Epidemiology and pathogenesis

Candida is a common fungal pathogen. In newborns, infection may be acquired vertically from the mother or horizontally by nosocomial transmission in the nursery. The increasing use of antifungal prophylaxis with azoles has changed the epidemiology of candidemia in immunocompromised pediatric patients. C. albicans is responsible for approximately 45% of neonatal fungal infections, while non-albicans candidal species are increasing in incidence. Other Candida species associated with neonatal disease include C. tropicalis , C. parapsilosis , C. lusitaniae , and C. glabrata . Normally, these yeasts are saprophytes, inhabiting the skin or gastrointestinal tract without invasion unless host defenses are altered. Candida spp. may also colonize endotracheal tubes and catheters without causing systemic illness, but associated clinical illness is common in very low-birthweight (VLBW) infants. In extremely low-birthweight (ELBW) infants (<1000 g), invasive candidiasis is more common. In one prospective study, 7% of 4379 infants had Candida isolated from blood or cerebrospinal fluid.

Virulence mechanisms associated with Candida infections include fungal proteinase, increased adherence of yeast to epithelial cells due to similarity to mammalian cell ligands, and resistance to neutrophil ingestion of hyphal forms. Secretory IgA, functional T lymphocytes, and phagocytic cells are important in defense against Candida infections. Hence, there is increased susceptibility to these infections in patients with secretory IgA deficiency, primary T-cell deficiency such as DiGeorge syndrome, severe combined immunodeficiency, chronic granulomatous disease, myeloperoxidase deficiency, and human immunodeficiency virus (HIV) infection. Recurrent or persistent yeast infections can be presenting symptoms of immunodeficiency. Host resistance to fungal infections also depends on activated macrophages, which in turn rely on T-lymphocyte release of interferon (IFN)-γ. Incomplete activation of macrophages by IFN in neonates contributes to increased susceptibility to invasive fungal disease.

Predisposing factors for Candida infections include excessive humidity, maceration, diabetes, and broad-spectrum antibiotics. Risk factors for systemic candidiasis in neonates include low birthweight, prematurity, broad-spectrum antibiotic therapy, indwelling catheters, prolonged endotracheal intubation, tracheostomy, prior fungal colonization, gastrointestinal pathology or abdominal surgery, enteral feeding, immunosuppression, defective neutrophil function or neutropenia, and steroid therapy. Similarly, pediatric patients with hematologic malignancies and neutropenia, short bowel syndrome with central vascular catheters or recent surgery or trauma (namely gastrointestinal/abdominal) are at increased risk of invasive candidiasis.

Various techniques in addition to culture are used to evaluate the epidemiology of fungal pathogens. They include polymerase chain reaction (PCR), restriction fragment endonuclease digestion of chromosomal DNA, electrophoretic karyotyping, and Southern blot hybridization analysis using DNA probes, β-glucan assay (β- d -glucan is a major component of the fungal cell wall) and gas chromatography mass spectrometry for d -arabinitol (a major metabolite of most Candida species).

Clinical presentations of candidal infections are discussed in this chapter, followed by diagnostic and treatment recommendations.

