Onychomycosis (Tinea Unguium) By Chris G. Adigun, MD, Board-Certified Dermatologist, Dermatology & Laser Center of Chapel Hill CLICK HERE FOR Patient Education NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version Nail Disorders Overview of Nail Disorders Nail Deformities and Dystrophies Onychomycosis Acute Paronychia Chronic Paronychia Ingrown Toenail Overview of Nail Disorders.) Tinea pedis psoriasis) Peripheral vascular disease or diabetes onycholysis) psoriasis or lichen planus is important because the therapies differ, so diagnosis is typically confirmed by microscopic examination and, unless microscopic findings are conclusive, culture of scrapings or rarely PCR of clippings. Scrapings are taken from the most proximal position that can be accessed on the affected nail and are examined for hyphae on potassium hydroxide wet mount and cultured. Histopathologic examination of periodic acid-Schiff (PAS)–stained nail clippings and subungual debris may also be helpful. cellulitis Diabetes or other risk factors for cellulitis (1–4). (5,6). Topical antifungal nail lacquer containing ciclopirox 8% or amorolfine 5% (not available in the US) is occasionally effective as primary treatment (cure rate of about 30%) and can improve cure rate when used as an adjunct with oral drugs, particularly in resistant infections. To limit relapse, the patient should trim nails short, dry feet after bathing, wear absorbent socks, and use antifungal foot powder. Old shoes may harbor a high density of spores and, if possible, should not be worn.
Impact Factor for 2017 is 2.229 Click here to view optimized website for mobile devices Journal is indexed with MEDLINE/Index Medicus and Science Citation Index Expanded SYMPOSIUM-NAILS PART I Year : 2011 | Volume : 77 | Issue : 6 | Page : 659-672 Onychomycosis: Diagnosis and management Archana Singal1, Deepshikha Khanna2 1 Department of Dermatology and STD, University College of Medical Sciences and GTB Hospital, University of Delhi, India 2 Chacha Nehru Bal Chikitsalaya, Delhi, India Date of Web Publication 21-Oct-2011 Correspondence Address: Archana Singal B-14, Law apartments, Karkardooma, Delhi - 110 092 India Source of Support: None, Conflict of Interest: None Check 10 DOI: 10.4103/0378-6323.86475 http://www.ijdvl.com/text.asp?2011/77/6/659/86475 Onychomycosis is a common condition affecting 5.5% of the population worldwide and represents 20-40% of all onychopathies and about 30% of cutaneous mycotic infections. [1] Onychomycosis of fingernails may lead to pain, discomfort, and impaired/lost tactile functions. Toenail dystrophy can interfere with walking, exercise, or proper shoe fit. In addition, onychomycosis has both psychosocially and physically detrimental effects. The prevalence of onychomycosis is determined by age, occupation, climate, and frequency of travel. Increase in the aged population, HIV infection or immunosuppressive therapy, avid sports participation, commercial swimming pools, and occlusive foot wear are responsible for an increased incidence. [1],[2] Men are affected more frequently possibly due to more frequent nail damage from sports and leisure activities. [1] Toe nails are about seven times more frequently affected than fingernails due to three times slower growth rate. [2] Walking barefoot, wearing ill-fitting shoes, nail biting (onychophagia), and working with chemicals further predispose Indian patients to onychomycosis. [3] Other predisposing factors include nail trauma, peripheral vascular disease (PVD), smoking, and psoriasis. [1],[2] There is a wide variety of fungi causing onychomycosis which varies from one geographic area to another primarily due to different climatic conditions. [3] Dermatophytes are the most frequently implicated causative agents in onychomycosis (approximately 90% in toenail and 50% in fingernail). Dermatophyte invasion of the nail plate is termed tinea unguium. Trichophyton rubrum (T. rubrum) is the most common causative agent followed by T. mentagrophytes. [1] Nondermatophyte molds (NDM) mainly affect toenails and occasionally fingernails. NDM account for 1.5-6% of all onychomycosis that fall into two main categories: first group encompasses fungi that are nearly always isolated from nails as etiologic agents, such as Scytalidium dimidiatum and Scytalidium hyalinum; the second group is formed by opportunistic fungi that may also be isolated as contaminants, such as Scopulariopsis brevicaulis, Aspergillus sydowii, and Onychocola canadensis. [1] Certain NDM such as Acremonium species can invade the nail surface, while others such as Scytalidium species are more often associated with distal and lateral subungual onychomycosis. [1],[4] Molds are considered pathogens when the following criteria are fulfilled: Nail abnormalities consistent with diagnosis. Positive direct microscopy visualizing hyphae in the nail keratin. Failure to isolate a dermatophyte in the culture Growth of more than five colonies of the same mold in at least two consecutive nail samplings. [5] Involvement of molds should be suspected in the absence of tinea pedis, history of trauma, presence of one or two affected toe-nails with periungual inflammation. [1] Yeasts: Previously regarded as contaminants, yeasts are now increasingly recognized as pathogens in fingernail infections. Candida albicans accounts for 70% of cases, while C. parapsilosis, C. tropicalis, and C. krusei account for the remainder. Candida onychomycosis (CO) is increasingly found in individuals with defective/lowered immunity consequential to aging, diabetes, vascular diseases, immunosuppression, and broad spectrum antibiotics, and is common in patients with DiGeorge syndrome, agammaglobulinemia, and thymus dysplasia. [6] Chronic exposure to moisture and chemicals including detergents and breached local immunity due to trauma, as seen in housewives, farmers, and fishermen, contributes to CO accompanied by Candida paronychia. [6] Candida can be a primary or secondary