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`CLINICAL MICROBIOLOGY REVIEWS
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`VOLUME 11 0 JULY 1998 0 NUMBER 3
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`Lynne S. Garcia, Editor (2002)
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`UCLA Medical Center
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`Los Angcies, Calif.
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`Betty A. Forbes, Editor in Chief (2002)
`SUNY Heaitii Science Center
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`Syracuse, NY.
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`Kenneth D. Thompson, Editor (2002)
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`Universint of Chicago Medicai Center
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`Chicago, Iii.
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`Judith E. Domer (1999}
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`Kevin Hazen (1998)
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`J. Michael Miller (2000)
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`Andrew Under-dank (2000)
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`Daniel F. Sahm (1998}
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`Steven C. Specter (2000)
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`Gregory A. Starch (1998)
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`Barbara H. lglewski, Chairman. Publications Board
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`Chief; Betty/4. Forbes, Department of Clinical Pathoiog’. SUNY Health Science Center. 750 East Adams St., Syracuse, NY 13210-2339.
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`Page 2 of 17
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`Page 2 of 17
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`I
`to.
`ICAL MICROBIOLOGY REVIEWS. July 1998. p. 415—429
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`93-85 12i08t$04.00 + 0
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`Copyright © 1998, American Society for Microbiology. All Rights Reserved.
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`Vol. 11. No. 3
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`Onychomycosis: Pathogenesis, Diagnosis,
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`and Management
`BONI E. ELEWSKI‘
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`Department ofDermnroioy, Universin Hospitals of Cleveland,
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`Case Westem Reserve Universitv, Cleveland. Ohio
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`u...."noun-nun-uuu-uuuuouuu
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`"no-noun. «nun...
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`ONYCHOMYCOSIS................. ..
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`Definition and Clinical Impact
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`Epidemiology and Risk Factors
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`DERMATOI’HYTES AND ONYCHOMYCOSI
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`CLINICAL
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`ANATOMY OF THE NAIL
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`CLASSIFICATION OF ONYCHOMYCOSIS
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`Distal Subungual Onychomycosis
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`Proximal Snbungual Onychomycosis
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`White Superficial Onychomycosis
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`Total Dystrophic Onychomycosis ..
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`DIAGNOSIS OF ONYCHOMYCOSI
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`Difl'erential Diagnosis.......................... ..
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`Collecting the Nail
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`Distal subungual onychomycosis
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`Proximal subungual onychomycosi
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`White superficial onychomycosis
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`Candida onychornycosis..
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`Specimen Analysis
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`ANTIFUNGAL SUSCEPTIBILITY
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`ANTIMYCOTIC AGENTS USED TO TREAT ONYCHOMYCOSIS..
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`Limitations of Traditional Antifungal Agents
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`Griseofulvin
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`«noun-nu
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`a - u- . nu nu us a n.
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`Advantages of Newer Antifungal
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`Fluconazole
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`Itraconazole
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`ANTIFUNGAL
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`Comparative Trials of Antifungal Agents.......
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`Recent years. however, have witnessed the development of a
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`..........4l8
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`""419
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`...41 9
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`..........42[l
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`...42|J
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`...421
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`".427
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`....427
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`Clinical Management of Treated Patients
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`Educating Patients about Their Role in Treatment
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`INTRODUCTION
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`Most cutaneous infections are the work ofthe homogeneous
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`group of keratinophilic fungi known as dcrmatophytes. The
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`dcrmatophyte Trichophyron moi-um is the major cause of tinea
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`pedis and onychomycosis {8). After originating in West Africa.
`Southeast Asia. Indonesia. and Northern Australia, 1“". mbmm
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`spread to Europe and North and South America in the late
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`19th and earl}.r 201h centuries, where it found a niche within a
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`" Mailing address: Department of Dermatology. University Hospi-
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`tals of Cleveland.
`lll[)(l Euclid Ave. Cleveland, OH 44106—5028.
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`Phone: [216) 844-3177. Fax: (216) 844-8093. E-mail: BEELEWSKI
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`@AOL.COM.
