Grand Rounds Conference

Janelle Fassbender, MD, PhDUniversity of Louisville

Department of Ophthalmology and Visual Sciences

January 3, 2014

SubjectiveCC: Blurred vision right eyeHPI: 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: NonePMH: HIV+ (CD4 count 336),

migraineEye Meds: Artificial tearsMeds: Stribild (HAART), Neurontin,

CelexaAllergies: Penicillin, sulfa, phenerganROS:

Positive: headaches, eye pressure, neck stiffnessNegative: fever, chills, recent illness

Objective

OD OSBCVA: 20/80 20/20Pupils: 4 to 2 mm OU, +/-

RAPD ODIOP: 17 18EOM: Full FullCVF : Inferior altitudinal

defect OD

ObjectiveSLE: External/Lids Normal OUConjunctiva/Sclera Normal OUCornea Clear OUAnterior Chamber Deep, quiet OUIris Normal OULens Clear OUVitreous Normal OU

Dilated Fundus ExamOD:Optic disc edema, Disc hemorrhages

OS:Normal

Visual Fields (30-2)OD: inferior altitudinal defectOS: full

OCT ODPatient referred to retina clinic for further work up. OCT of right eye demonstrated intact foveal architecture with no evidence of fluid or exudate.

Fluorescein angiographyFA 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

Non-infectious: Multiple sclerosis Sarcoidosis Anterior ischemic optic neuropathy Systemic lupus erythematosus Neuromyelitis optica

Infectious: Bartonella henselae (Cat Scratch Disease) Syphilis Lyme disease Toxoplasmosis Herpes simplex; Herpes zoster Tuberculosis

Workup Labs:

CBC, CMP, UA: Normal CSF:

Glucose: Normal; Protein: High VDRL, HSV, cryptoccal antigen: Negative Cultures: Negative

Serology: RPR, FTA-ABS, Toxoplasma, HSV/VZV,

Quantiferon, Lyme titers: Negative Bartonella henselae IgG antibodies: Positive

(1:512)

Imaging

CT Head (11/3/13) – Negative MRI Brain with contrast (11/06/13) –

Negative

Diagnosis

Atypical optic neuritis secondary to Bartonella henselae infection (Cat Scratch Disease).

Treatment plan

Doxycycline, 100 mg twice daily for 4 weeks.

Neurophthalmology referral

Follow-up Week 1-3:

VA improved to 20/60 Persistent CVF defect inferiorly Persistent optic disc edema

Week 7: VA 20/70 Resolution of disc edema, doxycycline

discontinued

Ocular Bartonellosis

Bartonella henselae is the principal etiologic agent of cat-scratch disease.

Feline-associated bacterial zoonotic disease found world-wide.

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 Cats (90% are < 1 yr old) are the primary

mammalian reservoir with the cat flea as the vector for transmission among cats. 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). Immunocompetent: granulomatous disease Immunocompromised: vasoproliferative

lesions

Pathogenesis

An erythematous papule may form at site of cutaneous injury 3-10 days after initial injury. 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). 2-5% Manifest Parinaud’s Oculoglandular

syndrome

Posterior segment findings

Neuroretinitis: Abrupt visual loss (20/25 to 20/200) Unilateral optic disc swelling Macular star formation 1-2% of patients with Cat-Scratch disease

Optic disc edema observed 2-4 weeks prior to appearance of macular star.

Diagnosis and Treatment Two types of serologic tests

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 Doxycycline Rifampin Ciprofloxacin Trimethoprim-sulfamethoxazole

Ocular Manifestation of Cat-ScratchDisease in HIV-Positive PatientsCuri AL, et al. 2006. Am J Ophthalmol, 141:400-1

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. 1 patient required additional course due to

recurrence.

Fluorescein angiogram OD demonstrating multiple angiomatous lesions.

Cat-Scratch disease in HIV

Anti-apoptotic bacterial effector protein BepA inhibits endothelial cell (EC) apoptosis. 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 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 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 Similar to causative agent for bacillary angiomatosis

(Rochalimaea henselae) 1994: First serologic link with a Bartonella

species Eight of 21 Bartonella species identified as causing

human disease Four of these eight associated with ocular

complications