responsible for the inability of these patients to eradicate Candida from mucous membranes and cutaneous structures [17]. The clinical manifestations are severe, recurrent thrush (picture 9), vaginitis, onychomycosis (picture 10), and chronic skin lesions. Hyperkeratotic, crusted skin lesions on the face, scalp, and hands can lead to psychosocial problems (picture 11). Visceral invasion is rare. Chronic suppressive antifungal treatment is required to achieve remission. (See "Chronic mucocutaneous candidiasis", section on 'Treatment'.)

INVASIVE CANDIDIASIS

Candidemia and acute disseminated candidiasis — Candidemia refers to the presence of Candida species in the blood. Neonates, immunocompromised hosts, and children in intensive care units are most at risk for the development of candidemia. Acute disseminated candidiasis occurs when several viscera are infected as a result of hematogenous spread. (See "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis", section on 'Risk factors'.)

The clinical manifestations of candidemia vary from minimal fever to a fulminant sepsis syndrome indistinguishable from severe bacterial infection. Signs of multiorgan system failure may be present. Clinical clues include characteristic eye lesions (picture 12A-B), skin lesions (picture 13A-B), and, less commonly, muscle abscesses. The clinical manifestations and treatment of candidemia are discussed in greater detail separately. (See "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis", section on 'Clinical manifestations' and "Candidemia and invasive candidiasis in children: Management".)

Invasive focal infections

Urinary tract infections — Candiduria is common in hospitalized patients, but it is difficult to distinguish colonization from infection of the bladder [18]. Risk factors for candiduria include indwelling bladder catheter, antibiotics, diabetes, and recent surgery [19].

Candida pyelonephritis is rare. It can be secondary to hematogenous seeding and is typically characterized by multiple microabscesses in the setting of disseminated candidiasis. It can also occur as an ascending infection in patients with obstruction. Ascending infection usually is unilateral and develops more insidiously than hematogenous infection. Although Candida infection of the bladder and Candida pyelonephritis may coexist, it is important to distinguish them because the treatments differ. The symptoms of Candida pyelonephritis are similar to those of bacterial pyelonephritis: fever, chills, flank pain, and dysuria. (See "Candida infections of the bladder and kidneys", section on 'Clinical characteristics' and "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Clinical presentation'.)

Patients with either lower or upper tract infection due to Candida can develop fungus balls that consist of masses of hyphae. Fungus balls can grow to a large size and lead to obstruction of the collecting system; surgical intervention or percutaneous drainage is required when obstruction occurs.

The diagnosis and treatment of Candida infections of the bladder and kidneys are discussed separately. (See "Candida infections of the bladder and kidneys".)

Peritonitis — Candida infection of the peritoneal cavity can occur as a result of postoperative wound infection, gastrointestinal perforation, or chronic peritoneal dialysis [20,21]. Peritonitis associated with primary perforation or secondary to a surgical procedure is usually polymicrobial. Prominent symptoms include fever, chills, and abdominal pain. These are the same as those of bacterial peritonitis, which is often coexistent. Complications of Candida peritonitis include bloodstream invasion with sepsis and abscess formation requiring surgical drainage. Diagnosis is best made by aspiration of fluid under computed tomographic (CT) or ultrasound guidance or at the time of surgery. Culture of Candida species from an indwelling drain is not adequate for the diagnosis of infection since it often reflects only colonization or contamination of the drain. (See "Fungal peritonitis in peritoneal dialysis", section on 'Laboratory findings and diagnosis'.)

Patients who have indwelling Tenckhoff catheters for chronic peritoneal dialysis usually develop Candida peritonitis only after they have had episodes of bacterial peritonitis [21]. The symptoms may be subtle, consisting of mild abdominal pain and low-grade fever; the first signs frequently are poor flow and cloudiness of the dialysate. The diagnosis is easily made by culturing the dialysate fluid. In contrast to bacterial peritonitis in these patients, treatment with antifungal agents is rarely effective unless the catheter is removed. (See "Microbiology and therapy of peritonitis in peritoneal dialysis", section on 'Indications for catheter removal'.)

Endophthalmitis — Candida endophthalmitis can develop following trauma or eye surgery or through hematogenous seeding of the retina and choroid as a complication of candidemia. Patients with Candida endophthalmitis may or may not have evidence of disseminated candidiasis in other organ systems. Diagnosis requires an ophthalmologic examination. Candida endophthalmitis can be sight-threatening if it is not treated. Thus, the 2016 Infectious Diseases Society of America guidelines for the management of candidiasis recommend at least one dilated retinal examination, preferably by an ophthalmologist early in the course of therapy for all patients with candidemia [1]. (See "Epidemiology, clinical manifestations, and diagnosis of fungal endophthalmitis", section on 'Clinical manifestations'.)

