Cutaneous fungal infections are common in the United States, and causative organisms include dermatophytes, yeasts, and nondermatophyte molds. These organisms are in constant competition for their ...particular environmental niche, often resulting in the emergence of one or more predominant pathogens and displacement of other less competitive species. Changes in the incidence of fungal pathogens can be followed from laboratory culture results of infected cutaneous tissues over time. These data can be used to ascertain past and present trends in incidence, predict increases in antifungal resistance and the adequacy of our current pharmacologic repertoire, and provide insight into future developments.
This study identifies epidemiologic trends and the predominant organisms causing superficial fungal infections in the United States.
A total of 15,381 specimens were collected from clinically suspected tinea corporis, tinea cruris, tinea capitis, tinea faciei, tinea pedis, tinea manuum, and finger and toe onychomycosis from 1999 through 2002. Specimens were submitted to the Center for Medical Mycology in Cleveland, Ohio, for fungal culture and identification, and the incidence of each species was calculated.
Dermatophytes remain the most commonly isolated fungal organisms except from clinically suspected finger onychomycosis, in which case
Candida species comprise >70% of isolates.
Trichophyton rubrum remains the most prevalent fungal pathogen, and increased incidence of this species was observed in finger and toe onychomycosis, tinea corporis and tinea cruris, tinea manuum, and tinea pedis. As the causal agent of tinea capitis,
T tonsurans continues to increase in incidence, achieving near exclusionary proportions in the United States.
Consideration of the current epidemiologic trends in the incidence of cutaneous fungal pathogens is of key importance to investigational efforts, diagnosis, and treatment.
Background: Clinical studies with topical onychomycosis agents typically involve daily application over 48 weeks. Some patients are cured earlier; however, individual data are limited. Objective: The ...aim of this study was to assess baseline demographics/disposition of onychomycosis patients completely cured at week 24 following daily efinaconazole treatment. Methods: We conducted a week-24 case review of 2 identical, multicenter, randomized, double-blind, vehicle-controlled studies on 1,655 patients with mild-to-moderate onychomycosis. Patients were randomized (3:1) to efinaconazole 10% solution or vehicle, once daily for 48 weeks, with a 4-week post-treatment follow-up. Complete cure was defined as 0% clinical involvement of the target toenail and mycological cure (negative KOH examination and fungal culture). Results: Overall, 19 patients had clear nails (0% clinical involvement) at week 24, and 13 (68%) were completely cured. Patients were predominantly younger (17/19 aged <65 years), female (12/19), and with recent disease (6/12). No patient had disease recurrence over the subsequent 28 weeks. Complete cure appeared independent of baseline severity. Two patients with moderate disease had clear nails by week 12, and 1 experienced recurrence. Conclusions: Efinaconazole 10% topical solution has been shown to be an effective and well-tolerated treatment for onychomycosis. Our case review highlights that some patients (typically those having faster growing, shorter nails) might expect complete cure within 24 weeks. Continued treatment appears to prevent recurrence.
Background Although griseofulvin is currently considered the primary antifungal agent used to treat tinea capitis in many countries, increasingly higher doses and longer durations of treatment are ...becoming necessary to achieve effective treatment. Alternative antifungal therapies with shorter/simpler treatment regimens may be important to develop for this indication. Objective To compare the efficacy and safety of a new pediatric formulation of terbinafine hydrochloride oral granules with griseofulvin oral suspension in the treatment of tinea capitis. Method Children (4-12 years of age) with clinically diagnosed and potassium hydroxide microscopy–confirmed tinea capitis were randomized in two identical studies (trial 1, trial 2) to once-daily treatment with terbinafine (5-8 mg/kg; n = 1040) or griseofulvin administered per label (10-20 mg/kg; n = 509) for a period of 6 weeks followed by 4 weeks of follow-up. End-of-study complete cure (negative fungal culture and microscopy with Total Signs and Symptoms Score TSSS = 0), and mycologic (negative culture and microscopy) and clinical cure (TSSS = 0) were primary and secondary efficacy variables, respectively. Efficacy analysis was based on pooled data using modified intent-to-treat population (those who received at least one dose of study drug and had positive baseline fungal culture, N = 1286). Safety assessments included monitoring of the frequency and severity of adverse events (AEs). Results Rates of complete cure and mycologic cure were significantly higher for terbinafine than for griseofulvin (45.1% vs 39.2% and 61.5% vs 55.5%, respectively; P < .05). A majority (86.7%) of patients received griseofulvin, 10 to 19.9 mg/kg per day; complete cure rate was not found to be higher among patients who received griseofulvin more than 20 mg/kg per day compared with those who received less than 20 mg/kg per day. Complete cure rate was statistically significantly greater for terbinafine compared to griseofulvin in trial 1 (46.23% vs 34.01%) but not in trial 2 (43.99% vs 43.46%). On the basis of pooled data, clinical cure was higher for terbinafine than for griseofulvin, but the difference was not found to be statistically significant ( P = .10). Subgroup analyses revealed that terbinafine was significantly better than griseofulvin for all cure rates—mycologic, clinical, and complete—among patients with Trichophyton tonsurans but not Microsporum canis ( P < .001). For M canis , mycologic and clinical cure rates were significantly better with griseofulvin than with terbinafine ( P < .05). Approximately 50% of patients in each group reported an AE; almost all were mild or moderate in severity. Nasopharyngitis, headache, and pyrexia were most common in both groups. There were no drug-related serious AEs, no deaths, and no significant effects on weight or laboratory parameters, including liver transaminases. Limitations In retrospect, a difference in the distribution of infecting microorganisms between the two trials was a limitation. Stringent adherence to griseofulvin doses recommended by prescribing information but smaller than those used in current clinical practice, and exclusion of adjuvant therapies such as shampoos or topical agents, which are routinely used in practice, are other limitations. Conclusions Data from this largest pediatric trial of terbinafine to date indicate that terbinafine is efficacious and well tolerated in the treatment of tinea capitis. Terbinafine is an effective alternative to griseofulvin against T tonsurans tinea capitis.
