Arryn Craney , Ph.D . University of Nebraska Medical Center - PowerPoint Presentation

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Arryn Craney, Ph.D.University of Nebraska Medical Center

It’s Just Allergies… or

i

s

i

t?

Patient History71 year-old male patient presents to the ED with 4 months of headaches and radiating pain on the left side of his face.

He reports a history of

sinusitis

with:

Multiple courses of antibiotics

over the past 6 months without resolving

symptoms.

Surgery was performed ~ 2 months prior to debride the

sinuses.

a large

fungal ball

was

removed.

Treated with

corticosteroids.

Headaches returned a few weeks after

surgery.

Patient was admitted for further work up.

Allergic Fungal Rhinosinusitis (AFR)Common infection of the sinuses where environmental fungi

cause an allergic reaction

resulting in the production of mucus that blocks the sinuses.

This results in a sticky ball of fungus and mucus called a

fungal ball

that must be removed

.

Treatment

: Removal of the fungal ball and corticosteroids are usually sufficient to resolve the disease (anti-

fungals

not needed unless the fungus invades the tissue).

However, our patients' symptoms returned and intensified warranting further investigation.

Is This an Invasive Disease?

Progression to invasive disease is rare, especially in immunocompetent patients but can be triggered by corticosteroid use.

Given the prolonged and severe symptoms of our patient, a nasal biopsy was taken to determine if the fungus had invaded the tissue.

Non-invasive AFR –

fungi have not invaded the tissue

Invasive AFR

–

fungal elements HAVE invaded the tissue

A biopsy of the tissue is necessary to diagnose invasive disease

Types of Invasive AFRAcute Invasive AFR = symptoms < 4 weeksSeen mainly in immunocompromised patients

Aspergillus

spp. or

Zygomyces

spp. most likely causative agents

Chronic Invasive AFR

= symptoms > 3 monthsGranulomatous Invasive AFREnlarging mass in the cheek, orbit, nose, and paranasal sinuses in immunocompetent patientsAspergillus flavus is the most common causeChronic Invasive AFRSlow destructive process affecting the ethmoid and sphenoid sinuses (OUR PATIENT)Usually seen in the context of AIDS, diabetes mellitus, and corticosteroid treatmentAspergillus fumigatus most likely cause

Note: Other environmental (saprophytic) molds may also be causative agents of AFR; especially dematiaceous molds like Alternaria spp., Bipolaris spp. and

Curvularia spp.Chakrabarti A et al., Laryngoscope. 2009. 119(9): 1809–1818.

Nasal Biopsy Revealed Fungal Elements in the TissueFungal Stains

Hematoxin

and eosin (H&E)

Best stain for host response, stains most fungi

Fungal elements may be missed when in low numbers

Gomori’s

methenamine silver (GMS) Best stain screening for fungal elements in the tissue (high contrast with minimal background)Periodic acid-Schiff reaction (PAS) Stains most fungi, generally used as a secondary stain Only stains living fungusGridley fungus (GF) Stains most fungi, generally used as a secondary stainFontana-Mason Stains melanin, can be used if dematiaceous mold suspected

GMS 400X

Invasive Disease!Photo Credit: Dr. Peter Iwen, University of Nebraska Medical Center

Which Fungi is it?Can rule out Zygomyces

spp

.

because:

They would be

pauciseptate

- wide ribbons with right angle branching

More likely seen in acute invasive AFR not chronic AFRAspergillus spp.?Septate hyphae with acute branchingMost common cause of AFR

GMS 400XSeptate Hyphae with

Acute Angle Branching

Many other molds can look like this in tissue including:

Fusarium

spp.,

Paecilomyces

spp.,

Scedosporium

spp.,

Trichoderma

spp. all of which have been reported as rare causes of AFR

But….

Photo Credit

: Dr.

Peter

Iwen

,

University of Nebraska Medical Center

Does it Matter Which Fungus?Yes!! When anti-fungal agents are required for AFR, Amphotericin B

or

Itraconazole

is empiric therapy

BUT

this therapy is directed towards

Aspergillus spp. since they are the most common cause of AFR.For other molds that cause AFR, amphotericin B and itraconazole may not be effective.Resistance to itraconazole had been reported in some environmental molds.Most azoles (voriconazole, itraconazole and fluconazole) cannot be used to effectively treat the Zygomycetes. Amphotericin B is the preferred anti-fungal for infections caused by Zygomyces spp. Recovering the fungus in culture allows microbiology to obtain anti-fungal MICs with the patient’s isolate.

Fungal Culture Grew Scedosporium apiospermum!

Fungal Culture Lactophenol Cotton Blue

Oval/tear dropped

conidia.

Conidia are in singles, small groups, or laterally along the

hyphae.

Colonies grow quickly within a within a few

days.

Initially looking hyaline (white) but slowly develop the dark brown melanin

pigment.

Phot Credit:

CDC Public Health Image

Laboratory

,

CDC Public Health Image Laboratory

.

The Scedosporium species causing human disease…With better identification methods the Scedosporium genus is expanding and now includes 3 species:

Scedosporium

apiospermum

.

Scedosporium

aurantiacum.Scedosporium boydii.Lomentospora  prolificans used to be a Scedosporium!Noted for its prolific resistance to anti-fungal agents.

Is it Scedosporium spp. or is it Pseudoallescheria?!?!

Anamorph (asexual state) =

Scedosporium

spp.

Telomorph

(sexual state) = Pseudoallescheria spp.Naming convention suggests the use of the anamorph state.And, production of the telomorph state does not generally occur on routine media for fungal culture (requires a nutritionally poor media).

Scedosporium spp. infections (including Lomentospora  prolificans

)

Environmental molds present in soil, sewage and polluted waters

Cause a broad range of clinical diseases:

Primarily infect the lungs, but can also cause sinus, ocular and skin and soft tissue infections (primarily

mycetomas

)

These infections range in severity from transient colonization to local invasive disease (like our patient!) to the rare cases of disseminated disease (immunocompromised) and can even have CNS involvement!

Cortez KJ et al., Clin Microbiol Rev. 2008. 21(1):157-97.

Anti-Fungal TherapyItraconazole and amphotericin B tend NOT to be effective against S. apiospermum

–

good thing we had a fungal culture!

Anti-fungal MICs vary by the individual

Scedosporium

isolate and show a wide range of variability. Susceptibility testing on the patients’ actual isolate is warranted to help guide therapy since

voriconazole

is the drug of choice.Our patients MIC to Voriconazole was 1 μg/ml (susceptible!).

Back to Our PatientPatient received voriconazole.

Our patients’ headaches have resolved over the past few weeks and he is expected to fully recovery!

Arryn Craney, Ph.D.Dr. Craney is a second year CPEP Clinical Microbiology Fellow training at the University of Nebraska Medical Center. Her areas of research interests include rapid diagnostics for antibiotic resistance and whole genome sequencing applications in clinical microbiology.

Photo Credit: Arryn

Craney

, Ph.D.