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AUGUST 2015 • PHARMACY PRACTICE • 13 An overview of athlete’s foot Dr. Vivienne Mak Senior Lecturer, School of Pharmacy Monash University Malaysia Bandar Sunway, Subang Jaya Esther Chan Research Assistant, School of Pharmacy Monash University Malaysia Bandar Sunway, Subang Jaya Introduction Pathogenesis thlete’s foot (tinea pedis) is a type of dermatophyte (fungal) infection which occurs commonly on the interdigital spaces, soles and sides of the feet.1,2 It is known as athlete’s foot as it is very common among athletes, and the fungi that causes it is found in areas where athletes often gather, such as locker rooms and public showers. This infection is contagious and recurrent in nature. The infection may also spread causing discolouration and thickening of the nails if the underlying cause is not treated.1 The most common pathogens involved in causing tinea pedis are Trichophyton rubrum sensu stricto, Trichophyton interdigitale and Epidermophyton floccosum, with T. rubrum as the most common pathogen.1–3 Athlete’s foot is a common condition and pharmacists are often consulted to provide advice on prevention and management of the condition. Tinea pedis is an infection caused by arthrospores or asexually reproducing conidia. These organisms favour high temperatures, alkaline pH and moist areas. Certain host factors such as damaged skin, maceration of the skin and immunodeficiency can facilitate the invasion of dermatophytes. The most common dermatophyte infections are due to the absence of a host factor, sebum, which is a natural inhibitory secretion. This fatty acid is not present in the plantar regions and therefore, infection may spread and occur on the plantar areas with no sebaceous glands.1,2 The dermatophyte fungi invade the superficial keratin of the skin by using enzymes such as keratinases, metalloproteases, lipases and ceramides. Very often, the infection is confined to the superficial layer. The immune system responds to the invasion of dermatophytes and a series or immune and inflammatory reac- A Earn 1 CPD point every month tions occur. However, certain dermatophytes such as T. rubrum, consists of mannans on their cells walls which can reduce the proliferation of lymphocytes, thereby inhibiting the body’s immune response. The clinical presentation of tinea pedis is thus dependent on the host’s defence mechanisms and the infecting dermatophyte.1,2 Clinical presentation Tinea pedis normally presents in four different forms: (i) interdigital, (ii) inflammatory (vesicular), (iii) chronic hyperkeratotic (moccasin) and (iv) ulcerative.1 Interdigital tinea pedis This is the most characteristic type of tinea pedis. The most common causative dermatophyte is T. rubrum followed by T. interdigitale.1,2 It presents with erythema, scaling, maceration and fissuring seen most often in the cleft between the fourth and fifth toes. The infection often starts with scaling first, and when the bacteria proliferate, maceration occurs.4 Typically, the dorsal surface of the foot is unaffected, but the neighbouring plantar areas may be involved.1,2 Inflammatory (vesicular) tinea pedis Inflammatory or vesicular tinea pedis is commonly caused by T. interdigitale. These hard, tense vesicles and lesions most often occur on the instep of the foot. The vesicular lesions settle deep in the epidermis and a bullae forms when the vesicles coalesce together. These bullae lesions with either clear or purulent fluid may rupture leaving an erythematous and scaly foot. The purulent fluid is a result of bacterial superinfection by Staphylococcus aureus or group A Streptococcus. These lesions develop rapidly and usually occur during warm weather.1,2 Chronic hyperkeratotic or moccasin tinea pedis This is another form of presentation which is most commonly caused by T. rubrum. This type is characterized by chronic plantar erythema with slight scaling on the sole of the foot and is often associated with nail involvement.4 Diffuse hyperkeratosis may also develop. The dry hyperkeratotic scaling normally involves the entire plantar surface without affecting the dorsal surface of the foot. However, lesions may spread across the dorsal surface of the foot in immunosuppressed patients and patients that apply topical corticosteroids.1 Patients with this type of tinea pedis normally will have a defect in their cell mediated immune response and are therefore unable to mount a delayed type hypersensitivity reaction to certain dermatophytes.4 This defect may predispose some people to tinea pedis. Ulcerative tinea pedis Ulcerative tinea pedis is typically caused by T. interdigitale, similar to inflammatory tinea pedis. It is characterized by rapidly spreading vesiculopustular lesions (macerated with scaly borders) appearing in the web spaces and it is frequently accompanied by a secondary bacterial