Tinea pedis is a chronic fungal infection of the feet, very often observed in patients who are immunosuppressed or have diabetes mellitus. The practicing allergist may be called upon to treat this disease for various reasons. Sometimes tinea infection may be mistaken for atopic dermatitis or allergic eczema. In other patients, tinea pedis may complicate allergy and asthma and may contribute to refractory atopic disease. Patients with recurrent cellulitis may be referred to the allergist/immunologist for an immune evaluation and discovered to have tinea pedis as a predisposing factor. From a molecular standpoint, superficial fungal infections may induce a type2 T helper cell response (Th2) that can aggravate atopy. Th2 cytokines may induce eosinophil recruitment and immunoglobulin E (IgE) class switching by B cells, thereby leading to exacerbation of atopic conditions.
Types of Tinea Pedis
- Tinea pedis (foot)
- Tinea unguium (nails)
- Tinea manuum (hand)
- Tinea cruris (groin)
- Tinea corporis (body)
- Tinea capitis (scalp)
- Tinea faciei (face)
- Tinea barbae (beard)
- Tinea imbricate (overlapping pattern)
- Tinea nigra (black)
- Tinea Versicolor (various colors)
- Tinea incognito (disguised)
Dermatophytosis
- Tinea pedis (athlete’s foot) – a fungal infection of the feet
- Tinea unguium – a fungal infection of the fingernails and toenails, and the nail bed
- Tinea corporis – a fungal infection of the arms, legs, and trunk
- Tinea cruris (jock itch) – a fungal infection of the groin area
- Tinea manuum – a fungal infection of the hands and palm area
- Tinea capitis – a fungal infection of the scalp and hair
- Tinea barbae – a fungal infestation of facial hair
- Tinea faciei (face fungus) – a fungal infection of the face
Other superficial mycoses (not classic ringworm, since not caused by dermatophytes)
- Tinea versicolor: caused by Malassezia furfur
- Tinea nigra: caused by Hortaea werneckii
Chronic intertriginous tinea pedis – is characterized by scaling, erythema, and erosion of the interdigital and subdigital skin of the feet, most commonly affecting the lateral 3 toes.
Acute ulcerative tinea pedis – (most often caused by T. mentagrophytes var. interdigitale) typically begins in the 3rd and 4th interdigital spaces and extends to the lateral dorsum and/or the plantar surface of the arch. These toe web lesions are usually macerated and have scaling borders. Secondary bacterial infection, cellulitis, and lymphangitis are common complications.
Vesiculobullous tinea pedis – in which vesicles develop on the soles and coalesce into bullae, is the less common result of a flare-up of interdigital tinea pedis; risk factors are occlusive shoes and environmental heat and humidity.
Causes of Tinea Pedis
- Fungi thrive in moist, warm areas, such as locker rooms, tanning beds, swimming pools, and skin folds; accordingly, those that cause dermatophytosis may be spread by using exercise machines that have not been disinfected after use, or by sharing towels, clothing, or footwear, such as rental bowling shoes, ski boots, ice skates or roller skates.
