Infectious Diseases Conference

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Infectious Diseases Conference

• April 28th 2003
• Charles de Comarmond MD

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Present Medical History

• 76 yr old AAM admitted 03/13/03 with intractable
  headache.
• Later found to have diverticulitis and
  diverticular polymicrobial abscess requiring
  percutaneous drainage (3/15/03) followed by
  Hartmans procedure on 3/29/03.
• On 3/30/03 patient complained of decreased visual
  acuity and developed NIII NVI palsy.

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Present Medical History

• Extensive work-up performed by ophthalmology and
  neurology including MRI unrevealing.
• Developed total loss of vision with worsening
  headache on 04/08/03

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Past medical history

• Chronic headache (12 week duration)
• Chronic sinusitis
• Diverticulitis
• DM type 2
• BPH
• Osteoarthitis
• Upper GI bleed
• CRF

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Family, social history ROS

• Chronic headache extensively worked up.
• Temporal artery biopsy negative s/p empiric
  steroid therapy
• Hx of chronic iritis

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Physical exam
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Physical exam

• Skin Colostomy site clean, surgical wound
  healed, no rash
• HEENT Blind, bilateral proptosis LgtR
• Neck Supple
• Chest Clear
• Heart S1S2 RRR
• Abdomen Soft

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Physical exam

• Extremities Grossly normal
• Neuro Cranial NIII and NVI palsy

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Labs
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WBC trend
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Creatinine trend
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Imaging

• MRI O4/07/03

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Imaging

• CT 04/09/03

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Hospital course

• 04/09/03
• ID consult requested
• Empiric Amphotericin B lipid complex recommended
• Strongly recommended surgical biopsy for cultures
  and histology

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Hospital course

• 04/11/03

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Operative report
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Gram stain and cultures
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Histology
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Histology
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Cultures
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Cultures
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Hospital course

• Abelcet changed to voriconazole
• Continues to be febrile
• Worsening mental state

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IMAGING
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PSEUDALLESCHERIA BOYDII RhinoSINUSITIS
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Introduction

• P. boydii (previously known as Allescheria boydii
  and Petriellidium boydii) and its asexual form,
  Scedosporium apiospermum (previously Monosporium
  apiospermum), are ubiquitous saprophytic fungi
  found in soil, manure, decaying vegetation, and
  polluted streams

Mark A. Nesky, E. Colin McDougal, and
James E. Peacock, Jr. Pseudallescheria boydii
Brain Abscess Successfully Treated with
Voriconazole and Surgical Drainage Case Report
and Literature Review of Central Nervous System
Pseudallescheriasis. Clinical Infectious
Diseases    200031673-677
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Introduction

• P. boydii most often causes cutaneous infection
  (i.e., mycetoma)
• Invasive disease can occur in
• Immunocompromised hosts
• Patients with impaired anatomic barriers (trauma,
  burns, etc.)
• Cases of massive inoculation (near-drowning in
  polluted water).

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Introduction
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Introduction

• Infection due to P. boydii presents both
  diagnostic and therapeutic challenges.
• Because of the organism's morphological
  similarity to other filamentous fungi, histologic
  differentiation is difficult, and accurate
  diagnosis is thus dependent upon culture

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Introduction

• Pseudallescheria and Scedosporium form slender,
  septate hyphae with parallel cell walls that
  cannot be reliably distinguished from Aspergillus
  species or Fusarium species unless conidia are
  present
• When conidia are seen with appropriate hyphae, a
  preliminary diagnosis can be made but should be
  confirmed with fungal culture

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Pseudallescheria Boydii branching hyphae
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Pseudallescheria Boydii PAS stain
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Scedosporium aspermiosum spores
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Scedosporium aspermiosum spores
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Fungal rhinosinusitis

• Three distinct forms of invasive fungal sinusitis
  recently have been characterized
• granulomatous invasive fungal rhinosinusitis
• chronic invasive fungal rhinosinusitis
• acute fulminant invasive fungal rhinosinusitis

Otolaryngologic Clinics of North AmericaVolume
33 Number 2 April 2000
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Fungal rhinosinusitis

• The three entities differ with regard to
• at-risk patient populations
• disease presentation
• histopathology
• therapeutic management.
• The acute fulminant form of invasive
  rhinosinusitis is the subtype that most commonly
  occurs in the hospitalized patient in the United
  States.

