These are fungal infections of the nails. These are frequently stubborn chronic infections with 40% of cases caused by dermatophytes. The most common dermatophytes include T. rubrum and T. mentagropytes var. interdigitale. The rest of infections are caused by various yeasts, with Candida albicans the most common.
Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
PATHOGENESIS CHARACTERIZATION TRICHOPHYTIN ANTIGEN
Reactivity to trichophytin antigen in patients with onychomycosis: Effect of terbinafine
Boni E. Elewski, MD
Maria El Charif, MD
Kevin D. Cooper, MD, etal.
Cleveland, Ohio, and East Hanover, New Jersey
J Am Acad Dermatol 2002;46:371-5 Abstract quote
Background: Many patients with chronic dermatophytosis and onychomycosis have depressed cell-mediated immunity (CMI) to trichophytin.
Objective: The fungicidal properties of oral terbinafine provide a unique opportunity to explore whether elimination of antigen could restore CMI response in these patients.
Methods: A double-blind, placebo-controlled study evaluated the effect of terbinafine (250 mg/d for 12 weeks) on skin immunoreactivity to intradermal trichophytin antigen (TRIPA), mycologic status of the nail, and nail growth in patients with toenail onychomycosis.
Results: Skin reactivity, in an optimized, dose response challenge series to TRIPA was inversely related to disease chronicity. Mycologic/clinical response rates were 72%/84% for terbinafine and 0%/7% for placebo. Terbinafine increased the number of TRIPA reactors 2-fold and the mean TRIPA reaction area 4-fold; responses in placebo-treated patients were relatively unchanged. Of the 7 (of 25) patients receiving terbinafine who still had positive mycology 6 months after treatment, all were anergic to TRIPA at baseline and all but one remained so after treatment.
Conclusion: Terbinafine treatment enhances and restores CMI to TRIPA in patients with Trichophyton rubrum onychomycosis and may thereby reduce susceptibility to reinfection. Terbinafine reversal of immunologic anergy may be an important model of microbial tolerance in chronic dermatophyte infections.
- J Am Acad Dermatol. 2006 Oct;55(4):620-6. Epub 2006 Jun 13. Abstract quote
OBJECTIVE: Our purpose was to estimate and compare the cost-effectiveness of the most commonly used diagnostic tests for onychomycosis: potassium hydroxide preparation (KOH), interpreted both by a dermatologist (KOH-CLINIC) and a laboratory technician (KOH-LAB); KOH with dimethyl sulfoxide (KOH-DMSO) and with chlorazol black E (KOH-CBE), interpreted by a dermatologist; culture using dermatophyte test medium, culture with Mycobiotic and Inhibitory Mold Agar (Cx); and histopathologic analysis using periodic acid-Schiff stain (PAS).
METHODS: This was a repeated-measure, blinded, cross-sectional study conducted at the Minneapolis Veterans Affairs Medical Center. Inclusion criteria included: at least one toenail with 25% or more clinical disease, which was defined as subungual debris with onycholysis and/or onychauxis. Exclusion criteria included other nail dystrophies, use of oral antifungal medication for 2 months or longer within the past year, or topical ciclopirox lacquer within 6 weeks of enrollment. The main outcome measure was the cost-effectiveness (Medicare and non-Medicare costs) of 7 diagnostic tests. Sensitivity (at least 3 positive tests) was the unit of effectiveness.
RESULTS: Two hundred four participants were enrolled; their average age was 69.5 years and 95.5% were male. PAS was the most sensitive test (98.8%); it was statistically significantly more sensitive than all other diagnostic tests except KOH-CBE (94.3%). Dermatophye test medium was the least sensitive test (57.3%). KOH-CBE was statistically significantly more cost effective than any other test, with the exception of KOH-CLINIC and KOH-LAB. PAS was the least cost effective.
LIMITATIONS: Test specificities were not evaluated.
CONCLUSION: KOH-CBE should be the test of choice for practitioners confident in interpreting KOH preparations because of its combination of high sensitivity and cost-effectiveness.
Comparison of diagnostic methods in the evaluation of onychomycosis.
Weinberg JM, Koestenblatt EK, Tutrone WD, Tishler HR, Najarian L.
Department of Dermatology at St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA.
J Am Acad Dermatol. 2003 Aug;49(2):193-7. Abstract quote
BACKGROUND: Onychomycosis is a common problem seen in clinical practice. Given the differential diagnosis of dystrophic nails, it is helpful to obtain a definitive diagnosis of dermatophyte infection before the initiation of antifungal therapy. Potassium hydroxide (KOH) preparation and fungal culture, which are typically used in the diagnosis of these infections, often yield false-negative results. Recent reports have suggested that nail plate biopsy using periodic acid-Schiff (PAS) (Bx/PAS) stain may be a very sensitive technique for the diagnosis of onychomycosis.
