Fungal Skin Infections Notes - PDF

Fungal (Tinea spp.) skin infections RHCHP School of Pharmacy Self-Care Fall Facilitators Reading and References...

Fungal (Tinea spp.) skin infections RHCHP School of Pharmacy Self-Care Fall Facilitators Reading and References Required Leticia Shea, PharmD, BCACP This note packet [email protected] Optional 303-964-6182 Audio powerpoint presentation Slides from audio powerpoint Learning Objectives After studying the required readings, the student will be able to: 1. Identify the genera of fungi that generally cause tinea infections. 2. Identify most prevalent cutaneous fungal infection in humans. 3. List the risk factors for tinea infections. 4. Explain and define the different clinical presentations of tinea infections. 5. List mechanisms for spreading the infection(s). 6. Identify environmental factors that may contribute to the formation of tinea infections. 7. List chronic health problems and medications that can increase the risk for development of tinea infections. 8. Describe and differentiate the presentation of tinea infections and other skin infections. 9. Identify the accepted variants of tinea pedis. 10. Explain of the signs and symptoms tinea unguium. 11. Explain of the signs and symptoms tinea corporis. 12. Explain of the signs and symptoms tinea cruris. 13. Explain of the signs and symptoms tinea capitis. 14. Explain of the signs and symptoms tinea pedis. 15. List the treatment goals of treating fungal skin infections. 16. Compare and contrast the mechanisms of action of the pharmacologic therapies for tinea infections. 17. List the antifungal products available OTC. 18. Identify the indications for use of different nonprescription topical antifungal agents. (Preventative or treatment?) 19. Discuss and describe the different dosage forms available for antifungals. 20. Identify currently approved treatment for the prevention of athlete’s foot. 21. Discuss the role in therapy of aluminum salts. 22. Identify potential side effects of nonprescription topical antifungal agents. 23. Discuss potential drug-drug interaction between warfarin and topical miconazole cream. 24. Identify the species in which topical clotrimazole and miconazole nitrate demonstrate fungistatic/fungicidal activity. 25. Create a treatment plan (this includes agent, dosing frequency, and duration of therapy) for tinea corporis- paying close attention to the length of therapy needed to eradicate the infection. 26. Create a treatment plan (this includes agent, dosing frequency, and duration of therapy) for tinea cruris- paying close attention to the length of therapy needed to eradicate the infection. 27. Create a treatment plan (this includes agent, dosing frequency, and duration of therapy) for tinea pedis- paying close attention to the length of therapy needed to eradicate the infection. 28. Differentiate between the signs and symptoms of tinea infections, that are appropriate for self-treatment from those that require additional medical attention. 29. Discuss and describe alternative therapy options for fungal infections. 30. Provide counseling points to ensure a patient understands the appropriate use of the product formulations for tinea infections.  Introduction In this packet we will be discussing superficial fungal infections, such as those found on the feet, body, groin, hair. Superficial fungal infections (tinea infections) Superficial fungal infections (tinea infections) are caused dermatophytes. The most common pathogenic dermatophytes are species of Microsporum, Trichophyton, and Epidermophyton. Dermatophytes are species of fungi that require keratin for growth. Since keratin is found in the stratum corneum, hair, and nails, these are common body sites for fungal infections. Dermatophytes secrete keratinase, an enzyme that digests this primary structural protein, resulting in scaling of the skin, loss of hair, or disfigured nails. While invasive fungal infections cannot be spread from person to person, superficial fungal infections are communicable through contact with infected people, animals, soil, or fomites. Clinical Presentation of Tinea Infections Tinea Infections Dermatophyte infections are referred to as tinea and then sub-classified based on the affected area of the body. Except for nail infections, patients may complain of itching. TABLE 1: Clinical Presentation Condition Body Part Affected Clinical Presentation Begins as small papules surrounding hair shafts; hairs may break off at level of scalp, leaving black dots on the surface; Tinea capitis Scalp if untreated, may lead to secondary bacterial infections, hair loss, or scarring. Lesions usually begin as small, circular, erythematous, scaly Tinea corporis (aka ringworm) Body surface areas Well demarcated red margins, usually on upper thighs or Tinea cruris (“jock itch”) Groin pubic area (more common in males) Tinea pedis Feet (most commonly between the toes) Usually characterized by fissuring, scaling and maceration Gradually lose shiny luster and become opaque; if untreated, Tinea unguium (aka onychomycosis) Nails become thick, rough, yellow and may separate from the nail bed  General Information on Tinea Please note the