Congenital candidiasis

Congenital candidiasis (CC) refers to Candida infection acquired in utero and presenting with symptoms in the first days of life. Classic congenital candidiasis presents as a diffuse cutaneous infection, presumed to arise from an ascending intrauterine chorioamnionitis. The typical patient is an otherwise healthy term neonate who, within the first 12 h of life, develops a monomorphous papulovesicular eruption that is intensely erythematous ( Figs. 14.1, 14.2, 14.3 ) progressing to pustules, crusting and desquamation. Any area of the body surface, including the face, palms, and soles, can be involved, and widespread involvement is often evident ( Fig. 14.4 ). Candida paronychia and onychomycosis have been reported. Congenital candidiasis is surprisingly uncommon given the 33% rate of vaginal colonization with Candida in pregnant women. The presence of a foreign body in the maternal uterus or cervix is a risk factor for CC. In the majority of term infants, systemic dissemination of CC is rare. The prognosis of a term infant with CC is excellent, with rapid clearance of the eruption using topical treatment. Occasionally, CC can present as pneumonia and sepsis without cutaneous manifestations. CC with systemic involvement is more commonly seen in premature, low-birthweight infants (<1500 g). Skin findings in these infants may be variable, with a burn-like dermatitis (similar to staphylococcal scalded skin syndrome) in addition to the usual red scaly or vesiculopustular eruption ( Fig. 14.5 ). A widespread rash in a premature or ill-appearing infant, respiratory distress in the immediate postnatal period, leukocytosis, or hyperglycemia should alert the physician to the possibility of systemic candidiasis despite negative blood cultures.

Congenital candidiasis. Diffuse erythematous, pustular eruption.

Congenital candidiasis. Palmar pustules with erythema.

(A) Congenital candidiasis in a premature infant. (B,C) Candidiasis with scald-like erythema. (D) Congenital candidiasis.

(A: Courtesy of Robert Silverman, MD; D: Courtesy of Ilona Frieden, MD.)

Congenital candidiasis. Diffusely distributed, distinct pustules.

Congenital candidiasis.

Systemic candidiasis

Systemic candidiasis (SC), defined as Candida infection in an otherwise sterile body fluid such as blood, urine, or cerebrospinal fluid, affects 2–7% of VLBW newborns. Skin manifestations occur in up to 60% of these infants. These infections can be acquired in utero (CC) or postnatally. In a multicenter prospective study, median gestational age and birthweight of neonatal invasive candidiasis was 30 weeks and 740 g, respectively. Only half of these patients had a central venous catheter at the time of diagnosis. Baley and Silverman described skin manifestations of VLBW infants with SC to include an extensive burn-like dermatitis followed by desquamation, progressive diaper dermatitis involving papules and pustules, and isolated diaper rash with or without thrush ( Fig. 14.6 ). Cutaneous abscesses at the site of intravascular catheters may also be seen. Systemic signs include apnea, bradycardia, abdominal distension, guaiac-positive stools, hyperglycemia, temperature instability, leukemoid reaction, and hypotension. During childhood, invasive candidiasis occurs in immunocompromised individuals, especially those having had a central vascular catheter placed within 7 days of diagnosis. After hematopoietic stem cell transplantation, the median time to invasive candidiasis diagnosis is 74.5 days. Systemic candidiasis in immunocompromised children presents as randomly distributed deep, firm and erythematous papules and nodules.

White plaques of oral thrush.

Invasive fungal dermatitis

Invasive fungal dermatitis (IFD) is a clinicopathologic entity of erosive crusting lesions in VLBW infants. It is described by Rowen and colleagues as a primary skin condition that leads to secondary dissemination and systemic disease. It is primarily due to Candida albicans or other Candida species. Aspergillus , Trichosporon asahii , and Curvularia are also etiologic agents of invasive fungal dermatitis. Skin biopsy demonstrates fungal invasion beyond the stratum corneum, well into the epidermis, and at times extending into the dermis. Onset several days after birth, the presence of erosions and crusts, and typical histologic findings help to differentiate IFD from congenital candidiasis. Risk factors include extreme prematurity (<25 weeks’ gestational age), vaginal birth, steroid administration, and hyperglycemia.

Localized candidiasis

Candida diaper dermatitis.

Candida infection of the diaper area may occur alone or in conjunction with thrush. Bright, erythematous plaques, papules, and pustules affect the moist intertriginous areas of the perineum, with a predilection for inguinal creases. White scale and satellite pustules are common along the periphery, often prominent at the border of involved and uninvolved skin ( Figs. 14.7 , 14.8 ). Perianal involvement is common. Pustules may be very superficial and rupture easily leaving collarettes of scale. Candidal dermatitis may be seen in 4–6% of term newborns, with the incidence peaking at 3–4 months of age. Similar bright erythema may be seen in inverse psoriasis. Further differential diagnoses including infectious and noninfectious entities are outlined in Chapter 17 .

