Manual of Dermatologic Therapeutics
7th Edition
© 2007 Lippincott Williams & Wilkins
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14
Fungal Infections
Sola Choi
Candidiasis
I. Definition and Pathophysiology
Candida albicans is a normal inhabitant of mucous membranes, skin, and the gastrointestinal tract, which can evolve from a commensal organism to a pathogen to cause mucocutaneous infection. Factors that predispose to infection include (i) a local environment of moisture, warmth, and occlusion, (ii) systemic antibiotics, corticosteroids and other immunosuppressive agents, or birth control pills, (iii) pregnancy, (iv) diabetes, (v) Cushing’s disease, and (vi) debilitated states. Immune reactivity to Candida is reduced in infants up to 6 months of age and in patients with lymphoproliferative diseases or acquired immunodeficiency syndrome (AIDS). However, most women with recurrent vulvovaginal candidiasis have normal cellular immunity. Recently, nonalbicans Candida strains have been recognized as an important pathogen, particularly in recurrent infections (1).
The resident bacteria on skin inhibit the proliferation of C. albicans. Cell-mediated immunity plays a major role in the defense against infection. In addition, C. albicans can activate complement through the alternative pathway. The innate immune system appears to respond to mannan, a C. albicans cell wall polysaccharide, through toll-like receptors 2 and 4 (2).
II. Subjective Data
In chronic paronychia, the area surrounding the nail is tender, and there is often a history of frequent wetting of the hands. Candida intertrigo, perlèche, and vulvovaginitis are often accompanied by pruritus and burning. The discomfort of oropharyngeal candidiasis may interfere with eating.
III. Objective Data
  • Paronychia is associated with rounding and lifting of the proximal nail fold, disruption of the cuticle, and erythema and swelling of the fingertip. The nail plate may display transverse ridging or greenish-brown discoloration.
  • Intertriginous lesions (inframammary, axillary, groin, perianal, interdigital) are red, macerated, and sometimes fissured. The lesions are well demarcated, with peeling borders, and often surrounded by satellite erythematous papules or pustules.
  • The white plaques of thrush can be scraped from mucous membranes with a tongue blade, in contrast to the fixed lesions of oral hairy leukoplakia. The underlying mucosa is bright red. Lesions may extend into the esophagus.
  • Perlèche presents with fissured erythematous moist patches at the angles of the mouth. Poorly fitting dentures or mouth breathing may be associated.
  • Candida vulvovaginitis is frequently associated with a vaginal discharge. There may be severe vulvar erythema and edema.
IV. Assessment
  • Direct examination of scrapings from lesions with potassium hydroxide (KOH) will reveal budding yeasts with or without hyphae or pseudohyphae. Hyphae are almost always seen in mucous membrane infection, but may be absent in skin infection. A rapid latex agglutination test is also available for diagnosis but offers little advantage over KOH in terms of sensitivity and specificity (3).
  • C. albicans grows readily within 48 to 72 hours on fungal or bacterial media. Specific identification is based on the presence of chlamydospores when the organism is subcultured on cornmeal agar.
  • Gram-negative rods may play a synergistic role in infection of intertriginous areas; Gram’s stain and culture of these areas can be helpful.
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  • It is important to address predisposing medical conditions and physical factors. For example, spermicide use increases susceptibility to recurrent vulvovaginal candidiasis.
V. Therapy
The imidazoles and broader-spectrum triazoles are used most often in the treatment of candidal infections. The pyridone derivative ciclopirox (Loprox) and the polyene antibiotic nystatin are also effective. The allylamines naftifine (Naftin) and terbinafine (Lamisil) and the benzylamine butenafine (Mentax) are fungistatic against Candida. Tolnaftate (Tinactin; see Chap. 40, Antiinfective Agents, sec. II.C.6) and undecylenic acid (Cruex; Desenex) are not effective against Candida.