infection.1,2 In certain cases, it can be severe enough to immobilize the patient. This infection usually begins between the third, fourth and fifth toes. It then extends to the lateral CONTINUED ON PAGE 14 14 • PHARMACY PRACTICE • AUGUST 2015 FROM “AN OVERVIEW OF ATHLETE’S FOOT” PAGE 13 dorsum and the plantar surface of the foot. This type of tinea pedis is normally seen in immunosuppressed or diabetic patients. The most common complications that may arise with this type are cellulitis, lymphangitis, fever and malaise.1,2 Prevalence It has been reported that more than 70 percent of the population will have this condition at some point in their life and approximately 15 percent of the world’s population has tinea pedis.2,5 It is estimated that the prevalence in Malaysia would be relatively high due to the hot and humid conditions which dermatophytes favour.6 Table 1 summarizes the prevalence studies conducted worldwide. There are also studies on tinea pedis in specific occupations and populations. One such study was conducted by Auger et al where rates of tinea pedis in marathon runners were explored—the prevalence rate was 22 percent.7 Due to the chronic nature of dermatophyte infections (tinea pedis in this case), the annual cost for treatment is estimated to be more than US$400 million in the US.1 Risk factors There are many risk factors for contracting tinea pedis. Although it affects all ages, it is more common in adults aged 31 to 60 with the incidence increasing with age. Children are also less likely to contract tinea pedis. Besides that, men are also more likely than women to be infected.2,3 Hot, humid, tropical environment, sweating, prolonged use of occlusive footwear, trauma to the feet and going to communal areas such as swimming pools and gymnasiums where bathrooms are shared are also risk factors for this infection.1,3,7 Moreover, certain occupational groups such as coal miners, soldiers and marathon runners are at a higher risk of contracting this infection as a result of prolonged use of occlusive footwear. Furthermore, having some form of immunodeficiency or cold feet resulting from poor circulation may also increase the risk of tinea pedis. Lastly, if the skin produces less fatty acid, the possibility of getting this infection is also higher.8 Symptoms Not everyone may experience symptoms due to tinea pedis. However, some may experience bothersome symptoms. Although these symptoms are minor, the infection can be persistent. Some of the symptoms include severe itching of the foot, blistering that itches, cracking and peeling of the skin between the toes and the soles, dry skin on the soles or sides of the feet, redness and scaling of the soles, unpleasant odour, burning and painful sensation in some instances (inflammatory tinea pedis), and occasionally discoloured, thick and crumbly toenails.8 Diagnosis Tinea pedis is normally diagnosed based on symptoms and a detailed patient history.9 However, this condition can be misdiagnosed as other scaly and pustular skin conditions such as psoriasis, herpetic infections, cellulitis, contact dermatitis, eczema, erythrasma, impetigo, bacterial toe-web infections, candidiasis and pemphigus.1,2 Hence, to obtain a definitive diagnosis, laboratory tests may be required. These tests include direct microscopic examination with potassium hydroxide (KOH) preparations and fungal culture of skin scrapings.1,9 Potassium hydroxide preparation This test can be used to identify fungal elements.1,2 Scaly specimen is required from the site of infection. For lesions without fluid, scales can be obtained from the border or the edge of the lesion whereas for blistering lesions, specimen can be obtained from the roof of the vesicle. As for pustular lesions, the purulent debris can be used.9 A positive KOH will show numerous septate hyphae.1 Fungal culture A fungal culture may be performed to confirm the diagnosis of tinea pedis and to ascertain its pathogenic species.1,2 Sabouraud’s glucose agar is the usual fungal culture medium. Antibiotics may be added to the medium to prevent bacteria from inhibiting the growth of the pathogenic dermatophyte. Adding cycloheximide in the media is useful to ascertain the pathogenic species.9 Studies for differential diagnosis To confirm the diagnosis of tinea pedis, studies for differential diagnosis may include a bacterial culture to rule out secondary infection; wood’s light inspection to rule out erythasma; and skin biopsy to differentiate a dermatophyte infection from other dermatoses.9 Complications There are several complications of tinea pedis which includes id reactions, bacterial superinfection, Majocchi’s granulomas, tinea incognito, lymphangitis and cellulitis. Spreading of infection to the nails, other skin areas and scalp is also another complication.1 Cellulitis Tinea pedis, especially interdigital tinea pedis, is the