LECTURE 3
MYCOTIC AFFECTION OF THE SKIN AND MUCOUS MEMBRANES.
FUNGAL INFECTIONS
There are a number of different types of infections caused by fungi, including …
· Superficial infections. These fungal infections affect the skin or mucous membranes. Superficial fungal infections (e.g., yeast vaginitis, oral thrush, and athletes foot) affect millions of people worldwide. Although rarely life-threatening, they can have debilitating effects on a person’s quality of life and may in some cases spread to other people or become invasive (systemic). Most superficial fungal infections are easily diagnosed and can be treated effectively.
· Systemic infections. These occur when fungi get into the bloodstream and generally cause more serious diseases. Systemic fungal infections may be caused either by an opportunistic organism that attacks a person with a weakened immune system, or by an invasive organism that is common in a specific geographic area, such as cocci and histoplasma. Unlike superficial infections, systemic fungal infections can be life-threatening.
· Opportunistic infections.As previously noted, the fungi attack people with weakened immune systems. These can be either systemic or superficial infections.
FUNGAL INFECTION SYMPTOMS
Fungi are a group of organisms that include microscopic ones like, yeast and mold, as well as bigger ones like, mushrooms. Various types of fungus are present on and inside the human body and most of them are beneficial. However, an overgrowth of beneficial fungi as well as presence of harmful fungi can both result in fungal infections, which can affect different body parts and can manifest themselves as infectious diseases. The symptoms of fungal infection differ with the affected body part and the causal agent.
Symptoms of Fungal Infections
Fungal infections are divided into three types – superficial, systemic and opportunistic. Superficial infections are very common and occur on the skin and mucous membranes of the body. There are various types of superficial fungal infections. This type is not considered life-threatening, but may affect the quality of life and sometimes become a systemic disease and disorder. Some of the superficial infections may also spread to other people. Unlike the first category, systemic fungal infections affect the organs inside the body as the fungus enters the blood stream. This type is more severe, as compared to the first category and can be life-threatening. The third type, called opportunistic fungal infections affects those with weak immune system and can be either superficial or systemic. These three categories have many sub-categories, which are classified on the basis of the affected body part and the type of fungus.
Infections on Skin and Nails.
There are different types of fungal skin infections, like, ringworm, tinea versicolor, jock itch and athlete’s foot. Fungus prefers the warm and moist areas of the skin and both molds and yeasts are found to affect the skin. Among the various types of fungal skin infections, athlete’s foot or Tinea pedis is the most common one and affects both men and women alike. It affects the web spaces between the toes and the skin of that part becomes soggy and itchy. It can turn pale and scaly too. Jock itch or ringworm of the groin (Tinea cruris) causes red rashes in the groin area. These scales can be itchy and are commonly found in men who sweat a lot. Ringworm of the body or Tinea corporis is mostly seen in exposed areas, like, limbs and abdomen. These red rashes have scaly edges that surround clear skin. Ringworm of the scalp is otherwise known as Tinea capitis, which causes patches on the scalp with hair loss and swelling of that area. Fungus on skin includes nail fungus infections (onychomycosis) and ringworm of the nails or Tinea unguium is the most common one. This condition makes the nails thick and crumbly.
TINEA VERSICOLOR: SIGNS AND SYMPTOMS
Tinea versicolor. It often looks like a rash.
The first sign of tinea versicolor is often spots on the skin.
The other signs and symptoms are:
The spots are lighter (sometimes darker) than the surrounding skin. The color of the spots can be white, pink, salmon, red, tan, or brown.
The spots can appear anywhere on the body.
Spots can be dry and scaly.
Skin may itch where the spots appear.
Spots become more noticeable as the skin tans. The yeast prevents the skin from tanning.
Spots grow slowly.
As the yeast grows, the spots can combine and form patches of lighter (or darker) skin.
The spots may disappear when the temperature drops and return in the spring or summer when the air gets warm and humid.
Sometimes the spots are so faint that people do not realize they have tinea versicolor. If tinea versicolor causes light spots on the skin, it can be mistaken for vitiligo. Vitiligo is a skin disease that causes the skin to lose its color.
TINEA VERSICOLOR: DIAGNOSIS, TREATMENT, AND OUTCOME
How do dermatologists diagnose tinea versicolor?
A dermatologist can often look at the skin and tell whether a patient has tinea versicolor. If there is any doubt, the dermatologist will do one of the following to make an accurate diagnosis:
· Gently scrape off a bit of the skin. This will be examined under a microscope.
· Look at the skin with a special device called a Wood’s lamp. The dermatologist will hold the Wood’s lamp about 4 or 5 inches from the affected skin. If the patient has tinea versicolor, the affected skin appears yellowish green in color when looked at with this lamp.
How do dermatologists treat tinea versicolor?
What a dermatologist prescribes depends on several things. These include where the tinea versicolor appears on the body, how much of the skin is affected, how thick the spots have grown, and climate.
