Lec 7 : Fungal Skin Infections

• Cutaneous Manifestations of Fungal Infections are covered in COM 5851 LEC7, focusing on the Integumentary System.
• The learning objectives include recognizing and identifying the cutaneous manifestations, epidemiology, medical characteristics, diagnosis, and treatment of common fungal infections.

Mucocutaneous Candidiasis

• Etiology: Candida albicans is responsible.
• Epidemiology: It is a worldwide infection, normally found in the mouth, skin, vagina, and gastrointestinal tract.
• Pathogenesis: Candida has three modes of growth: pseudohyphae, hyphae, and budding yeasts and can switch between phenotypes. Yeast cells adhere to host cells (via adhesins), then transition to hyphae, and invasins induce uptake of Hyphae into host cells by endocytosis.
• Virulence factors include candidalysin (peptide toxin), biofilm formation (protective), and phenotypic switching (adaptation).
• Host Response: T helper cells and Innate Lymphoid cells protect against Candida.
• In systemic candidiasis, Neutrophils, Monocytes, and Macrophages are the main immune cells in host defense.
• Clinical Manifestations: It presents as diffuse superficial scrapable white patches on the tongue and moist mucosae, often painless or with soreness.
• Diagnosis: Clinical inspection of the ora/recto-vaginal mucosa/diaper region, microscopy using KOH prep, and blood culture (Gold standard). T2Candida DNA Blood assay and Beta-D-Glucan antigen tests are available.
• It can manifest as oral thrush, diaper dermatitis, vulvovaginitis, or esophageal candidiasis.
• Disseminated Candidiasis (immunocompromised) is seen in IV drug abusers.
• Treatment involves oral fluconazole, nystatin, clotrimazole, and topical imidazole.
• Prevention includes oral hygiene, diet control, and stress management, with good diabetes control.

Tinea Capitis (Ringworm of Scalp)

• Etiology: Trichophyton rubrum is most common, along with Trichophyton tonsurans and Microsporum.
• Epidemiology: It is worldwide, mainly in the tropics, with transmission via direct contact (skin) or fomites.
• Pathogenesis: Fungal hyphae adhere to the skin of the scalp, grow into the hair shaft and hair follicles. Sporulation in the hair shaft causes it to burst and curl, creating a black dot on the scalp.
• Virulence factors include proteases to hydrolyze keratin in skin and hair, allowing penetration of fungus.
• Host Response: Cell-mediated immunity, proliferation of keratinocytes, and inflammation.
• Clinical Manifestation: Presents as circumscribed inflammatory lesions on the scalp with areas of alopecia. Favus presents as a superficial scaly circumscribed area of alopecia, and Kerion is an inflammatory, pus-filled circumscribed area of alopecia (abscess), sometimes with purulent drainage.
• Diagnosis: KOH Prep (hyphae and spores), fungal culture, and non-fluorescence of Trichophyton tonsurans with Wood's Lamp.
• Griseofulvin is the treatment.
• Complications include secondary bacterial infection/cellulitis.
• Prevention involves avoiding sharing hair/head items.

Tinea Corporis

• Etiology: Trichophyton rubrum is most common, along with Microsporum canis (dogs) and Microsporum catis (cats).
• Epidemiology: It is worldwide, preferring warmth and moisture, with cats being a common source of infection. Transmission via direct contact (skin).
• Pathogenesis: The fungus invades the epidermis (superficial/dead horny layer), with very resistant spores. Extremes of temperature (hot/cold) inhibit growth.
• Virulence factors include the fungus secreting the enzyme keratinase (proteases digest keratin).
• Host Response: Limited inflammatory response on the skin.
• Clinical Manifestation: "Ring worm" of the skin, characterized by a pruritic, mildly erythematous circular rash. Wood's Lamp (UV light; 365nm) results in fluorescence (brilliant green).
• Diagnosis: Microscopy of skin scrapings, KOH Prep, and fungal culture.
• Treatment involves oral griseofulvin, topical imidazoles, fluconazole, and terbinafine.

