Tenia Pedis: Epidemiology, Diagnosis, Pharmacotherapy and Emerging Role of Solid Lipid Nanoparticles in Therapy

Abstract

Tinea pedis is a very common fungal infection that affects a significantly large number of people globally. Tinea pedis is one of the most common superficial fungal infections of the skin, with various clinical manifestations and is predominantly caused by dermatophytes such as trichophyton rubrum and trichophyton interdigital. Conventional diagnostic techniques and antifungal pharmacotherapy remain effective but are limited by poor drug permeation, low bioavailability, and patient noncompliance. Recent advances in nanotechnology have highlighted solid lipid nanoparticles (SLNs) as a promising platform for topical antifungal delivery. SLNs enhance drug penetration across the stratum corneum, enable sustained drug release, and improve therapeutic efficacy while minimizing systemic toxicity. This review summarizes current knowledge on the pathogenesis and diagnosis of athlete’s foot, critically evaluates existing pharmacotherapeutic options, and highlights the emerging role of SLN-based formulations as an innovative strategy for optimized management of tinea pedis. Another aims to revisit this important topic and will detail the recent advances in the pathophysiology and management of tinea pedis while highlighting the lack of clarity of certain management issues.

Keywords

Introduction

Tinea Pedis is also called Athlete’s foot, is the single most common dermatophyte infection(1) Dermatophytes are a scientific label that refers to a group of three genera (Microsporum, Epidermophyton and Trichophyton) of fungus that cause skin diseases in humans and animals(2). Tinea pedis, commonly known as athlete’s foot, is a widespread dermatophyte infection that primarily affects the skin between the toes but can extend to other areas of the foot, including the sole, sides, and dorsal surface. In some cases, the infection may also spread to other body sites such as the groin, fingernails, and fingers. The term tinea refers to a fungal infection, while pedis is derived from Latin and denotes involvement of the foot(3). Tinea pedis is a very common infection in society. The prevalence is higher in older population. Wearing closed shoes for a long time, hyperhidrosis, working in a wet environment and common areas are predisposing factors for tinea pedis .  It has four clinical forms. The intertriginous subtype manifests itself with maceration, cracking and some scaling between the toes . Hyperkeratotic tinea pedis is a chronic type and manifests itself with dense plantar scaling and erythema. It also involves the lateral surfaces of feet. There is usually no involvement on the dorsal surfaces. It is usually bilateral and can infect the hands (4). The vesiculobullous variant of tinea pedis occurs infrequently, and its clinical resemblance to dyshidrotic eczema often makes accurate diagnosis challenging. The acute ulcerative form represents the least common presentation of tinea pedis. Recurrence of the infection is frequently associated with inadequately treated fungal involvement of the nails, which can act as a reservoir for reinfection. Hence, through examination of the nails is essential when evaluating patients with tinea pedis(5). Tinea pedis is a widespread condition, with over 70% of individuals affected at some point in their lives. Although antifungal treatments are widely available, the incidence of this infection has continued to rise in recent years. Onychomycosis associated with tinea pedis occurs more frequently in older adults. Certain populations, including miners, soldiers, and marathon runners, face a higher risk of dermatophyte infections due to factors such as wearing occlusive footwear, excessive sweating, and walking barefoot. Preventive supportive measures include keeping the spaces between the toes dry, using well-ventilated footwear and socks made from natural fibres, and protecting the feet when using shared facilities(6).

Types of  Tinea pedis:

1. Interdigital-type tinea pedis

Interdigital tinea pedis is the most frequent type of athlete’s foot. It typically appears between the fourth and fifth toes and can extend to the underside of the toes. Patients often report itching, burning, and an unpleasant odor. This condition has two main forms. One is a dry, scaly variety known as dermatophytosis simplex, where the skin between the toes becomes dry and shows mild peeling(8).

2. Bilateral Moccasin-type tinea pedis

Moccasin-type tinea pedis is a long-lasting and more serious form of athlete’s foot that affects the sole and sides of the foot. The infection looks as though a slipper or moccasin is wrapped around the foot, hence the name (Figures 2A and 2B). The moccasin type of tinea pedis is a persistent and more severe form of athlete’s foot that affects the sole and sides of the foot. Its name comes from the way the infection resembles a moccasin or slipper encasing the foot. The fungus Trichophyton rubrum is most often linked to this type. The infected skin usually becomes thickened, scaly, and inflamed, with redness spreading across the bottom and lateral edges. Small papules may also appear along the border of the reddened area surrounding the foot(9).