Candidal diaper dermatitis.

Candidal diaper dermatitis.

Candida infections of the nail plate and related structures.

Candidal infection of the nail plate and related structures may occur alone or in conjunction with systemic and congenital candidiasis. Candidal paronychia is common in finger-sucking children and presents with erythematous, edematous and tender nail folds with loss of cuticle. If present for months (chronic paronychia), resulting nail plate dystrophy can be seen distinguishing it from acute bacterial paronychia.

For onychomycosis secondary to Candida , finger sucking is a potential predisposing event ( Figs. 14.9, 14.10 , 14.11 ). The resultant onychodystrophy may lead to proximal-, distal-, and lateral-subungual, superficial white, or total dystrophic onychomycosis. The latter presents with a crumbling nail and an abnormally thickened nail bed. It is frequently seen in patients with chronic mucocutaneous candidiasis and other immunodeficiency states. Tinea unguium, hereditary onychodystrophy, ectodermal dysplasia, epidermolysis bullosa, psoriasis, and acrodermatitis may present with similar nail findings.

Nail changes secondary to congenital candidiasis.

Candidal paronychia.

Candidal paronychia.

Diagnosis

Skin scrapings from pustules or peripheral scale should be examined using KOH solution, Giemsa, Gram, or calcofluor stains. Pseudohyphae and spores may be visualized with direct staining. Satellite pustules are most likely to yield positive results. Cultures from multiple sites, including skin, blood, cerebrospinal fluid, and urine, should be collected if systemic disease is suspected in premature infants or immunocompromised children. Culture yield is inconsistent, and negative cultures do not rule out systemic disease in the symptomatic infant. Buffy coat smear microscopy, a rapid bedside test with 100% specificity, can confirm candidemia within 1–2 h. Sensitivity is 62%, compared with 44% for peripheral blood smear examination. In some centers, buffy coat culture may yield results faster than whole blood cultures. A skin biopsy specimen may reveal a subcorneal pustule with neutrophils, and periodic acid–Schiff (PAS) staining will highlight the organisms. Invasive fungal dermatitis demonstrates invasion and inflammation of the epidermis, and possibly invasion of the dermis. In both neonates and children, Candida albicans is the etiologic organism in approximately 50% of candidal infections. As a group, the non-albicans species comprise the remaining causes.

Treatment

Localized forms of candidiasis can be treated topically in most term infants and healthy children. For thrush, nystatin solution (100 000 units/mL) is applied to the oral mucosa four times per day for at least 1 week. Resistant thrush may respond to once-daily oral fluconazole (2–3 mg/kg per day) or itraconazole (2 mg/kg per day), particularly in immunocompromised children. Oral amphotericin B has been studied for treatment of recurrent thrush. Imidazole creams are useful for diaper dermatitis and nail infection. Nystatin, allylamines (including naftifine and terbinafine), or aqueous solutions of 1% gen­tian violet or 2% eosin are alternatives for localized disease. Inflamed or erosive monilial diaper dermatitis may require a combination of the above with a 1% hydrocortisone cream or ointment and barrier paste containing zinc oxide. Oral nystatin or fluconazole may also be a useful adjunct for the treatment of diaper dermatitis, especially for recurrent disease, concurrent oral candidiasis or persistent cutaneous candidiasis in the setting of prolonged oral antibiotics thereby reducing the load of gastrointestinal Candida . Congenital candidiasis in asymptomatic term infants can be treated with topical agents alone. However, for ill and VLBW preterm infants, systemic treatment is recommended.