Hidradenitis suppurativa (HS) is a skin disorder that causes chronic painful inflammation and hyperproliferation, often with the comorbidity of invasive keratoacanthoma (KA). Our research, employing ...high-resolution immunofluorescence and data science approaches together with confirmatory molecular analysis, has identified that the 5′-cap-dependent protein translation regulatory complex eIF4F is a key factor in the development of HS and is responsible for regulating follicular hyperproliferation. Specifically, eIF4F translational targets, Cyclin D1 and c-MYC, orchestrate the development of HS-associated KA. Although eIF4F and p-eIF4E are contiguous throughout HS lesions, Cyclin D1 and c-MYC have unique spatial localization and functions. The keratin-filled crater of KA is formed by nuclear c-MYC-induced differentiation of epithelial cells, whereas the co-localization of c-MYC and Cyclin D1 provides oncogenic transformation by activating RAS, PI3K, and ERK pathways. In sum, we have revealed a novel mechanism underlying HS pathogenesis of follicular hyperproliferation and the development of HS-associated invasive KA.
Display omitted
•eIF4F is associated with follicular hyperproliferation in HS•eIF4F targets Cyclin D1 and c-MYC are highly expressed activating Ras, PI3K, and ERK•The interplay of Cyclin D1 and c-MYC is associated with HS-related KA pathogenesis•nCyclin D1-CDK4 expressed throughout KA lesions providing oncogenic signaling
Biological sciences; Biochemistry; Medical biochemistry
Summary
Onychomycosis and tinea capitis are prevalent fungal diseases that are difficult to cure and usually require systemic treatment. Onychomycosis has high recurrence rates and can significantly ...affect a patient’s quality of life. Oral terbinafine has been approved for onychomycosis for 20 years in Europe and 15 years in the United States. Over these past 20 years, numerous studies show that oral terbinafine is a safe and efficacious treatment for onychomycosis. More recently, oral terbinafine also has been approved for tinea capitis. Once difficult to treat, terbinafine has revolutionised treatment of these fungal diseases. It has minimal side effects and its limited drug interactions make it an excellent treatment option for patients with co‐morbidities. This review discusses oral terbinafine and new insights into the treatment of onychomycosis and tinea capitis. Recent publications have enhanced our knowledge of the mechanisms of oral terbinafine and its efficacy in treating onychomycosis. Oral terbinafine vs. other antifungal therapeutic options are reviewed. Overall, terbinafine remains a superior treatment for dermatophyte infections because of its safety, fungicidal profile, once daily dosing, and its ability to penetrate the stratum corneum.
Metastasis of any malignancy to the nail unit is uncommon, and only a handful of cases of subungual renal cell carcinoma (RCC) metastasis have been reported. We describe a case of isolated nail ...dystrophy that proved to be the presenting symptom of a previously undetected RCC. In a patient presenting with a subungual lesion, tumor metastasis to the nail unit should be included in the clinical differential diagnosis in both oncology patients and previously cancer-free individuals, as a subungual metastasis may be the first indication of a clinically silent visceral malignancy.
Recurrence (relapse or re-infection) in onychomycosis is common, occurring in 10% to 53% of patients. However, data on prevalence is limited as few clinical studies follow patients beyond 12 months. ...It has been suggested that recurrence after continuous terbinafine treatment may be less common than with intermittent or continuous itraconazole therapy, probably due to the fungicidal activity of terbinafine, although these differences tended not to be significant. Relapse rates also increase with time, peaking at month 36. Although a number of factors have been suggested to play a role in recurrence, only the co-existence of diabetes has been shown to have a significant impact. Data with topical therapy is sparse; a small study showed amorolfine prophylaxis may delay recurrence. High concentrations of efinaconazole have been reported in the nail two weeks' post-treatment suggesting twice monthly prophylaxis with topical treatments may be a realistic option, and may be an important consideration in diabetic patients with onychomycosis. Data suggest that prophylaxis may need to be continued for up to three years for optimal effect. Treating tinea pedis and any immediate family members is also critical. Other preventative strategies include avoiding communal areas where infection can spread (such as swimming pools), and decontaminating footwear.
Scalp skin is unique on the body due to the density of hair follicles and high rate of sebum production. These features make it susceptible to superficial mycotic conditions (dandruff, seborrheic ...dermatitis, and tinea capitis), parasitic infestation (pediculosis capitis), and inflammatory conditions (psoriasis). Because these scalp conditions share similar clinical manifestations of scaling, inflammation, hair loss, and pruritus, differential diagnosis is critically important. Diagnostic techniques and effective treatment strategies for each of the above conditions will be discussed.
PDF
