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`JOURNAL OF THE AMERICAN ACADEMY OF
`
`DERMATOLOGY
`
`accrom 2000
`
`VOLUME 43
`Copy/jg/zt © 2000 by the Amentcz/2 Academy cfDemzar0/ogy, Inc.
`
`NUMBER4
`
`c,r\“" dc;
`~13
`*
`'4
`i.-<
`<AAD‘
`O4
`~.
`00 1938
`‘O
`"£11,310 ’
`
`l CONTINUING MEDICAL EDUCATION I
`
`Cicatricial pemphigoid
`Thomas E. Fleming, MD, and Neil]. Korman, MD, PhD Cleveland, Ohio
`
`Answers to CME examination (Identification No. 800-110), October 2000
`issue of the Journal of the American Academy of Dermatology
`
`CME examination
`
`Anti-CD4 monoclonal antibody treatment of moderate to severe
`psoriasis vulgaris: Results of a pilot, multicenter, multiple-dose,
`placebo-controlled study
`Alice B. Gottlieb, MD, PhD, Mark Lebwohl, MD, Sophie Shirin, MD,
`Amelia Sherr, RN, BSN, Pat Gilleaudeau, RN, BSN, Giselle Singer, BS,
`Galina Solodkina, MD, Rachel Grossman, MD, Elvira Gisoldi, Steven Phillips, MS,
`H. Mike Neisler, PhD, and James G. Krueger, MD, PhD New Brmzswic/e and
`S/eillmcm, New jersey; New Ibr/e, New Yor/<2; and1ndz'anapo[z's, Indiana
`
`Late metastases of cutaneous melanoma: An analysis of
`51 patients
`Monika—H. Schmid—\X/encltner, Jens Baumert, Michael Schmidt, Birger Konz,
`Dieter Holzel, Gercl Plewig, and Matthias Volker1anclt,Mum'c/J, Germany
`
`Effect of daily versus intermittent sunscreen application on solar
`simulated UV radiation-induced skin response in humans
`Tania]. Phillips, MD, Jag Bhawan, MD, Mina Yaar, MD, Ysabel Bello, MD,
`Danielle LoPiccolo, BS, and]. Frank Nash, PhD Boston, /Vlassac/msetts,
`and Cz'ncz'mzatz', O/9z'o
`
`The Journal is pleased to announce the addition of a new online feature, eBIueprint5. Articles published in the eB/ueprints
`section of the Internet version of the Journal at www.eblue.org will appear only online and will not appear in the print
`version of the Journal. Such articles are considered publications and will be assigned an ”e" folio for citation purposes
`(eg,J Am Acad Dermatol 2000;43:e1).The Journal will continue to provide preBIue, which contains papers accepted for
`publication in the print version but which appear first online.
`
`Comiizzled on page 7A
`
`Vol.‘ 43, No. 4, October 2000, the Journal of the American Academy of Dermatology (ISSN 0190-9622) is published monthly (six issues
`per volume, two volumes per year) by Mosby,|nc.,11830 Westline Industrial Dr, St Louis, MO 63146-3318; 800654-2452 or 407-345-4000. Periodicals
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`Cu,gs tents
`____»~
`
`continued
`
`Sensitivity and specificity of clinical, histologic, and immunologic
`features in the diagnosis of paraneoplastic pemphigus
`P. Joly, MD, PhD, C. Richard, MD, D. Gilbert, PhD, R Courville, MD,
`O. Chosidow, MD, PhD, J. C. Roujeau, MD, M. Beylot-Barry, MD, PhD,
`M. D’Incan, MD, PhD, Ph. Martel, MD, Ph. Lauret, MD, F. Tron, MD, PhD,
`and the members of the French Study Group on bullous diseases
`Rouen, Paris, Créteil, Pessac, and Cler7nont—Ferrand, France
`
`Prognostic indicators in venous ulcers
`TaniaJ. Phillips, MD, Fidelis Machado, MD, Richard Trout, PhD, John Porter, MD,
`Jeffrey Olin, MD, Vincent Falanga, MD, and The Venous Ulcer Study Group
`Boston, Massac/ousetts; Princeton and Piscataway, New jersey, Portland, Oregon,-
`and Cleveland, O/yio
`
`Raynaud’s phenomenon, anticentromere antibodies, and digital
`necrosis without sclerodactyly: An entity independent of scleroderma?