Treatment for tinea versicolor may include:
· Medicine applied to the skin: This is the most common treatment. There are anti-fungal shampoos, soaps, creams, and lotions that can keep the yeast under control. The active ingredient in these medicines is often selenium sulfide, ketoconazole, or pyrithione zinc.
· Medicated cleansers: Tinea versicolor often returns, especially when a person lives in a place that is warm and humid. Using a medicated cleanser once or twice a month, especially during warm and humid periods, can prevent the yeast from overgrowing again.
· Anti-fungal pills: A dermatologist may prescribe these pills if the tinea versicolor covers a large area of the body, is thick, or often returns after it is treated. These pills are taken for a short time. But anti-fungal pills can cause unwanted side effects. They can interfere with other medicine that you take. A dermatologist will monitor a patient who takes this medicine.
Outcome
With treatment, the yeast is easy to kill. The skin, however, may stay lighter (or darker) for weeks or months. The skin will eventually return to its normal color. To help even out your skin tone, you should protect your skin from the sun and not tan.
Tinea versicolor can return. When the air outdoors is warm and humid, the yeast can quickly grow out of control. Some people who live in a tropical climate may need to use a medicated cleanser to prevent the yeast from overgrowing. People who live in an area that becomes warm and moist each spring may see tinea versicolor return every year.
TINEA PEDIS
Background
Tinea pedis has afflicted humanity for centuries, so it is perhaps surprising that the condition was not described until Pellizzari did so in 1888. The first report of tinea pedis was in 1908 by Whitfield, who, with Sabouraud, believed that tinea pedis was a very rare infection caused by the same organisms that produce tinea capitis.
Tinea pedis is the term used for a dermatophyte infection of the soles of the feet and the interdigital spaces. Tinea pedis is most commonly caused by Trichophyton rubrum, a dermatophyte initially endemic only to a small region of Southeast Asia and in parts of Africa and Australia. Interestingly, tinea pedis was not noted in these areas then, possibly because these populations did not wear occlusive footwear. The colonization of the T rubrum –endemic regions by Europeaations helped to spread the fungus throughout Europe. Wars with accompanying mass movements of troops and refugees, the general increase in available means of travel, and the rise in the use of occlusive footwear have all combined to make T rubrum the world’s most prevalent dermatophyte.
Pathophysiology
T rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum most commonly cause tinea pedis, with T rubrum being the most common cause worldwide. Trichophyton tonsurans has also been implicated in children. Nondermatophyte causes include Scytalidium dimidiatum, Scytalidium hyalinum, and, rarely, Candida species.
Using enzymes called keratinases, dermatophyte fungi invade the superficial keratin of the skin, and the infection remains limited to this layer. Dermatophyte cell walls also contain mannans, which can inhibit the body’s immune response. T rubrum in particular contains mannans that may reduce keratinocyte proliferation, resulting in a decreased rate of sloughing and a chronic state of infection.
Temperature and serum factors, such as beta globulins and ferritin, appear to have a growth-inhibitory effect on dermatophytes; however, this pathophysiology is not completely understood. Sebum also is inhibitory, thus partly explaining the propensity for dermatophyte infection of the feet, which have no sebaceous glands. Host factors such as breaks in the skin and maceration of the skin may aid in dermatophyte invasion. The cutaneous presentation of tinea pedis is also dependent on the host’s immune system and the infecting dermatophyte.
Patients with tinea pedis have the following 4 possible clinical presentations:
Interdigital tinea pedis
The interdigital presentation is the most characteristic type of tinea pedis,
with erythema, maceration, fissuring, and scaling, most often seen between the fourth and fifth toes. This type is often accompanied by pruritus.
The dorsal surface of the foot is usually clear, but some extension onto the plantar surface of the foot may occur.
This type can be associated with the dermatophytosis complex, which is an infection with fungi followed by an infection with bacteria.
Chronic hyperkeratotic tinea pedis
The hyperkeratotic type of tinea pedis is characterized by chronic plantar erythema with slight scaling to diffuse hyperkeratosis.
This type can be asymptomatic or pruritic.This type is also called moccasin tinea pedis, after its moccasinlike distribution. Both feet are usually affected.
Typically, the dorsal surface of the foot is clear, but, in severe cases, the condition may extend onto the sides of the foot.
Inflammatory/vesicular tinea pedis
Painful, pruritic vesicles or bullae, most often on the instep or anterior plantar surface, characterize the inflammatory/vesicular type.
The lesions can contain either clear or purulent fluid; after they rupture, scaling with erythema persists.
Cellulitis, lymphangitis, and adenopathy can complicate this type of tinea pedis.
