Article 3. British Association of Dermatologists’ guidelines for the management of onychomycosis 2014 (fini)

Question 1

Définition. Quel terme on utilise pour une infection des ongles au dermatophyte ?

Answer 1

The term tinea unguium is used to describe dermatophyte
infections of the fingernails or toenails.

Onychomycosis is a
less specific term used to describe fungal disease of the nails.

Question 2

Définition. Qui sont les pathogènes les plus impliqués a/n des ongles ?

Answer 2

85–90% of nail infections are due to dermatophytes and about 5% are due to nondermatophyte moulds

The most commonly
implicated dermatophyte is the anthropophilic species Trichophyton rubrum, followed by Trichophyton interdigitale.

Question 3

Étiologie. Quels sont les risques de l’onycomycose ?

Answer 3

Facteurs de risques

• increasing ag
• peripheral vascular disease
• trauma
• hyperhidrosis

Fungal nail disease is more prevalent in men and in individuals with other nail problems such as psoriasis, in persons with immunosuppressive conditions such as diabetes mellitus or HIV infection, and in those taking immunosuppressive medications.

Question 4

Étiologie. Est-ce que l’onychomycose est plus commun chez les athlètes?

Answer 4

Specific aspects of athletics lead to a higher prevalence of onychomycosis
in athletes, such as trauma, previous tinea pedis infection, increased sweating and increased exposure to infectious dermatophytes.

The key predisposing factors that contribute to infection in sports persons are:

1. the speed/intensity involved with sport (runners)
2. the sudden starting and stopping nature of the sport (e.g. tennis, squash, football, cricketand ice skating)
3. practising sports without protective footwear (e.g. gymnasts, ballet dancers)
4. frequency of nail injuries
5. prevalent use of synthetic clothing and shoes that retain sweat, water sports and communal bathing.

Question 5

Étiologie. Quels pathogènes seraient le plus responsable du tinea pedis ou de l’onychomycose chez diabétique ?

Answer 5

recent reports have found that the most common
causative agent for tinea pedis and onychomycosis was T. rubrum,
followed by T. mentagrophytes in diabetic patients.15 The

Question 6

Étiologie. Pourquoi les personnes âgées ont plus tendance à développer des onychomycoses?

Answer 6

The correlation between increasing age
and onychomycosis may be attributed to reduced peripheral
circulation, inactivity, suboptimal immune status, diabetes,
larger and distorted nail surfaces, slower-growing nails, difficulty
in grooming the nails and maintaining foot hygiene,
frequent nail injury and increased exposure to disease-causing
fungi.

Question 7

Étiologie. Est-ce que les patients atteints de VIH (immunosupression) sont plus à risques ?

Answer 7

Individuals infected with HIV have an increased risk of developing
onychomycosis when their T-lymphocyte count is as
low as 400 cells mm³ (normal range 1200–1400), and their
onychomycoses tend to be more widespread, usually affecting
all fingernails and toenails

T. rubrum is the causative fungus in most cases, except for cases
of superficial white onychomycosis (SWO), which are usually
caused by T. mentagrophytes.

Question 8

Classification. Expliquer les différents types d’onychmycose

Answer 8

The five main clinical patterns are

1) Distal and lateral subungual onychomycosis

• Invades the nail and nail bed by penetrating the distal or lateral margins.
• thickened and discoloured, with a varying degree of onycholysis
• T. rubrum + commun
• Tinea unguium of the toenails is usually secondary to tinea
  pedis
• The first and fifth toenails are more frequently affected, probably because footwear causes more damage to these nails.

2) Superficial white onychomycosis

• Crumbling white lesions appear on the nail surface, particularly the toenails.
  These gradually spread until the entire nail plate is involved.
• T. interdigitale + commun, surtout vu chez enfant

3) Proximal subungual onychomycosis

• This infection can originate either in the proximal nail fold, with subsequent penetration into the newly forming nail plate, or beneath
  the proximal nail plate
• T. rubrum le plus commun
• Although PSO is the least common presentation of dermatophyte nail infection in the general population, it is common in persons with AIDS, and has sometimes been considered a useful marker of HIV infection.

