1. Tinea Pedis Natural History & Clinical Trials Joseph Porres, M.D., Ph.D. Medical Officer, DDDDP

2. Part I: Natural History Tinea pedis subtypes Causative organisms Dermatomycosis syndrome Predisposing factors Complicating factors & Complications Epidemiology & recurrence Diagnosis Treatment

3. Tinea Pedis Subtypes Interdigital: pruritus, erythema, scaling, fissuring, maceration Plantar:  Moccasin: scaling, pruritus, erythema  Vesicobullous: pruritus, vesicles, scaling, erythema Combinations of interdigital and plantar Athlete’s foot is the layman’s term and can be found in reference to any of these forms

4. Causative Organisms Trichophyton rubrum (60-80%)  Plantar, mocassin  Plantar small vesicles, may also affect distal subungual nail, other body sites Trichophyton mentagrophytes (10-20%),  Peri-plantar large vesicles, and may spread to white superficial nail Epidermophyton floccosum (3-10%)

5. Dermatlas, JHMI.EDU Tinea Pedis Interdigitalis

6. Tinea Pedis Plantaris Rebell, G. & Zaias, N. Cutis 2001, 67, 5S, 6-17

7. Dermatlas, JHMI.EDU Tinea Pedis Plantaris, Vesicular

8. Tinea Pedis Plantaris, Moccasin Rebell, G. & Zaias, N. Cutis 2001, 67, 5S, 6-17

10. Closed communities: army barracks, boarding schools Public baths, swimming pools Local trauma on dermatophyte carrying individual Occlusive footgear Immersion Warm weather Exposure to hair of infected animals (rats in Vietnam) Infected family members (~17% in one study) Familial predisposition Predisposing Factors

11. Immunosuppression Atopy Diabetes Compromised circulation Localized trauma Geriatric population Complicating Factors:

12. Tinea pedis unrecognized Treatment not given Treatment is inadequate Reinfection from the nail Complications: Cellulitis

13. Epidemiology 15-70 % of population at large 40 % of patients attending a general clinic Those seeking help often have nail involvement Many undiagnosed cases Dermatophytes isolated from:  2-40% “normal feet”  Public showers  Swimming pools  Shoes and Socks

14. Recurrence Topical terbinafine and clotrimazole in interdigital tinea pedis: A multicenter comparison of cure and relapse rates with 1- and 4- week treatment regimens. Bergstresser PR et al, JAAD 1993; 28: 648-51 Long-term outcome of patients with interdigital tinea pedis treated with terbinafine or clotrimazole. Elewski, B. et al. JAAD 1995; 32:290-2

15. Study Details 193 evaluable patients with interdigital tinea pedis Treatment twice daily with:  terbinafine cr or clotrimazole cr  1 or 4 weeks Observation for up to 18 months [Elewski] Mycology “Cure”

16. Study Results

17. Diagnosis Clinical: by clinical signs and symptoms Mycology: KOH (direct examination) and culture. Mycology [KOH] helps confirm diagnosis and avoid:  Delay of indicated treatment  Prescribing inappropriate treatment

18. Treatment. Efficacy rates reported*: AntifungalDosageWeeksRate %Type of Cure TerbinafineBID497Mycology Terbinafine-176Mycology Terbinafine-197- ClotrimazoleBID483Mycology ClotrimazoleBID135- Miconazole-487- * Treatment of Skin Disease. Lebohl, M. et al, Mosby. 2003

19. Part II: Clinical Trials Dose ranging studies Clinical trials for safety and efficacy

20. Dose Ranging Studies For Tinea Pedis Dose ranging studies for topical antifungals often recommended by FDA but usually not conducted Dose ranging studies for topical antifungals to select the best safety/efficacy dose:  Drug strength  Frequency of application  Duration of treatment

21. Clinical Safety and Efficacy Trials Assessment Outcomes

22. Assessment Mycology:  Direct microscopic examination (KOH)  Mycology culture Clinical. Signs and symptoms:  Erythema  Scaling  Pruritus, etc.

23. Outcomes Mycology “Cure” (MC): Negative KOH and negative culture Effective treatment: MC, no symptoms, only residual signs Complete Cure: MC, and no signs or symptoms

24. Clinical Safety and Efficay Studies Inclusion/exclusion criteria often do not mimic the populations expected to actually use the product Include: healthy patients with interdigital tinea pedis Exclude harder cases:  Onychomycosis  Mocassin type, keratotic feet  Diabetic  Immunosuppressed  Compromised circulation