CLINICAL MICROBIOLOGY REVIEWS,
`0893-8512/98/$04.0010
`Copyright © 1998, American Society for Microbiology. All Rights Reserved.
`
`July 1998, p. 415–429
`
`Vol. 11, No. 3
`
`Onychomycosis: Pathogenesis, Diagnosis,
`and Management
`BONI E. ELEWSKI*
`Department of Dermatology, University Hospitals of Cleveland,
`Case Western Reserve University, Cleveland, Ohio
`
`INTRODUCTION .......................................................................................................................................................415
`ONYCHOMYCOSIS...................................................................................................................................................416
`Definition and Clinical Impact .............................................................................................................................416
`Epidemiology and Risk Factors ............................................................................................................................416
`DERMATOPHYTES AND ONYCHOMYCOSIS....................................................................................................416
`CLINICAL TERMINOLOGY....................................................................................................................................417
`ANATOMY OF THE NAIL .......................................................................................................................................417
`CLASSIFICATION OF ONYCHOMYCOSIS .........................................................................................................417
`Distal Subungual Onychomycosis ........................................................................................................................417
`Proximal Subungual Onychomycosis ...................................................................................................................418
`White Superficial Onychomycosis ........................................................................................................................418
`Candida Infections of the Nail ..............................................................................................................................419
`Total Dystrophic Onychomycosis .........................................................................................................................419
`DIAGNOSIS OF ONYCHOMYCOSIS ....................................................................................................................419
`Differential Diagnosis.............................................................................................................................................419
`Collecting the Nail Specimen ................................................................................................................................420
`Distal subungual onychomycosis ......................................................................................................................420
`Proximal subungual onychomycosis.................................................................................................................420
`White superficial onychomycosis ......................................................................................................................420
`Candida onychomycosis ......................................................................................................................................420
`Specimen Analysis ..................................................................................................................................................420
`ANTIFUNGAL SUSCEPTIBILITY TESTING........................................................................................................421
`ANTIMYCOTIC AGENTS USED TO TREAT ONYCHOMYCOSIS..................................................................422
`Limitations of Traditional Antifungal Agents ....................................................................................................422
`Griseofulvin .........................................................................................................................................................422
`Ketoconazole........................................................................................................................................................422
`Advantages of Newer Antifungal Agents..............................................................................................................423
`Fluconazole ..........................................................................................................................................................423
`Itraconazole .........................................................................................................................................................424
`Terbinafine...........................................................................................................................................................425
`ANTIFUNGAL THERAPY.........................................................................................................................................426
`Comparative Trials of Antifungal Agents............................................................................................................426
`Adjuncts to Systemic Therapy...............................................................................................................................427
`Prevention of Relapse after Treatment................................................................................................................427
`Selection of an Appropriate Therapy...................................................................................................................427
`Clinical Management of Treated Patients ..........................................................................................................427
`Educating Patients about Their Role in Treatment ..........................................................................................427
`CONCLUSION............................................................................................................................................................428
`REFERENCES ............................................................................................................................................................428
`
`INTRODUCTION
`
`Most cutaneous infections are the work of the homogeneous
`group of keratinophilic fungi known as dermatophytes. The
`dermatophyte Trichophyton rubrum is the major cause of tinea
`pedis and onychomycosis (8). After originating in West Africa,
`Southeast Asia, Indonesia, and Northern Australia, T. rubrum
`spread to Europe and North and South America in the late
`19th and early 20th centuries, where it found a niche within a
`
`* Mailing address: Department of Dermatology, University Hospi-
`tals of Cleveland, 11100 Euclid Ave., Cleveland, OH 44106-5028.
`Phone: (216) 844-3177. Fax: (216) 844-8993. E-mail: BEELEWSKI
`@AOL.COM.
`
`recently shod populace (8). Subsequent 20th century develop-
`ments including wars, the modern health movement 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 onychomyco-
`sis (8).
`Dermatophytoses of the fingernails and toenails, in contrast
`to those at other body sites, are particularly difficult to eradi-
`cate with drug treatment. This is the consequence of factors
`intrinsic to the nail—the hard, protective nail plate, sequestra-
`tion of pathogens between the nail bed and plate, and slow
`growth of the nail—as well as of the relatively poor efficacy of
`the early pharmacologic agents.
`Recent years, however, have witnessed the development of a
`
`415
`
`ARGENTUM EX1048
`
`Page 1
`
`