Tinea Versicolor

• Etiology: Malassezia furfur (Pityrosporum orbiculare).
• Epidemiology: Ubiquitous, peaking in summer (humidity), with transmission via direct contact (skin).
• Pathogenesis: Monomorphic yeast, lipophilic (thrives on sebaceous skin), involving the epidermal area of skin (superficial), with mild cutaneous inflammation.
• Virulence Factors: Multifactorial (enzymatic; host immunity; environmental; genetic).
• Host Response: Cutaneous changes where skin areas involved fail to tan in summer, leading to superficial pigmentary changes.
• Clinical Manifestation: Diffuse fine macular scales with skin pigment changes (benign) (hyperpigmented/hypopigmented patches) common in adolescents. Commonly seen on the chest and back.
• Diagnosis: Microscopy (skin scrapings) and KOH Prep (hyphae + spores). PCR is rarely used.
• Treatment involves selenium sulfide shampoo and imidazoles.
• Complications are rare, mainly cosmetic.
• Prevention includes keeping skin dry and clean.

Tinea Unguium

• Etiology: Trichophyton rubrum, Trichophyton metagophytes, Candida albicans, and dermatophytes.
• Epidemiology: High prevalence in the elderly, with Candida more common in females.
• Pathogenesis: Onychomycosis (fungal infection of fingernails and toenails) manifests as spongiosis, acanthosis, papillomatosis with edema, and Subungal hyperkeratosis (scaling occurs under the nail, crumbling of the free end of the nail plate). Discoloration of the nail (white, yellow, grey, or green) and Onycholysis (separation of nail plate).
• Clinical Manifestations: Discoloration of the nail and nail bed (white, black, yellow or green), thickening of nail, brittle nails that chip or break easily, discoloration of skin around the nail (white or yellow), dry or scaly skin around the nail, and a foul smell.
• Tinea pedis is a fungal infection of the foot (due to warm moist unclean conditions), typically between toenails and commonly caused by Trichophyton rubrum.
• Diagnosis: Tinea Unguium
• Treatments include oral Griseofulvin, Terbinafine, Itraconazole and Ketoconazole.
• Complications include pain, transmission of fungal infection to other body sites, and bacterial cellulitis (in immunocompromised hosts).
• Prevention involves avoiding shared combs, hairbrushes, and headrests.

Tinea Nigra

• Etiology: Hortaea wernickii (formerly called Exophilia werneckii).
• Epidemiology: Mainly in S. America, Africa, Asia. Tropical/Sub-Tropical. Transmission: Direct contact (abraded skin).
• Pathogenesis: Involves the Epidermal area (stratum corneum) of skin (superficial infection). Hortea Wernicke is a Monomorphic Yeast with Brown pigmented (dematiaceous) branched septate hyphae + budding yeast cells.
• Virulence Factors: Melanin (antiphagocytic), crucial for growth. Proteolytic and lipolytic enzymes enable colonization of skin.
• Host Response: Inflammatory.
• Clinical Manifestation: Dark brown/black painless patches: palms of hands and soles of feet
• Diagnosis: Microscopy (Skin scrapings) and KOH Prep (hyphae and spores). Fungal Culture.
• Treatment: Topical Imidazole.
• Complications: Rare.
• Prevention: Skin hygiene; Treat skin lesions.

Mycetoma

• Etiology: Eumycetoma is caused by a fungus (Madurella mycetomatis). Formerly called "Maduro foot". Actinomycetoma is caused by bacteria (Nocardia).
• Epidemiology: Two types: Eumycetoma (fungal infection: Madurella mycetomatis) and Actinomycetoma (bacterial infection: Nocardia). Infection commonly through a break in the skin, often on a person's foot.
• Pathogenesis: chronic, suppurative disease of the skin and subcutaneous tissue, characterized by a triad: tumor, fistulas and granulomas (polymorphous inflammatory cells consisting of neutrophils, lymphocytes, plasma cells, histocytes). Infection is osteolytic. Caused by skin inoculation secondary to minor trauma.
• Clinical Manifestations: Firm, usually painless but debilitating granulomatous masses under the skin, with sinus tracts that drain pale, red, or yellow grains. Can affect underlying bone. Eumycetoma is more common on extremities (foot). Actinomycetoma is more common on chest, abdomen and head.
• Diagnosis: Mycetoma (Eumycetoma).
• Treatment: Antifungals, occasionally, surgery.
• Complications: Degenerative scars of foot, Cellulitis, Osteomyelitis, Sepsis.
• Prevention: Wearing shoes. Good foot hygiene.