`Evelyn M. Sachsenberg-Studer, MD, Christa Prins, MD, Jean-Hilaire Saurat, MD, and
`Denis Salomon, MD Fran/efurt, Germany, and Geneva, Switzerland
`
`Rapidly progressing mycosis fungoides presenting as follicular mucinosis
`Michelle D. Bonta, BA, Zeina S. Tannous, MD, Marie—France Demierre, MD, FRCPC,
`Ernesto Gonzalez, MD, Nancy L. Harris, MD, and Lyn M. Duncan, MD
`Boston, Massachusetts
`
`A large-scale North American study of fungal isolates from nails:
`The frequency of onychomycosis, fungal distribution, and antifungal
`susceptibility patterns
`M. A. Ghannoum, PhD, R. A. Hajjeh, MD, R. Scher, MD, N. Konnikov, MD,
`A. K. Gupta, MD, R. Summerbell, PhD, S. Sullivan, MD, PhD, R. Daniel, MD,
`P Krusinski, MD, R Fleckman, MD, P Rich, MD, R. Odom, MD, R. Aly, MD,
`D. Pariser, MD, M. Zaiac, MD, G. Rebell, MD, J. Lesher, MD, B. Gerlach, MD,
`G. F. Ponce—de—leon, A. Ghannoum, J. Warner, BA, N. Isham, BA, M(ASCP),
`and B. Elewski, MD Cleveland and Hudson, O/no; Atlanta and Augusta, Georgia;
`New lbr/e, New lbrle; Boston, ll/lassac/nzselts,- Toronto, Ontario, Canada,-
`fackson, Mississippi,- Bit-rlington, Vermont, Seattle, Washington, Portland, Oregon;
`San Francisco, California; Norfol/2, Virginia, and Miami Beach, Florida
`
`The prevalence of atopic dermatitis in Oregon schoolchildren
`Diane Laughter, MPH, Joseph A. lstvan, PhD, Susan J. Tofte, RN, BSN, and
`Jon M. Hanifin, MD Portland, Oregon
`
`Photodamage pilot study: A double-blind, vehicle-controlled study to
`assess the efficacy and safety of tazarotene 0.1% gel
`John Sefton, PhD, Albert M. Kligman, MD, PhD, Scott C. Kopper, BS,
`John C. Lue, MS, and John R. Gibson, MD Irvine, California, and
`Philadelphia, Pennsylvania
`
`Statements and opinions expressed in the articles and communications herein are those ofthe author(s) and not necessarily those of the
`Editor(s), pub|isher,or Academy, and the Editor(s), pub|isher,and Academy disclaim any responsibility or liability for such material. Neither
`the Editor(s), publisher, nor the Academy guarantees, warrants, or endorses any product or service advertised in this publication, nor do
`they guarantee any claim made by the manufacturer of such product or service.
`
`Continued on page 9A
`
`J AM ACAD DERMATOL
`
`OCTOBER 2000 7A
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`(Z untents
`
`continued
`
`Basal cell carcinoma in chronic arsenicism occurri_ng in Queensland,
`Australia, after ingestion of an asthma medication
`\X/aranya Boonchai, MD, Adele Green, MBBS, PhD, Jack Ng, PhD,
`Anthony Dicker, MBBS, and Georgia Chenevix-Trench, PhD
`Brisbane, Queensland, Australia
`
`THERAPY
`
`Ultraviolet A1 (340-400 nm) phototherapy for scleroderma in
`systemic sclerosis
`
`Akimichi Morita, MD, PhD, Keiko Kobayashi, MD, Iwao Isomura, MD,
`Takuo Tsuji, MD, and Jean Krutmann, MD Nagoya, japan, and
`Dz'lssela’o1_7§' Germany
`
`PUVA-cream photochemotherapy for the treatment of localized
`scleroderma
`
`Marcella Grundmann—Kollmann, MD, Falk Ochsendorf, MD, Thomas M. Zollner, MD,
`Konstanze Spieth, MD, Evelyn Sachsenberg—Studer, MD, Roland Kaufmann, MD,
`and Maurizio Podda, MD Fran/efzm, Germany
`
`Peristomal dermatoses: A novel indication for topical steroid lotions
`Calum C. Lyon, Amanda]. Smith, Christopher E. M. Griffiths, and Michael H. Beck
`Sa[fora’, United Kz'nga’om
`
`Therapeutic update: Use of risperidone for the treatment of
`monosymptomatic hypochondriacal psychosis
`Maj Kathleen B. Elmer, USAF, MC, FS, Maj Rita M. George, USAF, MC, FS, and
`Maj Karen Peterson, USAF, MC Yo/eota AB, japan, and Langley AFB, Vz'rgz'nz'a
`
`DERMATOLOGIC SURGERY
`
`Silicone auricular prosthesis
`David F. Butler, MD, Gregory G. Gion, BA, BS, and Ronald R Rapini, MD
`Lubboc/3, Texas
`
`CLINICAL REVIEW
`
`Potassium iodide in dermatology: A 19th century drug for the
`21st century—Uses, pharmacology, adverse effects, and
`contraindications
`
`J. Barton Sterling, BS, and Warren R. Heymann, MD Mar/ton, New jersey
`
`DERMATOLOGY GRAND ROUNDS AT THE NIH
`
`Widespread cutaneous vascular papules associated with peripheral
`blood eosinophilia and prominent inguinal lymphadenopathy
