Ti ps to Treat the 5 M os t

C o m m o n N a i l Di s o rde r s
Brittle Nails, Onycholysis, Paronychia,
Psoriasis, Onychomycosis
Matilde Iorizzo, MD, PhD

KEYWORDS
 Treatment  Brittle nails  Onycholysis  Paronychia  Psoriasis  Onychomycosis

KEY POINTS
 Nail disorders are difficult to treat and often frustrating for both patients and clinicians.
 Knowledge of the disease to be treated and the patient’s status are important for the choice of the
best treatment option.
 The nail plate is a dead structure and clinicians cannot act on it. Treatment should be focused on the
new growing nail.
 When facing a nail disorder, consider the presence of more than 1 disease at the same time (eg,
psoriasis and onychomycosis/paronychia and onychomycosis/psoriasis and fragility).

INTRODUCTION consequence of factors that alter nail plate pro-

duction and/or damage the already keratinized
Nail disorders are difficult to treat and often frus- nail plate (trauma, dermatologic/systemic disor-
trating for both patients and clinicians. Because ders, nutritional deficiencies, drug intake).4
of the slow growth rate of the nail plate (3 mm/ Scanning electron microscopy studies indicate
mo for fingernails and 1.5 mm/mo for toenails) that idiopathic nail brittleness is associated with
and the difficulty of getting the drug actives to an intrinsic defect in the intercellular cement that
penetrate the nail tissues, it is usually necessary holds together nail plate keratinocytes, with a
to wait several months before seeing the results disorganized protein and lipid structure and with
of treatments. This delay often leads to discontin- a disorganized orientation of keratin filaments (in
uation of therapy by the patients.1–3 normal conditions, keratin filaments, rich in
This article therefore helps clinicians (dermatol- cysteine, a high-sulfur amino acid, are oriented
ogists and general practitioners) to find the right parallel or perpendicular to the growth axis). This
treatment of each of the 5 most common nail condition leads to nails that split, flake, and
disorders and provides practical tips that might crumble, becoming soft and losing elasticity. In
improve patients’ compliance. women, the intercellular keratinocyte bridges are
constitutionally weaker than in men. Old age
further weakens these bridges.5,6 Environmental
BRITTLE NAILS
factors that produce progressive dehydration of
Nail fragility is a condition that almost exclusively the nail plate (eg, wet working conditions, minor
affects fingernails. It may be idiopathic or the trauma, and overaggressive manicuring) also
derm.theclinics.com

Disclosures: None.
Conflicts of interests: None.
Private Practice in Dermatology, Viale Stazione 16, Bellinzona 6500, Switzerland
E-mail address: matildeiorizzo@gmail.com

Dermatol Clin 33 (2015) 175–183

http://dx.doi.org/10.1016/j.det.2014.12.001
0733-8635/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
176 Iorizzo

