Fungi and Yeasts, Part II KCOM/Texas Dermatology Consortium Dan Ladd, DO November 2003.

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1 Fungi and Yeasts, Part II KCOM/Texas Dermatology Consortium Dan Ladd, DO November 2003

2 GEOTRICHOSIS Oral erythema, pseudomembranes, mucopurulent sputum Oral erythema, pseudomembranes, mucopurulent sputum Intestinal, bronchial and pulmonary forms are similar to Candida Intestinal, bronchial and pulmonary forms are similar to Candida Geotrichum candidum is pathogenic only when repeatedly cultured, usually just a contaminant saprophyte. Geotrichum candidum is pathogenic only when repeatedly cultured, usually just a contaminant saprophyte. Tx: Oral Nystatin, Amphotericin B, Itraconazole Tx: Oral Nystatin, Amphotericin B, Itraconazole

3 Geotrichum candidum Chains of rectangular cells, and branching septate mycelium

4 Tinea Nigra Black to brown spots on palms. Black to brown spots on palms. Not elevated or scaly Not elevated or scaly Young colonies are glossy, black whereas older colonies are filamentous and gray. Young colonies are glossy, black whereas older colonies are filamentous and gray. Exophiala phaeoannellomyces (werneckii) saprophyte produces melanin-like pigment Exophiala phaeoannellomyces (werneckii) saprophyte produces melanin-like pigment Tx: Topical econazole, ketoconazole Tx: Topical econazole, ketoconazole

5 Tinea Nigra–AOCD Grand Rounds Exophiala phaeoannellomyces

6 Piedra (Trichosporosis) Dark, pinhead-sized gritty formations on the hairs of the scalp, brows, lashes or beard. Minute round or ovoid, hard nodules distributed irregularly on the shaft of the hairs, not on the root. Dark, pinhead-sized gritty formations on the hairs of the scalp, brows, lashes or beard. Minute round or ovoid, hard nodules distributed irregularly on the shaft of the hairs, not on the root. White: Trichosporon beigelii White: Trichosporon beigelii Black: Piedraia hortai Black: Piedraia hortai Tx: Cutting hair, Lamisil Tx: Cutting hair, Lamisil

7 black Piedraia hortai white Trichosporon beigelii Trichosporon beigelii

8 Tinea Versicolor Upper trunk and arms Upper trunk and arms Young adults who perspire freely Young adults who perspire freely Hypopigmented: fungus causes production of abnormally small melanosomes that do not transfer to keratinocytes properly Hypopigmented: fungus causes production of abnormally small melanosomes that do not transfer to keratinocytes properly Hyperpigmented: Increase in size and distribution of melanosomes. Hyperpigmented: Increase in size and distribution of melanosomes.

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10 Malassezia furfur….

11 Tinea Versicolor Treatments Imidazoles, selenium sulfide, ciclopirox, olamine, zinc pyrithione, sulfur, salicyclic acid, propylene glycol, BPO. Imidazoles, selenium sulfide, ciclopirox, olamine, zinc pyrithione, sulfur, salicyclic acid, propylene glycol, BPO. Ketoconazole to damp skin 5 min x 3d. Ketoconazole to damp skin 5 min x 3d. Ketoconazole, Fluconazole, Itraconazole. Ketoconazole, Fluconazole, Itraconazole. Warn patients pigment slow to resolve. Warn patients pigment slow to resolve. Relapse likely in 2 to 12 months if no monthly prophylaxis is given. Relapse likely in 2 to 12 months if no monthly prophylaxis is given.

12 Pityrosporum Folliculitis Chronic, mildly pruritic dome shaped papules and tiny pustules on upper back and adjacent areas, seborrheic distribution Chronic, mildly pruritic dome shaped papules and tiny pustules on upper back and adjacent areas, seborrheic distribution Sometimes associated with TV or SD. Sometimes associated with TV or SD. Often associated with immunocompromise. Often associated with immunocompromise. Due to Malassezia furfur…. Due to Malassezia furfur….

13 Pityrosporum folliculitis

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15 Confluent and Reticulated Papillomatosis of Gougerot & Carteaud Greatest intensity between breasts and periumbilical, may spread to trunk. Greatest intensity between breasts and periumbilical, may spread to trunk. May be initially mistaken for TV. May be initially mistaken for TV. Minocycline 100mg BID for 6 weeks. Minocycline 100mg BID for 6 weeks. Etretinate 50mg daily x 4 weeks. Etretinate 50mg daily x 4 weeks.

