Superficial white onychomycosis—A syndrome withdifferent fungal causes and paths of infection

Robert Baran, MD,a Jan Faergemann, MD, PhD,b and Roderick J. Hay, DMc

Cannes, France; Gothenburg, Sweden; and Belfast, United Kingdom

Superficial white onychomycosis (SWO) is a clinical term used to describe onychomycosis in which theinvasion of the nail plate occurs from the dorsal surface. However, recent observations indicate that theclinical appearances may vary to include infection in patches or in a striate patter. This report shows that, insome cases, it may be combined with either distal and lateral subungual onychomycosis or proximal whitesubungual onychomycosis. Invasion of the dorsal nail surface, but originating from the proximal nail fold, isanother route of infection in SWO. A new classification of this condition is proposed with 4 main variants.Althoughbased on clinical features, often other factors such as immunosuppression or invading organism (eg,Trichophyton rubrum or Fusarium species) appear to play a role in the development of a particular pattern ofinfection. This is an observational study carried out by trained and experienced clinicians. The main clinicalimplication is that in combined forms, or where the infection emerges from beneath the proximal nailfold,systemic rather than topical antifungal therapy is advised. ( J Am Acad Dermatol 2007;57:879-82.)

The classic teaching on the route of infectionin onychomycosis proposes that in mostcases infection originates from the undersur-

face of the nail, subungual onychomycosis, usuallyfrom the distal margin (distal and lateral subungualonychomycosis or DLSO); the dorsal aspect of thenail plate is the route of infection in superficial whiteonychomycosis (SWO). In a third form, proximalwhite subungual onychomycosis (PWSO) infectionappears to originate from the proximal nailfold and issubungual. However, it has never been clear howfungi have invaded the proximal nailfold as thispattern of infection is not always accompanied byhistologic evidence of penetration around the nailplate by fungi from the dorsal surface of the proximalnailfold.1 Previously we have postulated that deepdermatophyte infections such as maladie dermato-phytique, rare conditions, may be complications oflymphatic or hematogenous spread with evidence of

From the Nail Disease Centre, Cannesa; Dermatology Department,

University of Gothenburgb; and School of Medicine and Den-

tistry, Queens University, Belfast.c

Funding sources: None.

Disclosure: Drs Baran and Faergemann have been speakers in

symposia sponsored by Galderma and Dr Baran for Novartis

and Galderma. Dr Hay is a member of advisory boards for

Galderma, Novartis, York Pharma and Barrier Therapeutics.

Reprint requests: Roderick J. Hay, DM, School of Medicine and

Dentistry, Queens University Belfast, 73 University Rd, Belfast

BT7 1NN, UK.

Published online July 5, 2007.

0190-9622/$32.00

ª 2007 by the American Academy of Dermatology, Inc.

doi:10.1016/j.jaad.2007.05.026

dermatophytes grown from lymph nodes and bloodcultures.2-4 In other instances of isolated deep der-matophyte infection, there has been evidence of thespread of infection internally from an affected nail.5

In addition, recently a case of invasive dermatophy-tosis with lymph node involvement was reported inan immunocompetent young man where skin andlymph biopsy specimens showed granulomatousinflammation and special stains demonstrated longseptate hyphae, while tissue cultures grewTrichophyton verrucosum.6 Subsequently, we pos-tulated that the establishment of PWSO was a possi-ble complication of systemic or deep spread in somecases.

The purpose of this article is to demonstrate thatcertain cases of PWSO and SWO share commonfeatures, suggesting that primary dorsal penetrationdoes not always occur in SWO. SWO itself is generallycaused by either dermatophytes such as T menta-grophytes var. interdigitale or nondermatophytessuch as Acremonium, Fusarium, or Aspergillus spe-cies.7 In their review of SWO, Piraccini and Tosti7

described the clinical features in 79 cases and pointedout the relationship between age and immunosup-pression and different patterns of infection.

Observations of a group of patients with atypicalSWO and a heretofore undescribed form of SWOcaused by dermatophyte infection have prompted usto review the development of this condition.

The cases reviewed were of 12 patients (agerange, 18- 60 years) (Table I). All had presentedwith nail dystrophy of the superficial white type, butwith atypical features. These are grouped into 3different patterns.