play important roles in the development of nail If nail brittleness is caused by a dermatologic or
brittleness.7 However, some investigators dis- a systemic condition, the first thing to do is to treat
agree that nail plate cohesion is related to water the disease to obtain an improvement of the
content.8 symptom.
When the amount of water in nails is reduced to Oral supplementation with vitamins (especially
less than 16%, they become brittle. Several biotin), oligoelements, and amino acids (especially
factors are able to influence this water content, cysteine) can be useful in improving nail
including lipids.9 Normal nails contain 5% lipids, strength.10,11
which are organized in a bilayer structure, parallel Biotin can be useful because it may improve
to the nail surface. Lipids fill certain ampullar dila- the synthesis of the lipid molecules that produce
tations of the dorsal plate and intercellular spaces binding between nail plate keratinocytes. The
in the ventral plate. Low lipid content decreases recommended oral dose is 5 to 10 mg/d, with
the nail’s ability to retain water. A study showing 2 months being the average time before clinical
a decrease in cholesterol sulfate in the nail plate improvements are observed. The recommended
with age, especially in women, suggests an im- time of treatment is 3 to 6 months, but it is not clear
portant role of lipids in the development of nail how long the improvement in nail strength lasts
brittleness in postmenopausal women.6 after cessation of treatment.
Nail fragility manifests with several nail plate Iron supplementation may be effective when
abnormalities (onychoschizia, onychorrhexis, kera- serum ferritin levels are less than 10 ng/mL, but
tin granulation, erosions, distal wedge-shaped inci- there are no studies showing that iron deficiency
sion) that may be associated with the same nail or is strictly correlated with nail fragility. Zinc defi-
be present in different nails of the same patient. ciency is known to cause soft and fragile nails,
Nail plate thinning caused by proximal nail ma- nail plate abnormalities, and chronic paronychia.
trix damage always involves the whole nail length Prolonged treatment with zinc 20 mg/d seems to
and is often associated with abnormalities in the improve brittle nails. Silica also seems to be impor-
superficial nail plate. In contrast, damage to the tant in improving the resistance of the nail plate
distal matrix may produce alterations in the shape through the cross-linking of keratins.12,13
of the nail plate free edge. Nail moisturizers are important in patients with
brittle nails because of their occlusives, such as
Treatment petrolatum or lanoline, and humectants, such as
glycerin and propylene glycol. Alpha-hydroxy
Nail fragility significantly impairs daily activities
acids and urea may also be added to increase
and occupational abilities. Its treatment requires
the water-binding capacity of the nail plate.14
time and patience (Box 1). Because the nail plate
Also available are lacquers specifically devel-
is a completely keratinized, dead structure, injuries
oped to restructure nails affected by dystrophy
cannot be repaired and each accident is added to
and fragility.15,16
the previous damage, rendering the nail plate
A first lacquer owes its effectiveness to the
more and more weak. The damaged portion is
presence of hydroxypropyl chitosan (HPCH),
cured only when it grows out and is cut away.
Equisetum arvense, and methylsulfonylmethane.
When applied to the nails, HPCH forms a highly
Box 1
elastic, smooth, and almost invisible film that
Treatment of brittle nails: key points
adheres to the nail structures, protecting them
1. Reduce trauma and contact with water and against physical injuries. HPCH is a chitosan
detergents. derivative that has the advantage of being soluble
2. Wear cotton gloves under rubber gloves in cold water without any pH correction, be-
during manual work. cause the chitosan polymer backbone bears
hydrophilic residues. These residues are thought
3. After any soaking, rehydrate nails with
topical moisturizers. to be the basis of the high affinity of HPCH with
keratin. The presence of HPCH in the formulation
4. Keep nails short and squared.
is specifically effective in decreasing lamellar
5. File nails in only one direction with a card- splitting.
board file. A second lacquer made of 16% polyureaur-
6. Avoid nail cosmetics; they might be poten- ethane, when applied to the nails, adheres tightly
tially harmful. to the surface forming a strong but flexible water-
7. Remember that the keratin filaments are proof barrier to environmental hazards. The active
harder at a slightly acid pH. penetrates intercellular spaces and nail ridges,
providing mechanical support.
 Tips to Treat the 5 Most Common Nail Disorders 177

