Fungal Infections...10. Van Zuuren EJ, Fedorowicz Z, El-Gohary M. Evidence-based topical treatments...
Transcript of Fungal Infections...10. Van Zuuren EJ, Fedorowicz Z, El-Gohary M. Evidence-based topical treatments...
Fungal InfectionsEugene 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
Corynebacterium
Head Lice
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
SporotrichosisPhaeohyphomycosisChromomycosisMycetoma (Madura foot) Lobomycosis RhinosporidiosisZygomycosis
BlastomycosisHistoplasmosis CoccidioidomycosisParacoccidioidomycosis
CryptococcosisAspergillosisFusariosisMucormycosisPenicilliosis
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 update: Onychomycosis. J Drugs Dermatol. 2014 Oct;13(10):1173-5.
22. Gupta AK, Ryder JE, Nicol K, Cooper EA. Superficial fungal infections: an update on pityriasis versicolor, seborrheic dermatitis, tinea capitis, and onychomycosis. Clin Dermatol. 2003 Sep-Oct;21(5):417-25.
23. Trief D, Gray ST, Jakobiec FA, Durand ML, Fay A, Freitag SK, Lee NG, Lefebvre DR, Holbrook E, Bleier B, Sadow P, Rashid A, Chhabra N, Yoon MK. Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus. Br J Ophthalmol. 2015 Jun 25.
24. Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G. Invasive fungal infections in the ICU: how to approach, how to treat. Molecules. 2014 Jan 17;19(1):1085-119.
25. Teixeira CA, Medeiros PB, Leushner P, Almeida F. Rhinocerebral mucormycosis: literature review apropos of a rare entity. BMJ Case Rep. 2013 Feb 5;2013.