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Nine patients (cases 1-9) presented with superfi-cially located transverse white lines, confirmed byscraping, separated by normal-colored nail, striatepattern. Among these, 5 (cases 5-9) showed thechanges of associated PWSO; one was receivinglong-term immunosuppressive therapy. T rubrumwas isolated from 8 patients and microscopy ofscrapings showed fungus in the superficial nail plate;however, in the 5 already referred to, scrapings fromthe nail surface over the PWSO clinical lesions didnot show superficial nail plate invasion in this site. Asan example (case 9), an 18-year-old boy presentedwith PWSO involving the lunula of one thumb, thecharacteristic white patches being adjacent to thecuticle, which was normally adherent to the nailplate. In addition, two transverse leukonychial bandsshaped like the distal border of the lunula andseparated from the latter and each other by nor-mal-colored nail (Fig 1). Microscopy of scrapingstaken from the striate white patches of the nailsurface showed hyphae typical of dermatophytes(SWO) and the culture was positive for T rubrum.The boy was completely healthy with normal routineblood chemistry and negative HIV test results.

Second, 3 other patients (cases 10-12) presentedwith the changes of PWSO associated with classicalpatches of SWO (confirmed by scraping), appearingfrombeneath theproximal nailfold; all grewT rubrum.Two of these patients had affected big toenails; thethird, two fingers (third and fourth) of the right hand.All the patients were otherwise healthy.

DISCUSSIONThese observations shed a new light on the

possibility of another route by which fungi causeSWO rather than via dorsal invasion of the nail plate.In patients who have PWSO associated with SWO,infection may be initiated from the dorsal surface andthe proximal nailfold independently or from beneaththe proximal nail fold alone, but the fungus may thenspread to affect either or both the dorsal and ventralnail surfaces. In cases 5-9, where there was both

Table I. Cases of atypical SWO

Cases Pattern Organism

1-4 SWO, striate T rubrum5-9 SWO, striate

plus PWSO, solidtypical pattern from lunula

T rubrum

10-12 SWO in typicalpatches; PWSO, solidtypical pattern from lunula

T rubrum

PWSO, Proximal white subungual onychomycosis; SWO, superficial

white onychomycosis.

PWSO and SWO the clinical appearance of thesuperficial nail plate infection was striate with af-fected bands alternating with unaffected nail. Inother instances (cases 10-12), there may be similarpathways of infection, but the clinical appearance ofthe superficial nail plate involvement shows diffusepatches, similar to classical SWO. Basuk and Scher8

have published the case of a 31-year-old man whounderwent an uneventful transplant for a matchedallogeneic bone marrow as treatment for his preleu-kemia associated with pancytopenia. Nail examina-tion showed SWO originating proximally frombeneath the cuticle in several of the toenails.

Fig 1. Patient shows both striate SWO and PWSO.

Table II. Classification of SWO

Classification Treatment options

SWO: Varieties:patches, striate

Typical antifungals (eg, amorolfine,cyclopiroxolamine). Closelyobserve progress in striatelesions as these may require oraltreatment.

SWO originating fromproximal nailfold

Oral antifungals (eg, terbinafine)*

SWO with deepinvasion

Oral antifungals; considerprolonged or topical plus oraltherapy if patient isimmunosuppressed.*

Mixed SWO (eg, withDLSO, PWSO)

Oral antifungals (eg, terbinafine)*or topical plus oral antifungals

DLSO, Distal subungual onychomycosis; PWSO, proximal white

subungual onychomycosis; SWO, superficial white onychomycosis.

*If a nondermatophyte mold such as Fusarium species is isolated,

the patient often does not respond to antifungals alone, and

surgical removal or chemical ablation of the nail may be necessary.

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Laboratory evaluation revealed positive directmicroscopy, a positive culture for T rubrum, andperiodic acideSchiffestained fungus on pathologi-cal examination of the nail plate with roundedarthroconidia restricted to the dorsal surface of thenail plate, as expected with classical SWO. In ourcases 1-4 a similar route of infection is possible,although the clinical appearances are different. In allcases in our series reported herein, the infectingorganism was T rubrum.

All these observations lead us to describe a newvariant of SWO in addition to those already pub-lished recently7,9 and to propose a new classificationof SWO (Table II), which can be divided into 4 mainforms, the frequency of which varies.

1. SWO fungal infection, which may present as eitherpatches diffusely distributed across, but restrictedto, the visible dorsal nail plate in the form ofdiscrete patches that coalesce as time passes orthe new variant, with striate superficial bands.The latter are single or multiple and separated by

Fig 2. Presentation of SWO similar to that of striateleukonychia. (Photograph courtesy of Dr E. Duhard,Tours, France.)