OBJECTIVE: The purpose of this study was to compare KOH preparation, culture, Bx/PAS stain, and calcofluor white (CW) stain in the diagnosis of onychomycosis and to determine their sensitivity and specificity.
METHODS: We evaluated 105 patients with suspected onychomycosis using 4 diagnostic methods: KOH preparation, culture, Bx/PAS, and CW stain. CW stain binds to cellulose and chitin, and fluoresces when exposed to UV radiation. It is a highly sensitive and specific technique for the detection of dermatophytes. To determine the clinical usefulness and performance characteristics of each test, CW was chosen as the gold standard for statistical analysis.
RESULTS: Of the patients, 93 had at least 1 of the 4 diagnostic methods positive for the presence of organisms. The following were calculated for each test: sensitivity; specificity; positive predictive value; and negative predictive value. The sensitivities of each of the techniques were as follows: KOH 80%; Bx/PAS 92%; and culture 59%. Both KOH and Bx/PAS methods were more sensitive than culture (P =.00002). Bx/PAS was also more sensitive than KOH (P =.03). The specificities were as follows: KOH 72%; Bx/PAS 72%; and culture 82%. The positive predictive value calculated for the different techniques were: KOH 88%; Bx/PAS 89.7%; and culture 90%. In terms of negative predictive value, the results were: KOH 58%; Bx/PAS 77%; and culture 43%.
CONCLUSION: Bx/PAS is the most sensitive method for the diagnosis of onychomycosis. It is also superior to the other methods in its negative predictive value. It is indicated if other methods are negative and clinical suspicion is high, and potentially is the single method of choice for the evaluation of onychomycosis.
CHARACTERIZATION Modified Zaias Classification Distal and lateral subungual onychomycosis (DLSO)
Fungus enters the hyponychium or the lateral nail fold infecting the stratum corneum distal to the hyponychium or ajacent to the lateral nail fold
North American pathogens include:
DLSO may be associated with three independent clincial features:
Proximal subungual onychomycosis (PSO)
Fungus invades under the cuticle at the proximal nail fold resulting in a whitish discoloration and onycholysis of the proximal nail plate
Proximal white subungual onychomycosis (PWSO) is a variant:
Often with AIDS and immunosuppresion
White superficial onychomycosis
Fungus invades the nail plate directly
Opaque white or yellow colored superficial islands of the nail plate
T. rubrum (May produce a superficial black onychomycosis)
White Superficial Onychomycosis
Epidemiological, Clinical, and Pathological Study of 79 Patients
Bianca Maria Piraccini, MD; Antonella Tosti, MD
Arch Dermatol. 2004;140:696-701 Abstract quote
Objective To analyze the epidemiology, responsible agents, clinical features, and outcome of white superficial onychomycosis (WSO).
Design Retrospective study.
Setting University hospital.
Patients A total of 79 patients with WSO seen at the Department of Dermatology of Bologna University from 1994 to 2002. Responsible agents included Trichophyton interdigitale in 58 cases (73%), Trichophyton rubrum in 4 (5%), Fusarium species in 9 (11%), Aspergillus species in 5 (6%), and Acremonium strictum in 3 (3%).
Results White superficial onychomycosis may have different clinical and epidemiological features. "Classic" WSO, characterized by superficial nail plate involvement, is usually due to Trichophyton mentagrophytes (var interdigitale), although Acremonium strictum or Onychocola canadiensis can sometimes be responsible. A deep and diffuse WSO, characterized by massive penetration of the nail plate by fungi, can be seen in nail infections by molds such as Fusarium species and Aspergillus species, or in nail infections by Trichophyton rubrum in healthy children and in patients infected with human immunodeficiency virus.
Conclusions Severity and spread of WSO is the result of complex host-parasite relationships. When dealing with a patient with WSO, we should always consider the causative organism and the host characteristics to choose the best therapeutic approach.
Candida onychomycosis Distal end of the digit is bulbous or pseudoclubbed with thickening of the nail bed Endonyx onychomycosis
Invasion of both the superficial and deeper nail plate
Lamellar splitting of the nail plate
T. violaceum (These are organisms usually associated with endothrix scalp infection)
Total nail dystrophy End point of any form of onychomycosis
Primary type seen in chronic mucocutaneous candidiasis
HISTOPATHOLOGY CHARACTERIZATION GENERAL
- A modified approach to the histologic diagnosis of onychomycosis.