`Andrew Blauvelt, MD, Mark W Cobb, MD, and Maria L. Turner, MD
`Bet/Jesda, Marylana’
`
`] AM ACAD DERMATOL
`
`OCTOBER 2000 9A
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`Con/inued on page IOA
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`

`
`Contents
`
`continued
`
`FROM THE ACADEMY
`
`American Academy of Dermatology 2000 Awards for
`Young Investigators in Dermatology
`
`CURRENT ISSUES
`
`The use of interferon alfa as adjuvant therapy for advanced
`cutaneous melanoma: The need for more evidence
`
`Arash Kimyai—Asadi, MD, and Adi] Usman, MD New ibrle, New Ybrle
`
`PEARLS
`
`Surgical Pearl: Digital imaging for mapping Mohs surgical specimens
`Christine A. Papa, DO, and Michael L. Ramsey, MD Dcmville, Pe7msy[z2anz'a
`
`Iotaderma #81
`
`BRIEF REPORTS
`
`Paraneoplastic pemphigus with circulating antibodies directed
`exclusively against the pemphigus vulgaris antigen desmoglein 3
`Anne Bouloc, MD, PhD, Pascal Joly, MD, PhD, Estelle Saint-Leger, MD,
`Janine Wechsler, MD, Jean—Claucle Roujeau, MD, and Jean Revuz, MD
`Créz‘ez'[ and Rouen, Frcmce
`
`Constipation presenting as recurrent vulvovaginitis in
`prepubertal children
`P A. F. A. van Neer, MD, and C. R. W. Korver, MD, PhD
`Roermomz’, Tbe Net/oerlcmds
`
`Disseminated superficial actinic porokeratosis associated with
`topical PUVA
`Angel L. Allen, MD, and Dee Anna Glaser, MD 52‘ Louis, Mz'ss0Lm'
`
`Derrnoscopic features of cutaneous local recurrent melanoma
`Angela Ferrari, MD, Ketty Peris, MD, Domenico Piccolo, MD, and
`Sergio Chimenti, MD L’Aquz'[a and Rome, Italy
`
`COMME N TARY
`
`Photochemotherapy for systemic and localized scleroderma
`Menno A. de Rie, MD, PhD, and Jan D. Bos, MD, PhD
`Amsterdam, T/ye Net/aerlcznds
`
`OPINION
`
`Evidence-based medicine: The epistemology that isn’t
`Jonathan Rees, FRCP, FMedSci Edmburg/9, Unz'ted Kmgdoiiz
`
`10A OCTOBER 2000
`
`JAM ACAD DERMATV‘
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`

`
`Contents
`
`continued
`
`Paradoxical effect of interferon alfa on lichen myxedematosus
`Franco Rongioletti, MD, and Alfredo Rebora, MD
`Genoa, Italy
`
`Pruritic urticarial papules and plaques of pregnancy and
`multiple pregnancies
`Frank C. Powell, FRCPI, FRCP(Eclinb) Dublin, Ireland
`
`Long latency of human herpesvirus type 8 infection and the
`appearance of classic Kaposi’s sarcoma
`Decio Cerimele, MD, Francesca Cottoni, MD, and Maria Vittoria Masala, MD
`Sassari, Italy
`
`Reply
`Thierry Simonart, MD, and Jean-Paul Van Vooren, MD
`Brussels, Belgium
`
`CORRECTIONS
`
`Kalka K, Merk H, Mukhtar H. Photodynamic therapy in dermatology
`(I Am Acad Dermatol 2000;42:389-413[March])
`
`Becker-Wegerich PM, Kuhn A, Malek L, Lehmann P, Megahed M,
`Ruzicka T. Treatment of nonmelanotic hyperpigmentation with the
`Q-switched ruby laser (1 Am Acad Dermatol 2000;/13:272-4[August])
`
`Tsai T-F, Paul BH[sic], Jee S-H, Maibach HI. Effects of glycolic acid on
`light-induced skin pigmentation in Asian and Caucasian subjects
`(J Am Acad Dermatol 2000;43:238-43[August])
`
`P RE B LU E
`
`WWW.Cl)11lC.01'g
`
`Concomitant administration of vitamin E does not change the side effects
`of isotretinoin as used in acne vulgaris: A randomized trial
`John S. Strauss, MD, Alice B. Gottlieb, MD, PhD, Terryjones, MD, John Y. M. Koo, MD,
`James}. Leyden, MD, Anne Lucky, MD, Anastasios A. Pappas, MD, John McLane, PhD, and
`Eileen A. Leach, MPH, RN Iowa Cz'2§y, Iowa; New Branswlc/a and Nutley, New jersey,-
`Bryan, Texas; San Francisco, Calz_7form'a,- P/yiladelp/9z'a, Pe7msj»lvarzz'a,- Cz'ncz'nnatz', Obz'o,-
`ana’ Sioux Falls, South Da/eozfa
`
`Analysis of current data on the use of intravenous ixnmunoglobulins in
`management of pemphigus vulgaris
`Leela Engineer, MD, Kailash C. Bhol, PhD, and A. Razzaque Ahmed, MD
`Boston, Massac/9useZz‘s
`
`Ultraviolet A1 (340-400nm) phototherapy for cutaneous T-cell lymphoma
`Harmut Stiinder, MD, and Thomas Schwarz, MD Miinstei; Germany
`
`Complimentary subscriptions to the Journal of the American Academy of Dermatology are available to
`dermatology residents, fellows, and osteopathic trainees in the United States and Canada as an educational
`service by Bristol—Myers Squibb Dermatology.
