Download adult cases of onychomycosis - Advanced Studies in Medicine

CASE STUDY
ADULT CASES OF ONYCHOMYCOSIS
—
Warren S. Joseph, DPM, FIDSA
BACKGROUND (CASE 1)
A 41-year-old woman presented with no complaints
of pain, but she was concerned about discoloration of
her toenails. She has a black belt in karate and works as
a karate teacher. She works out in her bare feet and is
embarrassed by the condition of her toenails.
She had approximately 25% to 30% distal involvement in her toenail, with no other nail involvement
(Figure 1A).1 The nail was not particularly thickened,
just discolored.
DISCUSSION
The patient had mild disease with no nail thickening.
Some clinicians may have considered several approaches
for this patient, such as “watchful waiting” (ie, waiting to
see if the nail grows out normally and debride if necessary), debridement plus topical antifungal cream/solution (prescription or over-the-counter [OTC]),
ciclopirox nail lacquer with or without debridement, or
oral terbinafine with or without debridement.
Although these all are essentially reasonable treatment approaches, watchful waiting is almost never recommended. Debridement would be a minimal and
beneficial first step. Ciclopirox lacquer would be a reasonable first treatment because the patient’s infection
is confined. Oral medication also could be a first-line
treatment, but some patients may choose to start with
a topical agent, possibly because of concerns about oral
medications, drug-to-drug interactions, or potential
cost issues, depending on their insurance coverage.
I elected to prescribe ciclopirox lacquer only. I saw
this patient at her karate school, thus I was unable to
perform debridement. She was a motivated patient,
and the ciclopirox lacquer cured the infection. At the
3-month follow-up visit, the patient showed a 100%
clinical cure of onychomycosis (Figure 1B).
one nail, but he had some involvement in other nails
(Figure 2).1 It was the first time he had seen a physician for this infection. He had no discomfort and
minimal nail thickening, but he was concerned
because the infection was spreading. The hallux nail
showed some involvement down to the level of the
lunula. The patient’s medical history reflected no
other diseases.
Figure 1A. 41-Year-Old Woman at Presentation
Reprinted with permission from Joseph and Scher. Podiatry Today.
2004;17(11a).1
Figure 1B. 3-Month Follow-Up
BACKGROUND (CASE 2)
A 75-year-old man came to the Veterans
Administration (VA) hospital with 80% involvement of
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DISCUSSION
Debridement alone or debridement plus a topical
antifungal preparation would be insufficient for this
patient. The infection had progressed to such a
degree that pharmacotherapy was needed. A good
treatment for this patient would be oral terbinafine
alone, but I prefer the combination of oral
terbinafine and ciclopirox lacquer. Although this
patient did not have a severe case of onychomycosis,
oral therapy would ensure more aggressive treatment. If the patient were diabetic, combination
therapy would be warranted because the sequalae are
more serious and more frequent in patients with diabetes mellitus.
In my experience, virtually all patients with onychomycosis have coexisting tinea pedis (fungal infection of the skin). In fact, onychomycosis usually
starts as tinea pedis and progresses into the hyponychium if there has been a trauma that broke the seal
between the nail and the nail bed. The fungus then
accesses the nail bed stratum corneum and causes
onychomycosis. Tinea pedis usually can be easily
treated, but onychomycosis will require treatment
because it can act as a reservoir that reinfects the
skin, creating an unending cycle of infection. For
this patient, the only disadvantage to treating tinea
pedis and onychomycosis was buying 3 different
medications, but the investment would be worth the
cost to prevent future or continuing infections.
BACKGROUND (CASE 3)
A 37-year-old patient with clinical AIDS and who
tested positive for human immunodeficiency virus
(HIV) returned to the clinic because he was concerned
about a rapidly spreading nail infection. At his first
clinic visit, his nail showed a small area of involvement, but the infection had spread in 1 month to most
of his nail. The infection remained only within the
hallux nail (Figure 3).1 He was diagnosed with proximal subungual onychomycosis (PSO).
DISCUSSION
Proximal subungual onychomycosis is the most
common presentation of onychomycosis among
patients with HIV. PSO has a unique presentation, as
compared with the other types of onychomycosis: It
starts at the eponychium (as opposed to the hyponychium) and spreads proximal to distal (as opposed to
distal to proximal with other onychomycotic infec-
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tions). This patient did not appear to have white
superficial onychomycosis.
Debridement would be a minimal first step in
treatment, especially in a patient with HIV. If this
patient did not have HIV, debridement and a topical antifungal, such as ciclopirox lacquer, may be
sufficient. However, this patient will require more
aggressive treatment because this is not a superficial
infection. Systemic therapy may be needed.