In pediatric patients with invasive candidiasis, successful treatment outcomes are related to the candidal species causing the infection. C. parapsilosis and C. albicans have significantly better treatment outcomes than the more virulent C. glabrata infections. The drug of choice for systemic antifungal therapy evolves with candidal species, concurrent medical conditions and balance of potential medication side-effects. Early empiric systemic therapy reduces mortality in pediatric patients with candidemia. In ELBW infants, empiric treatment improves survival without associated neurodevelopmental impairment. Once the candidal species is indentified, adjustment of the antifungal agent may be necessary. In neutropenic patients, therapy should be continued for at least 14 days after last positive blood culture.

Amphotericin B, a polyene macrolide antibiotic, has been a major therapeutic agent in systemic candidasis in immunocompromised patients. It is typically utilized in immunocompromised neutropenic patients with prior failed fluconazole prophylaxis or those at high risk of C. glabrata or C. krusei infections. Less commonly seen in neonates, the potential for nephrotoxicity warrants monitoring of renal function. Hepatotoxicity and bone marrow suppression are also potential side-effects. Lipid-associated amphotericin B formulations have less direct renal tubular toxicity and allow delivery of greater dosages, limits of infusion volume, and less toxicity. In addition to use in children, successful treatment of systemic fungal disease with these products has been reported in neonates. Both the liposomal and colloidal dispersion forms of amphotericin B were shown to be safe and effective in ELBW infants with candidemia and renal dysfunction. Furthermore, high-dose (5–7 mg/kg per day) liposomal amphotericin B may add a therapeutic advantage with more rapid eradication of infection when used as first-line therapy.

Systemic fluconazole is commonly used in pediatric invasive candidal infections and has even been used successfully for treatment of systemic candidiasis in neonates. The recommended daily dose is 6 mg/kg per day for patients over 4 weeks of age, with less-frequent dosing for infants with compromised renal function and for those less than 4 weeks old. It is particularly useful in those with C. albicans infection and in whom amphotericin B is ineffective or contraindicated. When given in the first trimester of pregnancy, fluconazole has been reported to be teratogenic, leading to multiple malformations. Resistance to fluconazole can be seen especially in non-albicans Candida species ( C. krusei , C. tropicalis , C. glabrata , C. parapsilosis ), and also some C. albicans . Susceptibility testing can be performed to document the utility of these agents.

Oral itraconazole administered at 5 mg/kg per day has been safe and well tolerated in infants and children; however, there are limited reports documenting its use in newborns with candidiasis. Oral ketoconazole (3–6.5 mg/kg per day) has been largely supplanted by the newer triazoles for candidiasis due to its risk of fulminant hepatitis.

The echinocandins such as caspofungin and micafungin are a relatively new class of pediatric-approved antifungal agents, which irreversibly inhibit 1,3-β- d -glucan synthesis. These medications are fungicidal against Candida spp., including fluconazole-resistant strains, making them especially important for cases of non-albicans candidal infection. In general, the echinocandins have similar efficacy as amphotericin, with fewer adverse side-effects. In one study of caspofungin use in neonates with invasive candidiasis unresponsive to amphotericin B, all cultures cleared after 3–7 days of therapy without adverse events.

Especially in C. parapsilosis infections, adjunctive therapy for systemic Candida infection includes changing or removing indwelling catheters when feasible. Possibly due to the inability to sterilize the subcutaneous tract of existing lines, exchange of peripherally inserted catheters is associated with a 25-fold increased risk of bloodstream infections. Placement of new vascular access at a different site is recommended.

