CASE STUDY ADULT CASES OF ONYCHOMYCOSIS. Warren S. Joseph, DPM, FIDSA

Size: px

Start display at page:

Download "CASE STUDY ADULT CASES OF ONYCHOMYCOSIS. Warren S. Joseph, DPM, FIDSA"

Eunice Curtis
5 years ago
Views:

1 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. 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 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 S614 Vol. 5 (6D) June 2005

2 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). 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 infections). 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 Year-Old-Man Figure Year-Old Patient with Clinical AIDS Advanced Studies in Medicine S615

3 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. 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 Year-Old Man Figure 5. A 55-Year-Old Man 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. 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 S616 Vol. 5 (6D) June 2005

4 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 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 Advanced Studies in Medicine S617

5 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 Table 1. Selected Drug Interactions with Itraconazole* Drug plasma concentration increased by itraconazole Antiarrhythmics Digoxin, dofetilide, quinidine, disopyramide Anticonvulsants Carbamazepine Antimycobacterials Rifabutin Antineoplastics Busulfan, docetaxel, vinca alkaloids Antipsychotics Pimozide Benzodiazepines Alprazolam, diazepam, midazolam, triazolam Calcium channel blockers Dihydropyridines and verapamil Gastrointestinal motility agents Cisapride HMG CoA-reductase inhibitors Atorvastatin, cerivastatin, lovastatin, simvastatin Immunosuppressants Cyclosporine, tacrolimus, sirolimus Oral hypoglycemics Oral hypoglycemics Protease inhibitors Indinavir, ritonavir, saquinavir Other Levacetylmethadol (levomethadyl), ergot alkaloids, halofantrine, alfentanil, buspirone, methylprednisolone, budesonide, dexamethasone, trimetrexate, warfarin, cilostazol, eletriptan Anticonvulsants Antimycobacterials Gastric acid suppressors/neutralizers Non-nucleoside reverse transcriptase inhibitors Macrolide antibiotics Protease inhibitors Decrease plasma concentration of itraconazole 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 Carbamazepine, phenobarbital, phenytoin Isoniazid, rifabutin, rifampin Antacids, H 2 -receptor antagonists, proton pump inhibitors Nevirapine Increase plasma concentration of itraconazole 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: Accessed May 3, S618 Vol. 5 (6D) June 2005

6 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): 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: Heikkila H, Stubb S. Long-term results in patients with onychomycosis treated with terbinafine or itraconazole. Br J Dermatol. 2002;146: 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: 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: Itraconazole US prescribing information. Sporanox (Itraconazole) Capsules Web site. Available at: px/sporanox.pdf. Accessed May 3, Terbinafine US prescribing information. Novartis Pharmaceuticals Corporation Web site. Available at: isil_tablets.pdf. Accessed May 3, Advanced Studies in Medicine S619

Core Safety Profile. Pharmaceutical form(s)/strength: Oral solution 10 mg /ml. Date of FAR:

Core Safety Profile. Pharmaceutical form(s)/strength: Oral solution 10 mg /ml. Date of FAR: Core Safety Profile Active substance: Itroconazole Pharmaceutical form(s)/strength: Oral solution 10 mg /ml P - RMS: UK/H/PSUR/0033/001 Date of FAR: 15.07.2010 CORE SAFETY PROFILE Based on EU SmPC sections