The inflammatory/vesicular type can be associated with an eruption called the dermatophytid reaction, which develops on the palmar surface of one or both hands and/or the sides of the fingers. Papules, vesicles, and occasionally bullae or pustules may occur, often in a symmetrical fashion, and it may mimic dyshidrosis (pompholyx). This is an allergy or hypersensitivity response to the infection on the foot, and it contains no fungal elements. The specific explanation of this phenomenon is still unclear. Distinguishing between a dermatophytid reaction and dyshidrosis can be difficult. Dermatophytid reactions are associated with vesicular tinea pedis; therefore, a close inspection of the feet is necessary in patients with vesicular hand dermatoses. The dermatophytid reaction resolves when the tinea pedis infection is treated, and treatment of the hands with topical steroids can hasten resolution.
Ulcerative tinea pedis
The ulcerative variety is characterized by rapidly spreading vesiculopustular lesions, ulcers, and erosions, typically in the web spaces, and is often accompanied by a secondary bacterial infection.
Cellulitis, lymphangitis, pyrexia, and malaise can accompany this infection.
Occasionally, large areas, even the entire sole, can be sloughed.
This type is commonly seen in immunocompromised and diabetic patients.
Patients may have other associated dermatophyte infections, such as onychomycosis, tinea cruris, and tinea manuum. Tinea manuum is often unilateral and associated with moccasin-type tinea pedis (2-feet–1-hand syndrome). One study suggests the scratching habits of the infected individual result in transmission of the dermatophytes from the feet to the hand.
Differential Diagnoses
Laboratory Studies
In suspected tinea pedis, order direct potassium hydroxide (KOH) staining for fungal elements. Usually, the fungal elements are easily identified from scaly lesions. Using counterstains may enhance the visibility of the hyaline hyphae found in dermatophyte infections. Examples include the chitin-specific stains chlorazol black E, which stains hyphae blue-black, and calcofluor, which fluoresces hyphae under a fluorescent microscope.
A sample from skin scrapings may be obtained using a No. 15 blade.
When blisters are present, the highest fungal yield is obtained by scraping the roof of the vesicle.
A fungal culture may be performed to confirm the diagnosis of tinea pedis and to identify the pathogenic species.
Common media include dermatophyte test medium, Mycosel, or mycobiotic agar.
Use caution when choosing the correct culture medium because certain media (eg, dermatophyte test medium) contain cycloheximide, which inhibits the growth of nondermatophyte molds. Because these fungi can be a factor in tinea pedis, use agar without cycloheximide.
Medication Summary
Tinea pedis can be treated with topical or oral antifungals or a combination of both. Topical agents are used for 1-6 weeks, depending on manufacturers’ recommendations. A patient with chronic hyperkeratotic (moccasin) tinea pedis should be instructed to apply medication to the bottoms and sides of his or her feet. For interdigital tinea pedis, even though symptoms may not be present, a patient should apply the topical agent to the interdigital areas and to the soles because of the likelihood of plantar-surface infection.
Recurrence of tinea pedis is often due to a patient’s discontinuance of medication after symptoms abate. A simple strategy to increase a patient’s compliance is to prescribe a large quantity of topical medicine, which may motivate a patient to continue use until the entire tube is empty.
Moccasin-type tinea pedis is often recalcitrant to topical antifungals alone, owing to the thickness of the scale on the plantar surface. The concomitant use of topical urea or other keratolytics with topical antifungals should improve the response to topical agents. In addition, for moccasin tinea pedis caused by Scytalidium species, Whitfield solution, containing benzoic and salicylic acids, can be beneficial. However, patients with extensive chronic hyperkeratotic tinea pedis or inflammatory/vesicular tinea pedis usually require oral therapy, as do patients with concomitant onychomycosis, diabetes, peripheral vascular disease, or immunocompromising conditions.
Topical imidazoles
Clotrimazole 1% (Mycelex, Lotrimin)
Econazole (Spectazole Topical)
Ketoconazole topical (Nizoral)
Miconazole topical (Monistat)
Oxiconazole 1% cream (Oxistat)
Sertaconazole nitrate cream (Ertaczo)
Topical allylamines
Naftifine 1% cream and gel (Naftin)
Terbinafine topical (Lamisil)
Topical benzylamines
Butenafine (Mentax)
Itraconazole (Sporanox)
Fluconazole (Diflucan).
TINEA CRURIS
Background
Tinea cruris, a pruritic superficial fungal infection of the groin and adjacent skin, is the second most common clinical presentation for dermatophytosis. Tinea cruris is a common and important clinical problem that may, at times, be a diagnostic and therapeutic challenge.
Pathophysiology
The most common etiologic agents for tinea cruris include Trichophyton rubrum and Epidermophyton floccosum; less commonly Trichophyton mentagrophytes and Trichophyton verrucosum are involved. Tinea cruris is a contagious infection transmitted by fomites, such as contaminated towels or hotel bedroom sheets, or by autoinoculation from a reservoir on the hands or feet (tinea manuum, tinea pedis, tinea unguium). The etiologic agents in tinea cruris produce keratinases, which allow invasion of the cornified cell layer of the epidermis. The host immune response may prevent deeper invasion. Risk factors for initial tinea cruris infection or reinfection include wearing tight-fitting or wet clothing or undergarments.
