Chapter 15 Diseases Resulting from Fungi and Yeasts

Chapter 15 Diseases Resulting from Fungi and Yeasts
Andrews’ Diseases of the Skin JoAnne M. LaRow, D.O.

Superficial mycoses AKA dermatophytes
Classified into three genera: Microsporum, Trichophyton, Epidermophyton Mycoses caused by dermatophytes are called dermatophytosis, tinea, ringworm On certain parts of body tinea has certain features characteristic of that site Hence the division into seven types (1)tinea capitis, (2)tinea barbae, (3)tinea faciei, (4)tinea corporis, (5) tinea manus, (6) tinea pedis, (7) tinea cruris, (8)onychomycosis Superficial mycoses can be divided into causative dermatophyte- Management is rarely assisted by ID of genus and species

Susceptibility They are soil saprophytes that have acquired ability to digest keratinous material in soil, becoming “keratinophilic fungi” Some have evolved to parasitize keratinous tissues of animals frequently in contact with soil and have lost their ability to survive in soil (zoophilic fungi) Anthropophilic dermatophytes are believed to have evolved from zoophilic fungi, adapting to human keratin and losing their ability to digest animal keratin Environmental conditions help promote propagation of many opportunistic fungi Host factors are also significant

Host factors Immunosuppressed pts Pts with AIDS may have severe forms
Genetic susceptibility to certain forms of fungal infections may be related to types of keratin or degree or mix of cutaneous lipids produced Surface antigens-ABO system-one study of 108 culture proven dermatophytosis pts noted that pts with type A blood were prone to chronic disease Human steroid hormones can inhibit growth of dermatophytes (androgens like androstenedione) One group believes this high susceptibility of Trichophyton rubrum & Epidermophyton floccosum to intrafollicular androstenedione is a reason why these species do not cause tinea capitis

Antifungal therapy Consider spectrum of activity of antifungal
Pharmacokinetic profile of the agent Clinical type of infection Additionally, safety, compliance and cost Griseofulvin is still therapeutic option but studies are showing that newer antifungals are more efficacious

Imidazoles Clotrimazole, miconazole, sulconazole, oxiconazole, and ketoconazole Mostly used for topical tx Inhibit cytochrome P alpha-demethylase (an essential enzyme in ergosterol synthesis) Ketaconazole has wide spectrum against dermatophytes, yeasts, and some systemic mycoses Ketaconazole has the potential for serious drug interactions and a higher incidence of hepatotoxicity during long-term daily therapy

Allylamines Naftifine, terbinafine, butenafine
Mode of action similar to thiocarbamates Inhibites squalene epoxydation Terbinafine has less activity against Candida species in vitro studies then triazoles, but is effective clinically Terbinafine is ineffective in the oral tx of tinea versicolor but is effective topically Few drug interactions have been reported, bioavailability is unchanged in food, hepatotoxicity, leukopenia, severe exanthems, and taste disturbances occur uncommonly but should be monitored for clinically and by lab testing if continuous dosing over 6 weeks occurs

Polyene Nystatin Irreversibly binding to ergosterol-an essential component of fungal cell membranes

Triazoles Itraconazole Fluconazole Affect P450 system
Numerous drug interactions occur Need to know pt’s current meds Broadest spectrum to dermatophytes and Candida species, and Malassezia furfur Itraconazole is fungistatic-food increases its absorption , antacids and gastric acid secretion suppressors produce erratic or lowered absorption Pulse dosing limits concern over lab abnormalities Fluconazoles’s absorption is unaffected by food

Tinea Capitis Occurs chiefly in children – less commonly in infants and adults Boys more frequently than girls; except in epidemics caused by Trichophyton tonsurans where there is equal frequency Divided into inflammatory and noninflammatory Tinea capitis can be caused by all pathogenic dermatophytes except Epidermophyton floccosum and T. concentricum In U.S. most caused by T. tonsurans(replacing Microsporum audouinii) & M. canis

Noninflammatory M. audouinii infections present as the classic form
Characterized by multiple scaly lesions (“gray-patch”), stubs of broken hair, and a minimal inflammatory response Occasionally glabrous skin, eyelids, and eyelashes are involved Sometimes observed in epidemics in schools and orphanages Over past 30 yrs, M. audouinii infections are being replaced by increasing numbers of “black-dot” ringworm, caused primarily by T. tonsurans and occassionally by T. violaceum In the U.S. T. tonsurans is the most common cause

Tinea Capitis “Black dot” ringworm, caused by T. tonsurans & occasionally T. violaceum presents as multiple areas of alopecia studded with black dots representing infected hairs broken off at or below the surface of the scalp

Black dot tinea

Black dot ringworm caused by Trichophyton tonsurans

Inflammatory Usually caused by M. canis
Can be caused by T. mentagrophytes, T. tonsurans, M. gypsem, or T. verrucosum M. canis infection begins as scaly, erythematous, papular eruptions with loose and broken-off hairs, followed by various degrees of inflammation A localized spot accompanied by pronounced swelling, with developing bogginess and induration exuding pus develops-kerion celsii A delayed type hypersensitivity reaction to fungal elements With extensive lesions fever, pain, and regional lymphadenopathy may occur

Kerion Widespread “id” eruptions may appear concomitantly on trunk and extremities These are vesicular, lichenoid, or pustular Kerion may be followed by scarring and permanent alopecia in areas of inflammation and suppuration Systemic steroids for short periods will greatly diminish the inflammatory response and reduce the risk of scarring

Kerion: inflammatory rxn of tinea capitis caused by Microsporum canis or Trichophyton mentagrophytes

Kerion caused by Microsporum canis

Kerion: heavily crusted, hairless plaque

Permanent scarring alopecia post kerion

Kerion: red, oozing, hairless plaque

Favus Rare in the U.S. Appears mainly on the scalp, but may occur on glabrous skin and nails On scalp, concave sulfur-yellow crusts from around loose, wiry hairs On glabrous skin lesions are pinhead to 2 cm in diameter with cup-shaped crusts called scutulae-usually pierced by a hair as on the scalp Scutula have a distinctive mousy odor Nail involvement causes brittle, irregularly thickened, and crusted nail changes Not seen typically in North America(has been reported in Kentucky and Canada) Called witkop in South Africa by the Bantus

