Onychomycosis and its treatment

Antonella Tosti, Robert Baran, Rodney PR Dawber, Eckart Haneke

Types of onychomycosis

Diagnosis

Treatment

Candida onychomycosis Further reading

Fungi may invade the nails in four different ways, leading to four separate types of onychomycosis with specific clinical features, prognosis and response to treatment. The type of nail invasion depends on the fungus responsible and the host susceptibility. Invasion occurs:

Table 8.1 Causes of onychomycosis

Type of organism

Prevalence (%)

Dermatophytes

83

Non-dermatophytic moulds

15 (approx.)

Yeasts

<1

1 Via the distal subungual area and the lateral nail groove, leading to distal lateral subungual onychomycosis (Figure 8.1).

2 Via the undersurface of the proximal nail fold leading to proximal subungual onychomycosis (see Figure 8.10).

3 Via the dorsal surface of the nail plate, producing superficial onychomycosis (see Figure 8.16).

4 Via the nail plate free margin, producing endonyx onychomycosis (see Figure 8.21).

TYPES OF ONYCHOMYCOSIS

Distal lateral subungual onychomycosis

Distal lateral subungual onychomycosis (DLSO) is the most common type of onychomycosis (Figures 8.3, 8.4, 8.5, 8.7-8.9). Responsible

Endonyx Onychomycosis

Figure 8.1

Nail invasion in distal lateral subungual onychomycosis.

Figure 8.1

Nail invasion in distal lateral subungual onychomycosis.

Rubrum Plantair

Figure 8.2

Plantar scaling due to Trichophyton rubrum infection in a patient with DLSO.

Figure 8.2

Plantar scaling due to Trichophyton rubrum infection in a patient with DLSO.

Nail Bed Hyperkeratosis

Figure 8.3

Nail bed hyperkeratosis and onycholysis of the great toe in DLSO.

Figure 8.3

Nail bed hyperkeratosis and onycholysis of the great toe in DLSO.

Hyperkeratosis Nail Tumor

Figure 8.4

The hyperkeratotic nail bed in DLSO is evident after clipping of the

Figure 8.4

The hyperkeratotic nail bed in DLSO is evident after clipping of the detached nail plate.

Lateral Onychomycosis

Figure 8.5

Distal lateral subungual onychomycosis of several fingers.

Figure 8.5

Distal lateral subungual onychomycosis of several fingers.

Palmar Plantar Psoriasis Treatment

Figure 8.6

Palmar involvement in the patient shown in Figure 8.5.

Figure 8.6

Palmar involvement in the patient shown in Figure 8.5.

Tinea Cruris Foto

Figure 8.7

Tinea cruris in a patient affected by DLSO of several finger nails due to Trichophyton rubrum.

Figure 8.7

Tinea cruris in a patient affected by DLSO of several finger nails due to Trichophyton rubrum.

Nails Trichophyton Violaceum

Figure 8.8

Distal lateral subungual onychomycosis due to Fusarium solanii.

Figure 8.8

Distal lateral subungual onychomycosis due to Fusarium solanii.

Melanonychia Onychomycosis

Figure 8.9

Fungal melanonychia due to Trichophyton rubrum.

Figure 8.9

Fungal melanonychia due to Trichophyton rubrum.

fungi (Table 8.1) include dermatophytes (most frequently Trichophyton rubrum), moulds (Scytalidium spp., Scopulariopsis spp., Fusarium spp., Acremonium spp., Onychocola canadensis) and yeasts (Candida spp.). The skin of the palms and soles is frequently involved, especially in dermatophytic infections with plantar scaling (Figure 8.2). Tinea cruris is common in patients with onychomycosis due to T. rubrum and Epidermophyton floccosum (see Figure 8.7).

Toe nails are most frequently affected (Figure 8.3). Finger nail infection is usually associated with toe nail infection, often presenting as the 'one hand, two feet' syndrome. Clinically the nail shows distal subungual hyperkeratosis and onycholysis; the onycholytic area appears yellow-white. Proximal spreading frequently occurs along longitudinal streaks. In some cases the nail plate is partially absent, the detached nail having been clipped by the patient (Figure 8.4).