Berlinger NT Sinusitis in immunodeficient and
immunosuppressed patients. Laryngoscope 9529-33,
1985  
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Acute fulminant invasive fungal rhinosinusitis

• Acute fulminant invasive fungal rhinosinusitis is
  a disorder characterized by mycotic infiltration
  of the mucosa of the nasal cavity and paranasal
  sinuses.
• In the absence of treatment, the disease is
  rapidly fatal in 50 to 80 of patients secondary
  to invasion of the orbit and intracranial cavity

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Acute fulminant invasive fungal rhinosinusitis

• The primary risk factor for the development of
  acute fulminant invasive fungal rhinosinusitis is
  an immunocompromised state
• The disorder always occurs in patients with
  poorly controlled type 1 diabetes mellitus, AIDS,
  hemochromatosis, aplastic anemia, iatrogenic
  immunosuppression, organ transplantation, or
  hematologic malignancy.

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Acute fulminant invasive fungal rhinosinusitis

• Significant secondary risk factors found in
  patients with acute fulminant invasive
  rhinosinusitis have been identified
• Prolonged courses of prednisone-equivalent
  steroids is present in up to 50 of patients.
• Most patients have received at least 2 weeks of
  broad-spectrum intravenous antibiotics at the
  time of clinical presentation.

Iwen PC, Rupp ME, Hinrichs SH Invasive mold
sinusitis 17 cases in immunocompromised patients
and review of the literature. Clin Infect Dis
241178-1184, 1997
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Acute fulminant invasive fungal rhinosinusitis

• The most common symptom in up to 90 of patients
  is fever of unknown origin that has not responded
  to 48 hours of appropriate broad-spectrum
  intravenous antibiotics
• The absence of fever does not rule out the
  disorder, especially in patients with localizing
  symptoms such as facial and periorbital pain,
  nasal congestion and rhinorrhea, and headache,
  which are variably present in 20 to 60 of
  patients.

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Acute fulminant invasive fungal rhinosinusitis

• Late signs and symptoms include loss of visual
  acuity, ophthalmoplegia, proptosis, change in
  mental status, focal neurologic signs, and
  seizure
• A mortality rate of 100 has been demonstrated in
  patients with intracranial involvement
• MR imaging scanning may prevent unnecessary
  procedures in patients who are unlikely to
  benefit from surgery.

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Chronic invasive fungal rhinosinusitis

• chronic invasive fungal sinus disease is divided
  into two types based on histopathology
• granulomatous invasive fungal sinusitis
• nongranulomatous form termed chronic invasive
  fungal sinusitis.

Stringer SP, Ryan M W., Otolaryngologic Clinics
of North AmericaVolume 33 Number 2 April
2000
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Chronic invasive fungal rhinosinusitis

• Chronic invasive fungal sinusitis and
  granulomatous invasive fungal sinusitis are
  characterized by
• a prolonged clinical course with slow disease
  progression
• sinusitis on radiologic imaging
• histopathologic evidence of hyphal forms within
  sinus mucosa, submucosa, blood vessel, or bone.

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Chronic invasive fungal rhinosinusitis

• Distinguishing features of granulomatous and
  nongranulomatous subtypes are indicated when
  appropriate.
• Presently the presence or absence of a
  granulomatous response does not alter the
  prognosis or the therapeutic intervention.

