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Show Cat Scratch Neuroretinitis: The Role of Acute and Convalescent Titers for Diagnosis Archit Gulati, Sushma Yalamanchili, MD, Karl C. Golnik, MD, Andrew G. Lee, MD Abstract: Cat scratch neuroretinitis (CSN) is a clinical diagnosis supported by serological testing. We present 2 cases of CSN in which initial acute titers were negative or equivocal for Bartonella henselae while convalescent titers were shown to be positive. We report these cases to emphasize that a single acute negative titer is insufficient to exclude the diagnosis of CSN and that convalescent titers should be obtained in patients for whom there is a high clinical suspicion of the disease. Journal of Neuro-Ophthalmology 2012;32:243-245 doi: 10.1097/WNO.0b013e318233a0a6 © 2012 by North American Neuro-Ophthalmology Society Cat scratch disease (CSD) is typically a self-limiting sys-temic disease caused by Bartonella henselae. CSD is char-acterized by a subacute regional lymphadenitis usually 2-3 weeks following inoculation via cat scratch or bite (1). Sys-temic symptoms including fever and malaise are often present and rarely patients may develop osteomyelitis or encephalitis (1,2). Patients with cat scratch neuroretinitis (CSN) typically present with unilateral blurred vision associated with fever and malaise (3-5). Ocular manifestations include retinitis (3), optic disc edema (3), angiomatous lesions involving the optic disc and peripapillary retina, retinal granuloma (6), uveitis (7), vasculitis (8), and Parinaud oculoglandular syndrome (3,5). Despite CSN being self-limited and patients usually have a good long-term visual prognosis, antibiotic treatment is often recommended. Reed et al (4) treated 7 patients with doxycycline and rifampin and reported reduced disc swelling within a few days of starting therapy, and most regained 20/20 visual acuity after 1-4 weeks of therapy. The hallmark of CSN, the macular star, appears in the late stage of the disease while the early phase consists of more nonspecific findings including subretinal fluid and optic disc edema. While the clinician often relies on serological confirmation of CSN, we present 2 cases to illustrate potential pitfalls in the interpretation of these serological tests. CASE REPORTS Case 1 A 43-year-old woman developed acute unilateral loss of vision in the lower portion of her right visual field. Medical history was significant for hypertension, gastric ulcers, degenerative arthritis, and anxiety. Her medications included paroxetine, aspirin, and olmesartan. She reported being scratched by kittens 2 weeks previously and had cat scratches on her lower extremities. She denied fever, malaise, weakness, regional lymphadenopathy, or flu-like symptoms. Visual acuity was 20/25, right eye, and 20/20, left eye. The pupils were isocoric and reactive to light with a small right relative afferent pupillary defect. External examination, ocular motility, and slit-lamp biomicroscopy were normal. Automated visual field testing showed an inferior altitudinal visual field in the right eye while the left field was normal. The right fundus showed optic disc edema with peripapillary hemorrhage and exudate (Fig. 1), and the left fundus was unremarkable. MRI of the brain and orbits was normal except for an old lacunar infarct in the left midbrain. Serological studies for B. henselae were equivocal for IgG, 1:128 (positive $ 1:256), and negative for IgM, ,1:16 (positive . 1:16). The patient was started on azithromycin (500 mg daily for 5 days). Two weeks later, convalescent serologies were positive for B. henselae IgG, 1:256 (positive $ 1:256), and remained negative for IgM, , 1:16 (positive . 1:16). The Department of Ophthalmology, The Methodist Hospital (AGL), Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medical College (AGL, SY), New York, New York; Department of Ophthalmology, University of Iowa Hospitals and Clinics (AGL), Iowa City, Iowa; Department of Oph-thalmology, University of Texas Medical Branch (AGL), Galveston, Texas; Baylor College of Medicine (AG, AGL); and Department of Ophthalmology, University of Cincinnati (KCG), Cincinnati, Ohio. The authors report no conflicts of interest. Address correspondence to: Andrew G. Lee, MD, Department of Ophthalmology, The Methodist Hospital, 6560 Fannin Street, Scur-lock 450, Houston, TX 77030; E-mail: AGLee@tmhs.org Gulati et al: J Neuro-Ophthalmol 2012; 32: 243-245 243 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. patient's signs and symptoms progressively improved, and 2 weeks later, vision was 20/20 in each eye, with normal visual field testing. Case 2 A 6-year-old boy developed blurry vision after being hospitalized for surgical drainage of a psoas muscle abscess. Medical history was significant for esotropia, corrected with strabismus surgery, and congenital left ptosis but no history of amblyopia. Visual acuity was 20/40, right eye, and count fingers, left eye. He correctly identified 4/8 Ishihara color plates with the right eye and none with the left eye. Pupils were isocoric and reactive to light with a left relative afferent pupillary defect. The patient had a left esotropia of 10-12 prism diopters with full extraocular movements. Funduscopy of the right eye showed optic disc edema with a macular star of exudates (Fig. 2A). On the left eye, there was an inflam-matory lesion obscuring the optic disc and exudates in the macula (Fig. 2B). Initial B. henselae serological results were negative for IgG, ,1:64 (positive $ 1:256), and IgM, ,1:64 (posi-tive . 