Tinea capitis

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[level-membership-for-dermatology-category]

Tinea capitis

Elisabeth M. Higgins

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Tinea capitis (scalp ringworm) is the term used to describe a fungal infection of the scalp caused by dermatophyte species. Infections may be passed from person to person (so-called anthropophilic, in which man is the primary host) or acquired from animals (zoophilic). Several different species of fungi may be responsible, predominantly Microsporum and Trichophyton species, and can be identified by their varied characteristics on microscopy and culture. Species that invade only the inside of the hair shaft are termed endothrix infections, whereas those that invade both the inside and the outside of the hair shaft are responsible for ectothrix infections. The disease is most prevalent in children and usually presents with areas of scaling and alopecia, with a varying degree of inflammation. There may be associated cervical lymphadenopathy. Some species of dermatophyte induce a very inflammatory, pustular reaction, which may lead to scarring and permanent alopecia. However, this is fortunately relatively rare with modern treatment regimens, in which full regrowth of hair is the norm.

Management strategy

Treatment of tinea capitis is aimed at eradicating the organism to prevent the spread of infection and minimize scarring. Established infections cannot be treated topically and oral therapy is required. In many countries, including the UK, griseofulvin remains the only licensed oral antifungal agent for use in tinea capitis in children. Although only weakly fungistatic, griseofulvin is effective in the treatment of most varieties of tinea capitis, but may need to be given in high doses over a prolonged period. Each case should be monitored to ensure adequate treatment and eradication of the organism. Traditionally this has been done using Wood’s light examination, but this is only viable in cases due to species that fluoresce (e.g., Microsporum infections). An increasing number of cases in the UK and North America today are due to the emergence of Trichophyton tonsurans, a non-fluorescent endothrix species. Treatment response therefore has to be followed mycologically, by sending specimens to the laboratory. Mycological cure should be the gold standard of treatment.

In recent years the azoles itraconazole, ketoconazole, and fluconazole, and the allylamine terbinafine have become available for systemic use. Many studies have demonstrated that these agents have at least equal efficacy to griseofulvin in a variety of types of tinea capitis, and treatment times are often shorter. Although these agents are more expensive, shorter treatment regimens may help compliance and reduce the spread of infection.

Over the past decade, the use of intermittent or pulsed treatment regimens using fluconazole or itraconazole have been explored. This treatment strategy is based on the long half-life of the drugs in keratin. Such regimens do not appear to confer any benefit in terms of cure rates, but may reduce the total cost of treatment.

There are variations in the response of different dermatophyte species to the different antifungal agents, and treatment should be tailored accordingly. Overall, griseofulvin appears superior in the clearance of Microsporum infections, but newer agents appear more effective against Trichophyton. Itraconazole probably has the broadest spectrum of action. However, so far no agent has been shown to achieve a 100% cure rate. Ectothrix infections are generally caused by Microsporum species, most notably the zoophilic M. canis or the anthropophilic M. audouinii, and almost always occur in children. Griseofulvin remains the standard treatment at a dose of 10–20 mg/kg/day, but clearance may be slow and treatment should be continued for as long as necessary, which is at least 6 weeks, but may be 12–16 weeks, and monitored as outlined above. Itraconazole may be considered an alternative. Although there are licensing restrictions in some countries, it has now superseded griseofulvin as the treatment of choice in parts of Europe.

Endothrix infections, most commonly with T. tonsurans or T. violaceum, are more prevalent in children, but may occasionally occur in adults (usually the contacts/carers of children). Higher-dose regimens of griseofulvin tend to be required to achieve cure. The newer azoles and terbinafine appear to achieve cure more rapidly (usually in 4 weeks). In adults with tinea capitis due to Trichophyton species, terbinafine 250 mg/day for 4 weeks is the treatment of choice. Although unlicensed in children, the current British National Formulary gives the dosing schedule for terbinafine in children, in recognition of its widespread use in tinea capitis in this age group (<20 kg, 62.5 mg/day; 20–40 kg, 125 mg/day; >40 kg, 250 mg/day). Current evidence suggests that either this or itraconazole should become the treatment of choice in children with Trichophyton infections. Both drugs are now licensed for use in children in several different countries, and have replaced griseofulvin, which is no longer available in some European countries.