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21 DEEP MYCOSES Inhalation of contaminated dust Inhalation of contaminated dust Animal droppings Animal droppings Puncture wounds, abrasions, traumas Puncture wounds, abrasions, traumas Chancriform nodules with ulceration and secondary lymphagitis Chancriform nodules with ulceration and secondary lymphagitis CXR to rule out internal focus with dissemination CXR to rule out internal focus with dissemination

22 Coccidiomycosis – CA and SW USA Coccidiodes immitis, San Joaquin Valley Fever Coccidiodes immitis, San Joaquin Valley Fever 1) Pulmonary: maculopapular or EN like rash – EN is favorable prognostic sign 1) Pulmonary: maculopapular or EN like rash – EN is favorable prognostic sign 2) Disseminated: (rare) Subcutaneous abcesses, may suppurate with sinuses – esp. face, scalp and nasolabial fold (HIV?) 2) Disseminated: (rare) Subcutaneous abcesses, may suppurate with sinuses – esp. face, scalp and nasolabial fold (HIV?) 3) Primary cutaneous (rare) = indurated nodule with sporotricoid spread 3) Primary cutaneous (rare) = indurated nodule with sporotricoid spread Most forms (1 and 3) resolve spontaneously Most forms (1 and 3) resolve spontaneously

23 Coccidioides immitis Arthrospores Endospores

24 Coccidio “endospores” PAS + Surrounded by infectious granulomatous pattern, ie neuts, plasma cells, epithelioid and giant cells

25 Coccidioides immitis Diagnosis by DNA probe, positive intradermal coccidioidin test, KOH, precipitin and latex agglutination tests Diagnosis by DNA probe, positive intradermal coccidioidin test, KOH, precipitin and latex agglutination tests Skin biopsy with Gridley or Gomori methenamine silver stain. Skin biopsy with Gridley or Gomori methenamine silver stain. TOC: Fluconazole 400 to 800mg/day. TOC: Fluconazole 400 to 800mg/day. If meningeal, need itraconazole or amphotericin intrathecally. If meningeal, need itraconazole or amphotericin intrathecally.

26 Histoplasmosis -> Ohio & Mississippi River Valleys 1) Pulmonary: acute pneumonitis, usually resolves quickly, 10% may have EN, but EM and panniculitis have also been described. 1) Pulmonary: acute pneumonitis, usually resolves quickly, 10% may have EN, but EM and panniculitis have also been described. 2) Disseminated: (rare) skin lesions in 6% nodules (granulomas) with “punched out” ulcerations, MC nasopharyngeal (HIV, etc) 2) Disseminated: (rare) skin lesions in 6% nodules (granulomas) with “punched out” ulcerations, MC nasopharyngeal (HIV, etc) 3) Primary cutaneous (rare) = cancre type lesion, usually on the penis, adenopathy 3) Primary cutaneous (rare) = cancre type lesion, usually on the penis, adenopathy Most forms (1 and 3) resolve spontaneously Most forms (1 and 3) resolve spontaneously African variant “cold abcesses” H. duboisii African variant “cold abcesses” H. duboisii

27 H&E stain (left) shows macs filled with organisms giving the cytoplasm a slightly vacuolated appearance. A GMS (Gomori methenamine stain) (right) shows clustered organisms in cytoplasm.

28 Geimsa stain: intracellular oval bodies surrounded by an artefactual “capsule”

29 Histoplasma capsulatum Transmission: soil, spore inhalation, bat or bird feces Transmission: soil, spore inhalation, bat or bird feces DX: urinary ELISA test avaliable DX: urinary ELISA test avaliable Skin biopsy with Wright’s, Geimsa, PAS or Gomori methenamine silver stain. Skin biopsy with Wright’s, Geimsa, PAS or Gomori methenamine silver stain. TX: Disseminated disease requires Amphotericin B or Itraconazole TX: Disseminated disease requires Amphotericin B or Itraconazole Minimal disease heals spontaneously Minimal disease heals spontaneously