`

`416
`
`ELEWSKI
`
`CLIN. MICROBIOL. REV.
`
`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.
`
`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, 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 effects and long dosing courses associ-
`ated with some of the earlier antifungal agents.
`In fact, onychomycosis 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 family 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 for jobs 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, onychomycosis 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
`those infected with human immunodeficiency virus (HIV), can
`pose a more serious health problem (55). Not only does the
`difficult-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 (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 onychomycosis are
`conflicting, with estimates ranging from 2 to 3% of the general
`U.S. population (27) to 13% of the male Finnish population
`(40). In a recent outpatient-based, cross-sectional survey of
`1,038 patients in a dermatology clinic waiting room in Cleve-
`land, Ohio, culture-confirmed dermatophyte onychomycosis
`was identified in 8.7% of the total population and in 6.5 and
`13.3% of the female and male subgroups, respectively (patients
`
`who presented for onychomycosis were excluded) (27). These
`figures are comparable to those for the general Finnish popu-
`lation (8.4%) (40). Several studies have shown that the prev-
`alence of onychomycosis increases with age. For example, none
`of the 200 Finnish subjects who were younger than 20 years
`had onychomycosis but almost 24% of those aged 70 years or
`older had the disorder. Similarly, 28.1% of the members of the
`Ohio cohort aged 60 years or older were culture positive for
`onychomycosis, versus 1.1 and 2.9% for those aged 10 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 cut the toenails or maintain good
`foot care (22, 27, 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 0% (United States,
`Wales, and Finland) to 2.6% (Guatemala) (38). To learn more
`about the prevalence of onychomycosis among children in
`North America, a prospective survey was conducted of 2,500
`young (#18 years) patients and family members in Canada and
`the United States. Subjects’ nails were examined for signs of
`onychomycosis and sampled for direct microscopy and culture.
`Onychomycosis was diagnosed in 11 children (10 with affected
`toenails, and 1 with affected fingernails), indicating a preva-
`lence of 0.44%; however, 7 of these children had been referred
`for treatment of onychomycosis 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
`0.16% (37). The reasons for this 30-fold decrease in the prev-
`alence of onychomycosis in children relative to adults may
`include reduced 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, Trichophyton verrucosum commonly in-
`fects the faces of farmers who lean against their cows as they
`milk them (64). 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 (e.g., HIV infection) or thera-
`peutic agents (e.g., immunosuppressive therapies associated
`with cancer or posttransplantation care, and the extensive use
`of broad-spectrum antibiotics) (25). Other factors that increase
`the risk of onychomycosis are direct trauma to the nail, includ-
`ing that resulting from certain tic disorders (e.g., nail biting).
`
`DERMATOPHYTES AND ONYCHOMYCOSIS
`The term “dermatophytosis” is used to describe infection by
`members of the genera Microsporum, Trichophyton, and Epi-
`dermophyton. The species that most often cause onychomycosis
`in North America and parts of Europe are T. rubrum, T. men-
`tagrophytes, and Epidermophyton floccosum: the first two spe-
`cies are much more often implicated than E. floccosum (58).
`Infections of the skin, nail, and hair by nondermatophytic
`molds such as Scytalidium and Scopulariopsis are termed “der-
`matomycoses.” Dermatophytes account for most (90%) cases
`of onychomycosis of the toenails and at least 50% of fingernail
`
`Page 2
`
`