Application of both lacquers is recommended 5. Avoid aggressive self-cleaning under the nail
once a day before bedtime. plate; this promotes the spreading of the
Over-the-counter hardeners may instead para- detachment.
doxically cause brittle nails if their use is pro- 6. Do not confuse the skin debris collected under
longed. They increase the cross-link density over the nail plate with onychomycosis. Collect
time, thus reducing the flexibility of the nail plate. samples if necessary (evaluation of the affected
When the nail plate is too rigid, it is also more area with the dermatoscope may help to rule
prone to breaking and peeling. Moreover, because out the presence of a fungus).23
the hardeners are lacquers, they need to be peri- 7. Wear cotton gloves under rubber gloves during
odically removed with a nail polish remover, which manual work.
is a dehydrating agent.14,17,18 8. Do not wear nail cosmetics and/or artificial nails
Artificial nails (sculptured acrylic nails, gel nails, until 3 months after the onycholysis has been
nail mending kits, preformed plastic nails) are resolved.
commonly used to cover and protect fragile nails
but they can be responsible for fragility because It is important to promote reattachment as soon
of the materials used and the salon procedures as possible, otherwise the nail bed becomes
used to apply these materials.14,17,18 cornified, producing dermatoglyphics like the tip
of the digit (disappearing nail bed).24 In this case
the nail plate no longer adheres to the nail bed. It
ONYCHOLYSIS
is generally assumed that the longer the disorder
Onycholysis means separation of the nail plate has been present, the less likely it is to resolve.
from the underlying nail bed caused by disruption
of the onychocorneal band. It generally starts at PARONYCHIA
the distal free margin of the nail plate and pro-
Paronychia is an inflammatory disorder affecting
gresses proximally. Less often, it is the other way
proximal and lateral nail folds. A minor trauma
around. It may be idiopathic, traumatic, or second-
(mechanical or chemical) usually breaks down
ary to nail bed disorders.19–21
the cuticle, the physical barrier between the nail
Onycholysis is rarely associated with inflamma-
plate and the nail folds, allowing the infiltration of
tion and the onycholytic area is usually smooth
infectious organisms, allergens, or irritants that
and whitish because of the presence of air under
cause an inflammatory reaction that impairs nail
the detached nail plate. It may occasionally show
fold keratinization, preventing the formation of a
a greenish or brown discoloration caused by colo-
new cuticle and maintaining the condition over
nization of the onycholytic space by chromogenic
time. Paronychia may occur in 2 forms: acute
bacteria (Pseudomonas aeruginosa). Fungi are
and chronic.
only secondary colonizers; treatment with sys-
temic antifungals does not improve onycholysis, Acute Paronychia
it just cures the sovrainfection.19–21
The affected digit is painful, showing erythema,
Treatment swelling, and sometimes pus discharge from the
proximal and/or lateral nail folds. If the infection
The cornerstone of treatment is to minimize spreads to the nail bed, it may generate enough
trauma to the affected digit and avoid as much pressure to uplift the nail plate. Beau lines and
as possible water/irritant environments. Nail bed onychomadesis may occur on the nail plate as a
disorders should always be ruled out first.22 consequence of nail matrix damage.
Then:
Chronic Paronychia
1. Clip away the onycholytic nail plate and repeat
this procedure every 2 weeks until the nail plate The proximal and lateral nail folds show mild
grows attached. erythema and swelling. Beau lines and, less
2. The exposed nail bed should be carefully dried frequently, onychomadesis may occur. The nail
after each soaking. plate sometimes presents a green discoloration
3. Application of a topical antiseptic solution of its lateral margins because of P aeruginosa
(2%–4% thymol in chloroform twice a day) on colonization. Secondary colonization with Candida
the exposed nail bed may be useful to prevent albicans and/or bacteria is also possible, causing
infections. self-limited episodes of painful acute inflam-
4. Sodium hypochlorite solution, 1 drop twice mation. Depending on the major causal factor,
daily around the nail, removes P aeruginosa chronic paronychia can be classified into several
when present. types.
178 Iorizzo

Irritative reaction Specifically, acute paronychia requires:

This is the most common form of paronychia. The
lesions are generally prominent with total in- 1. Drainage of the abscess, if present, and local
volvement of the proximal nail fold. The condition medications with antiseptics (2%–4% thymol
worsens, especially if there is an underlying in chloroform twice a day) to obtain relief of
eczematous condition, such as atopic dermatitis. inflammation and pain.
These patients have negative patch tests and ne- 2. Sodium hypochlorite solution 1 drop twice daily
gative provocative tests. They generally improve around the nail to remove P aeruginosa when
with preventive measures. present.
3. A topical combination of fusidic acid and beta-
Contact allergy methasone 17-valerate cream applied twice a
Chronic paronychia is caused by an acute day.25 This combination reduces pain first,
contact dermatitis of the proximal nail fold and then inflammation and swelling.
the cause of sensitization may be disclosed by 4. Mupirocin cream in the morning and clobetasol
patch testing. cream in the evening is an alternative option.