`
`i AM ACAD DERMATOL
`
`OCTOBER 2000
`
`13A
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`
`Contents
`
`continued
`
`EBLUEPRINTS
`
`Is it a divinity that shapes our ends?
`Leonard Laster, MD Worceslez; zvfassacbzzsetts
`
`ANNOUNCMENTS
`
`AAD seeks locations of clinics in developing countries
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`Donate your old books and journals
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`READER SERVICES
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`Information for authors
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`Information for readers
`
`Dermatology calendar
`
`Dermatology opportunities
`
`Instructions for category I CME credit
`
`CME examination answer sheet
`
`Statement of advertising in the journal
`
`Index to advertisers
`
`www.eblue.org and July 2000,
`pages 19A, 20A, and 21A
`
`23A
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`103A
`
`107A
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`29A
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`33A
`
`29A
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`112A
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`Full text of the Journal is now available free to AAD members at www.eblue.org.
`Nomnember subscribers may Contact Mosby at 800-453-4351 (in U.S.) or
`314-453-4351 (outside U.S.) or via e-mail at periodical.service@mosby.com
`about adding the on-line version to their print subscription.
`
`The Journal is pleased to announce that color illustrations will be printed at
`no additional cost to authors starting with manuscripts published
`in 2000. The decision to publish particular figures in color or in high-quality
`black and white will be made at the Editor’s discretion. High-quality black and white
`figures should still be submitted when color does not contribute substantial
`additional information. Black and white figures made from color negatives
`or slides should, in general, be avoided.
`
`OCTOBER 2000
`
`AM Ac/up Drum/\'
`I
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`This malarial may be praleaed by capyngm law (Title 17 us. Code}
`
`
`
`A large-scale North American study of fungal
`isolates from nails: The frequency of
`onychomycosis, fungal distribution, and
`antifungal susceptibility patterns
`
`M. A. Ghannoum, PhD,“ R. A. Hajjeh, MD,b R. Scher, MD,C N. Konnikov, MD,d A. K. Gupta, MD,€
`R. Summerbell, PhD,f S. Sullivan, MD, PhD,B R. Daniel, MD,8 R Krusinski, MD,h
`P. Fleckman, MD,i P. Rich, MD,l R. Odom, MD,k R. Aly, MD,k D. Pariser, MD,1 M. Zaiac, MD,m
`G. Rebell, MD,“1 J. Lesher, MD,“ B. Gerlach, MD,0 G. F. Ponce-de-Leon,b A. Ghannoum,“
`J. Warner, BA,“ N. Isham, BA, M(ASCP),“ and B. Elewski, MD?‘
`Cleveland and Hudson, Ohio; Atlanta and Augusta, Georgia; New York, New York;
`Boston, Massachusetts; Toronto, Ontario, Canada; Jackson, Mississippi; Burlington, Vermont;
`Seattle, Washington; Portland, Oregon; San Francisco, California; Norfolk, Virginia;
`and Miami Beach, Florida
`
`Background: Onychomycosis, a fungal infection of the nail bed, is responsible for up to 50% of nail
`disorders. Although several surveys have been conducted in different parts of the world, there have been
`no multicenter epidemiologic surveys of onychomycosis in North America.
`
`Objective: A 12-center study was undertaken to (1) determine the frequency of onychomycosis, (2)
`identify organisms recovered from the nails, and (3) determine the antifungal susceptibility of isolates.
`
`Methods: A total of 1832 subjects participated in this study and completed a comprehensive questionnaire,
`and nail clippings were collected for potassium hydroxide examination and culturing.
`
`Results: The frequency of onychomycosis, as defined by the presence of septate hyphae on direct
`microscopy and/or the recovery of a dermatophyte, was found to be 15.8%. In general, the dermatophyte
`isolates were susceptible to the antifungals tested.
