Case Conference

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Case Conference

• Toby Fugate, D.O.

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DisclosuresSection of Infectious Diseases

• Kevin High, M.D.
• Grant/Research Support Cubist Pharmaceuticals,
  Astellas Pharma US, Inc.
• Consultant Merck Co., Inc.
• Speakers Bureau Pfizer Pharmaceuticals
• James Peacock, M.D.
• Ownership in Common Stock Pfizer
  Pharmaceuticals
• Sam Pegram, M.D.
• Grant/Research Support Roche, Bristol-Myers
  Squibb, Gilead, Schering-Plough, Tibotec
  Pharmaceuticals
• Consultant Abbott Laboratories,
  GlaxoSmithKline, Boehringer Ingelheim, Gilead,
  Roche
• Speakers Bureau Abbott Laboratories,
  GlaxoSmithKline, Boehringer Ingelheim, Merck,
  Pfizer Pharmaceuticals

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Disclosure (continued)Section of Infectious
Diseases

• Aimee Wilkin, M.D.
• Grant/Research Support Abbott Laboratories,
  GlaxoSmithKline, Tibotec Pharmaceuticals,
  Bristol-Myers Squibb Company, Gilead
• Christopher Ohl, M.D.
• Grant/Research Support Cubist Pharmaceuticals,
  Gene-Ohm Sciences, Merck Pharmaceuticals
• Speakers Bureau/Consultant Ortho-McNeil
  Pharmaceuticals, Cubist Pharmaceuticals,
  Sanofi-Aventis Pharmaceuticals, Pfizer
  Pharmaceuticals, Bayer Pharmaceuticals

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Disclosure (continued)Section of Infectious
Diseases

• Tobi Karchmer, M.D.
• Grant/Research Support Gene-Ohm Sciences
• Speakers Bureau Pfizer Pharmaceuticals, Cubist
  Pharmaceuticals, Cepheid,
• Gene-Ohm Sciences
• Consultant C.R. Bard
• Robin Trotman, D.O.
• Speakers Bureau Pfizer Pharmaceuticals

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33 year old male

• Developed swelling on the right eyelid pt
  thought he had a stye and treated himself
  conservatively swelling worsened
• Presented to an OSH due to worsened swelling
  above his right eye and diplopia
• Fluctuance was noted by ED physician
• The area was drained (no cultures)
• CT head revealed severe sinusitis of b/l
  frontal, maxillary, and ethmoid sinuses. Erosion
  of anterior and inferior walls of R frontal sinus
  with extension into the R orbit
• Started on Levoquin and referred to WFUBMC ENT

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33 year old male

• PMHx/SHx
• Repair of nasal fracture at age 8 years
• Medications
• None
• Allergies
• Erythromycin and Amoxicillin
• Family Hx
• No chronic illnesses
• Social Hx
• Smokes ½ ppd
• Occasional MJ
• No ETOH/IVDA

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Visit with WFUBMC ENT

• Pt complained of draining sinus over R eye and
  ptosis
• CT head ordered

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Comments?
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Official Interpretation

• Changes consistent with chronic frontal
  sinusitis
• Process within the right frontal sinus which
  invades the orbit, displacing the globe, possibly
  a mucocele

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• Surgery
• Bilateral endoscopic maxillary antrotomy
• Bilateral endoscopic anterior ethmoidectomy
• Bicoronal osteoplastic flap
• Bilateral frontal sinus obliteration

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Thoughts?

• What eponym describes this condition?
• Which organisms are involved?
• What is the treatment?

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Outline

• History
• Anatomy
• Etiology
• Pathophysiology
• Microbiology
• Diagnosis
• Treatment
• Follow-up on our patient

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Potts Puffy Tumor

• First described in 1775 by Sir Percival Pott
• Subperiosteal abscess of the frontal bone
  complicating osteomyelitis after trauma to the
  forehead
• 75 of cases are due to frontal sinusitis --
  other causes will be discussed later
• Rare finding -- only 28 cases have been described
  since 1977 (mostly in teenagers)

• Huijssoon et al. International Journal of
  Pediatric Otorhinolaryngology, 2003

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Sir Percivall Pott1714-1788
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Sir Percivall Pott1714-1788

• Potts Puffy Tumor
• Potts Disease
• Potts Paraplegia
• Paraplegia caused by spinal cord compression and
  abscesses in Potts disease
• Pott's aneurysm
• Arteriovenous aneurysm in which blood flows from
  an artery directly into a vein without going
  through a connecting sac, reportedly described by
  Pott
• Pott's Fracture
• Fracture of the lower end of the fibula and
  medial malleolus of the tibia with rupture of the
  internal lateral ligament of the ankle, caused by
  outward and backward displacement of the leg
  while the foot is fixed
• Pott's Gangrene
• Mortification (gangrene or necrosis) of toes and
  feet due to arterial obstruction in the aged
• Potts Cancer (soot-wart)
• Coal tar-induced cancer of the skin particularly
  localized to the scrotum

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Etiology

• Frontal sinusitis
• Of all sinusitis seen by ENT, less than 1 is a
  frontal sinusitis
• Trauma
• Craniotomy
• Hair transplantation

Bagdatoglu et al. Pediatric Neurosurgery, 2001
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Quiz

• True or False
• The paranasal sinuses are sterile?

