Onychomycosis: Rapid Evidence Review.

Onychomycosis is a chronic fungal infection of the fingernail or toenail bed leading to brittle, discolored, and thickened nails. Onychomycosis is not just a cosmetic problem. Untreated onychomycosis can cause pain, discomfort, and physical impairment, negatively impacting quality of life. Onychomycosis should be suspected in patients with discolored nails, nail plate thickening, nail separation, and foul-smelling nails. Accurate diagnosis is important before initiating treatment because therapy is lengthy and can cause adverse effects. A potassium hydroxide preparation with confirmatory fungal culture, periodic acid-Schiff stain, or polymerase chain reaction is the preferred diagnostic approach if confirmative testing is cost prohibitive or not available. Treatment decisions should be based on severity, comorbidities, and patient preference. Oral terbinafine is preferred over topical therapy because of better effectiveness and shorter treatment duration. Patients taking terbinafine in combination with tricyclic antidepressants, selective serotonin reuptake inhibitors, atypical antipsychotics, beta blockers, or tamoxifen should be monitored for drug-drug interactions. Topical therapy, including ciclopirox 8%, efinaconazole 10%, and tavaborole 5%, is less effective than oral agents but can be used to treat mild to moderate onychomycosis, with fewer adverse effects and drug-drug interactions. Nail trimming and debridement used concurrently with pharmacologic therapy improve treatment response. Although photodynamic and plasma therapies are newer treatment options that have been explored for the treatment of onychomycosis, larger randomized trials are needed. Preventive measures such as avoiding walking barefoot in public places and disinfecting shoes and socks are thought to reduce the 25% relapse rate.

Quality of life and therapeutic regimen management in onychomycosis patients and in vitro study of antiseptic solutions.

Onychomycosis or tinea unguium (EE12.1) and Onychomycosis due to non-dermatophyte moulds (1F2D.5) (OM) is a fungal infection of the nail plates with a high prevalence that often affects vulnerable people with co-existing health problems. Gold standard pharmacological treatments for onychomycosis have been associated with low success rates and increasing antifungal resistance, suggesting that treatment outcome is dependent on multiple variables. Here, the prevalence of OM and quality of life were characterized in two vulnerable populations-Hospital patients and Homeless people. Comparing both groups, the most prevalent fungal species were identified in Hospital patients. Then, the in vitro fungicidal properties of the antiseptics povidone-iodine, polyhexamethylene biguanide-betaine, octenidine dihydrochloride, and a super-oxidized solution against two ATCC strains (Candida albicans and Aspergillus niger) and three clinical fungal isolates from Hospital patients (Candida parapsilosis, Trichophyton interdigitale, and Trichophyton rubrum) were tested. OM prevalence was high in both patient groups studied, who also reported a reduction in quality of life and concerns about the state of their feet. In addition, Hospital patients had a non-negligent therapeutic regimen management style. Antiseptics tested in vitro revealed antifungal properties. As antiseptics are low-cost and easy to apply and have few iatrogenic effects, the demonstration of fungicidal properties of these solutions suggests that they may constitute potential supportive therapeutics for OM.

PAS stain based histological classification and severity grading of toenail onychomycosis.

Onychomycosis is a common world-wide health issue. Accurate detection is essential for treatment. Multiple studies have shown that PAS-stain based histological visualization of fungal elements is superior to either direct microscopy with 20% potassium hydroxide, or fungal culture. However, PAS stain based histological classification and severity grading of onychomycosis are lacking in the literature. Here we reported a fungal detection rate of 47.87% based on an analysis of 13,805 toenails processed for H&E and PAS stains over a three year period. Based on the analysis of fungal density, distribution and infiltrating depth level in 858 PAS-positive toenails, we created a novel PAS stain based histological classification system to classify onychomycosis as occult onychomycosis (OO), focal or diffuse subungual onychomycosis (FSO or DSO), focal or diffuse plate onychomycosis (FPO or DPO), focal or diffuse subungual and plate onychomycosis (FSPO or DSPO) and superficial onychomycosis (SO). The severities of OO, FSO and FPO were graded as mild, DSO and DPO as moderate, FSPO and DSPO as severe infections, which revealed that more than 75% PAS positive toenails were severe infections. Evaluation of 97 paired toenails biopsied pre- and post-treatment from 47 patients demonstrated that the severity of infection was significantly reduced from severe to mild and moderate levels. These data indicate that the current histological classification evaluates not only the severity of the fungal infection but also the response to treatment. We further propose a guideline for treatment of onychomycosis based on the histological classification and severity.

