There is Fungus Amungus acetazolamide for pseudotumor cerebri with - - PDF document

▶
there is fungus amungus
SMART_READER_LITE
LIVE PREVIEW

There is Fungus Amungus acetazolamide for pseudotumor cerebri with - - PDF document

Mar 21, 2024 470 likes •633 views

2/19/19 Case 1 23 y/o F admitted for altered mental status 2 year history of chronic lymphocytic meningitis as follows Blurry vision and headache: treated by an ophthalmologist with There is Fungus Amungus acetazolamide for

slide-1
SLIDE 1

2/19/19 1

There is Fungus Amungus

Henry “Chip” Chambers, MD Professor of Medicine, UCSF

Case 1

  • 23 y/o F admitted for altered mental status
  • 2 year history of chronic lymphocytic meningitis as follows
  • Blurry vision and headache: treated by an ophthalmologist with

acetazolamide for pseudotumor cerebri with resolution of sxs

  • 18 months ago admitted with ophthalmoplegia, ataxia, and

paresthesias after a URI

  • CSF WBC 30 (87% lymphocytes), protein 68, glucose 49
  • Treated with IVIG for Miller-Fischer variant Guillain-Barre syndrome

More history

  • Now with one month of lightheadedness, vertigo, and nausea
  • Neurologic exam notable for nystagmus on leftward gaze,
  • therwise normal
  • CSF: 52 WBCs (92% lymphocytes), protein 186, glucose < 20
  • MRI: FLAIR hyperintensity in L cerebellar peduncles and facial

colliculus w/ enhancement; ongoing leptomeningeal enhancement; and hydrocephalous

  • Chest CT with 5 mm pulmonary nodules (stable)

More history

  • Extensive work-up for infectious, inflammatory, and neoplastic

etiologies was negative

  • Had positive PPD, attributed to BCG vaccination as a child
  • RIPE and dexamethasone were started empirically
  • Dexamethasone taper initiated
  • Repeat MRI: decreased hydrocephalus, decreased enhancement
  • CSF: WBCs 11 (83% lymphs), protein 71, glucose 40
slide-2
SLIDE 2

2/19/19 2

History, con’t

  • One month later presents to clinic with nausea, vomiting,

headache, low-grade fevers, and neck stiffness

  • MRI: Increased hydrocephalus and basilar leptomeningeal

enhancement

  • CSF: 86 WBCs (88% lymphs), protein 202, glucose < 20
  • RIPE stopped, patient discharged on dexamethasone taper

Further history, exam, management

  • One month later presents with one week of HA and nausea
  • In the ED developed fever to 39.5 C and became unresponsive
  • Exam: Mild L pronator drift, blurred disk margins, L dysmetria
  • MRI: Worse hydrocephalous, slight improvement in

leptomeningeal enhancement

  • CSF: 182 WBCs (37% PMNs), protein 206, glucose < 20
  • Treated for bacterial meningitis initiated, steroids restarted
  • Leptomeningeal biopsy: only dura obtained
  • Shunt placed for worsening hydrocephalus

PMHx/Meds/FHx

  • PMHx:
  • Chronic headaches x 4 years
  • +PPD
  • Seizures
  • Medications: Calcium/vitamin D, dexamethasone taper,

famotidine, zofran, prochlorperazine

  • Family history: Brother with diabetes

Epidemiologic history

  • Born in Ukraine, emigrated to NYC as a child
  • Currently a college student at SF State
  • After high school, drove across the US with a friend; stopped

along the way and did “usual” tourist activities, including hiking

  • Last travel back to Ukraine in 2006; has visited Mexico and

Colombia

  • No known TB contacts
  • No pets, no dietary exposures
slide-3
SLIDE 3

2/19/19 3

Laboratory data

  • WBC 7.1, hct 36.8, plt 337
  • BUN 14, Cr 0.52
  • LFTs: Normal
  • LP: Attempted multiple times but dry tap
  • VP shunt tap: WBC 3 (48 M, 50 L), protein 63, glucose 53

