Brent D. Michaels, DO; James Q. Del Rosso, DO, FAOCD
Dr. Michaels is Chief Resident (Dermatology, PGY-4), Valley Hospital Medical Center, Las Vegas, Nevada; Dr. Del Rosso is Dermatology Residency Program Director, Valley Hospital Medical Center, Las Vegas, Nevada; Clinical Professor (Dermatology), Touro University College of Osteopathic Medicine,
Henderson, Nevada; Las Vegas Skin & Cancer Clinics/JDRx Dermatology, Las Vegas and Henderson, Nevada
Disclosure: Dr. Michaels reports no relevant conflicts of interest. Dr. Del Rosso is a consultant, speaker, and/or researcher for Coria/Valeant, Allergan, Galderma, Graceway, Intendis, Medicis, Onset Dermatologics, Obagi Medical Products, Ortho Dermatologics, PharmaDerm/Nycomed, Promius, Ranbaxy, Stiefel/GSK, TriaBeauty, Triax, Unilever, and Warner-Chilcott.
Tinea capitis is a reasonably common infection among the pediatric population; however, it is still a relatively rare entity among infants less than one year of age. As such, a high index of suspicion is necessary for diagnosis among infants and an appropriate diagnostic work up should be employed in any case where a dermatophyte infection is suspected. Several methods are available for diagnosis. In addition, proper identification of the specific dermatophyte genera involved should be considered as treatment options may be altered based on the causative pathogen identified. (J Clin Aesthet Dermatol. 2012;5(2):49–59.)
Tinea capitis infection is on the rise in North America and continues to be a significant public health concern.[1,2] In fact, tinea capitis infection has been described as a “modern-day epidemic.” It is the most commonly diagnosed dermatophytosis of childhood and is more frequently seen among prepubescent children.In fact, it has been stated by Boni Elewski, MD, an international expert on cutaneous mycotic infections, that when scalp scaling is noted in children, “the fungus is guilty until proven innocent” (personal communication with Boni Elewski, MD, May 1999). However, among infants, while the infection still occurs, it is relatively rare. Further complicating the diagnosis in infants is the variability in clinical presentation. For these reasons, a high index of suspicion is needed for diagnosis, as one must first consider the possible presence of a disorder before the diagnosis can be made. The practitioner should approach each case of a potential dermatophyte infection with a similar diagnostic approach regardless of age, which includes direct microscopy and fungal culture.
The two more common genera of dermatophytes responsible for tinea capitis infection are Trichophyton tonsurans and Microsporum canis, with T. tonsurans the most common cause of tinea capitis in the United States. However, M. canis is increasing in incidence in parts of Europe and the United States. Diagnostically, there are several methods available for identifying a tinea capitis infection. In terms of treatment, the standard therapy for tinea capitis remains oral griseofulvin; however, depending on the specific pathogen identified, different treatment regimens may be employed.
An eight-month-old Caucasian girl presented to the authors’ office with a seven-month history of a “rash” on the scalp. Prior treatments included an unknown topical corticosteroid cream and most recently, topical nystatin cream. The patient’s mother reported some minimal improvement with the nystatin cream, but upon discontinuation of the cream, the rash returned to pretreatment intensity. Clinical examination and review of past medical history revealed an otherwise healthy female infant with no prior significant past medical or surgical history and normal progression of childhood development. The mother noted no change in her infant’s behavior since the development of the scalp eruption. A recent history of “ringworm” infection of the family cat was elicited with subsequent treatment and resolution by a veterinarian. The family cat completed treatment approximately two months prior to the mother noting the “rash” on her child’s scalp. No one else in the home was affected with any skin or scalp problems.
On physical examination, the patient presented with diffuse, erythematous, ill-defined patches with focal areas of scaling and hyperkeratosis on the scalp, predominantly involving the vertex region (Figure 1). The child had diffusely thin hair, which was unchanged by history according to the mother, with no appreciable alopecia noted clinically. The remainder of the physical examination revealed an active healthy-appearing, and playful infant with no cutaneous abnormalities noted other than the scalp eruption who was accompanied by a very anxious mother. There were no areas of pustulation, erosion, induration, or boggy inflammation noted on the scalp, with absence of cervical and occipital adenopathy on palpation.
Based on the history and physical examination, scrapings of the scale from the involved areas of the scalp were obtained as well as samples of plucked hairs from the affected scalp regions, with all of the obtained specimens placed on glass microscope slides. This was followed by application of potassium hydroxide (KOH) 10% with dimethyl sulfoxide (DMSO) for examination by light microscopy (KOH prep). Scale and hair samples from the scalp were also placed in dermatophyte test medium (DTM) for preliminary fungal culture. Examination of the KOH prep revealed an ectothrix pattern of hair shaft invasion by fungal elements with numerous spores located outside the surface of the hair shaft and with multiple long branched hyphae also noted (Figure 2a, Figure 2b). The results of the DTM assessed at Day 7 revealed positive growth with white fluffy colonies and turning of the medium color from yellow to red, indicating growth of a dermatophyte. The positive DTM culture containing the dermatophyte growth was subsequently sent intact to microbiology for specific identification of genera and species. Fungal sequencing completed on the already grown dermatophyte specimen in the positive DTM was determined to be genetically consistent with M. canis. Interestingly, there was a prior history of the family cat being treated for a “ringworm” infection, which if this was dermatophytosis affecting the cat, would be a very likely explanation for the M. canis infection affecting the infant, as the cat often sleeps next to the infant during naps according to the mother.