pathogen. Its role as a primary pathogen is almost always seen in severe immunosuppression such as HIV infection and chronic mucocutaneous candidiasis (CMC), while secondary invasion by Candida occurs in cases with PVD, malnutrition, and compromised local immunity at the nail complex. [6] Keratin in the nail substance is known to act as an excellent growth environment for virulent Candida strains. [6] There are five major clinical presentations of onychomycosis: Distal and lateral subungual onychomycosis (DLSO) Proximal subungual onychomycosis (PSO) Superficial white onychomycosis (SWO) Endonyx Total dystrophic onychomycosis (TDO) Distal and lateral subungual onychomycosis DLSO is the commonest clinical variant affecting both finger and toenails. The fungus enters via the distal subungual and lateral nail groove, invades the horny layer of the hyponychium and/or nail bed, and spreads proximally against the stream of nail growth and subsequently through the under surface of nail plate which becomes opaque. Clinically, there is onycholysis and subungual hyperkeratosis [Figure 1] which acts as a mycotic reservoir for fungal proliferation. [1] The commonest causative species is T. rubrum followed by T. mentagrophytes, T. tonsurans, and Epidermophyton floccosum. 'One hand two feet' tinea syndrome is a distinct clinical pattern in DLSO caused by T. rubrum in which the fungus spreads from the plantar and palmar surface of feet and hands [Figure 2]. Chronic dermatophytosis syndrome,caused by T. mentagrophytes var. interdigitale starts as minute plantar vesicles of 1 mm size and collarettes over the soles that are the site of abundant hyphae. The vesicles dry leaving a keratinous collarette and later on other sites become infected, especially the nail bed, leading to DLSO. [2] Figure 1: Distal and lateral subungal onychomycosis Click here to view Figure 2: One hand two feet' tinea syndrome Click here to view Proximal subungal onychomycosis
Dermatology Research and Practice Volume 2017, Article ID 1268130, 4 pages https://doi.org/10.1155/2017/1268130 Research Article Onychomycosis Caused by Fusarium spp. in Dakar, Senegal: Epidemiological, Clinical, and Mycological Study Khadim Diongue,1,2 Mouhamadou Ndiaye,1,2 Mame Cheikh Seck,1,2 Mamadou Alpha Diallo,1 Aïda Sadikh Badiane,1,2 and Daouda Ndiaye1,2 1Laboratoire de Parasitologie-Mycology, CHU Le Dantec, BP 5005, Dakar, Senegal 2Service de Parasitologie-Mycology, Faculté de Médecine, de Pharmacie et d’Odontologie, Université Cheikh Anta Diop, BP 16477, Dakar, Senegal Correspondence should be addressed to Khadim Diongue; [email protected] Received 28 June 2017; Accepted 23 October 2017; Published 4 December 2017 Academic Editor: Craig G. Burkhart Copyright © 2017 Khadim Diongue et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Fusarium spp. represent 9 to 44% of onychomycoses caused by fungi other than dermatophytes. This retrospective study describes 17 cases of Fusarium onychomycosis diagnosed at the Laboratory of Parasitology and Mycology of Le Dantec University Hospital in Dakar, Senegal, from 2014 to 2016. It included all patients received in the laboratory for suspicion of onychomycosis between January 1, 2014, and December 31, 2016. Diagnosis was based on mycological examination including direct examination and culture. Mycological analysis was considered positive when direct examination and culture were positive after at least one repeat. Seventeen Fusarium onychomycosis cases representing 12.9% of all onychomycoses reported were diagnosed. There were 5 cases on the fingernails and 12 on the toenails in 6 males and 11 females, and the mean age was 44 years (range: 26–64). Onychomycoses were diagnosed in immunocompetent patients except in a diabetic patient. The mean duration of lesions was 4.9 years (range: 1–15), and distal subungual onychomycosis was predominant. Almost all patients were from suburban areas of Dakar region. The most frequent species isolated belong to Fusarium solani complex. Because of the risk of disseminated infection in immunocompromised patients, realization of susceptibility tests is necessary to ensure better therapeutic management. 1. Introduction The genus Fusarium, described for the first time in 1809, contains saprophyte telluric species and plant pathogens. These organisms are also involved in human pathology, causing mycotoxicoses and infections which can be locally invasive or disseminated. Very cosmopolitan, Fusarium is found in tropical areas, temperate regions, deserts, and mountainous and even arctic zones [1]. Currently, the genus Fusarium comprises at least 300 phylogenetically distinct species, 20 species complexes, and nine monotypic lineages. Most of the identified opportunistic Fusarium pathogens belong to the F. solanicomplex (FSC), F. oxysporum complex (FOC), and F. fujikuroi complex (FFC) [2]. Among immunocompetent patients, tissue breakdown (as caused by trauma, severe burns, or foreign bodies) is the risk factor for fusariosis. Infections include keratitis, onychomycosis, and occasionally peritonitis and cellulitis [3]. Frequently, walking barefoot is the main cause for Fusarium onychomycoses, and they preferentially infect the big toe. They may be superficial or subungual. According to studies, they represent 9 to 44% of onychomycoses caused by fungi other than dermatophytes. Although Fusarium onychomycosis remains mostly localized, it could also represent the portal of entry for disseminated diseases in immunocompromised patients [1]. The genus Fusarium is ubiquitous in the environment and can hang on to the nail plate especially in case of dystrophy or local trauma. This mold may be just saprophytic or truly pathogenic, provided it is found repeatedly on multiple samples [4]. Here, we describe 17 cases of Fusarium onychomycosis diagnosed in the Laboratory of Parasitology and Mycology of Le Dantec University Hospital in Dakar, Senegal, from 2014 to 2016. 