Tinea PedisNatural History

&Clinical Trials

Joseph Porres, M.D., Ph.D.

Medical Officer, DDDDP

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

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

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%)

Dermatlas, JHMI.EDU

Tinea Pedis Interdigitalis

Tinea Pedis Plantaris

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

Dermatlas, JHMI.EDU

Tinea Pedis Plantaris, Vesicular

Tinea Pedis Plantaris, Moccasin

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

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

• 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

• Immunosuppression

• Atopy

• Diabetes

• Compromised circulation

• Localized trauma

• Geriatric population

Complicating Factors:

• Tinea pedis unrecognized

• Treatment not given

• Treatment is inadequate

• Reinfection from the nail

Complications: Cellulitis

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

RecurrenceTopical 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

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”

Study ResultsLong Term Outcome after Mycological “Cure” (JAAD 1995:290-292)

Number of Subjects (%)

Subjects in Original Study 12 Week Study 193

Patients with Mycology “Cure” at 12 weeks 130 (67% of 193)

Mycology “Cure” patients contacted for follow-up 15 – 18 months after baseline

93 (72% of 130)

Patients with clinical relapse requiring treatment within 15 – 18 months

44 (47% of 93)

Patients without clinical relapse within 15 – 18 months

49 (53% of 93)

Patients without clinical relapse but with positive mycology

24 (49% of 49)

Positive mycology for new organism 8 (33% of 24)

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

Treatment. Efficacy rates reported*:

Antifungal Dosage Weeks Rate % Type of Cure

Terbinafine BID 4 97 Mycology

Terbinafine - 1 76 Mycology

Terbinafine - 1 97 -

Clotrimazole BID 4 83 Mycology

Clotrimazole BID 1 35 -

Miconazole - 4 87 -

* Treatment of Skin Disease. Lebohl, M. et al, Mosby. 2003

Part II: Clinical Trials

• Dose ranging studies

• Clinical trials for safety and efficacy

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

Clinical Safety and Efficacy Trials

• Assessment

• Outcomes

Assessment

• Mycology: Direct microscopic examination (KOH) Mycology culture

• Clinical. Signs and symptoms: Erythema Scaling Pruritus, etc.

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

Clinical Safety and Efficay StudiesInclusion/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