Microbiology
`
`qwfiarterly by
`the American
`
`PubHshed
`
`_L
`
`Society for_
`
`‘ i
`
`”.-
`
`i"
`
`*-
`
`i It:
`' a
`
`' g.
`at
`
`: fi‘
`
`:9;
`
`. i
`
`«h
`
`: g
`
`. Q
`
`

`

`CLINICAL MICROBIOLOGY REVIEWS
`
`VOLUME 11 0 JULY 1998 0 NUMBER 3
`
`Betty A. Forbes, Editor in Chief (2002')
`.S'UNY Hettitit Science Center
`
`Lynne S. Garcia. Editor (2002}
`UCLA Medical Center
`[,th .--"lttgct'es. Cttiii‘:
`
`Kenneth D. Thompson. Editor (2002)
`Uttr'i-“tttin' of Chicago n-ictit'ctti Center
`Chicago. Hi.
`
`Syracuse. NY.
`
`Judith E. Dormer (1999)
`Kevin Hazen {1998}
`
`EDITORIAL BOARD
`
`J. Michael Miller [3000]
`Andrew Onderdonk {300“}
`Daniel F. Salim “998}
`
`Steven C. Specter (2001])
`Gregory A. Starch (1998]
`
`
`
`Barhara H. lglcwski. Ci'tttimttttt. Prtt’riir'utt'otts Board
`Beyerley .1. Bennett. Production Editor
`
`Linda M. Illig. Director. Jormtot's
`Victoria A. Cohen, Assistant Production Editor
`
`Citttt‘t'oi t't'iicrohioir'tgt: Rcvicws considers for pttbiicntiott not}: solicited and unsolicited reviews and monographs dealing with at! aspects
`of clinical t-nt'crohiot'ogv. Mt'tttuscrt‘pts. proposals. and correspondence regarding editorial nutttets shottid be addressed to tho Editor in
`Chief: BcttyA. Forbes. Department tJfC‘iitl'tC‘t’ti Putiroiogy. S UNl"Hcoitt’r Science Center. 750 East/{dams St. Syracuse. NY {3210-2330.
`
`
`Cit‘nt‘coi ilrt‘tcmbr'oiogr Reviews {ISSN “SUB-SSH) is published quarterly (January. April. July, and October), one volume per year,
`by the American Society for Microbiology [ASM). Nonmember print subscription prices (per your) are: ti I46. U.S.; 515”. Canada
`(plus W}?- GST. or 7% GST + 89?- HST where applicable}: $168. Europe: $169. Latin America: Still. rest of world. Member print
`subscription prices (per year] are: $40. L1.S.: 343. Canada (plus 1% GST. or 7‘}? GST + 8‘???- HST where applicable): $53. Europe;
`554. Latin America; 555. rest of world. Singles Copies are: $47. nonmembcr: $15. member (Canadians add 7‘}?- GST, or ”Vii.- (SST
`+ 8’}? HST where applicable}. For prices of CD-ROM versions. contact the Subscriptions Unit. ASM. Correspondcncc relating
`to subscriptions. defective copies. missing issues. and availability of back issues should be directed to the Subscriptions Unit. ASM;
`cm-rcspondencc relating to reprint orders should be directed to the chrint Order Unit. ASM: and correspondence relating to
`disposition of submitted manuscripts. proofs. and general editorial matters should be directed to the Journals Department,
`American Society for Microbiology. 1325 Massachusetts Ave.. N.W.. Washington. DC‘ zooms—no. Phone: (202] TST-Jhfltl.
`
`Claims tor missing issues from residents of the United States. Canada. and Mexico must be submitted within 3 months after
`publication of the issues: residents of all other countries must submit claims within 6 months of publication of the issues. Claims
`for issues missing because of failure to report an address change or for issacs “missing from files" will not be allowed.
`
`CODEN: CMlREX
`
`Periodicals postage paid at Washington. DC 20005. and at additional mailing offices.
`
`POSTMASTER: Send address changes to Cit‘m'crti .t-t'ict'oht‘oiogv Rcrt’cus. ASM. 1325 Massachusetts Ave.. N.W.. Washington. DC
`ZUIZlUS-éli 7! .
`
`_
`.
`.
`.
`.
`Made [It the United States of America. Prmtcd on acrd~free paper.
`
`I
`
`i
`--
`
`'
`I 5 l
`
`-
`
`.
`
`i".
`
`'i iii. my.
`
`.
`
`3
`
`Copyright II) 1998. American Society for Microbiology.
`
`9....
`_
`.
`.
`.
`. .ifm‘ disfig-
`
`
`
`All Rights Reserved.
`
`The code at the top of the first page ot’an article in this journal indicates the copyright owner‘s consent that copies of the article
`may be made for pcrsmral use or for personal use ol'spccitic clients. This consent is given on the condition, however. that the copier
`pay the stated pervcopy l'ec through the Copyright Clearance Center. Inc.. 222 Rosewood Drive. Dunvcrs. MA “1923, for copying
`beyond that permitted by Sections ill? and IUS ol’ the US. Copyright Law. This consent does not extend to other kinds of copying.
`such as copying for general distribution. for advertising or promolionai purposes. for creating new collective works. or for resale.
`
`