Treatment was initiated on the first visit after the positive KOH results. The risk-benefit ratio of various options was discussed, including the explanation that tinea capitis is poorly responsive to topical therapy alone, and necessitates treatment with oral antifungal therapy. The infant was treated with griseofulvin suspension 125mg/5cc and directed to take one teaspoon twice a day to achieve a daily dose closely approximating 25mg/kg/day of oral griseofulvin. The patient was also prescribed ciclopirox 1% shampoo for use every other day with instructions to avoid sharing combs, brushes, and towels used to dry the scalp of the child. The patient was treated for eight weeks in total with both medications. After just two weeks of treatment, improvement was noted, and complete clinical clearance was obtained after eight weeks (Figure 3a and Figure 3b). An additional KOH prep obtained from the previously affected scalp, including some hairs in the region, was performed with microscopic examination completed at the end of treatment (8 weeks) and was negative for any fungal elements. No adverse effects from either medication were reported by the mother, with the treatment regimen very well tolerated.
Additionally, the family cat was rechecked by the veterinarian immediately after the diagnosis of tinea capitis in the infant was made, and was retreated for possible dermatophyte infection prophylactically, although there was no evidence of feline infection.
Tinea capitis is a dermatophyte infection involving the scalp, which is characterized predominantly by involvement of the hair shaft as well as contiguous skin. Overall, there are more than 40 different known species of dermatophytes; however, a much more limited number of species commonly cause cutaneous infection, with between 6 to 8 of these species associated with causing tinea capitis worldwide.[7,8]
The predominant genus and species of dermatophytes causing tinea capitis often varies based on geographic location; however, children remain the predominant age group affected.
Dermatophytes causing tinea capitis in the United States. At present, the two main dermatophytes that cause tinea capitis in the United States in order of frequency are T. tonsurans and M. canis. T. tonsurans is by far the most common causative species, “accounting for more than 95 percent of positive cultures in the United States”. In other parts of the world, the specific species of dermatophyte responsible for tinea capitis will vary from each country. The overall incidence of tinea capitis in the United States has been estimated to be 3 to 8 percent; however, the incidence is reported to be on the rise. Although tinea capitis can affect individuals of any age, with cases reported as early as six days of life and as late as 70 years of age, the vast majority of cases of tinea capitis affect prepubescent children, with the average age reported between 3 and 7 years.10 One study cites the point prevalence in school-age children to be as high as 13 percent. Tinea capitis, however, still remains a relatively rare entity among infants. One reference cites only 50 known reported cases of tinea capitis in infants less than one year of age at the time of their evaluation.
Dermatophytes causing tinea capitis arise from one of three main reservoirs and can be classified by this host preference: anthropophilic (humans) fungi, which include T. tonsurans; zoophilic (animals) fungi, which include M. canis; and geophilic (soil) fungi, which include M. gypseum. The source for most tinea capitis infections in children are usually either anthropophilic or zoophilic dermatophytes. However, even if the infection is zoophilic, the main source of transmission in infants is from a visibly infected family member who transfers the organism directly, or in the case of anthropophilic fungus, may transfer from active infection sites or through asymptomatic carriage of the organism, as not all humans become clinically infected when exposed to anthropophilic fungi. Variability in host response to anthropophilic fungi is common, including with T. tonsurans, with affected individuals ranging from asymptomatic carriage, to non-inflamed or minimally inflamed patches of involvement, to affected regions of brisk inflammation that is likely related to a greater intensity of a cell-mediated host response to the specific organism by some individuals. On the other hand, asymptomatic carriage may occur in those individuals who are otherwise immunocompetent, but are typified by an “immunologic blind spot” against that specific dermatophyte. Therefore, these carriers can pass the dermatophyte (i.e., T. tonsurans) to others who eventually exhibit a clinical infection. However, the “silent” carrier does not develop clinically evident infection. Asymptomatic dermatophyte carriage can occur on the scalp of children and/or adults.
Modes of transmission in tinea capitis. A variety of different modes of transmission from these reservoirs are possible, making tinea capitis a contagious and communicable fungal infection.[2,4] Spore transmission has been described from person-to-person, such as among family members, classmates, and in infant day care centers. Animal contact and fomite contact spread are additional potential sources of infection. Fomite/inanimate objects responsible for transmission have included hats, brushes, towels, couches, pillows, fallen hair, sheets, rugs, telephone receivers, desquamated epithelial cells, soil, and toys.[2,4] Dermatophytes are hardy organisms, with the longevity of viable dermatophytes contributing to the communicable spread of tinea capitis. Dermatophytes, which are potentially contagious, can be present in fomites for months, with viable dermatophytes observed in stubs of hair for up to two years.[2,4]
The reason why prepubescent children are more prone to tinea capitis is at least partially explained by the fact that sebum, which is rich in lipids (i.e., fatty acids, certain precursor lipids) and fungistatic, is minimally present before the onset of puberty.
Modes of hair shaft invasion. In addition to designation by mode of transmission, tinea capitis can also be categorized by mode of hair invasion. The types of hair invasion include endothrix, ectothrix, and favus. In ectothrix infection, the fungus grows within the hair follicle and covers the hair surface, so fungal spores (and sometimes hyphae) are seen on the outside of the hair shaft (Figure 2a and Figure 2b). In endothrix infection, the dermatophyte progresses down the hair follicle, invades the hair shaft, and grows within the hair shaft. Therefore, the fungal spores are retained within the hair shaft, often appearing like “a bag of marbles” (Figure 4). In general, common endothrix dermatophytes include several species of the Trichophyton genera (i.e., T. tonsurans), and common ectothrix dermatophytes include several species of the Microsporum genera, with exceptions. In favus, the main causative organism is T. schoenleinii, with microscopic examination revealing hyphae arranged parallel to the hair shaft, along with bubbles of air in the hair shaft. Clinically, favus is typified around the hair shaft by a yellow “cup-shaped” crusting (“scutula”) as well as matted hair on the scalp. On Woods lamp examination, favus fluoresces a gray-green color.
Importantly, T. tonsurans infected hair does not fluoresce on Woods lamp exposure due to the endothrix growth pattern. Tinea capitis caused by M. canis does exhibit blue-green fluorescence of affected hair shafts on Woods lamp exposure as the pattern of hair invasion is ectothrix.