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Chronic invasive fungal rhinosinusitis

• Chronic invasive fungal rhinosinusitis may mimic
  many other disorders,
• benign or malignant neoplasms,
• pituitary tumors,
• syphilis,
• tuberculosis,
• sarcoidosis,
• Wegener's granulomatosis,
• lymphoma,
• inflammatory pseudotumor,
• myospherulosis, mucopyocele,
• allergic fungal rhinosinusitis, and
• rhinoscleroma

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Chronic invasive fungal rhinosinusitis

• Chronic invasive fungal rhinosinusitis usually
  occurs in healthy individuals, though many have a
  previous history of chronic rhinosinusitis-type
  symptoms, upper respiratory allergies, or nasal
  polyposis

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Chronic invasive fungal rhinosinusitis

• In one series, the patients with the
  nongranulomatous form all had diabetes.
• The granulomatous form may occur in diabetic
  patients as well.
• Symptoms directly related to the invasive disease
  may take months or years to appear and may only
  develop once the orbit or skull base are
  involved.

deShazo RD, A new classification and diagnostic
criteria for invasive fungal sinusitis. Arch
Otolaryngol Head Neck Surg 1231181-1188, 19
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Chronic invasive fungal rhinosinusitis

• Erosion into the orbit from the paranasal sinuses
  may produce proptosis.
• Proptosis is the most common presentation of the
  granulomatous cases
• Invasion of the maxillary floor may produce
  palatal erosions
• Erosion of the cribriform plate may cause chronic
  headache, seizures, decreased mental status, or
  focal neurologic findings.

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Chronic invasive fungal rhinosinusitis

• Extension through the sphenoid sinus may lead to
  orbital apex syndrome or cavernous sinus syndrome
• Extension to the pterygopalatine fossa
  predictably may cause cranial nerve deficits
• Catastrophic complications have been reported,
  including mycotic aneurysm, internal carotid
  artery rupture, and cavernous sinus thrombosis

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Chronic invasive fungal rhinosinusitis

• On intranasal examination, severe nasal
  congestion and polypoid mucosa may be noted
• There may be a soft tissue mass that can be
  either mucosally covered or ulcerated with
  overlying debris or dried secretions.
• It appears that no definitive physical findings
  have been documented to this point that reliably
  distinguish granulomatous from nongranulomatous
  subtypes.

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Chronic invasive fungal rhinosinusitis

• A sinus CT scan is an appropriate initial image
  in the evaluation of suspected fungal
  rhinosinusitis.
• Mucosal thickening may be noted with any form of
  fungal rhinosinusitis.
• Focal or diffuse areas of hyperattenuation within
  a sinus are a clue to fungal colonization, thick
  mucin plugs, infection, or AFS.

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Chronic invasive fungal rhinosinusitis

• It is important to note that both chronic
  invasive fungal rhinosinusitis and AFS can cause
  bone erosion or expansion, suggesting a
  potentially invasive process
• Soft tissue infiltration of periantral fat planes
  around the maxillary sinus provides early
  evidence of invasive fungal rhinosinusitis in the
  appropriate clinical setting

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Chronic invasive fungal rhinosinusitis

• MR imaging is useful for assessing dural
  involvement and intradural extension of disease.
• Differentiation between a malignant neoplasm and
  chronic invasive fungal rhinosinusitis by
  radiologic findings can be difficult or
  impossible.
• The ultimate distinction between invasive and
  noninvasive fungal rhinosinusitis and neoplasm is
  best made histologically.

