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Cutaneous Fungal Infections

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1 Cutaneous Fungal Infections
DR. NOUF TALAL MILEH DERMATOLOGY DEMONSTRATOR

2 Cutaneous Fungal Infections
Dermatomycosis  - 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.

3 Cutaneous Fungal Infections
Etiological agents are called dermatophytes .  Three important anamorphic genera are involved in ringworm. 1)Microsporum. 2)Trichophyton. 3) Epidermophyton.

4 Cutaneous Fungal Infections
Dermatophytes 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).

5 DERMATOPHYTES Classified 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).

6 DERMATOPHYTOSIS Pathogenesis 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 ).

7 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.

8 Transmission Close human contact.
Sharing clothes, combs, brushes, towels, bedsheets... (fomites). Animal-to-human contact (Zoophilic).

9 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).

10 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

11 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.

12 Tinea Pedis – Athlete’s Foot Infection

13 Dermatophytid Reaction

14 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.

15 Tinea corporis - body ringworm
All 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).

16 Tinea corporis – body ringworm

17 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.

18 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.

19 Tinea Cruris – Jock Itch

20 Tinea unguium - ringworm of the nails
Tinea unguium or onychomycosis can take 4 forms : Distal subungual onychomycosis Proximal subungual onychomycosis Superficial white onychomycosis Candidal onychomycosis

21 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.

22 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 .

23 Tinea Unguium – Nail Infection

24 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 : asymptomatic Characterized by a well-circumscribed erythematous patch, minimal scaling.

25 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.

26 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.

27 Tinea capitis classified 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.

28 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)

29 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.

30 Clinical Manifestations
Endothrix ( black dot ) Ectothrix ( gray patch ) Kerion favus

31 Tinea Capitis Clinical Manifestations
Clinical Characteristics according to Causative Agent Inflammatory 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

32 Diagnosis Clinical Diagnosis. Direct Examination :
( hyphae and arthrospores ) Culture : (Mycobiotic agar ,Sabouraud dextrose agar )

33 Ectothrix and Endothrix
Fluorescing hair (under Wood's lamp)

34 Diagnosis Immunologic Study :
( type I response and a delayed type IV response ) Histopathology : ( growth of hyphae and formation of arthroconidia )

35 Rapid identification and differentiation of fungal DNA in dermatological specimens by LightCycler PCR Ralf Gutzmer, Susanne Mommert, Uta Ku¨ ttler, Thomas Werfel and 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

36 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 folliculitis kerion celsi (inflammatory): Abscess, tumor.

37 Treatment Topical Treatment : Shampoo containing 2% selenium sulfide.
shampoos containing 2% ketoconazole. Topical antifungal cream : ketoconazole (nezoral), micinazole ( daktarin)

38 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-inflammatory Tablet or suspension form Recommended dose: for pediatric microsized 15 mg/kg/day, ultramicrosized 10 mg/kg/day For adults up to 250 mg/ day, Bid.

39 Griseofulvin between 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.

40 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 kg  62.5 mg, between kg  125 mg, > 40 kg  250 mg.

41 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 .

42 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.

43 Itraconazole Advantage. 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.

44 Fluconazole Ketoconazole
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 mg / day its use in children is limited by hepatotoxicity

45 Systemic Drug Recommended Dose Duration Griseofulvin Child. 15 mg/kg/d
Adult 250 mg/day BID 8-12 wk Terbinafine 10-20kg mg; 20-4-kg mg; > 40 kg mg 4- wk Itraconazole Child. 5 mg/kg/d Adult 200 mg/ day 1-4 wk

46 griseofulvin (45.1% vs 39.2% and 61.5% vs 55.5%, respectively; P.05 )
Terbinafine hydrochloride oral granules versus oral griseofulvin 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: /j.jaad ).

47 Additional measures Exclusion from school Familial screening
Cleansing of fomites. Soaking off crust from kerions or pustules Steroids ( predinsone 1mg/kg/day for 2 weeks, in child with sever painfull kerion)

48 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.

49 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. Carriers Person 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

50 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.

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

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

53 Microsporum gypseum Produces 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.

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

55 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.

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

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

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

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

60 THANK YOU

61 References Fitzpatrick’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. A clinicoetiologic 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:


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