`

`Clinical
`
`Microbiology
`
`Reviews
`
`A Publication of the Ari-teriean Sot‘ithfor Mierobioiogv
`
`VOLUMEH .
`
`JULY1998 . NUMBERS
`
`
`
`CONTENTS/SUMMARIES
`
`4054M
`
`Anne H. Rowley and Stanford T. Shulmzm. ..
`Kawasaki Syndrome.
`Santana)? Kin-I'asahi srndrome (KS) is an acute. sometimes fatai 1raseuiitis ofyoang ehiidrcn.
`KS has rephu'ed arate rheumatic fever as the most common reuse oi'aequired heart disease in
`ehiidrcn in the United States. The iihiess is manifested by proionged‘fia‘er. r‘onjiinetieai iniee—
`tion. enaathem. exanthein. enrthema and sit-'eiiiag oj'the hands and Jfeet. and ccn‘ieai adenop-
`nth}: Thesc acute _h'titities ofiihtess are seiiliiniiting. hut coroinnji-r artery aimormaiines ocear in
`209? of untreated patients. The etioiogv of the iihtess is unknown, hat its ciinieai and epide—
`n'iioiogic features are most consistent n-‘ith an inieetioas cause. Common eara'ioi'ascahn' man-
`ifestations of the iihiess inehuie nn‘m‘arditis, periearditd effusion. and coronary artery aneurysm
`formation. Treatu'teni with intrasenous gannna giohtdin {1' FCC) and aspirin within the first iii
`days of iiiness reduces the Itit't'l’ttitfrtflt' of eomnai)’ artery ahnornudttics from 2W3:-
`in those
`treated with aspirin aione to 45%.. Patients who c't'el-'t-'ir'i_.o coronary artery aneurysms. partieahirh'
`those who dereiop giant eoronaiy tii‘iL’ij' anetaji-Lsms. may sitiier ni_\-’oeara'iai infareiirm secondary
`to thrombosis or stenosis in the abuortnai resset'. .tldditionai researeh to determine the cause of
`K8 is amends needed to idhavior ittipt'fll-‘L’ti diagnosis. more speeiiic therapy, and prevention of
`the disorder.
`
`Boni
`Onychomycosis: Pathogenesis, Diagnosis. and Management.
`E.Elewski 415—429
`Summary: Ahhrntgh not iif'e—threatening. Otlj’t'itt'fltil-‘(Yls‘is (ahingai infliction oi'ihe naii. usuaih'
`roused by a derniatoph_\-'tel constitutes an important pttht’ie heahh prohicni because of its high
`prevalence (about i0")?- oi‘the L-‘ZS. popidation) and associated morhia'ity. The disease can have
`eertain t'iegatire eonseaaenees for patients. such as pain. and ean potentiat'h' undermine li-‘(Ji'ix'
`and sociai iii-es. This review discusses the etioiogr. ciassiiieation, diagnosis. and treatment of
`on].'ehoni_'.reosis. Four t_'.-'pes ofoii__\-'choni_reosis an: n'eogninfd based on the site and pattern of
`fliugai invasion. Deonatopityte fiatgi are the predon'tinant pathogens. but 's‘easts t'espeeiaiir
`Candida aiiiieans) and itotat'ermatophrte moids may aiso be implicated. :‘ieeiaate diagnosis
`remotes direct ntieroseogn' and fitngai caiture. The tiiii'ereatiai diagnosis inehides psoriasis.
`iichen pianos. oit_\'ehogrvphosis. and and trauma. Onrehonn‘eosis is more tiiflictdt to heat than
`most derntatophytoses beeause of the inherent sion' growth oi'the naii. ()ider antiiiaigat’ agents
`thetiu'onazoz‘e and griseofuh'int are unsuitahie for Ott_l't_‘il'I')iii_l-‘(‘r.t,\'i_\" inseause of their reiatil'eh'
`poor eiiieaey and potentiai adverse Lifer-ts. Three reeentis' devehiped antim_s'eotic agents (fla-
`ern-tazoie.
`itiaeonazoie. and teihinafinei oifer high cure rates and good safi’n' profiles.
`in
`addition. the short treatment times {<23 months} and intermittent dosing srhedt ties are iiheh‘ to
`enhance eotnpiianee and reduce the costs of tin-raps.
`
`('ontinued on ihiiouring page
`
`