[New clinical classification for onychomycoses]. / Nouvelle classification clinique des onychomycoses.

We have updated our clinical classification on onychomycosis (2011) to render it of more practical value for the clinician. It should provide a better understanding of onychomycosis and facilitate an improved approach to treatment, taking into account, for example, the link between the proximal subungual variety and some superficial forms emerging from beneath the cuticle.

Onychomycosis: Current trends in diagnosis and treatment.

Onychomycosis is a fungal infection of the nails that causes discoloration, thickening, and separation from the nail bed. Onychomycosis occurs in 10% of the general population, 20% of persons older than 60 years, and 50% of those older than 70 years. It is caused by a variety of organisms, but most cases are caused by dermatophytes. Accurate diagnosis involves physical and microscopic examination and culture. Histologic evaluation using periodic acid-Schiff staining increases sensitivity for detecting infection. Treatment is aimed at eradication of the causative organism and return to a normal appearance of the nail. Systemic antifungals are the most effective treatment, with meta-analyses showing mycotic cure rates of 76% for terbinafine, 63% for itraconazole with pulse dosing, 59% for itraconazole with continuous dosing, and 48% for fluconazole. Concomitant nail debridement further increases cure rates. Topical therapy with ciclopirox is less effective; it has a failure rate exceeding 60%. Several nonprescription treatments have also been evaluated. Laser and photodynamic therapies show promise based on in-vitro evaluation, but more clinical studies are needed. Despite treatment, the recurrence rate of onychomycosis is 10% to 50% as a result of reinfection or lack of mycotic cure.

Update: medical treatment of onychomycosis.

The diagnosis of onychomycosis should be made clinically and mycologically: clinically, by one of seven subtypes of onychomycosis, and mycologically, by evidence of dermatophytes or verified presence of molds and/or yeasts. Dermatophytes are usually considered as pathogens, whereas non-dermatophyte molds and yeasts are saprophytes. Basic anamnesis and close inspection should be performed to eliminate combined diseases (e.g., onychomycosis and trauma). The gold standard treatment for onychomycosis is basically systemic. Combination with topical agents, such as nail lacquer and/or chemical nail avulsion, produces better results than systemic treatment alone. Topical treatment as monotherapy is not efficient, excluding minor cases. Terbinafine is superior to itraconazole for dermatophyte onychomycosis. Evaluation of the outcome of clinical cure, mycological cure and total cure should be based on the well-defined worldwide criteria; otherwise, comparison of results is impossible due to lack of uniformity in different studies. In case of treatment failure, the reasons for each failure should be carefully considered.

A new classification system for grading the severity of onychomycosis: Onychomycosis Severity Index.

OBJECTIVE: To establish and validate a new system to define the severity of onychomycosis. The Onychomycosis Severity Index (OSI) score is obtained by multiplying the score for the area of involvement (range, 0-5) by the score for the proximity of disease to the matrix (range, 1-5). Ten points are added for the presence of a longitudinal streak or a patch (dermatophytoma) or for greater than 2 mm of subungual hyperkeratosis. Mild onychomycosis corresponds to a score of 1 through 5; moderate, 6 through 15; and severe, 16 through 35. DESIGN: Consensus conference. SETTING: Teleconference. PARTICIPANTS: The consensus group included 5 dermatologists, 1 dermatology resident with an interest in nail disorders, and a statistician. The meetings were held by closed teleconference. MAIN OUTCOME MEASURES: Index reliability. RESULTS: The reliability of the OSI system was assessed in 2 steps. The first assessment included 37 dermatologists who scored 8 photographs of onychomycosis after being taught how to use the OSI. The scoring system showed very high reliability (Cronbach α = 0.99 and intraclass correlation coefficient [ICC] = 0.95). The second assessment entailed evaluation of 49 nails by 3 dermatologists, including an expert in the OSI. This assessment was conducted at the University of Alabama at Birmingham and at the Oregon Dermatology and Research Center, Portland. The scoring system showed very high reliabilities at both sites (Cronbach α = 0.99 and ICC = 0.96 at the University of Alabama at Birmingham, and Cronbach α = 0.98 and ICC = 0.93 at the Oregon Dermatology and Research Center). CONCLUSION: The OSI is a new, simple, objective, reproducible numeric system to grade the severity of onychomycosis.