Clinical symptoms
Large patches of erythema with central clearing are centered on the inguinal creases and extend distally down the medial aspects of the thighs and proximally to the lower abdomen and pubic area.
Scale is demarcated sharply at the periphery.
In acute tinea cruris infections, the rash may be moist and exudative.
Chronic infections typically are dry with a papular annular or arciform border and barely perceptible scale at the margin.
Central areas typically are hyperpigmented and contain a scattering of erythematous papules and a little scale.
The penis and scrotum typically are spared in tinea cruris; however, the infection may extend to the perineum and buttocks.
Secondary changes of excoriation, lichenification, and impetiginization may be present as a result of pruritus.
Chronic infections modified by the application of topical corticosteroids are more erythematous, less scaly, and may have follicular pustules.
Approximately one half of patients with tinea cruris have coexisting tinea pedis.
Erythematous-scale plaques and erythematous-liquenificated plaques were the most frequently found clinical types in an excellent Brazilian study. T rubrum was the prevalent dermatophyte in 90% of the cases, followed by T tonsurans (6%) and T mentagrophytes (4%).
Causes
The dermatophyte T rubrum is the most common etiologic agent for tinea cruris. In a Brazilian series, T rubrum was the prevalent dermatophyte in 90% of the tinea cruris cases, followed by T tonsurans (6%) and T mentagrophytes (4%). Other organisms, including E floccosum and T verrucosum, cause an identical clinical condition. T rubrum and E floccosum infections are more apt to become chronic and noninflammatory, while infection by T mentagrophytes often is associated with an acute inflammatory clinical presentation.
Differential Diagnoses
Familial Benign Pemphigus (Hailey-Hailey Disease)
Laboratory Studies
Microscopic examination of a potassium hydroxide (KOH) wet mount of scales is diagnostic in tinea cruris. The procedure for KOH wet mount is as follows:
Clean the area with 70% alcohol.
Collect scales from the margin of the lesion; use a scalpel or the edge of a glass slide for this purpose. Cover the collected scales with a cover slip; allow a drop of KOH (10-15% wt/vol) to run under the cover slip.
The keratin and debris should dissolve after a few minutes. The process can be hastened by heating the slide or by the addition of a keratolytic or dimethyl sulfoxide to the KOH formulation.
The addition of 1 drop of lactophenol cotton blue solution to the wet mount preparation heightens the contrast and aids in the diagnosis.
Negative results on KOH preparation do not exclude fungal infection.
Scale culture is useful for fungal identification but is a more specific, albeit less sensitive, diagnostic test than KOH wet mount.
Growth on Mycosel or Sabouraud agar plates usually is sufficient within 3-6 weeks to allow specific fungal identification.
Medical Care
Clinical cure of an uncomplicated tinea cruris infection usually can be achieved using topical antifungal agents of the imidazole or allylamine family. Consider patients unable to use topical treatments consistently or with extensive or recalcitrant infection as candidates for systemic administration of antifungal therapy, which has been proven safe in immunocompetent persons.
Prevention of tinea cruris reinfection is an essential component of disease management. Patients with tinea cruris often have concurrent dermatophyte infections of the feet and hands.
Treat all active areas of tinea cruris infection simultaneously to prevent reinfection of the groin from other body sites.
Advise patients with tinea pedis to put on their socks before their undershorts to reduce the possibility of direct contamination.
Advise patients with tinea cruris to dry the crural folds completely after bathing and to use separate towels for drying the groin and other parts of the body.
Antifungal agents
Terbinafine (Lamisil)
Butenafine (Mentax)
Clotrimazole topical (Lotrimin, Mycelex)
Miconazole (Micatin, Monistat-Derm)
Ketoconazole topical (Nizoral)
Econazole (Spectazole)
Naftifine (Naftin)
Oxiconazole (Oxistat)
Tolnaftate (Tinactin)
Ciclopirox (Loprox)
Itraconazole (Sporanox)
Sulconazole (Exelderm)
Griseofulvin (Fulvicin-U/F, Grifulvin-V)
Complications
Tinea cruris can become infected secondarily by candidal or bacterial organisms. In addition, the area can become lichenified and hyperpigmented in the setting of a chronic fungal infection.
Mistreatment of tinea cruris with topical steroids can result in exacerbation of the disease. Although patients may note initial relief of symptoms, the infection may spread.
Tinea Corporis
Background
Tinea corporis is a superficial dermatophyte infection characterized by either inflammatory or noninflammatory lesions on the glabrous skin (ie, skin regions except the scalp, groin, palms, and soles). Three anamorphic (asexual or imperfect) genera cause dermatophytoses: Trichophyton, Microsporum, and Epidermophyton. Dermatophytes may infect humans (anthropophilic), infect nonhuman mammals (zoophilic), or reside primarily in the soil (geophilic).