difference in application frequency and length of therapy for OTC treatment of jock itch vs. athlete’s foot. Label examples for OTC products are provided. Clotrimazole for athlete’s foot and ringworm: apply twice daily for 4 weeks, for jock itch, apply twice daily for 2 weeks. Butenafine and terbinafine are fungicial rather than fungistatic so the length of time needed is generally shorter than clotrimazole, however they all exhibit equal efficacy if used as recommended (for the length of time recommended per product). Butenafine for jock itch: apply once daily for 2 weeks, for athlete’s foot there are 2 options: twice daily for 1 week, or once weekly for 4 weeks. The 4 week treatment has a higher rate of cure than the 1 week regimen, but 1 week regimen provides cure for some. Terbinafine provides guidance based on the severity of the athlete’s foot. Terbinafine for athlete’s foot (only presenting within the toes), the recommendation is to use twice daily between the toes for one week. Terbinafine for athlete’s foot that is presenting on side or bottom of feet: application frequency increased to twice daily for two weeks. Terbinafine for jock itch or ringworm is recommended with once daily application for one week. Review the labeling for each of the labels to obtain application guidance patients will see. It is important to remember that dermatophytes like moist areas! Areas of the body that are commonly affected include feet, groin, scalp, and under the arms where moisture can accumulate. Anything which increases the temperature and hydration of the skin will interfere with the barrier function of the stratum corneum and increase a patient’s risk for fungal infection. These fungi are found everywhere in the environment! So something else (direct contact, decreased immune function, trauma to the skin, poor hygiene, etc.) usually has to be present for a topical fungal infection to occur. Tinea corporis (aka ringworm) is referred to as “ringworm” because it presents as rings or round red patches, with clear centers and red, scaly borders. Risk Factors for Tinea Infections Trauma to the skin (blisters from ill-fitting footwear, long-distance running): Trauma enables infecting fungi the opportunity to invade the outer layers of the skin Immunosuppressive conditions or medications (See below for more information on this higher risk population) Common use of public pools and bathing facilities Diabetes mellitus (See below for more information on this higher risk population) Impaired circulation Poor nutrition and hygiene Hyperhidrosis (excessive sweating) Occlusion of the skin (including nonporous shoes such as plastic or leather; tight-fitting clothing) Warm, humid climates (or conditions, such as wearing wet clothing for long periods) Obesity General Treatment Approach for Tinea Infections Most patients can usually effectively self-treat Tinea pedis, Tinea corporis, and Tinea cruris with topical OTC antifungals and non-pharmacologic measures See below for exclusions for self-treatment Patients should be referred to a primary care provider for T. unguium or T. capitis as they require prescription treatment. Exclusions for Self-Treatment of Fungal Infections Unsuccessful initial treatment (after verifying their initial treatment attempt had been utilized properly- dosing AND length of time of therapy) Nails or scalp involved (prescription therapy required) Face, mucous membranes, or genitalia involved (Increased risk of complications) Signs of possible secondary bacterial infection Condition is extensive, debilitating, highly inflamed Patient has systemic symptoms of fever and/or malaise Over-the-counter antifungal products may not be appropriate for all patients and all superficial fungal infections. For example, in patients with diabetes, or in those who are immunosuppressed, systemic therapy may be warranted. (If a patient has diabetes and their blood glucose levels are well controlled, they may be appropriate for self-treatment, however they should be aware of the risk and the importance of seeking additional medical attention if symtoms do not improve or worsen over the recommended time of treatment. If a patient has poorly controlled diabetes (A1c >= 7%) , it is not appropriate for them to self-treat a superficial fungal infection as they are more likely to have complications and the treatment will not be sufficient to overcome the infection.) Additionally, systemic therapy is generally necessary in patients with tinea capitis, tinea unguium, extensive moccasin-type tinea pedis (tinea pedis that affects the feet in a moccasin-like distribution, with the top of the feet spared, and usually both feet affected) or extensive tinea corporis or folliculitis associated with tinea corporis. Topical (Superficial) OTC Fungal Treatment Options There are many topical antifungal agents available over-the-counter. These include butenafine (Lotrimin Ultra cream), clotrimazole (Lotrimin cream, lotion), miconazole (Monistat-Derm, Micatin, Lotrimin powder and spray), terbinafine (Lamisil AT cream and solution), and tolnaftate (Tinactin powder, cream, spray). These products are available in a variety of dosage forms such as