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Treatment of Tinea Capitis: Review Article
Treatment of Tinea Capitis: Review Article
a University
of Alabama Birmingham, School of Medicine, Birmingham, AL, USA; b UAB Department of
Dermatology, Dermatology at the Whitaker Clinic, Birmingham, AL, USA; c University of Alabama Birmingham,
Keywords in the United States (US), these surveys found the rate to
Tinea capitis · Griseofulvin · Terbinafine · Itraconazole · be stable [2, 3]. Tinea capitis is caused by dermatophytes
Fluconazole · Adjuvant therapy · Selenium sulfide · that can utilize keratin, the primary component of the
Ketoconazole hair [1]. The causative dermatophytes belong to two gen-
era: Trichophyton and Microsporum [1]. In the earlier half
of the 20th century, Microsporum audouinii was the pre-
Abstract dominant cause of tinea capitis in the US [4]. Currently,
Tinea capitis is a common fungal infection of the hair of the Trichophyton tonsurans is responsible for up to 95% of
scalp affecting predominately prepubertal children. In the cases in the US [5]. Trichophyton violaceum is the domi-
US, griseofulvin has been considered a first-line therapy nant organism in Eastern Europe and South Asia, while
agent for tinea capitis since the 1960s. However, it has been Microsporum canis causes the majority of tinea capitis
falling out of favor due to significant treatment failure, high cases in Africa, Western Europe, Australia, and South
cost, and long duration of treatment. Other antifungal America [4] (Table 1).
agents have been researched as an alternative to griseoful- The clinical manifestations of tinea capitis are classi-
vin. This paper will review the relevant pharmacologic fied as endothrix, ectothrix, or favus. In the endothrix
properties, dosing, cost, efficacy, and adverse events pro- form, hyphae grow down the follicle and penetrate the
file for griseofulvin, terbinafine, itraconazole, fluconazole, hair shaft, then grow completely within the hair shaft.
and some adjuvant therapy options such as selenium sul- This form is caused predominantly by T. tonsurans and
fide shampoos and topical ketoconazole. T. violaceum. In the ectothrix form, the hyphae invade the
© 2019 S. Karger AG, Basel hair shaft at mid follicle. Afterwards, hyphae grow out of
the follicle covering the hair surface. This form is caused
by M. canis, M. audouinii, Microsporum ferrugineum, and
Introduction Trichophyton verrucosum. The hyphae grow parallel to
the hair shaft in favus form then degenerate, leaving long
Tinea capitis is a common fungal infection of the hair tunnels within the hair shaft. Favus form is caused by
of the scalp affecting primarily preadolescents [1]. Recent Trichophyton schoenleinii and is characterized by yellow
surveys of elementary school children in Ohio in 2003 crust around the hair shafts and can result in permanent
and Alabama in 2011 found a prevalence rate of 11% [2, scarring alopecia [1].
3]. Despite concerns about the rise of tinea capitis cases
The dominant organism in US and Central America Africa, Australia, South America, and Western
Europe
Source of infection [1] Anthropophilic Zoophilic
Most commonly cats and dogs
Clinical presentation [82] Less inflammation Scaly, inflamed, with hair loss 2–3 mm or more
Hair loss at scalp level, characterized above scalp
as black dot Broken hair
Most common alopecia pattern [83] Multiple and small Few and can reach large diameter
Infectious pattern [1] Endothrix Ectothrix or mixed
Wood’s lamp exam [82] No fluorescence Yellow-green fluorescence, high specificity but
low sensitivity [84]
Typically resolves by puberty [1] No Yes
The treatment of tinea capitis requires systemic anti- cantly improved with dietary fat intake, which contributes
fungal therapy because topical antifungal agents cannot to the variability of the bioavailability [10]. The drug reach-
penetrate the hair shaft sufficiently to eradicate infection. es the skin through sweat and its hydrophobic properties
Griseofulvin, the former gold standard agent, has been allow it to concentrate in the hair follicle and the stratum
associated with treatment failure; a retrospective review corneum [11]. After the cessation of therapy, griseofulvin
of patients’ medical records revealed a failure rate of concentration is undetected in the stratum corneum with-
39.3% [6]. Consequently, the recommended dose has in 48 to 72 h possibly as a result of reversible protein bind-
been increased from 10–15 mg/kg to 20–25 mg/kg, creat- ing and poor affinity to keratin. It has a terminal half-life
ing an additional challenge and dramatically increased of 9.5–21 h, allowing for once-a-day dosing [4, 10]. The
cost [7]. The only available liquid form of griseofulvin liver metabolizes the majority of the drug through demeth-
comes at a concentration of 125 mg/5 mL, requiring a ylation and glucuronidation reactions [9]. Griseofulvin is
large amount of medicine to achieve the therapeutic dose an inducer of coumarin-type drugs and estrogen but over-
and resulting in increased cost. For instance, the required all has very few drug interactions [12].
