Cochrane review on systemic treatments for tinea capitis in children

1
Cochrane review on systemic treatments for tinea
capitis in children

• González U, Seaton T, Bergus G, Martínez C
  and Pinart M.
• Research Unit for Evidence-based Dermatology.
• Department of Dermatology. Clínica Plató.
  Barcelona. SPAIN.
• St. Louis College of Pharmacy. USA.
• Department of Family Medicine. University of
  Iowa. USA.

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• Tinea capitis (scalp ringworm) is an infection
  of the scalp skin and hair caused by fungi
  (dermatophytes)

endothrix
ectothrix
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• The clinical hallmark is single or multiple
  patches of hair loss, sometimes with a black
  dot pattern, which may be accompanied by signs
  of inflammation such as scaling, pustules and
  itching.

4

• Tinea capitis is very contagious and can be
  transmitted by people, animals or objects
  carrying the fungus

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• Although it is not life-threatening in people
  with normal immunity, if left untreated there may
  be persistent symptoms and / or permanent
  baldness

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• Tinea capitis always requires systemic
  medication
• Topical measures are only used as
• adjuvant therapy

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• Tinea capitis is uncommon in adults and is seen
  predominantly in children of some urban
  communities

Tinea capitis is the most common dermatophytosis
of children and is increasing in prevalence
worldwide
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FAST !
SAFE !
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• The primary aim of treatment in tinea capitis is
  to achieve complete clinical and mycological cure
  as quickly as possible with minimal adverse
  effects.

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• Griseofulvin (?)
• The most widely used treatment for tinea capitis
• Inexpensive
• Licensed
• Tablet and liquid formulation
• (accurate dosage in children)

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• Griseofulvin (?)
• Fungistatic
• At least 2 months (8-10 weeks), compliance is a
  problem
• Should be taken with meals
• Bitter
• 10-25 mg/Kg/day
• Nausea and rashes (8-15 )

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• New drugs being used against other fungal
  infections (mainly in adults)
• Itraconazole
• Terbinafine
• Fluconazole
• Pharmacological data exist to make them suitable
  for treating tinea capitis in children.

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• Cochrane systematic review
• Objetive
• To assess the effects of systemic anti-fungal
  drugs for tinea capitis in children

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• Selection criteria
• Randomised clinical trials
• Systemic interventions
• Patients with normal immunity under 18
• Tinea capitis confirmed by microscopy and/or
  culture.

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RCTs (to April 2007)

• 25 initially
• 3 excluded
• 22 RCTs 2692 patients
• Countries Asia, Europe, America, Africa and
  Oceania

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• Terbinafine
• Fungicidal
• Not licensed
• No liquid formulation
• 3-6 mg/Kg/day
• Gastrointestinal disturbances and rashes (3-5)

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• Terbinafine (4 weeks) compared to griseofulvin
  (8 weeks) had similar efficacies in Trichophyton
  infections
• 3 RCTs (Canada-South Africa, United Kingdom,
  Pakistan)
• RR 1.09, 95 CI 0.95, 1.26

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• In Microsporum species, griseofulvin appeared to
  work better than terbinafine in one small trial
• 1 RCT (United Kingdom)
• RR 0.64, 95 CI 0.19, 2.20
• Administering terbinafine for longer than 4
  weeks does not improve efficacy rates

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• Itraconazole
• Fungistatic and fungicidal
• Not licensed
• Liquid formulation
• 5 mg/Kg/day
• Pulsed shorter regimens?
• Interactions (antihistamine, phenytoin,
  rifampicin, )
• Gastrointestinal complains, headache and rashes

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• When comparing itraconazole to griseofulvin,
  both for 6 weeks, they have similar high efficacy
  rates at week 12 of follow-up
• 1 RCT (Spain)
• RR 1.06, 95 CI 0.81, 1.39
• Itraconazole for 2 weeks has slightly worst
  efficacy rates than Griseofulvin for 6 weeks
• 1 RCT (Canada-South Africa)
• RR 0.89, 95 CI 0.76, 1.04

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• Concerning Trichophyton species, there was no
  difference between itraconazole and terbinafine
  for treatment periods lasting 2-3 weeks
• 2 RCTs (Canada-South Africa, and Pakistan)
• RR 0.93, 95 CI 0.72, 1.19