creams, solutions, lotions, sprays, shampoos, and powders. When choosing a formulation, efficacy and patient preference should be considered. In general, creams and solutions are more effective because they can be rubbed into the area of infection whereas sprays and powders are often not. Solutions may be preferred in hairy areas because they are easier to apply to these areas. Sprays and powders can serve as useful adjuncts to creams and solutions or in the prevention of tinea infection. Powders are also a useful adjunct in cases where the infection is “wet” or oozing. Dosing is different based on the type of infection and whether using a fungicidal vs fungistatic agent. Terbinafine and butenafine are fungicidal (kill fungus – think “suicidal”) vs. other agents which are fungistatic (inhibit the growth of fungus). The cidal agents are used for a shorter duration of time. Brand names do not all have the same ingredients. This is a common theme throughout the OTC aisles. Become comfortable looking at the active ingredients in products so that you are aware of what product you are recommending. Example: Lotrimin AF topical spray or powder is miconazole 2%; LotriminAF cream or solution is clotrimazole 1%; Lotrimin Ultra is butenafine 1%. There are variations in active ingredients as well as directions depending on the severity and location of the infection. Below are examples of this variation for the brand name “Lamasil”: TABLE 3: Lamasil Product Variation Products Active Ingredients Formulation Application Location Length of Treatment Lamasil AT (R) Athlete’s Foot Between the toes Twice daily x 1 week Terbinafine HCl 1% Cream Cream Bottom and sides of feet Twice daily x 2 weeks Lamasil AT (R) Athlete’s Foot Terbinafine HCl 1% Spray Between the toes Twice daily x 1 week Spray LamasilAT (R) Defence(R)Athlete’s Affected areas and between Twice daily x 4 weeks; 1-2x Tolnaftate 1% Spray Powder Foot Powder the toes daily to prevent athlete’s foot Imidazoles: Clotrimazole and Miconazole These agents act by inhibiting the biosynthesis of ergosterol and other sterols and by damaging the fungal cell wall membrane, thereby altering its permeability and resulting in the loss of essential intracellular elements. These drugs have also been shown to inhibit the oxidative and peroxidative enzyme activity that results in intracellular buildup of toxic concentrations of hydrogen peroxide; this toxicity may then contribute to the degradation of subcellular organelles and to cellular necrosis. Clotrimazole and miconazole nitrate are applied once in the morning and once in the evening for up to 4 weeks for athletes foot, or twice daily for 2 weeks for jock itch. Rare cases of mild skin irritation, burning, and stinging have occurred with their use. No drug-drug interactions have been reported with topical use of clotrimazole and miconazole nitrate for up to 4 weeks. Tolnaftate Although tolnaftate’s exact mechanism of action has not been reported, it is believed that tolnaftate distorts the hyphae and stunts the mycelial growth of the fungi species. Tolnaftate is the only nonprescription drug approved for both preventing and treating tinea infections. It acts on fungi that are typically responsible for tinea infections. Tolnaftate is valuable primarily in the dry, scaly lesions. Relapse of superficial fungal infections has occurred after tolnaftate therapy has been discontinued. Relapse may be caused by inadequate duration of treatment, patient nonadherence with the medication, or use of tolnaftate when an oral antifungal should have been used. As a cream, tolnaftate is formulated in a polyethylene glycol 400/propylene glycol vehicle. The 1% solution is formulated in polyethylene glycol 400 and may be more effective than the cream. The solution solidifies when exposed to cold but liquefies with no loss in potency if allowed to warm. These vehicles are particularly advantageous in superficial antifungal therapy because they are nonocclusive, nontoxic, nonsensitizing, water miscible, anhydrous, easy to apply, and efficient in delivering the drug to the affected area. The topical powder formulation of tolnaftate uses cornstarch/talc as the vehicle. Because the two agents absorb water, this vehicle not only is an effective drug delivery system but also offers a therapeutic advantage. The topical aerosol formulation of tolnaftate includes talc, alcohol, and the propellant vehicle. Tolnaftate (1% solution, cream, gel, powder, spray powder, or spray liquid) is applied sparingly twice daily after the affected area is cleaned thoroughly. Effective therapy usually takes 2 to 4 weeks, although some individuals (patients with lesions between the toes or on pressure areas of the foot) may require treatment lasting 4 to 6 weeks. Tolnaftate is well tolerated when applied to intact or broken skin, although it usually stings slightly when applied. Delayed hypersensitivity reactions to tolnaftate are extremely rare. As with all topical medications, however, discontinuation is warranted if irritation, sensitization, or worsening of the skin condition occurs. No drug-drug interactions have been reported with topical use of tolnaftate. Butenafine Like