Dermatologic Mycology

John C. Hall MD

Fungi can be present as part of the normal flora of the skin or as abnormal inhabitants. Dermatologists are concerned with the abnormal inhabitants, or pathogenic fungi. However, socalled nonpathogenic fungi can proliferate and invade immunosuppressed persons.

Pathogenic fungi have a predilection for certain body areas; most commonly they infect the skin, but the lungs, the brain, and other organs can also be infected. Pathogenic fungi can invade the skin superficially and deeply and are thus divided into these two groups.

Superficial Fungal Infections

The superficial fungi live on the dead horny layer of the skin and elaborate an enzyme that enables them to digest keratin, causing the superficial skin to scale and disintegrate, the nails to crumble, and the hairs to break off. The deeper reactions of vesicles, erythema, and infiltration are presumably due to the fungi liberating an exotoxin. Fungi are also capable of eliciting an allergic or id reaction.

When a skin scraping, a hair, or a culture growth is examined with the microscope in a wet preparation, the three structural elements of the fungi are seen: the spores, the hyphae, and the mycelia.

Spores are the reproducing bodies of the fungi. Sexual and asexual forms occur. Spores are rarely seen in skin scrapings, but they are the identifying structures on microscopic examination of fungal cultures.

Hyphae are threadlike, branching filaments that grow out from the fungus spore. The hyphae are the identifying filaments seen in skin scrapings in potassium hydroxide (KOH) solution.

Mycelia are matted clumps of hyphae that grow on culture plates.

Culture media vary greatly in content, but modifications of Sabouraud’s dextrose agar are used to grow the superficial fungi. Sabouraud’s agar and corn meal agar are both used to identify the deep fungi. Hyphae and spores grow on the media, and identification of the species of fungi is established by the gross appearance of the mycelia, the color of the substrate, and the microscopic appearance of the spores and the hyphae when a sample of the growth is placed on a slide. Some media show a color change when pathogenic fungi are isolated.

Classification

Superficial dermatophyte fungi are divided into three genera: Microsporum, Epidermophyton, and Trichophyton. Species of only two of these invade the hair: Microsporum and Trichophyton. As seen in a KOH preparation, Microsporum species cause an ectothrix infection of the hair shaft, whereas Trichophyton species cause either an ectothrix or an endothrix infection. The ectothrix fungi cause the formation of an external spore sheath around the hair, whereas the endothrix fungi do not. The filaments of mycelia penetrate the hair in both types of infection.

The species of fungi is correlated with the clinical diseases in Table 25-1.

Clinical Classifications

Superficial fungal infections of the skin affect various sites of the body. The clinical lesions, the species of fungi, and the therapy vary for these different sites. Therefore, fungal diseases of the skin are classified, for clinical purposes, according to the location of the infection. These clinical types are as follows:

Tinea of the feet (tinea pedis)
Tinea of the hands (tinea manus)
Tinea of the nails (onychomycosis)
Tinea of the groin (tinea cruris)
Tinea of the smooth skin (tinea corporis)
Tinea of the scalp (tinea capitis)
Tinea of the beard (tinea barbae)
Dermatophytid (generalized allergic reaction)
Tinea versicolor
Tinea of the external ear.

1. Correct diagnosis of a fungal infection is necessary. An oral antifungal drug should not be prescribed for a patient if the diagnosis has not been confirmed. Systemic antifungal agents are of no value in treating atopic eczema, contact dermatitis, psoriasis, pityriasis rosea, and so on.

2. Except for tinea of the scalp and nails, true fungal infections are noticeably improved after only 1 to 2 weeks of oral antifungal therapy. If there is no improvement, the diagnosis of the dermatosis as a fungus disease is erroneous and the therapy should be stopped.

TABLE 25-1 ▪ Relationship of Fungi to Body Areas

Fungus		Feet and Hands	Nails	Groin	Smooth Skin	Scalp	Beard
Microsporum species
	M. audouini	0	0	0	Uncommon	Uncommon	0
	M. canis	0	0	0	Common	Uncommon	Rare
	M. gypseum	0	0	0	Rare	Rare	0
Epidermophyton species
	E. floccosum	Moderately common	Rare	Common common	Moderately	0	0
Trychophyton species Endothrix species
	T. schoenleini	0	Rare	0	Rare	(Favus) rare, especially tropics	0
	T. violaceum	0	Rare	0	0	Rare	Rare
	T. tonsurans	0	Rare	0	Rare	Common	0
Ectothrix species
	T. mentagrophytes	Common	Moderately common	0	Common	Rare	Moderately common
	T. rubrum	Common	Common	Moderately common	Common	0	Rare

3. An adequate dosage is necessary, including (a) the correct daily dose for the particular type of fungal infection and (b) the correct duration of such dosage.