- Opportunistic infections (infections that are caused by a diminished immune system) are frequent. The fungus from an athlete’s foot infection can spread to the groin through clothing. Tight, restrictive clothing, such as jockstraps, traps heat and moisture, providing an ideal environment for the fungus.[rx]
Innate Immune Response
- Dermatophytes contain cell wall carbohydrate molecules (β-glucan) that are recognized by innate immune mechanisms, such as Dectin-1 and Dectin-2, which activate toll-like receptor 2 and 4 (TLR-2 and TLR-4). Dectin-1 amplifies the production of tumor necrosis factor-α and IL-17, IL-6, and IL-10, all of which stimulate adaptive immunity.[rx,rx]
- Keratinocytes in the presence of dermatophyte antigens, such as trichophytin, release IL-8, a potent neutrophilic chemo-attractant. A recent study shows the involvement of TLR-2 and TLR-4 in localized and disseminated dermatophytosis due to T. rubrum. Reduced expression of TLR-4 in the lower and upper epidermis of both localized and disseminated dermatophytosis patients was found compared to controls; TLR-2 expression was preserved in the upper and lower epidermis of all three groups.[rx,rx]
Adaptive immune response
- Humoral immunity – Humoral immunity to dermatophytes is not protective. High levels of specific IgE and IgG4 are detected in patients with chronic dermatophytosis which is responsible for positive (IgE mediated) IH tests to Trichophyton. On the other hand, Ig levels are low in patients that present positive delayed type hypersensitivity (DTH) skin test. The IH skin test for Trichophyton is associated with the presence of serum IgE and IgG (mostly IgG4) against Trichophyton antigens, hallmarks of a Th2 response. Here, IL-4 produced by CD4 T-cells (Th2 cells) induces antibody isotype switching to IgG4 and IgE
- Cell-mediated immunity – Several experiments have shown that the resolution of dermatophytosis is mediated by DTH. Immunity to pathogens could be regulated by Th1 or Th2 subsets which would ultimately determine the outcome of the infection. An acute inflammatory response correlates with a positive DTH skin test to trichophytin and clearing of the infection whereas chronic infection is associated with high IH and low DTH.[rx]
Symptoms of Tinea Pedis
Specific signs can be
- Red, scaly, itchy or raised patches
- Patches may be redder on outside edges or resemble a ring
- Patches that begin to ooze or develop a blister
- Bald patches may develop when the scalp is affected
- Nails may thicken, discolor or begin to crack[10]
- Cracking and peeling skin on your feet, most commonly between your toes and on your soles
- Dry skin on your soles or sides of your feet
- Raw skin on your feet
- Discolored, thick, and crumbly toenails
- Ttoenails that pull away from the nail bed
- Itchy erosions and/or scales between the toes, especially between 4th and 5th toes
- Scale covering the sole and sides of the feet (hyperkeratotic/moccasin type, usually caused by T. rubrum)
- mall to medium-sized blisters, usually affecting the inner aspect of the foot (vesiculobullous type).
- It can also uncommonly cause oozing and ulceration between the toes (ulcerative type), or pustules (these are more common in tinea pedis due to T. interdigitale than that due to T. rubrum).
Diagnosis of Acute Ulcerative Tinea Pedis
Laboratory investigations
For a laboratory to provide optimal results, quantity and quality of material examined is critical. Scraping should be collected from the active margin and transported in a sterilized black chart paper which keeps the specimen dry thus, preventing overgrowth of bacteria contaminants. Following are the various laboratory tests that can be used for confirming a diagnosis of dermatophytosis.
- Direct microscopic examination – [rx] Treatment of skin specimen with 10–20% potassium hydroxide (KOH) is a quick and inexpensive bedside tool to provide evidence of dermatophyte infection. Positive scrapings are characterized by the presence of refractile, long, smooth, undulating, branching, and septate hyphal filaments with or without arthroconidiospores. False negative results are seen in 15% of cases. Fluorescent staining with optical brighteners (diaminostilbene) is the most sensitive method to microscopically detect fungi in skin scales as well as in specimens from nails and hair.[rx] These substances bind to chitin, the main cell wall component of fungi
- Culture and antifungal sensitivity – [rx] Sabouraud dextrose agar (SDA, 4% peptone, 1% glucose, agar, water) is the most commonly used isolation media for dermatophytosis and serves as the medium on which most morphologic descriptions are based. Development of the colony takes 7–14 days. Modified SDA, with the addition of gentamicin, chloramphenicol, and cycloheximide is more selective for dermatophytes as chloramphenicol inhibits the growth of saprophytic fungus. Dermatophyte test medium is an alternative to isolation media that contain pH indicator phenol red. It is incubated at room temperature for 5–14 days. Dermatophytes utilize the protein resulting in excess ammonium ion and alkaline environment which turn the medium from yellow to bright red.