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Answer

• TRUE
• The paranasal sinuses , although directly
  connected to the nasal passages (which are
  colonized with bacteria), are themselves sterile
  under normal conditions
• Mandell 6th Edition, page 773

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Question?

• By what mechanism(s) does/do the sinuses remain
  sterile?

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Answer

• Sterility is maintained in the sinus by
  mechanisms that are not fully understood but are
  believed to include
• Mucociliary clearance
• Immune system
• Possibly antibacterial concentrations of nitric
  oxide gas in the sinus cavity

Mandell 6th Edition, Pg 773
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Mandell 6th Edition
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Pathophysiology Extension of Frontal Sinusitis

• Venous spread (most common)
• Progressive thrombophlebitis through valveless
  diploic veins and septic emboli
• Thrombosis of the sagittal sinus or cavernous
  sinus
• Subdural empyema
• Meningitis
• Subdural abscess
• Brain abscess

Any of the veins, designated frontal, anterior
temporal, posterior temporal, and occipital,
located in the diploe and connected with the
cerebral sinuses by emissary veins.
Huijssoon et al. International Journal of
Pediatric Otorhinolaryngology, 2003
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Pathophysiology Extension of Frontal Sinusitis

• Direct extension (can occur in three direction)
• Anterior wall of the frontal bone
• Subperiosteal abscess (Potts Puffy Tumor)
• Posterior wall of the frontal bone
• Epidural empyema
• Subdural empyema
• Brain abscess
• Meningitis
• Inferior wall
• Intraorbital abscess
• Orbital cellulitis
• Optic neuritis

• Huijssoon et al. International Journal of
  Pediatric Otorhinolaryngology, 2003

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Microbiology

• Streptococcus species
• Staphylococcus species
• Enterococcus species
• Fusobacterium
• Bacteroides species
• Peptostreptococcus
• Haemophilus influenzae
• Klebsiella species
• Candida albicans

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Diagnosis

• Clinical Examination
• CT (study of choice)
• Opacification of frontal sinus with bony
  destruction of the anterior wall and pericranial
  fluid collection
• MRI
• Ultrasound ?

Huijssoon et al. International Journal of
Pediatric Otorhinolaryngology, 2003 Weinberg et
al. Journal of Clinical Ultrasound, 2005
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Treatment

• Combination of surgery (endoscopic or open) and
  antibiotics
• Empiric antibiotics should include coverage for
  Streptococcus species, Staphlyococcus aureus, and
  oral anaerobes
• Average duration of treatment is 6 weeks

Huijssoon et al. International Journal of
Pediatric Otorhinolaryngology, 2003 Goldfarb et
al. Otolaryngol Head Neck Surg, 2004
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Case Two
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26 year old African American Soldier

• Diagnosed with pleuropulmonary coccidioidomycosis
  while on active duty in Southern California in
  2003
• Complement fixation titer of 1256
• Left sided effusion requiring drainage
• All cultures were negative
• Extensive negative w/u for disseminated disease
• Treated with fluconazole 800 mg PO daily from the
  time of d/c in 2003 until time of presentation

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26 year old African American Soldier

• Since the time of diagnosis, the pt continued to
  have persistent SOB/cough, CP, and fevers
• October 2005, CF titer was 18
• April 2006, Honorable Discharge from US Air Force
• Returned to NC three weeks prior to presentation
• Persistent symptoms of SOB/cough, CP and fevers
  gradually worsened

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26 year old African American Soldier

• PMHx/SHx
• Pleuropulmonary coccidioidomycosis
• Asthma
• GERD
• HTN
• Medications
• Fluconazole 200 mg Four tabs PO daily

• Allergies
• NKDA
• Social Hx
• Denied tobacco, ETOH, and IVDA
• Married with one child
• Family Hx
• No chronic conditions

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Salisbury VA ED

• W/U including CBC, CMP, CXR, and EKG was
  unremarkable, except mild leukopenia (WBC4.5)
• Pt was given a refill on fluconazole and
  scheduled for f/u with ID the same day
• Physical exam at time of ID evaluation was
  unremarkable (Temp99.5)
• Complement Fixation and CT chest with contrast
  ordered

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CT Chest with contrast

• Irregular density lesion in the left lower lobe
  measuring 1.1 x 1.5 cm contiguous with a 1.8 x
  1.7 cm opacity with air bronchogrmas

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Thoughts?

