Entity

Common Pathogens

Clinical Manifestations

Histopathologic characteristics

 Prognosis

 Chromoblastomycosis

Fonsecaea pedrosoi

Cladosporium carrionii

F. compacta

Phialaphora verrucosa

Rhinocladiella

   aquaspersa

Chronic wart- or caulfilower-like lesions of skin and subcutaneous tissue

Sclerotic bodies

("copper pennies")

Limited infections: cure is possible; Extensive infections: cure is rare

 Mycetoma

 Madurella

   mycetomatis

M. grisea

Pyrenochaeta romeroi

Exophiala jeanselmei

Chronic skin and subcutaneous lesions with swelling and draining sinus tracts

Mycotic granules

Worse than chromoblastomycosis; Limited infections: cure is possible;

Extensive infections: cure is very rare

 Subcutaneous phaeohyphomycosis

E. jeanselmei

Wangiella dermatitidis

Phialophora spp.

Bipolaris spp.

Heterogenous: well-formed cysts; subcutaneous tissue invasion; extensive sinus tracts

Fungi within non-keratinized tissue beneath the dermal layer; no granules or sclerotic bodies

Cystic form: good

Non-encapsulated form: fair, depends on extent of tissue invasion; cures less likely in immunosuppressed patients

   Dermatomycosis          and onychomycosis

Alternaria spp.

Hendersonula     

   toruloidea

Phialophora spp.

Onychocola spp.

Indistinguishable from infections by dermatophytes

Fungi within keratinized tissue with extensive host response and tissue damage

Onychomycosis is difficult to eradicate; dermatomycosis has better prognosis

Keratitis

Curvularia spp.

Alternaria spp.

Exserohilum spp. Lasiodiplodia theobromae

 Nodule progressing to ulcer; feathery, branching pattern in cornea

 Superficial or deep fungal invasion of cornea; endopthalmitis rare

 Fair: residual visual damage common; 25% require penetrating keratoplasty

 Sinusitis:

   Allergic sinusitis      

Bipolaris spp.,

Curvularia spp.,

Exserohilum spp.,

Alternaria spp.

 Chronic sinusitis

 Sparse fungi; eosinophil-rich mucoid material (allergic mucin); Charcot-Leyden crystals

 Cure is uncommon; frequent relapses

 Sinusitis:

    Fungus ball

Bipolaris spp.,

Curvularia spp.,

Exserohilum spp.,

Alternaria spp.

 Nasal congestion; rhinosinusitis

 Fungus ball: abundant fungi within inflammatory mass

 Good

Allergic bronchopulmonary mycosis

Bipolaris spp.,

Curvularia spp.

Cough, wheezing

Airway inflammation

Good

Pneumonia

Bipolaris spp.

Ochroconis gallopavum

Chaetomium spp.

Chronic pneumonia

Granulomas

Immunocompetent pts: good

Immunocompromised pts: fair

Central nervous system infection

Cladophialophora bantiana

Ramichloridium mackenzei

Ochroconis gallopavum

Brain abscess (usually single)

Meningitis

Encephalitis (rare)

Acute and chronic (granulomatous) inflammation

Poor

Disseminated infection

Scedosporium prolificans

Bipolaris spp.

Wangiella dermatitidis

Fever, skin lesions, septic shock

Depends on sites of infection

Poor, despite aggressive therapy

Clinical entity

First-line therapy

Second-line therapy

Options for refractory infections

 Chromoblastomycosis

Itraconazole (oral 200-400 mg daily) for 2 - 3 months or longer

 Partial surgical resection and/or cryotherapy combined with itraconazole (200 - 600 mg daily) or voriconazole (400-600mg daily) until 2 - 3 months after apparent mycologic cure

Repeated surgical resection; itraconazole and flucytosine; amphotericin B and flucytosine; ketoconazole; ketoconazole and flucytosine; itraconazole and terbinafine

 Mycetoma

Itraconazole (200-400  mg daily) for 2 - 3 months or longer

Partial surgical resection combined   itraconazole (200 - 600 mg daily) or voriconazole (400-600mg daily); until 2 - 3 months after apparent mycologic cure

Repeated surgical resection; amphotericin B; ketoconazole and flucytosine; itraconazole and flucytosine; amphotericin B and flucytosine; itraconazole and terbinafine

Subcutaneous phaeohyphomycosis

     Immunocompetent hosts

Itraconazole (200-400  mg daily) for 2 - 3 months; if organisms are contained within a cyst, adjunctive antifungal therapy is not needed

Partial surgical resection combined with itraconazole (200 - 600 mg daily) or voriconazole (400-600mg daily) until 2 - 3 months after apparent mycologic cure

Repeated surgical resection; amphotericin B; ketoconazole; addition of flucytosine or terbinafine to medical regimen

      Immunocompromised hosts

Itraconazole (200 -400mg daily),  or amphotericin B (1 mg/kg/day) until 2 - 3 months after apparent mycologic cure

 Partial surgical resection combined with itraconazole (200 - 600 mg daily), voriconazole (400-600mg daily), amphotericin B (1 mg/kg/day), or ketoconazole (300 - 400 mg daily) until 2 - 3 months after apparent mycologic cure

Repeated surgical resection; addition of flucytosine or terbinafine to medical regimen

Cutaneous phaeohyphomycosis

     Dermatomycosis, onychomycosis  

Itraconazole (200 mg daily) until 2- 3 months after apparent mycologic cure

Voriconazole (400mg daily)

Terbinafine; Ketoconazole

      Keratomycosis

 Natamycin (5% solution) topically

Topical natamycin or amphotericin B (0.15%) combined with flucytosine (1% aqueous solution); topical itraconazole, ketoconazole, or miconazole; oral itraconazole (400 mg daily); oral voriconazole (400mg daily); oral ketoconazole (400 mg daily)

Prior therapy with penetrating keratoplasty

 Sinusitis

     Allergic fungal sinusitis

Surgical drainage and debridement, combined with postoperative corticosteroids; postoperative nasal saline irrigations and regular surveillance endoscopy

Itraconazole (200-400mg daily); voriconazole (400mg daily)

Allergen immunotherapy to decrease IgE production

      Fungus ball

Resection of fungus ball, with aeration of sinuses

In cases of local invasion of bone, itraconazole or amphotericin B are indicated as adjunctive therapy

 Voriconazole

Allergic bronchopulmonary mycosis

Corticosteroids

Corticosteroids with itraconazole (200-400mg daily)  or voriconazole (400mg daily)

Pneumonia

Itraconazole (400mg daily) or amphotericin B (1mg/kg daily) for severe disease

Voriconazole (400-600mg daily)

Amphotericin B with flucytosine

Central nervous system infection

Surgical resection (brain abscess) with high dose itraconazole (400-600mg daily) or voriconazole (400-600mg daily) + lipid amphotericin B +/- flucytosine

Repeated surgical resection with

high dose azole + echinocandin +/- flucytosine

Disseminated infection

High dose lipid amphotericin B (>5mg/kg daily) with intravenous itraconazole (400-600mg daily) or voriconazole (400-600mg daily) +/- echinocandin;

colony stimulating factors if neutropenic

High dose lipid amphotericin B with azole +/- echinocandin +/- flucytosine; colony stimulating factors if neutropenic