Clinical Case Conference

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Clinical Case Conference

• Vera P. Luther, MD
• April 3, 2006

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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

4
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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Case 1

• 20 y/o previously healthy male presented to an
  OSH complaining of fevers to 102F, sinus
  congestion, and HA over the past 3-4 days.
• Pt had developed diplopia, HA, and neck pain
  which became progressively worse in the hours
  pta.
• While at OSH, pts symptoms progressed ? right
  eye ptosis, dilated right pupil and inability to
  move right eye.

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Case 1

• LP was performed and revealed a neutrophilic
  pleocytosis. Pt was given a dose of ceftriaxone
  and vancomycin and was transferred to WFUBMC
• ROS nausea and vomiting over past few hours,
  otherwise unremarkable

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Case 1

• PMH Negative
• All NKDA
• Home Meds
• Afrin nasal spray
• Ibuprofen prn

• Social History
• Geology major at local college
• No recent travel
• No sick contacts
• No substance use

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Case 1

• Physical Examination
• T 99.0 P 117 bp 118/50 R 23
• HEENT
• Right eye ptosis
• Right pupil dilated and did not react to light
• Right ophthalmoplegia
• Unable to abduct left eye
• Neck meningismus

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Case 1

• Laboratory Data
• wbc 5.3 S 62/B 23/L 6/M 5/MM 5
• CMP glc 131 TP 8.1
• Lumbar Puncture
• prot 235
• glc 54
• wbc 4200 85 polys 15 monos
• rbc 78
• gram stain

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• Normal MRI T2 view

• Our patient T2 view

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T1
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T1
13

• Normal MRI

• Our patient T1 cor view

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T1
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T1
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T2
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T2
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T2
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QuestionsImpressionRecommendations
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Sphenoid Sinusitis

• Descriptive study reported on 30 pts with
  infectious sphenoid sinusitis
• 15 acute and 15 chronic
• Seen b/t 1968-1980

Lew et al. Sphenoid sinusitis a review of 30
cases. New Engl J Med 1983 3091149-54.
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Sphenoid Sinusitis
Lew et al. Sphenoid sinusitis a review of 30
cases. New Engl J Med 1983 3091149-54.
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Sphenoid Sinusitis
Lew et al. Sphenoid sinusitis a review of 30
cases. New Engl J Med 1983 3091149-54.
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Cavernous Sinuses

• Cavernous sinuses most frequent dural sinus to
  become infected and thrombosed

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Cavernous Sinus Thrombosis

• First described in 1778
• Commonly encountered in the preantibiotic era,
  but is now rare
• Cannon ML, Antonio BL, McCloskey JJ, Hines MH,
  Tobin JR, Shetty AK. Cavernous sinus thrombosis
  complicating sinusitis.Pediatr Crit Care Med.
  2004 Jan5(1)86-8.

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Cavernous Sinus Thrombosis

• Retrospective review of all dxd cases of septic
  dural venous sinus thrombosis from 1948-1984
• Cavernous sinus thrombosis (n8)
• Literature review (n88)

Southwick et al. Septic thrombosis of the Dural
venous sinuses. Medicine 1986 6582-106.
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• Cavernous sinus syndrome
• simultaneous involvement of the third, fourth,
  sixth, and first 2 divisions of the fifth cranial
  nerves in various combinations

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Cavernous Sinus Thrombosis

• Proposed clinical requirements for diagnosis
• Bilateral involvement or sequential progression
  to the second eye
• Proptosis, chemosis of the conjunctiva, lid edema
• Limitation of extraocular motion
• Meningismus /- CSF pleocytosis
• Residual CN palsy of III, IV, or VI after arrest
  of process

Price et al. Cavernous sinus thrombosis and
orbital cellulitis. South Med J. 1971
Oct64(10)1243-7.
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Septic Cavernous Sinus Thrombosis
Southwick et al. Septic thrombosis of the Dural
venous sinuses. Medicine 1986 6582-106.
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Radiographic imaging