most common entry point for bacteria in cellulitis. Dermatophytes do not cause cellulitis per se but they cause scaling and fissuring of the skin which results in skin exposure. This provides the bacteria an open access into the body. Patients with lower limb cellulitis should always be examined for tinea pedis. If results are positive, antifungal therapy should be administered to prevent reoccurrence.1 Id reaction Id (dermatophytide) reaction can be defined as an allergic rash caused by local inflammatory fungal infection at a distant site. The most common cause for id reaction is a superficial fungal infection, specifically tinea pedis. It has been reported that the incidence of dermatophytids due to tinea pedis is 17 percent. The rash is often located on the hands Country Subject characteristics Prevalence Australia6 2,491 students aged 4 to 18 Overall prevalence was 5.2 percent, increasing in age from 2.1 percent in 4- to 6-year-olds to 9.7 percent in 16- to 18-year-olds. A higher proportion of males (6.0 percent) had tinea pedis than females (4.3 percent). Spain3 1,000 healthy volunteers aged 20 to over 90. Overall prevalence was 2.9 percent with a prevalence of 4.2 percent for men and a prevalence of 1.7 percent for women. Libya6 1,180 patients out of the 2,224 patients attending the Dermatology Clinics of the Tripoli Medical Centre (TMC) were confirmed to have fungal skin infections. Overall prevalence of tinea pedis was 8.1 percent. 12,903 cases of superficial fungal infections were seen at the National Skin Centre. Tinea pedis comprised of 27.3 percent of the cases. Singapore 6 Table 1: The global prevalence of tinea pedis. and sides of the fingers.1 Treatment usually involves an antifungal agent to treat the underlying cause and a steroid to treat the immunological reaction. dida species and bacteria.11 Tolnaftate is less effective than azoles and terbinafine and it may irritate the skin.10 4. Topical pyridones Majocchi’s granuloma Majocchi’s granuloma is a deep folliculitis due to dermatophyte invasion. This complication commonly occurs as a result of long term usage of potent topical corticosteroids, chemotherapeutic agents or systemic immunosuppression on unsuspected tinea.1 Systemic antifungal agents are usually necessary to treat this. Pharmacological management Medical treatment is the mainstay of treating tinea pedis. It can be treated with either a topical or an oral antifungal agent or a combination of both. For topical agents, the duration of therapy is typically 1 to 6 weeks depending on the potency of the antifungal agent. Early diagnosis and treatment is recommended as this can diminish the incidence of tinea unguium (tinea of the nail).1 Topical therapy There are several topical antifungal agents that can be used to treat tinea pedis. The two main classes of antifungal products are imidazoles (clotrimazole, econazole, ketoconazole, miconazole, oxiconazole and sulconazole) and allylamines (naftifine and terbinafine).9 1. Topical imidazoles Azoles such as bifonazole and clotrimazole are the treatment of choice.10 They are effective in all forms of tinea pedis but are exceptionally effective for interdigital tinea pedis as they are effective against dermatophytes and also Candida species. Some agents in this class (eg, econazole) also have antibacterial activity.2 2. Topical allylamines Allylamines are useful in treating all forms of tinea pedis. In vitro studies have demonstrated the potent activity of allyamines against dermatophyte fungi. Therefore, these agents are effective in treating patients with intractable tinea pedis (eg, chronic hyperkeratotic tinea pedis). Patients with this type of tinea pedis require a longer duration of therapy, typically 4 weeks. A quicker response is seen for patients with interdigital tinea pedis (1 week).2 Although terbinafine has a faster response rate compared to azoles (7 days for terbinafine and 2 to 4 weeks for azoles), it is expensive and less affordable for patients.10 3.Tolnaftate Tolnaftate is a thiocarbamate antifungal agent which may be fungistatic or fungicidal against susceptible fungi. It is active against dermatophytes but it is inactive against Can- Pyridones (ciclopirox olamine) are broad-spectrum agents which target dermatophytes, bacteria and Candida species.9 This class of drugs can be used for all forms of tinea pedis but it is exceptionally effective in interdigital tinea pedis, similar to the azoles.2 5. Dermatological agents Examples of dermatological agents include aluminum acetate (Burow’s solution), urea and ammonium lactate lotion. Burow’s solution is useful for vesicular type tinea pedis as it helps dry the lesions. Urea and ammonium lactate lotion are useful to decrease the scaling in patients with hyperkeratotic soles.1,2 6.Combination with topical corticosteroid antifungal mixtures Topical corticosteroids should be