Topical antifungal creams and shampoos are sometimes used in conjunction with oral therapy, with the aim of reducing patient infectivity, but have no role in prophylaxis.

In the current urban epidemics of T. tonsurans, asymptomatic infection in household contacts is posing a significant problem in re-infection/relapse, and there is merit in screening all family members (including adults) where practical, to reduce re-infection rates.

Specific investigations

First-line therapies

imageGriseofulvin A
imageTerbinafine A
imageItraconazole A

Meta-analysis of randomized controlled studies comparing griseofulvin and terbinafine in the treatment of tinea capitis.

Tey HL, Tan AS, Chan YC. J Am Acad Dermatol 2011; 64: 663–70

A pooled analysis of seven studies, involving 2163 subjects, revealed no overall difference in efficacy between 8 weeks (range 6–12 weeks) griseofulvin and 4 weeks (range 2–6 weeks) terbinafine, but the latter had shorter treatment regimens (odds ratio=1.22 in favor of terbinifine; 95% CI=0.785–1.919; p=0.37). However, sub-analysis by species shows terbinafine has significantly greater efficacy against T. tonsurans (odds ratio=1.49; 95% CI=1.274–2.051; p<0.001). In contrast, griseofulvin was superior in the treatment of Microsporum species (odds ratio in favour of griseofulvin 0.48, 95% CI 0.254–0.656; p<0.001).

Terbinafine is superior in the treatment of T. tonsurans; griseofulvin is more effective in the treatment of Microsporum species, but the treatment course is longer. Both drugs are well tolerated in children.

Terbinafine hydrochloride oral granules versus oral griseofulvin suspension in children with tinea capitis: results of two randomised investigator-blinded, multicenter, international, controlled trials.

Elewski BE, Cáceres HW, Deleon L, El Shimy S, Hunter JA, Korotkiy N, et al. J Am Acad Dermatol 2008; 59: 41–54.

A multicenter, investigator-blinded, randomized controlled study comparing 6 weeks’ treatment with griseofulvin 10–20 mg/kg/day (n=509) with terbinafine 5–8 mg/kg/day (n=1040) in children with microscopy-proven tinea capitis. Complete cure rates (45.1% vs 33.01%) and mycological cure (61.55% vs 55.5%) were significantly higher for terbinafine than for griseofulvin (p<0.05), even at higher doses (>20 mg/kg/day). Subgroup analysis revealed that terbinafine was significantly better than griseofulvin for all cure rates (clinical, mycological, and complete) in T. tonsurans infection but not for M. canis (p<0.001). In contrast, for M. canis, mycological and clinical cure rates were significantly better with griseofulvin (p<0.05). Fifty percent of patients in each group reported mild side effects with treatment, but there was no significant effect on liver transaminases.

This largest pediatric study to date highlights the safety and efficacy of a new formulation of terbinafine in the treatment of tinea capitis in children. However, limitations of the study included not using a standard dose of griseofulvin in each center, inconsistency in the use of adjuvant topical therapy, and the inclusion of more than one causal species. Sub-analysis shows a clear differentiation in response rates between organisms, and therapy should probably be tailored, with terbinafine being the treatment of choice in T. tonsurans infection, while griseofulvin is superior in Microsporum infections.

Systemic anti-fungal therapy for tinea capitis in children.

González U, Seaton T, Bergus G, Jacobson J, Martínez-Mónzon C. Cochrane Database Syst Rev 2007; 4: CD004685.

