Cutaneous Fungal Infections

DR. NOUF TALAL MILEHDERMATOLOGY DEMONSTRATOR

Cutaneous Fungal Infectionso Dermatomycosis  - general name for any

skin disease caused by a fungus.

o Dermatophytosis - "ringworm" disease of the nails, hair, and/or stratum corneum of the skin caused by fungi called dermatophytes.

Cutaneous Fungal InfectionsEtiological agents are called dermatophytes . 

Three important anamorphic genera are involved in ringworm.

1)Microsporum. 2)Trichophyton. 3) Epidermophyton.

Cutaneous Fungal InfectionsDermatophytes are keratinophilic - "keratin

loving". Digest keratin by their keratinases

Keratin is a major protein found in horns, hooves, nails, hair, and skin.

Ringworm - disease called ‘herpes' by the Greeks, and by the Romans ‘tinea' (which means small insect larvae).

DERMATOPHYTESClassified into three groups depending on

their usual habitat

ANTROPOPHILIC keratin-utilizing on hosts - humans (e.g., M. audounii, T.

tonsurans, Trichophyton rubrum )

GEOPHILIC keratin-utilizing soil saprophytes (e.g., M. gypseum…).

ZOOPHILIC keratin-utilizing on hosts - living animals (e.g., M. canis, T. verrucosum).

DERMATOPHYTOSISPathogenesis and Immunity

Contact and trauma.Moisture.Crowded living conditions.Cellular immunodeficiency (chronic inf.).Re-infection is possible (but, larger

inoculum is needed, the course is shorter ).

Major sources of ringworm infection

Schools, military camps, prisons.

Warm damp areas (e.g., tropics, moisture accumulation in clothing and shoes). 

Animals (e.g., dogs, cats, cattle, poultry, etc.).

Historical note:  More people were shipped out of the Pacific Theater in WWII back to U.S. because of ringworm infection then through injury.

Transmission

Close human contact.

Sharing clothes, combs, brushes, towels, bedsheets... (fomites).

Animal-to-human contact (Zoophilic).

DERMATOPHYTOSIS Clinical Classification

Infection is named according to the anatomic location involved:

Tinea capitis - ringworm infection of the head, scalp, eyebrows, eyelashes.

Tinea facialis - of the face.Tinea corporis - of the body .Tinea cruris - of the groin (jock itch).Tinea unguium - of the nails.Tinea barbae - of the beard.Tinea manuum - of the hand.Tinea pedis - of the foot (athlete's foot).

CLINICAL MANIFESTATIONS OF RINGWORM Tinea pedis - Athletes' foot infection Between toes or toe webs (releasing of

clear fluid) - 4th and 5th toes are most common, sole .

Commonly, patients describe pruritic, scaly soles and, often, painful fissures between the toes.

Most frequently due to: - Trichophyton (T.) rubrum

- T. interdigitale, previously called T. mentagrophytes var. interdigitale

- Epidermophyton floccosum

Tinea pedis - Athletes' foot infection 3 possible clinical presentations: ( Interdigital, Chronic hyperkeratotic

(moccasin) Inflammatory or vesiculobullous )

Allergic reactions are sometimes associated with tinea pedis and other ringworm infections.

Tinea Pedis – Athlete’s Foot Infection

Dermatophytid Reaction

Tinea corporis - body ringworm

Generally restricted to stratum corneum of the smooth skin.

Symptoms result form fungi metabolites such as toxin/allergens.

Produces concentric or ring-like lesions on skin (annular plaques), and in severe cases these are raised and may become inflamed.

Tinea corporis - body ringwormAll forms of tinea corporis caused by T. rubrum, T. mentagrophytes, T. tonsurans, M.

canis, and  M. audouinii are treatable with topical agent containing ketoconazole, miconazole, etc...

Widespread tinea corporis and more severe types (lesions) require systemic griseofulvin treatment (about 6 weeks for effective treatment).