`

`VOL. 11, 1998
`
`ONYCHOMYCOSIS
`
`417
`
`infections (31). Both dermatophytes and nondermatophytes,
`especially Candida albicans, have been identified as sole etio-
`logic agents of onychomycosis; however, the incidence of true
`mixed infections (caused by dermatophytes plus nondermato-
`phytes) is difficult to determine accurately (58) and is discussed
`in detail below.
`The dermatophytes are hyaline septated molds. The hyphae
`of these mycelial organisms penetrate the stratum corneum of
`the skin and nails. The fungal cells manufacture keratinolytic
`proteases, which provide a means of entry into living cells (39).
`Some dermatophytic species, which are basically soil sapro-
`phytes that have acquired the ability to digest keratinous debris
`in soil, have evolved to be capable of parasitizing keratinous
`tissues of animals (1).
`The families that include many of the known keratinolytic
`fungi are the Arthrodermataceae and Onygenaceae in the phy-
`lum Ascomycota (52). Members of these families are homoge-
`neous with respect to appearance, physiology, taxonomy, anti-
`genicity, basic growth requirements,
`infectivity, and the
`diseases they cause (52). Some, such as Microsporum canis and
`T. mentagrophytes, have affinity for the keratin of animals and
`humans, whereas others are more specialized for a particular
`animal host (1).
`Variability with respect to the causative microorganism is
`both geographic and, within a given region, temporal. Because
`organisms that cause clinically apparent disease tend to receive
`the most attention, pathogens whose invasion leads to hard-
`to-detect disease may be present in a region but are less likely
`to be identified (1). By contrast, pathogens that cause readily
`apparent signs and symptoms are likely to be identified and
`their prevalence is likely to be noted. Thus, because reports
`during the 1970s focused primarily on scalp infections, T. vio-
`laceum was the most frequently isolated dermatophyte during
`that decade in Europe (1) although T. tonsurans is the principal
`agent of tinea capitis in the United States and is emerging in
`Europe.
`Changes over time within a region in the prevalence of
`particular dermatophyte species also are common: although M.
`audouinii and M. canis were the most common causes of scalp
`infection in Western and Mediterranean Europe 50 to 100
`years ago, tinea capitis has declined in incidence in Western
`Europe and, when present, is caused primarily by M. canis (1)
`or T. violaceum (1). Similarly, M. audouinii and M. canis were
`the main causes of tinea capitis in the United States earlier in
`this century; this role has been taken over by T. tonsurans (1).
`Another change that has occurred in recent years is the grow-
`ing prevalence of dermatophytoses of the foot (tinea pedis)
`and nails (tinea unguium) and decline in the prevalence of
`scalp infections (1).
`
`CLINICAL TERMINOLOGY
`
`As in many areas of medicine, the clinical terminology used
`to describe dermatophytic infections evolved in advance of
`accurate knowledge about causation or pathophysiology. Tinea
`(“a gnawing worm”) or “ringworm,” a term derived from the
`appearance of the characteristic skin lesions in this common
`dermatophytosis (64), affects the scalp (tinea capitis), glabrous
`skin (tinea corporis), groin (tinea cruris), nail (tinea unguium),
`feet (tinea pedis), beard (tinea barbae), and hand (tinea
`manuum). Other dermatophytoses are named for their appear-
`ance, such as tinea favosa (favus, or honeycomb-like due to T.
`schoenleinii) or tinea imbricata (“composed of overlapping
`parts”; ringworm due to T. concentricum).
`
`FIG. 1. The nail unit. Reprinted from reference 11 with permission of the
`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 1 (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 of the nail.
`As the nail grows, cells of the nail matrix divide, differentiate,
`and keratinize 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 (12). 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). Fingernails 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 6 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, characterized according to
`clinical presentation and the route of invasion, are recognized.
`
`Distal Subungual Onychomycosis
`Distal subungual onychomycosis (DSO) 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-
`ponychium (Fig. 2). The infecting organism migrates proxi-
`
`Page 3
`
`