Favus of scalp showing scutulae

Scarring after favus infection

Etiology Tinea capitis can be cause by any one of several species: T. tonsurans, M. audouinii, and M. canis First two are spread from human to human Latter is caught from animals such as kittens and dogs Most frequent invaders of scalp are endothrix types-T. tonsurans(black-dot ringworm) and T. violaceum T. tonsurans alone affects adults(chiefly women) regularly; others affect children Ectothrix found on scalp are T. verrucosum & T. mentagrophytes (less frequently seen is T. megninii-southwest Europe)

Pathogenesis Incubation period lasts 2 to 4 days
Hyphae grow downward into the follicle, on the hair’s surface, and the intrafollicular hyphae break up into chains of spores Period of spread (4 days to 4 months) during which lesions enlarge and new lesions appear At about 3 weeks hairs break off a few millimeters above the surface Intrapilary hyphae descend to exact upper limit of keratogenous zone and here form Adamson’s “fringe” on the twelfth day External portions of intrapilary hyphae segment into chains of ectothrix spores

Pathogenesis No new lesions develop during the refractory period (4 months to several yrs) Clinical appearance is constant-with host and parasite in equilibrium This is followed by a period of involution in which the formation of ectothrix spores and intrapilary hyphae gradually diminishes Asymptomatic carrier states among young black children may occur There has been a lack of correlation between number of asymptomatic carriers and index cases-suggesting that carrier cases are not primary mode of transmission of T. tonsurans

Histology Extensive inflammation leading to follicular destruction

Medium power: dense inflammation consists of mixed cell types

Neutrophils and other inflammatory cells surround this small follicle.
Fungal elements are present within hair shaft

Diagnosis Ultraviolet of 365 nm wavelength is obtained by passing a beam through a Wood’s filter composed of nickel oxide-containing glass This apparatus a Wood’s light , is available commercially A simple form is the 125-volt purple bulb In a dark room the skin under this light fluoresces faintly blue; however, infected hairs fluoresces bright green, beads on the hairs contrasting strongly with the dark field Bare, scaly areas show a turquoise blue color Fluorescent-positive infections are caused by :M. audouinii, M. canis, M. ferrugineum, M. distortum, T. schoenleinii

Diagnosis Hairs infected with T. tonsurans & T. violaceum and others of endothrix do not fluoresce The fluorescent substance is pteridine For microscopic demonstration of the fungus, two or three loose hairs are removed Hairs are placed on slide with a drop of 10-20% solution of KOH A cover slip is applied, specimen is warmed until hairs are macerated Examine under low, then high power Xylol is as satisfactory as KOH and need not be warmed Scales or hairs cleared with it can still be cultured

Diagnosis Fungus invades hair shaft in two ways-(1) ectothrix involvement in which hair is surrounded with a sheath of tiny spores Examples of these types are: Microsporum species, T. mentagrophytes & T. verrucosum (T. verrucosum is the fungus most frequently acquired by humans from cattle and causes a severe inflammatory tinea barbae in men or tinea capitis in children) Other mode of infection is endothrix type-where arthrospores are formed inside the hair shaft This type is seen in T. tonsurans, T. violaceum, and T. schoenleinii infections

Final and exact identification of causative fungus
Such identification is largely epidemiologic and academic-tx is the same Several infected hairs are placed on Sabouraud’s glucose agar or Dermatophyte Test Medium (DTM) On DTM a distinctive growth appears within 1-2 weeks Diagnosis is usually made by gross appearance of culture When questionable the culture is examined under a microscope for characteristic morphologic forms DTM contains antibiotics to reduce growth of contaminants and a colored pH indicator to denote the alkali-producing dermatophytes

DTM A few nonpathogenic saprophytes will also produce alkalinization and in the occasional case of onychomycosis of toenails caused by airborne molds, a culture medium containing an antibiotic may inhibit growth of the true pathogen Cultures are best taken by rubbing the lesion vigorously with a sterile cotton swab moistened with sterile water and them streaked over the agar surface

Ectothrix type in Microsporum canis-note small spores around hair shaft

Endothrix spores in hair with Trichophyton tonsurans

Endothrix in T. scoenleinii showing characteristic bubbles of air

Endothrix infection, (low-power KOH mount): arthroconidia noted within hair shaft
Endothrix infection (high-power KOH mount) showing total hair shaft involvement

T. tonsurans This microoraganism grows slowly in culture to produce a granular or powdery yellow to red, brown, or buff colony Crater formation with radial grooves may be produced Microconidia may be seen regularly Dx confirmed by the fact that cultures grow poorly or not at all without thiamine

T. mentagrophytes Cultural growth is velvety or granular or fluffy, flat or furrowed, light buff, white, or sometimes pink Back of the culture can vary from buff to dark red Round microconidia borne laterally and in clusters confirm dx within 2 weeks Spirals are sometimes present Macroconidia may be seen

T. verrucosum Growth is slow and cannot be observed well for at least 3 weeks Colony is compact, glassy, velvety, , heaped or furrowed, and usually white, but may be yellow or gray Chlamydospores are present in early cultures Microconidia may be seen

M. audouinii Gross appearance shows a slowly groing, matted, velvety, light brown colony Back of which is reddish brown to orange Under microscope a few large multiseptate macroconidia (macroaleuriospores) are seen Microconidia (microaleuriospores) in a lateral position on hyphae are clavate Racquet mycelium, chlamydospores, and pectinate hyphae are seen sometimes

M. canis Culture shows profuse, fuzzy, cottony, aerial mycelia tending to become powdery in the center Color is buff to ligth brown Back of colony is lemon to orange-yellow Numerous spindle-shaped multiseptate microconidia and thick-walled macroconidia are present Clavate microconidia ae found along with chlamydospores and pectinate bodies