• High res CT with contrast
• MRI
• Regions of decreased or irregular enhancement
• Thickening of lateral walls
• Bulging of sinuses
• Narrowing or occlusion of intercavernous segment
  of carotid artery secondary to spasm or
  thrombosis due to inflammation in cavernous sinus

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Septic cavernous sinus thrombosis
Southwick et al. Septic thrombosis of the Dural
venous sinuses. Medicine 1986 6582-106.
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Septic cavernous sinus thrombosis
Southwick et al. Septic thrombosis of the Dural
venous sinuses. Medicine 1986 6582-106.
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Corticosteroids

• Case report
• 53y/o male with persistent bilateral orbital
  edema and ophthalmoplegia 37d antibiotic and
  anticoagulation therapy
• Improvement in ocular sx within 2 days of steroid
  initiation
• Eventual complete clinical recovery

Solomon et al. Steroid therapy in cavernous sinus
thrombosis. Am J Ophthalmol. 1962 Dec541122-4.
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Anticoagulation
Differences in overall outcome were significant p
lt0.01
Einhaupl et al. Heparin treatment in sinus
venous thrombosis. Lancet 1991 338 597-600.
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Anticoagulation

• Also performed retrospective study on the
  relation b/t heparin treatment and ICH

• 102 pts with SVT treated
• from 1977-1991
• 43/102 had ICH
• 33 did not receive heparin
• 10 were receiving heparin

Einhaupl et al. Heparin treatment in sinus
venous thrombosis. Lancet 1991 338 597-600.
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Anticoagulation
Treatment of pts who had ICH with heparin
Einhaupl et al. Heparin treatment in sinus
venous thrombosis. Lancet 1991 338 597-600.
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Anticoagulation

• 59 patients with cerebral venous
• sinus thrombosis between
• 1992-1996 in Netherlands and UK
• Randomized to treatment
• with LMWH (nadroparin) or
• placebo
• Approx 50 in each group had
• evidence of cerebral hemorrhage
• on baseline imaging

de Bruijn et al. Randomized, placebo-controlled
trial of anticoagulant treatment with
low-molecular-weight heparin for cerebral sinus
thrombosis. Stroke 1999 Mar30(3)484-8.
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Anticoagulation
de Bruijn et al. Randomized, placebo-controlled
trial of anticoagulant treatment with
low-molecular-weight heparin for cerebral sinus
thrombosis. Stroke 1999 Mar30(3)484-8.
38
Septic cavernous sinus thrombosis
Southwick et al. Septic thrombosis of the Dural
venous sinuses. Medicine 1986 6582-106.
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Outcomes

• Literature reviews
• 878 cases b/t 1821-1960
• Mortality rate 80 Morbidity rate 75
• Yarington. The Prognosis and Treatment of
  Cavernous Sinus Thrombosis. Ann Otol Rhinol
  Laryngol 1961 70263-267.
• 28 cases b/t 1965-1975
• Mortality rate 13.6 Morbidity rate 22.7
• Yarington. Cavernous sinus thrombosis revisited.
  Proc R Soc Med. 1977 Jul70(7)456-9.

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Outcomes

• Follow-up report of 59 patients with sinus
  thrombosis 1 year after participation in
  nadroparin study
• 2 lost to follow-up (both moved overseas)
• 2 refused participation in follow-up study
• 8 died
• 47 patients remaining
• 16 (35) had cognitive impairments
• 3 (6) were dependent
• 19 (40) had sx that led to restrictions in
  lifestyle
• 19 (40) could not resume previous level of
  economic activity
• de Bruijn et al. Long-term outcome of cognition
  and functional health after cerebral venous sinus
  thrombosis. Neurology. 2000 Apr 2554(8)1687-9.

