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BLASTOMYCOSIS BLASTOMYCOSIS

- A rare infection caused by inhalation of

AUDREY DAVIDSON CASSIE GARLAND MATT FINAMORE Blastomyces dermatitidis

- 0.3-1.5/100,000 cases in endemic areas

-Blastomyces dermatitidis only known species

SOURCE: pharmacy-and-drugs.com

HISTORY HISTORY CONT’D

- Founded by Gilchrist in Baltimore (1890s) - Has 3 clinical forms: - Pulmonary (most common) - Thought to be a skin infection caused by a - Cutaneous protozoan and titled Gilchrist’s disease - Systemic - Pulmonary infection discovered by Witorsch - Gilchrist was wrong and Utz in 1968 - Disease not endemic to Baltimore - Is a fungus not a protozoan - Skin is secondary infection

Blastomycosis dermatidis BLASTOMYCOSIS

Dimorphic fungus: Asymptomatic – 50% - Conidia inhaled Acute Pulmonary – Very similar to pneumonia, and hard to distinguish - Transformed to yeast in lungs (37°C) Chronic Pulmonary – Can develop lobar infiltrates leading to carcinoma Chronic disease affecting: Skin – Ulcers, verrucous lesions, or subcutaneous - Lungs - Skin lesions - Bones Bones – Ribs and vertebrae (osteolytic) - GI tract GI – 10-30% mainly attacks prostate and epididymis - Other organs

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SYMPTOMS TAXONOMY

- Chest pain  Taxonomic Classification - Cough Kingdom: Fungi - Fatigue Phylum: Ascomycota - Fever Class: Euascomycetes - Stiffness Order: Onygenales - Rash Family: Onygenaceae - Shortness of breath Genus: Blastomyces - Weight loss Species:dermatitidis

ETIOLOGY BASIC BIOLOGY

 Blastomyces dermatitidis  Macroscopic Features  At 25°C  Growth rate--slow to moderately rapid.  Thermal dimorphic fungus Exists as a mycelial form in nature and a yeast  Colony diameter--0.5 to 3 cm following incubation form in tissue for 7 days on potato glucose agar.

Grows as a broad-based budding yeast at 37oC.  Texture is membranous and color white to beige At 25oC, produces mycelia and can produce conidia.

BASIC BIOLOGY (cont.) BASIC BIOLOGY (cont.)

 At 37°C  Microscopic Features  Growth rate--slow to moderately rapid.  At 25°C

 Colony diameter--0.5 to 3 cm following incubation for 7 days. Septate hyaline hyphae and unbranched short conidiophores are observed.

 Texture --appears granular to verrucose on the surface. Conidiophores arise. The conidia are hyaline and unicellular.  Color of the colony --white to beige.

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BASIC BIOLOGY (cont.) ECOLOGY

 At 37°C  Probable saprobe of the soil.  Inhibits decaying wood material. Fungus appears as budding yeast cells.  Proximal to large bodies of water.  Isolation is likely when sample contains soil and rich  The yeast cells (8-12 µm in diameter) typically organic material. have double-contoured refractile walls and a  Animal feces broad base attaching the bud to the parent cell.  Plant fragments  Insect remains These blastoconidia are globose in appearance.  Dust

ECOLOGY (cont.) ECOLOGY

 It is one of the endemic mycoses in the U.S.  Africa  Endemic areas include:  Within these endemic regions are hyperendemic  North America regions—high rates of blastomycosis Mississippi river valley Lincoln Country, Wisconsin—outbreak from Ohio river valley January to April 2006  Missouri river valley 27 confirmed cases compared to typical 8  Midwestern and Canadian providences Source-Pine needle pine bordering Great Lakes

CLINICAL MANIFESTATIONS PULMONARY

 Presentation is pneumonia with radiography revealing an alveolar or mass-like infiltrate.

 Chronic pneumonia  Weight loss, night sweats, fever, cough, and chest pain.

 Acute pneumonia Atlas of fungal infections. 2nd ed. / editor, Carol A. Kauffmann ; editor-in-chief,  Fever, chills, and productive purulent cough Gerald L. Mandell ; with 26 contributors.