Systemic treatment of vaginal infections has become widespread. Oral imidazoles and triazoles are also useful in chronic mucocutaneous candidiasis and recalcitrant candidal onychomycosis. Ketoconazole and, to a lesser degree, itraconazole have many drug–drug interactions owing to the inhibition of cytochrome P-450 3A4. Their use is contraindicated with simvastatin, lovastatin, cisapride, triazolam, midazolam, quinidine, dofetilide, and pimozide (4).
  • Paronychia
    • Successful treatment of a chronic paronychia often requires weeks to months, and nails will grow out normally within 3 to 6 months of the paronychia healing.
    • An imidazole such as ketoconazole (Nizoral), sertaconazole (Ertaczo), clotrimazole (Lotrimin, Mycelex), ciclopirox olamine (Loprox), or miconazole should be applied several times a day. Other effective agents include naftifine (Naftin), haloprogin (Halotex), or nystatin. If there is associated pain or edema, use a combined steroid-nystatin ointment (e.g., Mycolog II) or a topical corticosteroid cream along with the antifungal agent for the first several days. Overnight application under occlusion may increase effectiveness. Oral therapy may be helpful as well. In addition, the area should be protected during wet work by wearing waterproof gloves and cotton liners.
    • Two percent to 4% thymol in chloroform or absolute alcohol is a simple and effective alternative that is applied b.i.d. to t.i.d.
    • Amphotericin B (Fungizone) lotion or cream or 1% alcoholic solution of gentian violet may also be used. Because Amphotericin B and imidazole agents counteract one another, they should not be used simultaneously.
  • Intertriginous lesions
    • Education about the role of moisture and maceration is important. The following techniques may be recommended: (i) drying affected areas after bathing using a handheld hair dryer on low heat, at least once a day; (ii) supportive clothing and weight reduction; (iii) air conditioning in warm environments; and (iv) regular application of a plain or medicated powder (nystatin or miconazole) to the areas.
    • For very inflammatory lesions, open compresses three to four times a day with water or Burow’s solution (Domeboro) will expedite relief of symptoms.
    • A topical antifungal cream or nystatin or miconazole powder should be applied to the dried skin.
    • Gentian violet 0.25% to 2.0% and Castellani’s paint (fuchsin, phenol, and resorcinol) are older remedies which are effective but may sting and will stain clothing, bed linen, and skin.
  • Thrush
    • Clotrimazole buccal troches (10 mg) five times a day for 2 weeks are usually effective for oropharyngeal candidiasis in adults and older children. The dose for infants has not been well established.
    • Alternatively, nystatin oral suspension (400,000 to 600,000 units) q.i.d. is held in the mouth for several minutes before swallowing. The dosage for infants is 2 mL (200,000 units) q.i.d.
    • Oral fluconazole (50 mg daily) has been the mainstay of systemic therapy in the past (5). However, with frequent use in immunocompromised hosts, fluconazole-resistant candidiasis has been reported. In this situation, itraconazole 200 mg PO q.d. for 2 to 4 weeks may prove effective (4). Voriconazole (Vfend), a second-generation triazole antifungal, may also be useful (6). Anidulafungin,
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      a member of the novel class of antifungals, echinocandins, is equal in efficacy to fluconazole in the treatment of esophageal candidiasis, has few significant drug–drug interactions, and is well tolerated (7).
    • Amphotericin B (80 mg/mL) may be used as a rinse.
    • Gentian violet solution 1% to 2% may be tried in difficult or recurrent cases.
  • Vulvovaginitis
    • Imidazoles or triazoles are the first-line drugs. Fluconazole has the least potential for drug interactions and is considered the least toxic. Monthly treatment in women with chronic vulvovaginal candidiasis increases the time to recurrence, but long-term remission remains elusive (8).
    • Resistance to therapy may be due to infection with nonalbicans strains such as Candida glabrata and Candida tropicalis.