4. In general, systemic antifungal therapy should not be used to treat tinea of the feet. The recurrence rate after completion of therapy is very high.

5. Candidal infections should not be treated with oral griseofulvin. Very commonly, candidal intertrigo of the groin or candidal paronychias are erroneously treated with griseofulvin. Griseofulvin is of no value in these conditions. Because it is a penicillin-related drug, it can cause an allergic reaction in patients with a penicillin sensitivity.

6. Tinea versicolor does not respond to oral griseofulvin therapy.

7. So-called fungal infection of the ear does not respond to oral antifungal therapy. Most external ear diseases are not caused by a fungus.

There is a predilection for certain sites of tinea in which the frequency varies with the age of the patient. This is outlined in Table 25-2.

Tinea of the Feet (Tinea Pedis) (Figs. 25-1,25-2,25-3)

Tinea of the feet (athlete’s foot, fungal infection of the feet, and ringworm of the feet) is a very common skin infection. Many persons have the disease and are not even aware of it. The clinical appearance varies.

Primary Lesions

Acute form: Blisters (vesicular tinea pedis) occur on the soles and the sides of feet or between the toes.

TABLE 25-2 ▪ Sites of Tinea in Relationship to Age Groups

Tinea Site	Children (0-16 yr)	Adults
Tinea capitis (scalp)	Common	Very rare
Tinea corporis (body)	Common	Fairly common
Tinea cruris (groin)	Rare	Common (esp. males)
Tinea pedis (feet)	Rare (mimics eczema)	Very common
Onychomycosis (nails)	Very rare	Very common

FIGURE 25-1 ▪ Tinea of the foot. This dry, scaly form of fungus infection is usually due to T. rubrum. ▪ (Courtesy of Smith Kline & French Laboratories.)

Chronic form: Lesions are dry and scaly (“moccasin” tinea pedis).

Interdigital form: Macerated skin appears between the toes.

Secondary Lesions

Bacterial infection may occur in the acute and interdigital form. Fissures are not uncommon in the interdigital form.

Course

Recurrent acute infections can lead to a chronic infection. If the toenails become infected, a cure is highly improbable, because this focus is very difficult to eradicate and the fungus is ubiquitous and the patient’s susceptibility (almost always lifelong) cannot be decreased.

The species of fungus influences the response to therapy. Most vesicular, acute fungal infections are due to Trichophyton mentagrophytes and respond readily to correct treatment. The chronic scaly type of infection is usually due to Trichophyton rubrum and is exceedingly difficult, if not impossible, to cure.

FIGURE 25-2 ▪ (A and B) Acute vesicular tinea of the foot often due to T. mentagrophytes. (Courtesy of Schering Corp.)

Contagiousness

Experiments have shown that there is a susceptibility factor necessary for infection. Males are much more susceptible than are females.

Laboratory Findings

KOH-ink preparations of scrapings and cultures on Sabouraud’s media serve to demonstrate the presence of fungi and the specific type. A KOH preparation is a very simple office procedure and should be resorted to when the diagnosis is uncertain or the response to therapy is slow.

Differential Diagnosis

Contact dermatitis: Due to shoes, socks, gloves, foot powder usually on dorsum of feet; history of new shoes or new foot powder; fungi not found.

Atopic eczema: Especially on dorsum of toes in children; quite chronic; usually worse in winter; very pruritic; atopic family history; fungi not found.

Psoriasis: Affects soles and palms; pustular, thickened, well-circumscribed lesions; psoriasis elsewhere on body; fungi not found.

Pustular bacterid: Pustular lesions only especially on palms and soles; chronic; resistant to local therapy; fungi not found. This condition may be associated with a focus of infection, as in tonsil, teeth, or gallbladder.

Hyperhidrosis of feet: Can be severe and cause white, eroded maceration of the soles, accompanied by a foul odor. No fungi found. Zeasorb AF powder is helpful, as is Drysol solution.