2. Patients and Methods We conducted a retrospective and descriptive study including all patients received in the laboratory for suspicion of onychomycosis between January 1, 2014, and December 31, 2016. Diagnosis was based on mycological examination including direct examination and culture as described in a previous article [5]. A microscopic direct examination of all specimens was carried out in 20% KOH solution. The specimens were cultured in 2 plates/tubes, one containing Sabouraud-chloramphenicol dextrose agar and the other containing Sabouraud-chloramphenicol cycloheximide. Cultures were incubated at 22–27°C and evaluated for growth after 48 h and then once weekly for a month. The specimen was considered positive when microscopic examination and culture were positive. On the other hand, when Fusarium sp. was isolated alone, to assert its pathogenicity, rigorous criteria were used. They include the following [6]i)Positive direct (or histological) examination is carried out.(ii)Culture (preferably in Petri dishes rather than in tubes, so as not to miss out on an association with a dermatophyte) must show the growth of the fungus at the level of (almost) all the seeding points (and not elsewhere in the agar).(iii)It is strongly recommended to renew the samples collection at the same sites, in order to verify the isolation of the same fungus. Identification of fungi was based on the speed of growth and especially on the macroscopic and microscopic characteristics of the colonies and sometimes on their physiological (germ tube test) and biochemical (urease test) characteristics [2, 7–10]. Data were recorded in Microsoft® Excel 2007 and transferred into Epi Info® 7 where statistical analysis was done. 3. Results During the study period, 132 cases of onychomycosis were diagnosed. Figure 1 shows the case number evolution of both the mold and the Fusarium genus. Cases caused by Fusarium species were 17 (12.9%) in 6 males and 11 females, and the mean age was 44 years (range: 26–64). Figure 1: Evolution of the cases of mold and Fusarium onychomycoses throughout years. Table 1 shows the clinical and demographic findings and mycological details of these 17 cases. The most frequent isolated species belong to the FSC with 8 cases. Two concomitant infections were observed whereFusarium was associated with Candida albicans (cases 15 and 16). Table 1: Clinical and demographic findings and mycological details of infection in 17 cases of onychomycosis caused by Fusarium species. Onychomycoses were diagnosed in immunocompetent patients except in a diabetic patient (case 6). Almost all patients were from Dakar region and 2 cases were from Saint Louis and Thiès regions. The lesions were onychomycosis alone in 9 cases, while in 7 cases, onychomycosis was associated (due to the same Fusarium) with interdigital tinea pedis and in one case with interdigital and chronic hyperkeratotic (moccasin) tinea pedis (case 13). The mean duration of lesions was 4.9 years (range: 1–15). Concerning the location of onychomycoses, 5 were localized at the fingernails whereas 12 were at the toenails and 3 among the latter were on the big toe (cases 1, 8, and 17). Regarding the type of attack, onychomycosis was distal subungual in 7 cases, onycholysis in 2 cases, proximal with paronychia in 1 case, and secondary to interdigital tinea pedis in 7 cases. The majority of cases were treated with terbinafine (tablet and/or cream) according to what we have reported. 4. Discussion Fusarium onychomycoses are not rare since Fusarium spp. were reported to be the causative agent of 9–44% of nail invasions caused by nondermatophytic molds [4]. Several authors have shown the presence of Fusariumspp. as agents of onychomycosis, with a frequency in the range of 0.97–6% [11]. Our prevalence of 12.9% is outside this range, but it is very similar to that reported in a study conducted in Lyon (France) between 2008 and 2010, showing a prevalence of 12.6% [12]. In contrast, in other studies carried out around the world,Fusarium onychomycosis was diagnosed with prevalences within this range, with 0.09% in Tunis (Tunisia) between 1996 and 2010 [13], 3.1% in Guatemala (Guatemala) between 2008 and 2011 [14], 6.25% in Galle (Sri Lanka) published in 2008 [15], and 7.3% in Kanpur (India) between June and October 2011 [16]. Fusarium onychomycoses were exclusively diagnosed in adults with a mean age of 44 years (range: 26–64), and there was a predominance of females. The first observation has already been reported in a report of seven cases from Natal (Brazil) between 2002 and 2004 with an average age of 47 years (range: 31–66) [17]. Likewise, Ranawaka et al. found Fusarium onychomycoses in patients with ages ranging between 18 and 74 years with a mean of 43 years [15]. The high rate of isolation in females may be the result of the continuous use of open shoes, with a higher risk of injuries and contact with soil [11]. According to Chabasse and Pihet, frequencies ofFusarium onychomycoses increase with age. Thus, the frequency is between 15 and 20% in adults over 40 and exceeds 30% in people over 70 years of age. This prevalence, clearly superior in the elderly, is related to the following factors: smaller nail growth, bad blood circulation in the lower limbs, physiological immunosuppression related to age, ungual microtrauma, and sometimes inability to provide adequate feet care [6]. The majority of cases (12/17) were located in toenails. This toenail predominance of Fusarium onychomycosis was reported in Brazil [17] and also in Sri Lanka, where a particular predominance was also noted in the big toenail [15]. We found this location on the big toenail in three cases. These observations could be explained because contamination occurs from soil, especially in individuals who walk with open sandals or barefooted [3]. This practice is all the more a risk factor in Senegal, where, apart from the city centers of the regions, all the streets are sanded. This would justify the fact that 