Healthcare e-Compendium
A joint initiative of DPSRU & DRSC
Healthcare e-Compendium
A joint initiative of DPSRU & DRSC
Author: Dr. Shitij Goel
M.B.B.S., MD (Dermatology), Fellowship in Dermatosurgery, Professor of Dermatology, Sharda University School of Medical Sciences & Research, Noida
download ArticleAbstract
Athlete’s foot is a chronic fungal infection of the feet, very often observed in patients who are immuno-suppressed or have diabetes mellitus. Tinea infection sometimes may be mistaken for atopic dermatitis or allergic eczema. Three groups of fungal pathogens, known as dermatophytes, are known to cause tinea pedis: Trychophyton sp, Epidermophyton sp, and Microsporum sp. The disease demonstrates as a pruritic, erythematous, scaly eruption on the foot and depending on its location, three types have been described: interdigital type, moccasin type, and vesiculobullous type. Tinea pedis may be connected with recurrent cellulitis, as the fungal pathogens provide a gateway for bacterial invasion of subcutaneous tissues. Most often, protracted topical and/or oral antifungal agents are needed to treat this often frustrating and morbid disease. Topical Ketoconazole solutions are used to stop the growth of fungal pathogens which cause tinea pedis (Athlete’s foot). Nizral 2% formulated with micronized ketoconazole solution effectively stops the growth of fungus. Nizral 2% is a global brand of ketoconazole solution, mentioned in most of the medical textbooks with a clinical legacy of more than three decades.
Keywords: Tenia pedis, Athlete’s foot, Antifungal, Ketoconazole, Nizral 2% Solution
Introduction
Dermatophytosis or Tinea can occur in different anatomical regions of the body and have been named accordingly such as tinea capitis affects the scalp, tinea unguum for nails, tinea barbae for face, tinea cruris for groin area and tinea manuum for hands. Tinea pedis or athlete's foot, is a chronic fungal infection of the feet. Tinea pedis is the most common skin disease, effecting around 10% worldwide. Tinea pedis causes pruritic (itching) erythematous (redness), inflamed areas of the feet, which can be seen on the lateral aspects (moccasin type) or sole (vesicular type), as well as between the toes (interdigital type).
Trichophyton, Epidermophyton and Microsporum are the three main group of fungi that may cause tinea pedis. These fungi can be disseminated by contact with fomites, soil (geophilic), animals (zoophilic) or people (anthropophilic).
The clinical aspects of tinea pedis infection, the microorganisms implicated, and treatment choices for individuals with this condition will be discussed in this review.
Causative Factors
The three most common dermatophyte fungi causing tinea pedis are:
Trichophyton rubrum is the most common pathogen associated with chronic tinea pedis, while other fungal pathogens have also been associated with the disorder. The source of transmission of these dermatophytic pathogens is usually either human (anthropophilic), animal (zoophilic) or soil (geophilic) and the factors affecting transmission of these pathogens are depending on the source of infection. T. rubrum is the most common anthropophilic dermatophyte infection. T. rubrum accounted for over 76% of all dermatophyte infections and may account for over 2/3 of all tinea pedis infections, shown in recently conducted study [1]. T. rubrum appears in two forms - white and fluffy with several aerial hyphae and is called the “downy form” and the flat granular form with no aerial hyphae [2]. The granular form of T. rubrum is easily confused with T. mentagrophytes which is similar in appearance and causes a more inflammatory form of tinea pedis. T. rubrum is also common in other tinea infections.
Trichophyton mentagrophytes is characteristically and morphologically similar to T. rubrum and sometimes it is difficult to distinguish between both under the microscope. On the underside, T. mentagrophytes species might be pale yellow, but T. rubrum species are typically, but not always, wine colored on the bottom [2]. T. mentagrophytes affects many animal species including rodents, cats, dogs, and horses.
Another anthropophilic fungus that causes tinea pedis is Trichophyton tonsurans. T. tonsurans colonies can range in color from white to brown with an underside ranging from yellow to red [3]. Microsporum canis is a zoophilic fungus from dogs, a rarer cause of tinea pedis infections [2].