Terbinafine plus ciclopirox lacquer probably is the
best treatment option. Also, with patients who are
HIV positive, CD4 levels correlate with the activity
of fungal infection. When CD4 counts are low, the
infections progress more rapidly. However, with the
currently available treatments for HIV infection,
CD4 counts can be maintained at higher levels, thus
the response should be similar to that for a person
without HIV.
Figure 2. 75-Year-Old-Man
Reprinted with permission from Joseph and Scher. Podiatry Today.
2004;17(11a).1
Figure 3. 37-Year-Old Patient with Clinical AIDS
Reprinted with permission from Joseph and Scher. Podiatry Today.
2004;17(11a).1
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CASE STUDY
BACKGROUND (CASE 4)
A 70-year-old man who was seen at the VA hospital had severe pain from toenail infections. He was
unable to wear shoes, and there was significant
involvement (with marked thickening) of all of his
toenails (Figure 4).1
He was taking the following medications: atorvastatin 20 mg/day, aspirin 65 mg/day, hydrochlorothiazide 25 mg/day, and bupropion XL 300 mg/day.
DISCUSSION
Debridement alone would not be a sufficient
treatment, nor would the use of topical antifungal
cream or solution. Because of the extensive involvement of all of the toenails, systemic therapy was necessary. Oral terbinafine with or without debridement
could be a reasonable approach. A study by Gupta
and Lynch has recently shown that combination
Figure 4. 70-Year-Old Man
Reprinted with permission from Joseph and Scher. Podiatry Today.
2004;17(11a).1
Figure 5. A 55-Year-Old Man
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therapy in vivo can offer synergistic benefits not
found with terbinafine or ciclopirox lacquer alone.2 I
recommend treatment with a combination of oral
terbinafine and ciclopirox lacquer.
Because of the multiple medications, some physicians may be concerned about drug interactions when
using oral antifungal agents. Although there are significantly more interactions possible with itraconazole,
terbinafine should not have a clinically significant
interaction with any of the concomitant medications.
There is a theoretical interaction possible with bupropion, a selective serotonin reuptake inhibitor (SSRI).
The patient should be observed for any signs of
increasing levels of that drug.
BACKGROUND (CASE 5)
A 55-year-old man was seen at the VA hospital
with a severe infection but with no pain or itching. He
came to our office at his wife’s request. He had trouble
cutting his toenails and had asked his wife to do it for
him. His toenails had become so thick that the wife
could no longer cut them (Figure 5). The patient also
has severe tinea pedis that he treated with OTC topical creams, which were ineffective.
DISCUSSION
This patient had a classic case of onychomycosis:
no pain, no itching. Many patients with onychomycosis are unaware that they have coexistent tinea
pedis infection. Patients usually complain of dry skin
that will not resolve with any amount of moisturizer.
When patients have infected toenails, the clinician
should examine the skin of the foot and between the
toes to look for signs of tinea pedis. In fact, onychomycosis starts as tinea pedis, thus the coexistence
of this infection is not surprising. This patient
already had tried topical agents that did not treat the
tinea pedis, thus more aggressive treatment is necessary. Debridement alone would not be sufficient.
Because of the extensive involvement and thickening
of all nails, systemic therapy is necessary.
Oral terbinafine with or without debridement is a
reasonable approach; however, as with Case 4, the
Gupta and Lynch data support a combination treatment approach.2 I recommend oral terbinafine with
ciclopirox lacquer. Maintenance therapy must be discussed with this patient. Several studies have shown
relapse rates of onychomycosis ranging from 22% to
66% up to 3 years after treatment.3-6
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CASE STUDY
CLINICIAN INTERVIEW
Warren S. Joseph, DPM, FIDSA, has been appointed
as Consulting Editor to Podiatry Management. Dr
Joseph currently serves as editor of the Journal of the
American Podiatric Medical Association and is an
internationally recognized authority on onychomycosis
and infectious diseases of the feet. He is also Adjunct
Associate Professor, Internal Medicine, Section of
Infectious Diseases, Temple University School of
Medicine, Philadelphia, Pennsylvania.
A senior clinical editor for Advanced Studies in
Medicine (ASiM) interviewed Dr Joseph about diagnosing and managing onychomycosis in adult patients.
ASiM: In Cases 1 and 2, you listed debridement as
a good first step but not sufficient as a total treatment. In which cases would debridement be sufficient as treatment?
Dr Joseph: Debridement does nothing to specifically address the fungus, but it will help the nail look better and be less painful for the patient. There will be less
pressure because the nail won’t be as thick, thus
debridement does serve an important purpose.