15 of the 17 patients come from suburban areas of Dakar, other than the absence of a mycology laboratory in these regions. With the increasing number of immunocompromised patients, many species of fungi originally regarded as laboratory contaminants are now considered to be agents of mycosis and may sometimes also affect immunocompetent patients [11]. This is the case of Fusarium species. In our series, no immunodeficiency was noted in 16 of the 17 patients. Only one case of diabetes was observed, which probably contributed to the presence of microconidia at the direct examination. It is a rare observation but one we have already observed with Fusarium sp. The first case of interdigital tinea pedis due to Fusarium that we reported in Dakar had also shown this with hyphae associated with microconidia [18]. Néji et al. also showed a direct examination ofFusarium onychomycosis showing hyphae associated with sickle-shaped macroconidia [13]. The most common clinical presentations were distal subungual onychomycosis and onycholysis. This is contrary to what has been published by Dignani and Anaissie, who stipulated that the most common clinical presentations include proximal subungual onychomycosis with or without paronychia [3]. However, distal subungual attack was observed by Calado et al., in 6/7 cases [17]. These authors found the proximal subungual lesion associated with paronychia in one case like our results. We observed onychomycosis secondary to interdigital tinea pedis with the same proportion as the distal subungual attack. This association is frequent and could be explained by the anatomical proximity and mostly because interdigital tinea pedis is a rare motive of consultation in Dakar [5]. We found a mean duration of lesions of 4.9 years (range: 1–15). A similar history of infection has been reported in the report of seven cases of Fusarium onychomycosis from Natal (Brazil) showing a mean of 5 years, range from 8 months to 10 years. According to the literature, the most common Fusarium species responsive to human infections are F. solani(FSC, 50%), F. oxysporum (FOC, 14%), F. verticillioides (FFC, 11%), and F. moniliforme (FFC, 10%) [1]. The species found in our series are roughly the same mentioned above with the same order of medical importance except for F. lichenicola (FSC) which was isolated with the same proportion as F. solani and F. oxysporum.Fusarium oxysporum is the species most often isolated in toenails, while F. solani predominates in fingernails [6]. This repartition of the two species was noted mainly but not always. In contrast, in other studies carried out in Brazil, Calado et al. found only F. solani on 6 toenails and 1 fingernail onychomycosis [17]. Likewise, another study in Brazil showed that, out of ten cases of F. solani onychomycosis, eight were located on toenails and only two were on fingernails [11]. Among other species, we found F. moniliforme (FFC) with two cases like in the study of Ranawaka et al. in Sri Lanka [15] and F. subglutinans (FFC) in one case where other authors have found other species [11]. Concerning the treatment by terbinafine, it is explained that this molecule is among the rare available antifungals in Senegal, in a tablet form, with fluconazole. However, it is demonstrated that fluconazole is weakly active or inactive on filamentous fungi such as Aspergillus and Fusarium [19, 20]. 5. Conclusion The prevalence of Fusarium onychomycoses diagnosed in Dakar in the period 2014–2016 was not low and we remark that the number of cases increases throughout years. These infections were predominant in adults, especially in females. They are mostly located in toenails with a nonnegligible association with interdigital tinea pedis and affect immunocompetent patients. Although Fusarium onychomycosis is usually localized in immunocompetent individuals, it could also represent the portal of entry for disseminated diseases in immunocompromised patients such as diabetics. Hence, there is a need to carry out susceptibility tests to ensure better therapeutic management. Conflicts of Interest
PUBLISHED JUNE 19, 2014 PODIATRY Onychomycosis: Clinical Considerations and Recommendations Mickey Hart, PharmD Candidate 2015 Concordia University Wisconsin School of Pharmacy Mequon, Wisconsin Lynne Fehrenbacher, PharmD, BCPS-AQ ID Assistant Professor of Pharmacy Practice Concordia University Wisconsin School of Pharmacy Mequon, Wisconsin US Pharm. 2014;39(6):34-38. ABSTRACT: Onychomycosis (fungal infection of the nail) is a common dermatologic condition. Despite often being thought of as a purely cosmetic issue, it may be a source of morbidity and thus warrants treatment. Pharmacists, as highly accessible healthcare professionals, are able to play an important role in the prevention and treatment of onychomycosis. This article summarizes the prevalence, risk factors, prevention, diagnosis, and nonpharmacologic treatment of onychomycosis and also provides a review of available pharmacotherapy options. Onychomycosis is a fungal infection of the nail apparatus that is caused by dermatophytes, most often Trichophyton rubrum, or nondermatophyte molds and yeasts, most often Candida species.1 It is a common dermatologic condition; prevalence in the general population in North America is estimated to be 7% to 15%, with about 90% of cases involving the toenails.1-3Although some practitioners continue to view onychomycosis as a purely cosmetic issue, serious complications such as cellulitis can occur, particularly among patients with risk factors such as diabetes and peripheral vascular disease.1 Even patients at low risk for complications often report reduced quality of life; therefore, treatment should be considered whenever possible.1 Both topical and oral antifungal agents are available to treat onychomycosis, and it is important that pharmacists be aware of the efficacy, tolerability, and appropriate treatment duration of each antifungal. Risk Factors and