`

`Contained horn preceding page
`
`Robert A. Dudas and Ruth
`Respiratory Syncytial Virus Vaccines.
`A.Karron 430—439
`
`Summary: Respiratory svnq-‘tiai virus {RSI-’3 is the rrtost important cause of virai iau'cr' respi-
`ratory tract iiincss URI} in infants and chiidren waddwidc and causes significant LR! in the
`cideriy and in ininarrun-ornprorniscd patients. The guai ofRS I" vaccination is to prevent serious
`RSl-"'va.s.s-crc-itrteii LRi. There are scverai obstacies to the dcvehnnnent ofsuccesshd RSV vac-
`cines. inciuding the need to irnnrunize very young infirnts, who may nesponttT inadequateh- to
`vaccination: the erisrencc oftwo arrtigenicaih' distinct RSI-’grotrps. r] and B; and the history of
`disease enhancementfollowing administration ofa jorrrraiin—inacti1-'ated vaccine. it is iikch' that
`more titan one type of vaccine H'iii he needed to prevent RSV LRI in the. various popuiations
`at risk. .riithough vector dciivery svsterns. svr-rthetic peptide. and itnntune—stun[dating cornpiex
`vaccines have been et-‘aiuated in animal ntodcis. oniv the purified F protein (PFPi subunit
`vaccines and iivc attenuated vaccines have been marinated in recent ciinicai rr'iais. EFF-2
`
`appears to be a promising vaccine Jtor the eideriv and for RSI-"—seropositi1-'e children with
`underh’ing puhnonar}: disease. whereas iivc cohhpassagcd (rcpt. temperature-sensitive (tsi RSV
`vaccines (denoted cpts vaccines) wouhi most probabhr he uset'ui in young infants. The avail-
`ahiiitv of cDNA technologt shouid aiiow firr‘ther refinement of existing live attenuated cpts
`candidate vaccines to produce engineered vaccines that are satisfactoriiv attenuated, immuno—
`genic. and phenotvpicaiiv stable.
`
`Campyiobacter upsaiiensis: Waiting in the Wings.
`Voon Loong Chan, and Philip Sherman ...... .
`
`.
`
`.
`
`.
`
`.
`
`Billy Bourke.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`. ..
`
`.
`
`440—449
`
`Summary: Despite strr'rrrg cpidenrioiogicai evidence supporting an important mic. for Campy-
`iobactcr upsaiiensis as a human enteropathogen. it remains reiativeh‘ unknown in the reahrr of
`ciinicai rnicn'rhioiogg-t Ciinicai studies indicate that
`infection with this organism trstraii_'.-' is
`associated with herrign sch‘liirniting diarrhea. However. more serious iiinesse.‘. inciuding spon-
`taneous abortion and hemoivric—urernic syndrome. recerrriv have been associated with human
`infections. Undecstanding of the vindence properties and moiecrtiar hioiogv off. trpsaiiensis is
`beginning to er-‘ohre. There is now a pressing need for comroiied. prospective cpidcmioiagic
`studies in addition to firrthcr in—depth investigation ofthe pathogenesis of this enteric campy—
`iobacter to more preciseiy define its role in human disease. Furthermore. since C. upsaiiensis is
`sensitive to the antibiotics routineiv used in C'arnpyiohacter seiective media, widespread appre-
`ciation ofthc importance of this organism wiii reiy on the tier-’eiapntent of n-Jideiv appiicahie.
`cjh'ctive techniques for its isaiatt'on.
`
`Pathogenesis and Diagnosis of Shiga Toxin-Producing Escherichia and
`Infectious.
`James C. Paton and Adrienne W. Paton. .
`.
`.
`.
`.
`.
`.
`. ..
`
`450—4'i9
`
`Summary: Since their initiai recognition 20 years ago. Shiga rosin-producing Escherichia coii
`('STEC) strains have emerged as an important cause rri'scrious human gastrointestirrai i‘iisease.
`which ma): res-uh in uni—threatening compiiearions such as hernohttic-un'nric svndrome. Food—
`horne outbreaks of STEC disease appear to be increasing and. when nuns-produced and
`mass—distributed foods are concemed. can invohte (urge numbers ofpcopic. Del-'eiopnrent of
`thenrpeutic and preventative strategies to combat STEC' disease requires a thorough under-
`standing of the mechanisms by which STEC organisms eoionize die human inrestinai tract and
`cause focal and systemic pathoiogicai changes.
`i-iv’hiie our knot-viedge. remains inconnrt'etc.
`recent studies hat-re it‘itprm-’{’t'i our understanding of these pmcesses. panicrdar'h‘ the contpies
`interaction between Shiga toxins and host ceiis. which is centrui to the pathogenesis ofSTEC
`disease. in addition. severed putative accessory vindence factors have be at identrfiea’ and partiy
`characterized. The capacity to innit the scaIc and serenity of STEC disease is aiso dependent
`upon rapid and sensitive diagnostic procedures for anairsis of human sampt'es and suspect
`vehicics. The increased uppiication Uffltil’fltiflflti moiecuiar technoiogies in t.'iinicai iahoratories
`has signrfirantiy improved our capacity to diagnose STEC infection eariy in the course of
`disease and to detect ion' ieveis of envirorunentai conturniruuian. This. in turn. has created a
`potentiai Ivirrdrm' ofnrrportunity firrfitture tr’rer‘inxutie irrten’cnrion.
`
`{.ontrnrrcd on firihneurg page
`
`