30 Cryptococcosis MC pulmonary, with MC spread to CNS. MC pulmonary, with MC spread to CNS. MC cause mycotic meningitis MC cause mycotic meningitis Disseminated, immunosupp., Disseminated, immunosupp., 50% of HIV pts have MCV like lesions 50% of HIV pts have MCV like lesions 10-15% of cases have secondary skin infection MC head and neck, may be abcesses, tumors, draining sinuses etc. 10-15% of cases have secondary skin infection MC head and neck, may be abcesses, tumors, draining sinuses etc. Primary skin infection rare, so discovery of crypto in the skin should prompt work up to rule out other sites of infection Primary skin infection rare, so discovery of crypto in the skin should prompt work up to rule out other sites of infection

31 Cutaneous Crypto….

32 Teardrop shaped, “Crying Crypto” Oval thick walled spherule that stains with Methylene Blue, Alcian Blue (left) or Mucicarmine (right)

33 Mycology of Crypto, KOH… Without… & with India Ink

34 Cryptococcus neoformans Transmission from inhalation of soil, dust, pigeon droppings Transmission from inhalation of soil, dust, pigeon droppings Latex agglutination test, complement fixation and EIA (enzyme immunoassay) Latex agglutination test, complement fixation and EIA (enzyme immunoassay) Tx for disseminated is Amphotericin B followed by Fluconazole orally. Meningeal disease gets Ampho B plus Flucytosine, then Fluconazole orally. Tx for disseminated is Amphotericin B followed by Fluconazole orally. Meningeal disease gets Ampho B plus Flucytosine, then Fluconazole orally.

35 North American Blastomycosis Aka Gilchrist’s disease Aka Gilchrist’s disease Cutaneous form exhibits sporotricoid spread and if chronic almost always originates in the lungs. Cutaneous form exhibits sporotricoid spread and if chronic almost always originates in the lungs. Most common site of dissemination from lung is the skin. (80% of cases) Most common site of dissemination from lung is the skin. (80% of cases) MC hands and feet, nodular, draining sinuses or papillomatous and crusted. MC hands and feet, nodular, draining sinuses or papillomatous and crusted. LESIONS ARE USUALLY MULTIPLE LESIONS ARE USUALLY MULTIPLE

36 North American Blastomycosis Blastomyces dermatitides Southeastern US, Ohio & Mississipi river basins, Kentucky. Southeastern US, Ohio & Mississipi river basins, Kentucky. Transmission: soil in a beaver dam, dog bite (dog had pulmonary blasto), men (with prostatic blasto) to their sexual partners Transmission: soil in a beaver dam, dog bite (dog had pulmonary blasto), men (with prostatic blasto) to their sexual partners

37 Broad Based Budding yeast Blastomyces dermatitides KOH will show single or singly budding spherical cells with refractile walls

38 Blasto culture is difficult, requires Sabouraud’s dextrose agar, Mycosel and a brain-heart infusion agar to which blood has been added. DNA probe assay is commercially avaliable

39 North American Blastomyces BLASTO = BROAD BASED BUDS TX: Itraconazole, Amphotericin B, Fluconazole TX: Itraconazole, Amphotericin B, Fluconazole

40 South American Blastomycosis Aka Paracoccidiomycosis Aka Paracoccidiomycosis Lungs MC, but mucocutaneous type begins in the mouth -> nose, lips, face Lungs MC, but mucocutaneous type begins in the mouth -> nose, lips, face Lymphangitic type spread w/ regional lymphadenopathy mimics Hodgkins. Lymphangitic type spread w/ regional lymphadenopathy mimics Hodgkins. Visceral and mixed types exist. Visceral and mixed types exist. Brazil, Argentina, Venezuela, US, Mexico and Central America Brazil, Argentina, Venezuela, US, Mexico and Central America Dx: Complement fixation test avaliable Dx: Complement fixation test avaliable Tx: Itraconazole, Ketoconazole, Ampho B, Bactrim can be suppressive in HIV patients Tx: Itraconazole, Ketoconazole, Ampho B, Bactrim can be suppressive in HIV patients

41 Paracoccidioides brasilensis “MARINER’S WHEEL”

42 SPOROTRICHOSIS, Sporothrix schenckii SPOROTRICHOSIS, Sporothrix schenckii Localized skin wound -> regional lymphangitic spread “Sporotrichoid” Localized skin wound -> regional lymphangitic spread “Sporotrichoid” Most common and least serious of the deep mycoses. Most common and least serious of the deep mycoses. Disseminated disease is rare. Disseminated disease is rare.