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CUTANEOUS CUTANEOUS (cont.)

 Skin lesions with or without pulmonary lesions.  Either verrucous or ulcerative  Verrucous– has an irregular and raised border often with crusting and exudate above the abscess in the subcutaneous tissue.  Ulcerative– occurs when subcutaneous abscess spontaneously drains. Borders are raised and distinct.

Atlas of fungal infections. 2nd ed. / editor, Carol A. Kauffmann ; editor-in-chief, Gerald L. Mandell ; with 26 contributors.

CUTANEOUS (cont.) GENITOURINARY

 Often present at same time as infection in lung.

 Men are more likely to have extrapulmonary blastomycosis.  Prostatitis and epididymoorchitis are common.

 Female genitial tract less frequently diagnosed

 Atlas of fungal infections. Endometrial infection and tubo-ovarian abscess 2nd ed. / editor, Carol A. Kauffmann ; editor-in-chief, Gerald L. Mandell ; with 26 contributors.

OSTEOARTICULAR OSTEOARTICULAR (cont.)

 The vertebrae, pelvis, sacrum, skull, ribs or long bones are most frequent site of infection.

 Debridement may be required for cure.  Most resolve with antifungal therapy.

 Articular blastomycosis less common then osseous.

 Most patients have concurrent disease of skin Atlas of fungal infections. 2nd ed. / editor, Carol A. and lungs. Kauffmann ; editor-in-chief, Gerald L. Mandell ; with 26 contributors.

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CNS CNS (cont.)

 Least common area to be affected.

 Meningitis, cerebral abscesses, or blastomycomas are usual manifestations.

 Difficult to identify organism  Radiographic imagining—to biopsy the cranial abscesses or blastomycomca Atlas of fungal infections. 2nd ed. / editor, Carol A. Kauffmann ; editor-in-chief, Gerald L. Mandell ; with 26 contributors.

IMMUNOSUPPRESSED PATIENTS IDENTIFYING Blastomycosis dermatidis

Fluid or tissue from infected region are obtained and placed in 10% KOH

A mould form to yeast form conversion is required to pinpoint B. dermatitidis - Required because yeast of B. dermatitidis can be similar to other species of Coccidioides and

Atlas of fungal infections. Cryptococcus 2nd ed. / editor, Carol A. Kauffmann ; editor-in-chief, Gerald L. Mandell ; with 26 contributors.

CONT’D CONT’D

- First, yeast samples need to be spread on an agar From here, the conversion can be made by plate placing cells on a Kelley’s agar or blood agar supplemented with glutamine Agar plates used: SGA IMA (Mould Inhibitory Agar) Incubate at 37° C - IMA is preferable because it is a yeast-extract agar DNA can be examined to verify B. - Samples are inoculated at 30° C and dermatitidis kept for 4 weeks

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EPIDEMIOLOGY CONT’D PATHOGENICITY

- Disease is very sporadic  Inhalation of conidia - One endemic region may have few  Organism transforms into yeast in the alveoli outbreaks, while another has many (no  Induces inflammatory response – forms granuloma  Relatively resistant to phagocytosis consistency)  Growth occurs in the lungs - Have been as many as 42 cases per 100,000  Can also spread via bloodstream people - More reported cases in males than females by  Direct inoculation of the fungus into the skin 4-15 fold  Virulence factor – BAD1 - More prevalent in adults than children

DIAGNOSIS DIAGNOSIS (cont.)

 Cytology (sputum/biopsy of the lesion)  Common specimens  Histopathology (biopsy of the lesion)  Sputum  Bronchoalveolar lavage  Culture (sputum)  Transtracheal aspirate  Antigen (urine and serum)  Lung biopsy  KOH  Examine directly with KOH, calcofluor white, or both  Primary isolation media should contain antibiotics  Relatively easy to identify in tissue or exudates and cycloheximide to inhibit saprophytic fungi  All cultures should be incubated for 4-8 weeks

PREVENTION TREATMENT

- Due to sporadic nature, there is no specific - Itraconazole and Amphotericin B are most common prevention - No specific risk factors identified - Fluconazole and Ketoconazole also used - No vaccine, but getting close - Vaccine with the antigen WI-1 being tested - Antifungals may be used together and for prolonged - Prevents organism from binding to cells periods of time (6 months or more) - Maintain immune system - AIDS, transplant recipients, and other immune - Serious cases = high doses of Amphotericin B compromised patients at high risk - Minor cases = Itraconazole and other antifungals

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CASE REPORT CASE REPORT (cont.)