`

`Continued Iti'otn preceding page
`
`Dengue and Dengue Hemorrhagic Fever.
`
`Duane J. Gubler. .
`
`.
`
`.
`
`.
`
`.
`
`.
`
`.
`
`.
`
`480—496
`
`Summary: Dengue fi-‘l'i‘t'. u ['8th old disease. has reentetged in the past Eileen”- with an tu‘panded
`geographic distribution of both the viruses arid the mosquito vectors.
`increased epidemic
`activity. the t'lei-cloptnent ofltjt-peremlemicity (the ctnrireulation ofntultiple set-tropes}. attd the
`emergence ofdengue hemorrhagicfever in new geographic regions. lrt was thisinosauito—horne
`disease is the most important tropical infectious disease afier malaria, with an estimated Hill
`million cases oft'lengtte fever, 500,000 cases of dengue hemotrl'tagn'cfever. and 25.000 deaths
`annuallv. The reasons for this resurgence and emergence ofdengtte hemorrhagic fever in the
`waning years of the 20th century are cornpter and not fitllv understood. but demographic.
`societal. attd puhlic health infrastructure changes iii the past 30 years have contributed greath'.
`This paper reviews the changing epidemiologv of dengue arid dengue hemorrhagic fever by
`geographic region, the natural historv and transmission circles, clinical diagnosis ot'hoth dengue
`lever and dengue hemorrhagic firver. scrologie and vit'ologic laboratory diagnoses. pritltttgenesis.
`surveillance. prevention. and control. A major challengctor public health officials in all tropical
`areas of the world is to devleop and itrtplement sustainable prevention and c'ontml programs
`that will reverse the trend oj'etncrgent dengue hemorrhagic tel-er.
`
`Epidemiology of Group B Streptococcal Disease in the United States:
`Shifting Paradigms.
`Anne Schuchat. . ....................... .
`
`497—513
`
`Surrrrnarjv: Since its emergence 25 years ago. group B streptococcus has become recognized as
`a cause of serious illness in newborns. pregnant women. and adults with chronic medical
`conditions. Heavy colonization ofthe genital tract with group B strepun'oecus also increases the
`risk that a woman will deliver a preterm low-lritthweight infant. Eariv-onset infections {occur-
`ring at <7 days of age) are associated with much ion-“er fatality than when they were first
`described. and their incidence is finallv decreasing as the use of preventive antilrioties duringr
`childbirth increases among women at risk. New seron'pes of group B streptococcus have
`emerged as important pathogens in adults and newborns. Clinical and lahot'atoq practices—in
`obstetrics. pediatrics. and clinical microbiologv—have an impact on disease andlor its preven—
`tion. and protocols established at the institutional level appear to he critical tools for tltc
`redttction of perinatal disease due to gmup [l streptococcus. Since intraparturn antibiotics will
`prevent at best only a portion of the full harden of group B streptococcal disease. critical
`developments in vaccine evaluation. including study of polvsaechar'ide-pnnein conjugate vac-
`cines. ojler the potential for enhanced pt“£’l-'e’ttiit)tt in the relativelv near fitture.
`
`Serum Therapy for Tuberculosis Revisited: Reappraisal of the Role of
`Antibody-Mediated Immunity against Mycohacterium tuberculosis.
`Aharona Glatman-Freedman and Arturo Casadevall. .. ...........
`
`514—532
`
`Summary: Fifty years aficr the introt'lttction of the Jfirst effective antimicrobial agents against
`lib-'cobacterium tuberculosis. this pathogen continues to be a tremendous public health prob—
`lem. The rise in the number of resistt'tnt strains and the difficulties irn-‘oli-‘ed in the therapv of
`tuberculosis in intnntnoeompr'ornisetl .4 l[)5 patients have renewed the interest in the develop—
`ment qt'efhm'tive t-‘aceines. To evaluate whether a potential vaccine against tuberculosis could
`prevent infection hv eliciting a protective antihodv response. we reviewed the history ofarrtibod ‘-
`mediated immunity against tuberculosis. Review of the literature of the past llitl'years demon-
`strates that there is sufficient evidence to conclude that ataihodv—mediatetl immunity cart tnodilt‘
`the course of inflation in certain situations. Based on ourfina’ings and on what is h'th-‘tl' in
`other systems, we propose that the role of antibody-mcdiated humanity to M. tuberculosis be
`reetamined. using athaotced technology.
`
`Quantitation of Cytomegalovirus: Methodologic Aspects and Clinical
`Applications.
`Michael Boeckh and Guy Boivin .............. ..
`
`533—.54
`
`Summary: Cvtotncgalovirtis (Civil-"J is an important pathogen in transplant recipients and
`human inttnttnodeticiencr virus (Hllr’J-inl’ected indivii'luals. Major progress has been made in
`developing quantitative detection methods for CM l" in recent rears. Due to their high sensitivity
`
`(tantrum! on lolhnvirie page
`
`