    • Topical therapies
      • Imidazole compounds are effective and are available in a wide array of formulations: 500-mg clotrimazole vaginal tablet as a single dose (Gyne-Lotrimin), 200-mg miconazole tablet at bedtime for 3 days (Monistat-3), 100-mg vaginal tablet or suppository at bedtime for 7 days (Gyne-Lotrimin, Mycelex, Monistat-7), 2% butoconazole (Gynazole, Femstat) or miconazole (Monistat-7) cream daily at bedtime for 3 to 7 days, or 1% miconazole cream for 7 to 14 days (Gyne-Lotrimin, Mycelex). Prophylactic treatment may be helpful in chronic infection (see sec. 5c). Miconazole is pregnancy category C and clotrimazole, category B.
      • Terconazole (Terazol) is a fungicidal triazole topical preparation effective against many Candida strains. It is used as either a 3-day or a 7-day course (Terazol 7—0.4% cream for 7 days or Terazol 3—0.8% cream for 3 days). Terconazole is pregnancy category C and is not recommended for use during the first trimester.
      • Nystatin vaginal suppositories (100,000 units) may be slightly less effective. They are dosed twice daily for 7 to 14 days and then nightly for an additional 2 to 3 weeks. Topical nystatin is pregnancy category A.
      • Boric acid, 600 mg in a gelatin capsule, used intravaginally daily for 14 days, has been reported effective even in resistant Candida infections. It may cause local irritation or toxicity from systemic absorption.
      • In severe or very symptomatic Candida vulvitis, a topical corticosteroid for the first 3 to 4 days may be used.
    • Systemic therapies
      • A single oral dose of 150 mg of fluconazole has been U.S. Food and Drug Administration (FDA)-approved for the treatment of vaginal candidiasis. Its efficacy is equivalent to topical therapy and to oral itraconazole 200 mg at two doses 12 hours apart (9). Slightly greater efficacy may be achieved with fluconazole 100 mg/day for 5 to 7 days or itraconazole 200 mg/day for 3 to 5 days (10).
      • In a randomized controlled trial, neither oral nor intravaginal use of yogurt-containing Lactobacillus acidophilus was shown to decrease candidal infection (11).
      • Recurrent infection is defined as greater than three episodes/year in the absence of antibiotic use. Prophylactic regimens include clotrimazole (Gyne-Lotrimin) two 100-mg tablets intravaginally BIW, terconazole (Terazol) 0.8% cream one applicator/week, and fluconazole (Diflucan) 150 mg PO each month (12).
Dermatophyte Infections
I. Definition and Pathophysiology
The dermatophyte fungi are unique; having evolved to live on humans, they cannot survive elsewhere. However, what clinically resembles a dermatophyte infection can occasionally be caused by saprophytic or zoophilic fungi. In addition, although some dermatophyte species may tend to produce
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a specific clinical picture, reliable identification based on clinical characteristics alone is usually not possible.
Dermatophytes live in the superficial layers of the epidermis, nails, and hair. The presence of serum fungal inhibitory factor prevents them from invading living tissue. Poor nutrition and hygiene, a tropical climate, debilitating disease, atopy, and contact with infected animals, people, or fomites all predispose to fungal infection. Although pathogenic fungi are common in our environment, the overall incidence of infection is low, implying that host resistance is key. Acute infection tends to be associated with the rapid development of a delayed hypersensitivity to intradermal Trichophyton antigen. Protective cell-mediated immunity is acquired by 80% of patients after primary infection. Those who develop chronic infection tend to have poor cell-mediated immunity in vitro and immediate, as opposed to delayed, hypersensitivity to Trichophyton antigen.
II. Clinical Types of Infection
  • Tinea capitis may be transmitted by contact from child to child in an epidemic setting. Children between the ages of 3 and 7 are primarily affected. Pediatric infection has no gender predilection, but in the unusual case of adult infection, women outnumber men (13,14). Organisms have been cultured from such objects as barbers’ instruments, hairbrushes, theater seats, and hats. Crowded living conditions and low socioeconomic status may contribute to a high incidence in some urban areas. Trichophyton tonsurans has surpassed Microsporum audouinii as the primary causative organism in the United States.