Because ELBW infants and immunocompromised children are susceptible to and have a higher mortality risk from systemic Candida infections, prevention of infection by means of fluconazole prophylaxis should receive strong consideration. Potential concerns include unknown short- or long-term risks of fluconazole; uncertainty regarding the group of patients that would benefit most and the optimum dose and duration of therapy; and the potential for increased fluconazole resistance. Fluconazole has been shown to reduce rectal colonization with Candida . Bertini and colleagues gave fluconazole 6 mg/kg every 72 h for week 1, then daily for weeks 2–4 in neonates <1500 g with central venous access, and reduced the rate of candidemia from 7.6% to zero. Healy and coworkers initiated fluconazole prophylaxis in all ELBW infants of <5 days of age and reduced invasive candidiasis-related mortality from 12% to zero. As for dosing, twice-weekly fluconazole (3 mg/kg per dose) in ELBW infants with a central venous catheter or endotracheal tube was as effective as daily prophylaxis in decreasing Candida colonization and bloodstream infections. Meta-analysis of prophylactic fluconazole in this population found both agents to be safe and highly effective in preventing invasive candidiasis. Although these studies appear promising, larger multicenter studies looking closely at the morbidity and mortality rates from all causes, the emergence of resistant Candida strains, and unexpected consequences are still required.

Skin colonization with Malassezia species

Malassezia furfur is the main species responsible for human skin colonization and infection. Other Malassezia species, including M. sympodialis , M. globosa , and M. pachydermatis have also been implicated in human disease. Malassezia colonizes the skin of adults who are usually asymptomatic. Skin colonization begins in infancy, and the prevalence of colonization increases with age. The most common site of colonization in both infants (>78%) and neonates is the ear. Ashbee and collegues showed that 97.6% of infants (>28 days of age) and 31.8% of neonates were colonized; the mean age of colonization was 14 days. Risk factors for colonization include gestational age of <28 weeks and length of hospital stay >10 days. Fungal growth from skin and catheter cultures is not always associated with clinical sepsis.

Tinea versicolor

Due to the variation of sebum production during life, tinea versicolor (pityriasis versicolor) is less common in infants than in older children, adolescents, and young adults. However, young infants, particularly those less than 6 months of age, can have more sebum production under the influence of the fetal adrenal glands (so-called ‘mini-puberty of infancy’) and thus are more likely to develop tinea versicolor than older infants or pre-pubertal children. Facial involvement is very typical in affected infants and young children, although lesions may also be seen on the neck and upper trunk. Warm humid weather and immunosuppression induce greater growth of this yeast. A positive family history is variably present. Most commonly caused by M. globosa and M. furfur , tinea versicolor presents with multiple, 0.3–1 cm oval macules or plaques with fine scaling ( Figs. 14.12 , 14.13 ). Relative to normal skin, lesions may be hypopigmented, skin-colored, or hyperpigmented. Wood’s light examination highlights the pigmentary changes and may produce a golden fluorescence. Differential diagnoses include pityriasis alba and postinflammatory hypopigmentation and hyperpigmentation.

Tinea versicolor.

Tinea versicolor.

Neonatal cephalic pustulosis

Neonatal cephalic pustulosis (see Chapter 7 ) is a condition that was previously considered to be neonatal acne. During the second or third week of life, multiple, tiny, monomorphous papulopustules on an erythematous base begin on the face, scalp, and neck ( Fig. 14.14 ). Contrary to classic acne, comedones are not a feature, and follicular accentuation is absent. Both M. globosa and M. sympodialis have been reported in association with neonatal cephalic pustulosis. Higher rates of colonization were associated with increased severity of pustulosis. Diagnosis is suggested by onset at 1 month of age, cephalic distribution, microscopic findings of yeast forms suggestive of Malassezia , exclusion of other pustular eruptions, and response to topical ketoconazole. The differential diagnosis of this pustular eruption is discussed more extensively in Chapters 7 and 10 .

Neonatal cephalic pustulosis.