Food hypersensitivity Chronic paronychia instead requires:

Patients complain of worsening of the periungual
1. Application of a mild-potency topical steroid
inflammation and itching immediately after
(methylprednisolone aceponate 0.1% cream)
handling raw food ingredients. The diagnosis can
at bedtime.26
be made with a provocative test using fresh foods
2. Tacrolimus 0.1% ointment applied twice a day
on the proximal nail fold (20-minute open patch
as an alternative.27
test).
3. A cream containing piroctone olamine and
Candida hypersensitivity climbazole, applied twice a day for 3 months.28
Patients with chronic paronychia may develop a This product combines antiinflammatory, anti-
hypersensitivity to Candida antigens. These pa- microbial, and protective activities. Patients
tients usually have an immediate reaction to the using this cream showed disappearance of
intradermal skin test to Candida antigens. the inflammatory signs and growth of a normal
nail plate, smooth and shiny. Complete cuticle
True Candida paronychia regrowth was seen in greater than 50% of
This is very uncommon, except for patients with cases.
chronic mucocutaneous candidiasis and human 4. Systemic steroids (methylprednisone 20 mg/
immunodeficiency virus infection. Proximal nail kg/d) for few days in severe cases, when
fold inflammation is usually associated with several digits are affected.
proximal onycholysis or onychomycosis caused 5. Triamcinolone acetonide 2.5 mg/mL into
by Candida. affected nail folds (monthly injections) as an
alternative in severe cases. Topical lidocaine
can be applied 1 hour before the injections to
Treatment reduce pain.
Management of any form of paronychia always Systemic antifungals are often useless because
requires: chronic paronychia is not a mycotic infection.
Candida is just a colonizer of the proximal nail
1. Avoidance of wet environments, chronic micro-
fold that disappears when the proximal nail fold
traumas, and contact with irritants or allergens
barrier is restored.26
(for at least 3 months after the condition is
resolved).
2. Wearing cotton gloves under rubber gloves PSORIASIS
during manual work.
3. No aggressive/overzealous manicuring and nail Nail changes are reported in up to 50% of psoriatic
cosmetics of any kind. patients and they might be the only manifestation
4. Treatment of the underlying predisposing of the disease. Several nails are usually affected.
condition as well as drug interruption if these Depending on the anatomic area affected, the
are the causes. disease presents with different signs: irregular
5. Culture, radiographs, and/or biopsy, in recalci- pitting, surface ridging, and nail plate thickening
trant cases, in order to exclude responsible for psoriasis of the nail matrix; salmon patches,
disorders. They should always be ruled out onycholysis with erythematous border splinter
when only 1 digit is involved. hemorrhages, and subungual hyperkeratosis for
 Tips to Treat the 5 Most Common Nail Disorders 179