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• Fluconazole
• Fungistatic
• Not licensed
• 5-6 mg/Kg/day
• Liquid and tablet formulation
• Gastrointestinal complains, headache and rashes
  (16)

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• Fluoconazole 5-6 mg/Kg/day (2-4 weeks) in
  Trichophyton infections is comparable to 6 weeks
  of griseofulvin.
• 2 RCTs (Canda- South Africa, and Iran)
• RR 0.92 95 CI 0.80, 1.05
• When fluoconazole was given in higher doses (6
  mg) in Trichophyton infections the clinical
  improvement occurred slightly quicker.
• No studies for Microsporum infections

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• A RCT (Foster 2005) evaluated 880 patients (USA,
  Guatemala, Chile, Costa Rica and India) who where
  infected mainly with T. tonsurans and M. canis
  which accounted for 86 and 11 of the isolates.
• Fluconazole 6mg/kg/day for 3 and 6 weeks
• Griseofulvin 11mg/kg/day for 6 weeks
• Complete cure at week 10 was seen in 98/302
  (32.5), 111/286 (38.8) and 92/292 (31.5)
  patients in the fluconazole 3-week, fluconazole
  6-week and griseofulvin group, respectively.

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• One of the disadvantages of using the newer
  agents for tinea capitis is that not all are
  available in paediatric dosage formulations,
  which may worsen compliance.

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• All these anti-fungal drugs reviewed have
  reasonable safety profiles in children.

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• Newer azole agents are expensive, and cost is a
  concern in developing countries and poor
  comunityes where the prevalence of tinea capitis
  is high

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• RCT, single-blind study of a inexpensive, safe
  and easily implemented intervention in a poor
  community outside Cape Town (South Africa)
• (BAD Annual Meeting 2006)
• weekly high-dose intermittent regimen of
  griseofulvin was as effective and as safe as a
  daily low-dose regimen

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• 64 patients (50 boys from 4-12 years) with
  Trichophyton violaceum infections
• The primary outcome was mycologic cure at 6 weeks
  
• Three regimens
• two doses of griseofulvin 50 mg/kg administered 4
  weeks apart
• weekly 50 mg/kg doses for 6 weeks,
• 10 mg/kg daily for 6 weeks.

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Intermittent Dosing of Griseofulvin BAD Annual
Meeting 2006

• A total of 59 patients completed the study,
  returning at 6 weeks for evaluation, while 42
  returned for follow-up at 6 months.
• Mycologic cure rates were equivalent for the
  three groups at both time points, with the weekly
  regimen being slightly better.
• Clinical scores patients on the daily regimen
  improved more quickly, but at 6 weeks all groups
  had improved equally,
• Adverse events were minor and equally in all
  groups. Gastrointestinal, minor taste
  disturbances and no abnormalities in blood counts
  and liver function

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Conclusions
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• There is good evidence to support the use of
  Griseofulvin to treat tinea capitis in children
• ( Trichophyton and Microsporum infections ).

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• Terbinafine may be preferred because shorter
  treatment durations may improve patient adherence
  in Trichophyton infections.

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• There is no good evidence regarding the efficacy
  of itraconazole and fluconazole when compared to
  griseofulvin in Trichophyton infections.

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• In Microsporum infections, griseofulvin is still
  considered a better treatment in comparison with
  the newer antifungal drugs.

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• Adjunctive therapy for tinea capitis in adults
  and children
• Some RCT evidence suggests that antifungal
  shampoos can reduce the period of active shedding
  in patients treated with oral antifungals.
• Existing RCT evidence indicates that
  corticosteroids used with griseofulvin for
  inflammatory tinea capitis (kerion) give no
  additional or faster improvement.
•  
• Strategies to reduce spreading and re-infection
  in tinea capitis
• No RCT evidence exists for optimal management of
  symptom-free carriers.
•  
• There is insufficient evidence suggesting that
  antiseptic shampoos can reduce spread from
  carriers.

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• This review has been funded by
• The Cochrane Child Health Field. Alberta
  Research Centre for Child Health Evidence,
  University of Alberta, Canada
• The Sociedad Española de Dermato-Epidemiología
  y Dermatología basada en la Evidencia
  (SEDE-DBE), Spain