Malassezia sepsis

Malassezia fungemia is seen primarily in premature infants receiving intralipids through intravenous catheters. Skin colonization rates are much higher in premature infants than in full-term newborns, and the pathogenesis of disease probably involves organisms on the skin gaining venous access through indwelling catheters. Although in one study of VLBW infants (<1250 g), skin colonization with M. furfur was not predictive of catheter infection or systemic illness, the skin colonization rate was 63%, and positive M. furfur blood cultures were common (9.6%) in infants with central venous catheters. Clinical presentation ranges from asymptomatic colonization of the indwelling catheter to sepsis and death. Fever, apnea, bradycardia, and thrombocytopenia in the presence of negative routine bacterial cultures suggest fungal disease. Clusters of cases of infantile bronchopneumonia in neonatal units have also been attributed to M. furfur .

Diagnosis and treatment of Malassezia infections

Malassezia can be identified by KOH preparation or Giemsa stain examination of the fine scales or pus; this will reveal clusters of spherical yeast and associated filaments. Malassezia is differentiated from Candida and other yeasts by a broader budding base. Malassezia furfur is a lipophilic yeast that requires fatty acid supplementation for growth. Modified Dixon agar or an olive oil overlay on routine fungal media is used for isolation of these fungi from blood specimens.

Cutaneous infections can be treated with an imidazole cream. A high level of suspicion for Malassezia sepsis is appropriate in premature infants with clinical signs of sepsis and negative bacterial and viral cultures, especially if intravenous lipid emulsions are being infused through venous catheters. Removal of the catheter and cessation of intravenous lipids, without systemic antifungal therapy, may be sufficient therapy for catheter-associated sepsis. Systemic antifungals may be considered if the infant does not show rapid clinical improvement.

Primary cutaneous aspergillosis

Primary cutaneous aspergillosis (PCA) with infection limited to the skin is being reported more frequently in premature infants. It is often associated with breaks in normal skin integrity, such as occur with intravenous catheter insertion, or skin erosion or maceration secondary to the use of adhesive tape, monitor leads, or prolonged armboard use. Lesions are often confused with skin trauma or contact dermatitis, and diagnosis can be delayed unless a high level of suspicion is maintained. PCA may begin as a localized zone of erythema, evolving into a dark-red plaque with pustules, and finally a black eschar with a rim of erythema. Clustered, erythematous papules or pustules, or a necrotic plaque or nodule with an eschar, are characteristic ( Fig. 14.15 ). The differential diagnosis includes ecthyma gangrenosum, zygomycosis, noninfectious vasculitis, and pyoderma gangrenosum. Histologic evaluation and culture of a biopsy specimen from the affected area can be diagnostic. Microscopically, vesicular surface erosion of a granuloma with infiltrating dichotomously branched (at 45° angles) septate hyphae is apparent. Growth of Aspergillus is supportive of a diagnosis, but lack of a positive culture does not rule out disease, especially if hyphal elements are seen on histologic examination.

(A) Primary cutaneous aspergillosis. (B) Cutaneous aspergillosis in a premature neonate.

Systemic aspergillosis

Isolated pulmonary, gastrointestinal, and central nervous system aspergillosis may not be associated with skin findings; however, disseminated aspergillosis can have cutaneous manifestations, and cutaneous aspergillosis may disseminate. A morbilliform eruption that may become pustular is described with systemic aspergillosis. This presentation often represents embolic phenomena from fungal dissemination. Mortality from systemic aspergillosis in neonates is high compared with that of primary cutaneous aspergillosis (up to 100% vs 27%, respectively).

Systemic antifungal therapy is recommended for all forms of systemic aspergillosis. Voriconazole or lipid formulations of amphotericin have been the standard antimicrobial agents prescribed. It is unclear whether complete surgical excision of cutaneous lesions is necessary for cure, but progression of the lesion during therapy may warrant surgical intervention.