Other fungi causing onychomycosis.

Nondermatophyte onychomycosis account for 2% to 12% of all nail fungal infections and can be caused by a wide range of fungi, mainly Scopulariopsis brevicaulis, Aspergillus versicolor, A. flavus, A. niger, A. fumigatus, Fusarium solani, F. oxysporum and Scytalidium spp. Among the predisposing factors are footwear, hyperhidrosis, local trauma, peripheral circulatory disease, and immunosuppression. These nondermatophyte fungi lack the keratinolytic capacity of dermatophytes, but they still can infect alone or in combination with the latter. Because most are considered laboratory contaminants, special criteria have been created for the correct diagnosis of nondermatophyte onychomycosis. The etiologic agent does not determine the clinical pattern of nail invasion, but superficial onychomycosis is frequently observed; leukonychia and melanonychia can also be clinical manifestations.

Superficial white onychomycosis--a syndrome with different fungal causes and paths of infection.

Superficial white onychomycosis (SWO) is a clinical term used to describe onychomycosis in which the invasion of the nail plate occurs from the dorsal surface. However, recent observations indicate that the clinical appearances may vary to include infection in patches or in a striate patter. This report shows that, in some cases, it may be combined with either distal and lateral subungual onychomycosis or proximal white subungual onychomycosis. Invasion of the dorsal nail surface, but originating from the proximal nail fold, is another route of infection in SWO. A new classification of this condition is proposed with 4 main variants. Although based on clinical features, often other factors such as immunosuppression or invading organism (eg, Trichophyton rubrum or Fusarium species) appear to play a role in the development of a particular pattern of infection. This is an observational study carried out by trained and experienced clinicians. The main clinical implication is that in combined forms, or where the infection emerges from beneath the proximal nailfold, systemic rather than topical antifungal therapy is advised.

Onychomycosis in the elderly : drug treatment options.

The prevalence of onychomycosis is nearly 20% in patients aged >60 years. In North America, 90% of toenail onychomycosis is caused by dermatophytes (Trichophyton species). Distal-lateral subungual onychomycosis is the most common clinical presentation. The potassium hydroxide test is the most cost-effective diagnostic method. Although nail clipping for histology using periodic acid-Schiff stain is more sensitive, it is much more expensive. Elderly patients have specific risk factors for poor response to therapy for onychomycosis, including frequent nail dystrophy, slow growth of nails and increased prevalence of peripheral vascular disease and diabetes mellitus. Elderly people with diabetes should be treated for onychomycosis to prevent secondary bacterial infections and subsequent complications. Terbinafine is the drug of choice for dermatophyte onychomycosis, with greater mycological cure rates, less serious and fewer drug interactions, and a lower cost than continuous itraconazole therapy. Adjunct debridement may improve the clinical and complete cure rates compared with terbinafine alone. Common adverse effects of terbinafine in the elderly include nausea, sinusitis, arthralgia and hypercholesterolaemia. For onychomycosis caused by Candida or nondermatophyte moulds, there is no superior systemic therapy. In general, topical nail lacquers, amorolfine and ciclopirox are not practical for elderly patients because of the recommended frequency of application, periodic routine debridement of affected nails and long duration of therapy. However, nail lacquers may be a good option as monotherapy for patients with superficial white onychomycosis or in combination with systemic antifungal therapy for patients with predisposing factors for poor response or recurrence.

Epidemiology and clinical classification of onychomycosis.