`

`('utttintn'd ii'unt tacit-dine page
`
`these assays can detect Cit-ii” ettt'h’. and quantitation may he usetttt' in predicting the patients
`risit. for disease ttttti in monitoring the effect afantirirai theraoy. This review discusses ntetit—
`tnioiogicai aspects of currenth' used quantitative assays fitr CM!" tie, rit‘ai cuitttre techniques.
`antigtn t'ietectitn-t assay”. DNA detection assays ittchttiing PC.‘R. branched—DNA assay. and the
`UM"! hyht'id capture assay) and addresses the correlation of systemic and site-utectfit.‘ Chit”
`iauti and (MP disease itt different populations of itttatunosupprcssed patients as net? as the
`response to antil'it'ai treatment. To date tiia-‘ct antigen detection and ttttiitfcttiar techniques have
`hujaeh' tephtced tradititnuti caiture-hased tcchniqttesfhr CMV qttantitation. in generai. a high
`systemic (Til-fl“ hunt is cotreiateti with CML’ disease. This rotreiatian is strong in the hill-"-
`infected pupuintiutt and in soiidwman transpiant recipients hat iess ciear in ailogeneic tnatrow
`transpiant recipients. Measttring the rind hand at specific anatomic sites may he an aiternatice
`way tn assess disease actit-‘ity in situations where the. systct-nic virai iuad t'ott'eiates poarh‘ with
`disease activity.
`.4 rethtctiatt oi the systemic C'MV iond aiso con‘eiates with a response to
`antit'it‘ai treatment, hut tnotc t'eseatch is needed to en 'uhtate the mic ofrirat’ itntti as a stmugute
`utttrket‘jor tirug resistance. Due to the widespread use Qitftttttttitttiil-‘L’ ("Ml-"detection techniques
`to direct and monitor atttit'irai treatment.
`there is a great need for an assessment of thc
`reprothtcibiiity oftest resttits and hetter stantiartiization of the assa_'.‘s.
`
`and Guillain-Barré
`Species
`Cantpyiobacter
`Nachamkin, Ban Misha A1103, and Tony Ho
`
`Syndrome.
`.
`.
`.
`.
`.
`.
`.
`
`.
`
`.
`
`.
`
`.
`
`Irving
`.
`.
`.
`. ..
`
`SSS—.6?
`
`Since the enniicatiau oi’poiio in most parts of the world. Gttiiiain-Barré st'ndmnte (OBS) has
`become the must cununnn cause oiactttc flaccid {tenth-act's. GBS is tttt autoimmune disorder in"
`the pcn'pht't‘at' ncntous system characterized by weakness. usaat'h’ svntatetricah emitting over a
`period of set-end days or inure. Since iabotatories began to isoiate Cantpyiabacter species front
`stool specimens some EOyetus ago there have hcctt many reports of CBS fitiiowittg Campy-
`iohaeter infection. Ont} dating the pastfen-years has strong evidence supporting this association
`det'ehnted. C‘tutun'ioimctcr inflection is not-v known as the singic ntost identifiabie antecedent
`infection associated with the devcioptnent of CBS. Catntn'iohacter is thought to cause this
`autoinuuune disease through a mechanism cat'ieti ntoiecuiarntitnicrjt'. wherehy Cttnipyinbacter
`cut-nains gat'tgiioside-iike epitnpes in the iipopoiysaccharidc moiety that eit'cit aatnantibotiies
`reacting with peripheral-ti nerve targetn Canutviahacter is associated with .s‘c'l-‘c't‘tti pathoiolgrt'c
`forms of CBS. inchaiing the detnvciittating (acute itifituntntttoty dean-chanting poh‘uettmpatityi
`and round (acute tttotor tLl‘tttttti neat-apathy)flaunts. Different strains of C'anunriahacteras wcii
`as host tin-tats iiheiy piay an important roie in determining who deveiops (335‘ as weii as the
`t'tt’t'l’ti’ targets for the host immune attach triateripherai net-res. The ptttpase of this review is to
`sunutau‘ize our current itnon-‘ietige about the ciitticai. cnitiett-tiot'ttqicai. pathogenetic. and inh—
`orntoty aspects of cantpyh)bttctet'—associated 635.
`
`For your convenience, the full text of the 1998 CMR issues will be available unline by late July
`1998. Access will be free for all of 1998. Please visit www.journals.asm.0rg for more information.
`
`f'rttttttttteti int iitiirtu'tng page
`
`