Cutaneous zygomycosis (mucormycosis, phycomycosis)

Zygomycosis is the term for infection caused by fungi in the Zygomycetes class. There are six fungal genera that cause disease in humans: Rhizopus , Cunninghamella , Mucor , Rhizomucor , Saksenea , and Absidia . These fungi are found in soil, decaying food, and other organic matter. Although infections may follow ingestion or inhalation of spores, direct inoculation into skin is the cause of primary cutaneous zygomycosis. It is seen predominantly in premature infants, as well as those who are immunocompromised from immunosuppressive drugs or underlying disease. Due to the selective pressure of more frequent use of newer (non-amphotericin) antifungal medications, some centers have reported an increase in invasive zygomycosis. Similar to aspergillosis, zygomycosis can involve the skin alone (primary cutaneous) or may involve other organ systems, including the gastrointestinal, pulmonary, and central nervous systems. Skin lesions may represent dissemination, or primary cutaneous infection may disseminate. Zygomycosis in immunocompetent hosts includes cutaneous zygomycosis and sinusitis. The cutaneous lesions may present as pustules with or without discrete erythematous cellulitis, and may develop a sharply defined, black, necrotic plaque producing a pathognomonic black pus ( Fig. 14.16 ).

Cutaneous Rhizopus : pustules developed under tape adhesive.

In a review of 31 cases of neonatal zygomycosis, 22 were in premature infants, of which 12 had skin as the initial site of infection. Reports include an association with contaminated dressings and tongue depressors used as splints for intravenous and arterial cannulation sites. The Centers for Disease Control and Prevention (CDC) recommends that skin dressings be treated with cobalt irradiation as a preventive measure.

Diagnosis is made by tissue biopsy and culture. Histologic examination shows large, nonseptate hyphae with right-angled branching. The fungus invades downward into tissue and blood vessels, frequently leading to thrombosis with dermal edema and minimal inflammatory infiltrate. Vascular invasion results in cutaneous ischemia and necrosis.

Zygomycosis is treated with intravenous amphotericin B. As with aspergillosis, lipid formulations of amphotericin B can be used to deliver higher concentrations of drug, and other agents such as rifampin may be of use for antimicrobial synergy. In vitro data reveal resistance to azoles (except for Absidia ), flucytosine, and naftifine. Although one successful case of medical treatment alone is reported, surgical debridement is often imperative in the treatment of cutaneous zygomycosis, and wide excision with clear margins of involved tissue is recommended. Overall mortality in invasive zygomycosis is 64% in neonates and 56% in children.

Clinical findings

Dermatophyte infections in infants occur most commonly on the exposed scalp and face ( Fig. 14.17 ) Tinea capitis often presents as erythematous, scaling areas with partial alopecia. Clinical manifestations vary from noninflammatory ‘black dot’ alopecia to a scaling, seborrheic dermatitis-like eruption without obvious hair loss ( Fig. 14.18 ). Pustules may be present. Kerions can be seen in conjunction with tinea capitis. Kerions consist of pustules, nodules, and crusting, with underlying bogginess of scalp tissue. The inflammatory nature mimics a bacterial infection and often leads to unsuccessful therapy with antibacterial agents. Tinea capitis associated with kerion formation has been reported in a neonate. Posterior cervical lymphadenopathy is usually present. The kerion represents a delayed hypersensitivity reaction to the infection and may occur in 2% of patients with tinea capitis. Cultures from kerions can be negative in 40% of cases.

Annular, scaling plaques on this 2-week-old infant due to T. tonsurans infection.

Infant with tinea capitis.

Tinea infection on other parts of the body usually presents as annular plaques with superficial scaling and/or tiny pustules. These may be mistaken for dermatitis; facial tinea may mimic neonatal lupus. Cases of tinea faciei and tinea corporis have been reported in neonates. Cases of resistant diaper dermatitis in infants as a result of dermatophytes have been described. In tinea diaper dermatitis, the presence of annular or arcuate plaques with a scaling peripheral border is a clue to the diagnosis ( Fig. 14.19 ).

Dermatophyte diaper dermatitis (note scaling edge).

Tinea pedis was once thought to be rare in young infants. While certainly not as common as in teens or adults, many cases have been reported. A major risk factor is the presence of tinea pedis or onychomycosis in one or more family members. The clinical presentations are similar to those in older patients including web-space scaling as well as scaling of the forefoot. Because of low level of suspicion, many affected children are misdiagnosed as having a dermatitis.