Yellow streaks along the lateral margin of the nail and/or the presence of yellow onycholytic areas in the central portion of the nail (dermatophytoma) are associated with poor response to systemic antifungal medication. A poor prognosis is also reported for onychomycosis due to some moulds such as Scytalidium, Scopulariopsis and Fusarium, or for onychomycosis due to T. rubrum var. melanoides. The latter dermatophyte produces black pigmentation of the nail due to direct production of melanin-related pigment by the fungus (Figure 8.9).

subungual onychomycosis

Fungi reach the nail matrix keratogenous zone through the proximal nail fold horny layer (Figure 8.10) and are typically located in the ventral nail (Figures 8.11-8.15). Proximal subungual onychomycosis (PSO) is most frequently caused by moulds (Scopulariopsis brevicaulis, Fusarium spp. and Aspergillus spp.). It may also be caused

Figure 8.10

Nail invasion in proximal subungual onychomycosis.

by Trichophyton rubrum in people infected with human immunodeficiency virus (HIV). Finger nail invasion is rare. Proximal subungual onychomycosis presents as an area of leukonychia in the proximal portion of the nail plate; the leukonychia is due to the presence of fungal elements in the ventral portion of the proximal nail plate. The nail plate surface is normal. When PSO is caused by moulds, the periungual tissues are frequently inflamed and the condition may closely resemble a bacterial infection. A purulent discharge may be present, especially in Aspergillus infection. When PSO affects finger nails or the thin nails of children, fungal invasion may spread to the dorsal nail layers, resulting in opacity and fragility of the superficial nail plate. This has been frequently reported under the diagnosis of 'white superficial onychomycosis'.

Superficial onychomycosis (Figures 8.16-8.20) only affects toe nails. Most commonly the responsible fungus is Trichophyton Mentagrophytes var. interdigitale, but moulds (Fusarium, Acremonium and Aspergillus) can also be responsible (Table 8.2). The nail shows small, white opaque patches that can be easily

Figure 8.10

Nail invasion in proximal subungual onychomycosis.

Superficial onychomycosis

Dermatophytoma

Figure 8.11

(a, b) Proximal subungual onychomycosis: the proximal nail shows an area of leukonchia. The nail surface is normal.

Figure 8.11

(a, b) Proximal subungual onychomycosis: the proximal nail shows an area of leukonchia. The nail surface is normal.

Aspergillus Flavus Nail

Figure 8.12

Proximal subungual onychomycosis due to Aspergillus flavus—note periungual inflammation with purulent discharge.

Figure 8.12

Proximal subungual onychomycosis due to Aspergillus flavus—note periungual inflammation with purulent discharge.

Figure 8.13

(a, b) Proximal subungual onychomycosis with periungual inflammation due to Scopulariopsis brevicaulis.

Figure 8.13

(a, b) Proximal subungual onychomycosis with periungual inflammation due to Scopulariopsis brevicaulis.

Figure 8.14

Fingernail PSO due to Fusarium sp.—note leukonychia and periungual inflammation.

Erythema Proximal Nail Fold Toe

Figure 8.15

Proximal subungual onychomycosis due to Fusarium sp.—note erythema of the proximal nail fold.

Figure 8.15

Proximal subungual onychomycosis due to Fusarium sp.—note erythema of the proximal nail fold.

Proximal Subungual Onychomycosis

Figure 8.16

Nail invasion in white superficial onychomycosis.

Figure 8.16

Nail invasion in white superficial onychomycosis.

Friable Material Under The Nails

Figure 8.17

The nail plate surface in WSO presents numerous white, opaque and friable spots.

Figure 8.17

The nail plate surface in WSO presents numerous white, opaque and friable spots.

Figure 8.18

(a, b) White superficial onychomycosis due to Aspergillus candidus.

Figure 8.18

(a, b) White superficial onychomycosis due to Aspergillus candidus.

White Superficial Onychomycosis

Figure 8.19

White superficial onychomycosis due to Fusarium sp.

Figure 8.19

White superficial onychomycosis due to Fusarium sp.

Rare Nail Disorder Photos

Figure 8.20

Tinea pedis interdigitalis in a patient with WSO.

Figure 8.20

Tinea pedis interdigitalis in a patient with WSO.

scraped off (white superficial onychomycosis, WSO). Tinea pedis interdigitalis is frequently associated. Children presenting with WSO may have Candida infection.