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Case 1

• Treatment
• Pt txd with ceftriaxone, vancomycin,
  metronidazole
• Taken for emergent sphenoidotomy
• Started on anticoagulation
• Started on decadron
• Culture results
• CSF cultures and operative cultures were
  unrevealing
• 2/2 blood cultures from OSH grew Fusobacterium
  necrophorum

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Case 1

• When steroids were tapered, pt experienced AMS
• Repeat MRI revealed new infarcts, felt to be
  related to diffuse intracranial artery vasospasm
• Left cerebral hemisphere in a watershed
  distribution
• Small infarct in the right cerebellar hemisphere
• Possible infarct in right aspect of pons
• Probable thrombosis of the cervical segment of
  the left jugular vein
• Steroids restarted
• Neurologic symptoms continuing to improve

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Case 2

• 54 y/o HF with h/o DM, ESRD, on HD x 3 months
  admitted with AMS and hypoglycemia.
• ID consulted for persistent fevers to 103.4 F
  since admission (8 days) despite antibiotic Rx
• Pt c/o fevers, fatigue, malaise x 1 week pta.
• ROS anorexia, nausea, vomiting since admission

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Case 2

• Past Medical History
• Diabetes Mellitus
• ESRD on HD
• HTN
• Dyslipidemia
• Hypothyroidism
• All NKDA
• Social History married
• immigrated from Mexico several years ago
• no substance use

• Medications
• Vanc x 8 days
• Cipro x 8 days Synthroid
• Altace
• Plendil
• Lopressor
• Lasix
• Lipitor
• Humulin 70/30

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Case 2

• Laboratory Data
• wbc 6.0 S57/B26/L7/M8/E1
• Hgb 9.7 plts 119
• CMP TP4.7 Alb 2.3
• Alk phos 794 TB1.0
• AST 274 ALT 192
• GGT 1161

• Physical Examination
• T103.2 bp 143/65 P85
• Gen NAD
• HEENT wnl
• LN no LAD
• Lungs clear
• Abd BS No hsm
• Skin no rashes

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Case 2

• CXR NACPD
• CT scan abdomen and pelvis
• One too small to characterize hypoattenuating
  lesion in the right lobe of the liver
• Remaining liver is normal
• Pancreas, spleen, adrenal glands, and kidneys are
  normal
• No adenopathy or ascites.

• Micro
• Numerous blood cultures and urine cultures were
  negative

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Thoughts?
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ID consult recommendations

• Place PPD
• Serology
• HIV
• Hep A, B, C
• EBV
• CMV
• Brucella
• Q fever

• PCR/RNA
• Hep C
• CMV
• HIV
• Urine histoplasma Ag
• Serum crypto Ag
• Stop antibiotics
• Repeat blood cultures in 72hr
• AFB blood culture
• CMV blood culture

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Case 1

• Pt remained febrile
• LFTs continued to rise
• Results of initial workup unrevealing
• Liver biopsy performed

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Liver biopsy results

• Severe Granulomatous hepatitis, with rare acid
  fast bacilli consistent with tuberculosis

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Hepatic Tuberculosis
Chien et al. Hepatic tuberculosis Comparison of
Miliary and Local Form. Infection 199523 5-8.
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Hepatic Tuberculosis

• Reviewed 22 pts seen b/t 1977-1993
• 5 had local form 17 had miliary form
• No significant difference b/t
• Symptoms and signs at presentation
• Biochemical tests
• Pathologic features on liver biopsy

Chien et al. Hepatic tuberculosis Comparison of
Miliary and Local Form. Infection 199523 5-8.
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Tuberculous hepatitis

• Retrospective review of pathology records from
  1974-1981
• TB hepatitis constituted 96/8342 (1.2) of all
  cases of TB

Essop et al. Tuberculosis hepatitis a clinical
review of 96 cases. Q J Med 198453 (212)465-77.
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Tuberculous hepatitisSymptoms and signs at
presentation
Essop et al. Tuberculosis hepatitis a clinical
review of 96 cases. Q J Med 198453 (212)465-77.
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Tuberculous hepatitis
Essop et al. Tuberculosis hepatitis a clinical
review of 96 cases. Q J Med 198453 (212)465-77.
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Hepatic Tuberculosis Diagnosis
Sensitivity 88 (15/17) Specificity 100 (18/18)
Alcantara-Payawal et al. Direct detection of
Mycobacterium tuberculosis using Polymerase
chain reaction assay among patients with hepatic
granuloma. J Hepatol 1997 27620-7.
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Case 2

• Our patient remained persistently febrile with
  elevated LFTs after 3 weeks of treatment with
  INH, rifampin, ethambutol and pyrazinamide
• When should steroids
• be used?