`

`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`(‘1.1NltaL Mnnomoiom Rt vnaws. July was. p. iii-420
`uses-551erosional” it
`Copyright (Ci
`
`J‘JUH. American Socielt'
`
`l'or Mict'ol‘linlug). All Rights Rescued.
`
`VIII. H. No. 3
`
`Onychomycosis: Pathogenesis, Diagnosis,
`and Management
`BONI E. ELEWSKW
`
`I'Janrmicm in" Dcnnntoiogta lJ‘niI-'er.tii_\-‘ Hospitals of Cicreinmi.
`Case l-l-‘k’stcm Rosette Unit-(55in: Clot-ennui. Ohio
`
`INTRODUCTION
`ONYCHOMYCOSIS..........
`
`non-nu..." ................ "mu...
`
`........-“......”onun-"......."...-u..."-“sauna-......"-
`
`........................
`
`.........415
`.......................
`.......416
`
`...........416
`Definition and Clinical Impact.
`
`Epidemiology and Risk Factor5...
`
`DERMAIOPHYTES AND ONYCHOMYCOSIS
`«nun-"......
`
`CLINICAL TERMINOLOGY.
`.....417
`
`...
`ANATOMY OF THE NAIL ...
`....417
`
`CLASSIFICATION OF ONYC‘HOMYCOSIS
`....417
`
`....4]?
`Distal Suhungual OI'IX'CI'IOIIIMSUSIS
`. ..
`..
`..
`..
`
`....418
`Proximal Sultungual Onychomycusi
`
`.
`.
`...-418
`White Superficial Onychomycusis
`
`Candida Infections of the Nail
`....... 419
`“...-unusuu.
`419
`Total Dystrophic Onychomycosis
`DIAGNOSIS OF ONYCHOMYCOSIS
`
`419
`. 4..l9
`Differential Diagnosis...............
`
`........420
`Collecting the Nail Specimen...........
`
`
`Distal subungua] onyehomycosis .......
`
`....420
`Proximal subungual onychumycosis..........
`....unu...
`
`
`White superficial onychomycosismmm...
`Candida onpchomyeosis ......
`......
`
`
`ncunnuuu... ... nu .
`Specimen Analpsis...
`
`
`AN] LFUNGAL SUSCEPTIBILITY TESTING ..........
`
`ANI‘IMYCOTIC AGENTS USED TO 'I REA'F ONYCHOMYCOSIS..............
`.............«nu-......"...-..."...annun-".........-......
`
`
` .u-un
`Limitations of Traditional Antifungal Agents
`Grisenfulvin
`Ketoconaznle .................
`
`.....................
`
`
`
`
`Advantages of Newer Antifungal Agents
`Fluennazole
`Itraconazule
`Terbiuafine..................
`ANTIFUNGAL THERAPY...................
`
`“can..."...-..."..nn ...
`
`
`Comparative Trials of Antifungal Agents" ....................
`Adjunets to Systemic Therapy ...............
`.......
`...-"..."..uun." ....
`. "...“ “nun“..uu. ..
`
`Prevention of Relapse after TreatnIeIIt.....
`
`Selection of an Appropriate Thetapy .. ..
`
`Clinical Management of Treated Patients .......
`
`Educating Patients about Their Role in Treatment.
`
`CONCLUSION................... ................... .
`.
`
`
`REFERENCES .........
`........................ . ....... .................
`...................
`....................418
`
`INTRODUCTION
`
`Most cutaneous inlections are the work of the homogeneous
`group of keratinophilic l'ungi known as dcrutatophytes. The
`dermul'ophvte Tricimpitt'tr'm i'iiiu'um is the major cause ol" tineu
`pedis and onychonrveosis (ti). Al’tcr originating in West Africa.
`Southeast Asia. Indonesia. and Northern t-Xustrztlia. T. rm‘n‘nm
`spread to Europe and North and South America in the late
`ltlth and eariy Ellth centuries, where it found a niche within a
`
`
`" Mailing address: Department of Dermatology. University Hospi—
`tals of Cleveland.
`llltll} Euclid Ave. Cleveland, OH 44lilh-5IJJH.
`Phone: illn) 544-31”.
`[-ax: {Elm set—snot E-Inuil: BEELEWSKI
`in. AOL.C(.)M.
`
`recenlly shod populace (8}. Subsequent leth century develop-
`ments including wars, the modern hcalth rnLWeInenl and the
`associated use of occlusive footwear and locker rooms. and
`migration of people since the invention of the jumbo jet. pro-
`moted an increased incidence of tinea pedis and onyehomyco-
`sis (H).
`Dermatophytoses ol' the fingernails and toenails. in contrast
`to those at other body sites. are particularly ditlicult to eradi—
`cate with drug treatment. This is the consequence of [actors
`iolIinsie to the nail—the halrd protective nail plate sequestlu-
`lion of pathogens betwucn the nail bed and plate and slour
`growth ol the nail—as well as oi the relutivclv poor efficacy ol
`the early pharmacologie aoents
`Recent years. however. have witnessed the development of a
`
`415
`
`

