tinea pedis natural history & clinical trials joseph porres, m.d., ph.d. medical officer, ddddp
TRANSCRIPT
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