North American Endemic Fungi

Transcription

1 North American Endemic Fungi Boni Elizabeth Elewski, MD Chair Department of Dermatology University of Alabama at Birmingham James Elder Professor of Graduate Medical Education

2 DISCLOSURE OF FINANCIAL RELATIONSHIPS WITH INDUSTRY CLINICAL RESEARCH AND GRANTS TO UNIVERSITY Abbvie, Boehringer Ingelheim, Celgene, Incyte, Leo, Lilly, Merck, Novartis, Pfizer, Regeneron, Valeant (Ortho Dermatology) CONSULTING: RECEIVED HONORARIUM Boehringer Ingelheim, Celgene, Leo, Lilly, Novartis, Pfizer, Sun, Valeant (Ortho Dermatology) SPEAKER BOARDS: NONE STOCK: NONE

3 OBJECTIVES: UNDERSTAND the concept of dimorphism RECOGNIZE the clinical features and pathology of blastomycosis, coccidioidomycosis, histoplasmosis, sporotrichosis and cryptococcosis infections UNDERSTAND the treatment of American endemic fungi

4 Overview of Systemic Mycoses TRUE PATHOGENS Dimorphic organisms that cause infection in hosts with normal immune status Histoplasmosis- Mississippi and Ohio river valleys Blastomycosis- southeast and Midwest US Coccidioidomycosis Western US Paracoccidioidomycosis- not in the US but South America Sporotrichosis- usually subcutaneous infection but can be also opportunistic OPPORTUNISTIC MYCOSES Cause infections in hosts immunocompromised by disease or therapy Generally less virulent and take advantage of the immunocompromised state Cryptococcus spp and some dimorphic organisms also behave as opportunistic pathogens

5 Overview of Dimorphic Organisms Organisms exist in two forms Generally a mold in nature (with septate hyphae and conidia) and yeast in tissue (with the exception of Coccidioides spp) Each pathogen has certain geographic preferences Acquisition of infection is generally through inhalation of the organism leading to pulmonary symptoms and pneumonitis Occurs in immunocompetent patients and most cases resolve Some infections enter latent state which re-emerges later

6 Histoplasmosis Caused by Histoplasma capsulatum var. capsulatum Location- US, Canada; St. Lawrence, Ohio and Mississippi river valleys but may be endemic in river basins in areas of Australia, Africa, India, Southeast Asia Reservoirs- Birds, Fowl and bats; feces may contain the infectious spores Risk Factors: Cave exploration, demolition of buildings

7 Histoplasmosis: Clinical Features Pulmonary involvement common but spleen, lymph nodes, bone marrow, liver also occur; calcifications may indicate prior infection Non specific skin changes including plaques and nodules result from disseminated disease Oral and mucosa ulcers may occur Disseminated disease occurs in immunocompromised hosts who may present with mucocutaneous erosions

8 Histoplasmosis PAS positive yeasts Ovoid 2-4 microns Narrow base budding In giant cells and Dermal macrophages

9 Histoplasmosis Intracellular yeasts Surrounded by a rim of clearing parasitized macrophages

10 Parasitized Macrophages Differential Diagnosis Histoplasmosis- H. capsulatum Rhinoscleroma- Klebsiella rhinoscleromatis Granuoma inguinale- Calymmatobacterium granulomatis Leishmaniasis- Leishmania spp Penicilliosis- Talaromyces (Penicillium) marneffei Emmonsiosis- Emergomyces spp

11 Histoplasmosis: Treatment Initial treatment generally amphotericin B in patients with severe disease Itraconazole 200 to 400 mg daily for immunocompetent hosts with stable disease HIV infected patients with disseminated histoplasmosis require life long maintenance therapy with itraconazole but options include voriconazole and posaconazole

12 Blastomycosis Caused by Blastomyces dermatitidis Location - In US particulary Great Lakes region, Ohio River Valleys and Southeastern states. Has also been reported in Africa and India. Reservoirs- Moist soil and decomposing matter such as wood and leaves; at risk are those with outdoor exposure to infected spores

13 Blastomycosis: Clinical Features Primary process is pneumonitis from inhalation of organisms Subclinical in about 50% of patients May be flu-like syndrome Cutaneous involvement is common and often first sign of disease. Verrucous plaques and papulopustules/erosions or ulcers may occur Bone involvement may present with osteomyelitis Genitourinary disease is also possible but less common

14 Broad Based Budding Yeasts: Blastomycosis 8 to 15 microns: Note broad base budding

15 Pseudoepitheliomatous hyperplasia Blastomycosis

16 Blastomycosis: GMS Stain Pseudoepitheliomatous hyperplasia Suppurative and granulomatous inflammation Broad based budding yeast cells with thick cell walls May be seen in sputum or pus on KOH exam

17 Blastomycosis: Treatment Systemic Amphotericin B in severe infections In non CNS disease, itraconazole is the treatment of choice mg/day Options are voriconazole and posaconazole

18 Coccidioidomycosis Caused by Coccidioides immitis and C. posadasii- closely related virulent pathogens Location-Southwestern US and Northern Mexico C. immitis found mostly in California; C. posadasii in other areas Reservoirs- dust particles in endemic regions; the organism lives in the soil and dust storms result in airborne arthroconidia. Also known as Valley Fever, California Fever Coccidioides immitis and C. posadasii are the most virulent of all fungi On a federal list to restrict possession; bioterrorism potential