Epidemiology
According to several researches, using different study sizes, designs and target groups to examine the epidemiological characteristics of tinea pedis, the incidence of tinea pedis is not associated with a specific ethnic group or racial. Its prevalence increases with age, more frequent in adults (aged 31-60 years) and it is rare in children. Tinea pedis is more common in developed countries and risk of tinea pedis has shown to be higher in men than in women. There are certain occupational groups in which risk of tinea pedis infection is high. For example: up to 58% of soldiers, 31% of marathon runners and 72.9% of miners examined had mycologically proven tinea pedis. Tinea pedis was found to be prevalent in 29.5% of mosque attendance. These people are predisposed to tinea pedis because of their exposure to sweating, trauma, occlusive footwear, and communal settings [4]. Tinea pedis was the most prevalent concurrent dermatomycosis, based on the study which detected it in 33.8% of all patients with toenail onychomycosis. The interdigital subtype of tinea pedis was the most frequent kind of tinea pedis, with 65.4% of individuals having it.
Types of Tinea pedis
Moccasin-type tinea pedis is a prolonged form of tinea pedis. It is more severe and covers the bottom and lateral aspects of the foot. It is most commonly caused by T. rubrum. It appears as slipper or moccasin covering the foot, hence the name, and the skin of the inflamed area is often scaly and hyperkeratotic with erythema around the soles and sides of the foot [5,6]. Tender bump (papules) may also be noted around the separation line of erythema that surrounds the foot. Either foot may be affected, however involvement of both feet is most often seen [7]. T. rubrum most often cause Subungual onychomycosis coexisting with moccasin type dermatophytosis as well.
Interdigital tinea pedis is the most common form of tinea pedis, usually present in the interspace and may spread to the underside of the toes [5,6]. There are two types of interdigital tinea pedis. The first type is scaly, dry type called dermatophytosis simplex. In this type the skin of the interdigital space become dry with low-grade peeling. This type is usually asymptomatic. The second type called dermatophytosis complex presents with wet, macerated interdigital spaces and is symptomatic. This type may have fissuring of the interspace along with leukokeratosis, hyperkeratosis, or erosions [8]. Fungal invasion along with wet conditions increases the incidence of bacterial infection in these patients by breaking cutaneous integrity. Extensive spread of tinea lesions to the dorsum of the foot is seen in patients with Human Immunodeficiency Virus (HIV) infection and/or others with impaired T-cell function. And in these type of patient infection may also become resistant to therapy. Due to the inflammatory component, tinea pedis may mimic bacterial cellulitis in some cases, as described recently, and this may further lead to complications and damage and skin maceration.
The third type of dermatophyte infection of the feet is Vesiculobullous tinea pedis. Occasionally small bumps containing fluid or pus (pustules) may be seen on the instep and adjacent plantar surfaces of the feet [6]. This type of tinea pedis may be associated with dermatophytid. Bullous impetigo, allergic contact dermatitis, dyshidrotic eczema and bullous disease, all need to be considered in the differential diagnosis [7].
Diagnosis
Tinea pedis infections are usually straightforward to identify and diagnose. To confirm the diagnosis and guarantee adequate therapy, a full identification of the causative fungus must be obtained. Tinea pedis is diagnosed using a combination of history, clinical appearance of the feet, and direct microscopy of a potassium hydroxide (KOH) preparation. Rarely are cultures or histological studies necessary. KOH preparations are easy to make, affordable, and effective. They are also frequently used. In addition, the KOH preparation has a high positive predictive value. False negative findings can occur sometimes, especially if therapy has already begun.
The process for preparing a KOH slide of the suspected fungus must be followed meticulously. To begin, skin cells from the afflicted area's perimeter are scraped onto a glass microscope slide using a sterile scalpel blade. One to two drops of a 10% KOH solution are put onto the slide and slowly heated to disintegrate skin cells while preserving the fungal hyphae (figure 1). The slide preparations should next be viewed using a microscope with a low or medium power setting. When examining a vesicle, the roof may be removed so that the interior material may be studied.
Figure 1: KOH preparation of fungal hyphae
Treatment consideration for Tinea pedis
For the treatment of tinea pedis there are number of available medicines, including topical and systemic treatments. Antifungal shampoos/washes have been also used for many years. In most patients, topical antifungal therapy is the treatment of choice and systemic antifungals are primarily reserved for patients who fail topical therapy. Examples of topical antifungals effective for tinea pedis include Ketoconazole, Econazole, Naftifine, Clotrimazole etc.
Antifungal topical therapy is typically used once or twice daily for four weeks. Treatments with shorter durations may be more successful than those with longer durations [9]. A meta-analysis of randomised studies published before February 2005 found substantial evidence that topical antifungal medications (azoles, allylamines, ciclopirox, tolnaftate, butenafine, and undecanoate) are more effective than placebo [10].