Prior and current test results

  • Negative tests:
  • HIV
  • Cocci ID and comp fix
  • Serum and CSF CrAg
  • RPR and CSF VDRL
  • CSF PCR for MTB neg
  • SS-A and SS-B
  • Rheumatoid factor
  • ANCA
  • Q fever IgG
  • Bartonella Abs
  • Lyme Ab
  • Beta D glucan
  • Positive tests:
  • QFT: Indeterminate
  • PPD: Positive
  • ANA: 1:80 speckled
  • West nile virus: IgG positive,

IgM negative

  • Histoplasma serum ID: M band

positive, H band negative

  • CSF ACE: 6 (nl 0-2.5)

Microbiology

  • Bcx x 2 ngtd
  • Ucx 1000 gm pos bacteria
  • CSF gram stain negative, culture ngtd
  • CSF AFB smear negative, cx ngtd
  • CSF fungal KOH neg, cx ngtd
  • Fungal Bcx x 2 ngtd
  • CSF AFB cultures x 4 over a 4 month period
  • CSF fungal culture negative from 2 months prior

Imaging, con’t

slide-4
SLIDE 4

2/19/19 4

MRA Clinical course

  • Started on RIPE, steroids, and Ambisome on admission
  • Blood, urine, and CSF all negative for quantitative Histo Ag by

EIA: Ambisome d/c’d

  • MRI: Interval decrease in leptomeningeal and subarachnoid

enhancement likely tuberculosis, given treatment response

  • Discharged with plan for 12 months of RIPE unless alternative

diagnosis reached

  • One month later ID service notified that AFB cultures had growth

Diagnosis?

  • 1. Cryptococcosis
  • 2. Blastomycosis
  • 3. Histoplasmosis
  • 4. Coccidoidomycosis
  • 5. Tuberculosis

A diagnostic test returns…

slide-5
SLIDE 5

2/19/19 5

Histoplasmosis in mold phase Endemic Fungi in the Americas

Winthrop and Chiller, 2009

Duration of symptoms

  • < 1 month: 5/18 (28%)
  • 2-6 months: 8/18 (44%)
  • > 6 months: 5/18 (28%)

Wheat et al., 1990

Diagnosis of histoplasmosis

  • Skin tests: non-specific for acute disease
  • Culture
  • Histopathology
  • Antibody detection
  • Immunodiffusion: Tests antibodies to histoplasmin
  • H band: Clinically active cases
  • M band: Both acute and chronic diseases
  • Complement fixation
  • Yeast and mycelial antigens can be tested

Wheat, 2006

slide-6
SLIDE 6

2/19/19 6

Diagnostic studies

Culture = from any site; From the CSF, cultures were positive in 65% of literature cases and 27% of the case series

Wheat et al., 1990

False-positives

Positive tests/total samples (%) Infection ID CF Yeast Mycelial Histo 22/34 (65) 28/34 (82) 7/34 (21) Other fungi 5/99 (5) 15/90 (17) 6/90 (7) TB 5/46 (11) 12/41 (29) 12/41 (29)

Wheat et al., 1986

Sensitivity of CSF histo Ag

  • 75% in HIV patients with histoplasmosis meningitis
  • Only 25% sensitivity in non-HIV patients

Wheat et al., 2002

Antigen detection

Wheat et al., 1990; Wheat et al., 2002

  • Suspect false positive in serum positive and urine negative tests
slide-7
SLIDE 7

2/19/19 7

Sensitivity of diagnostic tests

Test

Acute pulmonary Subacute pulmonary Chronic pulmonary Disseminated

Antigen

75-81% 19-34% 6-14% 91-92%

Antibody

40-80% 78-89% 93% 63-81%

Histopathology

47% 9-38% < 10% 12-43%

Culture

34% 9-15% 65-85% 75-85%

Wheat, 2006

Case 2

  • 37 y/o M with h/o HTN, DM with worsening L-sided

weakness

  • Drenching night sweats x 1 month with
  • worsening left arm and leg weakness/numbness
  • 20 pound wt loss
  • Blurry vision
  • Diplopia with left gaze

Labs and clinical course

  • CSF: WBC 1944 (N 38%, L 52, M 10), RBC 325, gluc 50 (serum

144), prot 270

  • Serum Cocci ID neg. quantiferon neg, CSF AFB cx ngtd, CSF

VDRL neg, CSF Cocci Ab neg.