Antifungal Susceptibility Testing
- Microdilution method – The broth microdilution assay for antifungal susceptibility testing of dermatophytes has been previously developed as a modification of the Clinical and Laboratory Standards Institute M38-A2 standard method. The final concentrations of terbinafine and itraconazole used is 0.06–32.0 μg/ml and for fluconazole, 0.13–64.0 μg/ml.[rx] A standardized inoculum is prepared by counting the microconidia microscopically. Cultures are grown on SDA slants for 7 days at 35°C to produce conidia.
- Sterile normal saline (85%) – is added to the agar slant, and the cultures are gently swabbed with a cotton-tipped applicator to dislodge the conidia from the hyphal mat. The suspension is transferred to a sterile centrifuge tube, and the volume is adjusted to 5 ml with sterile normal saline. The resulting suspension is counted on a hemacytometer and is diluted in RPMI 1640 medium to the desired concentration. Microdilution plates are set up in accordance with the reference method. The microdilution plates are incubated at 35°C and read visually after 4 days of incubation. The minimum inhibitory concentration is defined as the concentration at which the growth of the organism will be inhibited by 80% compared with the growth in the control well
- Minimum fungicidal concentration (MFC) determination – For determination of the MFC, 100-μl aliquots are removed from the assay wells showing no visible growth at the end of incubation and streaked onto SDA plates. The plates are incubated at 30°C for 7 days. The MFC is defined as the lowest drug concentration at which no visible fungal growth or colonies developed
- Dermatophyte identification – This can be based on colony characteristics, microscopic morphology, and physiologic tests. Dermatophytes can be distinguished based upon their morphology of the macroconidia. Few physiological tests are available which help in confirmation of certain species. In addition, special amino acid and vitamin requirements can differentiate Trichophyton species from others. Ability to hydrolyze urea differentiates T. mentagrophytes (urease positive) from T. rubrum(urease negative).
Histopathology
- Histology may be used in the diagnosis of Majocchi’s granuloma in which KOH examination of scale on the surface may more often be negative.
- When present, hyphae may be appreciated in stratum corneum on hematoxylin and eosin staining. Special stains most commonly used are periodic acid-Schiff and Gomori methenamine silver which helps to highlight hyphae
Dermoscopy
- The comma hairs, which are slightly curved, fractured hair shafts, and corkscrew hair shave been described as the dermoscopic marker of tinea capitis. Broken and dystrophic hairs are also seen. However, in tinea corporis, the involvement of vellus hair as seen on dermoscopy is an indicator of systemic therapy.[rx]
Polymerase chain reaction and nucleic acid sequence based amplification
These tests not only help in the rapid and early diagnosis of infection but also help in determining drug resistance,[rx] and include:
-
Uniplex PCR for direct dermatophyte detection in clinical samples: A PCR for the direct detection of dermatophytes in skin scales is available as in-house PCR-ELISA assay which separately identifies numerous dermatophyte species. In a pilot study, the sensitivity and specificity of the test compared to cultures was 80.1% and 80.6%
-
Multiplex PCR for fungal detection in dermatophytes: Commercially available multiplex PCR tests enable simultaneous amplification of 21 dermatomycotic pathogens with subsequent DNA detection by means of agarose gel electrophoresis.
New molecular methods like matrix-assisted laser desorption ionization-time of flight mass spectrometry
- It is based on the detection of biochemical characteristics, proteolytic degradation product which is a result of the activity of mycological infections or noninfectious diseases. These are represented by proteolytic degradation products of native proteins.
- The peptide patterns of affected samples are identified by comparison with known peptide spectra from skin disorders stored in an already existing database. This procedure is immensely time-saving, as it enables simultaneous identification of up to 64 dermatophyte strains, with results coming back within 24 h.[rx]
Reflectance confocal microscopy
- It provides in vivo imaging of the epidermis and superficial dermis at cellular level resolution and can be used to detect cutaneous fungi and parasitic infestations.[rx] Branching fungal hyphae can be detected over an erythematous annular scaly patch. Advantage of the test is noninvasive and in a retrospective analysis of the test by Friedman et al. sensitivity was found to be 100%.
