Subclinical onychomycosis is associated with tinea pedis

Summary Background Onychomycosis is a common cause of nail dystrophy and may be associated with tinea pedis. The presence of dermatophyte fungi in clinically normal nails is unknown. Objectives To assess the presence of dermatophyte fungi in normal‐appearing toenails and to compare the risk of subclinical dermatophytosis in patients without and with concurrent tinea pedis. Methods This is a prospective, University‐based study of adults without and with microscopically confirmed tinea pedis. Subjects with dystrophy of any toenail were excluded, as were those ever previously diagnosed as having onychomycosis and those who had used topical antifungals in the past year. A great toenail clipping obtained from each subject was submitted for periodic acid–Schiff histology. Results One hundred and one subjects (63 men and 38 women, mean ± SD age 45·4 ± 15·7 years) were included. Overall, septate hyphae (ostensibly dermatophyte) were identified in seven specimens. Of the 66 control subjects, one case (1·5%) of nail dermatophyte was identified. Of the 35 subjects with tinea pedis, six cases (17%) of nail dermatophyte were identified (P = 0·0066; odds ratio 13·4, 95% confidence interval 1·6–117). There were no significant differences in age or gender between the experimental and control groups or between the nail dermatophyte‐positive and negative cohorts. Conclusions Dermatophyte fungi may be isolated from normal‐appearing toenails. The presence of dermatophytes in this situation is strongly associated with the presence of tinea pedis. Subclinical dermatophyte in the nail plate may serve as a reservoir for ongoing local infection.     

Inter-single-sequence-repeat-PCR typing as a new tool for identification of Microsporum canis strains

BACKGROUND: Microsporum canis is a ubiquitous dermatophyte that commonly causes human infections. Since contact with infected animals is the usual way of infection, tracing its source is an essential preventive measure. OBJECTIVE: To type isolates of M. canis from human patients whose skin was affected, and from some animals (dogs and cats) that were closely associated to the patients. METHODS: The inter-single-sequence-repeat-PCR (ISSR-PCR) technique has been used for typing 24 isolates of M. canis. Seventeen isolates tested were from human patients, 5 from cats and 1 from a dog RESULTS: A total of 21 genotypes were identified. The same genotype was found infecting a patient and a cat that was living closely with him, but another member of the same family proved to be infected with two genotypes different from that. Clinical specimens from two patients had been contaminated with the same genotype, probably in the laboratory where the samples were handled. CONCLUSION: These results demonstrate that ISSR-PCR polymorphism is a reliable method for the identification of the M. canis strains.     

Epidemiology of dermatophyte infection in Auckland, New Zealand

This report describes the epidemiology of culture-proven dermatophyte infection in Auckland, New Zealand. The authors undertook a retrospective review of laboratory data for the period from June 1999 to July 2002. There were 10 004 dermatophyte isolates. The most common isolates were Trichophyton rubrum (69%) and Trichophyton mentagrophytes (19%). Microsporum canis was mainly isolated from children. The prevalence of T. mentagrophytes increased with patient age (P < 0.001). Trichophyton rubrum was most common in those aged between 20 and 59 years. The incidence of culture-proven dermatophyte infection was 2.9/1000 population for the year 2000, and the incidence increased with patient age (P < 0.001). It is concluded that dermatophytes causing superficial mycoses in the Auckland region are essentially similar to Australia and other Western countries, although some new organisms are seen as a result of the migration of people from other countries. The incidence of local dermatophyte infection increases with age.     

Chronically Recurrent and Disseminated Tinea Faciei/Corporis—Autoinoculation from Asymptomatic Tinea Capitis Carriage

Abstract: We report clinical findings in a 12‐year‐old girl with long‐term recurrent and disseminated multiple eruptions of tinea faciei and tinea corporis, which persisted for 10 years. Mycological examination revealed the dermatophyte Trichophyton tonsurans in both scale samples from the body lesions and in brushing samples from her asymptomatic scalp, suggesting that she was an asymptomatic dermatophyte carrier on the scalp, and autoinoculation of the dermatophyte was responsible for the recurrent and disseminated tinea faciei/corporis.     

Comparison of the in vitro antifungal activities of clotrimazole, miconazole, econazole and exalamide against clinical isolates of dermatophytes

The in vitro antifungal activities of clotrimazole, miconazole nitrate, econazole nitrate, and exalamide against 64 clinical isolates of various dermatophyte species obtained from out-patients seen at the Nippon Medical School Hospital were simultaneously compared using a liquid microculture method. The rank order of activity against the 64 isolates of dermatophytes was clotrimazole > econazole nitrate > miconazole nitrate > exalamide. For a given antimycotic, the minimal inhibitory concentration was affected by the dermatophyte species.     