terbinafine, butenafine is a squalene epoxidase inhibitor. This action results in a deficiency in ergosterol and a corresponding accumulation of squalene within the fungal cell, causing fungal cell death. Similar to other antifungals, it also relieves the itching, burning, cracking, and scaling that can accompany the conditions that it treats. Effective treatment rates for interdigital tinea pedis with 1-week and 4-week application durations are reported to be approximately 38% and 74%, respectively. In clinical trials, Lotrimin Ultra (butenafine) kept users free of tinea pedis for up to 3 months.To date, clinical trials demonstrate a low incidence of side effects. No drug-drug interactions have been reported with topical use of butenafine hydrochloride. Terbinafine Like butenafine, this antifungal agent inhibits squalene epoxidase, a key enzyme in fungi sterol biosynthesis. Terbinafine hydrochloride is indicated for interdigital tinea pedis, tinea cruris, and tinea corporis. Similar to miconazole and clotrimazole, terbinafine hydrochloride should be applied sparingly to the affected area once to twice daily. (Once daily determined to be acceptable for longer lengths of therapy - i.e., 4 weeks instead of 1 week). In clinical trials, this drug demonstrated that it could cure tinea pedis with 1 week of treatment. However, complete resolution of symptoms may require up to 4 weeks of treatment. Clinical trials to date have demonstrated a low incidence of side effects for terbinafine hydrochloride. These side effects include irritation (1%), burning (0.8%), and itching/dryness (0.2%).No drug-drug interactions have been reported with topical use of terbinafine hydrochloride. How Do These Topical Agents Compare? Clinical trials evaluating the efficacy and cost of topical treatments in the treatment of superficial fungal infections of the skin found that that there is good evidence that clotrimazole, miconazole, tolnaftate, butenafine, and terbinafine are efficacious relative to placebo in the management of fungal infections of the skin. Agents such as terbinafine and butenafine are able to provide cure for superficial fungal infections faster; however, they are more expensive than the azole-type (clotrimazole, miconazole) antifungal agents. Overall findings suggest that they are not “more effective” in comparison to -azoles when each class is used for the appropriate length of time, however when you consider patient adherence to twice daily vs once daily, they may end up being more efficaceous based on how difficult it is to apply twice daily vs once daily- or twice daily for 2 weeks, vs twice daily for 4 weeks. Higher Risk Patient Popultion Considerations Patients with immunodeficiency or diabetes have a higher risk of complications. Patients with immunodeficiencies (which includes conditions such as HIV/AIDs and those with on immunosuppessive therapy- which may include patients with cancer, multiple sclerosis (MS), rheumatoid arthritis, etc.) should be referred for the treatment of any tinea infection (that includes those we are usually able to self-treat). Patients with diabetes MAY be appropriate for self-care, but it is important to obtain sufficient information about their condition- including their blood-glucose control, in order to determine if they are appropriate for self-care. It is equally important to obtaining information from your patient to take the time to counsel patients with diabetes as to the importance of when it is appropriate for them to self-treat and when it is imperative for them to seek additional medical attention. Diabetes, both types I & II, inhibit appropriate sugar (carbohydrate) metabolism. Patients who have their blood glucose under control are not necessarily at a higher risk. It is patients that do NOT have their blood glucose under control that are at higher risk for tinea infections as well as other infections and complications. These individuals should be referred to their physician in order to ensure they are able to treat their tinea infection appropriately. (More than likely will require stronger medication than that in which is available OTC.) Having high blood glucose provides an environment that promotes growth of fungi, in addition to bacteria. Depending on the severity of the patient’s condition- long term poor glucose control leads to damage throughout the body including nerve vessels, the heart, kidney... the list can be extensive. Patients with diabetes that have nerve damage (diabetic neuropathy) are unable or less able to feel sensations in their periphery- in particle, their feet. If they obtain a cut or sore on their feet, they may not be able to feel or see it. This can lead to infections and depending on the severity of the infections, it can even lead to amputations. So if a patient presents to the pharmacy with an inquiry on treatment for a superficial fungal infection, such as tinea pedis, it is important to know if they have diabetes- and if so, if their blood glucose is under control. Rather than simply stating that they are at risk for having an amputation (don’t laugh- I have heard a student counsel a patient with this threat)- explain the reasoning for the