Use of Ketoconazole Solution for Tinea pedis
Tinea pedis, caused solely by dermatophyte fungi, with Trichophyton spp. (T. rubrum and T. mentagrophytes) and Epidermophyton floccosum (most frequent agents identified), comes under fungal based classification. This mainly affects interdigital toe web space as well as the skin of the feet. Fungal infections can be tough to fight. There are many antifungal medicines which can be used for the treatment, such as azoles, allylamines, butenafine, ciclopirox, tolnaftate, and amorolfine. Ketoconazole is an antifungal agent belonging to azole group of an antifungal which is highly effective in treating such type of fungal infections either alone or as an adjunct to other treatments [11].
Ketoconazole: Mechanism of Action
The exterior cell wall and cell membrane make up a fungal cell. The ergosterol (ergosta-5,7,22-trien-3-ol), sterol, is found in fungus. It is a component of yeast and other fungal cell membranes, and it controls permeability and fluidity through preserving membrane integrity [12]. Fungi can't live without ergosterol, thus the enzymes that make it have become prime targets for therapeutic development. Because ergosterol is the primary sterol in fungal membranes but not in mammalian cells, it is a promising target for antifungal medicines [13].
Ketoconazole is an antifungal that belongs to the azole family. It's a fungistatic substance that stops the fungus from growing and spreading throughout the body by causing growth arrest in fungal cells. Ergosterol (the main fungal sterol) production is inhibited by ketoconazole [14]. Ketoconazole inhibits the enzyme that produces ergosterol (figure 2). The inhibition of the fungus cytochrome P450 enzyme is thought to be the mechanism of action. As a result, ergosterol production is hampered. Ergosterol is an essential component of fungal cell membranes that alters the makeup of the membrane's other lipid components. Impaired ergosterol production finally leads to cell death and fungal eradication [15].
Figure 2: Ketoconazole inhibiting the synthesis of ergosterol (the main fungal sterol)
Research Studies on Ketoconazole
Many studies on the use of ketoconazole solution for the treatment of fungal infections have shown that it is very efficient and well tolerated, with a considerable reduction in the eradication of the pathogenic organism.
In one trial, using an antifungal shampoo/solution in combination with an oral antifungal improved the fungal infection dramatically in just one month. The difference between the two groups was statistically significant (P<0.001), with 96% of patients in the intervention group and 60% in the non-intervention group showing improvement. The biggest issue is recurrence once the therapy is completed. The risk of recurrence in patients who received antifungal shampoo was 4% after 3 months and 6% after 6 months of therapy. However, after 3 months and 6 months of therapy, the recurrence rate in the non-intervention group, who did not get the antifungal wash, was 22% and 60%, respectively (figure 3) [16].
Figure 3: Trend of reoccurrence among intervention and non-intervention groups
Nizral 2% Solution
Globally established anti-dandruff shampoo solution is a textbook brand with consistent quality since three decades. A potent antifungal effectively kills the fungus and ensures treatment with lower recurrence rates. Nizral 2% solution contains micronized ketoconazole which is manufactured by using micronized technology. This unique formulation/technology leads to better penetration and gets uniformly distributed in the affected dermis/epidermis resulting in greater degree of efficacy. It has anti-inflammatory and anti-proliferative properties. With its low viscosity, it allows easy spread ability on the affected area. Nizral 2% treats the root cause of many fungal infections and relieves redness and itching. 2% Ketoconazole is recommended by Danish Society of Dermatology for Pityriasis Versicolor and Seborrheic Dermatitis. Adding Nizral wash to antifungal treatment ensures higher cure with lower recurrence rates.
Conclusion
Tinea pedis is a very common infection worldwide and if last for a long time, can have a substantial negative impact on one's quality of life. Topical application of ketoconazole solution offers direct access to the target and a higher retention rate, which is possibly the best method against tinea pedis. Topical administration reduces systemic toxicity and eliminates pre-systemic metabolism. Topical medication administration also has the advantages of site-specific drug delivery, less systemic toxicity, higher patient compliance, enhanced therapeutic effectiveness, and improved bioavailability. Antifungal medication coupled with antifungal wash (Nizral 2% Solution) prophylactically decreased the recurrence of fungal infections significantly. As a result, in addition to oral and topical medicine, preventative antifungal wash should be used to increase treatment efficacy and reduce the risk of recurrence while treating fungal infections like tinea pedis.
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