3. Vesiculobullous tinea pedis

Vesiculobullous tinea pedis is the third variety of fungal infection affecting the feet. In some cases, a pustular form may also occur. This type is characterized by the presence of blisters or pustules on the instep and nearby areas of the sole. It is considered less common compared to other forms of tinea pedis(Figure 3). When diagnosing this type of  tinea pedis, bacterial infection should also be considered and excluded through microscopy or culture. The fluid inside vesicles is typically clear, but the presence of pus usually suggests a secondary bacterial infection, most often caused by Staphylococcus aureus or group A Streptococcus(10 ).

Figure1: Interdigital tinea pedis

Figure 2: Bilateral moccasin type tinea pedis

Figure 3: Vesiculobullous type tinea pedis

Epidemiology :

Tenia pedis is a skin disorder characterized by a superficial fungal infection(11). Tinea pedis is most commonly caused by Trichophyton rubrum, though Trichophyton mentagrophytes and Epidermophyton floccosum are also frequent culprits. In addition, certain nondermatophyte molds such as Scytalidium hyalinum, Scytalidium dimidiatum, and Scopulariopsis brevicaulis can lead to infection, sometimes producing symptoms that resemble those caused by T. rubrum. The condition typically begins on the foot, and in some cases, patients develop the distinctive “two feet–one hand” pattern, the reason for which remains unclear. When tinea manuum is present, it is advisable to check for tinea pedis, although most individuals with tinea pedis do not simultaneously have tinea manuum. The same fungal species responsible for tinea pedis may also cause tinea manuum, with T. rubrum being the most frequent pathogen(12).

Diagnosis:

Doctors often diagnose tinea pedis by looking at the skin, but this method is not very reliable. Studies show that while clinical diagnosis has high specificity, its sensitivity is low, meaning many cases are missed. Reflectance confocal microscopy, which provides real-time imaging of the skin’s surface, can reveal branching hyphae and inflammation, but it is rarely used(13). A more common test is the KOH wet mount. In this method, scrapings from the edge of a lesion or vesicle are treated with potassium hydroxide (10–20%), sometimes with dimethyl sulfoxide. The KOH dissolves skin cells, leaving fungal hyphae and spores visible under the microscope. Adding dimethyl sulfoxide (20–40%) speeds up the process and avoids heating. Although the KOH test cannot identify the exact fungal species or confirm if the fungus is alive, it is simple, inexpensive, and results are available within two hours. Sensitivity is about 73% and specificity about 42%. If the first test is negative but symptoms strongly suggest tinea pedis, repeating the test is recommended(14).

Tinea pedis is a very common condition and can resemble many other skin disorders of the foot. The differential diagnosis includes infections such as Candida intertrigo, bacterial intertrigo, impetigo, cellulitis, herpes simplex, and interdigital erythrasma. It may also mimic inflammatory or dermatologic conditions like atopic dermatitis, xerosis, irritant or allergic contact dermatitis, dyshidrotic eczema, scabies, juvenile plantar dermatosis, psoriasis, pustulosis, keratoderma, keratolysis exfoliativa, pemphigus, mycosis fungoides, pityriasis rubra pilaris, friction blisters, and pitted keratolysis(15).

Pharmacotherapy:

Tinea pedis can be managed with topical antifungals, oral antifungals, or a combination of both. Medical therapy is the main treatment for tinea pedis; surgical care is usually not indicated in these patients. Tinea pedis is treated with topical antifungal agents; however, depending on patient’s response to topical agents and the severity of the infection, both topical and oral (i.e. systemic) agents may be used. Medications used to treat tinea pedis work by disrupting the synthesis of ergosterol, which is a crucial component of fungal cell membrane.

Topical antifungal therapy

Topical antifungal therapy is the primary treatment for superficial or localized tinea pedis. These medications are usually applied once or twice daily for 1–6 weeks (most often 2–4 weeks), depending on the severity of the infection, the drug used, and how well the lesions respond.

Several topical antifungal agents are available(16) including:

• Azoles: Clotrimazole, econazole, ketoconazole, sertaconazole, efinaconazole, miconazole, luliconazole, isoconazole, oxiconazole, sulconazole, tioconazole
• Allylamines: Naftifine, terbinafine
• Benzylamine: Butenafine
• Others: Ciclopirox, tolnaftate, amorolfine

Attaching topical antifungal drugs to special carriers such as noisomes, liposomes, ethosomes, or nanostructured lipids can improve their penetration through the stratum corneum and increase bioavailability, offering promising opportunities for future research.