Section of Dermatopathology, New York University School of Medicine, New York, New York 10016, USA.
- J Am Acad Dermatol. 2007 Nov;57(5):849-53. Abstract quote
BACKGROUND: Histologic examination of nail clippings with periodic acid-Schiff staining is the most sensitive diagnostic test for onychomycosis; however, difficulties in processing nail plates limit its use. In onychomycosis, fungi are most concentrated in the subungual hyperkeratosis rather than in the nail plate. We hypothesized that the diagnosis of onychomycosis could be effectively made from histologic examination of subungual hyperkeratosis alone. Specimens of subungual hyperkeratosis, unlike nail plates, can be processed in the same routine manner as skin specimens, allowing for the diagnosis of onychomycosis to be made more quickly and at lower cost.
OBJECTIVE: We investigated whether the diagnosis of onychomycosis could be effectively made from histologic examination of subungual hyperkeratosis alone.
METHODS: We selected all nail specimens submitted during an 8-month period to the New York University Dermatopathology Section for evaluation of onychomycosis that had subungual hyperkeratosis associated with the nail plate. Nail specimens were divided into two components: a subungual hyperkeratosis component and a nail plate component. The subungual hyperkeratosis was processed separately in a routine fashion and embedded in paraffin and examined. We determined the percentage of cases of onychomycosis in which hyphae were present in the subungual component.
RESULTS: Sixty-six cases of onychomycosis were diagnosed histologically during the study period. Ninety-seven percent of these cases had hyphae in the subungual component. In 3% of cases, hyphae were present in the nail plate component but not in the subungual component.
LIMITATIONS: This modified approach to diagnosing onychomycosis can only be utilized when an adequate amount of subungual hyperkeratosis is submitted.
CONCLUSIONS: The diagnosis of onychomycosis can be effectively made from histologic examination of subungual hyperkeratosis alone in most cases. This method circumvents the need to process nail plates in the vast majority of cases of onychomycosis (97%), resulting in a more efficient, less costly, and technically easier way of diagnosing onychomycosis. Submitting ample amounts of subungual hyperkeratosis is essential to increasing the diagnostic yield of nail clippings.
PROGNOSIS AND TREATMENT CHARACTERIZATION Treatment Oral antifungal agents
J Am Acad Dermatol. 2005 Oct;53(4):578-84. Abstract quote
BACKGROUND: Effective treatments for onychomycosis are expensive. Previous studies suggest that less costly, pulsed doses of antifungal medications may be as effective as standard, continuous doses. Terbinafine is the current treatment of choice for toenail onychomycosis.
OBJECTIVE: Our purpose was to determine whether pulse-dose terbinafine is as effective as standard continuous-dose terbinafine for treatment of toenail onychomycosis.
METHODS: We conducted a double-blind, randomized, noninferiority, clinical intervention trial in the Minneapolis Veterans Affairs Medical Center. The main inclusion criteria for participants were a positive dermatophyte culture and at least 25% distal subungual clinical involvement. Six hundred eighteen volunteers were screened; 306 were randomized. Terbinafine, 250 mg daily for 3 months (continuous) or terbinafine, 500 mg daily for 1 week per month for 3 months (pulse) was administered. The primary outcome measure was mycological cure of the target toenail at 18 months. Secondary outcome measures included clinical cure and complete (clinical plus mycological) cure of the target toenail and complete cure of all 10 toenails.
RESULTS: Results of an intent-to-treat analysis did not meet the prespecified criterion for noninferiority but did demonstrate the superiority of continuous-dose terbinafine for: mycological cure of the target toenail (70.9% [105/148] vs 58.7% [84/143]; P =.03, relative risk [RR] of 1.21 [95% confidence interval (CI), 1.02-1.43]); clinical cure of the target toenail (44.6% [66/148] vs 29.3% [42/143]; P =.007, RR =1.52 [95% CI, 1.11-2.07); complete cure of the target toenail (40.5% [60/148] vs 28.0% [40/143]; P =.02, RR=1.45 [95% CI, 1.04-2.01); and complete cure of all 10 toenails (25.2% [36/143] vs 14.7% [21/143]; P =.03, RR =1.71 [95% CI, 1.05-2.79). Tolerability of the regimens did not differ significantly between the groups (chi2 =1.63; P =.65).
LIMITATIONS: The study population primarily consisted of older men with severe onychomycosis.