dose to treat a 20-kg child, an average 5-year-old in the Griseofulvin has been used since the late 1960s in treat-
US, is 16–20 mL daily for 8 weeks. In addition, the long ing tinea capitis and is considered the gold standard ther-
duration of treatment decreases compliance and further apy [1]. It is listed on the World Health Organization
increases treatment failure. This paper will discuss the (WHO) essential medicines list. However, it is no longer
available antifungal agents that have shown high efficacy available in Canada and some European countries [13]. It
and safety profiles for this common infection. is FDA approved for tinea capitis in children of 2 years and
older with a recommended dosage of 10 mg/kg/day [14].
Many experts view this dose as insufficient due to in-
Griseofulvin creased cases of treatment failure. Therefore, the new rec-
ommended dose is 20–25 mg/kg/day for microsized and
Griseofulvin is a fungistatic agent produced by various 10–15 mg for ultramicrosized preparations for 6–12 weeks
species of the mold Penicillium. It binds microtubules and [7]. Treatment should be continued for 2 weeks after the
inhibits the contraction of the mitotic spindle [8]. Griseo- resolution of clinical symptoms [15]. Long duration of
fulvin is poorly absorbed after an oral dosage. Micronized treatment decreases compliance and contributes to treat-
(Grifulvin V) and ultramicronized (Gris-PEG) prepara- ment failure. Although the ultramicrosized preparation
tions are used to enhance absorption [9]. For micronized can be used at a lower dose, it is not available in an oral
preparations, a peak serum concentration is achieved at suspension formulation. The use of oral tablets is gener-
approximately 4 h after an oral dose. Absorption is signifi- ally not less expensive than the use of oral suspension.
First Year Patients, Country Terbinafine dose, Week Cure Griseofulvin dose, Cure
author n mg/kg/day, of rate, % mg/kg/day, rate, %
and duration therapy and duration
Deng [85] 2011 88 China 3.125–6.25 for 4 weeks 8 78.3 20 for 4 weeks 84.2
Elewski [22] 2008 1,549 International 5–8 for 4 weeks 10 45.1 10–20 for 6 weeks 39.2
Fuller [86] 2001 147 UK 3.125–6.25 for 4 weeks 12 57 10 for 8 weeks 57
Gupta [50] 2001 100 Canada and 3.125–6.25 for 2–3 weeks 12 94 20 for 6 weeks 92
South Africa
Cáceres-Ríos [15] 2000 50 Peru 3.125–6.25 for 4 weeks 12 76 6.25–12.5 for 8 weeks 44
Memisoglu [87] 1999 78 Turkey 3.125–6.25 for 4 weeks 12 38.5 6.25–12.5 for 8 weeks 43.6
Haroon [88] 1995 105 Pakistan 3.125–6.25 for 4 weeks 12 92.9 6.25–12.5 for 8 weeks 79.6
Table 3. Rare adverse events reported with the use of terbinafine due to decreased clearance and lack of safety studies in
for tinea capitis that population. It also should be avoided in patients with
liver disease due to some rare cases of liver failure. Al-
Subacute cutaneous lupus erythematosus [89]
though it is no longer recommended to monitor liver en-
Erythema multiforme [90]
Acute generalized exanthematous pustulosis [91] zymes during terbinafine treatment, physicians are ad-
Stevens-Johnson syndrome [92] vised to obtain a baseline ALT and AST [27]. Terbinafine
Anterior optic neuropathy [93] is the agent of choice in pregnancy, and it is the only sys-
Dermatomyositis [94] temic antifungal used for tinea capitis listed as pregnancy
Autoimmune hepatitis [95]
category B.