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Fever Duration

• Review of 13 pts seen b/t 1964-1969
• Duration of fever after therapy
• gt21 days for 4 pts
• lt21 days for 4 pts

Berger et al. Miliary Tuberculosis Diagnostic
methods with emphasis on chest Roentgenogram.
Chest 1970 58(6) 586-9.
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Corticosteroids

• Case report of 29 y/o female diagnosed with
  miliary TB and hepatic involvement
• Remained febrile, became jaundiced and confused
  despite antituberculous therapy
• Pt treated with oral prednisolone
• Fever and mental status normalized in 48hrs
• Biochemical profile normalized over the next 3
  weeks

Evans et al. Massive hepatosplenomegaly, jaundice
and pancytopenia in miliary tuberculosis. J
Infect. 1998 36 (2) 236-9.
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Corticosteroids

• Review of medical literature from 1966-1996
• Must have defined study grps and control grps
• Comparability of groups had to be addressed
• Adequate antituberculous therapy had to be
  administered
• Defined course of corticosteroid therapy

Dooley et al. Adjunctive corticosteroid therapy
for tuberculosis a critical reappraisal of the
literature. Clin Infect Dis. 1977 25 872-887.
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Corticosteroids

• Pulmonary TB
• Relief of severe systemic and respiratory
  morbidity of far-advanced disease
• No improvement in final endpoints can be expected
• Tuberculous meningitis
• Faster resolution of abnormal CSF parameters
• Reduction in sequelae
• Improved survival in pts with mod-severe disease
• Tuberculous pericarditis
• useful in acute phase
• Rapidly reduce size of pericardial effusions
• Reduced need for drainage procedures
• Decreased mortality

Dooley et al. Adjunctive corticosteroid therapy
for tuberculosis a critical reappraisal of the
literature. Clin Infect Dis. 1997 25 872-887.
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Corticosteroids

• Tuberculous pleurisy
• faster resolution of pain
• faster resolution of dyspnea
• faster resolution of fever
• Primary TB
• faster involution of intrathoracic adenopathy
• Miliary TB
• Inadequate data
• Hepatic TB
• Inadequate data

Dooley et al. Adjunctive corticosteroid therapy
for tuberculosis a critical reappraisal of the
literature. Clin Infect Dis. 1997 25 872-887.
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Corticosteroids

• Miliary Tuberculosis in China 1981
• 55 pts randomized to corticosteroids or placebo
  in addition to INH, streptomycin and
  para-aminosalicylic acid
• Death in 2/27 (7) of corticosteroids group vs
  5/28 (18) control group
• Trend towards better outcome (NS)

Dooley et al. Adjunctive corticosteroid therapy
for tuberculosis a critical reappraisal of the
literature. Clin Infect Dis. 1997 25 872-887.
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Tuberculous hepatitis Outcomes
Essop et al. Tuberculosis hepatitis a clinical
review of 96 cases. Q J Med 198453 (212)465-77.
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Case 2

• Culture results
• 10 COLONIES MYCOBACTERIUM TUBERCULOSIS
• INH(0.1)SENSITIVE
• RIF(2)SENSITIVE
• ETHAM(2.5)SENSITIVE
• SM(2)SENSITIVE
• PZA(100)SENSITIVE

• Pt defervesced
• TB 10.5 (peak 15.6)
• Alk phos 823
• (peak 1073)
• AST 43
• ALT 18

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