Clinical presentations of tinea capitis. There are also numerous recognized clinical patterns of tinea capitis, including seborrheic dermatitis-like, black dot type, alopecia areata type, kerion, and favus (described above). Additional terms have also been used to describe the clinical patterns of tinea capitis, including gray-type, moth-eaten, and pustular type.1 The clinical pattern of tinea capitis present in a given patient is dependent upon several factors, including the genus and species of dermatophyte, and the host response of the patient. As with dermatophyte infection involving other cutaneous locations, the degree of visible inflammation in tinea capitis also reflects the intensity of host response, and also the specific causative dermatophyte, with zoophilic organisms often producing visible inflammation.[1,4,7,10,11] In many cases of tinea capitis in children, cervical and/or occipital lymphadenopathy is often present, and “id” reactions may also occur especially after initiating treatment with an oral antifungal agent.
The most common pattern seen in the United States is the seborrheic dermatitis-like pattern that presents as diffuse scaling, is usually associated with erythema, without localized alopecia.11 This clinical presentation of tinea capitis is easily misdiagnosed as seborrheic dermatitis resulting in erroneous treatment, often with a topical corticosteroid. As with essentially all cases of tinea capitis, this clinical pattern requires use of oral antifungal agent for clearance, so use of an antifungal shampoo prescribed for the misdiagnosis of seborrheic dermatitis is not adequate for clearance of the fungal infection. Other clinical patterns of tinea capitis in children are also commonly encountered in the United States, including patterns often seen with T. tonsurans, such as round-oval scaly patches with or without localized hair loss and little-to-no visible inflammation, round-oval patches of hair loss with the appearance of black dots that are intrafollicular hair shafts that have fractured and broken off as the shaft protrudes above the skin surface (“black dot” fungus), round-oval patches of silver-gray scaling devoid of inflammation (gray-type) as shown in Figure 5 with the KOH exam from this patient shown in Figure 4 (endothrix pattern), round-oval patches of shiny skin completely devoid of hair and without inflammation (alopecia areata-type), and round-oval inflammatory patches or plaques with hair loss, the latter also commonly seen with M. canis infection.
Differential diagnosis and simulant disorders. The wide variation in clinical patterns as well as the similar appearance to other clinical disease states in some cases (i.e., seborrheic dermatitis, alopecia areata) can confound the accurate diagnosis of tinea capitis. This is especially true in the infant population where tinea capitis is a rare entity and may be dismissed easily as seborrheic dermatitis (“cradle cap”), a much more common diagnosis in this age group. In fact, the most common presenting sign of tinea capitis in infants is scaling, although alopecia has also been reported as a common clinical finding. It is important that the clinician keep in mind several other dermatological conditions that can present with scalp scaling in children, including common diagnoses, such as seborrheic dermatitis and psoriasis, and rare disorders, such as Langerhans cell histiocytosis, dermatomyositis, pityriasis rubra pilaris, leukemia cutis, and pemphigus foliaceous. Therefore, given the infrequent nature of tinea capitis in infancy, a high index of suspicion is warranted anytime an infant presents with a seborrheic dermatitis-like scalp eruption in addition to other clinical signs such as alopecia or hair thinning.
Dermatophytes associated with tinea capitis in infants. T. tonsurans is still the most common causative dermatophyte for tinea capitis in the United States. However, in terms of the specific causative species among infants, M. canis also appears to be one of the predominate dermatophytes causing infection worldwide, including the United States. This is due to common contact with house pets that are perceived as safe around children, including infants. The main sources of infection for tinea capitis caused by M. canis infection are cats and dogs. In a specific catch area in Spain, 90 percent of infant tinea capitis cases between 1991 and 1995 were caused by M. canis. Additionally, reported cases of tinea capitis in infants in the Spanish and English literature showed the predominate causative dermatophyte to be M. canis. This observation was further supported by a report from Italy where 9 of the 15 cases of tinea capitis in infants were caused by M. canis. Thus, based at least on these European reports, although T. tonsurans may cause tinea capitis in infants, M. canis is commonly the culprit pathogen in this age group, and a house pet, usually a cat, is often the reservoir source of M. canis.[12,15]
Diagnosis of tinea capitis. Given the rarity of tinea capitis in infants, a high index of suspicion is necessary in any infant presenting with scaling and/or alopecia. Diagnosis based only on presenting clinical symptoms is often difficult, and fraught with potential for misdiagnosis. If tinea capitis infection is suspected, both a KOH prep and fungal culture are important for diagnosis. For light microscopy examination, a scraping of the scale and samples of affected hair should be placed on a microscope slide and 10- to 20-percent KOH should be added. KOH with DMSO is preferred by the authors as this circumvents the need to heat-fix the slide. For culture, the hair and scalp samples should be placed on either Sabouraud dextrose agar with chloramphenicol and cycloheximide, dermatophyte identification medium or DTM. Growth on DTM typically occurs within 1 to 2 weeks; however, fungal growth by cultures may take 3 to 4 weeks with some media or at some laboratories. Before obtaining a sample for culture, the area should be cleaned with alcohol to avoid cross contamination with bacteria.
There are several methods for obtaining samples for culture, including using a surgical blade, brushing hair, plucking hair with forceps, or using adhesive tape. Less traumatic methods for obtaining culture samples include running a toothbrush over the hair or, as an alternative, rubbing a moistened, but sterile cotton swab or gauze pad over the affected area.1,7 It must be emphasized that attempts to be less traumatic than with hair plucking when obtaining specimen for KOH and culture are only of value if they do not significantly reduce the potential for a positive yield when tinea capitis is present.