Trichophyton rubrum var. melanoides and Scytalydium dimidiatum can be responsible for a rare variety of superficial onychomycosis, black superficial onychomycosis, in which the patches are black.

Endonyx onychomycosis

Endonyx onychomycosis (Figures 8.21, 8.22) is a rare type of onychomycosis caused by Trichophyton soudanense and T. violaceum. Plantar infection may be associated (Figure 8.23). The nail is diffusely opaque and white in the absence of onycholysis and subungual hyperkeratosis.

Total dystrophic onychomycosis

Total dystrophic onychomycosis (TDO) may rarely occur as a primary condition or, most commonly, represent the secondary evolution of untreated DLSO or PSO. Primary TDO is usually due to Candida and typically affects immunocompromised people, such as

Yeast Invasion

Figure 8.21

Schematic drawing of nail invasion in endonyx onychomycosis.

Figure 8.21

Schematic drawing of nail invasion in endonyx onychomycosis.

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Milky-white discoloration of the nail plate in endonyx onychomycosis in the absence of subungual hyperkeratosis and onycholysis.

Trichophyton Soudanense

Figure 8.23

Plantar infection due to Trichophyton soudanense in the patient seen in Figure 8.22.

Figure 8.23

Plantar infection due to Trichophyton soudanense in the patient seen in Figure 8.22.

patients with chronic mucocutaneous candidiasis or HIV infection. The nail is diffusely thickened and crumbled, and the periungual tissues are inflamed with pseudoclubbing.

DIAGNOSIS

Diagnosis of dermatophyte nail invasion can be established by the isolation and identification of the fungi from the affected nail, provided that no local or systemic antifungal treatment has been used recently by the patient. The site from which diagnostic specimens should be taken depends on the type of onychomycosis:

• In DLSO subungual debris should be collected from the nail bed after clipping off the overlying onycholytic nail plate (Figure 8.24). It is important to obtain material from

Finger nail fungal infection is rare in the absence of toe nail involvenment or tinea pedis the most proximal portion of the affected nail bed. • In PSO fungi are restricted to the ventral nail plate. When the affected area is far from the distal edge of the nail, collection of the specimens requires punch biopsy of the nail plate.

Subungual Debris

Figure 8.24

Collection of specimens in DSO. Subungual debris should be collected in the most proximal portion of the affected nail bed after clipping of the onycholytic nail plate.

Figure 8.24

Collection of specimens in DSO. Subungual debris should be collected in the most proximal portion of the affected nail bed after clipping of the onycholytic nail plate.

Fingernail Disorders

Figure 8.25

Collection of specimens in WSO. Nail debris can be obtained by scraping the areas of leukonychia on the superficial nail plate.

Figure 8.25

Collection of specimens in WSO. Nail debris can be obtained by scraping the areas of leukonychia on the superficial nail plate.

• In WSO the material can easily be obtained by scraping the areas of leukonychia or melanonychia from the superficial nail plate (Figure 8.25).

• In endonyx onychomycosis nail clippings contain numerous fungal elements and can be used directly for culture.

Direct microscopic examination of the specimens can be performed using potassium hydroxide preparations. Nail debris is placed on a glass slide and a drop of a 40% KOH solution with ink (3 ml of KOH solution mixed with 1 cartridge of ink) added. After applying a cover-slip, the slide is placed in a moist chamber for 2 hours to permit clearing of the keratin; it is then viewed under a microscope (Figures 8.26-8.28). A formulation of KOH and dimethylsulphoxide (DMSO) provides faster clearing of the specimen. Samples are cultured in Sabouraud's medium with 0.05% chloramphenicol with or without 0.4% cycloheximide, incubated at 26-28°C for 2-3 weeks. Gross colony morphology and microscopic examination of the mycelia stained with lactophenol cotton blue permit the identification of the causative fungus (Figures 8.29-8.31).

The failure rate for nail culture is high (20-30%) since fungi may be scarcely visible and fail to grow. When the clinical picture and direct examination are indicative of onychomycosis it is mandatory to repeat the culture. Examination of material taken from associated

Figure 8.26

Nail preparation in 40% KOH and ink showing dermatophyte filaments.

Figure 8.26

Nail preparation in 40% KOH and ink showing dermatophyte filaments.