43 Sporothrix schenckii “Asteroid body”

44 Cigar Bodies Conidia in sleeve like arrangement => Conidia in <=clusters

45 Sporothrix schenckii Pathogen lives as a saprophyte on grasses, shrubs, carnations, rose bushes, barberry, sphagnum moss. Pathogen lives as a saprophyte on grasses, shrubs, carnations, rose bushes, barberry, sphagnum moss. Has been found in horses, mules, dogs, cats, mice and rats. Has been found in horses, mules, dogs, cats, mice and rats. Dx: Sporotrichins skin test is like TB test, only shows previous or current exposure Dx: Sporotrichins skin test is like TB test, only shows previous or current exposure Agglutination test is best 1:80 Agglutination test is best 1:80

46 Sporothrix schenckii Tx: Treatment Itraconazole 200mg/day x 6 months Treatment Itraconazole 200mg/day x 6 months Potassium Iodide, begin with 5 drops TID with grapefruit juice or milk after meals, then gradually increase to 50 drops TID for a total of 12 weeks. Should check TSH as hypothyroidism may occur. Multiple side effects for this medication. Potassium Iodide, begin with 5 drops TID with grapefruit juice or milk after meals, then gradually increase to 50 drops TID for a total of 12 weeks. Should check TSH as hypothyroidism may occur. Multiple side effects for this medication.

47 Chromoblastomycosis Usually affects on leg or foot, slowly spreads with satellite lesions, may be nodular or verrucous “cauliflower-like” Usually affects on leg or foot, slowly spreads with satellite lesions, may be nodular or verrucous “cauliflower-like” Small lesions may mimic common warts. Also plaque-like, keloidal or cicatricial. Small lesions may mimic common warts. Also plaque-like, keloidal or cicatricial.

48 Chromoblastomycosis – 5 fungi Cladosporium carrionii Cladosporium carrionii Phialophorra verrucosa Phialophorra verrucosa Fonsecaea pedrosoi Fonsecaea pedrosoi Fonsecaea compacta Fonsecaea compacta Rhinocladiella aquaspersa Rhinocladiella aquaspersa MC barefooted farm laborers in Brazil, Cuba, West Indies, US, Russia, Madagascar.

49 Copper pennies, Medlar bodies, Sclerotic bodies

50 Chromoblastomycosis TX Best treated by surgical excision and grafting of the affected area Best treated by surgical excision and grafting of the affected area If lesions are chronic or burrowing Itraconazole 100mg/day for 18 months If lesions are chronic or burrowing Itraconazole 100mg/day for 18 months Lamisil 500mg/day has been remarkably effective Lamisil 500mg/day has been remarkably effective Application of heat is effective! Application of heat is effective! Amputation may be unavoidable Amputation may be unavoidable

51 Phaeohyphomycosis 30 causative fungi 30 causative fungi Exophiala jeanselmei is the MC in temperate climates Exophiala jeanselmei is the MC in temperate climates Bipolaris and Exserohilum genera are being MC recovered as causes of both subcutaneous lesions and systemic infections. Bipolaris and Exserohilum genera are being MC recovered as causes of both subcutaneous lesions and systemic infections. Black & White piedra are superficial examples Black & White piedra are superficial examples Has yeast-like cells, hyphae, pseudohypha-like elements, unlike Chromo, which has spherical cells Has yeast-like cells, hyphae, pseudohypha-like elements, unlike Chromo, which has spherical cells

52 Exophiala jeanselmei Exophiala jeanselmei Dactylaria gallopava Dactylaria gallopava Phialophora parasitica Phialophora parasitica Phaeoannellomyces werneckii Phaeoannellomyces werneckii Hendersonula toruloidea Hendersonula toruloidea Wangiella dermatitidis Wangiella dermatitidis Exserohilum rostratum Exserohilum rostratum Bipolaris spicifera Bipolaris spicifera Cladophialophora bantiana Cladophialophora bantiana Xylohypha bantiana Xylohypha bantiana

53 Multi-tasking fungi…. Exophiala jeanselmei may cause mycetoma in some patients, and phaeohyphomycosis in some patients, and chromoblastomycosis in others. Exophiala jeanselmei may cause mycetoma in some patients, and phaeohyphomycosis in some patients, and chromoblastomycosis in others. Phialophora verrucosa can cause both phaeohyphomycosis and chromoblastomycosis Phialophora verrucosa can cause both phaeohyphomycosis and chromoblastomycosis

54 Phaeohyphomycosis TX May respond to topical antifungals May respond to topical antifungals Surgical excision along with Itraconazole 400mg per day for 6 months needed for deeper lesions. Surgical excision along with Itraconazole 400mg per day for 6 months needed for deeper lesions.

