Saturday, 21 March 2015

Role of oral terbinafine in the treatment of tinea capitis

Tinea capitis, an infection of scalp hair follicles and the surrounding skin, is predominantly an infection of children, although adult cases are occasionally seen.

Whereas all three genera attack the skin, Microsporum does not infect nails and Epidermophyton does not infect hair. Tinea capitis is caused by dermatophyte fungi, species in the genera Microsporum and Trichophyton. Single fungus can produce more than one clinical type of tinea capitis. Hair shaft infection is preceded by invasion of the stratum corneum of the scalp.  Because of the cuticle, the fungi cannot cross over from the perifollicular stratum corneum into the hair but must go deep into the hair follicle to circumvent the cuticle. This helps explain why topical antifungals fail to treat tinea capitis. The fungus grows down through stratum corneum layer into the hair follicle and gains entry into the hair in the lower intrafollicular zone, just below the point where the cuticle of the hair shaft is formed. Thus, infection originates inside the hair shaft in all patterns of hair invasion. The growth of hyphae occurs within the hair above the zone of keratinization of the hair shaft (Adamson “fringe”) and keeps pace with the growth of hair. Distal to this zone of active growth, spores are formed within or on the surface of the hair, depending on the species of dermatophytes. Hyphae grow inside and fragment into short segments called spores. Endothrix infections have spores remaining within the hair shaft and the affected hair shaft breaks at the surface of the scalp being severely weakened but in favus endothrix pattern, the fungus does not fragment into spores thus the infected hair commonly grows to normal lengths. Ectothrix infections have spores dislodging outside the hair shaft, the cuticle is eventually destroyed and the hair shaft tends to fracture a few millimetres above the surface.

Factors to be considered when managing a case of tinea capitis are the anatomic structure of the hair follicle, the dormant sebum-production before onset of puberty, the organism isolated, and the antifungal to be chosen (see table). 

Terbinafine is an allylamine that acts on the cell membrane and is fungicidal. It shows activity against all dermatophytes, but has much higher efficacy against Trichophyton species than Microsporum. For M. canis infection, the minimum inhibitory concentration for terbinafine can exceed the maximum concentration reported in hair, which might lead to treatment failure.

Terbinafine hydrochloride is well absorbed from the gastrointestinal tract. It is distributed into the stratum corneum of the skin (by sebum and by direct diffusion from the vascular system), sebum, the nail plate, and hair where it reaches concentrations considerably higher than those found in plasma. It is not found in sweat. It appears in breast milk.  Terbinafine will not be built on the hair shaft because it is not found in sweat but it is integrated via the hair papilla in the newly formed keratin of the growing hair where it can eliminate the infection. Accordingly, it will not reach paediatric ectothrix hair infection via sweat, as mentioned above or via sebum because of the dormant sebum-production before onset of puberty and this might explain its lower efficacy in such circumstances. However, it has been said that Microsporum infections (ectothrix) just require higher doses and longer courses of therapy with terbinafine. The current British guidelines state that at higher doses, terbinafine is more effective against M. canis but prolonging treatment does not improve efficacy.

Prepubescent children have functioning sweat glands, and therefore griseofulvin, fluconazole, and itraconazole can reach the outside of the hair in this fashion.

There is a positive effect for terbinafine against Trichophyton spp. in paediatric tinea capitis. In patients who have not yet reached puberty, only the portion of terbinafine that is integrated in the keratin through the hair root is effective. It has been shown that 4 weeks of terbinafine is at least as effective as 8 weeks of griseofulvin in T. tonsurans infections and thus terbinafine is now considered the optimal choice, when cost-efficiency and compliance are taken into account in treating such infections.

Oral terbinafine is not recommended for patients with chronic or active liver disease. Any pre-existing liver disease should be assessed. Periodic monitoring of liver function test is recommended.

The terbinafine dose in tinea capitis is as follows, over 1 year, body-weight 10–19 kg, 62.5 mg (one-quarter of a 250 mg tablet) once daily; body-weight 20–39 kg, 125 (half of a 250 mg tablet) mg once daily; body-weight 40 kg and above , 250 mg once daily  usually for 4 weeks. The tablet may be split accordingly and hidden in food. Overall, terbinafine appears well tolerated in children. A granule formulation of terbinafine to be sprinkled on food has been licensed for use in children > 4 years of age in the USA. 

If itraconazole is selected as first-line therapy (because it has activity against both Trichophyton and Microsporum species), terbinafine is considered second line for Trichophyton infections and griseofulvin is considered second line treatment for Microsporum species, at standard dosing regimens. Ketoconazole shampoo left on the scalp for 5 minutes three times a week can be used as adjunctive therapy to oral antifungal agents to reduce the shedding of fungal spores. Fluconazole has been used in the treatment of tinea capitis but its use has been relatively limited.

Tinea capitis caused by Trichophyton species.

This page was last updated in December 2015

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Main Works of Reference List (The first eight are my top favourites)

  • British National Formulary
  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
  • Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health
  • Oxford Handbook of Medical Dermatology
  • Rook's Textbook of Dermatology
  • Simple Skin Surgery
  • Weedon's Skin Pathology
  • A Concise Atlas of Dermatopathology (P Mckee)
  • Andrews' Diseases of the Skin
  • Andrology (Nieschlag E FRCP, Behre M and Nieschlag S)
  • Bailey and Love's Short Practice of Surgery
  • Davidson's Essentials of Medicine
  • Davidson's Principles and Practice of Medicine
  • Fitzpatrick's Colour Atlas and Synopsis of Clinical Dermatology (Klaus Wolff FRCP and Richard Allen Johnson)
  • Fitzpatrick’s Dermatology in General Medicine
  • Ganong's Review of Medical Physiology
  • Gray's Anatomy
  • Hamilton Bailey's Demonstrations of Physical Signs in Clinical Surgery
  • Hutchison's Clinical Methods
  • Lever's Histopathology of the Skin
  • Lever's Histopathology of the Skin (Atlas and Synopsis)
  • Macleod's Clinical Examination
  • Martindale: The Complete Drug Reference
  • Oxford Handbook of Clinical Examination and Practical Skills
  • Oxford Textbook of Medicine
  • Practical Dermatopathology (R Rapini)
  • Sexually Transmitted Diseases (Holmes K et al)
  • Statistics in Clinical Practice (D Coggon FRCP)
  • Stockley's Drug Interactions
  • Treatment of Skin Disease: Comprehensive Therapeutic Strategies
  • Yen & Jaffe's Reproductive Endocrinology