An analysis of 21 randomized control trials involving 1812 subjects under the age of 18 years, in which systemic antifungal therapy was used in mycologically proven tinea capitis. In view of varying susceptibilities, studies were evaluated according to the causal organism. For Trichophyton species: terbinafine given on a weight-related dosage schedule for 4 weeks showed similar efficacy to griseofulvin given for 8 weeks in three studies involving 382 subjects (RR 1.09; 95% CI 0.95–1.26). Itraconazole and griseofulvin given for 6 weeks showed similar cure rates in a study of 35 children (RR 1.06; 95% CI 0.81–1.39). However, itraconazole given for short periods may also be as effective as griseofulvin given for 6 weeks (RR 0.89; 95% CI 0.76–1.04), and both itraconazole and terbinafine given for 2 to 3 weeks were equally effective in two studies involving 160 participants (RR 0.93; 95% CI 0.72–1.19). For Microsporum species: overall, no difference was found between the efficacy of griseofulvin and that of terbinafine in clearance of Microsporum infections, but there was little evidence on the use of systemic agents in this species that met the study inclusion criteria.

The authors conclude that terbinafine and itraconazole are probably preferable to griseofulvin in the treatment of Trichophyton tinea capitis because of the shorter treatment duration, even though these agents are more expensive and may not always be available in a pediatric formulation.

Second-line therapies

imageFluconazole B
imageShort-duration terbinafine B
imageShort-duration itraconazole B

Comparative evaluation of griseofulvin, terbinafine and fluconazole in the treatment of tinea capitis.

Grover C, Arora P, Manchanda V. Int J Dermatol 2012; 51: 455–8.

A prospective, non-blinded cross-sectional study of 75 children comparing griseofulvin, terbinafine, and fluconazole in the treatment of tinea capitis (predominantly T. violaceum) revealed cure rates of 96%, 88%, and 84%, respectively. Seven patients required more prolonged therapy, but all three drugs were well tolerated.

Although well tolerated, fluconazole had comparatively lower cure rates in this population, and therefore appears to confer no advantage over standard protocols using griseofulvin. However, some patients required prolonged treatment and these may have been due to infections with other species, but full sub-analysis by drug and organism was not undertaken due to the small numbers involved.

Therapeutic options for the treatment of tinea capitis caused by Trichophyton species: griseofulvin versus the new oral antifungal agents, terbinafine, itraconazole and fluconazole.

Gupta AK, Adam P, Dlova N, Lynde CW, Hofstader S, Morar N, et al. Pediatr Dermatol 2001; 18: 433–8.

A multicenter prospective, randomized single-blinded study of 200 children comparing the efficacy of griseofulvin (20 mg/kg/day for 6 weeks), terbinafine (62.5–250 mg/day according to weight for 2 weeks), itraconazole (5 mg/kg/day for 2 weeks), or fluconazole (6 mg/kg/day for 2 weeks). Patients on the shorter regimens were evaluated 2 weeks after the end of treatment and given an extra week of treatment if clinically indicated. All children had either T. tonsurans or T. violaceum infection. Evaluation at 12 weeks revealed no significant difference in the mycological cure rates between the groups (92% for griseofulvin, 94% for terbinafine, 86% for itraconazole, and 84% for fluconazole (p<0.33)). However, side effects (mostly nausea and gastrointestinal upset) were only noted in the griseofulvin group.

This study shows that short-duration therapy with itraconazole, fluconazole, and terbinafine is as effective as high-dose standard-duration griseofulvin in the treatment of Trichophyton tinea capitis, and newer agents appear better tolerated.

Once weekly fluconazole is effective in children in the treatment of tinea capitis: a prospective multi-centre study.

Gupta AK, Dlova N, Taborda P, Morar N, Taborda V, Lynde CW, et al. Br J Dermatol 2000; 142: 965–8.