Osteoarticular infections — Candida species infect bones and joints as a result of hematogenous seeding or exogenous inoculation during trauma, intra-articular injection, a surgical procedure, or injection drug use. Candida arthritis or osteomyelitis most often develops as a sequel to candidemia. Bone or joint involvement may become evident during an episode of fungemia or may have a more subtle presentation after the fungemia has resolved [22-24]. Swelling and decreased range of motion are the major symptoms (as in bacterial osteoarticular infections), but these may be mild [25]. Radiographic findings do not distinguish between bacterial and fungal infection. The etiologic diagnosis is established by obtaining synovial fluid or bone aspirate for culture. Even a single colony of Candida on culture of joint fluid or bone aspirate should be viewed as pathogenic, and the patient should be treated with antifungal agents. (See "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Clinical features' and "Hematogenous osteomyelitis in children: Evaluation and diagnosis", section on 'Diagnostic approach' and "Hematogenous osteomyelitis in children: Clinical features and complications", section on 'Clinical features'.)

Candida osteoarticular infections in neonates are discussed separately. (See "Clinical manifestations and diagnosis of Candida infection in neonates", section on 'Other focal infections'.)

Meningitis/central nervous system infection — Candida species can cause acute meningitis during the course of widespread dissemination. Candida meningitis most often occurs in neonates with candidemia. (See "Clinical manifestations and diagnosis of Candida infection in neonates", section on 'Central nervous system infection'.)

Candida species uncommonly can cause ventriculoperitoneal shunt infections [26]. (See "Candida infections of the central nervous system", section on 'CNS shunts and other devices'.)

Endocarditis — Risk factors for Candida endocarditis include indwelling central venous catheters, underlying congenital heart disease, and a history of cardiac surgery [27-29]. The clinical manifestations of Candida endocarditis are similar to those of bacterial endocarditis. They include fever, changing or new heart murmurs, and signs and symptoms of heart failure. (See "Infective endocarditis in children", section on 'Clinical manifestations'.) Peripheral embolization is more likely with candidal than with bacterial endocarditis, and affected patients can develop other complications of candidemia (eg, visual loss secondary to endophthalmitis). (See 'Endophthalmitis' above.)

The diagnostic criteria for Candida endocarditis are similar to those for bacterial endocarditis. Cultures of blood show persistent candidemia, and echocardiographic studies usually reveal large valvular vegetations. In some cases, an early manifestation of endocarditis is embolization of the large vegetation to a major vessel, such as the femoral artery. Examination of the embolus by histopathology shows yeasts and by culture yields Candida species. (See "Infective endocarditis in children", section on 'Diagnosis'.)

Hepatosplenic or chronic disseminated candidiasis — Hepatosplenic candidiasis (also called chronic disseminated candidiasis) is seen almost entirely in patients with hematologic malignancies who have just recovered from an episode of neutropenia [30]. Some patients have a documented history of candidemia; in others, it is assumed that the patient was candidemic during the period of neutropenia. (See "Chronic disseminated candidiasis (hepatosplenic candidiasis)", section on 'Clinical manifestations'.)

The classic presentation of hepatosplenic candidiasis consists of persistent fever, which is frequently high and spiking, in a patient who was recently neutropenic and whose neutrophil count has returned to normal. The fever is often accompanied by right upper quadrant discomfort or pain, nausea, vomiting, and anorexia. Laboratory testing typically reveals an elevated serum alkaline phosphatase concentration. Discrete persistent microabscesses occur in the liver, spleen, and, sometimes, kidneys.

The diagnosis can be established by visualizing multiple characteristic lucencies in the liver and spleen on ultrasonography, magnetic resonance imaging, or CT scan (image 1). Biopsy reveals multiple granulomas (picture 14); yeasts and hyphae can be seen using special stains. Blood cultures are negative, and even culture of liver obtained at biopsy frequently is also negative.

The treatment of hepatosplenic candidiasis is discussed separately. (See "Chronic disseminated candidiasis (hepatosplenic candidiasis)", section on 'Treatment'.)

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SUMMARY AND RECOMMENDATIONS

●Oropharyngeal candidiasis

•Clinical manifestations – Oropharyngeal candidiasis (thrush) is common in infants (picture 1). It is characterized by white plaques on the buccal mucosa, palate, tongue, or the oropharynx. Infants with thrush may be asymptomatic or may refuse to eat and swallow because of pain. (See 'Clinical manifestations' above.)

Thrush also may be seen in older children treated with antibiotics, inhaled glucocorticoids, chemotherapy, or radiation therapy and in children with cellular immunodeficiency. Older children may be asymptomatic or may complain of a "cottony" feeling in the mouth, loss of taste, and sometimes pain on eating and swallowing.