Prevention Several risk factors are associated with predisposition to onychomycosis, including increasing age, exposure to damp communal areas (e.g., gyms, swimming pools), poor foot hygiene, impaired immune status, diabetes mellitus, poor peripheral circulation, tinea pedis, and nail trauma.2-4 Patients at risk for onychomycosis should be counseled on appropriate prevention techniques. Footwear should be worn when in damp communal areas, toenails should be kept short and clean, feet should be dried completely immediately after bathing, socks should be made of absorbent material (e.g., cotton) and changed if wet, and symptoms of tinea pedis should be addressed in a timely fashion.5 Diagnosis Onychomycosis of the toenails may be clinically characterized by thickening of the toenails, onycholysis (separation of the nail plate from the nail bed), subungual hyperkeratosis (buildup of debris in the space created by onycholysis), and nail discoloration (usually yellow-brown or white) .1,4 Only about half of nail dystrophy cases are caused by fungi, making appropriate diagnostic technique necessary to rule out disease states with similar presentations (e.g., psoriasis, nail trauma).4 Currently, the most efficient screening test for onychomycosis is direct microscopy of a potassium hydroxide–prepared nail specimen; however, this technique has a false-negative rate of 5% to 15% and lacks differentiation between fungal pathogens.4 Fungal pathogens can only be identified by performing in vitro laboratory culture, which facilitates also antifungal susceptibility testing. Unfortunately, this technique suffers from a false-negative rate of nearly 50% .4 Due to their limitations, direct microscopy and in vitro laboratory culture of nail material should optimally be used together when diagnosing suspected onychomycosis. Despite this recommendation, onychomycosis is often treated empirically based on clinical presentation. Treatment Dosage and duration, mycological cure rate, and clinical considerations (including adverse effects) for each antifungal agent discussed are listed in TABLE 1. Oral Pharmacotherapy: In general, using an oral antifungal is the most effective treatment option for onychomycosis.1However, oral antifungals may be inappropriate for some populations, particularly those with liver dysfunction.1 Griseofulvin, which has an FDA indication for onychomycosis, and ketoconazole, which does not, were commonly used before the introduction of the newer antifungals discussed in this article.4 However, the newer antifungals have shorter treatment durations, improved efficacy, and improved safety profiles, leading to the replacement of griseofulvin and ketoconazole, which are no longer recommended for use in this indication. For any agent chosen, treatment duration will be long (at least 12 weeks), and time to complete regrowth of healthy, disease-free nails can take up to 6 months for fingernails and 12 to 18 months for toenails.4 Terbinafine is a fungicidal allylamine derivative with an antifungal spectrum that includes dermatophytes and molds.4 In one study, FDA-approved continuous terbinafine therapy was found to be significantly more effective than pulse terbinafinetherapy (patients take the drug for only 1 week per month), which is not an FDA-approved regimen (71% and 59%, respectively; P = .03) .6 Continuous terbinafine therapy offers the highest efficacy of any available therapy (71%-89% when used for 12 weeks for onychomycosis of the toenails) and should be recommended first-line for most patients without contraindications to therapy.6-8 Itraconazole is a fungistatic triazole with an antifungal spectrum that includes dermatophytes and molds.4 A continuousitraconazole regimen is FDA-approved for onychomycosis involving the toenails, and a pulse-dosing regimen (patients take the drug for only 1 week per month) is FDA-approved for onychomycosis with only fingernail involvement.9 Itraconazoletherapy is generally longer than terbinafine therapy and has been investigated for up to 48 weeks of continuous use foronychomycosis of the toenails; however, it is still less effective than terbinafine.10 Itraconazole also has a higher rate of adverse drug reactions than terbinafine and fluconazole. For these reasons, it is recommended that itraconazole be reserved for use as a second-line therapy for patients who do not have success with terbinafine. Fluconazole is a fungistatic triazole with an antifungal spectrum that is largely limited to Candida species and some dermatophytes.4 Fluconazole is not FDA-approved for the treatment of onychomycosis but has been studied for use off-label. One study compared a 12-week treatment regimen of fluconazole 150-mg once weekly to a 24-week regimen and found no significant difference in efficacy.7 Another study found no significant difference in efficacy between 150-mg, 300-mg, and 450-mg weekly regimens.11 Based on these results, to minimize risk of adverse effects while maintaining efficacy, the recommended dosing regimen for fluconazole is 150 mg once weekly for 12 weeks for onychomycosis of the toenails. Because of its similar efficacy, lower incidence of adverse events, and once-weekly dosing regimen, fluconazole may be considered a second-line option alongside itraconazole, despite its lack of FDA-approval for onychomycosis. Topical Pharmacotherapy: Nonprescription topical antifungals marketed for athlete’s foot (e.g., terbinafine, tolnaftate) are not recommended for treating onychomycosis of the toenails.4 These topical antifungals are unable to penetrate the nail, a requirement to eradicate the infection; however, they may be useful for prophylaxis.4 ,5 Ciclopirox is a fungicidal pyridone with an antifungal spectrum that includes dermatophytes, molds, and yeasts.12 Although less effective than the oral antifungal agents, ciclopirox nail lacquer is associated with a lower incidence and severity of adverse effects than the oral antifungals.12 Ciclopirox represents