With regard to diagnostic aids that serve to support clinical diagnosis, there are important nuances to diagnostic testing methods.[1,4,7,10,11] Unfortunately, some clinicians, especially non-dermatologists, rely on Woods light examination as a distinguishing method for diagnosis or exclusion of tinea capitis. Woods lamp may be helpful in ectothrix infection (i.e., M. canis) with a blue-green fluorescence noted, although sensitivity is poor. Therefore, a positive Woods lamp examination supports the diagnosis of tinea capitis. However, a negative examination does not exclude tinea capitis. Microscopic identification with KOH prep of long-branched hyphae, often with septation, confirms the diagnosis; however, the genus and species of dermatophyte remain unknown. DTM is a very effective “screening medium” for culturing dermatophytes, provided the site from where the specimen is obtained is properly prepped to reduce potential contamination by nonpathogenic bacteria or fungi, a proper specimen is obtained, the cap on the bottle is kept loose, and the medium is checked after one week and after two weeks of incubation. Positive growth of a dermatophyte on DTM occurs almost always within two weeks. Although growth of contaminant bacteria and/or fungi can appear on DTM at any time point, the potential for contaminant growth increases after two weeks. Also, overgrowth of the causative dermatophyte by contaminant organisms may occur and can preclude an accurate recognition of dermatophyte colonies on DTM. Given the differences in susceptibility of some genera and species to individual antifungal agents, identification of the specific dermatophyte that is causing tinea capitis may be clinically relevant in some cases. Therefore, if a dermatophyte is grown on DTM, and the clinician is not capable of further defining the actual dermatophyte that is present, the DTM bottle containing the fungal growth can be forwarded to a microbiology/mycology laboratory that is capable of determining the genus and species of dermatophyte, such as through fungal deoxyribonucleic acid (DNA) sequencing.
Fungal culture may be obtained using media other than DTM, with the inoculated medium sent to the reference mycology laboratory. The mycology laboratory is then responsible for proper incubation, organism identification, and reporting of results. It is best that the clinician work directly with the mycology laboratory to be certain that the laboratory provides the appropriate media for identification of dermatophytes along with information on proper storage of the culture media before use, and transport instructions.
Misdiagnosis of tinea capitis. It is common for the treatment of tinea capitis in an infant to be delayed, usually due to misdiagnosis. As tinea capitis is uncommon in infancy, the diagnosis is often not considered, especially when the eruption simulates seborrheic dermatitis of the scalp, or exhibits pustulation that is clinically diagnosed incorrectly as a bacterial infection. It has been reported that only seven percent of children with tinea capitis received appropriate antifungal treatment from their primary care provider before referral to a dermatologist.1,16 In one study of children with misdiagnosed tinea capitis, three were diagnosed as seborrheic dermatitis and were treated with topical corticosteroids, three were diagnosed as bacterial folliculitis and treated with topical antibiotics, and one was treated with oral antibiotics for a suspected bacterial infection when the correct diagnosis was kerion. The high potential for clinical misdiagnosis of tinea capitis, especially by a non-dermatologist, makes it all the more incumbent upon the dermatologist to ensure that tinea capitis is readily identified and properly treated on the presenting visit. Delay in diagnosis and/or improper treatment may lead to more extensive scalp involvement, spread to non-scalp locations such as the face, and if significant inflammation is present (i.e., kerion), to scarring alopecia. Moreover, tinea capitis is contagious and spread to other family members or other close contacts may occur.
Management of tinea capitis. Management of tinea capitis involves more than simply selecting the right medication. As this infection is common in children, dissuading parental fears and concerns regarding the disease and/or its treatment with oral antifungal therapy is a major responsibility for the clinician. Also, consideration of the specific causative organism with regard to selection of therapy, daily dose, and anticipated duration of treatment, incorporation of adjunctive topical antifungal therapy, and handling of fomites, which may promote transmission to others are significant aspects to address with parents of affected children. When tinea capitis is present in an infant, as the age of the child is very young, parental fears and concerns are likely to be heightened even further.
The importance of oral antifungal therapy in the treatment of tinea capitis. With very rare to no exception, oral antifungal therapy is needed to eradicate tinea captis.[1–4,7,8,10,11,19,22] Griseofulvin remains a very effective treatment for many cases of tinea capitis caused by both Trichophyton spp and Microsporum spp, provided an adequate daily dose is administered and an appropriate duration of therapy is completed commensurate with what is needed in each individual case. Unlike the “newer” oral antifungal agents, which include the allylamine agent, terbinafine, and the triazoles, fluconazole and itraconazole, griseofulvin does not persist in cutaneous tissue for a prolonged time period after discontinuation, often necessitating a longer duration of therapy in many cases in order to achieve complete cure (clinical cure + mycological cure).[4,7,8,10,22] Importantly, although use of oral griseofulvin in children was initially plagued by exaggerated fears of major side effects, such as hepatotoxicity and hematological disturbances, such side effects have proven to be very rare in both adults and children.[4,7,8,10,11,22]
Some reference sources, including approved product labeling with certain oral antifungal agents, suggest specific durations or duration ranges of treatment for tinea capitis. These general recommendations are made as they are effective overall based on available data, but their existence should not be interpreted to imply complete clearance in all cases. Almost without exception, “outlier cases” exist with all disease states and therapies for a variety of reasons, necessitating the clinician to adjust therapy based on clinical assessment and index of suspicion. It is clear to the authors from available literature that not all cases of tinea capitis respond to a specified “fixed course” of oral antifungal therapy. Depending on disease severity, the specific fungal pathogen, variations in pharmacokinetic and pharmacological properties of the oral antifungal agent, and/or characteristics of the individual patient, longer courses of therapy may be needed.
In this case of tinea capitis in an infant, the authors elected to repeat a microscopic examination by KOH exam at the end of eight weeks of oral griseofulvin treatment, as the eruption had cleared visibly. The purpose of this test was to further confirm the clinical assessment that the infection had resolved. The repeat KOH exam was negative and oral griseofulvin was discontinued at that time. In addition to the KOH exam, it is reasonable to also repeat a fungal culture (such as with DTM media) at the end of treatment if the clinician feels this additional test is warranted. However, a KOH exam allows for immediate determination of the possible need for a longer course of oral antifungal therapy, as if test results are positive for fungal elements, therapy can be continued at that time without the delay of waiting for culture results. This principle is especially true with oral griseofulvin as this agent exhibits little tendency to persist in tissue after discontinuation. However, with the newer antifungal agents (i.e., terbinafine, fluconazole, itraconazole), mycological clearance may not be noted until weeks after discontinuation of therapy (e.g., 4–8 weeks), as these agents tend to persist within cutaneous structures (e.g., epidermis, hair, nails) for several weeks after oral administration.[1,4,7,10,18–22] Therefore, clinical judgment is a major factor in the determination of when to discontinue oral antifungal therapy for tinea capitis.
