Download a 14-year-old boy with onychomycosis

CASE STUDY
A 14-YEAR-OLD BOY WITH ONYCHOMYCOSIS
—
Sheila Fallon Friedlander, MD
BACKGROUND
A 14-year-old boy has severe nail fungus affecting
several toes and a tender red streak beginning on the
left distal toe and proceeding up the posterior aspect of
his leg (Figure 1). He is otherwise healthy. His mother
reports a family history of “foot fungus” in his older
brother and father. The patient has had nail fungus for
several years but only recently noticed the tender
streak in his leg.
He has been treated previously with microsized
griseofulvin 1 g/d for 8 months (patient weight is 60
kg). There was no improvement in the patient’s toenails with this medication, thus he discontinued using
it 6 months before this office visit.
FOLLOW-UP
The patient’s laboratory tests were repeated at 4
weeks, and the test results were within the standard
ranges. After 6 months, the patient’s tinea pedis had
resolved and his nails showed significant improvement
(Figure 4).
DISCUSSION
Griseofulvin is the only US Food and Drug
Administration (FDA)-approved therapy for ony-
Figure 1. Presentation
PHYSICAL EXAMINATION
The red streak of induration extends from the
patient’s toe proximally to the lateral aspect of his
lower leg. He shows signs of erythema, maceration,
and tinea of his interdigital web spaces (Figures 2A and
2B), in addition to discoloration and subungual debris
of multiple toenails.
DIAGNOSIS
An aspirate of the leading edge of the red streak
showed Gram-positive cocci and a culture grew Group
A streptococci. A potassium hydroxide preparation of
subungual debris of the affected nails showed septate
hyphae, and cultures of the patient’s toenail clippings
grew Trichophyton rubrum on dermatophyte test medium and Mycosel agar (Figures 3A and 3B).
TREATMENT
The patient responded quickly to systemic antibiotic
therapy and topical antifungal therapy to the interdigital
web spaces. The patient’s baseline complete blood cell
count and liver function tests were obtained. He was prescribed terbinafine 250 mg daily for 3 months.
Advanced Studies in Medicine
n
Figure 2. Tinea of Interdigital Web Spaces
A
B
S629
CASE STUDY
Figure 3. Cultures of Toenail Clippings Growing
Trichophyton Rubrum
A
B
A, Dermatophyte test medium and B, Mycosel agar.
Figure 4. Follow-up at 6 Months
chomycosis in children, and it previously had been
ineffective in this patient. Other systemic therapy
options for onychomycosis in children include
terbinafine, itraconazole, and fluconazole.
Griseofulvin is available in microsized and ultramicrosized formulations. Microsized griseofulvin is
administered as 125 mg/5 cc or 250-mg tablets. The
ultramicrosized formulation is also available in 330mg tablets. Maximum doses are 1 g daily. The most
common adverse effects with griseofulvin are
headache, gastrointestinal disturbances, and (rarely)
hepatotoxicity and leukopenia. Griseofulvin may exacerbate lupus or porphyria. Prolonged therapy is often
required and the cure rates are suboptimal.1
Terbinafine is fungicidal and acts by inhibiting
squalene epoxidase and ergosterol synthesis for the
organism’s membrane. It is available in 250-mg tablets.
The most common adverse effects include rash, gas-
S630
trointestinal disturbance, headache, taste disturbance,
and, rarely, hepatotoxicity, neutropenia, and a flare of
subacute cutaneous lupus erythematosus. Monitoring
methods for patients who are on therapy are controversial, but many experts would recommend a baseline
complete blood cell count and liver function tests in
pediatric patients, with a repeat of these tests after 2 to
4 weeks of therapy or if symptoms develop.
Terbinafine should be administered for 6 weeks when
treating fingernails, and 12 weeks when treating toenails. The dosing schedule by patient weight is shown
in Table 1.2,3
Terbinafine provides the highest cure rates in adult
onychomycosis.2 However, it is not currently approved
by the FDA for use in children, but it can be used offlabel. Good cure rates with minimal adverse effects
have been observed in children ages 1 to 4 years.4-6 In
fact, complete cure was seen in 32 of 41 cases (78%)
after 12 weeks of treatment. Reported adverse effects
in children include urticaria, reversible neutropenia,
and rare taste disturbance. Terbinafine can be administered to children with or without food.3 Although
terbinafine is a reasonable first-line therapy, families
should be counseled regarding off-label use and the
rare adverse events associated with the drug (eg, liver
toxicity and neutropenia).
Itraconazole is also fungistatic and a good option
for onychomycosis treatment. The drug acts by
inhibiting fungal cell wall ergosterol synthesis. It is
available in 2 formulations that are convenient for
children: 100-mg capsules that should be taken on a
full stomach and can be opened and mixed with fatty
foods (eg, peanut butter) for ease of delivery, and a 10mg/mL solution that should be taken on an empty stom-
Table 1. Terbinafine Dosing in Children for
Onychomycosis
Child’s Weight, kg
Dose, mg
<20
62.5
20–40
125
>40
250
Adapted with permission from Gupta and Skinner. Pediatr Dermatol.