a valid option for patients who cannot tolerate other options due to adverse effects or contraindications or for those who are hesitant to start long-term oral antifungal therapy.12Concomitant use of systemic therapy (e.g., terbinafine) with topical ciclopirox may offer improved efficacy and decreased time to cure compared to either agent alone, although further research is required before this practice can be recommended routinely.4 Nonpharmacologic Treatment: Nail trimming and debridement can be used concurrently with pharmacologic treatments including topical therapies, to increase efficacy. Several laser devices are FDA-approved for the treatment of onychomycosis, including neodymium :yttrium-aluminum-garnet( Nd:YAG) devices and dual-wavelength near-infrared lasers.13 In one study, 61% of participants achieved mycological and cosmetic cure at week 16 of Nd:YAG therapy (mycological cure alone was not assessed).14 A second study demonstrated that 30% of participants with onychomycosis of the toenails achieved mycological cure at day 180 of dual-wavelength infrared laser therapy.15 Participants reported no adverse effects in either study.14,15 These therapies are much more expensive than pharmacologic methods and typically are not covered by insurance plans.13For this reason, it may be prudent to recommend laser therapy for those patients who are unable or unwilling to use conventional pharmacologic options, those who have experienced treatment failure, or those for whom out-of-pocket expense is not an issue.
Features Treatment of Onychomycosis in Diabetic Patients Jason A. Winston and Jami L. Miller, MD Clinical Diabetes 2006 Oct; 24(4): 160-166.https://doi.org/10.2337/diaclin.24.4.160 PreviousNext Article Figures & Tables Info & Metrics PDF Abstract IN BRIEF Onychomycosis is more common in diabetic than nondiabetic patients. It is more than a cosmetic problem, and diabetic patients have a greater risk of serious complications from the disease, including limb amputations. This article reviews the various diagnostic and therapeutic options available for onychomycosis with an emphasis on their roles in diabetic patients. In 2005, the estimated number of Americans with diabetes was 20.8 million people, with an additional 1.5 million cases diagnosed that year in those ≥ 20 years of age.1 Onychomycosis is a fungal infection of the nail that is estimated to cause up to 50% of all nail problems2 and 30% of all cutaneous fungal infections.3 Approximately one in three people with diabetes are afflicted with onychomycosis.4 Many studies have been undertaken to assess whether diabetic individuals suffer from a higher incidence of onychomycosis than those without diabetes,4-10and most have concluded that they do. One study observed an increased risk among all three major groups of organisms that can cause onychomycosis: dermatophytes, yeasts, and nondermatophyte molds.5 Onychomycosis in people with diabetes is more than a cosmetic nuisance; it increases the risk for other foot disorders and limb amputation.4,10-22 The outcome from not treating onychomycosis in diabetic patients can be worse than in those without diabetes. Thus, effective treatment in these patients is of paramount importance.13 Because onychomycosis in diabetic patients can lead to many complications, most insurance companies cover treatment in documented cases. Thickened, dystrophic nails can be very painful and make walking difficult. Injury to adjacent skin from mycotic nails may occur without patients' awareness and can lead to secondary infections, both fungal and bacterial, including paronychia and cellulitis.3,4,9,14,15 Thickened nails can cause erosions of the nail bed and hyponychium because of pressure, just as tight shoes can cause friction blisters in these patients. When combined with peripheral neuropathy, blisters and erosions may progress to cellulitis or osteomyelitis of the underlying bone.3,4,14,15 Extension of the fungal infection to surrounding skin causes tinea pedis, which may lead to fissures in the plantar and interdigital skin. These may also provide a route for the entry of bacteria.15 Patients with diabetes-related comorbidities are at especially increased risk for morbidity in onychomycosis. Diabetic patients suffering from decreased foot sensation are more prone to trauma, which damages the nail and nail matrix, opening portals of entry for the fungus to infect the nail.13,15 Some diabetic patients can be obese, which may make the act of bending over to examine their feet difficult.15 Diabetic patients with cataracts16 or retinopathy15 may be unable to properly examine their feet regularly. Retinopathy has been found to be an independent risk factor for onychomycosis in diabetes.9 Other risk factors include peripheral neuropathy,3,9,15 impaired peripheral circulation,4,9 age,4,9 family history,4 and intake of immunosuppressant drugs.4 In addition, duration of diabetes is correlated with severity of onychomycosis when present.4 Male diabetic patients have a three times higher risk of onychomycosis than female diabetic patients.4 The presence of fungal infection in the nails increases the risk of other infections of the foot and leg. In one study, diabetic patients with onychomycosis had a 15% rate of secondary infections compared with a 6% rate of secondary infections in diabetic patients without onychomycosis. Additionally, diabetic patients with onychomycosis had an approximately three times greater risk of gangrene or foot ulcer compared with diabetic patients without it.10 The total annual costs for toe, leg, and foot amputations in the United States in 2003 was almost $2 billion.17 These costs covered 112,551 total amputations, with an average cost of $16,826 for each procedure.17 In 2001, the total cost of amputations in diabetic patients was > $1.6 billion.18 The majority of lower limb amputations occur in diabetic patients.19 Because the risk of amputation increases with onychomycosis, it