Individual oral antifungal agents used to treat tinea capitis. Griseofulvin. Overall, griseofulvin remains the “gold standard” of oral antifungal treatment for tinea capitis in the United States and is approved for this indication by the FDA.[1–4,7,8,10,11,19,22] In use for about five decades, griseofulvin exhibits an excellent long-term safety profile and proven efficacy, provided it is dosed properly based on the weight of the patient, and administered over an adequate duration of treatment. Safety is an obviously important consideration, especially when dealing with infants. The most common side effects associated with oral griseofulvin are headache, gastrointestinal upset (GI), and “rash,” with the latter reported to occur in up to 15 percent of patients, with some cases representing “id” reaction.[1,7] The GI side effects are lessened when the medication is taken with meals. Rarely reported adverse events include various genitourinary, musculoskeletal, nervous system, and hematological effects.
Two main oral forms of griseofulvin are available, microsized and ultramicrosized, relating to the particle size of active ingredient incorporated into the formulation. These formulations were designed to reduce GI upset and to optimize GI absorption of griseofulvin. The microsized form has the advantage of a liquid formulation, which is highly acceptable and convenient for infants and young children. Optimal dosing in children is based on body weight.
Recommendations regarding the daily dose of microsized griseofulvin have ranged from 10 to 25mg/kg/day. However, the current recommendation in the United States is 20 to 25mg/kg/day, which differs from the older approved product labeling. Commonly, a treatment duration of 6 to 8 weeks is generally recommended, with longer durations often needed due to reported treatment failures.[4,7] One report suggests a duration of treatment of 6 to 12 weeks. Others suggest continuation of oral griseofulvin therapy for two weeks beyond resolution of clinical signs and symptoms of tinea capitis. The oral microsized suspension contains 125mg/5mL. For the ultramicrosized formulation, a dosing of 10 to 15mg/kg/day is suggested; however, it may be prudent to favor the higher end of the dose range, especially with M. canis infection. With oral griseofulvin, mycological cure rates have been reported between 80 and 95 percent and effective therapy (mycological and clinical cure) rates between 88 and 100 percent.
Interestingly, The American Academy of Pediatrics (AAP) suggests dosing of 10 to 20mg/kg/day for microsized griseofulvin and 5 to 10mg/kg/day for ultramicrosized in a single daily dosing for 4 to 6 weeks with possible continuation of treatment for two weeks beyond the resolution of clinical symptoms of tinea capitis. These AAP recommendations appear low, with the authors recommending a starting dose of 20mg/kg/day in children with tinea capitis, with an increase to 25mg/kg/day in some cases caused by M. canis.
For infants, different dosage regimens of griseofulvin have been reported to be efficacious. In one study involving tinea capitis in infants, micronized griseofulvin was the antifungal used most often at a dose of 15mg/kg/day for 45 to 60 days, and most patients using griseofulvin experienced full recovery. In another study, most infants received topical imidazole and oral griseofulvin (either ultramicronized formulation at 10mg/kg/day or 15mg/kg/day for micronized formulation) for 30 to 60 days and complete clinical and mycological recovery was noted in patients, regardless of whether the infection was caused by Trichophyton or Microsporum species.
However, effective treatment can often depend on the genus and species of dermatophyte causing tinea capitis. For Microsporum species, griseofulvin is still the preferred oral antifungal agent. In guidelines on the management of tinea capitis from the European Society of Pediatric Dermatology, it was concluded that griseofulvin is the treatment of choice for Microsporum species, with griseofulvin determined to be more efficacious than oral terbinafine. Although there was similarity in efficacy and oral treatment duration with griseofulvin, itraconazole, and fluconazole, griseofulvin was found to be less expensive. In the Cochrane Review, griseofulvin was also found to be the treatment of choice for tinea capitis caused by Microsporum species. Given the need for a high daily dose and a relatively long treatment duration with griseofulvin, other non-FDA approved oral antifungal agents are proposed as an alternative treatment for M. canis-induced tinea capitis where applicable. In general, the duration of oral griseofulvin therapy that is needed to clear tinea capitis caused by M. canis is likely to be longer than what is needed for effective treatment of T. tonsurans. With oral griseofulvin therapy, a good general rule is to treat for two weeks beyond the clearance of visible signs and symptoms of tinea capitis.
Itraconazole. Oral itraconazole has been studied in infants with tinea capitis caused by M. canis. In one study, infants between 3 and 46 weeks of age were treated with itraconazole for 3 to 6 weeks at a dose of 5mg/kg/day using the oral capsules. Not only was complete clinical and mycological cure achieved, no side effects were reported. Pulse dosing of itraconazole has also been shown to be effective, administered using oral capsules at 5mg/kg/day for one week per month (1 week on and 3 weeks off) for 2 to 4 months. As the oral capsules are filled with active drug encapsulated in small beads, the capsules can be opened and the beads placed in custard, peanut butter, or apple sauce, for administration to children. As the oral solution of itraconazole is better absorbed, a dose of 3mg/kg/day is recommended for children; however, due to use of cyclodextrin to better solubilize itraconazole into solution, diarrhea is more likely to occur with the solution formulation.
In one report, pulse dosing of oral itraconazole was used in treating an eight-month old patient. Itraconazole at a dose of 6.5mg/kg/day was employed for two pulse doses, each lasting one week (a total of two weeks treatment). As far out as eight weeks post-treatment, there were no clinical signs of infection on KOH and fungal cultures were negative. Thus, oral itraconazole appears to be an effective alternative therapy in infants with tinea capitis caused by M. canis, especially given its shorter treatment duration as compared to griseofulvin. Oral itraconazole is not FDA-approved for the treatment of tinea capitis in the United States.
