Cutaneous Fungal Infections

Cutaneous Fungal InfectionsDR. NOUF TALAL MILEHDERMATOLOGY DEMONSTRATOR

1Cutaneous Fungal InfectionsDermatomycosis - general name for any skin disease caused by a fungus.

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

2Cutaneous Fungal InfectionsEtiological agents are called dermatophytes .

Three important anamorphic genera are involved in ringworm.

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

4DERMATOPHYTESClassified 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).

5DERMATOPHYTOSISPathogenesis and ImmunityContact and trauma.Moisture.Crowded living conditions.Cellular immunodeficiency (chronic inf.).Re-infection is possible (but, larger inoculum is needed, the course is shorter ).

6Major 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.

7 TransmissionClose human contact.

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

Animal-to-human contact (Zoophilic).8DERMATOPHYTOSIS 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).

9CLINICAL 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

10Tinea 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.

11Tinea Pedis Athletes Foot Infection

12Dermatophytid Reaction

13Tinea 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.

14Tinea 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).

15Tinea corporis body ringworm

16Tinea 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.

17Tinea 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.

18Tinea Cruris Jock Itch

19Tinea unguium - ringworm of the nailsTinea unguium or onychomycosis can take 4 forms :Distal subungual onychomycosisProximal subungual onychomycosisSuperficial white onychomycosisCandidal onychomycosis

20Tinea unguium - ringworm of the nailsMost commonly caused by T. rubrum, then E. floccosum or other Trichophyton species.

Resistant to treatment, rarely resolves spontaneously.

21Tinea 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 .

22Tinea Unguium Nail Infection

23Tinea 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.24Tinea 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. 25Tinea 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.

26Tinea 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.27Tinea 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)

28Tinea 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.

29Clinical ManifestationsEndothrix ( black dot )Ectothrix ( gray patch )Kerionfavus

30Tinea CapitisClinical ManifestationsClinical Characteristics according to Causative Agent

InflammatoryNoninflammatoryBlack DotsFavusMicrosporum audouiniiM audouiniiTrichophyton tonsuransTrichophyton schoenleiniiMicrosporum canisM canisTrichophyton violaceumT violaceumMicrosporum ferrugineumT tonsuransT schoenleiniiT tonsuransT tonsurans31DiagnosisClinical Diagnosis.

Direct Examination : ( hyphae and arthrospores )

Culture : (Mycobiotic agar ,Sabouraud dextrose agar )

32Ectothrix and Endothrix

Fluorescing hair (under Wood's lamp)

33DiagnosisImmunologic Study : ( type I response and a delayed type IV response )

Histopathology : ( growth of hyphae and formation of arthroconidia )34Rapid identification and differentiation of fungal DNAin dermatological specimens by LightCycler PCRRalf Gutzmer, Susanne Mommert, Uta Ku ttler, Thomas Werfeland Alexander KappIn 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, 12071214ormation in a substantial number of patients35Differential Diagnosis According to Clinical PresentationDiffuse 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.36Treatment Topical Treatment :

Shampoo containing 2% selenium sulfide.

shampoos containing 2% ketoconazole.

Topical antifungal cream : ketoconazole (nezoral), micinazole ( daktarin)37Oral 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.38Griseofulvinbetween 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.

39Terbinafine

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.

40Terbinafine 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 .

41Itraconazole

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.42ItraconazoleAdvantage. 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.

43Fluconazole

Doses : 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

44 Systemic DrugRecommended DoseDurationGriseofulvinChild. 15 mg/kg/dAdult 250 mg/day BID8-12 wkTerbinafine10-20kg 62.5 mg; 20-4-kg 125 mg; > 40 kg 250 mg4- wk

ItraconazoleChild. 5 mg/kg/dAdult 200 mg/ day1-4 wk45Terbinafine 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).46Additional measuresExclusion 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)

47Treatment 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.

48options 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 scalpTreatment : twice weekly selenium sulphide or povidone iodine shampoo 49Follow-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.50Microsporum audouinii

Macroconidia are often irregular or non-uniform in shape. Colonies on culture media are flat, silky in appearance.

51Microsporum canisMacroconidia are abundant, thick-walled with many septa, up to 15. Macroconidia are often hooked or curved at ends.

52Microsporum 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.

53Trichophyton mentagrophytes

microconidia is grape-like clusters. Macroconidia, when present, are cigar-shaped. Spiral hyphal cells. Cultures tend to be white and downy.

54Trichophyton rubrum

Microconidium are clavate or "teardrop" shape with a broad attachment point of the hyphae. In culture the color is reminiscent of venous blood.

55Trichophyton tonsurans

Colonies whitish and folded. Colonies are yellowish-brown color on reverse of colony. Microconidia are longer and larger than in T. rubrum

56Trichophyton violaceum

Colony deep violent in color, purplish pigment diffuses into media. Hyphae coarser in appearance than seen in other dermatophytes

57Trichophyton verrucosum

Very slow growing, no pigment on reverse to yellow. produces many small microconidia and occasionally macroconidia are produced.Large-spored ectothrix

58Trichophyton schoenleinii

Endothrix infection of hair. Colonies waxy and may become convoluted from folds that develop.

59THANK YOU

60ReferencesFitzpatricks 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;48:189-93.61