Debridement is recommended with ciclopirox topical
nail lacquer to improve results, and there are some
recent data showing that debridement in combination
with oral antifungals may at least increase the efficacy.
In the study, terbinafine alone was compared to
terbinafine plus debridement; results showed there was
some increased improvement with debridement.
Debridement also improved the patients’ quality of
life. The data are from the IRON-CLAD study, which
is not yet published but was presented at the
Midwestern Podiatry Meeting.
Therefore, it certainly could be assumed that the
same results would occur with the use of topical antifungals—debridement may enhance their efficacy.
Debridement is an important adjunct of palliative
therapy, but it does not cure or treat the fungus.
ASiM: In Case 2, you mention the importance of
treating tinea pedis. What are the treatment options?
Dr Joseph: Tinea pedis can be treated in 2 ways:
topically and orally. There are several effective topical antifungals on the market, including ciclopirox,
a new drug sertaconazole, and even OTC drugs such
as terbinafine. All of these drugs can be used to treat
tinea pedis.
Oral antifungal therapy also can be used for the
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treatment of tinea pedis. Patients can take ultramicrosized griseofulvin for approximately 6 weeks. Although
griseofulvin commonly is thought of as a long-term
treatment (approximately 18 months) for onychomycosis, it is actually a relatively short-term therapy.
Terbinafine and itraconazole are exceptionally
effective in treating tinea pedis. Although the drugs
have no specific indications, short courses (2–3 weeks
of terbinafine or a single pulse of the itraconazole) will
clear up tinea pedis.
ASiM: Case 3 is a patient who tested positive for
HIV. You mention that these patients are prone to
developing onychomycosis. If they already are taking several drugs to treat HIV, why is it important
to treat the nail fungus?
Dr Joseph: I think treatment is important because
of the psychosocial issues connected with onychomycosis. Nail fungus is a strong indicator that a
patient has HIV. Nail fungus is a unique condition
in patients with HIV, and they often develop proximal subungual onychomycosis. Patients with HIV
and the coimmunity associated with HIV/AIDS
know that onychomycosis is a marker for HIV.
Therefore, having onychomycosis really screams,
“I’m HIV positive, I may have AIDS.”
Also, onychomycosis could serve as a source of
infection. Patients with HIV or AIDS are prone to systemic fungal infections. No data are available to support this statement, but I think that physicians who
have patients with HIV or AIDS would want to treat
and cure a fungus to eliminate the risk of fungus
becoming systemic.
The patients with HIV whom I’ve seen clinically
have been amenable to having the onychomycosis
treated. However, I don’t treat large numbers of
patients with HIV; perhaps physicians who do may
look at this differently.
ASiM: Case 4 was a patient who was taking several
medications. In terms of the medications available
for treating onychomycosis, what drug interactions
should prescribers be concerned about?
Dr Joseph: In this situation, physicians may be too
cautious about drug-to-drug interactions. For example, azoles—in particular itraconazole—is a potent
inhibitor of cytochrome P450 isoenzyme 3A4 and will
effect many drug-to-drug interactions. The package
insert even contains a large number of “black-box
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CASE STUDY
warnings.” Many common drugs,
including the statins prescribed for
patients with high cholesterol, are
metabolized by enzyme 3A4. Therefore,
there is potential for drug-to-drug interactions with a drug that is a potent
inhibitor of enzyme 3A4. There is a list
available for prescribing itraconazole
(Table 1).7
Terbinafine is not an inhibitor of
3A4, thus there are no drug-to-drug
interactions that occur with some of the
other oral antifungals. Terbinafine
instead inhibits isoenzyme 2D6, which
metabolizes fewer drugs than 3A4.
SSRIs or the β-blocker propranolol are
examples of drugs that are 2D6-metabolized. Patients, especially those patients
who take psychotropic drugs, such as
antidepressants or antiseizure medications, should be observed for any sign of
health-related changes because of drugto-drug interaction (Table 2).8
Interestingly, there is no black-box
warning for SSRIs, and I’m not aware of
any clinically significant cases that have
been reported in the literature, but theoretically drug-to-drug interactions are a
possibility. Clinically, there are few
drug-to-drug interactions, and I mentioned the statins only because so many
patients are taking them.
ASiM: Is it possible for an infection to
be so advanced that it’s no longer
treatable, as shown in Case 5?