`
`Conclusion: Because of the limited number of large—scale studies, the baseline incidence is not firmly
`established. However, the higher frequency of onychomycosis in this study may confirm the suspected
`increase in incidence of disease in North America. (I Am Acad Dermatol 2000;/£32641-8.)
`
`nychomycosis can be caused by dermato-
`phytes, yeasts, or a select few nondermato—
`phyte molds. Dermatophytes, particularly
`Trichopbyton ruhrum and Trichophyton 7nentagro-
`phytes, are responsible for the majority of infections.
`Onychomycosis is the most common nail disorder in
`
`adults, accounting for up to 50% of all nail diseases.
`Suggested predisposing factors include increasing
`age, immunosuppression, poor peripheral circula-
`tion, trauma, and tinea pedis. Although the inci-
`dence of onychomycosis in the United States has
`been arbitrarily estimated by Zaiasl to be 15% to 20%
`
`From the Department ofDermato|ogy, University Centerfor Medical
`Mycologya; Division of Bacterial and Mycotic Infections, Centers for
`Disease Control and Prevention, Atlantab; Columbia Presbyterian
`Medical Center, New York‘; the Department of Dermatology, New
`England Medical Center, Bostond; Division of Dermatology,
`Department of Medicine, Sunnybrook Health Science Center and
`the University of Torontoe; Ontario Ministry of Health Mycology
`Laboratory and the Department of Laboratory Medicine and
`Pathobiology, University of Torontof; Department of Medicine,
`University Medical Center, Jackson9; One South Prospect,
`Burlington“; Department of Medicine, Division of Dermatology,
`University of Washington, Seattle‘; Department of Dermatology,
`Oregon Health Sciences University, Portlandi; University of
`
`California, San Francisco Hospitals and Clinicsk; Division of
`Dermatology, Eastern Virginia Medical School, Norfolk‘; Greater
`Miami Skin and Laser Center, Mt Sinai Hospital, Miami Beach”;
`Section of Dermatology, Department of Medicine, Medical College
`of Georgia, Augusta"; and Hudson, Ohio.°
`Supported by Pfizer Pharmaceutical Group.
`Accepted for publication March 28,2000.
`Reprint requests: M. A. Ghannoum, PhD, University Center for Medical
`Mycology, 11100 Euclid Ave, Cleveland, OH 44106-5028. E—mail:
`mag3@po.cwru.edu.
`Copyright © 2000 by the American Academy of Dermatology, Inc.
`0190-9622/2000/$12.00 + 0
`16/1/107754
`doi:10.1067/mjd.2000.107754
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`
`642 G/aannoum et al
`
`J AM ACAD DERMATOL
`OCTOBER 2000
`
`in those persons 40 to 60 years of age, there have
`been no recent multicenter epidemiologic surveys in
`the United States. Previous studies from the United
`
`Kingdom} Spain,3 Finland,4 and Canada5 report the
`incidence of onychomycosis as 2.7%, 2.6%, 8.4%, and
`6.85%, respectively. In a representative sample of
`20,000 persons in the northeastern United States in
`the late 1970s,
`the US Health and Nutrition
`Examination Survey (NHANES I) found the overall
`prevalence of fungal nail infection to be 2.18%.6 A
`1997 cross—sectional survey conducted in a derma-
`tology clinic waiting room in Cleveland, Ohio, found
`8.7% of patients to have culture—confirmed dermato-
`phyte onychomycosis.7
`Because there are relatively few large multicenter
`studies, we sought to provide a benchmark on which
`trends in the incidence of onychomycosis may be
`determined. In this study, we performed a multicen-
`ter investigation to determine the frequency of ony-
`chomycosis, the range of fungal species isolated
`from nails, and the antifungal susceptibility patterns
`of the isolated organisms. Participants included 12
`centers covering various regions (East, West, North,
`South, and Midwest) of the United States and one
`Canadian site.
`
`METHODS
`
`The study was performed from June 1997 to May
`1998. All subjects attending primary care physician
`offices or persons accompanying them during their
`visits were approached and asked to participate in
`this survey Excluded persons were those who
`refused examination and patients who presented for
`onychomycosis or tinea pedis. Nail clippings were
`taken from the most severely affected nail. When
`both fingernails and toenails were involved, samples
`were obtained from both sites. In cases in which no
`
`signs of onychomycosis were evident, nail clippings
`were taken from the big toenail. Subjects signed a
`consent form and completed an exhaustive ques-
`tionnaire covering demographics, personal habits,
`and medical history. Information was not collected
`on persons who refused to participate.
