1. No category

Grand Rounds Conference
Janelle Fassbender, MD, PhD
University of Louisville
Department of Ophthalmology and Visual Sciences
January 3, 2014
Subjective
CC: Blurred vision right eye
HPI: 42 yo WM awoke 2 days ago with decreased
vision in the superior half of his right eye. Mild
pain with eye movement.
*Multiple feral cats at home of various ages.
History
POH: None
PMH: HIV+ (CD4 count 336), migraine
Eye Meds: Artificial tears
Meds: Stribild (HAART), Neurontin, Celexa
Allergies: Penicillin, sulfa, phenergan
ROS:
Positive: headaches, eye pressure, neck stiffness
Negative: fever, chills, recent illness
Objective
BCVA:
Pupils:
IOP:
EOM:
CVF :
OD
OS
20/80
20/20
4 to 2 mm OU, +/- RAPD OD
17
18
Full
Full
Inferior altitudinal defect OD
Objective
SLE:
External/Lids
Conjunctiva/Sclera
Cornea
Anterior Chamber
Iris
Lens
Vitreous
Normal OU
Normal OU
Clear OU
Deep, quiet OU
Normal OU
Clear OU
Normal OU
Dilated Fundus
Exam
OD:
Optic disc edema,
Disc hemorrhages
OS:
Normal
Visual Fields (30-2)
OS: full
OD: inferior altitudinal defect
OCT OD
Patient referred to retina clinic for further work up. OCT of right eye demonstrated
intact foveal architecture with no evidence of fluid or exudate.
Fluorescein angiography
FA of right eye showing optic disc hyperemia with leakage as well as patchy
hypofluorescence just temporal to the disc corresponding to intra-retinal
heme.
Differential Diagnosis of Optic
Neuritis
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Non-infectious:
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Multiple sclerosis
Sarcoidosis
Anterior ischemic optic neuropathy
Systemic lupus erythematosus
Neuromyelitis optica
Infectious:
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Bartonella henselae (Cat Scratch Disease)
Syphilis
Lyme disease
Toxoplasmosis
Herpes simplex; Herpes zoster
Tuberculosis
Workup
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Labs:
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CSF:
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CBC, CMP, UA: Normal
Glucose: Normal; Protein: High
VDRL, HSV, cryptoccal antigen: Negative
Cultures: Negative
Serology:
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RPR, FTA-ABS, Toxoplasma, HSV/VZV, Quantiferon,
Lyme titers: Negative
Bartonella henselae IgG antibodies: Positive (1:512)
Imaging
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CT Head (11/3/13) – Negative
MRI Brain with contrast (11/06/13) – Negative
Diagnosis
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Atypical optic neuritis secondary to Bartonella
henselae infection (Cat Scratch Disease).
Treatment plan
Doxycycline, 100 mg twice daily for 4 weeks.
 Neurophthalmology referral
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Follow-up
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Week 1-3:
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VA improved to 20/60
Persistent CVF defect inferiorly
Persistent optic disc edema
Week 7:
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VA 20/70
Resolution of disc edema, doxycycline discontinued
Ocular Bartonellosis
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Bartonella henselae is the principal etiologic agent of catscratch disease.
Feline-associated bacterial zoonotic disease found worldwide.
Incidence is 9.3 cases per 100,000 persons in the U.S.A.
Seasonal pattern: Fall and winter.
Most prevalent in southern states, California and Hawaii.
Transmission
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Cats (90% are < 1 yr old) are the primary mammalian
reservoir with the cat flea as the vector for transmission
among cats.
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Transmission to humans occurs by the scratches, licks and
bites of domestic cats (especially kittens).
Facultative intracellular gram negative rod that infects
endothelial cells or erythrocytes (Bincardi and Curi, 2013).
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Immunocompetent: granulomatous disease
Immunocompromised: vasoproliferative lesions
Pathogenesis
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An erythematous papule may form at site of cutaneous
injury 3-10 days after initial injury.
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1-2 weeks before systemic manifestations.
Evades the innate immune system because its LPS structure
is a TLR-4 antagonist (Popa et al, 2007).
Ocular involvement occurs in 5-10% of patients
(Bincardi and Curi, 2013).
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2-5% Manifest Parinaud’s Oculoglandular syndrome
Posterior segment findings
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Neuroretinitis:
Abrupt visual loss (20/25 to 20/200)
 Unilateral optic disc swelling
 Macular star formation
 1-2% of patients with Cat-Scratch disease
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Optic disc edema observed 2-4 weeks prior to
appearance of macular star.
Diagnosis and Treatment
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Two types of serologic tests
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Indirect fluorescence assay
Enzyme immunoassay
May obtain convalescent titer 2 weeks following initial
negative result (Gulati et al, 2012).
Immuno-competent vs –compromised: 4 weeks vs 4
months
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Doxycycline
Rifampin
Ciprofloxacin
Trimethoprim-sulfamethoxazole
Ocular Manifestation of Cat-Scratch
Disease in HIV-Positive Patients
Curi AL, et al. 2006. Am J Ophthalmol, 141:400-1
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Retrospective case series of 3 HIV+ patients with
diagnosed ocular cat-scratch disease.
Men, 27 to 53 yrs old
Presented with yellowish, subretinal lesions confirmed
by FA to be abnormal vascular network.
Angiomatous lesions resolved with 1 month treatment.
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1 patient required additional course due to recurrence.
Fluorescein angiogram OD demonstrating multiple angiomatous
lesions.
Cat-Scratch disease in HIV
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Anti-apoptotic bacterial effector protein BepA
inhibits endothelial cell (EC) apoptosis.
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Facilitates intra-cellular bacterial replication.
BepA translocates then localizes to the EC
membrane, triggering production cAMP in
quantities effective for blocking apoptosis (Schmid
et al, 2006).
References
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Roe, RH, et al. 2008. Ocular Bartonella Infections. Int Ophth Clinics, 48(3):93-105.
2013. BCSC: Uveitis.
Gulati, A, et al. 2012. Cat scratch neuroretinitis. J Neuroophthalmol. 32:243-5.
Toosy AT, Mason DF, Miller DH. 2012. Optic neuritis. Lancet Neurol, 13:83-99.
Curi AL, et al. 2006. Ocular manifestation of cat-scratch disease in HIV patients. Am J
Ophthalmol, 141:400-1.
Popa, et al. 2007. Bartonella quintana Lipopolysaccharide is a natural antagonist of
Toll-like receptor 4. Infect Immun, 75(10): 4831–4837.
Schmid, et al. 2006. Translocated bacterial protein protects vascular endothelial cells
from apoptosis. PLoS Pathog, 2(11):e115.
Bincardi and Curi. 2013. Cat-Scratch Disease. Ocul Immunol Inflamm, ePub ahead of
print.
Mosepele et al. 2012. Bartonella Infection in Immunocompromised Hosts:
Immunology of Vascular Infection and Vasoproliferation. Clinical and Developmental
Immunology, 2012.
Timeline
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1889: First report of Parinaud’s oculoglandular syndrome
(POGS)
1950: Debre first described Cat scratch disease (CSD)
1953: CSD associated with POGS
1970: CSD associated with neuroretinitis
1980s: Microbial agent isolated from lymph nodes of CSD
patients
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Similar to causative agent for bacillary angiomatosis (Rochalimaea henselae)
1994: First serologic link with a Bartonella species
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Eight of 21 Bartonella species identified as causing human disease
Four of these eight associated with ocular complications