Treatment Griseofulvin of ultramicronized form, 10 mg/kg/day, is the daily dose recommended for children Grifulvin V is the only oral suspension available for children unable to swallow tablets-dose is 20 mg/kg/day Tx should continue for 2-4 months, or for at least 2 weeks after a negative microscopic and culture examinations are obtained Griseofulvin does not primarily affect the delayed type hypersensitivity reaction responsible for the inflammation in kerion For this, systemic steroids, to minimize scarring, can be given simultaneously

Numerous other studies exist that demonstrate the effectiveness of other oral agents, such as itraconazole, terbinafine, and fluconazole These studies report these meds to be excellent alternatives, but the total reported experience to date is low Selenium sulfide shampoo or ketaconazole shampoo three times weekly can be used as adjunctive therapy to oral antifungal agents Herbert recommends culture of family members, caution regarding sharing potentially contaminated fomites, and simultaneous tx of all persons infected clinically or by culture Drake et al recommend tx family members with ketaconazole shampoo, selenium sulfide shampoo, or povidine-iodine even if they are asymptomatic

Prognosis Recurrence usually does not take place when adequate amounts of griseofulvin, fluconazole, or terbinafine have been taken Exposure to infected persons, asymptomatic carriers, or contaminated fomites will increase the relapse rate Without medication there is spontaneous clearing at about age 15, except with T. tonsurans which persists into adult life

Tinea Barbae AKA Tinea sycosis, barber’s itch Ringworm of the beard
Uncommon Occurs chiefly among those in agricultural pursuits Especially those in contact with farm animals Involvement is mostly one-sided on neck or face Two clinical types are: deep, nodular, suppurative lesions; and superficial , crusted, partially bald patches with follicultis

Tinea Barbae Superficial crusted type causes mild pustular folliculitis with broken-off hairs (T. violaceum) or without broken-off hairs (T. rubrum) Affected hairs are loose, dry, and brittle When extracted bulb appears intact

Tinea Barbae Deep type develops slowly and produces nodular thickenings and kerion-like swellings Caused mostly by T. mentagrophytes or T. verrucosum Swellings are usually confluent and form diffuse boggy infiltrates with abscesses Overlying skin is inflammed, hairs are loose or absent, pus may be expressed through the remaining follicular openings Lesions are limited to one part of face or neck in men Upper lip is not usually involved, although mustache area may be occasionally

Diagnosis-Tinea Barbae
Confirmed by microscopic findings of the fungus and by standard culture techniques for dermatophyte infections Rarely, Epidermophyton floccosum may cause widespread verrucous lesions known as verrucous epidermophytosis

Verrucous epidermophytosis from Epidermphyton floccosum

Complete resolution after 48 days of griseofulvin

Differential Diagnosis
Sycosis vulgaris-lesions are pustules and papules, pierced in the center by a hair, which is loose and easily extracted after suppuration has occurred Contact dermatitis Herpes infections

Tinea barbae-Trichophyton mentagorphytes

Treatment-Tinea Barbae
Oral antifungals are required Topical agents as adjunctive therapy Micronized or ultramicronized griseofulvin orally: dosage of 500–1000 mg or mg respectively Tx usually for 4-6 weeks

Treatment-Tinea Barbae
Other orals that have been effective: ketoconazole, fluconazole, itraconazole, and terbinafine Topical antifungals should be applied from the beginning of tx Affected parts should be bathed thoroughly in soap and water Healthy areas that are not epilated may be shaved or clipped When kerion is present a short course of systemic steriod therapy may help reduce inflammation and risk of scarring

Tinea Faciei Fungal infection of the face (apart from the beard)
Frequently misdiagnosed since typical ringworm is only uncommonly seen on the face Instead, erythematous, slightly scaling, indistinct borders are usually seen Diagnosis is easily established by direct microscopic examination Usually caused by T. rubrum. T. mentagrophytes, or M. canis Tinea faciei caused by T. nanum has been described in hog farmers and should be considered an occupational source

Tinea faciei (Microsporum canis) in a child

Tinea corporis involving the face (tinea faciei)

Treatment Topical clotrimazole, naftifine, micronazole, ciclopirox olamine cream, econazole, oxiconazole, ketaconazole, sulconazole, or terbinafine ususally bring about a prompt response Oral griseofulvin administered for 2-4 weeks, as well as fluconazole, itraconazole, or terbinafine are all effective particularly in combination with topical therapy

Tinea Corporis(Tinea Circinata)
Includes all superficial dermatophyte infections of the skin other than those involving the scalp, beard, face, hands, feet, and groin Sites of prediliction are neck, upper and lower extremities, and trunk Can be caused by any dermatophyte Characterized by one or more circular, sharply circumcsribed, slightly erythematous, dry, scaly, usually hypopigmented patches

Tinea corporis in a child, caused by Microsporum canis

Tinea Corporis Lesions may be slightly elevated, particularly at the border, where they are more inflamed and scaly than at the central part Progressive central clearing produces annular outlines that give them the name “ringworm” Lesions may widen to form rings many centimeters in diameter In some cases concentric circles form rings in one another, making intricate patterns (tinea imbricata) Multiple disseminated patches of both dry (macular) and moist (vesicular) types of tinea circinata are encountered in which much of skin surface is involved Widespread tinea corporis may be the presenting sign of AIDS

Tinea corporis (Trichophyton rubrum)
Note sharp margins and central clearing

Tinea corporis: large gyrate plaque with advancing border, perhaps worsened by diapering

Histopathology Rarely the question of microscopic pathology may arise
Better ways to make diagnosis But if compact orthokeratosis is found in a section, a search for fungal hyphae should be performed This is diagnostic