•Diagnosis – Oropharyngeal candidiasis is usually diagnosed clinically based upon the characteristic white plaques (picture 1). If necessary, the diagnosis can be confirmed with Gram stain or potassium hydroxide (KOH) preparation demonstrating budding yeast with or without hyphae (picture 4). (See 'Evaluation and diagnosis' above.)

•Management

-Age <1 month – Management of oropharyngeal candidiasis in infants <1 month is discussed separately. (See "Treatment of Candida infection in neonates", section on 'Mucocutaneous candidiasis'.)

-Age 1 through 11 months – For infants one through 11 months of age with oropharyngeal candidiasis, we suggest initial treatment with topical rather than systemic therapy (Grade 2B). We use nystatin suspension (algorithm 1). (See 'Infants 1 through 11 months' above.)

-Age ≥12 months – For children ≥12 months, we define mild thrush as involvement of <50 percent of the oral mucosa and absence of deep, erosive lesions. We define moderate/severe thrush as involvement of ≥50 percent of the oral mucosa or deep, erosive lesions (picture 5). (See 'Children ≥12 months' above.)

For mild oropharyngeal candidiasis in immunocompetent children ≥12 months, we suggest initial treatment with topical rather than systemic antifungal therapy (Grade 2B). We use nystatin suspension or lozenges four times per day or clotrimazole lozenges five to six times per day for 7 to 14 days (algorithm 2). (See 'Children ≥12 months' above.)

For mild thrush in immunocompromised children ≥12 months and moderate/severe thrush in all children, we recommend systemic rather than topical antifungal therapy (Grade 1B). We generally use oral fluconazole for a total of 7 to 14 days (algorithm 2). A different antifungal agent and evaluation for fluconazole-resistant Candida or immune deficiency may be warranted if the child does not respond to empiric fluconazole. (See 'Children ≥12 months' above.)

●Diaper dermatitis – Candida diaper dermatitis is common in young infants. Clinical features include involvement of the inguinal folds, confluent erythema with discrete papules, plaques, satellite lesions, and superficial scale (picture 6A-B). Persistent Candida diaper rash may be a sign of type 1 diabetes mellitus, chronic mucocutaneous candidiasis, or an underlying immunodeficiency. (See "Diaper dermatitis", section on 'Secondary infection'.)

●Intertrigo – Clinical features of Candida intertrigo include erythematous, macerated plaques and erosions with peripheral scale, and satellite papulopustules (picture 7). (See "Intertrigo".)

●Vulvovaginitis – Predisposing factors for vulvovaginal candidiasis in infants include diaper use, broad-spectrum antibiotics, and immunosuppression (including glucocorticoids and HIV infection). Additional risk factors in adolescents include certain contraceptive devices (vaginal sponges, diaphragms, intrauterine devices), estrogen therapy (including oral contraceptives), and pregnancy. Clinical features include itching, dysuria, vaginal irritation, vulvar erythema and swelling, vaginal erythema, and vaginal discharge. The diagnosis is typically made clinically but can be confirmed with a wet mount or KOH preparation of vaginal secretions demonstrating budding yeast, with or without hyphae (picture 8). (See 'Vulvovaginitis' above.)

●Esophagitis – Esophageal candidiasis occurs predominantly in individuals with hematologic malignancies and HIV infection. Retrosternal pain with swallowing is the hallmark clinical feature. The diagnosis is usually made endoscopically. However, in patients with HIV infection, a trial of systemic antifungal therapy may obviate the need for endoscopy. (See 'Esophagitis' above.)

●Chronic mucocutaneous candidiasis – Clinical manifestations of chronic mucocutaneous candidiasis include severe, recurrent thrush (picture 9), vaginitis, onychomycosis (picture 10), and chronic skin lesions (picture 11). (See "Chronic mucocutaneous candidiasis".)

●Candidemia and invasive focal infections – Candidemia refers to the presence of Candida species in the blood. Neonates, immunocompromised hosts, and children in intensive care units are at greatest risk. The clinical manifestations vary from minimal fever to a fulminant sepsis syndrome indistinguishable from severe bacterial infection. Clinical clues to candidemia include characteristic eye lesions (picture 12A-B), skin lesions (picture 13A-B), and, less commonly, muscle abscesses. (See "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis" and "Candidemia and invasive candidiasis in children: Management".)

Invasive focal infections may occur after trauma, surgical procedures, or hematogenous spread in patients with anatomic abnormalities or prosthetic devices. (See 'Invasive focal infections' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Carol Kauffman, MD, who contributed to earlier versions of this topic review.