Terbinafine. Oral terbinafine, available as oral granules, is FDA approved for treatment of tinea capitis in children four years of age or older. This agent has also been suggested as an alternative treatment for tinea capitis in children, including cases caused by M. canis. While the effectiveness of oral terbinafine in infants with M. canis-induced tinea capitis has not been extensively studied, there are reports of its use in such cases. Oral terbinafine was used in one infant patient with tinea capitis caused by M. canis and clinical and mycological recovery were achieved when used daily for 3 to 4 weeks.15 However, assessment of available data and case reports suggests that tinea capitis caused by M. canis is more refractory to oral terbinafine as compared to griseofulvin, with the former considered less effective than griseofulvin for this pathogen. The lower efficacy of oral terbinafine for ectothrix scalp infections (i.e., M. canis) in children may be related to the pharmacokinetic properties of the drug. After oral administration, terbinafine accumulates in high concentrations in sebum due to its marked lipophilicity, and thus would be expected to be effective for a dermatophyte infection involving scalp hair follicles. However, as sebaceous glands remain immature and do not develop fully in terms of size and functionality until puberty, access of terbinafine into the follicle is believed to be markedly reduced. Additionally, terbinafine does not penetrate into eccrine sweat after oral administration, which could serve as a potential secondary mode of passive access. Thus, the lack of penetration into eccrine sweat and the low levels of sebum before puberty are viable explanations for the lesser efficacy of oral terbinafine for tinea capitis caused by organisms that produce ectothrix hair invasion (i.e., M. canis).
Based on product labeling in the United States, the dosing of oral terbinafine granules for tinea capitis in children is 125mg/day (<25kg child), 187.5mg/day (25–35kg child), and 250mg/day (>35kg child), administered once daily, with the weight-based dosing recommendations differing slightly from previous reports in published literature with oral terbinafine. For use in children, oral granules can be sprinkled on nonacidic food such as pudding or mashed potatoes.
Although US product labeling suggests a treatment duration of six weeks for tinea capitis, the exact dosing and duration for effective treatment for M. canis has been debated in the literature. In one study, oral terbinafine was shown to be relatively ineffective in treating M. canis tinea capitis for six weeks. In contrast, another study suggests that a six-week course of oral terbinafine is safe, well tolerated and can result in at least an acceptable level of efficacy. Moreover, the study suggests that increases in cure rates may have more to do with increases in dosing, not duration. In regard to duration, some believe that while terbinafine is effective for M. canis, it still requires a longer duration of treatment and suggest the “lack of success is linked to treatment duration rather than drug dosage.” Regardless of the debate, terbinafine has been shown to be effective in M. canis infection and should be considered as a possible alternative given the potential for a shorter duration of treatment, although griseofulvin still remains the preferred treatment over oral terbinafine.
Fluconazole. Although approved for use in children for other types of fungal infections (primarily systemic), oral fluconazole is not FDA-approved for treatment of tinea capitis. However, oral fluconazole is active against dermatophytes and is another option for treatment of tinea capitis in children, available for oral administration as a freshly reconstituted oral suspension or as a tablet (multiple strengths available).[26–28]
The safety of systemic fluconazole use, both oral and intravenous, in the pediatric population (N=562), was evaluated based on data from 12 clinical trials. These studies, in which fluconazole was dosed based on body weight (1–12mg/kg), included predominantly immunocompromised children with severe underlying medical disorders, and with 98.6 percent also receiving a variety of concomitant medications. This assessment concluded that oral fluconazole in the pediatric population was very well tolerated, with the authors stating that “the safety profile of fluconazole in children mirrors the excellent safety profile seen in adults.” Additional studies have demonstrated that oral fluconazole is well tolerated in children treated for tinea capitis.[27,28]
Oral fluconazole 8mg/kg once weekly for 8 weeks was evaluated in an open study of children with tinea capitis. Longer durations of therapy were administered if clinically indicated based on clinical assessment. All cases of T. tonsurans (n=11) responded with clinical and mycological cure (complete cure) to eight weeks of once-weekly oral fluconazole. M. canis was cleared clinically in 12 of 17 cases after eight weeks of once-weekly oral fluconazole, with one case requiring 12 weeks, and three cases requiring 16 weeks to achieve complete cure. Overall, 16 of 17 cases of tinea capitis treated with once-weekly fluconazole were completely cured at eight weeks after completion of oral antifungal treatment.
In a multicenter, triple-blind study, fluconazole 6mg/kg/day for three weeks or fluconazole 6mg/kg/day for six weeks were shown to be comparable in efficacy to oral griseofulvin 11mg/kg/day for six weeks in children with tinea capitis. However, mycological cure rates were only approximately 50 percent in all three treatment groups at the end of treatment. Regardless of the genus and species of causative dermatophyte, the daily dose of oral griseofulvin suggested in this study was too low when using the microsize formulation based on the more common fungal pathogens currently encountered. In addition, a duration of treatment of six weeks or less (in one fluconazole arm) with both agents was also likely to be inadequate in many of the patients, with longer durations of therapy needed in some cases. Oral griseofulvin (microsize) is recommended at a dose of 20 to 25mg/kg/day for a usual duration of 6 to 2 weeks.