psoriasis of the nail bed. All these signs could next 6 months, and then every 2 months for 6 to
present together in the same patient and even in 12 months. Side effects include hemorrhages,
the same nail.29 pigmentary changes, and skin atrophy. Benefits
The impact on quality of life of this disorder is should be apparent in 2 to 3 months. Subungual
very high and the need for effective treatments hyperkeratosis and nail thickening respond better
should be met as soon as possible. There are than onycholysis and pitting. However, for
many treatments currently under clinical trials for improving pitting this is the best option.
psoriasis: the difficulty is to find an agent effective Local anesthesia with ethyl chloride or topical
for nail psoriasis with absent or minimal systemic lidocaine is generally necessary to make the treat-
side effects. The research on psoriasis should ment less painful. To reduce pain, needle-free jet
probably be focused on new vehicles for old drugs injectors are also available, although they may
rather than new actives. cause more side effects. The steroid can also be
mixed with a local anesthetic (this must not include
epinephrine). An anesthetic block might be neces-
Treatment
sary to treat nail bed psoriasis.
At present there is no cure for psoriasis. Available Oral acitretin 0.3 mg/kg/d for at least 6 months is
treatments require time and patience and, in most a good treatment of severe nail matrix and nail bed
cases, the results are scarce. It is important to psoriasis.36 The dosage can be increased to 0.5 to
remind patients that nail psoriasis is often wors- 0.75 mg/kg/d, but with more side effects. Subun-
ened by mechanical trauma (Koebner phenome- gual hyperkeratosis and thickening improve better
non). It is also scarcely influenced by sun than onycholysis and pitting. If the nail plate is thin
exposure and other environmental factors that and fragile, it is better not to use acitretin because
improve skin psoriasis. it could worsen the condition.
Reassuring the patient is generally the best Subcutaneous methotrexate (15 mg per week)
treatment option for mild nail psoriasis. No treat- and a low dosage of oral cyclosporin (2.5 mg/kg/
ment or mild emollients/lacquers containing urea d) have also been used with success.37,38 The
might be an option. former seems to give better results for nail matrix
For more severe cases, application of a cream psoriasis, the latter for nail bed psoriasis.
containing calcipotriol and betamethasone dipro- Biologic agents (adalimumab, etanercept, inflix-
pionate at bedtime is useful, especially for nail imab, ustekinumab) have enriched the therapeutic
bed psoriasis.30,31 The effectiveness can be armamentarium against psoriatic nails, but they
improved applying the product directly on the are generally restricted to patients with a concom-
nail bed, with an overnight occlusion, after trim- itant skin and/or joint psoriasis because of their
ming the detached nail plate. This treatment is high costs and toxicity. However, a consensus
easily accepted by patients, even though recur- on the use of these drugs for nail psoriasis is still
rences are frequent after discontinuation. Applica- lacking (Table 1).39
tion of topical tazarotene 0.1%, with or without
occlusion, is another good option. Irritation of the ONYCHOMYCOSIS
nail folds is a frequent side effect.32,33
Subungual hyperkeratosis and nail thickening Onychomycosis means the invasion of the nail by
respond better than onycholysis and pitting. fungi (dermatophytes, molds, yeasts). Different
Both calcipotriol and tazarotene are unable to clinical patterns of infection are described, de-
reach the nail matrix if applied on the proximal pending on the way and the extent by which fungi
nail fold and they are almost useless for nail matrix colonize the nail. The type of nail invasion depends
psoriasis. In nail matrix psoriasis, high-potency on both the fungus responsible and host suscepti-
steroids, such as clobetasol propionate 0.05% bility. Onychomycosis is an infection and should
cream, are a better option even though it has always be treated.
been proved that, if applied for long periods,
Treatment
they may cause acroatrophy (disappearing digit
syndrome).34 Treatment of onychomycosis is usually time
When few digits are affected, triamcinolone consuming and requires considerable patience,
acetonide 10 mg/mL (maximum 4 injections of because of the slow growth rate of the nail plate
0.1 mL per digit) could be injected into the prox- and the difficulty of getting actives to reach the in-
imal nail fold (in patients with nail matrix psoriasis) fected area.
or in the lateral nail folds (in patients with nail The choice of the best therapeutic approach is
bed psoriasis).35 Injections should be repeated based on numerous factors that should always
monthly for 6 months, then every 6 weeks for the be established before starting any treatment:
180 Iorizzo

Table 1
Treatment of nail psoriasis depending on the affected site

Nail Matrix Psoriasis Nail Bed Psoriasis

Clobetasol propionate 0.05% cream (1/d UO) Calcipotriol/betamethasone cream (1/d UO)
Triamcinolone acetonide 10 mg/mL (4  0.1-mL IL Tazarotene 0.1% cream or ointment (1/d UO)
injections) Clobetasol propionate 0.05% cream (1/d UO)
Acitretin 0.3 mg/kg/d (OA) Triamcinolone acetonide 10 mg/mL (4  0.1-mL IL
Methotrexate 15 mg/wk (SC) injections)
Biologics Acitretin 0.3 mg/kg/d (OA)
Cyclosporine 2.5 mg/kg/d (OA)
Biologics

Abbreviations: IL, intralesional; OA, oral administration; SC, subcutis; UO, under occlusion.