Etiology-Tinea Corporis
Various organisms may cause this type of fungal infection Microsporum canis, T. rubrum, T. mentagrophytes-most common T. rubrum is is the most common dermatophyte in the U.S. and worldwide T. tonsurans has experienced a dramatic rise as a cause of tinea corporis as it has for tinea capitis In children, M. canis is the cause of the moist type of tinea circinata

Epidemiology Tinea corporis is frequently seen in children-particularly those exposed to animals with ringworm(M. canis), especially cats, dogs and less commonly, horses and cattle In adults excessive perspiration is the most common factor Incidence is especially high in hot, humid areas of the world

Diagnosis-Tinea Corporis
Relatively easy via microscopic findings of fungus after skin scraping Skin scrapings can be cultured on a suitable medium Growth of fungus is apparent within a week or two at most and, most of the time is identifiable by gross appearance of the culture Identification of the fungus is of epidemiologic interest, and is not helpful in managing the infection

Treatment-Tinea Corporis
When tinea corporis is caused by T. tonsurans, M. canis, T. mentagrophytes, or T. rubrum , griseofulvin, terbinafine, itraconazole, and fluconazole are all effective The ultra-micronized form may be used at a dose of mg once/day for 4-6 weeks This dose may be increased to twice daily if needed Terbinafine, itraconazole, and fluconazole are effective Terbinafine at 250 mg/day for two weeks Itraconazole 200 mg B.I.D. for one week Fluconazole 150 mg once/week for 4 weeks

Treatment(cont) When only 1-2 patches occur, topical tx is effective
Sulconazole (Exelderm), oxiconazole (Oxistat), miconazole (Monistat cream or lotion, or Micatin cream), clotrimazole (Lotrimin or Mycelex cream), econazole (Spectazole), naftifine (Naftin), ketaconazole (Nizoral), ciclopirox olamine (Loprox), terbinfine (Lamisil), and butenafine (Mentax) are available and effective Most are between 2-4 weeks with twice daily use Econazole, ketaconazole, oxiconazole, and terbinafine may be used once daily With terbinafine the course can be shortened to 1 week

Treatment Creams are more effective than lotions
Sulconazole may be less irritating in folded areas Castellani paint (which is colorless if made without fuchin) is very effective Salicylic acid 3% -5%, or half-strength Whitfiels’s ointment, both standbys 30 yrs ago, are little used today Addition of a low-potency steroid cream during the initial 3-5 days of therapy will decrease irritation rapidly without compromising the effectiveness of the antifungal

Other Forms of Tinea Corporis
Trichophytic Granuloma or Perifollicular Granuloma or Majocchi’s Granuloma or Tinea Incognito A deep, pustular type of tinea circinata resembling a carbuncle or kerion observed on the glabrous skin A circumscribed, annular, raised, crusty, and boggy granuloma Follicles are distended with viscid purulent material

Tichophyton mentagrophytes infection on lower leg of American soldier in Vietnam

Trichophytic Granuloma
Occur most frequently on shins or wrists Caused most often by T. rubrum or T. mentagrphytes infecting hairs at sites of involvement Other dermatophytes have been reported:T. epilans, T. violaceum, M. audouinii, M. gypseum, M. ferrugineum, and M. canis In immunosuppressed pts lesions may be deep and nodular Early on such a deep lesion may be pale, circular edematous plaque, often KOH- and culture-neg.

Majocchi’s granuloma occurs naturally in situations of occlusion or may be related to superficial trauma ie shaving Diagnosis is made by demonstration of fungus via direct macroscopic potassium hydroxide slide and by culture or by clinical suspicion Occasionally diagnosis is made on bx specimen Tx is same as for tinea corporis-except that even that even for localized lesions oral therapy is needed

Majocchi’s granuloma H&E pale lue-staining fungal hyphae within hair shaft

Majocchi’s granuloma: PAS reveals multiple organisms that have replaced a fragment of hair shaft embedded in a sea of neutrophils

Tinea Imbricata (Tokelau)
Superficial fungal infection limited to southwest Polynesia, Melansia, Southeast Asia, India, and Central America Characterized by concentric rings of scales forming extensive patches with polycyclic borders Eruption begins with 1 or several small, rounded macules on trunk and arms Small macular patch splits in center and forms large, flaky scales attached at the periphery Resultant ring spreads peripherally and another brownish macule appears in the center and undergoes the process again

Tinea Imbricata When fully developed the eruption is characterized by concentrically arranged rings or parallel undulating lines of scales overlapping each other like shingles on a roof (imbrex means shingle) Causative fungus is T. concentricum TOC is griseofulvin- in same form as for tinea corporis Other options are terbinafine, fluconazole, and itraconazole Several courses of therapy may be needed May need to remove pt from hot, humid environment

Tinea imbricata in New Guinea native

Tinea imbricata: concentric rings of scale caused by T. concentrium

Tinea Cruris AKA jock itch Most common in men
On upper and inner thighs Begins as a small erythematous and scaling or vesicular and crusted patch Spreads peripherally and partly clears in the center Characterized by its curved, well-defined border, especially at lower edge Border ma have vesicles, pustules, or papules May extend downward on thighs and backward on the perineum or anus Penoscrotal fold or sides of scrotum are seldom involved

Tinea cruris in a man

Tinea cruris in a woman

Etiology-Tinea Cruris
T. mentagrophytes & E. floccosum & T. rubrum usual cause Infection with Candida albicans may closely resemble tinea cruris Most useful distinguishing feature it posses are the regular occurrence of small “daughter” macules, centrally desquamating to form collarette scales, satellite pustules, scattered along the periphery of the main macule

Epidemiology &Tx Heat and high humidity
Tight jockey shorts, which prevent evaporation of the increased perspiration produced during warm weather Tx: reduce perspiration and enhance evaporation from crural area Keep as dry as possible by wearing underclothing and trousers Plain talcum powder or antifungal powders are helpful Specific topical and oral tx is same as that described under tinea corporis