OBJECTIVES: To review recent data - what is new in the epidemiology of onychomycoses? To identify the most relevant diagnostic criteria for effective therapy. METHODS: The preliminary results of the European Onychomycosis Observatory (EUROO) study were analysed. In this international study, physicians completed questionnaires concerning patient profile and the disease. RESULTS: One of the most interesting novel findings was that sampling requests were often not made [only 3.4% of general physicians (GPs) and 39.6% of dermatologists]. This means that no information about causative agent(s) was available, hindering appropriate treatment choice. Furthermore, contrary to previous findings, 70.7% of participants did not practice sports. Lastly, these preliminary findings showed that treatment strategy depends largely on the type of treating physician, with GPs preferring monotherapy and dermatologists preferring combination therapy. CONCLUSIONS: A consensus was reached that treatment strategy should depend on the severity of nail involvement and the causative fungus. It is thus important to promote the importance of sampling. To simplify the choice of an appropriate treatment, onychomycosis may be divided into just two clinical groups: onychomycosis with and without nail matrix area involvement. However, the distinct clinical findings (number and type of affected nails, multimorbidity, drug interaction, etc.) in each individual case must be taken into account to ensure an appropriate treatment decision.

Nail dystrophies.

Various individual nail dystrophies that are not easily categorized within other articles are reviewed. Onychoatrophia, anonychia, onychorrhexsis, leukonychia, Beau's lines, onycholysis, onychomadesis, onychoschizia, haplonychia, longitudinal melanonychia, and ventral pterygium are included and clinically pictured. Their clinical description, etiology, associated conditions, differential diagnoses, and treatment are discussed and tabulated. In addition, several clinical severity-scoring methods are presented.

Superficial white onychomycosis revisited.

BACKGROUND: Superficial white onychomycosis (SWO) is a distinct pattern of fungal nail invasion, which is usually treated with topical antifungals. OBJECTIVE: This paper presents a case of SWO with deep penetration and records other similar cases. METHODS: The clues to deep invasion of the nail plate are twofold: an inability to clear the discoloration by scraping the nail and a clinical involvement of the nail plate in the proximal nailfold area. Histology of the nail keratin will confirm deep penetration beyond the superficial layers of the nail plate. RESULTS: In the light of this finding the authors propose a further subdivision of SWO to reflect previously unrecognized variants with therapeutic implications into: (i) the classical SWO type; (ii) the dual invasion of the nail plate, superficial and ventral; and (iii) the pseudo-SWO with deep fungal invasion of the nail plate. CONCLUSIONS: This subdivision of SWO allows the clinician to treat the patient appropriately using topical antifungals when the disease is restricted to the dorsum of the nail. Systemic drugs either in isolation or in combination with topical treatment are mandatory when deep penetration or ventral fungal invasion are observed.

Onychomycosis: classification and diagnosis.

Onychomycosis is a common infection of the nail predominantly caused by anthropophilic dermatophytes, and to a lesser extent by yeasts (Candida species) and non-dermatophyte molds. The treatment of onychomycosis is dependent on several variables, including the type of onychomycosis and the causative organism. Various techniques have been used to accurately diagnose onychomycosis, with microscopy and culture being used most frequently. Histological examination of the distal nail plate can aid in confirming the presence of invasive nail disease, but histological examination should not be limited to the nail plate as it may also be helpful in diagnosing subungual onychomycosis. Nucleic acid-based identification techniques may also be valuable when diagnosing onychomycosis; however, multiple steps may be necessary to determine the causative species. Confocal microscopy may also be a fast and reliable method of diagnosing onychomycosis, though it has very limited ability to distinguish between dermatophyte and mold infections. Prior to treatment an accurate diagnosis can provide guidance about the choice of antifungal agent, especially since the causative organism may vary in its response to the antifungal therapies available.

Onychomycosis: current treatment options.

PURPOSE: To describe current evidence regarding the treatment of clients with onychomycosis who have one or more chronic illnesses. DATA SOURCES: Current review of research articles, standard pharmaceutical texts, and case studies. CONCLUSIONS: Onychomycosis is often considered only as a cosmetic diagnosis. Treatment is based on factors such as the client's willingness to pay for expensive therapy and the ability to physically comply with daily regimens; however, treatment of onychomycosis in clients with chronic illnesses including diabetes and peripheral vascular disease should be strongly encouraged. For these clients, onychomycosis is not just a cosmetic diagnosis because it has the potential to decrease mobility and blood flow to the affected digits if left untreated. IMPLICATIONS FOR PRACTICE: The primary care clinician's successful management of client's with chronic illnesses such as diabetes and peripheral vascular disease should include the treatment of onychomycosis. Recognizing the best treatment is a crucial decision.