2004;21:74-79.2
Vol. 5 (6D)
n
June 2005
CASE STUDY
ach. Adverse effects with itraconazole can be problematic: Diarrhea is associated with the solution formulation.
Also, the cyclodextrin in the solution has been associated with pancreatic adenomas in rats; it is unclear what
relevance this has in humans. Hepatitis and neutropenia
are possible with itraconazole, but they are rare occurrences; headache and gastrointestinal disturbance are
more commonly seen adverse events.
Pulse therapy with itraconazole is recommended
for onychomycosis: 1 week on, 3 weeks off. For toenail
infections, 3 pulses are recommended; for fingernail
infections, 2 pulses are often sufficient. The dosing
schedule is shown in Table 2.2 Most reported cases of
itraconazole use in children used pulse dosing to
decrease cost and minimize adverse effects.2,7 The limited reports of itraconazole use in children show high
cure rates: a 94% cure rate in 17 prepubertal children
treated with pulse therapy for 3 to 5 months and a
complete cure in 49 of 63 children (78%) treated with
itraconazole capsules.2,8 Fluconazole is another option
and has been FDA-approved for pediatric candidal
yeast infections, but it is not approved for use in dermatophyte infections.
Severe onychomycosis in children, especially the
“total dystrophic” type of the disease, requires systemic
therapy and, perhaps, more than the traditional 3month course of treatment. Adjunctive topical therapy, such as chemical avulsion of infected nails with a
40% urea paste, may prove beneficial. Nails, such as
those nails shown in Figure 5, probably need chemical
or mechanical avulsion in addition to systemic therapy. In this patient, chemical avulsion of the nails with
a 40% urea paste and retreatment with oral antifungal
agents probably would increase the likelihood of cure.
There are several reasons why treating toenail fungal infections are important: These infections can
cause pain and difficulty in walking. Also, patients
with tinea pedis and onychomycosis are at an increased
risk for developing bacterial cellulitis of the contiguous
leg, as was seen in the patient in this case study.
Disruption of the skin barrier, particularly in interdigital web spaces, may allow for the ingress and invasion
of bacterial species that can lead to cellulitis. In fact,
onychomycosis is second only to a history of bacterial
cellulitis in increasing the risk (Table 3).9 Nonetheless,
families of pediatric patients may not wish to treat
fungal toenail infections in their children, which is a
reasonable option if the disease is not associated with
any symptoms.
Advanced Studies in Medicine
n
Table 2. Itraconazole Dosing in Children for
Onychomycosis
Child’s Weight, kg
Dosing
10–20
50 mg 3 times weekly
20–30
100 mg/d
30–40
100 mg/d, alternate with 200 mg/d
40–50
200 mg/d
>50
200 mg twice daily
Pulse dose = 5 mg/kg/day.
Adapted with permission from Gupta and Skinner. Pediatr Dermatol.
2004;21:74-79.2
Table 3. Disruption of Skin Barrier Increases the
Risk of Cellulitis
Nonmycological risk factors
OR
CI, %
History of bacterial cellulitis
29
11.7–72
Disruption of cutaneous barrier
18.2
9.2–36.2
Ulcer on target leg
9
3.7–21.8
Chronic leg edema
8.5
4.3–16.9
History of deep vein thrombosis
5.6
2.5–12.6
Varicose eczema
4.6
1.4–14.7
Abolition of peripheral pulse
2.9
1.3–6.1
Hyperpigmentation
2.9
1.8–4.5
Overweight
2.85
2.0–4.0
History of venous insufficiency
2.8
1.9–4.1
History of varicose veins
2.2
1.5–3.3
History of venous leg surgery
1.8
1.05–3.2
Results from a case-control study (243 cases, 467 controls) of patients with
acute bacterial cellulitis of the leg showed that disruption of the skin barrier, particularly in interdigital web spaces, may allow for the ingress and invasion of bacterial species that can lead to cellulitis.
CI = confidence interval; OR = odds ratio.
Adapted with permission from Roujeau et al. Dermatology.
2004;209:301-307.9
S631
CASE STUDY
Figure 5. Good Candidates for Nail Avulsion
Nails such as these probably need chemical or mechanical avulsion, in addition to systemic therapy.
As with my case study earlier in this monograph,
this patient had a strong family history of onychomycosis, which the mother generally referred to as “foot
fungus.” With onychomycosis, there often is a family
history of disease. Huang and Paller found that 59%
of pediatric patients had family members who were
affected, and Friedlander found that 100% of 33
affected children had first-degree relatives with the disease (Unpublished data, ongoing trial).8
CLINICIAN INTERVIEW
Dr Friedlander is a pediatric dermatologist with subspecialty training in infectious diseases and is a clinical
professor of pediatrics and medicine at the University of
California, San Diego School of Medicine, and the affiliated Children’s Hospital and Health Center. She treats
children with congenital and acquired skin conditions
and is particularly interested in cutaneous infections and
pediatric vascular lesions.
A senior clinical editor for Advanced Studies in
Medicine (ASiM) interviewed Dr Friedlander about this
case study involving a 14-year-old boy with onychomycosis, asking her to provide more insight into the practical
clinical aspects of diagnosing and treating onychomycosis
in primary care and the special considerations in pediatric patients.