Acute fulminant hepatic failure [96]
Long-term taste disturbance [97]
Itraconazole
other Microsporum species [36, 40]. Lipozencic et al. [41] Itraconazole, also known as Sporanox® or Onmel®, is
showed that longer courses of terbinafine do not improve one of the first-generation triazoles. These agents contain
its efficacy against Microsporum species, concluding that three nitrogen atoms in their characteristic five-mem-
terbinafine should not be a first line for tinea capitis infec- bered heterocyclic rings. It exhibits fungistatic properties
tions caused by Microsporum species. In the US, these in- by inhibiting the synthesis of ergosterol and leads to a
fections represent less than 5% of all cases of tinea capitis buildup of its sterol precursors. It interferes with 14-α-
and should be suspected in cases with an ectothrix pattern demethylase, a cytochrome P450-dependent enzyme,
or when contact with infected animals is found [5]. These which inhibits the conversion of lanosterol to 14-demeth-
patients generally fluoresce on Wood’s light exam [1]. Ta- yl lanosterol. Itraconazole oral suspension has a bioavail-
ble 2 lists all the major clinical trials that compared the ability of 60% that can be improved if given after a fatty
use of griseofulvin to the use of terbinafine. meal [43]. A peak plasma concentration is reached within
Oral terbinafine is well tolerated, with most adverse 4 h, but absorption appears to be dose dependent. There-
events being mild and reversible. Therefore, discontinu- fore, higher doses allow for higher plasma concentrations
ation related to adverse events is infrequent and occurs at [1]. More than 99% of the drug travels bound to plasma
a rate of 1.6% based on the largest clinical trial studying proteins. Its lipophilic properties allow it to concentrate
the use of terbinafine in tinea capitis [22]. Post-market in keratinous tissues. Skin concentrations can be several-
surveillance of 25,884 patients reported an adverse event fold higher than plasma and may persist for up to 3 weeks
incidence rate of 10.5%, with gastrointestinal system after discontinuation [44]. In the liver, it is converted to
(4.9%) and skin (2.3%) being the most frequently in- more than 30 inactive metabolites and 1 active metabolite
volved organs [42]. Serious adverse events are rare and known as hydroxyitraconazole [27]. This compound has
are further listed in Table 3. The FDA does not recom- a similar pharmacokinetic profile to itraconazole. The
mend terbinafine use in patients with renal impairment terminal half-life for itraconazole is 20–60 h, which al-
Systemic Recommended dosage for Available forms/dosages Estimated cost for generic, Approximate Cure
agents tinea capitis on the market USD cost to treat tinea rate
capitis in a 20-kg [50]
child, USD
lows for once-a-day dosing. In contrast to griseofulvin formulation. In animal models, they have been associated
and terbinafine, most of the drug and its metabolites are with reports of nephrotoxicity and tumorigenicity, but
excreted in feces, not urine. Therefore, no dose adjust- there is no evidence to support these adverse events in
ment is needed for patients with renal impairment [45]. humans [47]. Pulse therapy of one-pulse of 5 mg/kg/day
It is metabolized in the liver by CYP3A4 and interacts for 1 week with 2 weeks off between the first and second
with many clinically important agents such as warfarin, pulses and 3 weeks off between the second and third puls-
antihistamines, antipsychotics, anxiolytics, digoxin, ci- es has also been shown to be effective in treating tinea
closporin, and simvastatin. capitis including infections caused by M. canis [48, 49].
Despite being the most popular agent for tinea capitis According to a systemic review and a meta-analysis,
in some European countries, itraconazole is not approved itraconazole and terbinafine are the most effective agents
for this indication in the US [29]. However, it is approved in treating Trichophyton infections and have a similar ef-
for nail onychomycosis [46]. It comes in three formula- ficacy [16, 40]. A study has found terbinafine for 2 weeks
tions: oral solution, capsule, and tablets. The recom- to be superior in treating T. tonsurans when compared to
mended dose for tinea capitis is 5 mg/kg/day (Table 4), 2 weeks of itraconazole (91.1 vs 80%) [50], while in an-
and the duration varies based on causative agent: 2–4 other study, 2 weeks of itraconazole was found to be su-
weeks for T. tonsurans and 4–6 weeks for M. canis [1, 16]. perior in treating T. violaceum than 2 weeks of terbinafine
For young children, the capsule can be opened or chewed. [51]. However, these studies are small and there are no
The recommended dose for oral solution is 3 mg/kg/day large clinical trials published until this date to compare
due to improved bioavailability. However, there are safe- these two agents, making it inappropriate to conclude.
ty concerns associated with a compound, hydroxypropyl- Regarding its use in treating tinea capitis due to M. canis,
β-cyclodextrins (CDs), used to enhance solubility in this two studies with a total of 270 patients demonstrated a