used with caution as it can exacerbate tinea infections and result in treatment failure. It may be used for a few days along with topical antifungal agents if there is inflammation of the lesions. The steroid should only be applied onto the lesion.1,9 7. Other agents i. Tea tree oil Clinical studies have suggested that tea tree oil is effective in treating tinea pedis. It is known to have antimicrobial properties and it has been used as a natural remedy for various skin conditions. A study conducted in Australia displayed marked clinical response of 25 percent and 50 percent tea tree oil with a response rate of 72 percent for 25 percent tea tree oil and 68 percent for 50 percent tea tree oil.12 ii.Ajoene Ajoene is a garlic-derived organic trisulfur which contains antifungal activity. It has been shown that 0.4 percent of ajoene used topically in shortterm treatment resulted in 79 percent cure rates. This agent may be as effective as topical terbinafine in treating tinea pedis and may be a cheaper alternative to topical terbinafine.13 iii. Undecylenic acid Undecylenic acid liquid is a fungistatic antifungal agent. It is less effective compared to azoles, terbinafine and tolnaftate and it may irritate the skin.10 iv. Whitfield’s ointment Whitfield’s ointment consists of benzoic acid and salicylic acid in a white soft paraffin base. It is a cheap- CONTINUED ON PAGE 15 AUGUST 2015 • PHARMACY PRACTICE • 15 FROM “AN OVERVIEW OF ATHLETE’S FOOT” PAGE 14 er alternative to the other usual antifungal preparations. However, duration of therapy is usually longer (up to 1 month).14 v.Oleozon Oleozon is obtained from the reaction of sunflower oil and the ozone (also known as ozonized sunflower oil). This product has antimicrobial effects and germicidal action against viruses, bacteria and fungi. A complete clinical cure was seen in 75 out of 100 patients (75 percent cure rate).15 However, the safety of this ozonized product is still a concern in Malaysia and more studies are needed to confirm its safety and efficacy. Systemic therapy Tinea pedis is normally responsive to topical agents. However, oral therapy may be necessary if there is involvement of the nails, if infection becomes widespread or severe, is unresponsive to topical therapy, or is recurrent.8 Systemic treatment is also used in patients with extensive chronic hyperkeratotic and inflammatory/vesicular tinea pedis. Usually, patients with diabetes or peripheral vascular disease and patients with immunosuppressed conditions will also require oral treatment.2 Examples of oral treatment are terbinafine 250 mg, griseofulvin, fluconazole 150 mg and itraconazole 200 mg. Treatment should continue until clinical resolution of the infection is achieved, normally between 2 and 6 weeks. In most cases, a 4-week course is usually sufficient. Griseofulvin requires a longer duration of therapy and has a narrow spectrum of activity but it is as effective and a cheaper alternative.10 To assess the effectiveness among oral antifungal agents, several studies have been conducted. There have been four studies comparing terbinafine (250 mg/day for 2 weeks) and itraconazole (100 mg/day for 2 to 4 weeks). Three of the four tri- als demonstrated a higher cure rate for terbinafine.5 Besides that, there are also studies comparing agents in the same class (eg, azoles). The trials showed a similar cure rate comparing ketoconazole (200 mg/day) and fluconazole (50 mg/day) in one trial and itraconazole (100 mg/ day) and fluconazole (50 mg/day) in another. For studies involving terbinafine and griseofulvin, terbinafine appeared to have better cure rates. In summary, these trials all suggest that terbinafine is superior compared to all the other oral antifungal agents with a high cure rate.5 Counselling points Before application of the topical antifungal agent, the affected area should be washed and completely dried. A thin layer of drug should then be applied to the affected areas.10 Patients with hyperkeratotic tinea pedis should apply the antifungal medication to the bottom and sides of the feet. For patients with interdigital tinea pedis, it is important to apply the medication to the spaces between the toes and also to the soles of the feet to prevent plantar-surface infection.1,2 Counselling on patient adherence and compliance is also important to ensure that the infection is completely eradicated. Due to the chronic and recurrent nature of the infection, patients should be advised to continue topical treatment for 2 weeks after they feel better or after clinical signs have resolved (terbinafine is an exception). Even after topical and systemic therapy, recurrence occurs in up to 70 percent of patients. Recurrence is partly caused by reinfection of the dermatophyte and the failure to eradicate the original infection. The main factor contributing to re-infection is the persistence of infective