`

`418
`
`ELEWSKI
`
`CLIN. MICROBIOL. REV.
`
`FIG. 2. Distal subungual onychomycosis. Courtesy of Gary Palmer.
`
`mally through the underlying nail matrix. Mild inflammation
`develops, resulting in focal parakeratosis and subungual hyper-
`keratosis, with two consequences: onycholysis (detachment of
`the nail plate from the nail bed) and thickening of the subun-
`gual region. This subungual space then can serve as a reservoir
`for superinfecting bacteria and molds, giving the nail plate a
`yellowish brown appearance (12).
`DSO is usually caused by the dermatophyte T. rubrum (26,
`59), although T. mentagrophytes, T. tonsurans, and E. floccosum
`also are known to be causative. DSO may develop on the
`fingernails, toenails, or both, with infection of the toenails
`being much more common than infection of the fingernails; in
`the Finnish study (40), only 2 of the 91 patients with dermato-
`phyte-related onychomycosis of the toenails also had fingernail
`involvement. Toenail infections were approximately 20 times
`more common than fingernail infections in the Ohio cohort
`(27). The increased frequency of toenail in comparison to
`fingernail infections probably reflects the greater incidence of
`tinea pedis than of tinea manuum.
`
`Proximal Subungual Onychomycosis
`
`Proximal subungual onychomycosis (PSO) is also known as
`proximal white subungual onychomycosis (PWSO), a relatively
`uncommon subtype, and occurs when organisms invade the
`nail unit via the proximal nail fold through the cuticle area,
`penetrate the newly formed nail plate, and migrate distally
`(Fig. 3). The clinical presentation includes subungual hyper-
`keratosis, proximal onycholysis, leukonychia, and destruction
`of the proximal nail plate. In the United States T. rubrum is the
`principal causative agent of PSO.
`The pattern of growth in PSO is from the proximal nail fold
`on the lunula area distally to involve all layers of the nail (20).
`Although PSO is the most infrequently occurring form of on-
`ychomycosis in the general population, it is common in AIDS
`patients and is considered an early clinical marker of HIV
`infection (2). In one study of 62 patients with AIDS or AIDS-
`related complex and onychomycosis, 54 patients (88.7%) had
`PSO, with T. rubrum being the etiologic agent in more than
`half of these patients (20). In 54 patients, the feet were af-
`fected, and in 5 patients, the hands were infected; infections of
`both toenails and fingernails were present in 3 patients (20).
`Infection may also occasionally arise secondary to trauma.
`
`FIG. 3. Proximal subungual onychomycosis in a patient with AIDS. Courtesy
`of Gary Palmer.
`
`White Superficial Onychomycosis
`White superficial onychomycosis (WSO) is less common
`than DSO (estimated proportion of onychomycosis cases,
`10%) (66) and occurs when certain fungi invade the superficial
`layers of the nail plate directly (Fig. 4). (Later, the infection
`may move through the nail plate to infect the cornified layer of
`the nail bed and hyponychium.) It can be recognized by the
`presence of well-delineated opaque “white islands” on the
`external nail plate, which coalesce and spread as the disease
`progresses. At this point, the nail becomes rough, soft, and
`crumbly (12). Inflammation is usually minimal in patients with
`WSO, because viable tissue is not involved (12). WSO occurs
`primarily in the toenails (66).
`The most common etiologic agent in WSO is T. mentagro-
`phytes (12). In addition, several nondermatophyte molds, in-
`cluding Aspergillus terreus, Acremonium roseogrisum (later con-
`firmed to be Acremonium potronii), and Fusarium oxysporum,
`have been implicated by Zaias et al. (66).
`
`FIG. 4. White superficial onychomycosis.
`
`Page 4
`
`

`

`VOL. 11, 1998
`
`ONYCHOMYCOSIS
`
`419
`
`Candida Infections of the Nail
`
`Candida nail infections occur in patients with chronic mu-
`cocutaneous candidiasis, and are caused by C. albicans (3). The
`organism invades the entire nail plate. Candida spp. may cause
`other syndromes, including onycholysis and paronychia. These
`forms occur more commonly in women than in men (3) and
`often affect the middle finger, which may come into contact
`with Candida organisms that reside in the intestine or vagina
`(66). Candida onychomycosis can therefore be divided into
`three general categories. (i) Infection beginning as a paro-
`nychia (infection of the structures surrounding the nail; also
`called a “whitlow”), the most common type of Candida ony-
`chomycosis (54), first appears as an edematous, reddened pad
`surrounding the nail plate. Invasion by Candida spp., unlike
`dermatophytic invasion, penetrates the nail plate only second-
`arily after it has attacked the soft tissue around the nail (12).
`After infection of the nail matrix occurs, transverse depres-
`sions (Beau’s lines) may appear in the nail plate, which be-
`comes convex, irregular, and rough and, ultimately, dystrophic
`(3, 12).
`(ii) Patients with chronic mucocutaneous candidiasis are at
`risk for the second type of Candida onychomycosis, called
`Candida granuloma, which accounts for fewer than 1% of
`onychomycosis cases (12, 54, 66). This condition is seen in
`immunocompromised patients and involves direct invasion of
`the nail plate (30). The organism invades the nail plate directly
`and may affect the entire thickness of the nail, resulting, in
`advanced cases, in swelling of the proximal and lateral nail
`folds until the digit develops a pseudo-clubbing or “chicken
`drumstick” appearance (54).
`(iii) Finally, Candida onycholysis can occur when the nail
`plate has separated from the nail bed. This form is more
`common on the hands than the feet (3). Distal subungual
`hyperkeratosis can be seen as a yellowish gray mass lifts off the
`nail plate. The lesion resembles that seen in patients with DSO
`(3).
`
`Total Dystrophic Onychomycosis
`
`Total dystrophic onychomycosis is used to describe end-
`stage nail disease, although some clinicians consider it a dis-
`tinct subtype. It may be the end result of any of the four main
`patterns of onychomycosis. The entire nail unit becomes thick
`and dystrophic (65).
`
`DIAGNOSIS OF ONYCHOMYCOSIS
`
`The clinical presentation of dystrophic nails should alert the
`clinician to the possibility of onychomycosis; however, because
`fungi cause only about half of all nail dystrophies (30), the use
`of appropriate diagnostic techniques including direct micros-
`copy and fungal culture is important to ensure correct diagno-
`sis and treatment. The clinical appearance of the nail and the
`patient’s history will help differentiate fungal from nonfungal
`etiologies of nail dystrophies. For example, predisposing fac-
`tors for onychomycosis include diabetes mellitus, older age,
`hyperhidrosis, onychogryphosis, nail trauma, poor peripheral
`circulation, and immunosuppression (12). In the presence of
`subungual hyperkeratosis, yellow-brown discoloration, and on-
`ycholysis, onychomycosis is likely to be present. If the patient
`has a history of tinea pedis, particularly moccasin type, the case
`for this diagnosis is even stronger (12).
`
`FIG. 5. Psoriasis affecting the nail. Courtesy of C. R. Daniel III.
`
`Differential Diagnosis
`
`Care 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-
`matic onychodystrophies, pachyonychia congenita, nail bed tu-
`mors, yellow-nail syndrome (rare), and idiopathic onycholysis.
`When psoriasis affects the nails, it is usually also present at
`other skin sites; however, in some cases nail involvement is the
`only sign (6). When psoriasis affects the nails, it can produce
`onycholysis resembling that associated with DSO (Fig. 5). A
`diagnosis of psoriasis is supported by the presence of fine
`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 10% of patients with lichen planus have ab-
`normal nails. “Twenty-nail” dystrophy is a condition of un-
`known cause. Onychorrhexis (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 known 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. If the onycholytic
`nail is clipped to allow examination of the nail bed, the 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.
`
`Page 5
`
`

