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Fixed cutaneous sporotrichosis
P1820
P1822
Incidence of dermatophytoses in the United States as captured by the National Ambulatory Medical Care survey, 1990-1999 Aditya Gupta, MD, PhD, Mediprobe Research Inc, London, Ontario, Canada
Fixed cutaneous sporotrichosis Loan Towersey, MD, PhD, Instituto de Dermatologia Prof. Ruben David Azulay da ´ rdia do Rio de Janeiro; AIDS Division Hospital Carlos Santa Casa de Miserico Tortelly, Rio de Janeiro, Brazil; Larissa Hanauer de Moura, MD, Instituto de Dermatologia Prof. Ruben David Azulay da Santa Casa de Misericordia do Rio de Janeiro, Rio de Janeiro, Brazil; Regina Casz Schechtman, MD, PhD, Instituto de Dermatologia Prof. Ruben David Azulay da Santa Casa de Miserico´rdia do Rio de Janeiro, Rio de Janeiro, Brazil; Roderick James Hay, MD, PhD, Faculty of Medicine and Health Science, Queen’s University, Belfast, United Kingdom
Dermatophytoses affect large numbers of patients worldwide; however,widespread surveys of prevalence are rare caused by the difficulty and costs involved in obtaining large-scale sample sizes. Trichophyton species and Microsporum fungal species, particularly Trichophyton rubrum, may infect any part of the body. Infection may spread from one body area to another, and from one patient to another by direct or indirect contact. Recurrence of infection is common. Because of these issues, dermatophytosis infections may affect large proportions of the US population over time. This data investigates the projected prevalence of dermatophytosis infection in the United States during the years 1990-1999, as collected from the National Ambulatory Medical Care Survey (NAMCS), administered nationally to a sample of United States non-federally employed physicians by the National Center for Health Statistics. Data from 316,928 visits between 1990 and 1999, when weighted, estimated the experience of 7.3 billion physician visits. Dermatophytosis is captured in the NAMCS dataset as an ICD-9 diagnosis code between 110.0-110.9. Individual codes designate tinea corporis (110.5 = ‘‘dermatophytosis of the body’’), tinea unguium (onychomycosis; 110.1 = ‘‘dermatophytosis of the nail’’), tinea pedis (110.4 = ‘‘dermatophytosis of the foot’’) and tinea cruris (110.3 = ‘‘dermatophytosis of the groin/perianal region’’). Pityriasis versicolor was also considered, and is presented in the NAMCS as an ICD-9 code of 111.0. Dermatophytosis or pityriasis versicolor were found in 0.46%, or 20,806,000 visits, of a possible 7.3 billion visits modeled by the NAMCS data. The most frequent dermatophytosis infection specified was tinea corporis (22%), followed by tinea unguium (19%), dermatophytosis of unspecified sites (16%), tinea pedis (12%), and tinea cruris (10%). Pityriasis versicolor was found in 9% of primary diagnoses of fungal infection surveyed. The distribution of infections noted among the regions of the US surveyed (northeast, midwest, south, and west) was similar. Based on the NAMCS data, a large number of Americans have experienced at least one type of dermatophytosis. Infection is likely underestimated, as the survey only captures those patients who seek medical treatment for their infection. There is a continuing need for adequate antifungal therapy, particularly in infections that can predispose to onychomycosis and tinea corporis/cruris, such as tinea pedis.
Sporotrichosis is a subcutaneous mycosis caused by Sporothrix schenckii. Infection occurs with traumatic inoculation of the fungus from plants, infected cats bites or scratches, dog bites, and other traumas. It can be divided into cutaneous forms (lymphocutaneous, fixed cutaneous, mucocutaneous, and dissemininated cutaneous), extracutaneous, and disseminated sporotrichosis. Fixed sporotrichosis lesions can be pleomorphic, including verrucous erythematous plaques, do not involve local lymphatics and remain fixed. A polymorphic case of sporotrichosis is reported with fixed lesion resistant to itraconazole therapy. A 46-year-old man presented a nonhealing lesion on the dorsum of his right foot. He worked as a wood chopper in Santa Maria Madalena, RJ, Brazil. His lesion began as a painless papule on the foot. It progressed to a verrucous plaque followed by nodular lesions on the leg which drained pus. He had hurt his foot with a log 2 years before. Histopathology was suggestive of deep mycosis and he was treated with itraconazole 200 mg/day for 2 years. Nodular lesions healed and left atrophic scars but the verrucous fixed plaque on the foot still drained pus on expression. Direct examination of pus was negative and the diagnosis of sporotrichosis was made on basis of S scheckii growth in culture. He was treated with saturated solution of potassium iodide (SSKI; 3 g/day) and responded well to this therapy. Verrucous lesions may occur in lymphocutaneous sporotrichosis and in fixed sporotrichosis. Coexistence of both forms with different response to itraconazole therapy is unusual. Repeated exposure causes sensitizing to S schenckii and there may be differences in infecting fungal strains. Other therapeutic options include amphotericin B, itraconazole, fluconazole, and terbinafine. Itraconazole is useful in cases resistant to SSKI, and although rare, cases of resistance to itraconazole treatment have been reported to respond to SSKI. Commercial support: None identified.