Tinea in diapered area

Tinea of Hands and Feet Popularly called athlete’s foot
Most common fungal disease(by far) Primary lesions often are macerated, slightly scaly, with occasional vesiculation, and fissures between the toes Most commonly the third toe web is involved Pt usually seeks relief because of itching If allowed to progress may lead to overgrowth of gram-negative organisms Eventually leading to an ulcerative, exudative process

Tinea pedis showing interdigital scalping
T. mentagrophytes

Interdigital scaling with vesiculation caused by T. mentagrophytes

Trichophyton mentagrophytes produces an acutely inflammatory condition
If invasion of skin of toes or soles, an acutely vesicualr or bullous eruption may occur Vesicular eruption tends to spread by extension and unless checked, may involve the entire sole Vesicles usually 2-3 mm in diameter-sometimes they coalesce to form bullae of various sizes These are firm to touch and have a bluish tint They do not rupture spontaneously but dry up as the acute stage subsides-leaving yellowish brown crusts Burning and itching of vesicles may cause great discomfort-relieved by opening tense vesicles

Dermatophytosis of the soles
Trichophyton mantagrophytes

Acute vesiculobullous eruption on sole caused by Trichophyton mentagrophytes

Tinea Pedis Vesicles contain clear tenacious fluid the consistency of glycerin Extensive or acute eruptions on soles may become incapacitating Fissures between toes may become secondarily infected with pyogenic cocci This may lead to attacks of lymphangitis and inguinal adenitis Hyperhidrosis is frequently present Sweat on soles and in between has a high pH, and keratin damp with a good culture medium for the fungus

TP-Trichophyton rubrum
T. rubrum causes the majority of cases Produces a relatively noninflammatory type of dermatophytosis characterized by a dull erythema and prnounced scaling involving the entire sole and sides of feet Producing a moccasin or sandel appearance

Tinea pedis and onychomycosis in father/son pair.
Father shows classic moccasin distribution of tinea pedis and son shows distal subungual onychomycosis

Tinea manus Tinea infection of hands that is dry, scaly, and erythematous may occur Suggestive of infection with T. rubrum Other areas are frequently affected at the same time

Trichophyton rubrum infections

Moist, vesicular, eczematous types characterize infection with T
Moist, vesicular, eczematous types characterize infection with T. mentagrophytes Organism seen more frequently on the feet-but can be on the hand T. rubrum & T. mentagrophytes are the two most common types of fungus causing hand and feet dermatophytosis Occurring more frequently perhaps than true fungus is dermatophytid of hands These commonly begin as groups of minute, clear vesicles on palms and fingers Itching may be intense As a rule, usually both hands are involved however there are cases in which only one hand is affected

Differential diagnosis
Allergic contact or irritant dermatitis-especially occupational Pompholyx Atopic dermatitis Psoriasis Lamellar dyshidrosis Eczematoid or dyshidrotic lesions of unknown cause on hands should prompt a search for clinical evidence of dermatophytosis of feet etc.

Etiology T. rubrum most frequent causative fungus
Culture of organism are usually fluffy-but can be granular or folded Backside of culture is usually deep red; sometimes no color is produced Microconidia are found in clusters and singly on the hyphae Macroconidia, chlamydospores, coils, and racquet hyphae are rarely seen Less frequent causes are T. mentagrophytes and E. floccosum

Diagnosis Demonstration of fungus by microscopic examination of scrapings Cultures made from affected skin However, failure to find fungus does not exclude a fungal cause Tissue is scrapped off and placed on a glass slide When lesion is a vesicle, it is clipped off close to the margin by a small, pointed scissors; when dry or scaly, material is scraped off with a scalpel or curet(obtain material from deep beneath the surface of chronic eruptions) A drop of 20% KOH added Gentle heat applied until scales are macerated

Diagnosis Mycelium may be seen under low power, but better observation of both hyphae and spores is obtained by use of high dry objective with reduced illumination Lines of juncture of normal epidermal cells are hyaloid and greenish, and nay be easily mistaken for fungus structures If you wonder whether it is really mycelium or not it is not Rapid staining method using 100mg of chlorazol black E dye in 10 ml of dimethyl sulfoxide (DMSO) and adding it to 5% aqueous solution of KOH can be helpful

Fungus filaments under KOH mount

Diagnosis(continued)
Solution is then prepared in same way as ordinary KOH solution Viewed under bright illumination; hyphae and spores are green against a gray background Other portion is planted on Sabouraud’s glucose agar or Mycosel agar, and cultured at room temperature Adequate growth for id occurs in 5-14 days-depending on type of fungus Taplin et al revised the medium-DTM for diagnosis DTM inhibits growth of bacterial and saprophytic contaminants

DX-continued Alkaline metabolized of the dermatophytes change color of the pH indicator in medium from yellow to red If a dermatophyte is present medium will turn red Saprophytes turn medium green C. albicans does not cause any color change, but produces a typical yeast colony One often finds the so-called mosaic fungus It is caused by overlapping cell borders A positive KOH preparation should reveal definite hyphal elements traversing several epidermal cells

Mosaic fungus

Prophylaxis Hyperhidrosis is a predisposing factor
Dry toes after bathing Dryness is essential if re-infection is to be avoided Use good antiseptic powder on feet after bathing-particularly between toes Tolnaftate powder or Zeasorb medicated powders for feet Plain talc, cornstartch, or rice powder may be dusted into socks and shoes to keep feet dry

Treatment Clotrimazole, miconazole, sulconazole, oxiconazole, econazole, ketaconazole, naftifine, terbinafine, butenafine-all effective Severs disease with significant maceration wet dressings or soaks with solutions such aluminum acetate, one part to 20 parts of water are beneficial Antiinflammatory effects of corticosteroids are markedly beneficial Topical antibiotic ointments, such as gentamicin, effective against gram-negative organisms, are helpful additions in tx of the moist type of interdigital lesions In ulcerative type of gram-neg toe web infections, systemic floxins are needed