is imperative for clinicians to examine diabetic patients' feet and, when suspicious, obtain a sample for diagnosis. Causes of Onychomycosis Three classes of fungi can cause nail infections in humans: dermatophytes (especially Trichophyton species), yeasts (e.g., Candida albicans), and nondermatophyte molds.2,20Dermatophytes constitute the vast majority of infectious etiologies.21 In one epidemiological survey, dermatophytes were found in 82% of isolates and Candida albicans in ∼ 7%.22 Diagnosis of Onychomycosis Clinical diagnosis Infected nails appear thick, brittle, and discolored, often with a yellow hue. The nail plate may separate from the nail bed (onycholysis), and there may be inflammation of the skin near the nail edge (paronychial inflammation).20 Onychomycosis has four classic clinical presentations in nails. Distal and lateral subungual infection is the most common type. In this pattern, the infection spreads proximally from the distal or lateral aspects of the nail, eventually raising the free edge of the nail plate and causing onycholysis and nail-plate thickening with subungual hyperkeratosis. The infection spreads proximally, causing yellow-brown discolorations.23 The most common organism is Trichophyton rubrum, followed by Trichophyton mentagrophytes. Candida species also cause this pattern of infection, as can molds such as the Aspergillis and Fusarium species. When complicated by infection with pigmented molds or bacteria such as Pseudomonas aeruginosa, the nails may appear dark green to black.23 Proximal subungual infection is rare but more common in AIDS and immunosuppressed patients. In this pattern, the organisms invade via the proximal nail fold and spread to the nail matrix and then the deep surface of the nail plate.23 White superficial onychomycosis is normally limited to the toenails. It presents with small well-defined superficial white patches on the nail that can merge to cover the entire nail.16,23 The diseased nails are brittle and may crumble. The vast majority of the cases are caused by the fungus Trichophyton interdigitale. Total dystrophic onychomycosis is the most severe clinical manifestation of onychomycosis. In this form, the entire nail except for small fragments is destroyed, leaving a thickened nail bed.23 Differential diagnosis Only 57% of diabetic patients with abnormal-appearing toenails are confirmed to have onychomycosis.4 Many common disorders, including psoriasis, lichen planus, onychogryphosis, trauma, and idiopathic dystrophic nails are included in the differential diagnosis. Psoriasis is the most common disorder that mimics onychomycosis24 and can show subungual hyperkeratosis, onycholysis, and onychodystrophy of the entire nail.23 Although psoriasis usually also has classic manifestations on other skin areas, it can be limited to the nails. Pitting and “oil drop” spots are far more common in psoriasis than in onychomycosis.23,24 Often in psoriasis a “salmon patch,” an irregular yellow or pink area under the nail plate, will be present. This does not occur in onychomycosis.25 Patients with lichen planus can have nail manifestations of the disease.24 Clinicians should carefully examine patients' extremities and mucous membranes for the pathognomic violaceous papules.26 Lichen planus can affect both fingernails and toenails, causing them to become brittle and ridged. Subungual hyperkeratosis and distal onycholysis may also occur.27 Onychogryphosis is a severe deformation of the nail, most often affecting the great toes. The nail becomes very thick and discolored, resembling a ram's horn. The nail bed can become hypertrophied. Onychogryphosis is most commonly caused by infrequent nail cutting and impaired peripheral circulation but may also be caused by trauma.28 Repeated trauma to the nails, which can increase the risk of onychomycosis,5 can cause distal onycholysis with subsequent microbial colonization and altered pigmentation.24 In addition, a subungual hematoma from trauma may cause discolorations that can be confused with onychomycosis.25 Normal nails can have morphological variation, especially as an individual ages. White spots and lines in the nails, leukonychia punctata, and transverse striate leukonychia are benign and may result from minor trauma to the nail matrix.27 Onycholoysis can be idiopathic or caused by trauma.28 Dermatophytes can be found in idiopathic onycholysis but are considered to be commensal.29 Laboratory diagnosis The standard of care in diagnosing onychomycosis is clinical impression with one confirmatory laboratory finding, such as KOH-prepared direct microscopy, fungal culture, or histopathology with periodic acid Schiff (PAS) staining.30-32 It is important to verify clinical suspicion with laboratory investigations. One study compared the costs of empirically treating all patients with onychodystrophy with antifungals versus PAS staining all nails and treating only those with a positive histology. The study found that it was cost-effective to first diagnose and then treat empirically.33 Samples for microscopy, culture, or histopathology can be collected from the nail plate or subungual debris. When collecting a sample, care should be taken with diabetic patients to avoid injuring the nail bed, which may increase the risk of secondary bacterial infection.15 Histological examination. Most clinicians find it easiest to send nail clippings for histopathological evaluation with a PAS stain. Clippings are sent to the pathology laboratory in formalin, are embedded in paraffin, and are stained with haematoxylin, eosin, PAS, and toluidine blue.23 This method, also called “PATHPAS,” has been shown to be the most sensitive test.30,32,34 One study evaluated 105 patients with suspected onychomycosis using KOH preparation, culture, biopsy with PAS stain, and biopsy with calcoflur white stain. Biopsy with calcoflur white stain was considered the gold standard. The study found that the KOH preparation was 80% sensitive