Chromoblastomycosis

• Etiology: Fonsecaea pedrosoi (commonly); Fonsecaea monophora; Cladophialophora carrionii.
• Epidemiology: Worldwide; tropics; black molds found in soil. Associated with plants (palm tree leaf and cacti).
• Pathogenesis: Chronic cutaneous and subcutaneous fungal infection resulting from traumatic implantation of dematiaceous fungi through the ski. Slow-growing verrucous nodules that coalesce and form hyperkeratotic plaques. Typically, transcutaneous puncture wound by plant (Cactus; Palm leaf).
• Clinical Manifestations: Painless, non-pruritic. Wart-like lesions on exposed areas of the skin such as the legs or forearms. (>10 cm in diameter). Appear flattened (plaque-like) + central scarring or atrophy.
• Diagnosis: Chromoblastomycosis.
• Treatment: Itraconazole, Terbinafine; Surgical excision.
• Complications: Secondary bacterial infection.
• Prevention: Avoid walking barefoot in endemic areas.

Diagnoses Case Studies

• Case #1: Tinea ungium (Onychomycosis) presents as thickening and discoloration of nails and nailbeds of fingers and/or toes, making them crisp and fragile, with separation of nail plate and foul smell. The infective agent is a dermatophyte (fungus).
• Case #2: Mycetoma presents as firm, painless, debilitating subcutaneous granulomatous masses (typically of feet) characterized by tumors, fistulas, and extrusion of colored grains, with chronic local putrid infection. The infective agent is a unique bacterium/fungus inoculated at the site of skin trauma. Complications include cellulitis, osteomyelitis, and risk of amputation.
• Case #3: Tinea versicolor presents as diffuse fine macular scales on the trunk (anterior +/- posterior) characterized by hypopigmented/hyperpigmented patches. The infective agent is a dermatophyte fungus. It is commonly seen in adolescents, with skin moisture and sun exposure making it more apparent. Selenium sulfide shampoo helps.
• Case #4: Tinea capitis presents as a circumscribed inflammatory scaly lesion on the scalp consisting of papules, vesicles, and pustules (manifest as favus or kerion + focal alopecia). The infective agent is a fungus (dermatophyte) that sporulates in the hair shaft and causes it to burst and curl.
• Case #5: Mucocutaneous Candidiasis presents as diffuse superficial scrapable white, painless/sore patches on the tongue and moist mucosae (particularly flexural creases). The infective agent is a fungus with three modes of growth (pseudohyphae, hyphae, and budding yeasts). It manifests as diaper rash in infants, vulvovaginitis, and mouth/esophageal colonization.
• Case #6: Chromoblastomycosis presents as painless, non-pruritic wart-like (verrucous) hyperkeratotic plaques and nodules with central scarring and atrophy on exposed areas of skin of extremities (>10cm), slow-growing and chronic. The infective agent is a black mold, and it is secondary to a puncture wound by plants (cactus; palm leaves).
• Case #7: Tinea Nigra presents as dark brown/black painless patches on the palm of the hand/sole of the foot. The infective agent is a monomorphic dematiaceous yeast with branched septate hyphae + budding yeast cells commonly found in the tropics.
• Case #8: Tinea corporis presents as mildly pruritic and erythematous circumscribed (“ring-like”) rash on the trunk or extremities. The infective agent is a dermatophyte fungus, some of which are found on dogs and cats, and is contagious.

Most Common Infective Agents

• Tinea ungium: Trichophyton rubrum
• Mycetoma (Eumycetoma): Madurella mycetomatis
• Tinea versicolor: Malassezia furfur (Pityrosporum orbiculare)
• Tinea capitis: Trichophyton rubrum and Trichophyton tonsurans
• Mucocutaneous Candidiasis: Candida albicans
• Chromoblastomycosis: Fonsecae pedrosoi
• Tinea Nigra: Hortaea wernicke
• Tinea corporis: Trichophyton rubrum and Microsporum canis/catis