Dermatophyte test medium culture for evaluating toenail infections in patients with diabetes.

OBJECTIVE: To evaluate the performance of the in-office dermatophyte test medium (DTM) culture when used to confirm the diagnosis of onychomycosis in diabetic patients. RESEARCH DESIGN AND METHODS: Nail samples from 184 diabetic patients who exhibited symptoms consistent with toenail onychomycosis were screened for dermatophyte fungal infection using DTM, potassium hydroxide evaluation, and central mycology laboratory culture tests. The diabetic patient group investigated in this study is a subset of a heterogeneous set of patients who participated in a nationwide survey designed to investigate the use of fungal culture tests by dermatologists, podiatrists, and primary care physicians described in detail elsewhere. The overall sensitivity of the DTM and central laboratory culture methods was estimated and compared. Sensitivity differences between DTM and central laboratory culture methods were tested for statistical significance using the McNemar statistic. RESULTS: DTM culture was positive in 102 of 184 patients (55%), while the central laboratory culture test detected the existence of fungal infection in 78 of 184 (42%). The two tests were in agreement (both positive or both negative) in 114 of 184 patients (62%). Central laboratory culture identified dermatophytes as the pathogen in 91% of positive cases. CONCLUSIONS: DTM is a convenient and inexpensive culture test that can be used to confirm dermatophyte infections in diabetic patients with presumed onychomycosis. We found this test to be well suited for use in the primary care setting. Because oral antifungal agents are effective against dermatophyte species, which cause the vast majority of nail infections, diagnosis of onychomycosis requires confirmation of dermatophyte infection only, not identification of genus and species. DTM fulfills this requirement and has a diagnostic yield comparable to central laboratory culture.

[Clinical types of onychomycosis]. / Variétés cliniques des onychomycoses.

Clinical classification of onychomycosis is based on how the pathogenic agent penetrates the unguis. The disto-lateral sub-ungual variety is the most common. Dermatophytes (especially Trichophyton rubrum) and Scytalidium in tropical regions (Sc hyalium, Sc dimidiatum) are the most frequent toenail pathogens. Progression of a yellow friable sub-ungual hyperkeratosis associated with longitudinal striations and/or xanthonychial or leuconychial zones (sometimes pigmented with Trichophyton rubrum nigricans or Scopulariopsis brevicaulis) lead rapidly to onycholysis and later to total dystrophy of the ungual plate. Associated paronychia is more common in scytalidiasis. Candida species (tropicalis, parapsilosis) and fungi (Aspergillus sp. Fusarium sp, Acremonium sp, Penicillium sp, Scopulariopsis brevicaulis) generally colonize pre-existing onycholysis. For the fingernails, candidal colonizations secondary to pre-existing onycholysis is much more frequent than primary dermatophyte or scytalidium onychomycoses which are much less hyperkeratotic than on toenails. The one hand two feet tinea syndrome caused by Trichophyton rubrum is a particular entity. Proximal sub-ungual onychomycoses without fingernail or toenail paronychia is generally caused by Trichophyton rubrum in immunodepressed subjects (AIDS). Initial proximal leuconychia progresses to the distal part of the nail. Proximal lesions associating proximal leuconychia and paronychia result from fungi, Fusarium being the most commonly identified agent. Onyxis complicating chronic paronychia, generally related to Candida colonization, occurs in subjects with particular conditions (immunodepression, distal vascular disorders). Superficial onychomycosis, e.g. superficial toenail leuconychia, is mainly due to Trichophyton interdigitale, more exceptionally to Trichophyton rubrum (children, immunodepressed), and rarely Candida (children). Endonyx onychomycosis occurs when the pathogen invades the entire thickness of the nail (milky leuconychia without sub-ungual hyperkeratosis). Trichopnyton violaceum or soudanense is the most common pathogen. Even though the clinical presentation of onychomycosis is highly suggestive of the pathogenic agent, the lack of specific criteria implies a mycological sample to confirm the diagnosis and identify the causal agent before initiating treatment.