    • Subjective data. Tinea capitis may be asymptomatic. Kerion, which is a deep, boggy swelling caused by an exaggerated host response to infection, is often painful.
    • Objective data. Patchy hair loss and broken hairs, inflammation, and scaling are characteristic. In kerion, a pustular folliculitis within an area of purulence and swelling is present which may heal with scarring.
  • Tinea barbae, infection of the beard area, is seen in adult men, much less commonly now than in decades past. It is typically acquired from animals.
    • Subjective data. Pruritus or pain may occur.
    • Objective data
      • Superficial infection is scaly, slightly to moderately erythematous, and may have an annular border (see sec. C.2).
      • Deeper infection is associated with kerion formation. Loss of facial hair is common, and commonly involves the angle of the jaw.
  • Tinea corporis, or infection of glabrous skin, affects all ages, but children are most susceptible. It is more prevalent in hot, humid climates and in rural areas.
    • Subjective data. Tinea corporis may be either asymptomatic or mildly pruritic.
    • Objective data. The typical lesions start as erythematous macules or papules that spread outward and develop into annular and arciform lesions with well-defined scaling or vesicular borders and central clearing. Tinea corporis is most common on the face, arms, and shoulders.
  • Tinea cruris, or “jock itch,” is often accompanied by tinea pedis. Friction and maceration predispose to infection, which is most common in warm climates.
    • Subjective data. Symptoms may be absent or may include pruritus and irritation from rubbing.
    • Objective data (see color insert). The eruption affects both the groin and upper inner thigh symmetrically with clearly defined borders. Lesions often extend into the gluteal fold and onto the buttocks.
  • Tinea of the hands (tinea manuum) and feet (tinea pedis). Tinea pedis is the most common of all fungal diseases, with 30% to 70% of the population having been infected at some time. Unlike other tinea infections, tinea pedis is generally a disease of adults. Like the others, it is seen more often in warm climates or seasons. The causative fungi may be found in shoes, flooring, and socks. Occlusive footwear is a predisposing factor. Simple contact is not sufficient for infection; concomitant disruption of the skin barrier is necessary. Various bacteria and yeasts can also produce symptomatic intertriginous scaling and maceration. For
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    example, Scytalidium dimidiatum and Scytalidium hyalinum produce an infection that is clinically indistinguishable from the moccasin or interdigital types of tinea pedis (14).
    • Subjective data. Pruritus is the most common symptom. Fissures may be painful and also predisposed to secondary bacterial infection. This is of particular importance in patients with diabetes, chronic lymphedema, and venous stasis.
    • Objective data
      • Tinea pedis may take several forms.
        • Interdigital scaling and maceration with fissures is most common.
        • Widespread fine scaling in a “moccasin” distribution is also frequent. The scaling usually extends up onto the sides of the feet and lower heel, where it exhibits a characteristic, well-defined, polycyclic scaling border.
        • A highly inflammatory, vesicular, or bullous eruption is uncommon and caused by a small subset of often zoophilic dermatophytes.
      • Tinea manuum is most often a mild erythema with hyperkeratosis and scaling over the palmar surfaces. Hand infection almost always accompanies foot involvement. Inflammatory lesions on the feet may cause a sterile vesicular “id” reaction on the hands, which may be confused with a primary fungal infection. Unilateral involvement of one hand and both feet is so characteristic that it immediately suggests this diagnosis.
  • Onychomycosis, or fungal infection of the nails, is seen in approximately 40% of patients with fungal infections in other locations. Clinical subtypes of infection include distal subungual, proximal subungual, white superficial, and candidal onychomycosis. The most common subtype, distal subungual, fungi spread from the distal lateral nail fold through the hyponychium to the nail. Fingernails are less commonly involved than toenails. Nondermatophyte molds such as Scopulariopsis brevicaulis, Fusarium sp., Acremonium, and Aspergillus sp. can account for up to 17% of cases (15).