Tinea corporis – body ringworm

Tinea cruris - ringworm of the groin and surrounding region

More common in men than women.

Infection seen on scrotum and inner thigh, the penis is usually not infected.

Several causes of tinea cruris include T. rubrum , E. flocossum.

Predisposing factors include persistent perspiration, high humidity, tight clothing , diabetes and obesity, topical glucocorticoid application.

Tinea cruris - ringworm of the groin and surrounding region

Symptom: none, prurits.

Signs: large, scaling well demarcated red / tan/ brown/ plaques.

Diagnosis

If lesion "weep", it is likely caused by a yeast, such as,  Candida albicans, and not by a  dermatophyte, especially if infections are seen in a woman.

Tinea Cruris – Jock Itch

Tinea unguium - ringworm of the nails

Tinea unguium or onychomycosis can take 4 forms :

Distal subungual onychomycosisProximal subungual onychomycosisSuperficial white onychomycosisCandidal onychomycosis

Tinea unguium - ringworm of the nails

Most commonly caused by T. rubrum, then E. floccosum or other Trichophyton species.

Resistant to treatment, rarely resolves spontaneously.

Tinea unguium - ringworm of the nails

Topical treatments - poor record of cure. If the disease involve one or two nails

loceryl nail loquer ( amorolfiene ).If the disease involve multable nails

lamfine (terbinafine) 250 mg (6 w for fingure nail, 12 w for toe nail )

Systemic griseofulvin therapy can lead to remission .

Tinea Unguium – Nail Infection

Tinea facialis Dermatophytosis of the glabrous facial skin.More common in children.Etiology : T. tonsurans , T. rubrum, T.

mentagrophytes ,

M. audouinii, M. canis .Predisposing factors : animal exposure,

topical application of glucocorticoid.Symptoms : asymptomaticCharacterized by a well-circumscribed

erythematous patch, minimal scaling.

Tinea Barbae Involving the beard and moustache areas.Males only, adult.Etiology : T. verrucosum, T. mentagrophytes.Predisposing factors : more common in

farmers.Symptoms : pruritus, tenderness, pain.Signs : scattered, discrete follicular pustules

and papules.D.D. : Beard folliculitis ( s.aures )Treatment : see tinea capitis.

Tinea capitis - ringworm of the scalp, eyebrows and eyelashes

Predominantly a disease of preadolescent children

Caused by species of Microsporum and Trichophyton.

Fungus grows into hair follicle.

Using a Wood's lamp, on hair Microsporum species tend to fluoresce green while Trichophyton species generally do not fluoresce.

Lack of fluorescence does not mean it isn't Microsporum.

Tinea capitisclassified according to the microscopic pattern of fungal invasion as endothrix, ectothrix, and favus.

Endothrix : Fungi invade the inside of the hair shaft.composed of fungal arthroconidie and

hyphae, without cuticle destruction. The causative organisms TVS.

Tinea capitis Ectothrix : Fungi invade the outside of the hair shfat.The process of ectothrix invasion is similar to endothrix invasion, with the exception that the hyphae destroy the hair cuticle, then convert into infectious arthroconidia.

The causative organisms are M. audouinii, M. canis, M distortum, T. ferrugineum. All these organisms cause fluorescence under Wood light.

( to remamber, SEE CATS AND DOGS FIGHT)

Tinea capitis Favus Is a type of inflammatory tinea that is

characterized by invasion of hair by hyphyae not produce conidia, and presence of linear air spaces.

Mainly caused by T schoenleinii.

Clinical Manifestations

Endothrix ( black dot )Ectothrix ( gray patch )Kerionfavus

Tinea CapitisClinical ManifestationsClinical Characteristics according to

Causative AgentInflammatory Noninflammatory

Black Dots Favus

Microsporum audouinii

M audouinii Trichophyton tonsurans

Trichophyton schoenleinii

Microsporum canis

M canis Trichophyton violaceum

T violaceum Microsporum ferrugineum

T tonsurans

T schoenleinii T tonsurans

T tonsurans

DiagnosisClinical Diagnosis.