Fig 3. Deep nail penetration originating from SWO.

normal-colored nail plate as in striate transverseleukonychia (Fig 2). Such patients should beclosely examined as it is important to ensure thatthe subungual surface is not involved. It is possi-ble, even likely, that in many cases where SWOpresents in a striate pattern the source of infectionis from the proximal nailfold (type 2). Only one ofour patients was immunosuppressed.

2. In the next form (SWO originating from theproximal nailfold), the pattern of invasion ofthe superficial nail plate may be clinically sim-ilar to that seen in type 1 (diffuse or striate),but it originates from beneath the proximalnailfold and usually involves several toenails

Fig 5. Routes of infection in nail plate infection. A, Frombeneath proximal nailfold; however, note that infectionmay spread under nail plate (PSO), or across upper surface(SWO), or in both directions from this site. B, From uppernail surface (SWO). C, From distal nail plate margin(DLSO).

Fig 4. Mixed SWO and DLSO.

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882 Baran, Faergemann, and Hay

simultaneously.7 This is often seen in patientswith forms of immunosuppression and is remi-niscent of the acute polydactylous type of PWSOobserved in similar patients.

3. A third variant (SWO with deep invasion) ischaracterized by deep invasion of the nail plateoriginating from an area of SWO (ie, from thedorsal surface)7,9 (Fig 3). Piraccini and Tosti7

described this as a form seen in childhood aswell as in the immunosuppressed patient. Pa-tients previously described with histologic con-firmation by our group were immunocompetentadults infected by Fusarium spp.9 So infectionwith other organisms is possible.

4. Finally, there are true mixed forms (mixed SWO)where SWO and other forms of onychomycosiscoexist independently; different variants havebeen recorded. These include white patches onthe dorsal nail plate associated with DLSO9,10

(Fig 4). Alternatively, there are superficial bandsof leukonychia emerging from under the proxi-mal nailfold and combined with PWSO present-ing as transverse or arcuate lines or patches or asa nonhomogeneous opaque nail plate. This hasbeen described in HIV-positive patients,8,10 butour patients were immunocompetent (Fig 1).

The potential routes of infection are shown dia-grammatically in Fig 5. The apparent origin of infec-tion from beneath the posterior nailfold in somevariants of SWO and the possible overlap with PWSOmay be grounds for arguing that they share a com-mon route of infection in some cases. The linkbetween PWSO and immunosuppression has beendescribed by several authors. However, to date thepresence of deep spread by dermatophytes hasonly been clearly established in a few patients3-6

and whether this is the route for invasion of der-matophytes in PWSO remains unproven, althoughantigenemia is demonstrable in patients with uncom-plicated T rubrum infections.11 In our cases only 1 of8 patients with changes of both PWSO and SWO wasimmunosuppressed. We do not yet know how theseorganisms survive, if this is the case, away fromkeratinized surfaces, although it is clear from theliterature that survival occurs both in deep humaninfections4-6 and animal models.12 In an experimen-tal model in guinea pigs, there is genotypic variationin the ability of different dermatophytes to producegeneralized dermatophytosis after intravenous inoc-ulation but to date the pathogenetic mechanisms areunknown.12

The pattern of infection, therefore, has therapeu-tic implications as, except for the classic type of SWO

(see form 1 above) where only the visible portion ofthe nail plate is involved and scrapings from thesuperficial nail plate are positive, the other variantsneed to be treated with systemic antifungals alone orin combination with topical antifungal nail lacquers.In addition, clinicians should be suspicious if there isa superficial striate pattern as, even though it mayrespond to topical therapy, it is likely that it mayindicate spread from a hidden focus beneath thenailfold; therefore systemic therapy may be indicatedif there is no response to topical agents. The sourceof infection in those types that originate from be-neath the proximal nailfold presumably reflects asimilar origin of infection as PSO itself. Generally, theisolation of T rubrum or Fwusarium species fromcases of SWO should alert the clinician to examinethe affected nail very closely to see if there is likely tobe a mixed pattern of infection or if the infectionoriginates from beneath the proximal nailfold; analternative treatment strategy using systemic antifun-gals may be necessary, although this needs to beestablished by an appropriately designed treatmentstudy. This does not exclude the possibility that otherdermatophytes, such as T interdigitale, may alsocause complicated infections.

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