Onychomycosis, fungal infection of the nail, can be caused by dermatophytes, nondermatophyte molds, and Candida . Tinea unguium, caused by dermatophytes, is uncommon in prepubertal children but is occasionally seen. Candida onychomycosis is a relatively common finding in neonates with congenital cutaneous candidiasis. Nails may have superficial white opaque patches, or yellowish discoloration with subungual hyperkeratosis. Hereditary onychodystrophy, acquired trachyonychia, psoriasis, lichen planus, and trauma may cause similar findings.

Diagnosis

Diagnosis of dermatophytosis can be confirmed by several tests. A Wood’s light examination may have limited usefulness in the diagnosis of tinea capitis; positive fluorescence is seen in ectothrix hair infections, but is absent in the more common endothrix infections such as those caused by Trichophyton . All suspected tinea infections should be confirmed by culture, or lesional scale or hair microscopically examined under 10% potassium hydroxide (KOH) solution or alternative stains (see Chapter 6 ). Although KOH preparations may demonstrate spores and hyphae, false-negative examinations are common. Scrapings of scales, brush or cotton-tipped applicator swabbings of the affected skin, or collections of hair are cultured on fungal media. Dermatophytes are slow growing and may take up to 1 month to grow in culture, although common pathogens generally grow within 2 weeks. Skin biopsy, although rarely necessary for diagnosis, may reveal hyperkeratosis with parakeratosis and a mixed inflammatory perivascular dermal infiltrate. Staining with periodic acid–Schiff (PAS) or Grocott–Gomori methenamine silver nitrate reveals fungal elements in the stratum corneum and possibly the hair follicle.

Treatment

Treatment of tinea capitis usually requires systemic antifungal therapy. Griseofulvin has been used for decades and successful safe treatment even in neonates has been reported. Griseofulvin suspension doses of 20–25 mg/kg per day for 8 weeks may be needed. Ultramicrosized griseofulvin is better-absorbed allowing for reduced dosages at 15–20 mg/kg per day. Fluconazole (6 mg/kg per day) may also be effective. Terbinafine is fungicidal and may require shorter treatment durations. Experience with terbinafine in neonates is limited, but has been studied in children as young as 2 years of age with good tolerance demonstrated. Terbinafine, dosed at 5–8 mg/kg daily for 6 weeks, has been shown to have efficacy against both Trichophyton and Microsporum species in pediatric cases of tinea capitis. Although topical therapy alone was successful in treatment of infants (mostly preterm infants with M. canis tinea capitis) during a nursery outbreak, it is not generally recommended for tinea capitis. A well-reported complication of tinea capitis is auto-eczematization (‘id’ reaction) which occurs in a minority of patients, typically those with either severe or long-standing disease. This reaction typically manifests as intensely pruritic monomorphic and symmetrically distributed papules on the hair line, ears, and upper torso and proximal extremities. Onset is usually just after the initiation of systemic treatment of tinea capitis, however it does not represent true allergy to the oral antifungal medication.

Tinea faciei, corporis, and pedis can be successfully treated with topical applications of azoles such as clotrimazole, econazole, and miconazole. Ciclopirox, as well as allylamines such as terbinafine or naftifine and amorolfine, may also be used. If persistent, systemic griseofulvin or fluconazole for a period of 4–8 weeks may be required. Majocchi’s granuloma is a follicular dermatophyte infection on non-scalp locations. These granulomatous dermatophyte infections typically occur when the initial superficial fungal infection is mis-treated with topical steroids allowing the dermatophyte to invade hair follicles. Systemic treatment is necessary to eradicate this deeper dermatophyte infection. It is important to identify the potential source of the fungal infection in family members. The prognosis for dermatophyte infections is excellent.