An open, multicenter assessment of 61 children treated with oral fluconazole 8 mg/kg once weekly for 8 weeks (extended for a further 4 weeks if clinically indicated). Causal organisms were T. violaceum (n=33), T. tonsurans (n=11), and M. canis (n=17). All 44 children with Trichophyton infections had mycological and clinical cure at 16 weeks after the start of treatment; the majority (35/44) only required 8 weeks of therapy, but nine out of 33 of the T. violaceum group required treatment for 12 weeks. Twelve out of 17 of the M. canis group were clinically clear after 8 weeks. Treatment was extended for a total of 12 weeks in one and 16 weeks in three patients, but overall 16 of 17 children in this group had complete cure 2 months after the end of therapy. One child had asymptomatic and reversible elevation of liver function tests.

Short duration treatment with terbinafine for tinea capitis caused by Trichophyton or Microsporum species.

Hamm H, Schwinn A, Brautigan M, Weidinger G. Br J Dermatol 1999; 140: 480–2.

A double-blind study of 35 children comparing the efficacy of 1 or 2 weeks of oral terbinafine, 62.5–250 mg/day according to weight. Patients were followed up for 12 weeks and non-responders were given an additional 4 weeks of therapy. Twenty-three children had Trichophyton infections (n =12 with T. tonsurans infection) and 12 had M. canis infection; cure rates after 1 and 2 weeks of therapy were 86% and 56%, respectively. However, only one of the 12 children with Microsporum infection responded initially, although a further four cleared with 4 more weeks of treatment.

Short-duration (2 weeks) and intermittent treatment regimens show remarkable clearance rates, particularly in infections with Trichophyton species, and may offer a significant cost saving.

Third-line therapies

image2% ketoconazole B
imageSelenium sulfide shampoo B
imagePrednisolone B

A randomised comparative trial of treatment of kerion celsi with griseofulvin plus oral prednisolone vs. griseofulvin alone.

Hussain I, Muzzafar F, Rashid T, Jahangir M, Haroon TS. Med Mycol 1999; 37: 97–9.

A randomized study of 30 patients with scalp kerion comparing treatment with griseofulvin and prednisolone to griseofulvin alone. Evaluation at 12 weeks revealed similar cure rates in both groups.

Although traditionally many clinicians have used prednisolone to reduce the inflammation of kerions, in an effort to minimize scarring and hence the possibility of permanent alopecia, the limited evidence that exists does not support its use. Kerion formation is not uncommon in the current spate of T. tonsurans infections in the UK. However, scarring is exceptionally rare and full regrowth of hair can be expected after appropriate oral antifungal therapy alone.

Prophylactic ketoconazole shampoo for tinea capitis in a high risk pediatric population.

Bookstaver PB, Watson HJ, Winters SD, et al. J Pediatr Pharmacol Ther 2011; 16: 199–203.

A retrospective analysis of 97 vulnerable children considered at high risk of tinea capitis showed no benefit from twice weekly use of 2% ketoconazole shampoo in the prevention of infection.

These small studies support the use of an antifungal shampoo to reduce surface counts of the organism, and therefore aid clearance and possibly reduce the risk of transmission. If systemic therapy is contraindicated or unavailable, there may be a limited benefit in using 2% ketoconazole shampoo alone. However, shampoos have not been shown to prevent infection, even in vulnerable subjects, and therefore have no place in prophylaxis.

[/level-membership-for-dermatology-category][not-level-membership-for-dermatology-category]

Tinea capitis

Elisabeth M. Higgins

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Tinea capitis (scalp ringworm) is the term used to describe a fungal infection of the scalp caused by dermatophyte species. Infections may be passed from person to person (so-called anthropophilic, in which man is the primary host) or acquired from animals (zoophilic). Several different species of fungi may be responsible, predominantly Microsporum and Trichophyton species, and can be identified by their varied characteristics on microscopy and culture. Species that invade only the inside of the hair shaft are termed endothrix infections, whereas those that invade both the inside and the outside of the hair shaft are responsible for ectothrix infections. The disease is most prevalent in children and usually presents with areas of scaling and alopecia, with a varying degree of inflammation. There may be associated cervical lymphadenopathy. Some species of dermatophyte induce a very inflammatory, pustular reaction, which may lead to scarring and permanent alopecia. However, this is fortunately relatively rare with modern treatment regimens, in which full regrowth of hair is the norm.