4) endonyx onychomycosis

• instead of invading the nail bed through the nail plate margin, the fungus immediately penetrates the nail plate keratin. The nail plate is discoloured white in the absence of onycholysis and subungual hyperkeratosis.
• T. soudanense and T. violaceum + communs

5) total dystrophic onychomycosis (TDO)

• Primary TDO is rare and is usually caused by Candida species, typically affecting immunocompromised patients.

Question 9

Quel est le type d’onychomycose le plus commun ?

Answer 9

Distal and lateral subungual onychomycosis

DLSO is the most common presentation of dermatophyte nail
infection.

Question 10

L’onychomycose au Candida peut avoir 4 présentations cliniques, quelles sont ses dernières ?

Answer 10

1) Chronic paronychia with secondary nail dystrophy

• Swelling of the posterior nail fold occurs secondary to chronic immersion in water or possibly due to allergic reactions to some foods, and the cuticle becomes detached from the nail plate thus losing its water-tight properties.

2) Distal nail infection

• virtually all patients have Raynaud phenomenon or some other
  form of vascular insufficiency, or are on oral corticosteroids.
• It is unclear whether the underlying vascular problem gives rise
  to onycholysis as the initial event or whether yeast infection
  causes the onycholysis.

3) Chronic mucocutaneous candidosis

• Clinical signs vary with the severity of immunosuppression, but in
  more severe cases gross thickening of the nails occurs,
  amounting to a Candida granuloma

4) Secondary candidosis

• Secondary candidal onychomycosis occurs in other diseases of
  the nail apparatus, most notably psoriasis.

Question 11

Est-ce qu’un non-dermatophyte (mold) peut causer une infection fongique ?

Answer 11

OUI !

• There is wide geographical variation in the causative organisms, but Scopulariopsis brevicaulis, a ubiquitous soil fungus, is the most common cause of nondermatophyte nail infection. Neoscytalidium dimidiatum (formerly called Scytalidium dimidiatum or Hendersonula toruloidea) has been isolated from diseased nails as well as from skin infections of the hand and foot in patients from the tropics. Other causes of nail infection include Acremonium species, Aspergillus species, Fusarium species and Onychocola canadensis.
• Unlike dermatophytosis, these mould infections are not contagious, but many of them will not respond to the standard treatments for dermatophyte or Candida onychomycosis.
• These infections often affect only one
  nail.The toenails, especially the big toenail, are more frequently
  affected than the fingernails.

Question 12

Diagnostic. Fait intéressant

Answer 12

Nonfungal causes of nail dystrophies include chronic trauma, psoriasis, onycholysis, onychogryphosis, subungual malignant melanoma and lichen planus.

Other less common dystrophic nail conditions mimicking
onychomycosis are Darier disease and lichen planus, and ichthyotic
conditions such as keratosis, ichthyosis and deafness
syndrome.

Bacterial infection, particularly when due to
Pseudomonas aeruginosa, tends to result in green or black discoloration
of the nails.

Question 13

Diagnostic. Est-ce qu’on devrait toujours prendre une culture ?

Answer 13

OUI

Laboratory confirmation of a clinical diagnosis of tinea unguium should be obtained before starting treatment. This is important for several reasons: to eliminate nonfungal dermatological conditions from the diagnosis; to detect mixed infections; and to diagnose patients with less responsive forms of onychomycosis, such as toenail infections due to T. rubrum.

Question 14

Molécular diagnosis.

Answer 14

Molecular diagnostics
Real-time polymerase chain reaction (PCR) assays have been
developed, which simultaneously detect and identify the
most prevalent dermatophytes directly in nail, skin and hair
samples and have a turnaround time of < 2 days.31–34 It
appears that real-time PCR significantly increased the detection
rate of dermatophytes compared with culture. However,
PCR may detect nonpathogenic or dead fungus, which could
limit its use in identifying the true pathogen. Restriction
fragment length polymorphism analysis, which identifies fungal
ribosomal DNA, is very helpful for defining whether the
disease is caused by repeat infection or another fungal strain
when there is a lack of response to treatment.35 However,
this technique has not been implemented into routine clinical
practice.