Treatment of Acute Ulcerative Tinea Pedis
Non-pharmacological
Non-pharmacological treatment focuses on educating patients about the predisposing factors, and the chronic nature of the disease. Also, measures that are aimed at eliminating the moisture that provides the environment for infection and its recurrence should be discussed fully with the patients. Instructions about wearing open-toed shoes and avoiding skin maceration are essential.
Some of the prescription medications your doctor may prescribe for athlete’s foot include:
- Topical, prescription-strength clotrimazole or miconazole
- Oral antifungal medications such as itraconazole (Sporanox), fluconazole (Diflucan), or prescription-strength terbinafine (Lamisil)
- Topical steroid medications to reduce painful inflammation
- Oral antibiotics if bacterial infections develop due to raw skin and blisters
List of Oral Antifungal Therapies, Their Dosages, and Their Possible Side Effects
| DRUG | DOSE | SIDE EFFECTS |
| 1. Griseofulvin* | 375–500 mg qd 3–6 months | Nausea, Hepatotoxic, Photosensitivity, Headache, Leukopenia+, Neutropenia+ |
| 2. Azoles | ||
| A. Ketoconazole** | 200–400 mg qd 6–8 weeks | Hepatotoxic, Hepatitis Idiosyncratic rxn, Nausea, Vomiting, Diarrhea |
| B. Itraconazole | 100 mg qd 2–4 weeks | Abdominal pain, Increased transaminases |
| 400 mg qd 1 week | ||
| C. Fluconazole | 50 mg qd 6 weeks | Hepatotoxic+, Anaphylaxis |
| 100 mg qd 8 weeks | ||
| 150 mg q week 6 weeks | ||
| 3. Allylamines | ||
| A. Terbinafine | 125 mg qd 8 weeks | Headache, Rash, Cholestatic hepatitis, Blood dyscrasia Steven-Johnson Syndrome |
| 250 mg qd 2–6 weeks |
* Contraindicated in pregnancy ** Contraindicated in nursing women, + Rare side effect
Antifungal Agents for the Treatment of Tinea Infections
| AGENT | DOSAGE | COST (GENERIC)* | |
|---|---|---|---|
|
Tinea unguium |
|||
|
Terbinafine (Lamisil) |
250 mg orally every day for 12 weeks†or |
$1,171 ($1,047 to $1,080) |
|
|
500 mg orally every day during the first week of each month for four months |
$780 ($696 to $720) |
||
|
Itraconazole (Sporanox) |
200 mg orally every day for 12 weeksor |
$1,38 ($1,241 to $1,713) |
|
|
400 mg orally every day during the first week of each month for four months‡ |
$1,225 ($828 to $1,142) |
||
|
Tinea capitis |
|||
|
Griseofulvin, micronized (Grifulvin) |
20 mg per kg per day for eight weeks |
$467 ($467 to $578) for a child weighing 30 kg |
|
|
Terbinafine |
62.5 mg per day for four weeks§ |
$105 (—) for a child older than two years weighing 20 kg |
|
|
Tinea corporis, pedis, cruris |
|||
|
Butenafine (Mentax) |
Applied to the lesion and a 2-cm area surrounding the lesion once daily for approximately 14 days |
30 g: $84 (—) |
|
|
Terbinafine |
Applied to the lesion and a 2-cm area surrounding the lesion twice daily for approximately 14 days |
15 g: — ($32 to $38) |
|
|
Miconazole (Micatin) |
Applied to the lesion and a 2-cm area surrounding the lesion twice daily for approximately 14 days |
30 g, 2%: — ($3.20 to $3.30) |
|
|
Clotrimazole (Lotrimin AF) |
Applied to the lesion and a 2-cm area surrounding the lesion twice daily for approximately 14 days |
24 g: $9.77 ($6.42 to $8.60) |
|
*— Estimated cost to the pharmacist based on average wholesale prices (rounded to the nearest dollar) in Red Book. Montvale, N.J.: Medical Economics Data; 2008. Cost to the patient will be higher, depending on prescription filling fee.
†— Higher cure rate among nail regimens.
‡— Lowest cost among nail regimens.
§— Lower cost among scalp regimens.