`All nail specimens were sent to the Mycology
`Reference Laboratory, Center for Medical Mycology,
`Cleveland, Ohio, for direct microscopic observation
`(with calcofluor in 10% potassium hydroxide) and
`culture (with the exception of the New York and
`Canadian specimens, whose laboratory results were
`provided to us). Furthermore, the Canadian site did
`not preserve the isolates and therefore susceptibility
`testing was not performed on these organisms.
`Primary isolation media included Mycosel agar (BBL,
`Cockeysville, Md) and potato dextrose agar with
`chloramphenicol and gentamicin. All cultures were
`
`incubated at 50°C for up to 4 weeks. Dermatophyte
`isolates were identified by microscopic morphology,
`urea testing, and Tric/aopbyton agars. All recovered
`yeasts were identified, using the germ tube test (for
`Candida albicoms) and the API 20C identification
`system (bioMerieux Vitek, Hazelwood, Mo). Only
`those nondermatophyte molds, which in the past
`have been implicated in nail disease, were identi-
`fied,8 again using microscopic morphology. Thus
`molds considered as highly unlikely to be significant,
`such as Alternaria, Curvularia,
`and most
`Aspergillus and Pem'cz'Zlz'um spp, were not included
`in the analysis of data.
`A case of onychomycosis was defined as a person
`with any one of the following: specimen positive for
`septate hyphae by microscopic examination and cul-
`ture positive for a dermatophyte, specimen positive
`for septate hyphae by microscopic examination and
`negative for dermatophyte culture, or specimen neg-
`ative by microscopy and positive for dermatophyte
`culture. The presence of septate hyphae and/or a
`dermatophyte was classified as a case of onychomy-
`cosis, regardless of the appearance of the nail.
`Because none of the cultures which grew C albicans
`were correlated with positive microscopic findings
`for yeast cells, it could not be ascertained whether
`the organism was a contaminant or was causing dis-
`ease (eg, paronychia). Therefore these C albicans
`isolates were not included in the data for ony-
`chomycosis cases. Similarly, no attempt was made to
`implicate any nondermatophyte mold isolated from
`these subjects as a causative agent of onychomycosis
`because no results from serial cultures were avail
`
`able. Nondermatophytes are included here for the
`purpose of organism distribution in the nail and anti-
`fungal susceptibility pattern information only.
`A microdilution broth assay, developed at the
`Center for Medical Mycology under the auspices of
`the National Committee for Clinical Laborator;
`Standards (NCCLS), was used to determine the pat-
`tern of antifungal susceptibility of all identified
`organisms.9 Dermatophytes were grown on oatmeal
`agar (100 g Heinz baby oatmeal cereal, 15 g granu-
`lated agar, and 30 mg gentamicin per liter). Although
`approximately 15% of T rubrumlo isolates make fe‘-'1’
`conidia, we were able to produce excellent conidia-
`tion from all isolates in this study by growing them
`on the oatmeal agar. Conidia were harvested with "-
`cotton-tipped applicator and transferred to sterile
`saline. The resulting suspension was counted with ;.
`hemocytometer and diluted in RPMI 1640 (with .'~
`glutamine, without
`sodium bicarbonate
`and
`buffered with MOPS at pH 7.0, Bioorganic, Niagam
`Falls, NY) to the desired concentration. Nonderma
`tophyte molds and yeasts were purified and harvest-
`
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`} AM ACAD DERMATOL
`“/OLUME 43. NUMBER 4
`
`Gbannoum er al 643
`
`Table 1. Selected characteristics of patients with onychomycosis in a multicenter onychomycosis survey (1997-
`1998, North America)
`
`Factor
`
`Median age (y) (range)
`Male
`Circulatory disease
`Athlete's foot
`Nail troubles
`
`Dystrophic nails
`Caucasian
`African American
`Hobbies
`
`Sports
`Painting/music
`Gardening
`Family members with nail
`disease or athlete's foot
`
`All
`participants
`Total No. (%)
`
`Onychomycosis
`cases
`No. (%)
`
`Nononychomycosis
`cases
`N0. (%)
`
`57 (
`23-98)
`58 (58)
`24 (29)
`8 (10)
`12 (15)
`
`51 (20)
`77 (79)
`10 (10)
`
`23 (30)
`8 (10)
`12 (16)
`39 (15)
`
`40 (1-87)
`265 (38)
`80 (19)
`14 (3)
`23 (6)
`91 (6)
`531 (84)
`39 (6)
`
`211 (45)
`74 (16)
`73 (16)
`312 (20)
`
`608 (84)
`49 (7)
`
`234 (43)
`82 (15)
`85 (16)
`351 (19)
`
`Percentages represent the proportion of subjects with the specified characteristic out of all subjects who supplied pertinent information.
`*This odds ratio was obtained by comparing cases with noncases using 56 years as a cut-off point.