55 Mycetoma Clinical entity, not a etiologic one. Clinical entity, not a etiologic one. Actinomycetomas, Eumycetomas (true fungi), Staph and Strep can cause mycetomas Actinomycetomas, Eumycetomas (true fungi), Staph and Strep can cause mycetomas Subcutaneous swelling of instep or toe web, painless, firm, rubbery with draining sinuses that secrete grains of the causative organism. Underlying bone may be involved. Subcutaneous swelling of instep or toe web, painless, firm, rubbery with draining sinuses that secrete grains of the causative organism. Underlying bone may be involved.

56 Mycetoma

57 Eumycetomas (true fungi)… Pseudallesceria boydii Pseudallesceria boydii Acremonium falciforme & recifei Acremonium falciforme & recifei Leptosphalaeria senegalensis & tompkinsii Leptosphalaeria senegalensis & tompkinsii Madurella grisea & mycetomatis Madurella grisea & mycetomatis Exophiala jeanselmei Exophiala jeanselmei Pyrenochaeta romeri Pyrenochaeta romeri Phialophora verrucosa Phialophora verrucosa

58 Black grain mycetoma: subcutaneous nodule due to Madurella mycetomatis Black grain mycetoma: subcutaneous nodule due to Madurella mycetomatis

59 mycetoma caused by Madurella grisea mycetoma caused by Madurella grisea

60 Actinomycetomas… Nocardia asteroides Nocardia asteroides Nocardia brasilensis Nocardia brasilensis Nocardia caviae Nocardia caviae Actinomadura madurae Actinomadura madurae Actinomadura pelletier Actinomadura pelletier Actinomyces israelii Actinomyces israelii

61 Grains = White/Cream/Sulfur Yellow Actinomyces israeli Actinomyces israeli Actinomadura madurae Actinomadura madurae Nocardia sp. Nocardia sp. Streptomyces somalensis Streptomyces somalensis Pesudallescheria boydii Pesudallescheria boydii Acremonium sp. Acremonium sp. Aspergillus nidulans Aspergillus nidulans Fusarium sp. Fusarium sp. Neotestudinea rosati Neotestudinea rosati

62 Grains = red Actinomadura pelletieri Actinomadura pelletieri

63 Black Grains Curvularia geniculata Curvularia geniculata Helminthosporium spiciferum Helminthosporium spiciferum Leptosphaeria senegalensis Leptosphaeria senegalensis Madurella grisea Madurella grisea M. mycetomatis M. mycetomatis Exophiala jeanselmei Exophiala jeanselmei Phialophora verrucosa Phialophora verrucosa Pyrenochaeta romeri Pyrenochaeta romeri

64 Epidemiology DX & TX Mycetoma occurs everywhere Mycetoma occurs everywhere Mexico, Venezuela, Argentina, Senegal, Sudan Somalia Mexico, Venezuela, Argentina, Senegal, Sudan Somalia Probably acquired from soil -> barefoot Probably acquired from soil -> barefoot Dx Triad: Tumefaction, Sinuse, Granules Dx Triad: Tumefaction, Sinuse, Granules TX: Antibiotics or Antifungals if organism dictates, then surgical excision TX: Antibiotics or Antifungals if organism dictates, then surgical excision

65 Lobomycosis Aka Keloidal Blastomycosis Aka Keloidal Blastomycosis Central and South America Central and South America Keloidal plaques +/- sinuses Keloidal plaques +/- sinuses MC ear, may resemble cauliflower ear MC ear, may resemble cauliflower ear Dolphins may harbor this infection Dolphins may harbor this infection TX: Excision, Amphotericin B usually unsuccessful. TX: Excision, Amphotericin B usually unsuccessful.