Pathophysiology
Dermatophytes preferentially inhabit the nonliving, cornified layers of the skin, hair, and nail, which is attractive for its warm, moist environment conducive to fungal proliferation. Fungi may release keratinases and other enzymes to invade deeper into the stratum corneum, although typically the depth of infection is limited to the epidermis and, at times, its appendages. They generally do not invade deeply, owing to nonspecific host defense mechanisms that can include the activation of serum inhibitory factor, complement, and polymorphonuclear leukocytes.
Following the incubation period of 1-3 weeks, dermatophytes invade peripherally in a centrifugal pattern. In response to the infection, the active border has an increased epidermal cell proliferation with resultant scaling. This creates a partial defense by way of shedding the infected skin and leaving new, healthy skin central to the advancing lesion. Elimination of dermatophytes is achieved by cell-mediated immunity.
Trichophyton rubrum is a common dermatophyte and, because of its cell wall, is resistant to eradication. This protective barrier contains mannan, which may inhibit cell-mediated immunity, hinder the proliferation of keratinocytes, and enhance the organism’s resistance to the skin’s natural defenses.
Clinical symptoms
1. Infected patients may have variable symptoms.
Patients can be asymptomatic.
A pruritic, annular plaque is characteristic of a symptomatic infection. Patients occasionally can experience a burning sensation.
HIV-positive or immunocompromised patients may develop severe pruritus or pain.
2. Tinea corporis may result from contact with infected humans, animals, or inanimate objects. The history may include occupational (eg, farm worker, zookeeper, laboratory worker, veterinarian), environmental (eg, gardening, contact with animals), or recreational (eg, contact sports, contact with sports facilities) exposure.
A few clinical variants are described, with distinct presentations.
Majocchi granuloma, typically caused by T rubrum, is a fungal infection in hair, hair follicles, and, often, the surrounding dermis, with an associated granulomatous reaction. Majocchi granuloma often occurs in females who shave their legs.
Tinea corporis gladiatorum is a dermatophyte infection spread by skin-to-skin contact between wrestlers. Tinea imbricata is a form of tinea corporis found mainly in Southeast Asia, the South Pacific, Central America, and South America. It is caused by Trichophyton concentricum.[9]
Tinea incognito is tinea corporis with an altered, nonclassic presentation due to corticosteroid treatment.
Tinea corporis can manifest in a variety of ways.
Typically, the lesion begins as an erythematous, scaly plaque that may rapidly worsen and enlarge, as shown in the image below.
As a result of the inflammation, scale, crust, papules, vesicles, and even bullae can develop, especially in the advancing border.
Rarely, tinea corporis can present as purpuric macules, called tinea corporis purpurica.One report describes 2 cases of tinea corporis purpurica resulting from self-inoculation with Trichophyton violaceum.
Infections due to zoophilic or geophilic dermatophytes may produce a more intense inflammatory response than those caused by anthropophilic microbes.
HIV-infected or immunocompromised patients often have atypical presentations including deep abscesses or a disseminated skin infection.
Majocchi granuloma manifests as perifollicular, granulomatous nodules typically in a distinct location, which is the lower two thirds of the leg in females.
Tinea corporis gladiatorum often manifests on the head, neck, and arms, which is a distribution consistent with the areas of skin-to-skin contact in wrestling.
Tinea imbricata is recognized clinically by its distinct scaly plaques arranged in concentric rings.
Causes
Tinea corporis can be caused by a variety of dermatophytes, although prevalence and patient history are very helpful in identifying the most likely organism.
Internationally, the most common cause is T rubrum.
T tonsurans, Trichophyton mentagrophytes, interdigitale, Trichophyton verrucosum, Microsporum canis, and Microsporum gypseum are also known to produce infection.
Tinea imbricata is caused by Trichophyton concentricum.
Dermatophytoses may be acquired from different sources, such as people, animals, or soil.
Contact with contaminated household pets, farm animals, and fomites (eg hair brushes, towels) can spread infection.
T verrucosum causes 98% of dermatophyte infections in cattle and is showing increasing prevalence of infection in human contacts.
T mentagrophytes is spread by rabbits, guinea pigs, and small rodents.[14]
Infection with M gypseum, a geophilic organism, can mimic tinea imbricata in presentation.
Because fungal arthroconidia can survive in the environment, recurrent outbreaks may occur.
Differential Diagnoses
Lupus Erythematosus, Subacute Cutaneous
Lymphocytic Skin Infiltration
Psoriasis, Annular
Laboratory Studies
A potassium hydroxide (KOH) examination of skin scrapings may be diagnostic in tinea corporis.
A KOH test is a microscopic preparation used to visualize fungal elements removed from the skin’s stratum corneum.
The sample should be taken from the active border of a lesion because this region provides the highest yield of fungal elements. A KOH preparation from a vesicular lesion should be made from the roof of the vesicle.