Partially supported by Pharmaderm.
P1821 Determination of griseofulvin efficacy in tinea capitis treatment using meta-analysis Aditya Gupta, MD, PhD, Mediprobe Research Inc, London, Ontario, Canada Griseofulvin was the first oral antifungal available for the treatment of dermatophyte fungal infection, and greatly increased the ability of physicians to treat such infections. The long history of griseofulvin use has made it a trusted component for treatment of children with tinea capitis, and griseofulvin is currently the only oral antifungal approved for use in tinea capitis in the United States. Despite the long use of griseofulvin, no clear expected efficacy rate has been established in clinical trials of tinea capitis. Efficacy rates for griseofulvin reported in clinical trials from the medical literature show relatively wide variability (effective cure = 44-92%). A previous meta-analysis demonstrated that the average griseofulvin efficacy of 6 comparative trials was similar to the efficacy of terbinafine in those same trials; however, the average efficacy rate was not reported. To determine an average efficacy rate for griseofulvin use in tinea capitis, an updated meta-analysis is planned. A PubMed search was performed using the terms ‘‘griseofulvin,’’ and ‘‘tinea capitis,’’ limited to reports of type ‘‘clinical trials’’ in language ‘‘English.’’ This search found 15 trials which involved griseofulvin, either individually or in comparative trials. Efficacy parameters to be investigated include mycological cure (MC: negative KOH and negative culture), clinical cure (ClinC: no visible signs of infection present) and complete cure (CC: simultaneous clinical cure and mycological cure). Primary efficacy outcomes will be measured at week 12/16 after drug initiation. Outcomes at the end of treatment, and after follow-ups of greater than 12/16 week, will be performed, where sufficient data is reported in the literature. Analysis will consider Trichophyton and Microsporum infections separately, where there are a sufficient number of studies. This meta-analysis will provide a weighted average efficacy outcome that will help define the efficacy of griseofulvin meaningfully, using mathematically-sound methods. Partially sponsored by Pedinol.
FEBRUARY 2007
P1823 An open-label, multiple-dose study of the absorption and systemic pharmacokinetics of AN2690 applied as a 7.5% solution to all toenails of adult patients with moderate to severe onychomycosis Karl Beutner, MD, PhD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Virginia Sanders, PhD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Karin Hold, PhD, Anacor Pharmaceuticals, Palo Alto, BC, United States; Robin Bullington, MS, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States AN2690 is a new novel antifungal being developed for the treatment of onychomycosis. AN2690 has demonstrated excellent nail plate penetration in ex vivo studies as well as favorable early clinical efficacy results. In preclinical studies, the plasma half life of AN2690 in rats was 11 minutes following intravenous dosing. Systemic exposure in the minipig was very low following a topical dose of 8.59 6 0.34 mg/kg (10% solution applied to 5% body surface area). A Cmax of 184 6 110 ng/mL was observed at 2 hours. At the 10-fold lower dose of 0.859 6 0.034 mg/kg, all plasma concentrations were below the limit of quantitation. The purpose of this study was to define the extent of human systemic exposure when AN2690 solution, at 7.5%, was applied to all 10 toenails of subjects with moderate to severe onychomycosis. Fifteen subjects with a body mass index between 19 and 35, onychomycosis involving greater than 80% of both great nails, a combined thickness of the nail plate and nail bed [3 mm, and at least 6 additional onychomycotic nails were enrolled to be treated daily for 28 days. A total dose of 0.25 ml was distributed over the subjects’ 10 toenails daily for 28 days at the study site. Plasma samples for quantitation of AN2690 were collected prior to and 0.25, 0.5, 1, 2, 3, 4, 6, and 8 hours after test agent application on days 1, 14, and 28. Samples were analyzed for AN2690 by a LC/MS/MS method with a lower limit of quantitation of 25 ng/mL. Plasma levels of AN2690 were below the limits of quantitation, indicating minimal systemic exposure. Commercial support: None identified.