66 Lobomycois (Keloidal Blasto) Thick walled refractile spherules larger than those of Paracoccidiodes Thick walled refractile spherules larger than those of Paracoccidiodes

67 Rhinosporidiosis Polypoid, nasal mucosa MC Polypoid, nasal mucosa MC Begin as small papilloma, become pedunculated tumors, friable, may resemble cauliflower Begin as small papilloma, become pedunculated tumors, friable, may resemble cauliflower Rhinosporidium seeberi Rhinosporidium seeberi Characteristic large sporangia Characteristic large sporangia Endemic in Ceylon and India, but seen in Argentina and Brazil. Endemic in Ceylon and India, but seen in Argentina and Brazil.

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69 Actinomycosis Anaerobic Gram + bacteria Anaerobic Gram + bacteria MC cervicofacial areas MC cervicofacial areas Middle aged men MC Middle aged men MC Lesions are characteristic local dusky red swellings; firm fluctuating nodules; and sinuses exuding purulent discharge including yellow sulfur granules. Lesions are characteristic local dusky red swellings; firm fluctuating nodules; and sinuses exuding purulent discharge including yellow sulfur granules. TX: PCN G in large doses 10-20 million units daily for 1 month TX: PCN G in large doses 10-20 million units daily for 1 month

70 Actinomycosis – sulfur granules

71 Nocardiosis Usually pulmonary, but 1/3 CNS Usually pulmonary, but 1/3 CNS May resemble TB clinically May resemble TB clinically Nocardia asteroides MC disseminated Nocardia asteroides MC disseminated N. brasilensas MC sporotrichoid pattern N. brasilensas MC sporotrichoid pattern Traumatic implantation or dust inhalation Traumatic implantation or dust inhalation Bactrim DS drug of choice, may use Minocycline or Augmentin Bactrim DS drug of choice, may use Minocycline or Augmentin

72 Zygomycosis (Phycomycosis) Entomophthoromycosis - 2 sites Entomophthoromycosis - 2 sites Face – Conidiobolus coronatus Face – Conidiobolus coronatus Trunk – Basidiobolus ranarum Trunk – Basidiobolus ranarum MC Indonesia, Africa, Asia & Americas MC Indonesia, Africa, Asia & Americas Mucormycosis - characteristic skin lesions as it has a propensity for invasion of blood vessels and therefore leads to infarction, gangrene and black necrotic lesions. Mucormycosis - characteristic skin lesions as it has a propensity for invasion of blood vessels and therefore leads to infarction, gangrene and black necrotic lesions. Ubiquitous molds. Ubiquitous molds.

73 Mucormycosis

74 Hyalohyphomycosis Non dematiaceus molds Non dematiaceus molds Fusarium, Penicillium, Paecilomyces Fusarium, Penicillium, Paecilomyces Ubiquitous Ubiquitous Fusarium oxysporum superficial white onychomycosis in HIV. Fusarium oxysporum superficial white onychomycosis in HIV. Excision and Amphotericin B have a low success rate. Excision and Amphotericin B have a low success rate.

75 Aspergillosis Second only to Candida as fungal opportunistic in HIV, transplant pts. Second only to Candida as fungal opportunistic in HIV, transplant pts. Blood cultures and serologic tests usually negative Blood cultures and serologic tests usually negative Usually pulmonary involvement Usually pulmonary involvement Aspergillus fumigatus MC disseminated. Aspergillus fumigatus MC disseminated. Aspergillus flavus MC primary cutaneous, may look like hemorrhagic bullae or molluscum lesions Aspergillus flavus MC primary cutaneous, may look like hemorrhagic bullae or molluscum lesions

76 Aspergillosis septate hyphae, 45 degree angles.

77 Alternariosis Genus of molds that are common plant pathogens, but rarely infect humans. Genus of molds that are common plant pathogens, but rarely infect humans. Usually immunocompromised patients. Usually immunocompromised patients. Standard antifungal therapy. Standard antifungal therapy.

78 Protothecosis (Algae etiology) Prototheca wickerhamii and zopfi Prototheca wickerhamii and zopfi Stagnant water and soil Stagnant water and soil Olecranon bursa if healthy, or any type of immunocompromised. Olecranon bursa if healthy, or any type of immunocompromised. PAS stains positive PAS stains positive Amphotericin B and TCN synergistic Amphotericin B and TCN synergistic Diflucan Diflucan