Ketoconazole. Oral ketoconazole has been suggested for treatment of dermatophyte infections in cases where griseofulvin is not tolerated. However, due to the higher apparent risk of hepatotoxicity with oral ketoconazole as compared to other oral antifungal agents, reported overall as serum transaminase elevation in 5 to 10 percent of cases and estimation of symptomatic hepatitis in up to 1 in 10,000 patients, the authors do not consider oral ketoconazole to be as prudent an alternative as oral terbinafine, fluconazole, or itraconazole.[30–32]
Use in tinea capitis caused by Trichophyton species including T. tonsurans. When Trichophyton species are implicated, other agents have been shown to be as efficacious as griseofulvin, but with the additional advantage of requiring shorter dosing periods. This advantage is helpful, especially when considering treatment for infants. Again, however, no agent has been specifically approved for treatment in infants by the FDA. In tinea capitis caused by Trichophyton spp in children, the guidelines for European Society of Pediatric Dermatologists note that itraconazole, fluconazole, and terbinafine have “efficacy rates and potential adverse effects similar to those of griseofulvin” and although more expensive, they require shorter dose durations. One report further suggests that “several small studies have shown that short-term terbinafine, itraconazole, and fluconazole therapy were comparable in efficacy and safety to griseofulvin.” The Cochrane report also establishes that there is evidence that terbinafine, dosed based on body weight, for 2 to 4 weeks is effective in the treatment of tinea capitis caused by Trichophyton spp. Terbinafine has been shown to be at least as effective as griseofulvin in Trichophyton-induced tinea capitis in other reports.[5,33,34] In fact, one study noted that terbinafine oral granules achieved a higher complete cure and mycological cure rate than terbinafine oral suspension for T. tonsurans-induced tinea capitis. Thus, in situations in which griseofulvin fails, an adverse reaction results in discontinuation of griseofulvin, or griseofulvin is not an available option, terbinafine, fluconazole, or itraconazole can be considered as viable alternatives in tinea capitis caused by T. tonsurans.
Monitoring considerations when using oral antifungal agents in children with tinea capitis. Overall, oral antifungal therapy has been safe and well tolerated in children with a variety of superficial and systemic fungal infections, including infants with tinea capitis and other mycotic infections in some analyses and case reports.[3–9,11–14,16,20–29] As with any other therapy, especially with a systemic agent, patient monitoring to assess both efficacy and safety is vital to the success of treatment and allows for adjustments in therapy if needed based on clinical response and/or suspicion of adverse reactions.
Clinical monitoring. Clinical monitoring of oral antifungal therapy necessitates obtaining a complete medical history. Suggestions for use or avoidance of some oral agents and monitoring recommendations during treatment relate to the presence of underlying medical disorders, especially pre-existing hepatic or hematological disorders. For example, use of terbinafine oral granules “is not recommended for patients with chronic or active liver disease,” according to approved product labeling.
As a general recommendation, when treating tinea capitis in children, including infants, the authors suggest monthly follow-up appointments to assess tolerability, safety, and clinical response. With regard to education of the parents or legal guardian of the child undergoing treatment, or with patients mature enough to understand, it is important to explain that although most patients experience little to no difficulty with oral antifungal treatment, side effects may occur and are best detected early. Therefore, if the patient complains of any potential side effects, such as frequent, severe, or intractable cephalgia, gastrointestinal upset, an inexplicable feeling of weakness or fatigue without resolution after an adequate rest, or flu-like symptoms, such complaints may reflect an adverse drug reaction and the clinician should be contacted. The same would be true if the patient experienced abdominal discomfort, nausea, vomiting, diarrhea, dizziness, or other symptoms that are “out of step” with the individual’s normal course of behavior. In children and infants too young to express symptoms verbally, changes in behavior, especially poor eating, excessive tiredness, or listless behavior may reflect an adverse drug reaction, as can other gastrointestinal signs such as vomiting or diarrhea.
Laboratory monitoring. There are several publications, including those reviewed and referenced in this article that discuss the use of oral antifungal agents in children with tinea capitis and other superficial fungal infections, with some including use in infants. General recommendations regarding laboratory monitoring guidelines with the use of oral antifungal therapy, including griseofulvin, terbinafine, fluconazole, and itraconazole, appear in the literature, including in approved product labeling, and may serve as a guide to the clinician.[31,32,35–37] Importantly, FDA approval status in pediatric patients for tinea capitis with available oral antifungal agents does not necessarily encompass all clinical situations that the clinician may encounter in clinical practice. Although general monitoring guidelines exist in the literature with the use of oral griseofulvin, terbinafine, fluconazole, and itraconazole, the authors feel that clinical monitoring is of primary importance. The risk of hepatocellular injury or hematological reactions with these agents is low in both adults and children.[31,32,35,36]
With oral griseofulvin, although there was some suggestion of periodic laboratory monitoring in the past, clinical monitoring appears to be sufficient, especially in children with tinea capitis who are without underlying major medical disorders.[31,32,37] The long track record of extensive experience with oral griseofulvin in children with dermatophyte infections (e.g., tinea capitis) for more than four decades supports a very favorable safety profile, with a conspicuous absence in the literature of any new or major side effects that appear to be common.[31,32,37] Overall, it does not appear necessary to routinely perform laboratory monitoring, such as complete blood cell counts (CBC) or serum transaminase testing in children treated with oral griseofulvin for tinea capitis including infants, although in the latter subset experience is more limited. Ultimately, the clinician may elect in individual cases to perform baseline and/or follow-up monitoring if he or she feels that details of the patient history warrant this approach (e.g., major underlying medical disorders, strong parental concern).
General laboratory monitoring guidelines with the use of oral terbinafine (e.g., >4–6 weeks) suggest baseline testing of serum transaminases (e.g., alanine transaminase [ALT]; aspartate transaminase [AST]) and CBC in cases where hematological side effects may be of specific concern or with duration of therapy greater than six weeks. Repeat testing periodically (e.g., after 1 month and after 3 months) during active treatment has also been suggested.[31,32] Specifically, with the use of terbinafine oral granules, which are FDA-approved for treatment of tinea capitis in patients four years of age or older, “pretreatment serum transaminase (ALT and AST) tests are advised for all patients,” according to approved product labeling.35 Notably, aganulocytosis has been reported rarely with oral terbinafine after 4 to 6 weeks of therapy, with an overall estimated incidence of 1 in 400,000.