question. If they have diabetes, explain the importance of monitoring their feet during the treatment process and the importance of seeking additional medical attention if their condition does not improve or worsens. (Immediate discussion of amputation risks is not necessary). Alternative Therapy Options There are many “alternative” products available for superficial fungal infections. It is important to note they are not likely to have much research/studies to support their claims. “Harness the power of natural extracts” “100% natural” These statements have not been evaluated by the FDA. This product is not intended to diagnose, prevent, or cure any disease. Directions for product depicted to the right: “For alternative healing. Apply 3 times per day to the affected area until the condition has cleared.” Active Ingredients: Cymbopogon Citratus , Melaleuca Alternifolia , Lavandula Angustifolia , Eucalyptus Globulus , Pogostemon , Jojoba , Other natural ingredients Cymbopogon Citratus (Lemongrass): no studies for treatment of fungal infections. Lavandula Angustifolia (lavender): no studies for treatment of fungal infections. Eucalyptus Globulus topical application: Prolonged exposure or large amounts of eucalyptus oil can cause agitation, ataxia, drowsiness, muscle weakness, seizures, and slurred speech. The risk of toxicity greater in children. In a clinical study, treatment with a combination of eucalyptus oil and lemon tea tree oil caused burning, redness, itching, or stinging in up to 20% of the patients Pogostemon (Patchouli oil): no evidence Jojoba: no evidence The only one of these ingredients studied for fungal infections is Tea Tree oil (M. alternifolia). Tea Tree: Melaleuca alternifolia Some clinical research suggests that topical pure tea tree oil exhibits benefit for onychomycosis, if applied 3 times daily for 6 months. Studies evaluating diluted tea tree oil result in less or no benefit. Contraindications: Eczematous or inflamed skin (may cause irritation). Oral administration is associated with toxicity. Common side effects (topical application): Allergic reactions, burning, dryness, irritation, pruritus, redness, and stinging. What Factors Should I Consider When Recommending an Antifungal Product to a Patient? Review the patient’s medical history This will help you with patient counseling points specific to their disease state that should be followed to prevent future recurrence of infection Example: patients with diabetes mellitus need to control blood glucose levels because increased glucose in perspiration may promote fungal growth Patient Counseling Points: Taking an Antifungal Medication Apply the antifungal to the clean, dry, affected area; avoid getting the product in the eyes Massage the medication into the area Wash hands thoroughly with soap and water after applying the product Patients should be counseled on the importance of adherence/compliance, as these conditions may take between 2 and 4 weeks to resolve Patient Counseling Points: Non-Pharmacologic Therapy and Life-style Modifications for Topical Tinea Infections Don’t forget to ask for / review the patient’s medical history Patients living with diabetes should be counseled on appropriate glucose control, foot hygiene; or refer to be safe Patients with frequent recurrence of any superficial fungal infection should consult a primary care provider (as they may have another underlying medical condition) Patients should always be counseled on non-pharmacologic measures that should be followed during and after treatment of any of the previously dis- cussed fungal infections Keep skin clean and dry (cleanse skin daily) To prevent spreading to other parts of the body, use a separate towel to dry the affected area or dry it last Avoid sharing personal articles such as towels or clothing Launder contaminated items in hot water Avoid contact with infected fomites For patients with Tinea pedis, tips such as wearing protective footwear when using a common shower (like at the gym); wearing shoes that allow feet to “breathe” ; dust shoes with foot powder to help keep them dry Patient preference/Formulation Efficacy Some dosage forms are preferred for delivery of the active ingredient to the epidermis ӽ In general, creams, gels, and solutions are efficient and effective dosage forms ӽ Sprays and powders may be less effective since they are not rubbed into the skin ӽ Sprays and powders are best used as adjunctive therapy or as preventative therapy ӽ Obese patients may benefit from adjunctive topical talcum powders (to “absorb” excessive sweating) Monitoring Efficacy and Toxicity of Topical Antifungals Most of these products are well-tolerated, with only rare cases of local side effects such as mild skin irritation, burning, stinging, itching, and dryness No drug-drug interactions reported In general, the patient should begin to have some relief from itching, scaling, and/or inflammation within 1 week If improvement, patient should be counseled to continue therapy for recommended duration listed in table above If the disorder has not improved or has worsened, patient should be referred to primary care provider for further work-up / more aggressive therapy