Scopulariopsis Under Microscope

Figure 8.27

Scopulariopsis brevicaulis onychomycosis: KOH preparation showing the lemon-shaped conidia.

Figure 8.27

Scopulariopsis brevicaulis onychomycosis: KOH preparation showing the lemon-shaped conidia.

Koh Aspergillus Imagenes

Figure 8.28

Onychomycosis due to Aspergillus niger KOH preparation showing several black conidial heads visible within the nail plate.

Figure 8.28

Onychomycosis due to Aspergillus niger KOH preparation showing several black conidial heads visible within the nail plate.

Koh Aspergillus Imagenes

Figure 8.29

Aspergillus niger in culture.

Figure 8.29

Aspergillus niger in culture.

Tinea Pedis Culture

Figure 8.30

Culture of Trichophyton rubrum on Sabouraud's medium after 20 days' incubation at 26°C.

Figure 8.30

Culture of Trichophyton rubrum on Sabouraud's medium after 20 days' incubation at 26°C.

Reflexive Branching

Figure 8.31

Microscopic examination of a culture of Trichophyton soudanense showing septate hyphae with reflexive branching and chains of arthrospores.

Figure 8.31

Microscopic examination of a culture of Trichophyton soudanense showing septate hyphae with reflexive branching and chains of arthrospores.

skin lesions is advisable since these usually give profuse dermatophyte growth. Diagnosis of onychomycosis due to moulds requires a strict correlation between clinical picture and mycological results. Isolation of a mould from culture is not a sufficient criterion to make the diagnosis, since moulds may be contaminants or secondary colonizers of the nail as well as laboratory contaminants.

Onychomycosis may be secondary to other factors—important to consider if treatment fails

Differential diagnosis

Differentiating between onychomycosis and psoriasis can be difficult since subungual hyperkeratosis, onycholysis, splinter haemorrhages and diffuse nail 'crumbling' are clinical signs of both conditions. Moreover, dermatophytes or other fungi can occasionally colonize psoriatic nails, especially when the nail plate is grossly deformed. Therefore, positive culture does not exclude the diagnosis of psoriasis.

TREATMENT

Except for superficial onychomycosis, which can be treated with any topical antifungal agent after scraping of the affected areas, treatment of dermatophyte onychomycosis usually requires systemic antifungal therapy. However, when only the distal nail is affected and the patient's general condition makes systemic treatment questionable, topical therapy using the transungual drug delivery system (TUDDS) can be tried, using daily 8% ciclopirox or weekly 5% amorolfine nail lacquer. Therapy should be continued for at least 6 months in finger nail onychomycosis and 12 months in toe nail infection: 8% ciclopirox once daily, 5% amorolfine nail lacquer once or twice weekly. A combination of bifonazole 1 % in a 40% urea ointment is a possible alternative.

Formerly oral treatment of onychomycosis consisted of two antifungal drugs: griseofulvin and ketoconazole, the latter being rarely used in recent years because of its hepatotoxicity. Treatment of onychomycosis with griseofulvin, however, requires long-term administration of the drug (6 months for finger nails, up to 18 months for toe nails), and high drug dosages (up to 2 g per day). Toe nail infection often fails to respond and recurrence is common. Three new systemic antimycotic agents have now been introduced: fluconazole, itraconazole and terbinafine. All these drugs have been shown to reach the distal nail soon after therapy is started and to persist in the nail plate for long periods (2-6 months) after the end of treatment. The persistence of high drug levels in the nail following treatment allows for shorter treatment periods with fewer relapses and side-effects. Partial nail avulsion and concomitant treatment with a topical antifungal agent further reduce relapses and shorten the duration of treatment. Onychomycosis of the toe nails is more difficult to cure and recurs more frequently than onychomycosis of the finger nails.

Fluconazole and itraconazole are triazole derivatives with a broad spectrum of fungistatic activity. Itraconazole is effective at dosages of 200 mg per day for 2-4 months. This agent has been shown to be effective even when given as intermittent therapy (400 mg daily for 1 week every month for 3-6 months). Terbinafine is an allylamine derivative with primary fungicidal properties against dermatophytes. This drug is probably more effective and safer than other antimycotics for long-term treatment of onychomycosis due to dermatophytes. Recommended dosage is 250 mg per day for 2 months (finger nails) to 4 months (toe nails). Preliminary studies show that terbinafine may also be effective at the dosage of 500 mg daily for 1 week a month (intermittent therapy).

