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Fungal Infections Fungal Infections Eugene Sanik, D.O. 3rd Year Dermatology Resident Disclosures • No financial relationships to disclose Learning Objectives • Understand the causes of fungal infections • Illustrate and recognize their clinical presentations • Review latest evidence-based treatment guidelines Introduction to Mycology • Fungi first appeared 1.5 billion years ago • Among earliest organisms domesticated by humans • Serious problem only since 20th century • 1.5 million fungal species known • Less than 100 are pathogenic to humans • Except for dermatophytes, not contagious Classification of Fungal Diseases • Superficial - Do not have ability to invade skin, hair, or nails • Cutaneous - Dermatophytes • Deep - Localized subcutaneous (implantation or dermal spread) - Dimorphic systemic (hematogenous spread) - Opportunistic (immunocompromised patients) Classification of Fungal Diseases • Superficial - Do not have ability to invade skin, hair, or nails • Cutaneous - Dermatophytes • Deep - Localized subcutaneous (implantation or dermal spread) - Dimorphic systemic (hematogenous spread) - Opportunistic (immunocompromised patients) Superficial Fungal Infections • Pityriasis versicolor • Tinea nigra • Black piedra • White piedra Pityriasis Versicolor Treatment of Pityriasis Versicolor • Topical ketoconazole very effective against Malassezia • Oral fluconazole and itraconazole as effective with lower recurrence • Oral ketoconazole not recommended (FDA warning) • Oral terbinafine not effective Tinea Nigra Hortaea werneckii (melanin-producing yeast) Black Piedra and White Piedra Piedra Hortae Trichosporon beigelii Differential Diagnosis of Piedras Trichomycosis axillaris Head Lice Corynebacterium Pediculus humanus capitis Classification of Fungal Diseases • Superficial - Do not have ability to invade skin, hair, or nails • Cutaneous - Dermatophytes • Deep - Localized subcutaneous (implantation or dermal spread) - Dimorphic systemic (hematogenous spread) - Opportunistic (immunocompromised patients) Cutaneous Mycoses • Dermatophytoses of skin, hair, and nails • Candidiasis of skin, mucous membranes, and nails • Do not invade subcutaneous tissue Dermatophytosis • Microsporum, Trichophyton, and Epidermophyton • Most common causes: • Tinea capitis – T. tonsurans • Tinea faciei – T. rubrum • Tinea corporis – T. rubrum • Tinea pedis – T. rubrum • Bullous tinea pedis – T. mentagrophytes • White superficial onychomycosis – T. mentagrophytes • Distal & proximal subungual onychomycosis – T. rubrum • betamethasone did not compromise the antifungal effects of clotrimazole • clinical endpoints consistently favored the combination drug, which relieved symptoms more rapidly • Once daily application is as effective as twice daily, with better compliance • Azoles, benzylamines, and allylamines show no difference in clinical effectiveness • Azole-corticosteroid combination achieved higher clinical cure rates than azole monotherapy • Duration inadequately addressed • When given for 2 weeks, Terbinafine has statistically significantly better cure rates than Itrazonazole, Fluconazole, Ketoconazole, and Griseofulvin. • Itraconazole for 4 weeks as effective as 2 weeks of Terbinafine Tinea Treatment: Summary TOPICAL • Any topical antifungal, once daily for 2-4 weeks - optional: add moderate potency topical steroid ORAL • Terbinafine 250mg once daily for 2 weeks Fungal folliculitis • Tinea capitis • Tinea barbae • Majocchi’s granuloma • Require treatment with oral antifungals • Fungi thought to have evolved to survive harsh winters and resist temperatures < 50°C, but authors conjecture: - Fungi may be secondarily destroyed as tissue necrosis occurs - Rapid cooling forms intracellular ice crystals and disrupts the cell membrane - rewarming damages the cell membrane again and stimulates the immune system Dermatophytid (“id”) reaction • Hypersensitivity reaction to dermatophyte antigens • Classic presentation is vesicular eruption on the sides of fingers with inflammatory tinea pedis • Examine the feet in all cases of suspected hand eczema! • Eruptions can also be urticarial and panniculitic Onychomycosis (Tinea Unguium) • T. rubrum (most common), yeast, nondermatophyte molds • Superficial white onychomycosis • Distal lateral subungual onychomycosis • Proximal subungual onychomycosis Onychomycosis Treatment Mycologic Cure Rate (negative KOH and culture) Topical Ciclopirox (Penlac) 29% Topical Tavaborole (Kerydin) 35% Topical Efinaconazole (Jublia) 55% Oral Fluconazole (Diflucan) 48% Oral Itraconazole (Sporanox) 54% Oral Terbinafine (Lamisil) 77% Candidiasis • C. albicans inhabits skin, GU, and GI tract • Opportunistic pathogen • Frequently infects intertriginous areas • Predisposing factors include hygiene, diabetes, antibiotic use, and immunosuppression • Clinical spectrum can range from short-lived superficial to overwhelming systemic infections Candidiasis Treatment TOPICAL • Any topical antifungal for cutaneous candidiasis • Rinse-and-spit with fluoconazole solution is superior to nystatin and amphotericin B for thrush ORAL • Fluconazole 50-100mg/day (95%+ success rate) Classification of Fungal Diseases • Superficial - Do not have ability to invade skin, hair, or nails • Cutaneous - Dermatophytes • Deep - Localized subcutaneous (implantation or dermal spread) - Dimorphic systemic (hematogenous spread) - Opportunistic (immunocompromised patients) Deep Fungal Infections Subcutaneous Systemic Opportunistic Sporotrichosis Blastomycosis Cryptococcosis Phaeohyphomycosis Histoplasmosis Aspergillosis Chromomycosis Coccidioidomycosis Fusariosis Mycetoma (Madura foot) Paracoccidioidomycosis Mucormycosis Lobomycosis Penicilliosis Rhinosporidiosis Zygomycosis Sporotrichosis • DDX: Atypical mycobacterium, Nocardia, Leishmania, Tularemia Chromomycosis • Fonsecaea pedrosoi (most common cause) Madura Foot (Mycetoma) Lobomycosis • Lacazia loboi • “keloidal blastomycosis” • Dolphins Histoplasmosis Blastomycosis Coccidiomycosis Paracoccidiomycosis Opportunistic Systemic • Disseminate in immunocompromised patients - Organ transplant, post-chemotherapy, HIV • Candida species most common Mucormycosis References 1. Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology. 3rd edition. Saunders Elsevier, PA; 2012. 2. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th edition. Saunders Elsevier, PA; 2011. 3. Ally R, Schürmann D, Kreisel W, Carosi G, Aguirrebengoa K, Dupont B. Esophageal Candidiasis Study Group. A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis. 2001;33:1447–54. 4. Taillandier J, Esnault Y, Alemanni M. A comparison of fluconazole oral suspension and amphotericin B oral suspension in older patients with oropharyngeal candidosis. Multicentre Study Group. Age Ageing. 2000;29:117–23. 5. López-Martínez R. Candidosis, a new challenge. Clin Dermatol 2010; 28: 178–84. 6. Dehghan M, Akbari N, Alborzi N et al. Single-dose oral fluconazole versus topical clotrimazole in patients with pityriasis versicolor: A double-blind randomized controlled trial. J Dermatol 2010; 37: 699–702. 7. Kaaman T, Torssander J. Dermatophytid – a misdiagnosed entity? Acta Derm Acta Derm Venereol 1983; 63: 404–8. 8. Neblett Fanfair R et al. N Engl J Med 2012;367:2214-2225. 9. Garcia-Cuesta C, Sarrion-Pérez MG, Bagán JV. Current treatment of oral candidiasis: A literature review. J Clin Exp Dent. 2014 Dec 1;6(5):e576-82. 10. Van Zuuren EJ, Fedorowicz Z, El-Gohary M. Evidence-based topical treatments for tinea cruris and tinea corporis: a summary of a Cochrane systematic review. Br J Dermatol. 2015 Mar;172(3):616-41. 11. El-Gohary M, van Zuuren EJ, Fedorowicz Z et al. Topical antifungal treatments for tinea cruris and corporis. Cochrane Database Syst Rev 2014; 8:CD009992. 12. Wortzel MH. A double-blind study comparing the superiority of a combination antifungal (clotrimazole)/steroidal (betamethasone dipropionate) product. Cutis 1982; 30:258–61. 13. Rotta I, Ziegelmann PK, Otuki MF et al. Efficacy of topical antifungals in the treatment of dermatophytosis: a mixed-treatment comparison meta-analysis involving 14 treatments. JAMA Dermatol 2013; 149:341–9. 14. Rotta I, Otuki MF, Sanches AC et al. Efficacy of topical antifungal drugs in different dermatomycoses: a systematic review with meta-analysis. Rev Assoc Med Bras 2012; 58:308–18. 15. Smith ES, Fleischer AB Jr, Feldman SR. Nondermatologists are more likely than dermatologists to prescribe antifungal/corticosteroid products: an analysis of office visits for cutaneous fungal infections, 1990–1994. J Am Acad Dermatol 1998; 39:43–7. 16. Rotta I, Sanchez A, Gonçalves PR et al. Efficacy and safety of topical antifungals in the treatment of dermatomycosis: a systematic review. Br J Dermatol 2012; 166:927–33. 17. Pietrzak A1, Tomasiewicz K, Kanitakis J, Paszkowski T, Dybiec E, Donica H, Wójtowicz A, Terlecki P, Chodorowska G. Trichophyton mentagrophytes-associated Majocchi's granuloma treated with cryotherapy. Folia Histochem Cytobiol. 2012 Oct 8;50(3):486-9. 18. Romano C, Rubegni P, Ghilardi A, Fimiani M. A case of bullous tinea pedis with dermatophytid reaction caused by Trichophyton violaceum. Mycoses. 2006 May;49(3):249-50. 19. Elgart GW. Subcutaneous (deep) fungal infections. Semin Cutan Med Surg. 2014 Sep;33(3):146-50. 20. Fernandez-Flores A, Saeb-Lima M, Arenas-Guzman R. Morphological findings of deep cutaneous fungal infections. Am J Dermatopathol. 2014 Jul;36(7):531-53 21. Rose AE. Therapeutic
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