Question 15

Fait intéressant sur Candida

Answer 15

• Candida infection accounts for 5–10% of all cases of onychomycosis.
• Three forms of infection are recognized:

1. infection of the nail folds (or Candida paronychia)
2. distal nail infection
3. Total dystrophic onychomycosis.
4. The last is a manifestation of chronic mucocutaneous candidosis

• These infections often occur in individuals whose occupations
  necessitate repeated immersion of the hands in water, and the
  nails affected tend to be those of the dominant hand.

Question 16

Pourquoi est-ce que les traitements topiques sont souvent inefficases ?

Pour qui devrait-être utiliser les traitements topiques ?

Answer 16

The hard keratin and compact structure of the dorsal nail plate act as a barrier to topical drug diffusion into and through the nail plate.

The hydrophilic nature of the nail plate also precludes absorption of most lipophilic molecules with high molecular weights.

The role of monotherapy with topical antifungals is limited to
SWO (except in transverse or striate infections), early DLSO
(except in the presence of longitudinal streaks) when < 80%
of the nail plate is affected with lack of involvement of the
lunula, or when systemic antifungals are contraindicated.

Question 17

Traitement topique. Amorolfine (Loceryl; Galderma, Amersham, U.K.)

Couvre qui ?

Answer 17

Amorolfine (Loceryl; Galderma, Amersham, U.K.)

• morpholine group of synthetic antifungal drugs

Couvre:

• C. albicans
• T. mentagrophytes

Dosage

• It is available as a 5% lacquer and is applied to the affected nail once or twice weekly for 6–12 month
• Amorolfine has also been found to be effective as a prophylactic
  treatment for recurrence of onychomycosis.

Effet secondaire:

• rare and are limited to local burning, pruritus and erythema.

Question 18

Traitement topique. Ciclopirox

Answer 18

Ciclopirox

• hydroxypyridone derivative

Contre qui ?

• T. rubrum
• S. brevicaulis
• Candida species

Dose?

• is available as an 8% lacquer applied once daily for up to 48 weeks

Effet secondaire?

• Periungual and nail fold erythema are the most common side-effects.

Question 19

Traitement topique. Tioconazole (Trosyl; Pfizer, Sandwich, U.K.).

• imidazole antifungal

Dose?

• 28% solution

Effet secondaire?

• Allergic contact dermatitis to tioconazole is not
  uncommon.

Question 20

Traitement topique. Efinaconazole

Once-daily application of topical 10% efinaconazole, a new triazole antifungal agent, has recently been found to be more effective than vehicle in the treatment of onychomycosis, with mycological cure rates approaching 50% and complete cure (defined as mycological and clinical cure) in 15% of patients after 48 weeks of application

Question 21

Traitement systémique possible. Qui sont-ils ?

Answer 21

1. Allylamine terbinafine
2. Triazole itraconazole.
3. Griseofulvin (moins utilisé)
4. Fluconazole (not liscensed)
5. Ketoconazole (risk of hepatotoxicity with long-term therapy limits its use)

Question 22

Traitement systémique. Griseofulvin (Fulcin; Grisovin; GlaxoSmithKline, Uxbridge,
U.K.)

Qu’est-ce qui est recommandé ?

Answer 22

Griseofulvin (Fulcin; Grisovin; GlaxoSmithKline, Uxbridge, U.K.)

(moins bon que les autres)

Particularité:

• It is the only antifungal agent licensed for use in children with onychomycosis, with a recommended dose for the age group of 1 month and above of 10 mg kg ^-1 per day.

Dose adulte:

• 500–1000 mg per day for 6–9 months in fingernail infection and 12–18 months in toenail infection

Effets secondaire:

• nausea and rashes

C-I

• pregnancy and the manufacturers
• caution against men fathering a child for 6 months after therapy.

Griseofulvin has several limitations including lower efficacy, long treatment duration, risk of greater drug interactions and the availability of newer antifungal agents. For these reasons it is no longer a treatment of choice for onychomycosis unless other drugs are unavailable or contraindicated

Question 23

Traitement systémique. Terbinafine (Lamisil; Novartis, Camberley, U.K.)