The KOH helps dissolve the keratin and leaves fungal elements intact, revealing numerous septate, branching hyphae amongst epithelial cells.
A counterstain, such as chlorazol black E or Parker blue-black ink, may help visualize hyphae under the microscope.
A fungal culture is often used as an adjunct to KOH for diagnosis. Fungal culture is more specific than KOH for detecting a dermatophyte infection; therefore, if the clinical suspicion is high yet the KOH result is negative, a fungal culture should be obtained.
A few culture mediums are available for dermatophyte growth.
Sabouraud agar containing neopeptone or polypeptone agar and glucose is often used for fungal culture. However, it does not contain antibiotics and may allow overgrowth of fungal and bacterial contaminants.
Mycosel, a commonly used agar, is similar to Sabouraud agar but has antibiotics.
Commonly, dermatophyte test medium (DTM) is used. It contains antibacterial (ie, gentamicin, chlortetracycline) and antifungal (ie, cycloheximide) solutions in a nutrient agar base. This combination isolates dermatophytes while suppressing other fungal and bacterial species that may contaminate the culture.
Following culture inoculation, potential fungal growth is monitored for 2 weeks.
Positive culture results vary depending on the medium used.
DTM contains phenol red solution, which causes a color change from straw-yellow to bright-red under alkaline conditions, indicating a positive dermatophyte culture result. However, the color makes identification of culture morphology (particularly pigmentation) difficult.
Sabouraud or Mycosel agar should be used to assess gross and microscopic colony characteristics.
If the above clinical evaluations are inconclusive, the molecular method of polymerase chain reaction for fungal DNA identification can be applied.[16]
For atypical presentations of tinea corporis, further evaluation for HIV infection and/or an immunocompromised state should be considered.
Treatment
Topical allylamines
Naftifine 1% cream or gel (Naftin)
Topical pyridones
Ciclopirox olamine 1% cream (Loprox)
Topical benzylamines
Systemic azoles
Systemic allylamines
Other systemic antifungals
Topical azoles
Clotrimazole 1% cream (Mycelex, Lotrimin)
Ketoconazole topical (Nizoral)
Miconazole topical (Monistat)
Oxiconazole 1% cream (Oxistat)
Sertaconazole 2% cream (Ertaczo)
Sulconazole 1% cream or solution (Exelderm)
ONYCHOMYCOSIS
Background
Onychomycosis (OM) refers to a fungal infection that affects the toenails or the fingernails. Onychomycosis may involve any component of the nail unit, including the nail matrix, nail bed, or nail plate. Onychomycosis is not life threatening, but it can cause pain, discomfort, and disfigurement and may produce serious physical and occupational limitations. Psychosocial and emotional effects resulting from onychomycosis are widespread and may have a significant impact on quality of life.[1]
The main subtypes of onychomycosis are distal lateral subungual onychomycosis (DLSO), white superficial onychomycosis (WSO), proximal subungual onychomycosis (PSO), endonyx onychomycosis (EO), and candidal onychomycosis. Patients may have a combination of these subtypes. Total dystrophic onychomycosis refers to the most advanced form of any subtype.
Pathophysiology
The pathogenesis of onychomycosis depends on the clinical subtype. In distal lateral subungual onychomycosis, the most common form of onychomycosis, the fungus spreads from plantar skin and invades the nail bed via the hyponychium. Inflammation occurring in these areas of the nail apparatus causes the typical physical signs of distal lateral subungual onychomycosis. In contrast, white superficial onychomycosis is a rarer presentation caused by direct invasion of the surface of the nail plate. In proximal subungual onychomycosis, the least common subtype, fungi penetrate the nail matrix via the proximal nail fold and colonize the deep portion of proximal nail plate. Endonyx onychomycosis is a variant of distal lateral subungual onychomycosis in which the fungi infect the nail via the skin and directly invade the nail plate.
Nail invasion by Candida is not common because the yeast needs an altered immune response as a predisposing factor to be able to penetrate the nails. Despite the frequent isolation of Candida from the proximal nail fold or the subungual space of patients with chronic paronychia or onycholysis, in these patients Candida is only a secondary colonizer. In chronic mucocutaneous candidiasis, the yeast infects the nail plate and eventually the proximal and lateral nail folds.
Clinical Presentation
The subtypes of onychomycosis may be distinguished on the basis of their usual presenting clinical features.
In distal lateral subungual onychomycosis, the nail shows subungual hyperkeratosis and onycholysis, which is usually yellow-white in color. Yellow streaks and/or yellow onycholytic areas in the central portion of the nail plate are commonly observed.
Endonyx onychomycosis presents as a milky white discoloration of the nail plate, but, in contrast to distal lateral subungual onychomycosis, no evidence of subungual hyperkeratosis or onycholysis is present.