J AM ACAD DERMATOL
AB129
P1822
Incidence of dermatophytoses in the United States as captured by the National Ambulatory Medical Care survey, 1990-1999 Aditya Gupta, MD, PhD, Mediprobe Research Inc, London, Ontario, Canada
Fixed cutaneous sporotrichosis Loan Towersey, MD, PhD, Instituto de Dermatologia Prof. Ruben David Azulay da ´ rdia do Rio de Janeiro; AIDS Division Hospital Carlos Santa Casa de Miserico Tortelly, Rio de Janeiro, Brazil; Larissa Hanauer de Moura, MD, Instituto de Dermatologia Prof. Ruben David Azulay da Santa Casa de Misericordia do Rio de Janeiro, Rio de Janeiro, Brazil; Regina Casz Schechtman, MD, PhD, Instituto de Dermatologia Prof. Ruben David Azulay da Santa Casa de Miserico´rdia do Rio de Janeiro, Rio de Janeiro, Brazil; Roderick James Hay, MD, PhD, Faculty of Medicine and Health Science, Queen’s University, Belfast, United Kingdom
Dermatophytoses affect large numbers of patients worldwide; however,widespread surveys of prevalence are rare caused by the difficulty and costs involved in obtaining large-scale sample sizes. Trichophyton species and Microsporum fungal species, particularly Trichophyton rubrum, may infect any part of the body. Infection may spread from one body area to another, and from one patient to another by direct or indirect contact. Recurrence of infection is common. Because of these issues, dermatophytosis infections may affect large proportions of the US population over time. This data investigates the projected prevalence of dermatophytosis infection in the United States during the years 1990-1999, as collected from the National Ambulatory Medical Care Survey (NAMCS), administered nationally to a sample of United States non-federally employed physicians by the National Center for Health Statistics. Data from 316,928 visits between 1990 and 1999, when weighted, estimated the experience of 7.3 billion physician visits. Dermatophytosis is captured in the NAMCS dataset as an ICD-9 diagnosis code between 110.0-110.9. Individual codes designate tinea corporis (110.5 = ‘‘dermatophytosis of the body’’), tinea unguium (onychomycosis; 110.1 = ‘‘dermatophytosis of the nail’’), tinea pedis (110.4 = ‘‘dermatophytosis of the foot’’) and tinea cruris (110.3 = ‘‘dermatophytosis of the groin/perianal region’’). Pityriasis versicolor was also considered, and is presented in the NAMCS as an ICD-9 code of 111.0. Dermatophytosis or pityriasis versicolor were found in 0.46%, or 20,806,000 visits, of a possible 7.3 billion visits modeled by the NAMCS data. The most frequent dermatophytosis infection specified was tinea corporis (22%), followed by tinea unguium (19%), dermatophytosis of unspecified sites (16%), tinea pedis (12%), and tinea cruris (10%). Pityriasis versicolor was found in 9% of primary diagnoses of fungal infection surveyed. The distribution of infections noted among the regions of the US surveyed (northeast, midwest, south, and west) was similar. Based on the NAMCS data, a large number of Americans have experienced at least one type of dermatophytosis. Infection is likely underestimated, as the survey only captures those patients who seek medical treatment for their infection. There is a continuing need for adequate antifungal therapy, particularly in infections that can predispose to onychomycosis and tinea corporis/cruris, such as tinea pedis.
Sporotrichosis is a subcutaneous mycosis caused by Sporothrix schenckii. Infection occurs with traumatic inoculation of the fungus from plants, infected cats bites or scratches, dog bites, and other traumas. It can be divided into cutaneous forms (lymphocutaneous, fixed cutaneous, mucocutaneous, and dissemininated cutaneous), extracutaneous, and disseminated sporotrichosis. Fixed sporotrichosis lesions can be pleomorphic, including verrucous erythematous plaques, do not involve local lymphatics and remain fixed. A polymorphic case of sporotrichosis is reported with fixed lesion resistant to itraconazole therapy. A 46-year-old man presented a nonhealing lesion on the dorsum of his right foot. He worked as a wood chopper in Santa Maria Madalena, RJ, Brazil. His lesion began as a painless papule on the foot. It progressed to a verrucous plaque followed by nodular lesions on the leg which drained pus. He had hurt his foot with a log 2 years before. Histopathology was suggestive of deep mycosis and he was treated with itraconazole 200 mg/day for 2 years. Nodular lesions healed and left atrophic scars but the verrucous fixed plaque on the foot still drained pus on expression. Direct examination of pus was negative and the diagnosis of sporotrichosis was made on basis of S scheckii growth in culture. He was treated with saturated solution of potassium iodide (SSKI; 3 g/day) and responded well to this therapy. Verrucous lesions may occur in lymphocutaneous sporotrichosis and in fixed sporotrichosis. Coexistence of both forms with different response to itraconazole therapy is unusual. Repeated exposure causes sensitizing to S schenckii and there may be differences in infecting fungal strains. Other therapeutic options include amphotericin B, itraconazole, fluconazole, and terbinafine. Itraconazole is useful in cases resistant to SSKI, and although rare, cases of resistance to itraconazole treatment have been reported to respond to SSKI. Commercial support: None identified.