Tx Keratolytic agents, such as salicylic acid, lactic acid lotions, and Carmol are therapeutic when fungus is protected by a thick layer of overlying skin (ie soles) Tx of fungal infection of feet and hands with griseofulvin is effective when infection is caused by pathogens such as T. mentagrophytes, T. rubrum, E. floccosum, and others Not effective in tx of Candida albicans Griseofulvin is only effective against dermatophytes When infection is caused by T. mentagrophytes griseofulvin does not decrease inflammatory rx

Tx-doses Griseovulvin in ultramicronized particles taken orally in doses of mg daily Doage for children is 10 mg/kg/day Period of tx depends on response Repeated KOH scrapings and culture should be neg Recommended adult doses for newer agents: terbinafine, 250 mg/day for 2 weeks; itraconazole, 200 mg twice daily for 1 week; fluconazole, 150 mg once weekly for 4 weeks

Onychomycosis(Tinea Ungium)
Fungal infection of nail Represents up to 30% of diagnosed superficial fungal infections Etiologic agents are species: Epidermophyton, Microsporum, and Trichophyton fungi May also be caused by other dermatophytes, yeasts, and nondermatophytic molds Nondermatophytic molds usually involve toenails and are rarely seen in fingernails

Onychomycosis Frequently clinical appearance of onychomycosis caused by one species of fungus is indistinguishable from that caused by another However, various clues could allow one to speculate as to organism responsible Four classic types:1.) distal subungual onychomycosis: primarily involves distal nail bed and hyponychium, with secondary involvement of underside of nail plate of fingernails and toenails

Onychomycosis caused by Trichophyton rubrum

Trichophyton mentagrophytes
2.) white superficial onychomycosis(leukonychia trichophytica):this is an invasion of the toenail plate on the surface of the nail It is produced by T.mentagrophytes,species of Cephalosporium and Aspergillus, and Fusarium oxysporum fungus

Onychomycosis 3.) Proximal subungual onychomycosis: involves the nail plate mainly from proximal nail fold, producing a specific clinical picture It is produced by T. rubrum & T. megninii and may be an indication of HIV infection 4.) Candidaonychomycosis involves all the nail plate; it is due to Candida albicans and is seen in pts with chronic mucocuataneous candidiasis

Onychomycosis caused by Candida albicans in mucocutaneous candidiasis

Onychomycosis Onychomycosis caused by T. rubrum is usually a deep infection Disease usually starts at distal corner of nail and involves the junction of nail and its bed First a yellowish discoloration occurs, which may spread until entire nail is affected Beneath discoloration nail plate becomes loose from nail bed

Gradually entire nail becomes brittle and separated from its bed due to piling up of keratin subungually Nail may break off, leaving an undermined remnant that is black and yellow from dead nail and fungi that are present

Onychomycosis Caused by T. mentagrophytes is usually superficial, and there is no paronychial inflammation Infection generally begins with scaling of nail under overhanging cuticle and remains localized to a portion of nail However, in time whole nail may be involved Leukonychia trichophytica is name given to this fungal infection Small, chalky white spots appear on or in nail plate May be multiple and variously shaped or just a single spot Superficial so that they may be shaved off easily

Nail lesions caused by C. albicans there is usually paronychia
Begins under lateral or proximal nail fold-small amount of pus may be expressed Adjacent cuticle is swollen, pink, and tender on pressure Fingernails more commonly infected than toenails Encountered mostly in homemakers, canners, and others who have hands in water a great deal Nail plate does not become friable, yellow, or white as in trichophyton infections Remains hard and glossy unless immunocompromise is present Associated paronychia is characteristic

Distal subungal, onchomycosis occurring simulataneously with superficial white onchmycosis
Superficial white onchomycosis

Differential Scopulariopsis brevicaulis infrequently
Infection usually begins at lateral edge of nail, burrows beneath plate, produces large quantities of cheesy debris Hendersonula toruloidea & Scaytalidium hyalinum have been reported to cause onychomycosis, as well as moccasin-type tinea pedis Other fugi: T. violaceum, T. schoenleinii, & T. tonsurans

Diagnosis Microscopic and culture
Immediate examination of very thin shavings taken from diseased portions of nail Cover slip, KOH, heat gently Culture medium-Mycosel agar or DTM

Treatment Terbinafine 250 mg/day for 6 weeks (fingernails) 12 weeks for toenails Itraconazole, 200 mg twice daily for 1 week of each month for 2 months (fingernails) & 3 months for toenails Fluconazole experience is less-but 150 –300 mg once weekly for 6-12 months Griseofulvin? Therapy continued until nails are clinically normal Low success rates 15-30% for toenails and 50-70% for fingernails Griseofulvin does not tx nail disease caused by candida

Candidiasis Candida proliferates in both budding and mycelial forms in outer layers of the stratum corneum where horny cells are desquamating Organism usually is found outside living portion of the epidermis It does not attack hair, rarely involves nail, and is incapable of breaking up the stratum corneum It is largly an opportunisitic organism, able to behave as a pathogen mainly in impaired immune status, or in body folds Moiture promotes its growth, in moist lip corners

Diagnosis Demonstration of the pathogenic yeast C. albicans establishes the diagnosis Under microscope KOH prep may show spores and peeudomycelium On gram stain yeast forms are dense, gram-positive, ovoid bodies, 2-5 um in diameter In culture C. albicans should be differentiated from other forms of Candida that are only rarely pathogenic Culture on Sabouraud’s glucose agar shows a growth of creamy, grayish, moist colonies in about 4 days In time colonies form small, rootlike penetrations into agar

Mycelium and spores of Candida albicans

Candidiasis KOH mount from infant with thrush showing pseudohyphae and yeast forms

Topical Anticandidal Agents
These include, but are not limited to: clotrimazole (Lotrimin, Mycelex), econazole (Spectazole), ketaconazole (Nizoral), miconazole (MonistatDerm Lotion, Micatin), oxiconazole (Oxistat), sulconazole (Exelderm), naftifine (Naftin), terconazole (vaginal candidiasis only), cicloprox olamine (Loprox), butenafine (Mentax), nystatin, and topical amphotericin B lotion Terbinafine has been reported to be less active against Candidaspecies by some authors