Management strategy

Treatment of tinea capitis is aimed at eradicating the organism to prevent the spread of infection and minimize scarring. Established infections cannot be treated topically and oral therapy is required. In many countries, including the UK, griseofulvin remains the only licensed oral antifungal agent for use in tinea capitis in children. Although only weakly fungistatic, griseofulvin is effective in the treatment of most varieties of tinea capitis, but may need to be given in high doses over a prolonged period. Each case should be monitored to ensure adequate treatment and eradication of the organism. Traditionally this has been done using Wood’s light examination, but this is only viable in cases due to species that fluoresce (e.g., Microsporum infections). An increasing number of cases in the UK and North America today are due to the emergence of Trichophyton tonsurans, a non-fluorescent endothrix species. Treatment response therefore has to be followed mycologically, by sending specimens to the laboratory. Mycological cure should be the gold standard of treatment.

In recent years the azoles itraconazole, ketoconazole, and fluconazole, and the allylamine terbinafine have become available for systemic use. Many studies have demonstrated that these agents have at least equal efficacy to griseofulvin in a variety of types of tinea capitis, and treatment times are often shorter. Although these agents are more expensive, shorter treatment regimens may help compliance and reduce the spread of infection.

Over the past decade, the use of intermittent or pulsed treatment regimens using fluconazole or itraconazole have been explored. This treatment strategy is based on the long half-life of the drugs in keratin. Such regimens do not appear to confer any benefit in terms of cure rates, but may reduce the total cost of treatment.

There are variations in the response of different dermatophyte species to the different antifungal agents, and treatment should be tailored accordingly. Overall, griseofulvin appears superior in the clearance of Microsporum infections, but newer agents appear more effective against Trichophyton. Itraconazole probably has the broadest spectrum of action. However, so far no agent has been shown to achieve a 100% cure rate. Ectothrix infections are generally caused by Microsporum species, most notably the zoophilic M. canis or the anthropophilic M. audouinii, and almost always occur in children. Griseofulvin remains the standard treatment at a dose of 10–20 mg/kg/day, but clearance may be slow and treatment should be continued for as long as necessary, which is at least 6 weeks, but may be 12–16 weeks, and monitored as outlined above. Itraconazole may be considered an alternative. Although there are licensing restrictions in some countries, it has now superseded griseofulvin as the treatment of choice in parts of Europe.

Endothrix infections, most commonly with T. tonsurans or T. violaceum, are more prevalent in children, but may occasionally occur in adults (usually the contacts/carers of children). Higher-dose regimens of griseofulvin tend to be required to achieve cure. The newer azoles and terbinafine appear to achieve cure more rapidly (usually in 4 weeks). In adults with tinea capitis due to Trichophyton species, terbinafine 250 mg/day for 4 weeks is the treatment of choice. Although unlicensed in children, the current British National Formulary gives the dosing schedule for terbinafine in children, in recognition of its widespread use in tinea capitis in this age group (<20 kg, 62.5 mg/day; 20–40 kg, 125 mg/day; >40 kg, 250 mg/day). Current evidence suggests that either this or itraconazole should become the treatment of choice in children with Trichophyton infections. Both drugs are now licensed for use in children in several different countries, and have replaced griseofulvin, which is no longer available in some European countries.

Topical antifungal creams and shampoos are sometimes used in conjunction with oral therapy, with the aim of reducing patient infectivity, but have no role in prophylaxis.

In the current urban epidemics of T. tonsurans, asymptomatic infection in household contacts is posing a significant problem in re-infection/relapse, and there is merit in screening all family members (including adults) where practical, to reduce re-infection rates.

Specific investigations