`

`ullt’i
`
`bl..l:.WSl~il
`
`(Us. Mn ttoutot. Rrv.
`
`new generation of antifungal drugs that prodttce impressive.
`long-lasting cure rates with shorter treatment times and better
`safety prot'iles than ketoconazole and griseofulvin. In this pa-
`per. current knowledge of the pathogenesis. diagnosis. and
`management of onychomycosis with these new agents is re—
`viewed and evaluated.
`
`ONYCHOMYCOS [5
`
`Definition and Clinical Impact
`
`“Onyehomycosis” traditionally referred to a nondermato—
`phytic infection of the nail but is now used as a general term to
`denote any fungal nail
`infection (63) [tinea unguium specifi-
`cally describes a dermatophytic invasion of the nail plate}. In
`spite of the clearly diseased appearance associated with this
`condition- onychomycosis is all too often regarded as merely a
`cosmetic problem of relatively minor importance that is hardly
`worth the effort to resolve. This belief may have been sup-
`ported by the adverse etfccts and long dosing courses associ-
`ated with some of the earlier antifungal agents.
`In fact. onychomycosis can have significant negative elfecls
`on patients‘ emotional- social. and occupational functioning
`and can. in addition. consume a sizable proportion of health
`care dollars. Alfeeted patients may experience embarrassment
`in social and work situations. where they feel blighted or on-
`clean. unwilling to allow their hands or feet to be seen. Patients
`may fear that they will transmit their infection to family mem—
`bers. friends, or coworkers. fears that can lead to diminished
`self-esteem and the avoidance of close relationships (55]. Etn—
`ployment suffers if employers are reluctant to hire individuals
`with abnormal nails. particularly l'orjobs such as food handling
`or modelling or where interaction with the public is required.
`A more tangible barrier to work success is the discomfort some
`patients experience that prevents them from carrying ottt work-
`relaled tasks such as prolonged standing, writing. or typing.
`Finally. onychomycosis can compel workers to take periodic
`sick leave. a problem even for treated patients if therapy is
`ineffective andfor long-lasting (55). This lack of success.
`in
`turn. can cause patients to feel discouraged or even to stop
`treatment. resigning themselves to permanent disfigurement
`and discomfort.
`
`Onyehomycosis in immunocompromised patients. such as
`those infected with human immunodeficiency virus {HIV}. can
`pose a more serious health problem [55). Not only does the
`diflicult—to—treat infection serve as a constant reminder to the
`patient of his or her own deteriorated condition. but the pos-
`sibility exists of transfer of a very high titer of fungal pathogens
`to another person {55).
`
`Epidemiology and Risk Factors
`
`Dermatophytoses of the stratum corneum. hair. and nails
`are common. whereas infection of the dermis and subcutane—
`ous tissue by these agents is rare ((14). Although dermatophytic
`infections are rarely life—threatening. their high incidence and
`prevalence and the associated morbidity ((14) make them an
`important public health problem t
`| ).
`Reports concerning the prevalence of onychomycosis are
`conflicting, with estimates ranging from 2 to 3'25? of t he general
`US. population (I?) to I3“?- of the male Finnish population
`(still.
`to a recent outpatient-based. cross—sectional survey of
`l.ll3ti patients in a dermatology clinic waiting room in Cleve-
`land. Ohio. culture-confirmed dermatophyte onyehomyeosis
`was identified in 8.79; of the total population and in 6.5 and
`|3.3"5:i- of the female and male subgroups. respectively {patients
`
`who presented for onychotnycosis were excluded) (.717). These
`figures are comparable to those for the general Finnish popu—
`lation {lists-i) (4m. Several studies have shown that the prcv~
`alcnee of onychomycosis increases with age. For example. none
`of the 31m Finnish subjects who were younger than Ell years
`had rmychomyeosis but almost 349?.— ot’ those aged 70 years or
`older had the disorder. Similarly. 23.15.??- ol‘ the members of the
`Ohio cohort aged so years or older were culture positive for
`onychomyeosis. versus H and 3.99-2.-
`t‘or those aged 11] to .18