Dr Joseph: Overall, this is not a
common occurrence. If the nail has
been dystrophic, thick and painful,
and causing pressure on the nail bed,
the cells of the nail matrix may be
destroyed over a prolonged period. In
this scenario, the infection could cause
so much damage to the underlying
structures of the nail that nothing can
be done to save the nail because it is
not growing appropriately. There are
cases in which the fungus can be mycologically cured, but the nail is not
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Table 1. Selected Drug Interactions with Itraconazole*
Drug plasma concentration increased by itraconazole
Antiarrhythmics
Anticonvulsants
Antimycobacterials
Antineoplastics
Antipsychotics
Benzodiazepines
Calcium channel blockers
Gastrointestinal motility agents
HMG CoA-reductase inhibitors
Immunosuppressants
Oral hypoglycemics
Protease inhibitors
Other
Digoxin, dofetilide,† quinidine,† disopyramide
Carbamazepine
Rifabutin
Busulfan, docetaxel, vinca alkaloids
Pimozide†
Alprazolam, diazepam, midazolam,† triazolam†
Dihydropyridines and verapamil
Cisapride†
Atorvastatin, cerivastatin, lovastatin,† simvastatin†
Cyclosporine, tacrolimus, sirolimus
Oral hypoglycemics
Indinavir, ritonavir, saquinavir
Levacetylmethadol (levomethadyl), ergot alkaloids, halofantrine, alfentanil, buspirone, methylprednisolone, budesonide, dexamethasone,
trimetrexate, warfarin, cilostazol, eletriptan
Decrease plasma concentration of itraconazole
Anticonvulsants
Antimycobacterials
Gastric acid suppressors/neutralizers
Non-nucleoside reverse
transcriptase inhibitors
Carbamazepine, phenobarbital, phenytoin
Isoniazid, rifabutin, rifampin
Antacids, H2-receptor antagonists, proton
pump inhibitors
Nevirapine
Increase plasma concentration of itraconazole
Macrolide antibiotics
Protease inhibitors
Clarithromycin, erythromycin
Indinavir, ritonavir
*This list is not all-inclusive.
†Contraindicated with itraconazole based on clinical and/or pharmacokinetic studies.
Reprinted with permission from Itraconazole US prescribing information. Available at: http://www.sporanox.com/active/janus/en_US/assets/spx/sporanox.pdf. Accessed May 3, 2005.7
Table 2. Drug Interactions with Terbinafine
The following classes of drugs are metabolized predominantly by CYP 2D6. They should be
administered with careful monitoring and may require reduced doses when administered
with terbinafine.
•
•
•
•
Tricyclic antidepressants
Selective serotonin reuptake inhibitors
β blockers
Monoamine oxidase inhibitors type B
No information is available from adequate drug-to-drug interaction studies for oral contraceptives, hormone replacement therapies, hypoglycemics, theophyllines, phenytoins,
thiazide diuretics, and calcium channel blockers.
Data from Terbinafine US prescribing information.8
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CASE STUDY
going to be restored to any form of normalcy because
it has been dystrophic for such an extended time.
Some patients strongly object to their toenails
being removed, but patients can function quite well
without the infected toenails.
REFERENCES
1. Joseph WS, Scher RK. Understanding the Realities of
Antifungal Therapy. Podiatry Today. 2004;17(11a).
2. Gupta AK, Lynch LE. Management of onychomycosis:
examining the role of monotherapy and dual, triple, or
quadruple therapies. Cutis. 2004;74(suppl 1):5-9.
3. Tosti A, Piraccini BM, Stinchi C, Colombo MD. Relapses of
onychomycosis after successful treatment with systemic antifungals: a three-year follow-up. Dermatology. 1998;
197:162-166.
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4. Heikkila H, Stubb S. Long-term results in patients with onychomycosis treated with terbinafine or itraconazole. Br J
Dermatol. 2002;146:250-253.
5. Jansen R, Redekop WK, Rutten FF. Cost effectiveness of continuous terbinafine compared with intermittent itraconazole
in the treatment of dermatophyte toenail onychomycosis: an
analysis based on results from the L.I.ON. study. Lamisil versus Itraconazole in Onychomycosis. Pharmacoeconomics.
2001;19:401-410.
6. Sigurgeirsson B, Olafsson JH, Steinsson JB, et al. Long-term
effectiveness of treatment with terbinafine vs itraconazole in
onychomycosis: a 5-year blinded prospective follow-up
study. Arch Dermatol. 2002;138:353-357.
7. Itraconazole US prescribing information. Sporanox
(Itraconazole) Capsules Web site. Available at:
http://www.sporanox.com/active/janus/en_US/assets/s
px/sporanox.pdf. Accessed May 3, 2005.
8. Terbinafine US prescribing information. Novartis
Pharmaceuticals Corporation Web site. Available at:
http://www.pharma.us.novartis.com/product/pi/pdf/Lam
isil_tablets.pdf. Accessed May 3, 2005.
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