19 C. immitis Colony may resemble a dermatophyte Infectious particle- Barrel shaped arthroconidia

20 Coccidioidomycosis: Clinical Features Infection occurs in immunocompetent people May be an opportunistic infection in HIV infected patients, organ transplant patients Cycle of infection: arthroconidia are inhaled on dust particles and transform into spherules in the lungs which will eventually release endospores; endospores produce additional spherules

21 Endosporulating Spherules in Lung Endospores are 2 to 5 microns and are globular Structures that Become new spherules Spherules are microns but can be up to 200 microns

22 Coccidioidomycosis: Clinical Features Inhalation of spores results in pneumonitis or flu like syndrome Highest risk of disseminated disease: Mexicans, African Americans, Filipinos; also HIV infection and pregnancy Cutaneous manifestations: 1. Organism specific- disseminated- viable organisms present Nonspecific papules, plaques, abscesses often on head/neck 2. Reactive pattern on skin has no viable organisms and is more common

23 Coccidioidomycosis: Clinical Features REACTIVE: Toxic erythema with diffuse macular or morbilliform eruption Begins in the first 48 hours Erythema nodosum (valley fever EN, respiratory symptoms plus fever) Erythema multiforme- early in the disease course Sweet s syndrome Reactive interstitial granulomatous disease

24 Coccidioidomycosis Endosporulating spherules 30 to 60 microns Surrounded by suppurative Granulomatous reaction

25 Rhinosporidiosis: Endosporulating Spherules 300 microns Coccidioidomycosis: Spherules 20 to 80 microns Rhinosporidium seeberi

26 Coccidioidomycosis: Treatment Systemic Amphotericin B is treatment for severe disseminated disease Most immunocompetent patients can be treated with fluconazole 400 mg per day or itraconazole 200 mg twice daily for three to six months Amphotericin B treatment of choice in pregnancy Vaccine???

27 Sporotrichosis Caused by Sporothrix schenckii ( also S. braziliensis, S. globose, S. mexicana) Location- Worldwide in soil; endemic in Mexico, Central America and South America, South Africa Reservoirs- sphagnum moss, gardeners- exposure to orchids and roses; acquired by cutaneous inoculation to organic debris such as thorns or wood

28 Sporotrichosis Subcutaneous infection Disseminated

29 Sporotrichosis Generally a subcutaneous infection presenting as a nodule or papule at site of skin inoculation (generally several weeks after injury) followed by a lymphocutaneous spread sporotrichoid pattern In immunocompromised hosts, extensive cutaneous disease may occur Inhaled sporotrichosis with cutaneous and systemic dissemination may occur similar to histoplasmosis

30 Sporotrichosis: GMS Stain Cigar shaped yeast forms rarely seen Asteroid bodies more common Yeasts are 2 by 3 to 3 by 10 microns

31 Sporotrichosis: Asteroid Body

32 Sporotrichosis Treatment Itraconazole is treatment of choice for lymphocutaneous sporotrichosis dosed at 100 to 200 mg daily Other options: SSKI Amphotericin B may be needed for severe or disseminated infection

33 Cryptococcosis Caused by Cryptococcus neoformans but there are other strains including C. gatti, C. laurentii Location- worldwide in natural environment Reservoir- pigeons, bird feces, soil, plants, dust Organism is an encapsulated yeast and NOT dimorphic C. neoformans usually acquired from inhalation into lungs and then disseminates Disseminated most common in with impaired T cell mediated immunity such as transplant recipients, HIV infection

34 Cryptococcus Colony: Yeast with Gelatinous capsule Inhale spores from environment Incubation period unknown May be dormant for years and reactivate CD4 Count <100 No person to person transmission Round to oval yeast 4-6 microns Surrounded by a gelatinous capsule that can be 30 microns thick

35 Gelatinous capsule does not Stain with PAS Cryptococcus neoformans

36 India Ink Preparation Shows Capsule

37 Diagnosis of Cryptococcosis Biopsy and tissue culture Serum capsular antigen tests New dipstick test (serum, plasma and urine) positive in few minutes

38 Cryptococcosis Treatment Fluconazole crosses blood brain barrier and was FDA approved fast track in early 1990 s to prevent Cryptococcus dissemination in at risk patients Amphotericin B plus flucytosine may be used for primary induction therapy in disseminated disease followed by fluconazole for maintenance therapy Reduction in immunosuppressive therapy may also be helpful in patient management

39 KEY POINTS Dimorphic fungi have two different forms- one in tissue (yeast) and another (mold) in nature Each dimorphic fungus has a specific endemic region Inhalation of spores results in pneumonitis followed by dissemination Blastomyces dermatitidis frequently disseminates to the skin (most common) C. immitis and C. posadasii are the most virulent of fungi Sporotrichosis can present in a subcutaneous pattern or disseminated (inhalational) distribution in immunocompromised patients Cryptococcus neoformans is not dimorphic but occurs in immunocompromised patients, especially when CD4 counts <100