 Case #1- 15 year old African American female  1 month later  Multiple skin nodules  Multiple subcutaneous nodules  Swelling of the right ring finger  Right upper eyelid, upper arms, and right side of chest  Developed productive cough

 2 months prior – small, nontender lesion was noticed  Occasional haemoptysis  Increased in mass and became tender  Progressive fatigue  Was incised and drained  Fever  Given oral Cephalexin  Night sweats  Weight loss

CASE REPORT (cont.) CASE REPORT (cont.)

 Chest Radiography  Silver stain  Large posterior infiltrate  Numerous thick-walled, broad-based yeast forms  Radiograph of right ring finger  Allow for diagnosis of Blastomycosis  Lytic cortical defect of proximal phalanx  Computed Tomograph of the head  Several small lytic areas in brain stem  Wounds were irrigated and closed  Bronchoscopy  Bronchoalveolar lavage

CASE REPORT (cont.) CASE REPORT (cont.)

 Did not tolerate Amphotericin B  Case #2 - 43 year old white male  Developed prostatis  Only partial responsive to oral Ciprofloxacin  Abelcet – lipid soluble form of the drug  1 month later – onset of cutaneous lesions  Dysuria, daily fevers, lost 5 kg in weight  Discharged in 10 days  Multiple verrucous and uclerative lesions  Face, hands, trunk, legs  Mild bibasilar rales on ausculation of the chest  Outpatient treatment 3 times a week for 6 weeks  Swollen right ankle  Obvious effusion  Fluconazole orally for one year  Ulcerative lesion of the right lateral foot

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CASE REPORT (cont.) CASE REPORT (cont.)

 Urine Analysis  Haematuria and proteinuria

 Chest Radiography  Right foot – lucency of dome of talus, consistent with osteomyelitis  Left hand – cortical lytic lesion of middle phalanx of middle figer

 KOH prep  Yeast forms consistent with Blastomycosis

CASE REPORT (cont.) CITATION

 Treated with Amphotericin B  http://medical-dictionary.thefreedictionary.com/  Continued for 9 days blastomycosis  http://www.health.state.mn.us/divs/idepc/  Abcesses were incised and drained diseases/blastomycosis/basics.html  Atlas of fungal infections. 2nd ed. / editor, Carol A.  Daily whirlpool bath treatments Kauffmann ; editor-in-chief, Gerald L. Mandell ; with 26 contributors.  Itraconazole orally for 6-12 months  http://www.doctorfungus.org/thefungi/ Blastomyces.htm

CITATION QUESTION 1

 http://www.nlm.nih.gov/medlineplus/ency/article/ Serious infections of Blastomycosis are treated with? 000102.htm  http://emedicine.medscape.com/article/296870- treatment A) Itraconazole  http://www.medscape.com/viewarticle/477697_2 B) Ketoconazole  http://www.medscape.com/viewarticle/477697_7 C) Voriconazole  Dismukes, W.E.,M.D., Pappas, P.G.,M.D., & Sobel, D) Amphotericin B J.D.,M.D. (2003). Clinical mycology. New York, NY: Oxford University Press.  Anaissie, E.J., McGinnis, M.R., & Pfaller, M.A. (2003). Clinical mycology. New York, NY: Churchill Livingstone.

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QUESTION 2 Question 3

What is the virulence factor for B. dermatitidis? B. dermatitidis is endemic to which continent?

A) BAD1 A) South America B) TGF-ß B) North America C) TNF-α C) Asia D) BALB D) Europe

Question 4 Question 5

Where is the prominent location of dissemination? Inside the body B. dermatitidis is in the form of?

A) Bloodstream A) Conidia B) Lungs B) Yeast C) Cutaneous surfaces C) Mold D) Liver D) Hyphae

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