Direct Examination : ( hyphae and arthrospores )

Culture : (Mycobiotic agar ,Sabouraud dextrose

agar )

Ectothrix and Endothrix

Fluorescing hair (under Wood's lamp)

DiagnosisImmunologic Study : ( type I response and a delayed type IV

response )

Histopathology : ( growth of hyphae and formation of

arthroconidia )

Rapid identification and differentiation of fungal DNAin dermatological specimens by LightCycler PCRRalf Gutzmer, Susanne Mommert, Uta Ku¨ ttler, Thomas Werfeland Alexander Kapp

In conclusion, we developed a fast and simple LightCyclerbased PCR to detect DNA of the dermatologically most relevant fungi and to differentiate dermatophytes, yeasts and non-dermatophyte moulds.

This can complement mycological culture and direct microscopy in the diagnosis of fungal skin disease and provides additional diagnostic information in a substantial number of patients.

Journal of Medical Microbiology (2004), 53, 1207–1214ormation in a substantial number of patients

Differential Diagnosis According to Clinical Presentation

Diffuse scaling (noninflammatory) : Seborrheic and atopic dermatitis, psoriasis.

Alopecia plaque (noninflammatory) :Seborrheic and atopic dermatitis, psoriasis.

Black dots : Alopecia areata, trichotillomania.Diffuse pustular (inflammatory) : Bacterial

folliculitiskerion celsi (inflammatory): Abscess, tumor.

Treatment Topical Treatment :

Shampoo containing 2% selenium sulfide.

shampoos containing 2% ketoconazole.

Topical antifungal cream : ketoconazole (nezoral), micinazole ( daktarin)

Oral Griseofulvin ( treatment of choice )Fungistatic, and inhibits nucleic acid synthesis,

arresting cell division at metaphase and impairing fungal cell wall synthesis.

It is also anti-inflammatoryTablet or suspension formRecommended dose: for pediatric microsized 15 mg/kg/day, ultramicrosized 10

mg/kg/day

For adults up to 250 mg/ day, Bid.

Griseofulvinbetween 8 and 12 weeks.Side effects nausea and rashes in 8-15%.  contra-indicated in pregnancy, lupus

erythematosus, porphyria and severe liver disease.

Advantages inexpensive, effective, safe. Disadvantages: Prolonged treatment

required.Drug interactions : warfarin, cyclosporin

and the oral contraceptive pill.

Terbinafine

Acts on fungal cell membranes and is fungicidal.

It is effective against all dermatophytes

Effective as griseofulvin and is safe for the management of scalp ringworm due to Trichophyton sp.

Dosage : 250 mg qd, depends on the weight of the patient ( if the weight 10-20 kg 62.5 mg, between 20-40 kg 125 mg, > 40 kg 250 mg.

Terbinafine

Side-effects include; gastrointestinal disturbances and rashes in 5% and 3% of cases,

Advantages. Fungicidal so shorter therapy required (cf. griseofulvin) so increased compliance more likely.

Disadvantages. No suspension formulation .

Itraconazole exhibits both fungistatic and fungicidal activity

Fungistatic through depletion of cell membrane ergosterol, which interferes with membrane permeability.

Doses in children 5 mg/kg per day.

in adult 200 mg/day.

Duration 4 weeks.

ItraconazoleAdvantage. Pulsed shorter treatment

regimens are possible.

Disadvantage. possible side-effects. Potential drug interactions.

Drug interactions. Enhanced toxicity of anticoagulants (warfarin), antihistamines (terfenadine and astemizole), antipsychotics (sertindole), anxiolytics (midazolam), digoxin.