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`Page 3 of 17
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`recently shod populace (8). Subsequent 20th century develop-
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`ments including wars. the modern health movement and the
`associated use of occlusive footwear and locker rooms, and
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`migration of people since the invention of the jumbo jet, pro-
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`moted an increased incidence of tinea pedis and onychomyco-
`sis (8).
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`Dermatophytoses of the fingernails and toenails, in contrast
`to those at other body sites, are particularly difiicult to eradi—
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`cate with drug treatment. This is the consequence of factors
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`intrinsic to the nail—the hard, protective nail plate, sequestra-
`tion of pathogens between the nail bed and plate, and slow
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`growth of the nail—as well as of the relatively poor efficacy of
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`the early pharmacologie agents.
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`Page 3 of 17
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`

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`CLIN. M1010 ,,
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`who presented for onyehomyeosis were excluded) (21); ,
`figures are comparable to those for the general Finnish
`lation (8.4%) (40). Several studies have shown that
`It”
`alence of onyehomyeosis increases with age. For examp
`of the 200 Finnish subjects who were younger than 3 ,
`liad onyehomyeosis but almost 24% of those aged 70
`of“
`older had the disorder. Similarly, 28.1% ofthe member; )1 ~
`Ohio cohort aged 60 years or older were culture posi
`onyehomyeosis, versus LI and 2.9% for those aged 10“.
`years and I9 to 30 years. respectively (27). Reasons
`(-
`age-related increase in onyehomyeosis may include . I .
`ripheral circulation, diabetes, repeated nail trauma. lo 5
`posure to pathogenic fungi, suboptimal immune functi
`activity, or the inability to cut the toenails or 'maintain..
`foot care (22. 27, 55).
`As is the case among adults. prevalence rates for M;
`mycosis among children are quite variable: a recent r ‘
`'
`studies of the subject in several countries outside North 2'. :.
`ica lists prevalence rates varying from 0% (United .7
`Wales. and Finland) to 2.6% (Guatemala) (38). To learn“
`about
`the prevalence of onyehomyeosis among chil 6.
`North America, a prospective survey was conducted of 4‘
`young (5 18 years) patients and family members in Canada ‘
`the United States. Subjects’ tiails were examined for si
`onyehomyeosis and sampled for direct microscopy and en!
`Onychomycosis was diagnosed in 11 children (10 with a
`toenails, and l with affected fingernails), indicating a n
`lence of 0.44%; however, 7 of these children had been ref 1
`for treatment of onychomycosis or tinea pedis. Thus, the _ _'.
`alcnec of onychomycosis in children with primary 3-.
`other than onyehomyeosis or tinea pedis was 4 of 2 Hr.
`0.16% (37). The reasons for this 30-fold decrease in the v
`alcnee of onyehomyeosis in children relative to adults
`include reduced exposure to fungus because less time is ~-
`w
`in environments containing pathogens; faster nail
`1:
`smaller nail surface for invasion; and lower prevalence of -~._~’
`pedis (37).
`Contact with the source of the infection constitutes a
`factor; for example, Tn'chophyton venucosum commonly
`fccts the faces of farmers who lean against their cows as n..-
`milk them (64). There is no doubt that several faCtors uni
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`to modern life have resulted in an increased prevalence}-
`onyehomyeosis. These include the wearing of shoes. p ,
`larly fashionably tight, high-heeled shoes; the increased use-
`large numbers of people of damp spaces such as locker r .
`and gymnasiums; the declining health of the aging Amati
`population, and the increased number of immunocom r
`mised patients through disease (e.g.. HIV infection) or
`_
`peutic agents (e.g., immunosuppressive therapies assoc“ '
`with cancer or posttransplantation care. and the extensive .
`of broad-spectrum antibiotics) (25). Other factors that incre
`the risk of onyehomyeosis are direct trauma to the nail. inf:l
`ing that resulting from certain tic disorders (e.g., nail bit!!!
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`DERMATOPHYTES AND ONYCHOMYCOSIS
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`The term “dermatophytosis” is used to describe infection "
`members of the genera Microsporum, Trichophyton, and E ’
`‘
`demiophyton. The species that most often cause onyehomy N -'
`in North America and parts of Europe are T. rubrum. T.