Onychomycosis in Hong Kong

Background Onychomycosis in temperate countries has been studied extensively, but few data are available on its epidemiology in tropical countries. We performed a survey of patients seen in Hong Kong for the 8-year period from January 1987 to December 1994. Methods A retrospective study of the mycology laboratory records of patients attending the Government Dermatology Clinics was carried out. Nail samples examined included clippings, scrapings, and drillings. Microscopy was performed on all specimens. Sabouraud dextrose agar was used for culture. Results Out of a total of 2382 nail samples (1024 (43.0%) toe, 1148 (48.2%) finger, and 210 (8.8%) unspecified site) examined, 340 (14.3%) were microscopy positive; 165 (48.5%) of these were culture positive, including 160 (97%) with dermatophyte and/or yeast, and 5 (3%) with molds. Men were affected more in the –19 and >50 years age groups, whereas women were affected more in the 20–50 years age group. Women were affected significantly more than men with yeasts, dermatophytes occurred more during adolescence. Dermatophytes showed a high peak in late spring, although both dermatophyte and yeast cases peaked in the summer months. Dermatophytes (29.1%) occurred more commonly than yeasts (19.4%) in microscopy-positive onychomycosis cases in Hong Kong. Trichophyton rubrum was the commonest dermatophyte, and Candida spp., other than C albicans, were the commonest yeasts. Mixed infections (5%) were uncommon. Conclusions Dermatophytes are more important than yeasts as a cause of onychomycosis in Hong Kong. Changes in climatic conditions affect the prevalence of dermatophytes more than yeasts.     

First report of Arthroderma benhamiae in Switzerland

BACKGROUND: Dermatophytes are usually identified on the basis of macroscopic characteristics and microscopic examination of the cultures. Identification of dermatophytes often remains difficult or uncertain because there are variations from one isolate to another and overlapping characteristics between species. OBJECTIVE: To identify dermatophyte species producing numerous microconidia and resembling Trichophyton mentagrophytes by DNA sequence analysis. METHODS: The complete ITS1 + 5.6s + ITS2 rDNA region of various dermatophytes isolated in culture was amplified by PCR and sequenced. RESULTS: Nine isolates of a fast-growing dermatophyte species were identified as Arthroderma benhamiae by DNA sequencing. Retrospective investigations revealed that the isolates were from 8 children and 1 adult suffering from inflammatory dermatophytosis. Eight of the 9 patients had had previous contact with rodents, mostly guinea pigs. CONCLUSION: It is the first time that A. benhamiae is reported in Switzerland. In cases of dermatophytosis attributed to A. benhamiae, a rodent is the most likely cause of infection.     

Polymerase chain reaction in the diagnosis of onychomycosis: a large,single‐institute study

Summary Background  Tests commonly used in the diagnosis of onychomycosis include potassium hydroxide (KOH) preparation, histopathological examination with periodic acid–Schiff stain (PAS) and culture. These tests are either time‐consuming or require specially trained personnel. A recently developed polymerase chain reaction (PCR) assay has the potential to provide a quick, inexpensive, operator‐independent diagnosis of onychomycosis. Objective  To determine the range of fungal species detected by the PCR technique and to compare this technique with KOH, PAS and culture on patient specimens. Methods  A total of 176 dermatophytic and nondermatophytic fungal culture isolates were tested by PCR. Five hundred and fifty nail specimens from 550 patients with suspected onychomycosis were split and tested concurrently with PCR, PAS, KOH and culture. Results  PCR was positive in 65 out of 66 dermatophyte culture isolates and negative in all 110 nondermatophyte and yeast isolates. Overall, PAS, PCR, KOH and culture were positive in 54%, 37%, 40% and 22% of specimens, respectively. Fifty‐two per cent were positive for KOH and PCR. Conclusion  PCR is a specific, relatively sensitive test for onychomycosis. When used in conjunction with KOH, PCR can produce positivity rates similar to those with PAS alone.     

Trichophyton mentagrophytes var. nodulare–Ein seltener Fußpilzerreger auf dem Vormarsch?

Background: The spectrum of organisms causing dermatophytoses is changing continuously. Patients/Methods: Two strains of Trichophyton mentagrophytes var. nodulare are characterized mycologically; both were isolated for the first time in our laboratory within the past 2 years from patients with tinea pedis. Results: Distinctive features of Trichophyton mentagrophytes var. nodulare are a bright yellow‐orange pigmentation of the thallus, a marked exudation of pigment, and the development of nodular bodies. Trichophyton mentagrophytes var. nodulare is an anthropophilic variety of Trichophyton mentagrophytes causing tinea and onychomycosis. Conclusions: Trichophyton mentagrophytes var. nodulare has been found only very rarely in Germany and is relatively unknown. An increased awareness of this dermatophyte is needed in order to track its possible spread.     