    • Subjective data. The nails become brittle, friable, and thickened. Patients may be disturbed by the appearance, experience tenderness, or report that the nails catch on clothing.
    • Objective data. In distal subungual infection, changes are first seen at the free margin or distal lateral border of the nail as a white or yellow discoloration and progresses proximally. The nail may become thickened, crumbly, and lifted by accumulated debris. In some cases, the nail plate becomes entirely replaced by this keratinaceous debris.
III. Assessment
  • Definitive diagnosis is made by the microscopic identification of hyphae in scales or hair. In nails, the presence of hyphae usually indicates dermatophyte infection; however, secondarily invading saprophytic fungi may also be present. The sensitivity of the KOH can be enhanced with the addition of dyes or a fluorescent brightener (e.g., calcofluor white).
  • Histologic evaluation of nails using a periodic acid-Schiff (PAS) stain and fungal culture of nail clippings may be even more useful than KOH, depending on the clinical situation. Of the three methods, PAS is the most sensitive, and fungal culture, the most specific (16).
  • In the past, examination with a Wood’s lamp was routine in the assessment of tinea capitis, because fluorescing Microsporum species were the most common causative agents in the United States. Nonfluorescent T. tonsurans is now most common. Wood’s lamp examination is still helpful in certain circumstances.
IV. Therapy
  • Prophylactic measures
    • Intertriginous or interdigital areas should be dried thoroughly after bathing and a talc or antifungal powder should then be applied.
    • Footwear should fit well and be nonocclusive (avoid sneakers and plastic or rubber footwear).
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    • Patients with hyperhidrosis should wear absorbent cotton socks and avoid wool and nonwicking synthetic fibers. Control of the hyperhidrosis is vital to the therapy of concomitant fungal infection.
    • Clothing and towels should be changed frequently and laundered in hot water.
  • Local therapy. Limited infections can be usually treated with topical therapy alone.
    • Acute, inflammatory lesions with blistering and oozing should be treated with open wet compresses at least three times a day.
    • Many effective topical antifungals are available. The most effective classes include the imidazoles sertaconazole (Ertaczo), econazole (Spectazole), ketoconazole (Nizoral), clotrimazole (Lotrimin, Mycelex), miconazole (Micatin), oxiconazole (Oxistat), and sulconazole (Exelderm); the allylamines naftifine (Naftin) and terbinafine (Lamisil); the benzylamine butenafine (Mentax); and the pyridone derivative ciclopirox olamine (Loprox). Other useful topicals include haloprogin (Halotex) and tolnaftate (Tinactin). All but tolnaftate are also active against C.albicans infections.
      • Apply one of the medications mentioned in the preceding text b.i.d. Most lesions will respond in 1 to 3 weeks, but treatment should continue for at least 4 weeks to prevent relapse. Most topical antifungal agents have a high initial cure rate (80% to 90%), but relapse or reinfection is very common.
    • Undecylenic acid and its salts (Desenex and others) are modestly effective.
    • In thick, hyperkeratotic infection, such as on acral skin, concomitant therapy with keratolytic agents such as salicylic acid is helpful. This allows for more effective penetration of the antifungal agent as well as decreasing the burden of organisms through exfoliation. One regimen is to apply salicylic acid or lactic acid under occlusion overnight and to use an antifungal agent at another time of the day.
    • Severe interdigital tinea pedis is often associated with bacterial overgrowth. Aluminum chloride hexahydrate 20% applied b.i.d. for 7 to 10 days will decrease odor, itching, and maceration in most cases, because it is both drying and bactericidal.
    • Topical treatment of the nails is significantly less effective than oral therapy for onychomycosis from dermatophytes. It may be helpful in decreasing the chance of relapse after a course of systemic therapy. One small study showed relapse in 22% of patients at 36 months of follow-up after systemic treatment (17). More long-term studies need to be performed to properly evaluate relapse rates with various antifungal regimens.