White superficial onychomycosis is confined to the toenails and manifests as small, white, speckled or powdery patches on the surface of the nail plate. The nail becomes roughened and crumbles easily. Molds produce a deep variety of white superficial onychomycosis characterized by a larger and deeper nail plate invasion.
Proximal subungual onychomycosis presents as an area of leukonychia in the proximal nail plate that moves distally with nail growth. In proximal subungual onychomycosis caused by molds, leukonychia is typically associated with marked periungual inflammation.
Total dystrophic onychomycosis presents as a thickened, opaque, and yellow-browail.
In Candida onychomycosis associated with chronic mucocutaneous candidiasis or immunodepression, several or all digits are affected by total onychomycosis associated with periungual inflammation. The digits often take on a bulbous or drumstick appearance.
Causes
Onychomycosis is caused by 3 main classes of fungi: dermatophytes, yeasts, and nondermatophyte molds. Dermatophytes are by far the most common cause of onychomycosis. Two major pathogens are responsible for approximately 90% of all onychomycosis cases. Trichophyton rubrum accounts for 70% and Trichophyton mentagrophytes accounts for 20% of all cases. Onychomycosis caused by nondermatophyte molds (Fusarium species, Scopulariopsis brevicaulis,Aspergillus species) is becoming more common worldwide, accounting for up to 10% of cases.[5] Onychomycosis due to Candida is rare.
T rubrum is the most common pathogen in distal lateral subungual onychomycosis. Proximal subungual onychomycosis due to T rubrum infection is typical of immunosuppressed patients . Additionally, Proximal subungual onychomycosis with periungual inflammation is usually caused by molds
White superficial onychomycosis is usually caused by T mentagrophytes; nondermatophyte molds cause deep white superficial onychomycosis.
Candida albicans nail infection is observed in premature children, in immunocompromised patients, and in persons with chronic mucocutaneous candidiasis.
Risk factors for onychomycosis include family history, increasing age, poor health, prior trauma, warm climate, participation in fitness activities, immunosuppression (eg, HIV, drug induced), communal bathing, and occlusive footwear.
Differential Diagnoses
Traumatic onycholysis
Laboratory Studies
The clinical features of onychomycosis may mimic a large number of other nail disorders. Therefore, laboratory diagnosis of onychomycosis must be confirmed before beginning a treatment regimen. A negative mycological result does not rule out onychomycosis, because direct microscopy may be negative in up to 10% of cases and culture in up to 30% of cases.
Direct microscopy
A 20% potassium hydroxide (KOH) preparation in dimethyl sulfoxide (DMSO) is a useful screening test to rule out the presence of fungi. Before obtaining a specimen, the nails must be clipped and cleansed with an alcohol swab to remove bacteria and debris. The preparation does not require heating or prolonged incubation if DMSO is a component of the KOH solution.
In distal lateral subungual onychomycosis, a specimen should be obtained from the nail bed by curettage. The onycholytic nail plate should be removed and the sample should be obtained at a site most proximal to the cuticle, where the concentration of hyphae is greatest.
In proximal subungual onychomycosis, the overlying nail plate must initially be pared with a No. 15 blade. Then, a sample of the ventral nail plate may be taken. A No. 15 blade may also be used to remove a specimen from the nail surface in white superficial onychomycosis.
Specimens suspected of candidal onychomycosis should be taken from the affected nail bed closest to the proximal and lateral edges.
Nail fragments must be small enough for examination under low power. Large pieces of nail plate may be pulverized prior to microscopy by using a hammer or a nail micronizer. Counterstains, such as chlorazol black E or Parker blue-black ink, may be used to accentuate the hyphae. Shemer et al reported that drilling to obtain specimens and taking the sample from a more proximal site yield better results.
Culture
Direct microscopy cannot identify the specific pathogen involved in onychomycosis. A fungal culture must be used to identify the species of organism. Nondermatophyte molds may be resistant to the conventional therapy used for the more common dermatophytes. Therefore, 2 types of growth medium should be used, one with cycloheximide (dermatophyte test medium [DTM], Mycosel, or Mycobiotic) to select for dermatophytes and one without cycloheximide (Sabouraud glucose agar, Littman oxgall medium, or inhibitory mold agar) to isolate yeasts and nondermatophyte molds.
Cultures should be obtained from pulverized nail scrapings or clippings while the patient has abstained from antifungal medication for at least 2 weeks. The specimen should be kept at room temperature with the cap placed loosely over the inoculated medium.
The clinical features of onychomycosis may mimic a large number of other nail disorders. Therefore, laboratory diagnosis of onychomycosis must be confirmed before beginning a treatment regimen. A negative mycological result does not rule out onychomycosis, because direct microscopy may be negative in up to 10% of cases and culture in up to 30% of cases.