Oral Candidiasis (Thrush)
Mucous membrane of the mouth may be involved in healthy newborn & marasmic infant Newborn infection may be acquired from contact with vaginal tract of mother Grayish white membranous plaques are found on surface Base of plaques are moist, reddish, and macerated It is spread angles of mouth may become involved, and lesions in intertriginous areas may occur, especially in marasmic infants Diaper areas is especially susceptible to this Most of intertriginous areas and even exposed skin may be involved

In adults the buccal mucosa, lips, and tongue may become involved
Papillae of tongue are atrophied, surface is smooth, glazed, and bright red Sometimes there are small erosions on edges Frequently infection extends onto angles of the mouth to form perleche(seen in elderly, debilitated, and malnourished pts, and diabetics It is often the first manifestation of AIDS Is present in nearly 100% of all untreated pts with full-blown AIDS Observation of oral “thrush” in an adult with no known predisposing factors warrants a search for other evidence of infection with HIV, such as lymphadenopathy, leukopenia, or HIV antibodies in serum

One predisposing factor to oral thrush is broad-spectrum antibiotics
During the 1980s there was a dramatic increase in number and severity of cases of oropharyngeal candidiasis Reported increase of 4.7 times, from 0.34 to 1.6 cases per 1000 pediatric admission, and the number of deaths among pts tx with oropharyngeal candidiasis increased fivefold Greatest increase was among yr old pts at thirteenfold Rate of increase between 1985 & 1989 among pts with HIV infection was tenfold, compared with a twofold increase among pts with malignancies or transplants

Thrush with extension to vermilion border

Tx Various tx options are available
Babies with thrush may be allowed to suck on a clotrimazole suppository inserted into the slit tip of a pacifier four times a day for 2-3 days An adult can let tablets of clotrimazole or Mycelex troches dissolve in the mouth In the immunocompromised goal is to reduce symptoms since continuous oral systemic therapy has led to a clinically relevant problem of drug resistance Fluconazole, mg/day for 5-10 days with doubling the dose if it fails, or itraconazole, 200 mg daily for 5-10 days with doubling the dose if it fails-both are available in liquid forms

Perleche

Perleche Or more aptly, angular cheilitis
Maceration with transverse fissuring of oral commissures Earliest lesions are ill-defined, grayish white, thickened areas with slight erythema of the mucous membrane at the oral commissure When more fully developed thickening has a bluish white or mother-of-pearl color and may be contiguous with a wedge-shaped erythematous scaling dermatitis of the skin portion of commissure Fissures, maceration, and rust formation occur Soft, pinhead-sized papules may appear Involvement is bilateral-usually

Perleche Analogous to intertrigo elsewhere, that may come from infection by C. albicans, by coagulase-positive Staphylococcus aureus, or from manifold other causes Similar changes may be seen in riboflavin deficiency, and iron deficiency anemia Identical fissuring occurs in persons with malocclusion caused by ill-fitting dentures and in the aged whom atrophy of alveolar ridges has occurred Seen in children who drool, lick their lips, or suck their thumb

Tx Depends on the cause If due to C. albicans anticandidal creams and lotions Occasionally diabetes complicates this disease, which will persist until diabetes is brought under control It can be seen in AIDS pts with or without thrush Antibiotic topical meds are used when a bacterial; infection is present If due to vertical shortening of lower third of the face, dental or oral surgical intervention may help Injection of collagen into depressed sulcus at the oral commissure may be helpful Softform implants are a more permanent tx

Candidal Vulvovaginitis
C. albicans is a common inhabitant of vaginal tract May cause severe pruritus, irritation, and extreme burning Labia may be erythemtous, moist, and macerated and cervix hyperemic, swollen, and eroded, showing small vesicles on its surface Vaginal discharge is not usually profuse but is frequently thick and tenacious May develop during in pregnancy, in diabetes, or secondary to therapy with a broad- spectrum antibiotic Recurrent vulvovaginal candidiasis has been associated with long-term tamoxifen tx

Candidal Vulvovaginitis
Candidal balanitis may be present in an uncircumcised sexual partner If not recognized, repeated reinfection of a partner may occur Diagnosis is by clinical symptoms and findings as well as demonstration of fungus via KOH microscopic exam & culture Tx is frustrating & disappointing due to recurrences Oral fluconazole 150 mg times 1 dose; Fluconazole, 100mg/day for 5-7 days, itraconazole, 200 mg/day for 2-3 days..other options

Tx Topical options include miconizole (Monistat cream), nystatin vaginal suppositories or tablets (Mycostatin), or clotrimazole (Gyne-Lotrimin or Mycelex G) vaginal tablets inserted once daily for 7 days

Candidal Intertrigo Pruritic intertriginous eruptions caused by C. albicans may arise between folds of genitals; in groins or armpits; between buttocks; under large pendulous breasts; under overhanging abdominal folds; or in umbilicus Pinkish intertriginous moist patches are surrounded by a thin, overhanging fringe of somewhat macerated epidermis (“collarette” scale) Some eruptions in inginal area may resemble tinea cruris, but usually there is less scaliness and a greater tendency to fissuring Topical anticandidal preparations are usually effective Recurrence is common

Pseudo Diaper Rash In infants, C. albicans infection may start in perianal region and spread over entire area Dermatits is enhanced by maceration produced by wet diapers Scaly macules and vesicles with maceration in involved areas cause burning, pruritis, and extreme discomfort Diaper friction may contribute to skin irritation and compromised function of stratum corneum Diagnosis may be suspected by finding involvement of folds and occurrence of many small erythematous desquamating “satellite” or “daughter” lesions scattered around edges