      • Ciclopirox solution, 8%, in a nail lacquer formulation (Penlac) is applied daily to the entire nail surface and surrounding skin. The accumulated lacquer is removed weekly, and unattached nail and debris are trimmed regularly. The clinical cure rate is 5.5% after a 48-week course of therapy.
      • Naftifine (Naftin), terbinafine (Lamisil), and ciclopirox (Loprox) creams have some efficacy in onychomycosis. One study demonstrated clinical improvement in 8 of 10 patients after 6 months of therapy with 1% naftifine gel (18).
      • Urea ointment may be a useful adjunct to topical antifungal therapy. In one placebo-controlled study of 60 patients, 20% urea and 2% butenafine hydrochloride were used twice daily under occlusion to chemically avulse the nail. Clinical and mycologic cure by culture were achieved in 73%, with no relapses in 36 weeks of follow-up (19).
      • Reduction of a thickened, crumbling nail with an emery board or electric rotary sandpaper drill may reduce cosmetic and mechanical problems.
  • Systemic therapy
    • Allylamines
      • Terbinafine (Lamisil), a second-generation allylamine, is FDA approved for the treatment of onychomycosis and is considered the treatment of choice for this indication. Efficacy has also been demonstrated in tinea capitis and in certain deep fungal infections. It is well absorbed and rapidly delivered to the stratum corneum and nails where therapeutic levels are achieved within
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        hours and days, respectively. Levels remain therapeutic in the nails for up to 36 weeks after drug discontinuation. It is metabolized by the liver, necessitating dose adjustment in liver failure. The dose should be halved in patients with a creatinine clearance <50 mL/min. The recommended dose for the treatment of onychomycosis is 250 mg q.d. for 6 weeks for fingernails and for 12 weeks for toenails. Studies comparing pulse therapy of 250 mg b.i.d. 1 week of each month to continuous therapy over 3 months showed no difference in efficacy. For the treatment of tinea capitis, recommended doses are 250 mg q.d. for weight >40 kg, 125 mg q.d. for weight 20 kg to 40 kg, and 62.5 mg q.d. for weight <20 kg. Adverse effects include gastrointestinal disturbance (4.9%), taste disturbance, cutaneous eruptions including (rarely) Stevens–Johnson syndrome/toxic epidermal necrolysis, hepatobiliary dysfunction, visual disturbance, and rare hematologic disturbance including neutropenia. Liver enzyme abnormalities are typically asymptomatic and reversible. Symptomatic liver injury may occur in approximately 1 in 50,000 exposures, and fulminant liver failure has been reported (25). As with itraconazole, liver function testing is recommended in patients treated for longer than 6 weeks. Drug interactions through cytochrome P-450 enzymes include rifampin, cimetidine, terfenadine, caffeine, and cyclosporine. Terbinafine may be more efficacious than either pulse-dose or continuous-dose itraconazole (26).
    • Triazoles
      • Fluconazole (Diflucan) is FDA approved for the treatment of vaginal, oropharyngeal, and systemic candidiasis and cryptococcosis. It has also been effective in dermatophyte infections and onychomycosis. It has good oral absorption, is well tolerated, and is preferentially taken up in keratinized tissues, reaching concentrations up to 50 times that in plasma. This allows for once-weekly dosing in most cases. Drug interactions are less likely to be significant than with itraconazole (20). Doses for treating tinea corporis, cruris, and pedis are 150 mg/week for up to 4 weeks. For onychomycosis, recommended doses are 200 to 400 mg qwk for 3 months for fingernails and for 6 months for toenails. For kerion, the dose is 50 mg/day for 20 days. It is FDA approved for use in children and infants as young as 6 months, albeit for invasive infection, and is available as a liquid that may be given as 6 mg/kg day for 20 days or 8 mg/kg each week for 4 to 6 weeks in the treatment of tinea capitis.