Direct microscopy
A 20% potassium hydroxide (KOH) preparation in dimethyl sulfoxide (DMSO) is a useful screening test to rule out the presence of fungi. Before obtaining a specimen, the nails must be clipped and cleansed with an alcohol swab to remove bacteria and debris. The preparation does not require heating or prolonged incubation if DMSO is a component of the KOH solution.
In distal lateral subungual onychomycosis, a specimen should be obtained from the nail bed by curettage. The onycholytic nail plate should be removed and the sample should be obtained at a site most proximal to the cuticle, where the concentration of hyphae is greatest.
In proximal subungual onychomycosis, the overlying nail plate must initially be pared with a No. 15 blade. Then, a sample of the ventral nail plate may be taken. A No. 15 blade may also be used to remove a specimen from the nail surface in white superficial onychomycosis.
Specimens suspected of candidal onychomycosis should be taken from the affected nail bed closest to the proximal and lateral edges.
Nail fragments must be small enough for examination under low power. Large pieces of nail plate may be pulverized prior to microscopy by using a hammer or a nail micronizer. Counterstains, such as chlorazol black E or Parker blue-black ink, may be used to accentuate the hyphae. Shemer et al reported that drilling to obtain specimens and taking the sample from a more proximal site yield better results.
Culture
Direct microscopy cannot identify the specific pathogen involved in onychomycosis. A fungal culture must be used to identify the species of organism. Nondermatophyte molds may be resistant to the conventional therapy used for the more common dermatophytes. Therefore, 2 types of growth medium should be used, one with cycloheximide (dermatophyte test medium [DTM], Mycosel, or Mycobiotic) to select for dermatophytes and one without cycloheximide (Sabouraud glucose agar, Littman oxgall medium, or inhibitory mold agar) to isolate yeasts and nondermatophyte molds.
Cultures should be obtained from pulverized nail scrapings or clippings while the patient has abstained from antifungal medication for at least 2 weeks. The specimen should be kept at room temperature with the cap placed loosely over the inoculated medium.
Other Tests
Polymerase chain reaction (PCR) assays have been developed to detect fungal DNA from infected nails. A highly sensitive nested PCR assay using species-specific primer pairs based on the 28S ribosomal RNA gene has been developed. This methodology permits detection of both dermatophytes and nondermatophytes.
TREATMENT & MANAGEMENT
Medical Care
Treatment of onychomycosis depends on the clinical type of the onychomycosis, the number of affected nails, and the severity of nail involvement. A systemic treatment is always required in proximal subungual onychomycosis and in distal lateral subungual onychomycosis involving the lunula region. White superficial onychomycosis and distal lateral subungual onychomycosis limited to the distal nail can be treated with a topical agent. A combination of systemic and topical treatment increases the cure rate. Because the rate of recurrence remains high, even with newer agents, the decision to treat should be made with a clear understanding of the cost and risks involved, as well as the risk of recurrence. Photodynamic therapy and lasers may represent future treatment options.
Topical antifungals
The use of topical agents should be limited to cases involving less than half of the distal nail plate or for patients unable to tolerate systemic treatment. Agents include amorolfine (approved in other countries), ciclopirox olamine 8% nail lacquer solution, and bifonazole/urea (available outside the United States).
Topical treatments alone are generally unable to cure onychomycosis because of insufficient nail plate penetration. Ciclopirox and amorolfine solutions have been reported to penetrate through all nail layers but have low efficacy when used as monotherapy. They may be useful as adjunctive therapy in combination with oral therapy or as prophylaxis to prevent recurrence in patients cured with systemic agents.
Oral therapy
The newer generation of oral antifungal agents (itraconazole and terbinafine) has replaced older therapies in the treatment of onychomycosis.They offer shorter treatment regimens, higher cure rates, and fewer adverse effects. Fluconazole and the new triazole posaconazole (both not approved by the US Food and Drug Administration [FDA] for treatment of onychomycosis) offer an alternative to itraconazole and terbinafine. The efficacy of the newer antifungal agents lies in their ability to penetrate the nail plate within days of starting therapy. Evidence shows better efficacy with terbinafine than with other oral agents (see Prognosis).
To decrease the adverse effects and duration of oral therapy, topical treatment
Antifungals
Terbinafine (Lamisil)
Itraconazole (Sporanox)
Fluconazole (Diflucan)
Ciclopirox (Penlac)
Further Outpatient Care
Although hepatotoxic reactions are unlikely, periodic monitoring of patients undergoing oral antifungal therapy should include a CBC count and measurements of liver enzyme levels approximately every 4-6 weeks.
Treatment may be discontinued after standard dosing with terbinafine or itraconazole wheo evidence of fungal infection (by microscopy or culture) is present. Nails may continue to look dystrophic after a cure is achieved in the laboratory.
After antifungal therapy, disease-free nail growth should be measured at every visit. Nails should grow at a rate of 1.5-2 mm per month and may take up to 1 year to look normal. A clinician may consider an additional dose of antifungal medication if the outgrowth distance slows or stops after discontinuing therapy.
