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

OD OS BCVA: 20/80 20/20 Pupils: 4 to 2 mm OU, +/- RAPD OD IOP: EOM: CVF : 17 Full 18 Full Inferior altitudinal defect OD

SLE: External/Lids Conjunctiva/Sclera

Objective

Normal OU Normal OU Cornea Anterior Chamber Iris Lens Vitreous Clear OU Deep, quiet OU Normal OU Clear OU Normal OU

Dilated Fundus Exam OD:

Optic disc edema, Disc hemorrhages OS: Normal

OS: full

Visual Fields (30-2)

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

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-Scratch Disease in HIV-Positive Patients Curi 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