      • Itraconazole (Sporanox) is effective in the treatment of histoplasmosis, blastomycosis, candidiasis, and dermatophyte infection. Its efficacy in the treatment of tinea capitis in children is equal to griseofulvin, and it is usually better tolerated (21). It is metabolized by the cytochrome P-450 system and may increase the levels of warfarin, cyclosporine, and digoxin among others. Its use is contraindicated with certain medications. Adverse effects include nausea, vomiting, and elevated aminotransferase levels in 5% to 10% of patients, and monitoring of liver function tests is recommended if therapy exceeds 6 weeks. The suggested daily dose is 200 mg q.d. for 7 days for tinea corporis/cruris and 200 mg b.i.d. for 7 days for tinea pedis/manus (22). For onychomycosis, pulse therapy with 200 mg b.i.d. for 1 week out of each month may be used instead of continuous therapy with 200 mg daily for 3 months (4). Two monthly pulses are recommended for fingernails, and three for toenails. Despite the lower overall dose drug during pulse therapy, there has been a case report of fulminant hepatic failure requiring transplantation associated with this dosing method (23). Levels of drug are higher in the epidermis than in the plasma, although not as high as with fluconazole. Therapeutic concentrations of itraconazole remain present in the nails up to 11 months following a three-pulse course. Itraconazole is also effective in onychomycosis due to nondermatophyte molds (24).
    • Imidazoles
      • Ketoconazole (Nizoral) is a broad-spectrum imidazole antifungal which is excreted in eccrine sweat. Therefore, methods to promote delivery of the drug to the skin, such as exercise 1 hour after dosing, are helpful. Although usually
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        well tolerated, there is a definite risk of hepatic injury (incidence between 1 in 10,000 and 1 in 15,000), including fatal hepatic necrosis. Other adverse side effects include anaphylaxis, interference with anabolic steroid synthesis, interaction with oral anticoagulants, and inhibition of hepatic metabolism of cyclosporine.
        • Therapy for dermatophyte infections is 200 mg (occasionally up to 400 mg) daily for the same period of time noted earlier for griseofulvin.
        • Use of ketoconazole in the treatment of dermatophyte infections has been largely replaced by the triazoles and allylamines because of their better safety profile.
    • Griseofulvin, a fungistatic antibiotic derived from Penicillium species, is effective against all dermatophyte fungi but not against bacteria, Malassezia, or Candida. The oral triazoles and allylamines are broader spectrum, better tolerated, and usually more cost effective and, therefore, have become the treatments of choice for most fungal infections requiring oral therapy (27). Griseofulvin is still useful in treating tinea capitis in children, particularly as it is the only systemic therapy currently FDA approved for this indication in this age-group. However, ongoing trials and accumulated data may soon make the use of griseofulvin even for this indication obsolete (28).
      • Tinea capitis requires griseofulvin administration for 6 weeks or longer. The recommended daily dose is 10 to 11 mg/kg for children. In general, children weighing 14 to 23 kg may take 125 to 250 mg/day of the oral suspension, and children weighing over 23 kg, 250 to 500 mg/day. Alternatively, a single dose of 1.5 to 2.0 g (which may be repeated in 3 to 4 weeks) will be effective in most children. In general, infections with Microsporum species require longer courses of treatment than those due to Trichophyton. Therapy should be continued for at least 2 weeks after clinical and mycologic cure. Shampooing with ciclopirox (Loprox), ketoconazole, or 2% selenium sulfide shampoo is recommended as adjuvant therapy.
Tinea Versicolor
I. Definition and Pathophysiology
Tinea versicolor is a chronic superficial fungal infection caused by members of the fungal genus Malassezia (Pityrosporum). These organisms are a part of normal skin flora and only produce color changes when they flourish beyond normal levels. Although historically Malassezia furfur has been implicated as the cause, recent evidence suggest that Malassezia globosa may be the predominate species in most cases. The eruption is found worldwide, is seen most commonly in young adults in temperate zones, and accounts for approximately 5% of all fungal infections. Factors predisposing to clinical infection include (i) pregnancy, (ii) serious underlying diseases, (iii) a genetic predisposition, (iv) high plasma cortisol, as in patients taking corticosteroids, and (v) a warm and humid climate. Tinea versicolor often persists for years because of inadequate treatment, reinfection, or an inherent predisposition to infection.