`tagrophytes, and Epidermophyton floceosum: the first two 5 "
`eies are much more often implicated than E. floccm'um (58 -
`Infections of the skin, nail. and hair by nondermatophyfl?
`tnolds such as Scylulidium and Scopulafiopsis are termed “dare
`matomycoses." Dermatophytes account for most (900/1) 08'
`of onyehomyeosis of the toenails and at least 50% of finge
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`4 l6
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`ELEWSKI
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`new generation of antifungal drugs that produce impressive,
`long-lasting cure rates with shorter treatment times and better
`safety profiles 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.
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`ONYCHOMYCOSIS
`
`Definition and Clinical Impact
`
`“Onychomycosis” 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, onyehomyeosis 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 effects and long dosing courses associ-
`ated with some of the earlier antifungal agents.
`In fact, onyehomyeosis can have significant negative effects
`on patients' emotional. social, and occupational functioning
`and can, in addition, consume a sizable proportion of health
`care dollars. Affected patients may experience embarrassment
`in social and work situations. where they feel blighted or un-
`clean. unwilling to allow their hands or feet to be seen. Patients
`may fear that they will transmit their infection to fartiin mem-
`bers. friends, Or coworkers, fears that can lead to diminished
`self-esteem and the avoidance of close relationships (55). Em-
`ployment suffers if employers are reluctant to hire individuals
`with abnormal nails, particularly forjobs 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 out work-
`related tasks such as prolonged standing, writing. or typing.
`Finally. onyehomyeosis can compel workers to take periodic
`sick leave. a problem even for treated patients if therapy is
`ineffective and/or 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.
`
`Onychomycosis in immunocompromised patients, such as
`thme infected with human immunodeficiency virus (HIV), can
`pose a more serious health problem (55). Not only does the
`difiicult-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).
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`Epidemiology and Risk Factors
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`Dermatophytoses of the stratum corneum, hair, and nails
`are common, whereas infection of the dermis and subcutane-
`ous tissue by these agents is rare (64). Although dermatophytic
`infections are rarely life-threatening. their high incidence and
`prevalence and the associated morbidity (64) make them an
`important public health problem (1).
`Reports concerning the prevalence of onyehomyeosis are
`conflicting, with estimates ranging from 2 to 3% of the general
`US. population (27) to 13% of the male Finnish population
`(40).
`In a recent outpatient-based. cross-sectional survey of
`l,038 patients in a dermatology clinic waiting room in Cleve-
`land, Ohio, culture-confirmed dermatophyte onyehomyeosis
`was identified in 8.7% of the total population and in 6.5 and
`13.3% of the female and male subgroups. respectively (patients
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`Page 4 of 17
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`1998
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`ONYCHOMYCOSIS
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`417
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`ponychium (Fig. 2). The infecting organism migrates proxi-
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`fl». (31). Both demtatophytes and nondermatophytcs.
`1y Candida albicans, have been identified as sole etio-
`'
`ts of onychomycosis; however. the incidence of true
`5». actions (caused by dermatophytes plus nondermato-
`.5‘,
`. difficult to determine accurately (58) and is discussed
`below.
`"2 nnatophytcs are hyalinc scptatcd molds. The hyphac
`' mycelial organisms penetrate the stratum corneum of
`u and nails. The fungal cells manufacture keratinolytic
`which provide a means of entry into living cells (39).
`'ermatophytic species. which are basically soil sapro-
`'v-u at have acquired the ability to digest keratinous debris
`, have evolved to be capable of parasitizing keratinous
`j'of animals (1).
`families that include many of the known keratinolytic
`re the Anhmdermataceae and Onygenucmc in the phy-
`i r ycora (52). Members of these families are homoge-
`'th respect to appearance. physiology. taxonomy, anti-
`" , basic growth requirements.
`inl'ectivity, and the
`'
`they cause (52). Some, such as Microspomm (ants and
`w agrophylcs, have affinity for thc keratin of animals and
`whereas others are more specialized for a particular
`host (1).