CONCLUSIONS: This study demonstrated the superiority of continuous- over pulse-dose terbinafine. We also found this expensive therapy to be much less effective than previously believed, particularly for achieving complete cure of all 10 toenails.
Long-term efficacy of antifungals in toenail onychomycosis: a critical review.
Cribier BJ, Paul C.
Clinique Dermatologique des Hopitaux Universitaires, 1 place de l'Hopital 67091 Strasbourg, France.
Br J Dermatol 2001 Sep;145(3):446-52 Abstract quote
BACKGROUND: Modern antifungal drugs achieve high mycological and clinical cure rates in onychomycosis of the toes, but little is known about the long-term evolution of the treated patients.
OBJECTIVES: The aim of this review was to analyse the therapeutic results recorded more than 1 year after initiation of therapy.
METHODS: We used two endpoints for the analysis: EP1 (the number of patients with negative mycology after follow-up, divided by the number of patients included at day 0, including all patients lost to follow-up), and EP2 (the number of patients with negative mycology after follow-up divided by the number of patients with negative mycology at week 48). Clinical cure rate (EPclin) was the number of patients clinically cured or with minimal residual lesions divided by the number of patients included at day 0.
RESULTS: From a Medline search we identified 17 studies providing results beyond 48 weeks. Ketoconazole 200 mg d(-1) up to 1 year resulted in EP1 of 11% at 18 months, and EP2 of 43%. Griseofulvin 1 g d(-1) for 1 year allowed an EP1 of 43% at 18 months, and EP2 of 71%. The mean EP1 after fluconazole once weekly up to 1 year was 49% at 18 months, and EP2 was 91%. With itraconazole 200 mg d(-1) or 400 mg d(-1) for 1 week each month for 3-4 months, EP1 was 37% at 18 months, and 53% at 2 years; EP2 was 76% at 4 years. Terbinafine 250 mg d(-1) for 12-16 weeks achieved an EP1 of 62% at 18 months, 72% at 2 years, and 60% at 4 years; EP2 was 80% at 18 months, 81% at 2 years, and 71% at 4 years. In the only study planned to compare the long-term efficacy of terbinafine and itraconazole, EP1 at 18 months was significantly higher with continuous terbinafine than with intermittent itraconazole (66% vs. 37%, P < 0.001). The clinical cure rates were 21% at 60 weeks and 37% at 72 weeks with fluconazole. EPclin was 27% at 18 months and 35% at 2 years with itraconazole. EPclin was 48% at 18 months, 69% at 2 years and 50% at 4 years with terbinafine.
CONCLUSIONS: Considering the stringency of the criteria we used, this critical review suggests that the long-term efficacy achieved with terbinafine is superior to that obtained with griseofulvin, ketoconazole, fluconazole or itraconazole.
Long-term Effectiveness of Treatment With Terbinafine vs Itraconazole in Onychomycosis
A 5-Year Blinded Prospective Follow-up Study
Bárur Sigurgeirsson, MD, PhD; Jón H. Ólafsson, MD, PhD; Jón þ Steinsson, MD; Carle Paul, MD; Stephan Billstein, MD; E. Glyn V. Evans, MD
Arch Dermatol. 2002;138:353-357 Abstract quote
To examine long-term cure and relapse rates after treatment with continuous terbinafine and intermittent itraconazole in onychomycosis.
Long-term prospective follow-up study.
Three centers in Iceland.
The study population comprised 151 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte toenail onychomycosis.
In a double-blind, double-dummy study, patients were randomized to receive either terbinafine (250 mg/d) for 12 or 16 weeks or itraconazole (400 mg/d) for 1 week in every 4 for 12 or 16 weeks (first intervention). Patients who did not achieve clinical cure at month 18 or experienced relapse or reinfection were offered an additional course of terbinafine (second intervention).
Main Outcome Measures
The primary efficacy criterion was mycological cure, defined as negative results on microscopy and culture at the end of follow-up and no requirement of second intervention treatment. Secondary efficacy criteria included clinical cure without second intervention treatment and mycological and clinical relapse rates.
Median duration of follow-up was 54 months. At the end of the study, mycological cure without second intervention treatment was found in 34 (46%) of the 74 terbinafine-treated subjects and 10 (13%) of the 77 itraconazole-treated subjects (P<.001). Mycological and clinical relapse rates were significantly higher in itraconazole vs terbinafine-treated patients (53% vs 23% and 48% vs 21%, respectively). Of the 72 patients who received subsequent terbinafine treatment, 63 (88%) achieved mycological cure and 55 (76%) achieved clinical cure.