A twenty-year survey of dermatophytoses in Braga, Portugal

Background Modifications in social habits together with the increase of emigration have contributed not only to increased dermatophytoses but also to an altered etiology. During the last few years, Braga has suffered a radical change from a rural to a cosmopolitan life‐style. Methods A statistical study of dermatophytoses and the etiology of their causative agents was performed by a retrospective survey carried out among patients of Hospital de São Marcos, Braga, Portugal, from 1983–2002. In this study, a total of 10 003 patients were analyzed. Results Over this period the frequency of dermatophytoses, as defined by the recovery of a dermatophyte in culture, was found to be 23.6%, whereas nondermatophytic infections accounted for 7.0%. Analysis of the clinical forms and the isolated fungi supports that the dermatophyte species have a predilection for certain body areas (P ≤ 0.01). Age is a very important factor regarding the occurrence of dermatophytoses (P ≤ 0.0001), with a correlation between increasing age and infection, positive for Trichophyton rubrum and negative for Microsporum canis. Overall the gender of the patients is not an association factor for the development of dermatophytoses; however, significant differences were detected in the distribution of some etiologic agents (P ≤ 0.05). Conclusions The results showed the main etiologic agent of dermatophytoses to be Trichophyton rubrum (37.4%). Moreover, dermatophytoses are both decreasing and showing a new profile in Braga, and a pronounced decrease of Trichophyton megninii was observed throughout the study.     

Opportunistic toenail onychomycosis. The fungal colonization of an available nail unit space by non‐dermatophytes is produced by the trauma of the closed shoe by an asymmetric gait or other trauma. A plausible theory

Opportunistic onychomycosis is defined, when a non‐dermatophyte mould is cultured from an abnormal nail unit in the absence of a dermatophyte. The presumption is that the mould has caused the abnormal clinical appearance of the nail unit, yet there are no data available to substantiate this claim. Reports have only identified the mould being recovered from the nail unit niche. A review of the published dermatologic literature describing toenail opportunistic onychomycosis by non‐dermatophyte fungi has shown toenails with onycholysis, nail bed (NB) keratosis and nail plate surface abnormalities. The appearance of these clinical changes is indistinguishable from the diagnosis of the Asymmetric Gait Nail Unit Signs (AGNUS). AGNUS is produced by the friction of the closed shoe in patients with an asymmetric gait, resulting primarily from the ubiquitous uneven flat feet. Most commonly, species of Acremonium (Cephalosporium), Aspergillus, Fusarium, Scopulariopsis and rarely species of many different fungi genera are capable of surviving and reproducing in a keratinous environment and change the clinical appearance of the involved nail unit. AGNUS toenails predispose to the colonization by the non‐dermatophyte opportunistic fungi but not by dermatophyte fungi.     

Diagnosis of common dermatophyte infections by a novel multiplex real-time polymerase chain reaction detection/identification scheme

BACKGROUND: In the absence of a functional dermatophyte-specific polymerase chain reaction (PCR), current diagnosis of dermatophytoses, which constitute the commonest communicable diseases worldwide, relies on microscopy and culture. This combination of techniques is time-consuming and notoriously low in sensitivity. OBJECTIVES: Recent dermatophyte gene sequence records were used to design a real-time PCR assay for detection and identification of dermatophytes in clinical specimens in less than 24 h. PATIENTS AND METHODS: Two assays based on amplification of ribosomal internal transcribed spacer regions and on the use of probes specific to relevant species and species-complexes were designed, optimised and clinically evaluated. One assay was for detecting the Trichophyton mentagrophytes species complex plus T. tonsurans and T. violaceum. The second assayed for the T. rubrum species complex, Microsporum canis and M. audouinii. RESULTS: The analytical sensitivity of both assays was 0.1 pg DNA per reaction, corresponding to 2.5-3.3 genomes per sample. The protocol was clinically evaluated over 6 months by testing 92 skin, nail and hair specimens from 67 patients with suspected dermatophytosis. Real-time PCR detected and correctly identified the causal agent in specimens from which T. rubrum, T. interdigitale, M. audouinii or T. violaceum grew in culture, and also identified a dermatophyte species in an additional seven specimens that were negative in microscopy and culture. CONCLUSIONS: This highly sensitive assay also proved to have high positive and negative predictive values (95.7% and 100%), facilitating the accurate, rapid diagnosis conducive to targeted rather than empirical therapy for dermatophytoses.     