FluconazoleDoses : for pediatric 6 mg/kg per day for 4

weeks for adult : 200 mg/ day

Ketoconazole

Doses : for pediatric 5 mg/kg per day for adult 200-400 mg / dayits use in children is limited by hepatotoxicity

Systemic Drug Recommended

DoseDuration

Griseofulvin Child. 15 mg/kg/dAdult 250 mg/day BID

8-12 wk

Terbinafine 10-20kg 62.5 mg; 20-4-kg 125 mg; > 40 kg 250 mg

4- wk

Itraconazole Child. 5 mg/kg/dAdult 200 mg/ day

1-4 wk

Terbinafine hydrochloride oral granules versus oralgriseofulvin suspension in children with tinea capitis:Results of two randomized, investigator-blinded,multicenter, international, controlled trials*Objective: To compare the efficacy and safety of a

new pediatric formulation of terbinafine hydrochloride

oral granules with griseofulvin oral suspension in the treatment of tinea capitis.

Results: Rates of complete cure and mycologic cure were significantly higher for terbinafine than for

griseofulvin (45.1% vs 39.2% and 61.5% vs 55.5%, respectively; P.05 )

2008 by the American Academy of Dermatology, Inc.doi:10.1016/j.jaad.2008.02.019).

Additional measures

Exclusion from schoolFamilial screeningCleansing of fomites.Soaking off crust from kerions or pustulesSteroids ( predinsone 1mg/kg/day for 2

weeks, in child with sever painfull kerion)

Treatment failures

The reasons for this include:Lack of compliance with the long courses of

treatment. Suboptimal absorption of the drug. Relative insensitivity of the organism. Reinfection.

options include Increase the dose or duration of the original

drug.Change to an alternative antifungal e.g.

switch from griseofulvin to terbinafine or itraconazole.

CarriersPerson who does not have clinical signs of tinea

capitis but has a positive fungal culture from the scalp

Treatment : twice weekly selenium sulphide or povidone iodine shampoo

Follow-up

Repeat mycology sampling is recommended at the end

of the standard treatment period and then monthly

until mycological clearance is documented. Or by clinical imporovment.

Microsporum audouinii

Macroconidia are often irregular or non-uniform in shape.

Colonies on culture media are flat, silky in appearance.

Microsporum canisMacroconidia are abundant, thick-walled

with many septa, up to 15.  Macroconidia are often hooked or curved at ends.

Microsporum gypseumProduces abundant macroconidia brownish-

yellow due to large numbers macroconidia.   Surface of culture colony often is powdery in appearance.

Macroconidia usually have 4-6 septa or crosswalls.

Microconidia are smaller than in M. canis.

Trichophyton mentagrophytes microconidia is grape-like clusters. Macroconidia, when present, are cigar-

shaped. Spiral hyphal cells. Cultures tend to be white and downy.

Trichophyton rubrum

Microconidium are clavate or "teardrop" shape with a broad attachment point of the hyphae.

In culture the color is reminiscent of venous blood.

Trichophyton tonsurans

Colonies whitish and folded. Colonies are yellowish-brown color on reverse of

colony. Microconidia are longer and larger than in T.

rubrum

Trichophyton violaceum

Colony deep violent in color, purplish pigment diffuses into media.

Hyphae coarser in appearance than seen in other dermatophytes

Trichophyton verrucosum

Very slow growing, no pigment on reverse to yellow.

produces many small microconidia and occasionally macroconidia are produced.

Large-spored ectothrix

Trichophyton schoenleinii

Endothrix infection of hair. Colonies waxy and may become

convoluted from folds that develop.

THANK YOU

ReferencesFitzpatrick’s Dermatology in General Medicine.

6th ed. NewYork: Mc Graw Hill; 2003;Elewski BE. Tinea capitis: A current perpspective.

J Am Acad Dermatol. 2000;42 1 Pt 1:1-20.Jhangir M, Hussain I, Khushid K, Haroon TS. Aclinicoetiologic correlation in tinea capitis. Int J

Dermatol. 2002;38:275-8.Ghannoum M, Isham N, Hajjeh R, Cano M, Al-

Hasawi F, Yearick D, et al. Tinea capitis in Cleveland: Survey of elementary school students. J Am Acad Dermatol. 2003;48:189-93.