In the treatment of onychomycosis, continuous terbinafine provided superior long-term mycological and clinical efficacy and lower rates of mycological and clinical relapse compared with intermittent itraconazole.
Oral treatments for toenail onychomycosis: a systematic review.
Crawford F, Young P, Godfrey C, Bell-Syer SE, Hart R, Brunt E, Russell I.
The Dental Health Services Research Unit, The University of Dundee, Park Place, Dundee DD1 4MR, Scotland.
Arch Dermatol 2002 Jun;138(6):811-6 Abstract quote
OBJECTIVE: To identify and synthesize the evidence for the efficacy of oral treatments for fungal infections of the toenails.
DESIGN: Systematic review of randomized controlled trials.
INTERVENTIONS: Oral treatments for dermatophyte infections of the toenails.
MAIN OUTCOME MEASURES: Cure confirmed by microscopy and culture results in patients with clinically diagnosed fungal infections. Data relating to the clinical cure rates were also extracted from the trials.
RESULTS: A pooled analysis of 2 trials comparing mycological cure rates from continuous treatment with terbinafine (250 mg/d for 12 weeks) and continuous treatment with itraconazole (200 mg/d for 12 weeks) found a statistically significant difference in 11- and 12-month outcomes in favor of terbinafine (risk difference, -0.23 [95% confidence interval, -0.32 to -0.15]; number needed to treat, 5 [95% confidence interval, 4 to 8]). An analysis of clinical cure rates was not possible because of the diversity of definitions used in researching the effectiveness of oral antifungal drugs for onychomycosis. Only 3 trials gave a clear definition of clinical cure and presented data for these outcomes.
CONCLUSIONS: There is good evidence that a continuous regimen of terbinafine (250 mg/d) for 3 months is the most effective oral treatment for fungally infected toenails. Consensus among researchers evaluating oral antifungal drugs for onychomycosis is needed to establish meaningful definitions of clinical cure. Most trials were funded by the pharmaceutical industry; we found little independent research, and this may have introduced bias to the review.
Oral treatments for fungal infections of the skin of the foot (Cochrane Review).
Bell-Syer SE, Hart R, Crawford F, Torgerson DJ, Tyrrell W, Russell I.
Department of Health Sciences, University of York, Genesis 6, Heslington, York, North Yorkshire, UK, YO10 5DQ. are more effective than no treatment.
Cochrane Database Syst Rev 2002;(2):CD003584 Abstract quote
BACKGROUND: About 15% of the population have fungal infections of the feet (tinea pedis or athlete's foot). Whilst there are many clinical presentations of tinea pedis the most common are between the toes (interdigital) and on the soles, heels and sides of the foot (plantar) which is known as moccasin foot. Once acquired the infection can spread to other sites including the nails, which can be a source of reinfection. Oral therapy is usually used for chronic conditions or when topical treatment has failed.
OBJECTIVES: To assess the effects and costs of oral treatments for fungal infections of the skin of the foot (tinea pedis).
SEARCH STRATEGY: Randomised controlled trials were identified from MEDLINE, EMBASE and CINAHL from the beginning of these databases to January 2000. We also searched the Cochrane Controlled trials Register (Cochrane Library issue 1, 2000) the Science Citation Index, BIOSIS, CAB-Health, Health star and Economic databases. Bibliographies were searched, podiatry journals hand searched and the pharmaceutical industry and schools of podiatry contacted.
SELECTION CRITERIA: Randomised controlled trials including participants who have a clinically diagnosed tinea pedis, confirmed by microscopy and growth of dermatophytes in culture.
DATA COLLECTION AND ANALYSIS: Study selection was done by two independent reviewers. Methodological quality assessment and data collection was also assessed by two independent reviewers.
MAIN RESULTS: Twelve trials, involving 700 participants, were included. The two trials comparing terbinafine and griseofulvin produced a pooled risk difference of 52% (95% confidence intervals 33% to 71%) in favour of terbinafine's ability to cure infection. No significant difference was detected between terbinafine and itraconazole; fluconazole and either itraconazole and ketoconazole; or between griseofulvin and ketoconazole, although the trials were generally small. Two trials showed that terbinafine and itraconazole were effective compared with placebo. Adverse effects were reported for all drugs, with gastrointestinal effects most commonly reported.
REVIEWER'S CONCLUSIONS: The evidence suggests that terbinafine is more effective than griseofulvin and that terbinafine and itraconazole are more effective than no treatment.
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Last Updated November 16, 2007
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