Susceptibility of dermatophyte isolates obtained from a large worldwide terbinafine tinea capitis clinical trial

Background  Our group, in collaboration with seven other laboratories, has recently developed a method to determine the susceptibility of dermatophytes.
Objectives  The objective of this study was to determine the terbinafine susceptibility profile of dermatophyte isolates obtained from patients with tinea capitis enrolled in two large worldwide clinical trials and to investigate whether these susceptibilities differ by geographical location.
Methods  Susceptibilities were determined according to the Clinical and Laboratory Standards Institute M38-A2 standard.
Results  From a total of 978 baseline dermatophyte isolates, we selected 301 isolates at random. These included: Trichophyton tonsurans ( n  = 125) , Microsporum canis ( n  = 94), T. violaceum ( n  = 63) and M. audouinii ( n  = 19) . The terbinafine minimum inhibitory concentration (MIC) range was 0·001–0·25 μg mL⁻¹, while MIC₅₀ and MIC₉₀ ranged between 0·002 and 0·125 μg mL⁻¹ and 0·03 and 0·25 μg mL⁻¹, respectively, for all species tested. MIC₅₀ and MIC₉₀ varied by individual species; however, there was no difference in terbinafine MIC among the different species isolated from U.S. and non-U.S. sites.
Conclusion  Terbinafine demonstrates potent antifungal activity against dermatophyte isolates obtained from patients with tinea capitis worldwide.     

The immunofluorescence staining of fungi in chronic dermatophyte infections

Indirect immunofluorescence staining of fungi with specific antisera was demonstrated in biopsy specimens taken from six patients with chronic Trichophyton rubrum infections. However, there was no evidence of immunoglobulin or C₃ deposition in the vicinity of the organisms or elsewhere in the sections. Circulating antibodies to dermatophyte fungi are often not demonstrable in these patients. However, these results suggest that antibody affinity for epithelium docs not account for their absence in patients' serum.     

Comparative study of direct polymerase chain reaction, microscopic examination and culture-based morphological methods for detection and identification of dermatophytes in nail and skin samples

The positive rates of dermatophytes isolated and identified by conventional methods are rather low. Moreover, clinical isolates sometimes show atypical morphology, and in such cases microscopic methods are not applicable for identification. The present study was performed to assess the utility of specific polymerase chain reaction (PCR)-based methods for Trichophyton rubrum and Trichophyton mentagrophytes as diagnostic tools for dermatophytoses. Both conventional morphological identification and specific PCR methods based on the nuclear ribosomal internal transcribed spacer (ITS)1 DNA sequence were performed to identify dermatophyte species from clinical specimens of patients who visited Kawasaki Social Insurance Hospital between 16 May and 17 August 2005. Specific PCR methods were also directly applied to clinical specimens, and the results of the two methods were compared. The clinical samples examined consisted of 126 skin scale specimens and 80 nail specimens. The positive rates of culture isolation from clinical specimens were 67% and 33% for skin scale and nail specimens, respectively. In contrast, PCR analysis yielded a positive rate of 100% for clinical isolates from both skin scales and nails, and rates of 95% and 99% were obtained by direct application to clinical specimens. The results of the present study indicated that specific PCR is highly advantageous as a diagnostic tool for detection and identification of dermatophytes on direct application to skin scale or nail specimens.     

TREATMENT OF SUPERFICIAL MYCOSES IN THE TROPICS: WHITFIELD'S OINTMENT VERSUS CLOTRIMAZOLE

Background. In tropical primary health care, essential drugs should be safe, effective, and as inexpensive as possible. To treat the very common dermatophyte infections of the skin, one may use inexpensive Whitfield's preparations, more expensive topical imidazole derivatives, or extremely expensive oral antifungals. Because a cream base is felt to be more appropriate than an ointment in tropical conditions, we wanted to compare the effectiveness of Whitfield's cream and a topical imidazole derivative in field conditions in the tropics. Methods. A double-blind trial was performed involving 153 patients with a dermatophyte infection of the skin in Karonga District, Northern Malawi, including 25 patients who were Hiv-i-seropositive, comparing Whitfieid's cream with clotrimazole cream. Results. 75 patients were treated with Whitfield's cream and 78 with clotrimazole cream for a period of 6 weeks. Cure rates ranged from 80% to over 90% depending on the definition of cure. If positive cultures after treatment were used as criterion for treatment failure, six were found in each treatment group. One in each treatment failure group was an mv-i-seropositive patient. Conclusions. The great majority of patients in the tropics with a dermatophyte infection of the skin can be cured with a topical antimycotic preparation and do not need expensive oral therapy. This also proved to be valid for HIV-I-seropositive patients. Whitfield's cream and clotrimazole cream are both very effective. The lower cost makes Whitfield's cream the treatment of choice in dermatophyte infections of the skin in tropical primary health care.     