`

`420
`
`ELEWSKI
`
`CLIN. MICROBIOL. REV.
`
`FIG. 6. Potassium hydroxide preparation of a nail specimen showing onychomycosis.
`
`Collecting the Nail Specimen
`
`The first step of the sample collection process is thorough
`cleansing of the nail area with alcohol to remove contaminants
`such as bacteria. Because the sites of invasion and localization
`of the infection differ in the different types of onychomycosis,
`different approaches, depending on the presumptive diagnosis,
`are necessary to obtain optimal specimens (25). The following
`collection techniques are recommended.
`Distal subungual onychomycosis. Because dermatophytes in
`patients with DSO invade the nail bed rather than the nail
`plate, the specimen must be obtained from the nail bed, where
`the concentration of viable fungi is greatest (25). The nail
`should be clipped short with nail clippers, and the specimen
`should be taken from the nail bed as proximally to the cuticle
`as possible with a small curet or a no. 15 scalpel blade (25, 30).
`If debris is insufficient, material should be obtained from the
`nail bed. Material should also be obtained from the underside
`of the nail plate, with emphasis placed on sampling from the
`advancing infected edge most proximal to the cuticle. This is
`the area most likely to contain viable hyphae and least likely to
`contain contaminants (25).
`Proximal subungual onychomycosis. Because the fungus in-
`vades under the cuticle before settling in the proximal nail bed
`while the overlying nail plate remains intact, the healthy nail
`plate should be gently pared away with a no. 15 scalpel blade.
`A sharp curet can then be used to remove material from the
`infected proximal nail bed as close to the lunula as possible (25,
`30).
`White superficial onychomycosis. Since the infection affects
`the nail plate surface, a no. 15 scalpel blade or sharp curet can
`
`be used to scrape the white area and remove the infected
`debris.
`Candida onychomycosis. Material is needed from the prox-
`imal and lateral nail edges. If Candida onycholysis is suspected,
`the lifted nail bed should be scraped. Scrapings can be taken
`from the undersurface of the nail
`if insufficient debris is
`present in the nail bed (30).
`
`Specimen Analysis
`
`Both direct microscopy and in vitro laboratory culture of
`sampled material are necessary to definitively identify the eti-
`ologic agent (25). The specimen should be divided into two
`portions for direct microscopy and culture. It is important to
`understand the limitations of direct microscopy in diagnosing
`the cause of onychomycosis. The test serves only as a screening
`test for the presence or absence of fungi but cannot differen-
`tiate among the pathogens (Fig. 6). Direct microscopy is often
`time-consuming, because nail debris is