`years and 19 to 30 years. respectively {27]. Reasons for the
`age-related increase in onychomycosis may include poor pe-
`ripheral circulation. diabetes. repeated nail trauma. longer ex-
`posure to pathogenic fungi, suboptimal immune function. in-
`activity. or the inability to cttt the toenails or maintain good
`foot care (22. 3.7. 55).
`As is the case among adults. prevalence rates for onycho—
`mycosis among children are quite variable: a recent review of
`studies of the subject in several countries outside North Amer-
`ica lists prevalence rates varying from [1% (United States.
`Wales. and Finland) to 2.0”}? {Guatemala} {38}. To learn more
`about
`the prevalence of onychoniycosis among children in
`North America, a prospective survey was conducted of 2.5UlJ
`young (5 18 years] patients and family members in Canada and
`the United States. Subjects nails were examined for signs of
`onychomyeosis and sampled for direct microscopy and culture.
`Onyehomyeosis was diagnosed in It children {10 with alfeeted
`toenails. and .l with affected fingernails], indicating a preva-
`lence of 0.445%: however. 7 of these children had been referred
`for treatment of onychomyeosis or tinea pedis. Thus. the prev-
`alence of onychomycosis in children with primary diagnoses
`other than onychomycosis or tinea pedis was 4 of 2.500, or
`tt.l(r‘:-‘é (3?). The reasons for this fill—fold decrease in the prev—
`alence of onychontycosis in children relative to adults may
`inclttde redttccd exposure to fungus because less time is spent
`in environments containing pathogens;
`faster nail growth;
`smaller nail surface for invasion; and lower prevalence of tinea
`pedis (37).
`Contact with the source of the infection constitutes a risk
`factor; for example. Int-liophyron trerrueosnm commonly inv
`fects the faces of farmers who lean against their cows as they
`milk them {fist}. There is no doubt that several factors unique
`to modern life have resulted in an increased prevalence of
`onychomycosis. These include the wearing of shoes, particu—
`larly fashionably tight. high-heeled shoes: the increased use by
`large numbers of people of damp spaces such as locker rooms
`and gymnasiums: the declining health of the aging American
`population. and the increased number of immunocompro—
`mised patients through disease te.g., HIV infection} or thera-
`peutic agents {e.g.,
`immunosuppressive therapies associated
`with cancer or posttransplatitation care. and the extensive use
`ofhroat‘l-spectrum antibiotics] (25}. Other factors that increase
`the risk ofonychomyeosis are direct trauma to the nail. includ—
`ing that resulting from certain tic disorders (cg. nail biting).
`
`DERMATUPHY'I‘ES AND ONYCHOMYCOSIS
`
`The term “dcrmatophytosis" is used to describe infection by
`members of the genera i't-fici'osportini. Ti‘t‘cl'roplrvmn. and Ept?
`Jet'trttill'lftl-‘fflrt. The species that most oftc n cause onyeltomycosis
`in North America and parts of Europe are T. i'tihr'tmi. T. men-
`tngropftlt-‘tt‘s. and Epidctrnopfn'ton flra't'ostiin: the first two spe-
`cies are much more often implicated than E. fleeces-tint (58).
`Infections of the skin. nail. and hair by nondcnnatophytic
`molds such as .S'tytnfitfitmi and Scopuftniripsr's are termed "der-
`malomycoses." Dcrmatophytcs account for most (90%] cases
`of onyclloinycosis ol' the toenails and at least Sl'l‘I-i. of fingernail
`
`

`

`Vi'ti
`
`ll. “NH
`
`[JN\"(.‘I-[OMYC'OSIS
`
`4|?
`
`infections {3]}. Both dcrmatophytes and nondcrmatophytes.
`especially Candida rrfhicrms. have been identified as sole etio.
`logic agents of onychomycosis: however. the incidence of true
`mixed infections [caused by dcrmatophytcs plus nondermato-
`phyles) is difficult to determine accurately (SH) and is discussed
`in detail below.
`
`The dcrmatophytcs are hyalittc scptated molds. The hyphac
`of these mycclial organisms penetrate the stratum corneum of
`the skin and nails. The fungal cells manufacture kcratinolytic
`proteases. which provide a means of entry into living cells {3-9}.
`Some dermatopltytic species. which are basically soil sapro—
`phytcs that have acquired the ability to digest kcratinous debris
`in soil. have evolved to be capable of parasitizing kct'atinotts
`tissues of animals [I].
`The familie