`lstatistically significant factors (P S .05).
`
`ed from potato dextrose agar. Conidial suspensions
`were prepared and standardized as
`already
`described.
`
`Table II. Distribution of dermatophytes,
`nondermatophyte molds, and yeast species in the
`cultured nails
`
`Total
`isolates
`
`%
`
`Microdilution plates were set up in accordance with
`the NCCLS M—27A reference method,“ with the excep-
`tion of inoculum preparation as described earlier.
`RPMI 1640 was used as a medium, 35°C and 4 days as
`incubation temperature and time, respectively, and 2
`to 5 X 103 conidia/mL as an inoculum. The minimal
`
`inhibitory concentration (MIC) end point was defined
`as the concentration at which the organism was inhib-
`ited 80% as compared with the growth in the control
`well. Antifungal susceptibility was determined against
`fluconazole (Pfizer Pharmaceuticals, New York, NY),
`terbinafine (Novartis Pharmaceuticals, East Hanover,
`NJ),
`itraconazole (Janssen Research Foundation,
`Beerse, Belgium), and griseofulvin (Sigma Chemical
`Company, St Louis, Mo).
`Statistical analysis was performed at the Centers
`for Disease Control and Prevention (CDC), Atlanta,
`Georgia (CDC investigators were not involved in the
`design of this study or in the data collection).
`Univariate analysis was performed by means of Epi-
`Info version 6.03 and SAS 6.3 (SAS Institute, Cary,
`NC). Odds ratios (ORs) and 95% confidence intervals
`(CIs) were calculated with the statcalc option with
`Epi—Info. Chi—square tests were used to test for sig-
`nificant associations between defined variables.
`
`Values of P less than .05 were considered significant.
`The study was limited by the lack of information on
`basic demographics in many questionnaires, as well
`
`Organism
`
`Dermatophytes
`Trubrum
`
`Tmentagrophytes
`T tonsurans
`M canis
`E floccosum
`
`All dermatophytes
`
`Nondermatophytes
`Acremonium
`Fusarium
`
`Scopulariopsis
`Scytalidium
`A flavus
`
`A fumigatus
`A terreus
`A versicolor
`
`All nondermatophytes
`
`Yeasts
`C albicans
`
`C parapsilosis
`C guilliermondii
`C tropicalis
`C Iusitaniae
`
`All yeasts
`
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`
`644 Gbmmoum er al
`
`I AM ACAD DERMATOL
`OCTOBER 2000
`
`Table III. Percent distribution of dermatophytes, nondermatophyte molds, and yeast species from different
`regions of the United States and Canada
`
`Region
`
`Midwest
`
`Dermatophytes
`Total isolates
`
`KOH positive
`Trubrum (%)
`Tmentagrophytes (%)
`T tonsurans (%)
`M canis (%)
`E floccosum (%)
`Nondermatophytes
`Total isolates
`
`Acremonium (%)
`Fusarium (%)
`Scopulariopsis (%)
`Scytalidium (%)
`A flavus (%)
`A fumigatus (%)
`A terreus (%)
`A versicolor (%)
`Yeasts
`Total isolates
`C albicans (%)
`C parapsi/osis (%)
`C gui/Iiermondii (%)
`C tropicalis (%)
`C Iusitaniae (%)
`
`18
`16.7
`61 .1
`1 1.1
`5.6
`5.6
`
`East, Maine, New York, Vermont, Virginia; South, Florida, Georgia, Mississippi; Midwest, Ohio; West, California; North, Oregon, Washington,
`Canada.
`
`as lack of information on persons who refused to
`participate in this study These limitations prevented
`the use of multivariate analysis.
`
`RESULTS
`
`A total of 1832 persons agreed to participate in
`this survey, of whom 253 (13.8%) met the case defi-
`nition for onychomycosis as described above. If pos-
`itive microscopy is taken as the sole criterion, the
`frequency of onychomycosis would be 11.8% (n =
`217), whereas 7.2% (n = 131) of the subjects were
`dermatophyte culture positive alone. The median
`age of all patients with onychomycosis was 57 years
`(range, 1-98 years), 58% were male, and 10% were
`African American. Univariate analysis identified sev-
`eral factors to be associated with increased risk of
`
`disease (Table I). These included some demograph-
`ic factors such as age (those with onychomycosis
`were older than those without), sex (those with ony-
`chomycosis were more likely to be male), and clini-
`cal factors (the presence of diseases that affect the
`circulatory system, such as diabetes, vascular dis-
`
`eases, and hypertension, was associated with
`increased risk of onychomycosis (OR = 2.0; 95% CI,
`1.4-9.4), as well as having dystrophic nails (OR = 4.1;
`95% CI, 2.8-6.1). Race, a family history of nail prob
`lems or athlete’s foot, and participation in various
`sports or gardening activities were not associated
`with increased risk. In fact, participation in sports
`was associated with a decreased risk of having ony-
`chomycosis (Table 1).