Answer 23

Terbinafine clearance is decreased when
patients have severe liver or kidney disease.

Dose terbinafine:

250 mg par jour pour 12-16 semaines. Réevaluaton dans 3-6 mois.

Contre qui ?

• Terbinafine has broad and potent fungicidal effects against dermatophytes, particularly T. rubrum and T. mentagrophytes, but has lower fungistatic activity against Candida species than the azoles

Temps d’action?

It is detected in the nail within 1 week of starting therapy and persists for 6 months after the completion of treatment, as it has a long half-life

Effets secondaires?

• Stevens–Johnson syndrome and toxic epidermal necrolysis.
• most common side-effects were gastrointestinal
  (4-9%), such as nausea, diarrhoea or taste disturbance,
  and dermatological events (2-3%) such as rash,
  pruritus, urticaria or eczema.

C-I

• Although studies have demonstrated that
  terbinafine is associated with only minimal hepatic toxicity
  there have been rare reports of serious hepatic toxicity, which
  occurred usually in patients with pre-existing liver disease. Therefore, systemic terbinafine is not recommended in patients with active or chronic liver disease.

Quand faire des tests ?

• Baseline liver function tests and a complete full blood count are recommended in patients with a history of heavy alcohol consumption,
  hepatitis or haematological abnormalities.Baseline monitoring should also be considered for children, as terbinafine is not licensed for use in treating paediatric onychomycosis.

Interraction médicamenteuse ?

• potentially significant drug interaction with terbinafine is
  with drugs metabolized by the cytochrome P450 2D6 isoenzyme.

Question 24

Traitement systémique. Itraconazole (Sporonox; Janssen-Cilag, High Wycombe, U.K.)

Answer 24

Itraconazole (Sporonox; Janssen-Cilag, High Wycombe, U.K.)

Dose Itraconazole:

• 200 mg per day for 12 weeks continuously, or alternatively as pulse therapy at a dose of 400 mg per day for 1 week per month. Three pulses for toenail onychomycosis.

Contre qui?

• is active against a range of fungi including yeasts, dermatophytes and some nondermatophyte moulds

Temps d’action:

• it also penetrates the nail quickly and is detectable in the nail as early as 7 days after starting therapy, and persists in the nails for up to 6–9 months after therapy discontinuation.

Effet secondaire:

• headache and gastrointestinal upset
• Hepatitis tends to occur with continuous therapy
  usually after 4 weeks. Monitoring hepatic function tests is
  recommended in patients with pre-existing deranged results,
  those receiving continuous therapy for more than a month,
  and with concomitant use of hepatotoxic drugs.

C-I:

• Itraconazole is contraindicated in patients with congestive cardiac failure
  due to the increased risk of negative inotropic effects. Itraconazole
  may also prolong the QT interval, and therefore coadministration
  with other drugs that also increase the QT
  interval is contraindicated.

Question 25

Traitement systémique. Quels devrait être l’antifongique systémique de choix ?

Answer 25

Unless there are contraindications, terbinafine should be considered as the first choice based on its higher efficacy and tolerability.

Dose terbinafine:

• 250 mg par jour pour 12-16 semaines. Réevaluaton dans 3-6 mois.

Dose Itraconazole:

• 200 mg per day for 12 weeks continuously, or alternatively as pulse therapy at a dose of 400 mg per day for 1 week per month. Three pulses for toenail onychomycosis.

Question 26

Traitement systémique. Fluconazole

Answer 26

• Fluconazole 450 mg per week for 3 months in fingernail infections, and for at least 6 months in toenail infections, may be a useful alternative in patients unable to tolerate terbinafine or itraconazole, and its once-weekly dosing regimen may improve compliance in some patients compared with daily terbinafine or itraconazole.
• The common adverse effects of fluconazole include headache, skin rash, gastrointestinal complaints and insomnia. Adverse effects leading to treatment discontinuation occur in 2-0% of patients receiving fluconazole 150 mg per week, which increases to 5-8% for higher weekly doses (300– 450 mg).88 Fluconazole is a weaker inhibitor of the cytochrome

P450 enzymes than itraconazole, and therefore may
have fewer drug interactions.