Trichophyton species of Arthroderma benhamiae – a new infectious agent in dermatology

In Germany, infections due to the zoophilic dermatophyte Trichophyton (T.) species of Arthroderma benhamiae are being more frequently diagnosed. The source of infection of this emerging pathogen overlaps with that of the zoophilic species T. interdigitale. The most common source are guinea pigs. T. species of Arthroderma benhamiae causes inflammatory dermatophytosis in children and adolescents. In addition to tinea capitis, it may cause both tinea corporis, tinea manus and frequently tinea faciei. In Germany, T. species of Arthroderma benhamiae is a frequent zoophilic dermatophyte, which in regions is probably more frequent than Microsporum canis. The mycological identification of the isolates with their yellow stained colonies is based on their macroscopic and microscopic features. However, some exhibit colony features consistent with those of T. interdigitale. These strains only can be identified unambiguously by means of molecular techniques. Using detection methods such as PCR‐ELISA or real‐time PCR, the dermatophyte can be identified directly from clinical material. Sequencing of the internal transcribed spacer region (ITS) of the ribosomal DNA has been approved as culture confirmation test for T. species of Arthroderma benhamiae. In addition, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI TOF MS) is useful. Widespread dermatophytosis due to T. species of Arthroderma benhamiae, in particular of tinea capitis, requires oral antifungal agents. Terbinafine is most effective, alternatives are fluconazole and itraconazole.     

A Clinical and Mycologic Study of Tinea Corporis and Pedis in Puerto Rico

A study of the causative agents of tinea corporis and pedis in Puerto Rico in 1982 disclosed four different dermatophytes from a total of 97 cases. Among the total of 49 fungus specimens collected in tinea corporis, the mycologic flora consisted of four different fungus species: Trichophyton rubrum, 42 isolates (85.7%); Epidermophyton floccosum, 4 (8.1%); Trichophyton mentagrophytes, 2 (4%); and Microsporum ferrugineum, 1 (2%). Among the total of 48 fungus specimens collected in tinea pedis, the mycologic flora consisted of 3 different fungus species as follows: T. rubrum, 35 isolates (72.9%); T. mentagrophytes 8 (16.6%); and E. floccosum, 5 (10.4%). Trichophyton rubrum caused 77 of 97 fungal isolates (79.3%). One surprising finding was the isolation of M. ferrugineum in a case of tinea corporis, documenting the first autochtonous case of this species in the island. This dermatophyte had previously been known only in Japan and adjacent areas of the Far East, Southern Europe, and Africa.     

Non-dermatophytes in onychomycosis of the toenails

A multicentre trial for the treatment of dermatophyte onychomycosis of the toenails with terbinafine was carried out in Australia and New Zealand. Between eight and 12 nail samples were obtained from each of the 118 patients in the 48-week trial, and each sample was investigated by direct microscopy and culture for dermatophyte and non-dermatophyte fungi. Patients were randomized to treatment with terbinafine at 250 mg/day or placebo for the first 12 weeks of the study, then non- responders were offered a 12-week course of terbinafine from week 28. All patients had a dermatophyte infection. In 42 patients (36%) microscopy and mycological culture identified dermatophytes alone. In the remaining 76 patients (64%), a non-dermatophyte mould or yeast was also isolated at some stage during the trial, but in only three patients did the same non- dermatophyte persist in two or more successive nail specimens. The presence of a fungal con- taminant in addition to a dermatophyte had no apparent effect on the efficacy of treatment with terbinafine. We conclude that non-dermatophyte moulds and yeasts are generally found as contaminating organisms in dermatophyte onychomycosis, secondary to the dermatophytes, and that they do not infiuence the outcome of treatment.     

Trends in Tinea Capitis in an Irish Pediatric Population and a Comparison of Scalp Brushings Versus Scalp Scrapings as Methods of Investigation

A retrospective study of 391 children with suspected tinea capitis was analyzed to examine the prevalence of dermatophyte species and to compare the efficacy of the scalp scraping method with that of the hairbrush method for diagnoses over a 6‐year period. Trichophyton tonsurans tinea capitis is the most common pathogen. The hairbrush method of obtaining specimens for fungal culture was superior to scalp scrapings (p = 0.03) in making the diagnosis, and using two methods (p < 0.001) increased the yield of identifying a dermatophyte infection.