  • Presumed demyelinating dz --> high dose steroids
  • Improvement in L-sided weakness, which worsened towards

end of steroid taper

  • Acute worsening of left sided arm/leg weakness
  • Fall, readmitted for further work-up
slide-8
SLIDE 8

2/19/19 8

PMH/SH

  • PMH
  • HTN
  • DM
  • Meds: Lisinopril, Insulin
  • NKDA
  • Lives in Salinas. Born in Mexico, but immigrated in
  • 1997. Works on a farm (picked lettuce). No animal
  • exposures. Drank 6 beers/day until ~1 yr PTA. No tob
  • r IVDA.

Physical Exam

  • Normal VS, exam except for neuro
  • Neuro
  • Mild R facial weakness.
  • Motor: 4/5 left triceps, 4/5 left hamstring.
  • Sensation: decreased LT sensation on L arm and leg
  • Finger to nose, RAM intact.
  • Gait: Wide based with difficulty on heels

Admission Labs

\ 11 / 137 | 101 | 9 / 6.5 ---------- 295

  • 248

/ 32 \ 3.6 | 27 | 0.5 \ AST 14, ALT 14, T bili 0.6, Alk phos 64 UA: Neg, Urine tox neg. CSF: WBC 1850 (N 23%, L44%, large L 10%, M 13%, E 1%); RBC 2; glucose 93 (serum 263); protein 288 PPD negative Blood cultures neg x2

CT Chest

slide-9
SLIDE 9

2/19/19 9

Negative Serum Studies

Bacterial

  • Lyme IgM, IgG (Total Ab equivocal)
  • Brucella IgM, IgG
  • Bartonella henselae IgM, IgG
  • Bartonella quintana IgM, IgG
  • Q Fever Phase 1 IgG and IgM,

Phase II IgM, Phase II IgG pos.

  • RPR NR

Viral

  • West Nile IgM, IgG
  • HIV Ab, HTLV I/II EIA NR
  • HCV Ab

Fungal

  • CrAg
  • Cocci ID
  • Histo ID
  • Urine Histo Ag

Parasite

  • T. Whipplei PCR
  • Schistosoma IgG Ab
  • Cysticercus AB, ELSA
  • Toxo IgM, IgG
  • Toxocara Ab
  • Giemsa smear for Trypanosoma; T.

cruzi IgG 1:16, IgM neg.

Negative CSF Studies

  • Cocci CF x 2
  • VDRL
  • West Nile IgM, IgG
  • CMV PCR
  • HSV 1,2 PCR
  • VZV PCR
  • Balamuthia
  • HHV6
  • Enterovirus PCR
  • Mycoplasma pneumoniae DNA
  • MTB PCR
  • Fungal Cx for Cocci
  • AFB Cx x 2
  • 2nd LP: 21 cc sent for fungal

and AFB culture

Other negative studies

Serum

  • TSH
  • RF
  • ANA
  • Anti-DS DNA
  • Anti-SSA/SSB (Sjogren’s)
  • NMO Ab (Neuromyelitis
  • ptica)

CSF

  • NMO Ab
  • Paraneoplastic panel
  • CSF Flow Cytometry: Neg for

lymphoproliferative disorder x 3

Hospital Course

  • PET/CT neg
  • Due to progressively worsening LL weakness, given

solumedrol 1 gm IV daily x 5 days

  • Mild improvement in weakness
slide-10
SLIDE 10

2/19/19 10

CSF Results

WBC 1850 (N33, L44, LL10, M13, E1) 825 (N23, L52, LL12, M13) 87 (N3, L96, M1, E0) 1550 (N 19, L78, M3, E1) RBC 2 4 44 3325 Glucose (Serum glucose) 106 (263) 93 (217) 40 (84) 92 (216) Protein 288

Not documented

107 71

Steroids

MRI Spine

Diagnosis?

