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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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  • Paracoccidioidomycosis Surveillance and Control

    Paracoccidioidomycosis Surveillance and Control

    Received: January 6, 2010 J. Venom. Anim. Toxins incl. Trop. Dis. Accepted: January 6, 2010 V.16, n.2, p.194-197, 2010. Full paper published online: May 30, 2010 Letter to the Editor. ISSN 1678-9199. Paracoccidioidomycosis surveillance and control Mendes RP (1) (1) Department of Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP – Univ Estadual Paulista), Botucatu, São Paulo State, Brazil. Dear Editor, Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides brasiliensis, a thermally dimorphic fungus known to produce disease, primarily in individuals whose profession is characterized by intense and continuous contact with the soil. PCM presents a high incidence in Brazil, especially in the southeastern, southern and center-western regions of the country. On reporting the first two cases, in 1908, Adolpho Lutz presented the clinical picture and histopathological findings – tubercles with giant epithelioid cells and fungal specimens with exosporulation – of the infection. He cultured the fungus at different temperatures, demonstrating its mycelial and yeast phases, and reproduced the disease in guinea pigs (1). Few researchers in that era were so comprehensive when reporting a new disease and its etiological agent. This deep mycosis prevails among men aged between 30 and 59 years, comprising their most productive working phase, with a gender ratio of 10:1 (2). Analysis of 3,181 death certificates that reported PCM during the 16-year period from 1980 to 1995 revealed a mortality rate of 1.487 per one million inhabitants, indicating its considerable magnitude but low visibility (3). PCM was the eighth greatest cause of death from predominantly chronic or repetitive types of infectious and parasitic diseases in Brazil, surpassed only by AIDS, Chagas’ disease, tuberculosis, malaria, schistosomiasis, syphilis and Hansen’s disease.