`'bility with respect to the causative microorganism is
`"1 ' ographic and, within a given region. temporal. Because
`ms that cause clinically apparent disease tend to receive
`sin attention, pathogens whose invasion leads to hard-
`”w
`tdiscasc may bc present in a region but are less likely
`identified (1). By contrast, pathogens that cause readily
`« nt signs and symptoms are likely to be identified and
`. prevalence is likely to be noted. Thus, because reports
`5; the 1970s focused primarily on scalp infections, T. vio-
`was the most frequently isolated derrnatophyte during
`'t‘ ' aide in Europe (1 ) although 7‘. tmtsurans is the principal
`.-'I of tincu capitis in the United States and is emerging in
`pe.
`angcs over time within a region in the prevalence of
`5,3 v lar dermatophyte species also are common: although M.
`"ta‘nii and M. crmis were the most common causes of scalp
`'n in Western and Mediterranean Europe 50 to 100
`‘
`~ ago. tinca capitis has declined in incidence in Western
`7
`it -- and. when present. is caused primarily by M. canis (l)
`4 . vinlaccum ( l). Similarly, M. nudouinii and M. (unis were
`Imain causes of tinea capitis in the United States earlier in
`century; this role has been taken over by T tonsurans (l).
`' ther change that has occurred in recent years is the grow-
`» prevalence of dermatophytoscs of the foot (tinea pedis)
`‘ mils (tinca unguium) and decline in the prevalence of
`-u infections (1).
`
`CLINICAL TERMINOLOGY
`
`in many areas of medicine, the clinical terminology used
`(describe dennatophytic infections evolved in advance of
`.* rate knowledge about causation or pathophysiology. Tinea
`F gnawing worm") or "ringworm," a term derived from the
`-, ’arance of the characteristic skin lesions in this common
`Imatophytosis (64), affects the scalp (tinea capitis), glabrous
`’_«‘- (tinea corporis), groin (tinea cruris), nail (tinca unguium).
`7 ‘«
`(tinca pedis). beard (tinca barbac), and hand (tinca
`. 1 Hum). Other dermatophytoses are named for their appear-
`such as tinea favosa (favus. or honeycomb-like due to T.
`f‘ nleinii) or tinea imbricata (“composed of overlapping
`'
`“; ringworm due to T. concentricum).
`
`Page 5 of 17
`
`DORSAL VIEW
`
`Lateral
`"all
`
`.
`
`Nail plate
`Nail bed
`Lunula (distal matrix)
`Proxtmal nail told
`
`LATERAL VIEW
`
`Nail plate
`Cuticle
`Nail bed/ Mam
`
`I. The nail unit. Reprinted from reference 11 with permission of the
`FIG.
`publisher.
`
`ANATOMY OF THE NAIL
`
`A review of the anatomy of the nail unit and the process of
`nail growth may be helpful in understanding the pathogenesis
`of dermatophytic fungi in the nail unit. A diagram of the nail
`unit is presented in Figure I (11). It consists of the following
`structures: proximal and lateral folds. cuticle. matrix. nail plate
`(commonly called the nail), nail bed. and hyponychium. The.
`cuticle is the horny layer of the proximal nail fold; it consists of
`modified stratum corneum and protects the nail matrix from
`infection (12). The nail matrix is the growth center ofthe nail.
`As the nail grows. cells of the nail matrix divide, differentiate.
`and kcratinizc and are incorporated into the nail plate. The
`distal. visible part of the matrix looks like a "half moon” and is
`called the lunula. The matrix extends approximately 5 mm
`proximally beneath the proximal nail fold (l2). The nail plate
`is the largest structure of the nail unit and grows by sliding
`forward over the nail bed, whereupon the distal end becomes
`free of the nail bed (44). The hyponychium, the most distal
`component in the nail bed.
`is composed of epidermis that
`includes a granular layer similar to that seen in plantar and
`volar surfaces (12). Fingcrnails grow at a rate of 2 to 3 mm per
`month. and toenails grow at a rate of 1 mm per month. There-
`fore. it takes about 0 months to replace a fingernail and be-
`tween 12 and 18 months to replace a toenail (12). This rate of
`growth is often decreased in the presence of peripheral vascu-
`lar disease and onychomycosis and in the elderly (12).