`Of the organisms identified from all of the nail
`samples, dermatophytes were the most commonly
`isolated fungi (59%), followed by nondermatophyte
`molds and yeasts (representing approximately 20%
`each). Of the dermatophytes, Tricbop/9yz‘on rubrzmz
`was the most common isolate, followed by Tmem‘(.~
`gropbytes. T tonsumns, Microsporum cams, and
`Epidermopbyton floccosum accounted for 0.8% of
`the dermatophytes each. Acremomum, Fusarm/."~’.
`and Scopulariopsis spp were the most common iso-
`lates among the nondermatophytes (representing
`29.5%, 34.1% and 20% of nondermatophyte isolates.
`respectively). Small percentages (2.3%-4.5%) Of
`
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`1 AM ACAD DERMATOL
`VOLUME 43, NUMBER 4
`
`G/Jmmoum er L2] 645
`
`Table IV. Comparison of the percent distribution of
`fungal isolates in the United States and Canada
`Canada
`United States
`
`Organism
`
`%
`
`Dermatophytes
`Trubrum
`
`Tmentagrophytes
`T tonsurans
`M canis
`E floccosum
`
`Nondermatophytes
`Acremonium
`Fusarium
`
`Scopulariopsis
`Scytalidium
`A flavus
`
`A fumigatus
`A terreus
`A versicolor
`
`Yeasts
`C albicans
`
`C parapsilosis
`C guilliermondii
`C tropicalis
`C lusitaniae
`
`ScymZz‘dz'um, Aspergillus uersicolor, A _f/anus, A
`_fumz'gaz‘us, andA I.‘61”7‘€uS were also cultured. Among
`yeast species, Ccmdida pampsz'[osz's represented
`66.7%. C albiccms was recovered from 16.7% of cul-
`
`tures. Lower numbers of C gm‘!/z'er7nona'z'z', C [ropi-
`Calis, and C lusz'tam'ae were also isolated (Table II).
`In general, the same pattern of frequency of all
`organisms was observed when isolate distribution
`was queried by US regions, although there was a
`slight
`variation
`in
`distribution
`(Table
`III).
`Comparison of species distribution between the US
`and the Canadian sites revealed that although similar
`fungal species were isolated in the two countries, a
`difference in frequency patterns exists (Table IV).
`Interpretive breakpoints for clermatophytic fungi
`have not yet been established, and the clinical rele-
`vance of MIC results remains uncertain.“ However,
`
`all 4 antifungal drugs tested (terbinafine, flucona-
`zole, itraconazole, and griseofulvin) appear effective
`against the tested dermatophyte isolates, although
`several T memagrop/9y2.‘es isolates had elevated MICs
`to fluconazole. Overall, terbinafine (MIC§0 and MIC90
`of 0.001 ug/mL and 0.002 ug/mL, respectively) had a
`significantly greater activity than the other agents
`tested against the dermatophytes. For example, the
`mean MIC of terbinafine was 0.0012 as compared
`with a mean MIC of 0.104 for itraconazole (Table V).
`
`Table V. In vitro susceptibilities of 117
`dermatophyte isolates to fluconazole, itraconazole,
`terbinafine, and griseofulvin*
`MIC
`MIC
`
`Antifungal
`
`(pg/1nL,
`range)i
`
`(pg/mL,
`mean)
`
`MIC50
`(rig/mL)i
`
`MIC90
`(rig/mL)§
`
`Fluconazole
`ltraconazole
`Terbinafine
`Griseofulvin
`
`O.125—32
`<0.06—1.0
`<0.001~0.004
`<0.125—2.0
`
`2.77
`0.104
`0.0012
`0.44
`
`1.0
`0.06
`0.001
`0.25
`
`4.0
`0.125
`0.002
`0.5
`
`*|solates include Trubrum (n = 82), Tmentagrophytes (n = 33), Tron-
`surans (n = 1), and M canis (n : 1). No statistical differences in MIC
`ranges among species were noted.
`llnclusive M|Cs of all organisms tested.
`*Defined as the level at which 50% ofall organisms were inhibited.
`§Defined as the level at which 90% of all organisms were inhibited.
`
`Terbinafine had higher in vitro antifungal activity
`compared with the other
`3
`agents
`against
`Acremonium, Scopzz./a77'0psz'5, and Scytalz'dz'um spp
`(Table VI). In contrast, itraconazole had lower MIC
`values than the other 5 drugs againstAspergz'[[us and
`C pampsi/osz's. Finally, fluconazole was more active
`than the other agents against C albicans (Table VI).
`Of relevance for the antifungals evaluated, the mean
`