Tinea versicolor has a unique propensity to present either hyper- or hypopigmented lesions, hence its name. Hypopigmentation has been attributed to the causative organism’s production of azelaic acid, a dicarboxylic acid that interferes with melanin synthesis and may also be directly cytotoxic to melanocytes (29). The cause of hyperpigmented lesions remains obscure, although these lesions have a thicker keratin layer, and more organisms are present.
II. Subjective Data
The eruption is usually asymptomatic, and most patients object to its appearance.
III. Objective Data
Lesions vary in color from white and pink to brown but usually consist of round, coalescing macules and patches with fine scale found primarily on the trunk and neck. Facial lesions are more common in children than in adults and in women than in men, and these usually involve the forehead. Hypopigmented lesions are
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often noted by patients during summer months when they are accentuated by tanning of surrounding normal skin.
IV. Assessment
  • Examination of a KOH preparation will reveal numerous short, straight, and angular hyphae and clusters of thick-walled, round, and budding yeasts (see Chap. 38, Cytologic Smears, sec. II.G). In contrast to dermatophyte infections, a negative microscopic examination virtually excludes the diagnosis.
  • The causative organism can only be cultured on media enriched in C12- to C14-sized fatty acids.
  • Wood’s light examination will intensify the pigmentary changes and allow the extent and margins of involvement to be seen more readily. Affected areas may show a gold-to-orange fluorescence.
V. Therapy
  • There is an abundance of treatment options. Topical treatments should be applied to the entire torso from the neck to the waist, because lesions may be widespread as well as clinically unapparent. The appearance of the rash will improve within days, but to achieve a durable response, therapy should be continued for several weeks. The pigmentary changes resolve much more slowly, over months. Despite seemingly adequate therapy, relapse or reinfection is common, but typically responds to retreatment. The frequency of relapse has led some to recommend that therapy be continued for two consecutive nights each month for 1 year.
  • Useful agents
    • Topical
      • Ketoconazole (Nizoral) 2% shampoo applied to the skin, allowed to dry, and left on overnight either as a single dose or daily for 3 consecutive days (30).
      • Ciclopirox (Loprox) shampoo is effective when left on for several minutes before rinsing for 2 weeks.
      • Antifungal creams or solutions, including all imidazoles, allylamines, haloprogin, and tolnaftate, should be applied b.i.d. for 2 weeks.
      • Zinc pyrithione is found in many shampoos (DHS-Zinc, Head and Shoulders) and should be applied for 5 minutes daily for 2 weeks.
      • Selenium sulfide suspension (Selsun) applied and left in place for 5 to 10 minutes before rinsing is used for 7 to 14 consecutive days.
      • Keratolytic creams, ointments, or lotions containing 3% to 6% salicylic acid (Sebulex shampoo, 3% to 6% sulfur and salicylic acid ointment, 6% salicylic acid cream, 3% salicylic acid in 70% alcohol) applied overnight for 1 to 2 weeks in addition to a salicylic acid–containing soap may be helpful.
      • Sodium hyposulfite 25% should be applied to lesions b.i.d. for several weeks.
      • Retinoic acid cream (Retin-A cream) applied b.i.d. for 2 weeks will treat the tinea versicolor and may lighten pigmentation where it is applied. It is therefore useful in those particularly distressed by hyperpigmentation.
    • Systemic
      • Fluconazole given as a single oral dose of 400 mg cleared 65% of 20 patients treated at 8 weeks (31). A higher cure rate may be achieved by giving a second dose of 200 to 400 mg 1 week after the first dose.
      • Itraconazole 200 mg daily for 5 to 7 days is also effective (32).
      • Ketoconazole given as a 400-mg dose repeated in a week is equivalent in efficacy to 300 mg of fluconazole dosed in the same manner (33).
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