June 2000
With a newer generation of antifungal agents now available, pediatricians should re-examine the treatment and management of tinea capitis in their young patients.
Gone are the days of telling parents to keep their children with this infection out of the classroom until regrowth of hair is complete. Such advice is impractical, explained members of a consensus panel on t. capitis, which convened recently in Chicago. An important epidemiological reason that this advice is impractical is that shedding of spores can continue for three to five weeks, despite treatment since spores may be resistant to some therapies. Panel members agreed that a higher frequency of spore transmission has been documented among children in close physical contact, prolonged contact or both, rather than among classmates.
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"The most common place for close, prolonged contact is the household," said Paul J. Honig, MD, director of pediatric dermatology at the Children's Hospital of Philadelphia. "In fact, data from several studies have indicated that the home may be an even more important source for the spread of infection than the school."
Recent studies have documented the presence of pathogenic organisms in asymptomatic individuals, according to Ilona J. Frieden, MD, clinical professor in the departments of dermatology and pediatrics at the University of California-San Francisco School of Medicine. She noted that most studies have found prevalence rates of approximately 15% for recovery of viable spores from clinically noninfected classmates and family members. Furthermore, asymptomatic carriage has been demonstrated in both adults and children living with an index case of t. capitis.
T. capitis often is not suspected in adults, Honig said, and therefore, goes untreated. "Adults are less likely to be receiving treatment. This asymptomatic carrier state has been shown to persist in 10% to 25% of untreated individuals for as long as six weeks to eight months." Based on these findings, Honig recommended a systematic assessment when evaluating a school outbreak of t. capitis.
When dealing with an outbreak of t. capitis, understand the variations in causative pathogens within different geographic areas and how the distribution has changed and has resulted in different presentations. For example, according to Raza Aly, PhD, professor of dermatology and microbiology-immunology at the University of California-San Francisco, Trichophyton tonsurans appears to have supplanted Microsporum audouinii and Microsporum canis is the primary etiologic agent in the United States.
"By the early 1980s, T. tonsurans was the source of approximately 90% of t. capitis cases at a large dermatology clinic in Brooklyn," he said. "In a survey conducted at the dermatology clinic of the University of California, San Francisco, in the 1970s, 60% of cases were due to T.tonsurans, but results of a second survey conducted from 1986 to 1993 documented that the incidence of scalp infections caused by T.tonsurans had increased to 91%."
This changing epidemiology affects how the diagnosis is made. Wood's light examination, which traditionally has been used to diagnose infection caused by Microsporum sp., is not suitable for diagnosing t. capitis caused by T. tonsurans. "T. tonsurans results in an endothrix infection that does not fluoresce," explained Aly. Potassium hydrochloride preparation may be used for diagnosis, but it often is difficult to interpret, and there may be false negatives in early or inflammatory lesions.
Culture is the gold standard for diagnosing t. capitis. Aly recommended running a toothbrush over the patient's scalp approximately 10 times to collect infected scale and debris that then is placed on appropriate culture media. "It is probably the best diagnostic technique for both symptomatic and asymptomatic children, because the procedure is painless and nonthreatening, and it samples a wide area of the scalp," he said.
Not only have the diagnostic techniques changed, but so have the treatment options. Historically, griseofulvin was the drug of choice. However, there is increasing evidence that griseofulvin does not always work and often requires long treatment periods.
The dosing of griseofulvin for t. capitis has steadily increased over the past 20 years. Therefore, three newer classes of oral agents are being investigated: azoles, triazoles, and allylamines.
"Griseofulvin, ketoconazole [Nizoral, Janssen], itraconazole [Sporanox, Janssen] and fluconazole [Diflucan, Pfizer] are fungistatic agents; terbinafine [Lamisil, Novartis] is fungicidal," explained Kevin C. Hazen, PhD, director of clinical microbiology and associate professor of pathology and microbiology at the University of Virginia Health Sciences Center. "However, even though they are not fungicidal, the azoles and triazoles can achieve in vitro killing."
He asserted that itraconazole and fluconazole are capable of inhibiting growth of dermatophytes at drug levels that are achieved within nails and statuary corneum. Terbinafine is fungicidal, and in vitro killing is faster than with other agents. This finding implies that the other agents must remain at high levels at the site of infection in vivo for a longer time than required with terbinafine.