`
`CLASSIFICATION OF ONYCHOMYCOSIS
`
`Four types of onychomycosis. charactcrizcd according to
`clinical presentation and the route of invasion, are recognized.
`
`Distal Subungual Onychomycosis
`
`Distal subungual onychomycosis (D50) is the most common
`form of onychomycosis. It is characterized by invasion of the
`nail bed and underside of the nail plate beginning at the hy-
`
`

`

`

`

`
`
`Candida Infections of the Nail
`
`321/ nail infections occur in patients with chronic mu-
`. us candidiasis. and are caused by C. albicans (3). The
`:invades the entire nail plate. Candida spp. may cause
`.a
`u omes. including onycholysis and paronychia. These
`‘qu more commonly in women than in men (3) and
`'
`the middle linger, which may come into contact
`:1 i
`I organisms that reside in the intestine or vagina
`‘ In onychomycosis can therefore be divided into
`f oral categories. (i) Infection beginning as a paro-
`‘fection of the structures surrounding the nail; also
`“whitlow"). the most common type of Candida ony-
`...:
`(54), first appears as an cdcmatous. reddencd pad
`mg the nail plate. Invasion by Candida spp.. unlike
`‘hytic invasion. penetrates the nail plate only second-
`.u r it has attacked the soft tissue around the nail (12).
`.t ection of the nail matrix occurs.
`transverse depres-
`t: au’s lines) may appear in the nail plate. which be-
`unvex. irregular. and rough and. ultimately. dystrophic
`
`5 tients with chronic mucocutaneous candidiasis are at
`
`the second type of Candida onychomycosis. called
`.-
`‘T'r granuloma. which accounts for fewer than 1% of
`'<-. ycosis cases (12, 54. 66). This condition is seen in
`. it mpromised patients and involves direct invasion of
`'j“ plate (30). The organism invades the nail plate directly
`affect
`the entire thickness of the nail. resulting,
`in
`‘1» d cases.
`in swelling of the proximal and lateral nail
`" til the digit develops a pseudo-clubbing or "chicken
`'_'»
`'ck” appearance (54).
`it Finally, Candida onycholysis can occur when the nail
`} has separated from the nail bed. This form is more
`on on the hands than the feet
`(3). Distal subungual
`_ eratosis can be seen as a yellowish gray mass lifts off the
`late. The lesion resembles that seen in patients with DSO
`
`Total Dy'slmphic Onychomycosis
`
`tal dystrophic onychomycosis is used to describe end-
`nail disease. although some clinicians consider it a dis-
`'v2 subtype. It may be the end result ofany of the four main
`7" ms of onychomycosis. The entire nail unit becomes thick
`1 dystrophic (65).
`
`DIAGNOSIS OF ONYCHOMYCOSIS
`
`i
`
`‘ e clinical presentation of dystrophic nails should alert the
`' ian to the possibility of onychomycosis; however, because
`' i cause only about half of all nail dystrophies (30). the use
`appropriate diagnostic techniques including direct micros-
`i.- and fungal culture is important to ensure correct diagno-
`and treatment. The clinical appearance of the nail and the
`'ent's history will help differentiate fungal from nonfungal
`logics of nail dystrophies. For example. predisposing fac-
`‘t
`for onychomycosis include diabetes mellitus. older age.
`j“ rhidrosis. onychogryphosis. nail trauma. poor peripheral
`"- ulation. and immunosuppression (l2). In the presence of
`bungual hyperkeratosis, yellow-brown discoloration. and on-
`holysis, onychomycosis is likely to be present. If the patient
`~
`21 history of tinea pcdis. particularly moccasin type. the case
`*t
`.I this diagnosis is even stronger (l2).
`Page 7 of 17
`
`()NYCI-IOMYCOSIS
`
`41‘)
`
`FIG. 5. Psoriasis affecting the nail. Courtesy of C. R. Daniel Ill.
`
`Differential Diagnosis
`
`(‘arc should be taken to correctly identify signs and symp-
`toms of other diseases that clinically mimic onychomyCosis.
`These include psoriasis (the most common such disorder).
`lichen planus. bacterial
`infections. contact dermatitis.