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Chronic invasive fungal rhinosinusitis

• Most patients with chronic invasive fungal
  rhinosinusitis are immunologically intact.
• In one series, extensive battery of tests were
  performed in an effort to uncover a hidden
  immunologic abnormality.
• The battery included absolute neutrophil and
  monocyte counts, percentage of nonspecific
  esterase and myeloperoxidase-positive mononuclear
  cells, phagocytic and fungicidal activity of
  peripheral blood monocytes, chemiluminescence,
  nitroblue tetrazolium reduction, chemotaxis,
  total lymphocyte counts, lymphocyte
  subpopulations and natural killer activity, serum
  immunoglobulin levels, and tests of delayed type
  hypersensitivity.
• No specific immunologic defects were identified

Washburn RG Fungal sinusitis. Curr Clin Top
Infect Dis 1860-74, 1998
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Chronic invasive fungal rhinosinusitis

• Histologically, granulomatous chronic invasive
  fungal rhinosinusitis are composed of
  eosinophilic material surrounded by fungus, giant
  cells, and palisading nuclei, variable numbers of
  lymphocytes, and plasma cells.

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Chronic invasive fungal rhinosinusitis

• Nongranulomatous chronic invasive fungal
  rhinosinusitis was characterized by tissue
  necrosis with little inflammatory infiltrate and
  dense hyphal accumulation resembling a fungus
  ball (mycetoma)

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Chronic invasive fungal rhinosinusitis

• Chronic invasive fungal rhinosinusitis has
  specifically been associated with
• Aspergillus
• Mucor
• Alternaria
• Curvularia
• Bipolaris
• Candida
• Drechslera
• Sporothrix schenckii
• Pseudallescheria boydii

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Chronic invasive fungal rhinosinusitis

• Aspergillus, Candida, Pseudallescheria, and
  Zygomycetes (Mucoraceae) can usually be
  distinguished histologically
• Differentiating Aspergillus and Pseudallescheria
  may sometimes be problematic

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Chronic invasive fungal rhinosinusitis

• Fungi can occasionally be picked out in tissue
  stained with hematoxylin and eosin (HE), but in
  general, stains such as Giemsa, PAS, GMS, and
  alcian blue are required for a sensitive
  examination

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Chronic invasive fungal rhinosinusitis

• There has been no systematic evaluation of
  treatment options for patients with chronic
  invasive fungal rhinosinusitis
• Most published cases have been treated with a
  combination of surgery and antifungal
  chemotherapy

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Chronic invasive fungal rhinosinusitis

• There is no general agreement on the extent of
  surgery necessary to arrest or eradicate invasive
  fungal rhinosinusitis or whether the
  granulomatous form should be treated differently
  from the nongranulomatous form

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Chronic invasive fungal rhinosinusitis

• Recommendations have ranged from wide aeration of
  the sinuses to a thorough exenteration of
  diseased tissue.
• Some reports suggest that cure might be achieved
  with surgical debridement alone or with a
  combination of debridement followed by antifungal
  therapy

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Chronic invasive fungal rhinosinusitis

• Chronic invasive fungal rhinosinusitis frequently
  recurs despite surgical debridement and a
  prolonged course of amphotericin B exceeding 2 g
  for adults after surgery is recommended

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Chronic invasive fungal rhinosinusitis

• Current recommendation for patients with
  histologic invasion and extension beyond sinus
  confines is sinus debridement and wide aeration
  followed by 1 to 2 g of amphotericin B
• If persistent or recurrent disease develops,
  itraconazole 200 to 400 per day for 6 to 12
  months may be added
• Fungal cultures are necessary because not all
  fungi are sensitive to amphotericin B or
  itraconazole.

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Chronic invasive fungal rhinosinusitis

• One limitation is that P boydii is resistant to
  amphotericin
• Recent reports have shown some success with
  voriconazole and posaconazole

Mark A. Nesky, E. Colin McDougal, and
James E. Peacock, Jr. Pseudallescheria boydii
Brain Abscess Successfully Treated with
Voriconazole and Surgical Drainage Case Report
and Literature Review of Central Nervous System
Pseudallescheriasis. Clinical Infectious
Diseases    200031673-677 Ingo K. Mellinghoff,
Drew J. Winston, Geoffrey Mukwaya, and
Gary J. Schiller. Treatment of Scedosporium
apiospermum Brain Abscesses with Posaconazole.
Clinical Infectious Diseases  2002341648-1650