With prolonged incubation, the organism may become more tolerant of fluconazole and itraconazole. "Based on its mechanism of action, terbinafine, with its anticipated rapid killing rate and fungicidal activity, appears to be more likely to prevent disease recurrence than the azoles or griseofulvin," said Hazen. Thus, shorter treatment periods may be more likely with terbinafine.
Effective treatment of t. capitis with griseofulvin requires weeks or months of continuous oral therapy. This may be particularly true for M. canis because evidence shows that this dermatophyte is less sensitive to the newer antifungal agents than T. tonsurans. Longer treatment courses raise concerns about noncompliance and adverse effects, key considerations particularly when prescribing for children. Effective treatment time for terbinafine and the azoles has yet to be established.
In addressing the issue of noncompliance, Sheila Fallon Friedlander, MD, said that itraconazole, fluconazole, and terbinafine have been shown to compartmentalize in skin, nails and hair, leading to a reservoir that maintains therapeutic levels of drugs in these tissues long after discontinuation of therapy. This enhances compliance by shortening the duration of therapy. Adjunctive therapy with shampoos containing selenium sulfide, zinc pyrithione and providone iodine can also help eradicate spores from the scalp surface.
The flexibility of dosage form can affect compliance. Friedlander, assistant professor in the department of pediatrics and medicine, division of dermatology at the University of California-San Diego School of Medicine and Children's Hospital, reported that griseofulvin is available in suspension and tablets, as is fluconazole.
Small children prefer the liquid form, but taste has been an issue with these formulations. Itraconazole offers suspension and capsule formulations, but the liquid formulation contains cyclodextrin, which is not recommended for pediatric use. Some have suggested that the capsule formulation may work well with young patients, as it can be opened and easily mixed with food. In contrast to itraconazole suspension, which is indicated only for adults, fluconazole suspension is approved for children 6 months of age and older. Terbinafine is a tablet that can be split and mixed into food.
"Side effects with griseofulvin are generally uncommon," reported Jeffrey L. Blumer, PhD, MD, "especially when the drug is ingested with meals." Headache is the most frequent, but it usually disappears with continued use. Side effects that occur infrequently involve the skin and the gastrointestinal, nervous, genitourinary and musculoskeletal systems. Blumer is with the departments of pediatrics and pharmacology at Case Western Reserve University and the division of pediatric pharmacology and critical care at Rainbow Babies and Children's Hospital of University Hospitals, Cleveland.
He noted that the predominant adverse effects associated with itraconazole, fluconazole, ketoconazole and terbinafine are gastrointestinal, typically nausea and vomiting.
Friedlander pointed out that there is a potential for drug interactions with fluconazole and itraconazole, because they affect the cytochrome P450 3A4 enzyme system. "The concurrent use of itraconazole and nonsedating antihistamines is absolutely contraindicated. Significant drug interactions also may occur with cisapride (Propulsid, Janssen), digoxin and midazolam [Versed, Roche]," she noted. "Because terbinafine does not affect the 3A4 subset of the cytochrome P450 enzyme system as the triazoles, drug interactions are not a major concern with this agent."
However, Friedlander added that the plasma concentrations of rifampin and cimetidine might be affected by terbinafine, although the changes are not clinically significant. Terbinafine may cause cyclosporine levels to fluctuate, but the differences are less than 20%, which are not clinically relevant.
When choosing any new antifungal agent to treat t. capitis, remember these drugs are not yet indicated for such use. Nonetheless, the best available data do support the safety and efficacy of the newer antifungals.
For more information:
- Wilmington M, Aly R, Frieden IJ. Trichophyton tonsurans tinea capitis in the San Francisco Bay area: increased infection demonstrated in a 20-year survey of fungal infections from 1974 to 1994. J Med Vet Mycol. 1996;34:285-287.
- Laude TA, Shah BR, Lynfield Y. Tinea capitis in Brooklyn. Am J Dis Child. 1982;136:1047 -1050.
- Aly R. Incidence of dermatophytes in the San Francisco Bay area. Dermatologica. 1980;161:97-100.
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