patient’s age and health, responsible fungus, clin-  DSO affecting more than 2 nails
ical type of onychomycosis, number of affected  Proximal subungual onychomycosis
nails, and severity of nail involvement. The con-  WSO in their deep form
comitant presence of tinea pedis (and tinea capitis  Patients not responding after 6 months of
in children) should always be ruled out.40 topical monotherapy alone
The goal of antifungal therapy should be myco-
logical cure, obtained when both microscopic and Penetration of a topical antifungal through the
cultural examinations are negative. To assess clin- nail plate requires a vehicle that is specifically
ical cure, patients should be followed for at least formulated for transungual delivery. Two vehicles
6 months after discontinuation of treatment. are currently available:
Recurrences and reinfections are always possible. 1. Water-insoluble polymers that create a film on
There are currently 3 main strategies to treat the nail surface. Daily or weekly application
onychomycosis: oral therapies, topical therapies, and removal with organic solvents is required;
and a combination of both.41 Oral treatments are nail filing is also necessary to reduce nail thick-
much more effective than topical ones, but they ness, thus allowing better penetration of the
are also associated with more systemic side actives.
effects and drug interactions. Topicals cause 2. Hydroalcoholic solutions of HPCH forming an
fewer side effects but their poor nail penetration invisible non-irritating film that is easily remov-
limits their efficacy. For this reason, clinical studies able with water.
are trying to find better penetration enhancers as
well as new actives. Topical agents well known to be effective
Topical monotherapy is usually recommended against onychomycosis are amorolfine 5%, a mor-
for: pholine derivative with a broad-spectrum fungi-
cidal and fungistatic activity, and ciclopirox
 Distal subungual onychomycosis (DSO) olamine 8%, a hydroxypyridone derivative with a
affecting less than 50% of the nail without broad-spectrum fungicidal and sporicidal activity.
matrix involvement, without yellow streaks Amorolfine nail lacquer should be applied twice
along the lateral margin of the nail, and per week for 6 to 12 months. Adverse events are
without yellow onycholytic areas in the central rare (<5%) and include burning, itching, redness,
portion of the nail (dermatophytoma). and pain near the application site. In the literature,
 White superficial onychomycosis (WSO) in the randomized controlled trials evaluating the effi-
classic form cacy and safety of this agent are scarce. More-
 Onychomycosis caused by molds (except for over, it is more cost-effective than ciclopirox
those caused by Aspergillus sp) olamine 8% nail lacquer.
 Patients unwilling or unable to tolerate oral Ciclopirox olamine nail lacquer should be
therapy applied daily for 6 to 12 months. Adverse events
 Patients requiring maintenance therapy after a are rare (<1%) and include burning, itching, and
course of oral therapy redness near the application site. It is widely used
Oral monotherapy is more suitable for: in children with successful outcomes.42 In a multi-
centre, randomized, 3-arm, placebo-controlled,
 DSO affecting greater than 50% of the nail, parallel groups, evaluator-blinded study, ciclopirox
including matrix olamine 8% in hydroalcoholic solution of HPCH
 Tips to Treat the 5 Most Common Nail Disorders 181