List of Possible Drug-Drug Interactions with Oral Antifungal Therapy
| 1. Griseofulvin: |
| Aspirin, Oral contraceptives, Phenobarbital, Porfimer, Theophylline, Warfarin |
| 2. Ketoconazole: |
| Alcohol, Oral hypoglycemics, Phenytoin |
| 3. Itraconazole: |
| Alfentanil, Alprazolam, Amphotericin B, Agenerase, Antacids, Atorvastatin, Bexarotene, Buspirone, Busulfan, Carbamazepine, Cilostazol, Cimetidine, Cisapride, Citalopram, Clarithromycin, Cyclosporine, Diazepam, Didanosine, Digitoxin, Docetaxel, Dofetilide, Erythromycin, Famotidine, Felodipine, Grapefruit juice, Haloperidol, Indinavir, Isoniazid, Lansoprazole, Lovastatin, Methylprednisone, Midazolam, Nevirapine, Nifedipine, Omeprazole, Oral hypoglycemics, Phenobarbital, Phenytoin, Pimozide, Quinidine, Ranitidine, Rifabutin, Rifampin, Ritonavir, Saquinavir, Sildenafil, Simvastatin, Sirolimus, Sodium bicarbonate, Sucralfate, Tacrolimus, Triazolam, Trimetrexate, Verapamil, Vincristine, Warfarin |
| 4. Fluconazole: |
| Amphotericin B, Celecoxib, Cimetidine, Cisapride, Citalopram, Cyclosporine, Dofetilide, Felodipine, Glipizide, Glyburide, Hydrochlorothiazide, Lovastatin, Midazolam, Oral hypoglycemics, Phenytoin, Pimozide, Prednisone, Quinidine, Rifabutin, Rifampin, Sildenafil, Simvastatin, Sirolimus, Tacrolimus, Theophylline, Triazolam, Warfarin, Zidovudine |
| 5. Terbinafine: |
| Cimetidine, Cyclosporine, Nortriptyline, Rifampin, Terfenadine, Theophylline, Warfarin |
Home Care
- Your doctor may recommend that you soak your feet in salt water or diluted vinegar to help dry up blisters.
Alternative Therapy
- Tea tree oil has been used as an alternative therapy for treating athlete’s foot with some success. A study from 2002 reported that a 50 percent solution of tea tree oil effectively treated athlete’s foot in 64 percent of trial participants.
Prevention
Because fungi grow particularly well in a moist environment, it’s important to make sure you keep your feet dry. You might try the following, for example:
- Wash your feet with soap and water every day and dry them thoroughly, especially between the toes.
- Wash socks, bedding, and towels in water that’s 140°F (60°C) or higher. Combining washing socks and application of OTC antifungal recommendations should treat most cases of athlete’s foot. You can disinfect your shoes by using disinfectant wipes (like Clorox wipes) or sprays.
- Put antifungal powder on your feet every day.
- Don’t share socks, shoes, or towels with others.
- Wear sandals in public showers, around public swimming pools, and in other public places.
- Wear socks made out of breathable fibers, such as cotton or wool, or made out of synthetic fibers that wick moisture away from your skin.
-
Thoroughly dry your feet with a towel after having a shower or bath, or after swimming
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Wearing shoes that aren’t too tight and let your feet breathe
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Not wearing the same pair of shoes two days in a row
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Taking your shoes off as often as possible
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Dry feet and toes meticulously after bathing
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Use desiccating foot powder once or twice daily
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Avoid wearing occlusive footwear for long periods
-
Thoroughly dry shoes and boots
-
Clean the shower and bathroom floors using a product containing bleach
- Great shoes with antifungal powder. If treatment of tinea pedis is unsuccessful, consider reinfection, coexistent untreated fungal nail infection, reinfection due to an untreated family member, or an alternative diagnosis.
The following things can help keep you from getting athlete’s foot from infected flakes of skin and stop it from coming back:
-
Wearing flip-flops when using swimming pools, communal showers and changing rooms
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Not sharing towels, shoes, or socks
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Washing socks, bedding, and towels at 60 degrees Celsius or more
References
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