Partially supported by Pharmaderm.
P1821 Determination of griseofulvin efficacy in tinea capitis treatment using meta-analysis Aditya Gupta, MD, PhD, Mediprobe Research Inc, London, Ontario, Canada Griseofulvin was the first oral antifungal available for the treatment of dermatophyte fungal infection, and greatly increased the ability of physicians to treat such infections. The long history of griseofulvin use has made it a trusted component for treatment of children with tinea capitis, and griseofulvin is currently the only oral antifungal approved for use in tinea capitis in the United States. Despite the long use of griseofulvin, no clear expected efficacy rate has been established in clinical trials of tinea capitis. Efficacy rates for griseofulvin reported in clinical trials from the medical literature show relatively wide variability (effective cure = 44-92%). A previous meta-analysis demonstrated that the average griseofulvin efficacy of 6 comparative trials was similar to the efficacy of terbinafine in those same trials; however, the average efficacy rate was not reported. To determine an average efficacy rate for griseofulvin use in tinea capitis, an updated meta-analysis is planned. A PubMed search was performed using the terms ‘‘griseofulvin,’’ and ‘‘tinea capitis,’’ limited to reports of type ‘‘clinical trials’’ in language ‘‘English.’’ This search found 15 trials which involved griseofulvin, either individually or in comparative trials. Efficacy parameters to be investigated include mycological cure (MC: negative KOH and negative culture), clinical cure (ClinC: no visible signs of infection present) and complete cure (CC: simultaneous clinical cure and mycological cure). Primary efficacy outcomes will be measured at week 12/16 after drug initiation. Outcomes at the end of treatment, and after follow-ups of greater than 12/16 week, will be performed, where sufficient data is reported in the literature. Analysis will consider Trichophyton and Microsporum infections separately, where there are a sufficient number of studies. This meta-analysis will provide a weighted average efficacy outcome that will help define the efficacy of griseofulvin meaningfully, using mathematically-sound methods. Partially sponsored by Pedinol.
FEBRUARY 2007
P1823 An open-label, multiple-dose study of the absorption and systemic pharmacokinetics of AN2690 applied as a 7.5% solution to all toenails of adult patients with moderate to severe onychomycosis Karl Beutner, MD, PhD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Virginia Sanders, PhD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Karin Hold, PhD, Anacor Pharmaceuticals, Palo Alto, BC, United States; Robin Bullington, MS, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States AN2690 is a new novel antifungal being developed for the treatment of onychomycosis. AN2690 has demonstrated excellent nail plate penetration in ex vivo studies as well as favorable early clinical efficacy results. In preclinical studies, the plasma half life of AN2690 in rats was 11 minutes following intravenous dosing. Systemic exposure in the minipig was very low following a topical dose of 8.59 6 0.34 mg/kg (10% solution applied to 5% body surface area). A Cmax of 184 6 110 ng/mL was observed at 2 hours. At the 10-fold lower dose of 0.859 6 0.034 mg/kg, all plasma concentrations were below the limit of quantitation. The purpose of this study was to define the extent of human systemic exposure when AN2690 solution, at 7.5%, was applied to all 10 toenails of subjects with moderate to severe onychomycosis. Fifteen subjects with a body mass index between 19 and 35, onychomycosis involving greater than 80% of both great nails, a combined thickness of the nail plate and nail bed [3 mm, and at least 6 additional onychomycotic nails were enrolled to be treated daily for 28 days. A total dose of 0.25 ml was distributed over the subjects’ 10 toenails daily for 28 days at the study site. Plasma samples for quantitation of AN2690 were collected prior to and 0.25, 0.5, 1, 2, 3, 4, 6, and 8 hours after test agent application on days 1, 14, and 28. Samples were analyzed for AN2690 by a LC/MS/MS method with a lower limit of quantitation of 25 ng/mL. Plasma levels of AN2690 were below the limits of quantitation, indicating minimal systemic exposure. Commercial support: None identified.
J AM ACAD DERMATOL
AB129