Monitoring of serum transaminases may also be prudent with itraconazole and fluconazole and are suggested in patients with baseline liver function abnormalities.[32,36] In fact, the risk of clinically relevant hepatic reactions with these agents are low, general guidelines with these agents have not been consistently emphatic, and the available guidelines are not definitive mandates with these agents in otherwise healthy patients.31,32,36 If the clinician elects to perform laboratory monitoring, a reasonable general recommendation is serum transaminase testing at baseline, after one month, after three months, and at three-month intervals thereafter, although such prolonged therapy (e.g., >12–16 weeks) with these agents is not likely to be needed for tinea capitis in children. The decision to perform baseline and repeat serum transaminase testing during treatment of tinea capitis with fluconazole or itraconazole in children and infants is ultimately left to the decision of the clinician along with the patient (or parent/legal guardian when applicable) on a case-by-case basis after discussion of the benefits versus risks of oral antifungal therapy. Additionally, in the presence of underlying major medical disorders of concern, the clinician may elect to monitor more closely, both clinically and through laboratory testing, when treating tinea capitis in children and infants with oral antifungal therapy.
Importantly, as oral ketoconazole does not offer any advantage over the other available oral antifungal agents for treatment of dermatophyte infections (including tinea capitis) and is associated with a higher risk of both symptomatic and asymptomatic hepatotoxicity than other agents, its use is not recommended.[31,32]
With regard to tinea capitis specifically in infants, the relative infrequency of this clinical scenario warrants clinical judgment regarding both clinical and laboratory monitoring with oral antifungal therapy. As stated above, clinical monitoring to assess therapeutic response and tolerability of treatment is of primary importance, with baseline and periodic laboratory monitoring incorporated to support clinical assessment and follow up.
Drug interactions with oral antifungal agents. An extensive review of drug interactions with oral antifungal agents is beyond the scope of this article and is provided in detail elsewhere.[38,39] The vast majority of drugs that are associated with potentially significant interactions with any of the available oral antifungal agents are not commonly used in children, although they may be clinically relevant in selected cases. These include certain antihypertensive or cardiac medications (nifedipine, quinidine, digoxin, metoprolol), some cholesterol-lowering agents (atorvastatin, simvastatin, lovastatin), certain antidepressants (nortrypityline, some selective serotonin reuptake inhibitors [SSRIs]), certain sedative-hypnotic drugs (triazolam), and warfarin. In any event, it is prudent in all patients to “cross check” against their medication list, and to update their medication list at each visit. In children with underlying medical disorders who are likely to be using systemic medications, it is also prudent to exclude potentially significant drug interactions, which vary depending on the oral antifungal agent prescribed.[38,39]
The following two scenarios are examples of notable drug interactions that the clinician may be more likely to encounter when treating children for tinea capitis with certain oral antifungal agents. In these situations, the affected children have specific medical disorders necessitating systemic immuno-suppressive therapy or the child may be undergoing sedation for a procedure. Oral cyclosporine is sometimes used in children with severe atopic dermatitis, severe psoriasis, some autoimmune disorders, and in organ transplant recipients. Serum levels of cyclosporin may be increased by concurrent use of fluconazole or itraconazole.38,39 Also, in children who are undergoing sedation for a surgical procedure, serum levels of the hypnotic agent midazolam may be markedly increased by oral itraconazole, leading to excessive and prolonged sedation.38,39
Adjunctive topical therapies. Adjunctive topical antifungal therapies are also an important consideration in management of tinea capitis, but they are not to be used as monotherapy, as their cure rate is very low for tinea capitis.1–4,7,8,10,11,26 Adjunctive topical antifungal agents (i.e., selenium sulfide 1% or ketoconazole 2%), usually utilized as a shampoo formulation for ease of use especially in children, have been shown to decrease dermatophyte colony counts and shorten the duration of oral antifungal therapy in some cases of tinea capitis.17,19,26,40–42 Shampoos are applied for 5 to 10 minutes before rinsing, with an application frequency of at least three times a week, although daily use is likely to be optimal.17,19,26,40 Lotion, solution, cream, or gel formulations of antifungal agents (i.e., ketoconazole, selenium sulfide, ciclopirox, sulconazole) may also be utilized on the scalp as adjunctive treatment for tinea capitis, but may be harder or messier to use and will likely require more time for application, which may be difficult with children who are less cooperative.
Ketoconazole 2% shampoo used daily for eight weeks has exhibited clinical improvement of tinea capitis caused by T. tonsurans in 15 children 3 to 6 years of age, with culture negativity in 6 of 15 (40%) at Week 8, although use of shampoo therapy alone is not recommended for tinea capitis.[26,40]
Careful hair hygiene should also be practiced. Patients should not share such items as hats, combs, or pillows. Also, in the event a family pet is the source of infection, appropriate treatment of the cat or dog by a veterinarian is recommended.
Tinea capitis is the most common fungal infection seen in children, but is rare in infants. As tinea capitis can look identical to seborrheic dermatitis of the scalp, with the latter very common in infants, and as tinea capitis in infants is rare, is it not surprising that tinea capitis in infancy is often misdiagnosed and improperly treated. The importance of appropriate treatment is essential, especially given the potential long-term sequelae. While the only FDA-approved oral antifungals in children are griseofulvin and terbinafine, no agent has been specifically approved for the treatment of tinea capitis in infants. However, data are available on the use of other oral anitfungal agents, in addition to griseofulvin and terbinafine, for tinea capitis in children, including some cases in infants. Some differences appear to exist in efficacy, suggested daily dose, and duration of therapy among the different oral antifungal agents for tinea capitis depending on the genera and species of dermatophyte and disease severity. Proper diagnosis and identification of the causative fungal pathogen are both important components of optimal management. Ultimately, as tinea capitis may affect both sides of the age spectrum, practitioners are encouraged to employ a heightened awareness of the multiple clinical presentations of tinea capitis and remain cognizant of the fact that tinea capitis can affect any patient at any age. Oral antifungal therapy is needed to eradicate tinea capitis. In addition, adjunctive topical antifungal therapy (e.g., shampoo) may be beneficial in expediting clinical and mycological response, in decreasing the fungal organism load, reducing transmission to others, and mitigating the asymptomatic carrier state on the scalp.
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