Pitted keratolysis (keratolysis plantare sulcatum): Produces circular areas of erosions with a punched-out appearance on the soles of the feet; associated with hyperhidrosis; filamentous, gram-positive, branching microorganisms are found on skin scrapings caused by corynebacterium, actinomyces, Kytococcus sedentarius (Dermatococcus sedentarius) or Dermatophilus congolensis. Topical or systemic erythromycin is usually beneficial.

FIGURE 25-3 ▪ Tinea of the foot. (Courtesy of Schering Corp.) (A) Chronic tinea of side of foot. (B) Chronic tinea of sole due to T. rubrum (C) Chronic extensive tinea on patient on corticosteroids. (D) Chronic tinea extending up leg.

Treatment

Case Example: Acute Infection. An acute vesicular, pustular fungal infection of 2 weeks duration is present on the soles of the feet and between the toes in a 16-year-old boy. This clinical picture is usually due to the organism T. mentagrophytes.

First Visit

1. The fear of the infectiousness of athlete’s foot should be minimized but normal cleanliness emphasized, including the wearing of slippers over bare feet, wiping the feet last after a bath (not the groin last), and changing socks daily (white socks are not necessary).

2. Debridement. The physician or the patient should snip off the tops of the blister with small scissors. This enables the pus to drain out and allows the medication to reach the organisms. The edges of any blister should be kept trimmed, since the fungi spread under these edges. This debridement is followed by a foot soak.

3. Burow’s solution soak

Sig: One packet of Domeboro powder to 1 quart of warm water. Soak feet for 10 minutes b.i.d. Dry skin carefully afterward.

4. Antifungal cream 15.0

Miconazole (Monistat-Derm, Micatin), clotrimazole (Lotrimin, Mycelex), econazole (Spectazole), ketoconazole (Nizoral), ciclopirox (Loprox), oxiconazole (Oxistat), naftifine (Naftin), terbenifine (Lamisil), butenafine (Mentax, Lotrimin AF is over the counter), econazole(Ertaczo), and tolnaftate (Tinactin) (see Table 25-3 for detailed list of antifungal agents).

Sig: Apply b.i.d. locally to feet after soaking.

Sig: Apply b.i.d. locally for long term.

5. Rest at home for 2 to 4 days may be advisable, if severe.

6. Place small pieces of cotton sheeting or cotton between the toes when wearing shoes.

Five days later, the secondary infection and blisters should have decreased.

7. Oral terbenifine 250 mg once a day for 1 week is safe and very effective.

Subsequent Visits

1. The soaks may be continued for another 3 days or stopped if no marked redness or infection is present.

TABLE 25-3 ▪ Antifungal Agents

Antifungal Agents		Route of Administration	Organism Responsive	Side Effects
Allylamines
	Naftifine (Naftin)	Cream, gel	Dermatophytes	Rare
	Terbinafine (Lamisil)	Cream, spray, oral	Dermatophytes, tinea versicolor	Oral, rarely liver toxicity
Benzylamines
	Butenafine HCL (Mentax, Lotrimin Ultra Cream)	Cream	Dermatophytes	Rare
-Azoles
	Clotrimazole (Mycelex, Lotrimin cream, solution Troches suppositories)	Cream	Dermatophytes, tinea versicolor, Candida	Rare
	Econazole (Spectazole)	Cream	Dermatophytes, tinea versicolor, gram(+) bacteria	Rare
	Fluconazole (Diflucan)	Oral	Dermatophytes, tinea versicolor,cryptococcosis, Candida	Rare
	Itraconazole (Sporanox)	Oral (with food)	Dermatophytes, tinea versicolor, Candida, sporotrichosis, some deep fungi	Rare liver toxicity
	Ketoconazole (Nizoral)	Cream shampoo, oral	Dermatophytes, some deep fungi, Candida, tinea versicolor	Liver toxicity when oral
	Miconazole (Micatin, Monistat, Zeasorb AF)	Cream, powder spray, suppositories	Dermatophytes, tinea versicolor, Candida	Rare
	Oxiconazole (Oxistat)	Cream	Dermatophytes, tinea versicolor, Candida	Rare
	Sertaconazole (ertaczol)	Cream	Dermatophytes, tinea versicolor, Candida	Rare
Polyenes
	Amphotericin B (Fungizone, Abelcet)	Intravenous	Deep fungi sepsis, Candida sepsis	Common renal toxicity thrombophlebitis, hypokalemia
	Nystatin (Mycostatin)	Cream, ointment, powder, oral (not absorbed), pastilles, with triamcinolone (Mycolog II cream, ointment)	Candida	Rare
Miscellaneous
Flucytosine (Ancobon)		Oral, usually given with amphotericin B	Deep fungi sepsis, Candida sepsis	Liver, renal, bone marrow toxicity, gastrointestinal
Ciclopirox (Loprox, Penlac) Penlac Nail Lacquer		Gel, cream, shampoo, suspensions	Dermatophytes, Candida	Rare
Griseofulvin (Gris-Peg), Fulvicin, Grifulvin		Oral (evening with fatty meal) tablets, suspension		Rare
Selenium sulfide (Selsun, Head & Shoulders Intensive Treatment)		Shampoo (sometimes used as lotion)	Tinea versicolor	Irritation
Saturated solution of potassium iodide (SSKI)		Oral	Sporotrichosis	Gastrointestinal toxicity, bitter-taste, goiter if long-term
Tolnaftate (Tinactin)		Cream	Dermatophytes	Rare
Undecylenic acid (Desenex)		Cream	Dermatophytes	Rare
Capsofungin (Candidas)		Intravenous	Candidiasis sepsis, Aspergillosis sepsis	Common, fever, headache thrombophlebitis, rash
Micafungin (Mycoviral)		Intravenous	Candidiasis sepsis, esophagitis	Common, headaches, rash, fever, bone marrow thrombophlebitis
Vericonazole (Ufend)		Intravenous, oral	Candida sepsis, esophageal, Aspergillosis sepsis, Fusariesis sepsis	Visceral impairment, liver toxicity, fever, cardiac toxicity