When onychomycosis is cured it is advisable to continue application of a topical conventional antifungal agent on the previously affected nails, soles and toe webs to reduce the chance of relapse, unless the new transungual antifungal delivery systems (5% amorolfine and 8% ciclopirox) are used in a preventive manner.

CANDIDA ONYCHOMYCOSIS

Candida albicans can frequently be isolated from the subungual area of onycholytic nails as well as from the proximal nail fold of chronic paronychia. In both these conditions, however, Candida colonization is only a secondary

Candida invasion of the nail is always a secondary phenomenon, due to local or systemic factors

Table 8.2 Routes of nail invasion by non-dermatophytic moulds_

_Distal Proximal Superficial

Scopulariopsis brevicaulis Fusarium spp. Acremonium spp. Aspergillus spp. Scytalydium spp. Onychocola canadensis Alternaria spp.

Aspergillus Spp

Figure 8.32

(a, b) Candida onychomycosis in a patient with HIV infection.

Figure 8.32

(a, b) Candida onychomycosis in a patient with HIV infection.

Onychomycosis Candida Hiv

Figure 8.33

Candida onychomycosis in a child with chronic mucocutaneous candidiasis.

Figure 8.33

Candida onychomycosis in a child with chronic mucocutaneous candidiasis.

Candida Onychomycosis

Figure 8.34

Chronic mucocutaneous candidiasis: the affected digits have a bulbous appearance with erythema and swelling of the proximal and lateral nail folds. The nail bed is hyperkeratotic and the nail plate is thickened and highly dystrophic due to diffuse crumbling. Complete destruction of the nail plate is commonly observed.

Figure 8.34

Chronic mucocutaneous candidiasis: the affected digits have a bulbous appearance with erythema and swelling of the proximal and lateral nail folds. The nail bed is hyperkeratotic and the nail plate is thickened and highly dystrophic due to diffuse crumbling. Complete destruction of the nail plate is commonly observed.

Reason For Crumbling Nails

Figure 8.35

Oral candidiasis in the patient seen in Figure 8.33.

Figure 8.35

Oral candidiasis in the patient seen in Figure 8.33.

phenomenon since topical or systemic antimycotics do not cure the nail abnormalities. Nail invasion by Candida albicans usually indicates an underlying immunological defect (Figure 8.32) and is almost exclusively seen in chronic mucocutaneous candidiasis; in the latter, Candida albicans invasion of the nail plate is associated with an inflammatory reaction of the proximal nail fold, nail matrix, nail bed and hyponychium (Figure 8.33). The affected digits have a bulbous appearence with erythema and swelling of the proximal and lateral nail folds. The nail bed is hyperkeratotic and the nail plate is thickened and highly dystrophic owing to diffuse 'crumbling'. Complete destruction of the nail plate is commonly observed (Figure 8.34). Oral candidiasis is present in almost all patients (Figure 8.35).

Diagnosis

The diagnosis of Candida nail invasion is made by culturing nail scrapings in Sabouraud's medium at 37°C. Isolated Candida strains should be tested for sensitivity to imidazoles.

Treatment

Nail lesions of chronic mucocutaneous candidiasis require systemic treatment. Ketoconazole (400 mg daily) and itraconazole (200 mg daily) are both effective, the latter having a safer side-effect profile.

FURTHER READING

Baran R, Dawber RPR (1994) Diseases of The Nails and Their Management, 2nd edn (Oxford, Blackwell Scientific).

Baran R, Hay RJ, Tosti A et al (1998) New classification of onychomycosis, Br J Dermatol 119:567-571.

Baran R, Hay R, Haneke E et al (1999) Onychomycosis. The Current Approach to Diagnosis and Therapy (London, Martin Dunitz).

Haneke E (1991) Fungal infection of the nail, Semin Dermatol 10:41-53.

Tosti A, Piraccini BM, Lorenzi S (2000) Onychomycosis caused by non-dermatophytic moulds: chemical features and response to treatment of 59 cases, J Am Acad Dermatol 42:217-224.

Zaias N (1985) Onychomycosis, Dermatol Clin 3: 445-460.

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