fungal elements on the skin.9 Prevention strategies Occlusive footwear gives rise to infection by creating an environment where dermatophytes thrive in. Thus, patients should try to keep their feet dry and cool and reduce moisture in shoes to prevent infection and also to prevent recurrence of infection. Old or worn out shoes that may be contributing to infection or the recurrence of infection should be discarded. Besides that, permeable, breathable or open-toe footwear is recommended for those with excessive sweating. Frequent sock changes are also important particularly during warm weather. Moreover, it is also important to remind patients to dry the spaces between the toes after bathing and to use a separate towel for infected areas. Sharing of towels and worn garments should also be avoided to prevent the spread of infection. Drying agents such as antifungal powders (miconazole), gentian violet, Burow’s solution soaks and aluminium chloride solution are also recom- mended to prevent the growth of fungi when occlusive footwear is worn.1,8,10 Dermatophytes can survive in chlorinated swimming pools at temperatures of 28 to 31oC for at least 123 days.1 Therefore, it is important to have regular feet washes and have protective footwear on (eg, thongs) in communal areas as contact with infected scales or dermatophytes on bath or pool floors may increase the chances of infection. Frequent washing of apparel is also recommended as infected scales can be present on clothing as well.1,8,10 Conclusion Tinea pedis is a common disease of the skin and it constitutes an important health problem to the society albeit not life threatening.1 There are many factors which may have contributed to the increasing incidence of tinea pedis. This includes the aging population, more fitness fanatical individuals and increasing participation in leisure-related activities such as swimming.5 This infection has become a worldwide epidemiological and economic problem not only to the health authorities but also to the public. As the saying goes ‘prevention is better than cure.’ As healthcare professionals, it is our duty to educate the public on prevention strategies and to have the public’s best interest in mind, to ensure patient compliance and comfort, whenever recommending a drug to them. References: 1.Ilkit M, Durdu M. Tinea pedis: The etiology and global epidemiology of a common fungal infection. Crit Rev Microbiol 2014. doi:10.3109/1040841X.2013.856853 2. Robbins CM. Tinea Pedis. New York © 1994-2015 by WebMD LLC; [updated 2014 Dec 10 cited 2015 April 8 ]. Available at: http://emedicine.medscape.com/article/1091684overview#a0104 3. Perea S, Ramos MJ, Garau M, et al. Prevalence and risk factors of tinea unguium and tinea pedis in the general population in Spain. J Clin Microbiol 2000;38(9):3226– 3230. 4. Leyden JL. Tinea pedis pathophysiology and treatment. J Am Acad Dermatol. 1994;31(3 Pt 2):S31–33. 5. Bell-Syer SE, Khan SM, Torgerson DJ. Oral treatments for fungal infections of the skin of the foot. Cochrane Database Syst Rev 2012;10:CD003584. 6. Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses worldwide. Mycoses 2008;51 Suppl 4:2–15. 7. Auger P, Marquis G, Joly J, et al. Epidemiology of tinea pedis in marathon runners: prevalence of occult athlete’s foot. Mycoses 1993;36(1–2):35–41. 8. DermNet NZ. Tinea Pedis © 2015 DermNet New Zealand Trust; [updated 2014 Sep 23 cited 2015 Apr 9]. Available at: http://dermnetnz.org/fungal/tinea-pedis.html 9. Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for superficial mycotic infections of the skin: tinea corporis, tinea cruris, tinea faciei, tinea manuum, and tinea pedis. Guidelines/Outcomes Committee. American Academy of Dermatology. J Am Acad Dermatol 1996;34(2 Pt 1):282–286. 10. Tinea. In: Australian Medicines Handbook 2015 [Internet]. Adelaide Australian Medicines Handbook Pty Ltd. Available at: https://amhonline.amh.net.au.ezproxy.lib.monash.edu.au/chapters/chap-08/fungal-yeast-infections/tinea.t 11. Drugs.com. Tolnaftate Bethesda © 2000-2015 Drugs.com; 2004 [cited 2015 Apr 15]. Available at: www.drugs.com/monograph/tolnaftate.html 12. Satchell AC, Saurajen A, Bell C, et al. Treatment of interdigital tinea pedis with 25% and 50% tea tree oil solution: a randomized, placebo-controlled, blinded study. Australas J Dermatol 2002;43(3):175–178. 13. Ledezma E, Marcano K, Jorquera A, et al. Efficacy of ajoene in the treatment of tinea pedis: a double-blind and comparative study with terbinafine. J Am Acad Dermatol 2000;43(5 Pt 1):829–832. 14. IFD. Management of Tinea Pedis United Kingdom: ©IFD 2015; [cited 2015 Apr 16 ]. Available at: www.ifd.org/protocols/tinea-pedis 15. Menéndez S, Falcón L, Simón DR, et al. Efficacy of ozonized sunflower oil in the treatment of tinea pedis. Mycoses 2002;45(8):329–332. To answer the quiz for your CPD points, please go to www.mims-cpd.com.my