showed superior properties in terms of affinity to continuous dosage of 250 mg daily or as pulse
keratin, nail permeation, and easiness to use therapy (also called intermittent) at the dosage of
compared with the vinyl resin–based lacquer.43 500 mg daily (250 mg  2) for 1 week a month.
Recently, 2 new agents have been approved by Treatment duration is at least 6 weeks for finger-
the US Food and Drug Administration for the nails and 12 weeks for toenails. Dosages in chil-
topical treatment of onychomycosis: efinacona- dren are: less than 20 kg, 62.5 mg/d; 20 to
zole and tavaborole. 40 kg, 125 mg/d; more than 40 kg, 250 mg/d. Ter-
Efinaconazole 10%, a triazole with a broad- binafine is available in tablets or granules.
spectrum antifungal activity, has been released Interactions with other drugs are rare, even
on the market to treat DSO caused by dermato- though terbinafine is a competitive inhibitor of the
phytes in adults.44 It presents as a solution that cytochrome P450–linked enzyme 2D6. Terbinafine
has to be applied daily for 9 to 12 months. No is usually well tolerated and mild adverse events
periodic removal is required. Its low affinity for involve the gastrointestinal system. Taste alter-
keratin results in very good nail penetration. ations (metallic taste) typically occur 5 to 8 weeks
Adverse events are rare (comparable with vehicle) after starting treatment. Skin rashes are common
and include mild site dermatitis and vesicles. and are sometimes severe. Terbinafine is not
Tavaborole 5% is an oxaborole, also with a recommended in patients with liver disorders but
broad-spectrum antifungal activity, and was it is safe for diabetic patients. It can be used for pa-
released to treat onychomycosis caused by der- tients with celiac disease but the formulation is not
matophytes in adults.45 It is a solution that should lactose free.
be applied daily for 12 months to the entire nail Itraconazole is a synthetic triazole, fungistatic
surface and under the tip of the plate. The degree and with a much broader spectrum of action. For
of penetration through the nail plate has been this reason it has shown more efficacy in mixed in-
shown to be superior to ciclopirox. Adverse fections and Candida onychomycosis. Itracona-
events include application site exfoliation and zole can be detected in nails 1 week (fingernails)
erythema. to 2 weeks (toenails) after the start of therapy
The cure rate of onychomycosis treated with and it is still detectable in nails 27 weeks after
topicals can be improved by mechanical or chem- stopping administration, which is why it is admin-
ical avulsion of the affected nail plate in order to istered with a pulse therapy, at the dosage of
enhance penetration of the actives. Microporation 200 to 400 mg daily for 1 week a month. Treatment
(drilling of small holes), phonophoresis (low- duration is at least 6 weeks for fingernails and
frequency ultrasonography), or the use of 40% 12 weeks for toenails. Dosages in children are
urea–based preparations have been found to 5 mg/kg/d pulsed (2 pulses for fingernails and 3
enhance drug permeation through the nail plate. pulses for toenails). Itraconazole is available in tab-
Chemical enhancers are usually more practical lets or oral suspension.
than physical enhancers; they are cheaper and This drug should be administered with a high-fat
more easy to use (they are placed on the affected meal and/or acidic beverage to improve its ab-
nail, under occlusion, for 1 week maximum). With sorption (the suspension needs an empty stom-
this technique, topical antifungals otherwise inef- ach). Agents that increase gastric alkalinity
fective to treat onychomycosis, can be used with reduce itraconazole absorption. If there are no
success. For example, terbinafine cream, applied therapeutic alternatives, itraconazole should be
twice a day and preferably under occlusion, is a administered 2 hours before one of these agents.
good option. With itraconazole, the basis of drug interactions
Among systemic treatments, terbinafine has is the inhibition/induction of the cytochrome P450–
been proved to be more effective than other linked enzyme 3A4. Care must be taken with
agents such as itraconazole, fluconazole, or gris- elderly people taking multiple drugs. Adverse
eofulvin and is, therefore, considered the first-line effects may involve the gastrointestinal system,
treatment. Percentages of cure rates obtained the liver, and the skin. Its use has also been asso-
with systemic drugs vary from study to study.41 ciated with congestive heart failure. Itraconazole is
Terbinafine is an allylamine with a fungistatic safe for patients with celiac disease and is lactose
and fungicidal effect. Following oral administra- free.
tion, terbinafine is rapidly absorbed and widely In patients with poor prognostic factors sug-
distributed to body tissues including the nail ma- gesting possible treatment failure, options are46:
trix. Nail terbinafine concentrations are detected
within 1 week after starting therapy and persist  Combination therapy: association of a sys-
for at least 30 weeks after the completion of temic treatment and a topical treatment, with
treatment. Terbinafine can be administered at the the latter to be continuously applied even
182 Iorizzo

when onychomycosis is cured, for at least 2. Piraccini BM, Iorizzo M, Antonucci A, et al. Treat-
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 Supplemental therapy with terbinafine or 3. Shemer A, Daniel CR III. Common nail disorders.
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nazole 400 mg/d for 1 week a month. At nails. J Cosmet Dermatol 2004;3:138–44.
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the patient can have an extra month of the plates. Skin Pharmacol Appl Skin Physiol 2000;13:
drug. 111–9.
 Sequential therapy with itraconazole followed 6. Brosche T, Dressler S, Platt D. Age-associated
by terbinafine: the suggested regimen is 2 changes in integral cholesterol and cholesterol sul-
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