Diagnosis Direct KOH microscopic and culture exams
Swabbing is inadequate for making smears; one must scrape surface to remove the horny material Floor of opened pustules may be similarly scraped for specimens Such exams are rarely needed, however Pierard-Franchimont et al showed a decrease in candidal cultures and skin irritation after use of a miconazole nitrate-containing paste for prevention of diaper dermatitis Pseudo diaper rash also responds well to topical antifungals that cover Candida species

Congenital Cutaneous Candidiasis
Infection of an infant during passage through birth canal Eruption usually noted within first few hrs of delivery Erythematous macules progress to thin-walled pustules, which rupture, dry, and desquamate within a week of so Lesions are usually widespread, involving trunk, neck, and head, at times palms and soles, icluding nail folds Oral cavity and diaper area are spared

Congenital Cutaneous Candidiasis
This is in contrast to the usual type of neonatal infections Differential dx: listeriosis, syphilis, staphylococcal and herpes infections, ETN, transient neonatal pustular melanosis, miliaria rubra , drug eruption, congenital icthyosiform erythroderma (neonatal pustular disorders) If suspected early amniotic fluid, placenta, and cord should be examined for evidence of infection Infants with disease limited to skin have favorable outcomes

CCC Disseminated infection is suggested by (1) bw <1500g (2) evidence of respiratory distress or labs indicating neonatal sepsis (3) tx with broad-spectrum antibiotics (4) extensive instrumentation during delivery or invasive procedures in neonatal period (5) positive systemic cultures, or (6) evidence of an altered immune response Infants with congenital cutaneous candidiasis with any of these 6 criteria would be considered for systemic antifungal therapy More than 16 cases of systemic disease have been reported, resulting in 2 deaths Most did well with a combination of topical and oral antifungal therapy-uncomplicated cases topicals only are needed

Perianal Candidiasis When pruritis ani is present C.albicans should be suspected Frequently entire GI tract is involved Can be precipitated by oral antibiotic therapy Perianal dermatitis with erythema, oozing, and maceration is present Psychogenic etiology is more common than is candidiasis Differential dx: psoriasis, seborrheic dermatitis, streptococcal and staphylococcal infections, and contact dermatits-extramammary Paget’s disease Fungicides, meticulous cleansing of perianal region after bowel movements, topical corticosteroids and antipruritics (Atarax)

Candidal Paronychia Chronic inflammation of nail fold produces occasional discharge of thin pus, cushionlike thickening of paronychial tissue, slow erosion of lateral borders of nails, gradual thickening and brownish discoloration of nail plates, and development of pronounced transverse ridges Mostly fingernails are affected, frqently only one nail Usually chronic acute forms have been reported Caused by C. albicans ,but a secondary mixed bacterial infection can occurthose who frquently have hands in water or who handle moist objects are affected; cooks, dishwashers,bartenders,nurses,canners, etc

CP Manicuring nails sometimes is responsible for mechanical or chemical injuries leading to infection Ingrown toenails with chronic paronychia Seen in pts with diabetes Avoid chronic moisture exposure; get diabetes under control Oral fluconazole once weekly or pulse dose itraconazole should be effective Anticandidal lotions are probably preferable to creams and may also be effective Topical therapy should continues for 2-3 months to prevent recurrence

Erosia Interdigitalis Blastomycetica
Oval-shaped area of macerated white skin on web between and extending onto sides of fingers Usually at center of lesion are one or more fissures with raw, red bases With progression macerated skin peels off, leaving painful, raw,denuded area surrounded by a collar of overhanging white epidermis Nearly always affects third web Moisture beneath rings macerates skin and predisposes to infection Also seen in diabetics, those who do housework, launderers, and others exposed to macerating effects of water and strong alkalis

EIB Intertriginous lesions between the toes are similar
Usually white, sodden epidermis that is thick and does not peel off freely On feet fourth interspace is most often involved Areas are apt to be multiple Clinically indistinguishable from tinea pedis Dx made by culture Tx is with topical anticandidal preparations

Chronic Mucocutaneous Candidiasis
A heterogeneous group of pts whose infection with Candida is chronic but superficial Onset before age 6 Onset in adult life may herald the occurrence of thymoma Cases are either inherited or sporadic When inherited an endocrinopathy is often found Msot cases have well-defined limited defects of cell-immunity Oral lesions are diffuse and perleche and lip fissures are common

CMC Entire thickness of nail plates is involved
Nails become thickened and dystrophic There is associated paronychia Hyperkeratotic, hornlike, or granulomatous lesions are often seen Systemic fluconazole, itraconazole, or ketaconazole is needed for prolonged and repeated and higher doses than usual Management protocols vary and experience is limited

Systemic Candidiasis Capable of producing severe, destructive, disseminated disease, invariably when host defenses are down High risk pts: pts with malignancies, AIDS pts, transplant pts requiring immunosuppressive drugs, pts receiving oral cortisone, pts who have had multiple surgical operations especially cardiac, pts with indwelling catheters, and heroin addicts Initial sign is varied: FUO,pulmonary infiltrates,GI bleeding, endocarditis, renal failure, meningitis, osteomyelitis, endophthalmitis, peritonitis, or a disseminated maculopapular eruption

SC Cutaneous findings are erythematous macules that become papular, pustular, and hemorrhagic, and may progress to necrotic, ulcerating lesions resembling ecthyma gangrenosum Deep abscesses may occur Trunk and extremities are usual sites of involvement Proximal muscle tenderness is a common finding Demonstration of microorganisms or a positive culture plus clinical picture will aid diagnosis Candida colonization of endotracheal tubes in low-birth-wt neonates predisposes to systemic disease

SC If candida is cultured within the first week of life there is a high rate of systemic disease There is a 50% chance of systemic disease if 1 or more cultures is positive Mortality has declined from 80% in the 1970’s to 40% in the 1990’s because of early empiric antifungals and better prophylaxis

THE END Thank You

Chapter 15 Diseases Resulting from Fungi and Yeasts

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Chapter 15 Diseases Resulting from Fungi and Yeasts

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