`trau-
`inatic onycliodystt‘opltics, pacltyonycliia cottgenita. nail bed tu-
`mors. yellow~nail syndrome (rare). and idiopathic onycholysis.
`When psoriasis all'ects the nails.
`it
`is usually also present at
`other skin sites; however. in some cases nail involvement is the
`only sign (6). When psoriasis alfccts the nails.
`it can produce
`onycholysis resembling that associated with 050 (Fig. 5). A
`diagnosis of psoriasis is supported by the presence of line
`pitting on the nail surface. the small salmon-colored “oil drop"
`sign of onycholysis that
`is not seen in onychomycosis. and
`fingernail involvement of both hands (28).
`Approximately um of patients with lichen planus have ab-
`normal nails. "'l‘wenty-nail" dystrophy is ti condition of un-
`known cause. Onychorrhcxis (exaggerated longitudinal ridg-
`ing) and “angel wing deformity." in which the central portion
`of the nail is raised and the lateral portion is depressed (28).
`are manifestations of lichen planus. A patient with 20 dystro-
`phic nails is unlikely to have onychomycosis. Contact derma-
`titis occasionally resembles onychomycosis. The correct diag-
`nosis is facilitated by knowledge of kn0wn contactants and the
`presence of contact dermatitis elsewhere on the body.
`Finally. repeated nail trauma can cause distal onycholysis.
`leading to colonization of the affected space by microorgan-
`isms that produce pigmentation of the area. It the onycholytic
`nail is clipped to allow examination of the nail bed. [he latter
`will be normal if the symptoms are caused by trauma rather
`than onychomycosis. Nail products containing formaldehyde
`may also cause onycholysis.
`In this situation.
`the nails may
`become yellow and all exposed nails are affected. A habit tic.
`often manifesting as a median furrow or depression in the
`middle of the nail. developed from picking at the nail cuticle.
`may also cause abnormalities of the nail.
`
`

`

`

`

`. 998
`
`ONYCHOMYCOSIS
`
`42]
`
`
`
`9 half of all specimens taken from onychomycotic nails
`'cld a pathogen in culture. In onychomycosis, direct
`L. is the most efficient screening technique (26, 63).
`g: . cimen can be mounted in a solution of 20 to 25%
`' NaOH mixed with 5% glycerol. heated to emulsify
`h at 51 to 54°C). and examined under X40 magnifi-
`tAn alternative formulation consists of 20% KOH and
`'ethyl sulfoxide (63). The specimen may be counter-
`'with chitin-specific Chlorazol black E to accentuate
`‘ that are present; this is of particular value if the num-
`t. al elements is small. This stain is especially useful
`1- it does not stain likely contaminants such as cotton or
`-- fibers. which can help prevent false-positive identifica-
`ju ). Parker blue-black ink also can be added to the KOH
`': tion to improve visualization, but this stain is not chitin
`
`'
`
`7‘ re is the only method by which the causative microor-
`can be identified. Caution should be used in analyzing
`results, because nails are nonsterile and fungal and
`4‘
`'i: contaminants may obscure the nail pathogen (63).
`ens should be plated on two different media: a primary
`‘m that is selective against most nondermatophytic molds
`teria, and a secondary medium that allows such growth.
`it admide inhibits the growth of nondermatophytes and is
`m rated into media such as dermatophyte test medium or
`,1: ud peptone-glucose agar (Emmons' modification) with
`_:t ximide, available under a variety of names (Mycobiotic
`'-' Laboratories, Detroit, Mich.) and Mycosel [BBL Cock-
`i Md.]) (63). Cyclohcximidc-frcc media that are com-
`; used include Sabouraud’s glucose agar. Littman’s oxgall
`~I- u and inhibitory mold agar (Sabouraud‘s glucose agar
`'7 the addition of antibiotics) (25). if growth occurs on both
`-: of media, the infective agent is probably a dermatophyte,
`growth only on the cycloheximide-free medium indi-
`. that the infective agent may be a nondermatophyte such
`pulariopsis brevicaulis, Scytalidium dimidiatum. or Scy-
`hyalinum.