2. The previously described salve is continued or the following salves are substituted: A combination of an antifungal cream and a corticosteroid, as in Lotrisone cream, is beneficial. Antifungal solutions, such as Lotrimin or Mycelex or Loprox are quite effective. Apply a few drops on affected skin and rub in.

3. Antifungal powder q.s. 45.0.

Zeasorb AF, Micatin, Tinactin, and Desenex.

Sig: Supply in powder can. Apply small amount to feet over the salve and to the shoes in the morning.

Case Example: Chronic Infection. A patient presents with chronic, scaly, thickened fungal infection of 4 years duration. In the past week, a few small tense blisters on the sole of the feet had developed. This type of clinical picture probably is due to the organism T. rubrum.

First Visit

1. The patient is told that the acute flare-up (the blisters) can be cleared but that it will be difficult and time-consuming to cure the chronic infection. If the toenails are found to be infected, the prognosis for cure is even poorer (see Tinea of the Nails section).

2. The blisters are debrided and trimmed with manicure scissors.

3. Any of the antifungal creams,

Sig: Apply locally to soles b.i.d., or

Antifungal solution 10.0.

Sig: Rub in a few drops b.i.d.

Subsequent Visits

1. Systemic antifungal therapy: This type of oral therapy is not recommended for chronic tinea of the feet. But the patient may have heard or read about the “pill for athlete’s feet,” so it would be wise for you to discuss this with the patient. If you mention that you cannot guarantee a cure, most patients will be content with keeping the chronic infection in an innocuous state with sporadic local therapy.

2. However, if the patient still wants to try oral therapy, then consider the systemic antifungal agents listed in the following section on Tinea of the Hands and in Table 25-3. Long-term pulse therapy is indicated.

Tinea of the Hands (Tinea Manum)

A primary fungal infection of the hand or hands is quite rare. In spite of this fact, the diagnosis of “fungal infection of the hand” is commonly applied to cases that in reality are contact dermatitis, atopic eczema, pustular bacterid, or psoriasis. The best differential point is that tinea of the hand usually is seen only on one hand, not bilaterally. It mimics dry skin in the common chronic form and may have fingernail involvement (Fig. 25-4A-E).

Primary Lesions

Acute form: Blisters on the palms and the fingers are seen at the edge of red areas.

Chronic form: Lesions are dry and scaly; usually there is a single patch, not separate patches.

Secondary Lesions

Bacterial infection is rather unusual.

Course

This gradually progressive disease spreads to fingernails. It usually is asymptomatic.

FIGURE 25-4 ▪ (A) Tinea of the left palm only, due to T. mentagrophytes. (B) Deep tinea of left hand, due to T. mentagrophytes. (C) Tinea of the palm, due to T. rubrum. (D) Tinea of the palm, of dry, scaly type, due to T. rubrum. (E) Tinea on the back of the hand.

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