and 72% specific, biopsy with PAS stain was 92% sensitive and 72% specific, and culture was 59% sensitive and 82% specific.34 Direct examination. Collected pieces are placed on a slide and treated with 10-30% KOH solution. The slide may be warmed over a flame to quicken the clearing of the nail and highlight the fungal features. Some recommend a combination of KOH and dimethylsulfoxide for clearer and faster results.23 Onychomycosis caused by dermatophytes can be diagnosed based on the appearance of long, regularly-shaped hyphae. If yeasts are the etiological agent, the appearance of budding spores can often be seen.21 Although the appearance of the nail may provide clues to the etiological agent, it cannot be used to diagnose the agent.23 Culture. Culture alone without clinical manifestations should not be used to diagnose onychomycosis.21 Cultures may be positive without a truly invasive infection because of contamination with comorbid onychodystrophy.5 For culture, samples from the nail plate and subungual keratosis should be placed in Sabouraud's agar and incubated at 26° C for 7-14 days.20,23 Antibiotics in the agar prevent the growth of coexisting bacteria. If possible, samples should be placed on agar both with and without cycloheximide because cycloheximide inhibits the growth of most nondermatophytes.23 Unfortunately, culture is less sensitive than direct microscopy, especially when a patient has already been given treatment. However, culture is the only method available for identification of the specific pathogen, which may be helpful in the choice of therapy, particularly if the nails do not respond to therapy with oral terbinafine (discussed below).20 Treatment of Onychomycosis in Diabetes The treatment of onychomycosis in diabetic patients is the same as in patients without diabetes.13 Toenails grow at one-third to one-half the rate of fingernails and thus need to be treated longer.23 Elderly diabetic patients' nails may grow even slower and require a longer duration to treat.15 Several modalities can be used for the treatment of onychomycosis in diabetic patients: topical therapy, systemic therapy, combination therapy, and nail removal.15,23 Patients > 55 years of age may have a higher rate of relapse. In addition, patient education is vital to reduce the risk of recurrence. Many studies have compared the mycological cure rates, recurrence rates, and cost-effectiveness of the various treatment options. Although it has been shown that diabetic patients with onychomycosis have a higher rate of complications and infections than diabetic patients without onychomycosis,10 to our knowledge, no study has compared treatment options with outcomes such as diabetic complications or secondary infections.
Treating Onychomycosis PDF PRINT COMMENTS SHARE This is a corrected version of the article that appeared in print. PHILLIP RODGERS, M.D., and MARY BASSLER, M.D., University of Michigan Medical School, Ann Arbor, Michigan Am Fam Physician. 2001 Feb 15;63(4):663-673. See patient information handout on infected fingernails and toenails, written by the authors of this article. Onychomycosis accounts for one third of fungal skin infections. Because only about one half of nail dystrophies are caused by fungus, the diagnosis should be confirmed by potassium hydroxide preparation, culture or histology before treatment is started. Newer, more effective antifungal agents have made treating onychomycosis easier. Terbinafine and itraconazole are the therapeutic agents of choice. Although the U.S. Food and Drug Administration has not labeled fluconazole for the treatment of onychomycosis, early efficacy data are promising. Continuous oral terbinafine therapy is most effective against dermatophytes, which are responsible for the majority of onychomycosis cases. Intermittent pulse dosing with itraconazole is as safe and effective as short-term continuous therapy but more economical and convenient. With careful monitoring, patients treated with the newer antifungal agents have a good chance of achieving relief from onychomycosis and its complications. Onychomycosis (tinea unguium) is a fungal infection of the nail bed, matrix or plate. Toenails are affected more often than finger-nails.1,2 Onychomycosis accounts for one third of integumentary fungal infections and one half of all nail disease.1 Tinea unguium occurs primarily in adults, most commonly after 60 years of age. The incidence of this infection is probably much higher than the reported 2 to 14 percent.1 Occlusive footwear, locker room exposure and the dissemination of different strains of fungus worldwide have contributed to the increased incidence of onychomycosis.3 Tinea unguium is more than a cosmetic problem, although persons with this infection are often embarrassed about their nail disfigurement. Because it can sometimes limit mobility, onychomycosis may indirectly decrease peripheral circulation, thereby worsening conditions such as venous stasis and diabetic foot ulcers.4 Fungal infections of the nails can also be spread to other areas of the body and, perhaps, to other persons. Dermatophytes, yeasts and nondermatophytic molds can infect the nails.1 The clinical significance of molds is uncertain, because they may be colonizing organisms that are not truly pathogenic.3,5 Classification of Onychomycosis DISTAL SUBUNGUAL ONYCHOMYCOSIS The most common form of tinea unguium is distal subungual onychomycosis, which can also be distal and lateral (Figures 1 and 2). Distal subungual onychomycosis may develop in the toenails, fingernails or both. Some degree of tinea pedis is almost always present. The infection is usually caused byTrichophyton rubrum, which invades the nail bed and the underside of the nail plate, beginning at the hyponychium and then migrating proximally through the underlying nail matrix2,3(Figure 3). Susceptibility to distal superficial onychomycosis may occur in an autosomal dominant pattern within families.1