• What would you do now?
• What is the value of serology?
• Does serology correlate with disease activity?

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Outline

• History
• Predictors of Severe Disease
• Traditional Treatments
• Other Treatments
• Follow-up on Our Patient

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History

• Discovered by Alejandro Posadas, a medical
  intern, in 1891 in Buenos Aries, Argentina
• Posada A. Un nuevo case de micosis fungoldea con
  psorospermias. Annales del Circulo Medico
  Argentino. 1892 15 585-597
• Patients name was Domingo Ezcurra
• Organism was initially though to be a parasite
• Fewer than 30 cases were reported before 1967
• Remains of Domingo Ezcurra was found in an
  anatomy lab in Buenos Aries in 1948 and is now on
  display at the medical school

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Predictors of Severe Disease/Complications

• HIV/AIDS
• Immunosuppression medications used in transplant
  patients
• Steroids (20 mg or more per day of prednisone or
  its equivalent)
• Lymphoma
• Anti-tumor TNF therapy
• Chemotherapy for solid tumors
• DM
• Pregnancy
• Preexisting cardiopulmonary conditions

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Deresinski et al. Current Opinion in Infectious
Diseases, 2001

• Independent Risk Factors for Severe Pulmonary
  Disease
• DM
• Cigarette smoking
• Lower socioeconomic class (annual income 15,000)
• Older age
• Risk Factors for Disseminated Disease
• Lower socioeconomic class
• Pregnancy
• Black Race

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Certain Racial Groups are at Higher Risk of
Disseminated Disease

• Persons of Filipino ancestry accounted for a
  large proportion of the cases of disseminated
  disease
• Gifford et al. Kern County (California) Public
  Health Annual Report, 1936
• African Americans gt Native Americans gt Hispanics
  gt Asians are at greater risk than whites for
  extrapulmonary disease
• Specific genetic differences not identified
• Chiller et al. Infect Dis Clin N Am, 2003

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Quiz

• What is the geographical significance of the two
  species of Coccidioides
• C. immitis
• C. posadasii

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Answer

• Two genetically distinct populations have been
  identified among the etiologic agents of
  coccidioidomycosis
• The two populations correlate with separate
  endemic regions where patients resided
• Most C. immitis isolates have been from
  California
• C. posadasii isolates have been obtained from
  patients in other states and from other countries

Mandell 6th Edition, Pg 3041
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Fluconazole vs Itraconazole

• Randomized, double-blinded, placebo-controlled
  trial
• 191 pts with chronic pulmonary, soft tissue, or
  skeletal coccidioidal infections
• Oral fluconazole 400 mg/d vs itraconazole 200 mg
  BID
• At 8 and 12 months, a scoring system was used to
  assess the severity of infection

Galgiani et al. Annals of Internal Medicine, 2000
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?? Mistake in P value at 12 months in ALL
Ptsshould be 0.05
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Voriconazole

• Case Report - -Successful Treatment of
  Coccidioidal Meningitis with Voriconazole
• 47yo male with fluconazole treatment failure
  (400mg QD) at 4 months
• Dosage eventually increased as high as 1200mg QD
  with little improvement
• Started on voriconazole 6mg/kg x 2 doses and then
  4mg/kg q 12 hrs thereafter - - gradual
  improvement
• After 6 days, change to 300mg PO q 12 hrs
• Eventually over a peroid of 2 ½ years, dose was
  reduced to 200mg BID - - asymptomatic, LP normal,
  serum/CSF antibodies undetectable (CF)

Cortez et al. CID, 2003
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Posaconazole

• Multinational, multicenter, open-label trial in
  subjects with invasive fungal infections of the
  nervous system who had refractory disease or who
  were intolerant of standard antifungal therapy
• 39 subjects (29 with Cryptococcal infection, 10
  with other neural fungal infections, one of which
  was due to C. immitis)
• Subjects treated with posaconazole suspension 800
  mg/day in divided doses (400 mg BID) for up to 1
  year

Pitisuttithum et al. Journal of Antimicrobial
Chemotherapy, 2005
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Partial response clinically meaningful
improvement in attributable symptoms, signs and
radiographic abnormalities
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Follow-up on Our Patient (three weeks later)

• Continued SOB/cough, CP, HA, and fevers
• Fever ranged from 99.5 to 101
• CF titer lt12
• IgG Positive
• IgM Positive
• IgA Positive