`i ever. growth of a nondermatophyte alone from a spec-
`that has tested positive for fungi on direct microscopy
`: not prove conclusively that the infective agent is a non-
`1- tophyte (63). The last three decades have seen unequiv-
`-," documentation of the role of nondermatophytes as causal
`-* in onychomycosis (59). The most common yeast that is
`_lved is C. albicans (58). Of the nondermatophytic filamen-
`~: fungi, agents implicated in onychomycosis include mem-
`_ of Scapulariopsis (particularly S. brevicault's) and Scy-
`' m (the two most common genera), which are both
`6‘ ht to digest keratin in vivo, as well as members of the
`A fit Allemaria, Aspelgillus, Acremom’um, and Fusarium (59).
`.24 y of these nondermatophyte fungi invade the nail unit
`1'
`fly and cause WSO. Other nondermatophytic fungi that
`7 cause onychomycosis include Onychocola canadertsis, Pyre-
`?- eta tmguierominis, and Bohyodiplodia Ihcobromac (Ta-
`« l) (57, S9).
`1 Part of the difficulty in evaluating the role of nondermato-
`7 c fungi cultured from the nail arises because the same
`in i that can be laboratory contaminants are also occasionally
`'1 nd to be pathogens (58). Reference laboratories should
`*1 Vide data on whether the isolated fungus was a likely patho-
`i n or an unlikely one. All dermatophytes should be consid-
`ed pathogens. All other isolated organisms are probably lab-
`i atory contaminants unless KOH or microscopy indicates
`'cy have the atypical frondlike hyphae associated with non-
`ermatophyte molds or if the same organism is repeatedly
`latcd. Potential pathogens associated with onychomycosis
`‘2 e listed in Table l.
`
`Page 9 of 17
`
`TABLE I. Major causes of onychomycosis
`
`Dcrmatophytc fungi
`Epidemmphymn floccnsum
`Tfichophylon menmgmphylcs
`Tfichophyton mbmm
`
`Nondcrmatophyte fungi
`Acremom'um
`Altcmaria species
`Aspelgillus species
`Borryodiplodia thcnbmmac
`Fusarium species
`Onycochola canadcnsis
`I’yrruoclmcm ultguis-Iiuminix
`Scyialidium dimidiamm scopulariopsis species
`Scytalidium hyalimum
`
`Yeast
`Candida albicans
`
`To increase the predictive power of a diagnosis of nonder-
`matophytic invasion of a nail, Summerbell (58) suggested that
`nonfilamentous nondermatophytes identified in nail tissue be
`categorized as one of the following: contaminant
`(species
`growing in culture from dormant propagules on the nails):
`normal mammalian surface commensal organism; transient sa-
`probic colonizer (colonizer of accessible surface molecules but
`noninvasive); persistent secondary colonizer (colonizer of ma-
`terial infected by a dermatophyte but incapable of remaining
`after the dermatophyte is eliminated): sueccssional
`invader
`(species that can cause infection after gaining entry into a nail
`via the disruption caused by a primary pathogen); or primary
`invader (able to infect and cause onychomycosis in a previously
`uncolonized nail). Such an analysis has the value of identifying
`for treatment only nondermatophytic infections that are truly
`mvaswc.
`
`As an additional confirmatory technique, definitive identifi-
`cation of nondermatophytic invasion in nails may require the
`isolation of the agent from successive specimens from the
`infected region (03). If the infective pathogen is a dermato-
`phyte, subsequent cultures will most probably grow out the
`dermatophyte itself, a second contaminant unrelated to the
`first, or no growth at all. Some investigators believe that claims
`of an increasing proportion of mixed infections in onychomy-
`cosis are exaggerated and have gone so far as to state that
`nondermatophyte molds and yeasts are usually contaminants
`secondary to dermatophyte onychomycosis and that their pres-
`ence need not affect treatment outcome (31).
`
`ANTIFUNGAL SUSCEPTIBILITY TESTING
`
`Part of the diagnosis and treatment strategy might include
`fungal susceptibility testing. Susceptibility testing for antifun-
`gal drugs was virtually unknown in the 19803 but is now the
`focus of interest of the Subcommittee for Antifu