Question 27

Traitement systémique. Quel serait le meilleur traitement pour Candida ?

Answer 27

Clinical studies have demonstrated that itraconazole has significantly
greater efficacy than terbinafine for the treatment of onychomycosis.

In summary, unless there are contraindications against its
use, itraconazole should be considered the first-line treatment
for Candida onychomycosis, given its shorter treatment. duration. This also means that itraconazole is more cost–effective and more likely to be associated with greater compliance. Fluconazole can be used as an alternative if there are contraindications to using itraconazole

Question 28

Traitement systémique. Qui devrions-nous utiliser pour non-dermatophytes ?

Answer 28

Onychomycosis caused by nondermatophyte moulds is often
difficult to eradicate. Although clinical studies have shown that
terbinafine is more efficacious than itraconazole for onychomycosis
caused by dermatophytes, itraconazole has broader
antimicrobial coverage for Candida and nondermatophyte
moulds.

• Aspergillus has excellent susceptibility to itraconazole
• Scopulariopsis had wide MIC ranges for nearly all antifungal drugs including terbinafine.

Tosti et al. recommend either terbinafine (250 mg per day) or pulse
itraconazole (400 mg per day for 1 week per month) for 2–
3 months for the treatment of Aspergillus species distal lateral
subungual onychomycosis.

Question 29

Traitement systémique. Quel traitement devrions-nous utiliser chez les enfants ?

Answer 29

• As the nail plate in children is thin and grows faster than in adults, topical treatment is often advocated

Si non fonctionnement :

• the three drugs that are proposed for use in the systemic management of paediatric onychomycosis are terbinafine, itraconazole and fluconazole.
• The azoles are advocated when onychomycosis is caused by Candida species.
• Griseofulvin is no longer recommended as the first line of treatment for paediatric onychomycosis, because of long treatment duration and low efficacy.

Dose:

Itraconazole: Pulse itraconazole therapy (5 mg/ kg^-1 per day for 1 week every month) is recommended for 3 months for toenail infection.

Fluconazole: is recommended at 3–6 mg kg^-1 once weekly for 12–16 weeks for 18–26 weeks for toenail infection.

Terbinafine: Daily terbinafine is recommended for 12 weeks for toenail infection at 62-5 mg per day if weight is < 20 kg, 125 mg per day for 20–40 kg weight, and 250 mg per day if weight exceeds 40 kg

Important:

• Griseofulvin is the only systemic antifungal drug licensed for use in children.
• Although terbinafine is presently not licensed for use in children under the age of 12 years, it is now accepted as being recommended by consensus for the treatment of paediatric onychomycosis.

Question 30

Traitement systémique. Quel médicament est recommandé pour les diabétiques ?

Answer 30

Low risk of drug interactions and
hypoglycaemia makes terbinafine the oral antifungal agent of
choice in the treatment of onychomycosis in diabetics

Il ne faut pas oubier que:

As there is increased prevalence of cardiac disease in diabetics, terbinafine is preferred over itraconazole in the treatment of onychomycosis in this population.

Question 31

Traitement systémique. Quel est le traitement de choix pour les immunosuprimés ?

Answer 31

As there is an increased risk of interaction of itraconazole and ketoconazole with antiretrovirals, terbinafine and fluconazole are preferred for the treatment of onychomycosis in this patient population.

Question 32

Important

Answer 32

Question 33

A quoi il faut penser

Answer 33

Recommended audit points

• In the last 30 consecutive patients with onychomycosis treated with a systemic agent, has a positive culture been obtained before commencing therapy?
• In the last 30 consecutive patients with onychomycosis, has an appropriate treatment agent been chosen based on the type of organism cultured?
• In the last 30 consecutive patients with onychomycosis, were arrangements made for adequate duration of treatment to be supplied from the hospital or general practitioner?
• In the last 30 consecutive patients with atypical onychomycosis and in nonresponders, has immunosuppression been considered?
• In the last 30 consecutive patients, has culture at the end of treatment to confirm mycological clearance been considered, at least in high-risk groups?