  • 1. Neurocysticercosis
  • 2. Blastomycosis
  • 3. Histoplasmosis
  • 4. Coccidoidomycosis
  • 5. Tuberculosis

Hospital Course

  • Meningeal biopsy --> Pathology: normal dura
slide-11
SLIDE 11

2/19/19 11

Hospital Course

  • R VATS and RML excisional biopsy

Hospital Course

  • Cultures from lung tissue biopsy eventually grew…

Lung Tissue Micro Lung Tissue

slide-12
SLIDE 12

2/19/19 12

Lung Tissue Biopsy

  • GS neg
  • AFB smear neg, Cx ngtd after 4 weeks
  • Pathology
  • Necrotizing granulomatous inflammation with fungal forms c/w

Coccidioides species.

  • Mucicarmine, GMS, and PAS confirm dx of Cocci.
  • Cx: Rare Coccidioides immitis
  • Culture identification by DNA probe

Diagnosis

  • IgM detectable in 50% @ 1 week, 90% @ 3 weeks
  • IgG detectable @ 4-6 weeks, 85-90% positive @ 3 months
  • Enzyme immunoassay (EIA) (IgM+ IgG)
  • Screening test, most sensitive (80-90+%), least specific (IgM)
  • Immunodiffusion (ID) (IgM+IgG)
  • Screening test, sensitive (~70%), good specificity
  • Complement fixation (CF) (IgG)
  • Sensitivity of 60-80%
  • ID + CF combined has sensitivity of > 90% for symptomatic cases
  • PCR
  • Serology less reliable in immunocompromised hosts, early infection

Case 3

History

  • 40 yo homeless man, altered mental status,

found sitting in the shower at a shelter

  • 60 lb weight loss over 3 months, fever, chills,

sweats

  • Recently moved from Chicago
  • No alcohol, tobacco, or drugs
  • No past medical history
slide-13
SLIDE 13

2/19/19 13 Exam

  • VS: 36.3oC, 106/60, 66, 16, O2 Sat 100%RA
  • General: Severely cachectic man, temporal wasting
  • Skin: Dry skin tented skin
  • HEENT: dry MM, normal oropharynx, no thrush,

neck supple.

  • Pulm: clear
  • CV: RRR, no m/r/g

Exam - continued

  • Abd: normal
  • MSK: normal ROM, no joint swelling, no peripheral

edema.

  • Lymph: no cervical LAD
  • Neuro: AO to name and place, normal strength,

nonfocal

Labs

11.7 242 9.2

89% N

AST 27 ALT 26 Total bili 1.2 Alk Phos 76 Utox neg TSH 2.6 HIV neg UA neg. SG 1.027 Serum osm 368 Urine osm 917 Urine Na 52 3.9 179 137 26 0.96 106 52 CSF: RBC 1 WBC 0 Glu 65 Protein 32 CrAg neg

Chest X-ray and CT

slide-14
SLIDE 14

2/19/19 14 Workup

  • AFB smears neg x3
  • Cocci CF < 1:2
  • Blasto CF < 1:8
  • CrAG neg
  • Aspergillus IgG neg
  • Urine histo positive

BAL Cytology

Diagnosis?

  • 1. Cryptococcosis
  • 2. Blastomycosis
  • 3. Histoplasmosis
  • 4. Coccidoidomycosis
  • 5. Tuberculosis

Candida

10-12 uM

Crypto

4-7 uM

Cocci spherules

30-60 uM

Histo

2-4 uM

Blasto!!

8-15 uM