ASiM: How often does cost become an issue when
you are talking about treatment? How do you
respond to patients who don’t have the money?
Dr Friedlander: Most insurance carriers or healthcare plans will cover griseofulvin, and some will cover
terbinafine. I have not had much success in getting
S632
ciclopirox covered for my pediatric patients.
Griseofulvin is the only drug that is FDA approved for
children, which was not effective in this case study. If
a patient has not responded to griseofulvin, then I can
request, and usually receive [coverage for], terbinafine.
Fluconazole also could be prescribed, but I think
terbinafine is more effective.
Cost is an issue because 9 months of griseofulvin is
usually more expensive than 3 months of terbinafine.
Some are concerned that the newer drugs are more
expensive, but all treatments can be expensive. It
would be interesting to see the cost data on ciclopirox
nail lacquer versus oral therapies. I remind patients
who are concerned about treatment costs that onychomycosis is a health issue, in addition to a cosmetic
issue. If the patient is symptomatic, I try to submit
coverage requests to their insurance company.
There was a time when the HMOs (Health
Maintenance Organizations) were attempting to deny
coverage for toenail infection treatment. Practitioners
were able to show that there were complications from
toenail fungus, particularly in patients with compromised immune systems and in patients with diabetes,
who can develop severe cellulitis. In addition, for any
patient there is the issue of pain from deformed nails.
Thus, now it is often possible to get medications covered by insurance. Does everyone who has toenail fungus need to be treated? Probably not; however, if the
disease progresses, patients can experience discomfort,
difficulty wearing shoes, and embarrassment from the
discolored thickened nails. Also, they are at risk for
developing a secondary infection.
ASiM: When should the primary care physician
refer children to a dermatologist or a podiatrist?
Dr Friedlander: If the child’s disease is problematic
to the family, the primary care physicians and podiatrists can obtain a culture. If the practitioner obtains a
culture from the patient and is satisfied with the diagnosis, they should be able to initiate therapy. Primary
care physicians certainly can prescribe topical
ciclopirox nail lacquer, and they can prescribe other
agents if they think it is appropriate. Although clinicians may not wholly approve of off-label usage, I
think it is reasonable for them to use the off-label
agents, if documentation is done. Then, if a patient is
unresponsive to the treatment, the primary care physician can refer the patient to a specialist. It all depends
on the “comfort level” of the practitioner.
Vol. 5 (6D)
n
June 2005
CASE STUDY
General practitioners may have less experience with
treating pediatric onychomycosis because the disease is
less common in children. Therefore, if clinicians are
doubtful about the diagnosis, the patient should be
referred to a specialist.
ASiM: We know aggressive treatment is important
in patients who are HIV (human immunodeficiency virus) positive and in patients with diabetes.
Why should children with onychomycosis be treated, especially when there are no secondary infections, as was true in this case?
Dr Friedlander: You can look at this problem in
another way. This disease is a major concern for many
families. They may want to have treatment started
early before extensive nail involvement occurs.
Obviously, discomfort is sometimes a problem for the
patient. If the nails are dystrophic, the children’s shoes
will not fit properly, and they may be embarrassed to
participate in outdoor sports and swimming or to wear
sandals. The clinician should acknowledge the
patient’s degree of discomfort, the symptoms involved,
and the family’s concerns.
Advanced Studies in Medicine
n
REFERENCES
1. Gupta, AK, Sibbald RG, Lynde CW, et al. Onychomycosis
in children: prevalence and treatment strategies. J Am Acad
Dermatol. 1997:36:395-402.
2. Gupta AK, Skinner AR. Onychomycosis in children: a brief
overview with treatment strategies. Pediatr Dermatol.
2004;21:74-79.
3. Jones TC. Overview of the use of terbinafine (Lamisil) in children. Br J Dermatol. 1995;132:683-689.
4. Aly R, Hafeez ZH, Rodwell C, et al. Rapid response of
Trichophyton tonsurans-induced onychomycosis after treatment
with terbinafine [published correction appears in Int J Dermatol.
2002;41:826]. Int J Dermatol. 2002;41:357-359.
5. Ungpakorn R, Reangchainam S, Kullavanijaya P.
Onychomycosis in a 2-year-old child successfully treated with
oral terbinafine. J Am Acad Dermatol. 1998;39:654-655.
6. Aguilar C, Mueller KK. Reversible agranulocytosis associated with oral terbinafine in a pediatric patient. J Am Acad
Dermatol. 2001;45:632-634.
7. Friedlander SF, Suarez S. Pediatric antifungal therapy.
Dermatol Clin. 1998;16:527-537.
8. Huang PH, Paller AS. Itraconazole pulse therapy for dermatophyte onychomycosis in children. Arch Pediatr Adolesc
Med. 2000;154:614-618.
9. Roujeau JC, Sigurgeirsson B, Korting HC, et al. Chronic
dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: a case-control study. Dermatology.
2004;209:301-307.
S633
NOTES
S634
Vol. 5 (6D)
n
June 2005