Systemic antifungal therapy

Systemic therapy is recommended when tinea pedis is widespread, recurrent, chronic, resistant to topical treatment, associated with onychomycosis, or occurs in immunocompromised patients. Common oral antifungals include:

• Terbinafine: 62.5 mg/day (10–20 kg), 125 mg/day (>20–40 kg), 250 mg/day (≥40 kg) for 2 weeks
• Itraconazole: 3–5 mg/kg/day in two doses for 1 week (max 200 mg twice daily)
• Fluconazole: 6 mg/kg once weekly (max 150 mg weekly) for 2–6 weeks

Oral ketoconazole is no longer used due to serious side effects, especially liver toxicity, along with risks such as neurotoxicity, renal damage, pancytopenia, hormonal suppression, drug interactions, gastrointestinal upset, rash, rhabdomyolysis, headache, fatigue, and even suicidal ideation(17).

Alternative and complementary therapies

Natural remedies to treat tinea pedis (athlete’s foot). Several medicinal plants have antifungal properties and can help with this condition. Examples include:

• Red onion (Allium cepa) extract
• Griseococcin from puffball mushroom (Bovistella radicata)
• Impatiens tinctoria root extract
• Cestrum schlechtendalii leaf extract (from the Solanaceae family)
• Isodan flavidus leaf and twig extract (a traditional Miao medicine)
• Eucalyptus globulus leaf extract (from the Myrtaceae family)
• Coptis extract (from the Ranunculaceae family)
• Soleshine, a herbal mix made from Sal tree resin, neem leaves, henna, sesame oil, and castor oil
• Essential oils from Portuguese lavender (Lavandula luisieri) and lemon grass (Cymbopogon citratus)

Nanoparticle-based formulations are becoming more important for treating tenia pedis because they can deliver medicine directly to the target, improve absorption through the skin, and release the drug in a controlled way. They also help the active ingredients stay effective longer at the site of infection, increasing their overall availability. Nanotechnology is a safe and effective way to deliver medicines(18).

Solid Lipid Nanoparticles

Solid lipid nanoparticles (SLNs) have been recognized as one of the most successful lipid-based carriers since the early 1990s. They are widely used to improve the absorption of medicines that do not dissolve well in water when taken orally. SLNs are made of solid lipids that remain stable at room temperature and are safe for the body. Their size usually ranges between 50 and 1000 nanometers. SLNs offer several benefits: they are highly biocompatible, less toxic, and especially effective in delivering fat-loving (lipophilic) drugs(19). Solid lipid nanoparticles (SLNs) are tiny particles made of biocompatible fats. They can hold both water-loving (hydrophilic) and fat-loving (hydrophobic) drugs inside their solid structure. Once inside the body, they slowly release the medicine at the target site. Compared to other drug delivery systems, SLNs show greater promise because they are non-toxic, safe for the body, and easy to produce. That’s why they are widely used in biomedical applications(20).

Figure 4. Structure of Solid Lipid Nanoparticle

Drug release pattern from SLNs :

The way drugs are released from nanoparticles depends mainly on the particle size and how the drug is trapped inside the solid lipid nanoparticles (SLNs). Other factors, like how the drug interacts with the lipid matrix, also play a role. The release pattern of SLNs can be changed by external or internal triggers, such as temperature. For example, Chen and colleagues studied SLNs coated with cholesterol-PEG that carried the cancer drug doxorubicin. They found that the drug was released faster at acidic pH (4.7) than at normal pH (7.4). This happens because, at lower pH, the negatively charged lipid (lauric acid) becomes protonated and loses its attraction to the positively charged drug, allowing the drug to be released more easily in the acidic environment of cancer tissue. In general, SLNs often show a quick initial release of the drug (called burst release)(21).

Advantages(22):

• Lowers the risk of long-term or short-term toxicity
• Uses natural, biodegradable lipids (safe for the body)
• Can target specific sites in the body
• Improves absorption of medicine through the skin
• Allows controlled and steady release of the drug
• Can be preserved by freeze-drying (lyophilization)
• Boosts bioavailability of drugs that don’t dissolve well in water

Disadvantages(23):

• Limited capacity for pharmaceutical packaging.
• Drug extraction following a polymeric shift that happens in storage.
• A rather high percentage of dispersed water (70–99.9%).
• The low loading capacity of water-soluble drugs during the production cycle was caused by the partitioning effects.
• Incredible mobility of polymeric transitions

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