1:64). The patient was started on azithromycin (60 mg daily for 4 weeks) and rifampin (175 mg twice daily for 4 weeks). Repeat testing 2 weeks later showed convalescent titers to B. henselae of IgG, .1:1024 (pos-itive $ 1:256), and remained negative for IgM, ,1:64 (positive . 1:64). Over the following month, the patient's vision improved to 20/40, right eye, and 20/30, left eye. There was resolution of the optic disc swelling in the right eye and reduction in the size of the lesion overlying the left optic nerve head (Fig. 3). DISCUSSION Serology antibody testing for B. henselae is used to support a clinical diagnosis of CSD (9). Elevated IgM titer is evidence for an acute infection, but by 3 months, only 4% of CSD patients have a positive IgM (10). In contrast, the IgG anti-body level rises following the IgM titers and then will decrease with time. Yet the IgG titer may remain positive for 2 or more years following the onset of symptoms (10). In patients for whom there is a high suspicion of CSD, it is our practice to obtain a convalescent titer 2 weeks following a negative initial result, as the initial test may have been performed before IgG titers have risen and after IgM titers return to normal. It is important to note that a high sero-prevalence in the general population limits the utility of a single IgG titer (11). In addition, there appears to be limited association between the serological titers and either the clin-ical manifestations of CSD or the duration of symptoms (10), so titers alone should not be used to measure the out-come or prognosis of disease. Despite these limitations, the Centers for Disease Control and Prevention recommend that a single highly elevated IgG or a positive IgM antibody titer is generally sufficient to confirm CSD (12,13). A 4-fold change in IgG antibody titer in acute and convalescent serum samples is also used as laboratory criteria for recent infection (11-14). FIG. 1. Case 1. Optic disc edema with peripapillary cotton wool patches and a partial macular star figure of exudate in the right eye. FIG. 2. Case 2. A. Right eye shows marked optic disc edema with macular star formation. B. Left eye shows angiomatous or inflammatory lesion of the optic disc; exudates are present in the macula. 244 Gulati et al: J Neuro-Ophthalmol 2012; 32: 243-245 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Two types of serological diagnostic tests are available for B. henselae : indirect fluorescence assay (IFA) and enzyme immunoassay (EIA). Both have been documented to have low sensitivity in establishing the diagnosis of CSD (11,15-19). For the EIA test, IgM sensitivities range from 65% to 71% with IgG sensitivities from 9.5% to 28% (11,15,19). The IFA test, which is more commonly used, has been shown to have similar low sensitivities with IgM values ranging from 46% to 53% and IgG values from 32% to 67% (11,19). This may be due to the fact that some patients may remain serologically positive long after recov-ery, while others never mount a detectable response (11). The short duration of the rise in IgM antibodies is also problematic, and negative or equivocal results should not exclude infection (18). In patients with a high likelihood of CSD, acute and convalescent titers are strongly recommended. Laboratory testing with polymerase chain reaction (PCR) also might be valuable in patients with negative serologic results (11). This technique has been reported to be highly specific and sensi-tive for detecting Bartonella DNA in lymph node specimens (11). PCR has also detected Bartonella species in iris tissue and aqueous humor (7,20). In our clinical practice, we have not used PCR in this setting. REFERENCES 1. Lamps LW, Scott MA. Cat-scratch disease: historic, clinical, and pathologic perspectives. Am J Clin Pathol. 2004;121 (suppl):S71-S80. 2. Reynolds MG, Holman RC, Curns AT, O'Reilly M, McQuiston JH, Steiner CA. Epidemiology of cat-scratch disease hospitalisations among children in the United States. Pediatr Infect Dis J. 2005;24:700-704. 3. Curi AL, Machado D, Heringer G, Campos WR, Lamas C, Rozental T, Gutierres A, Orefice F, Lemos E. Cat-scratch disease: ocular manifestations and visual outcome. Int Ophthalmol. 2010;30:553-558. 4. 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Pitfalls and fallacies of cat scratch disease serology: evaluation of Bartonella henselae-based indirect fluorescence assay and enzyme-linked immunoassay. J Clin Microbiol. 1997;35:1931-1937. 20. DrancourtM, Berger P, Terrada C, Bodaghi B, Conrath J, Raoult D, LeHoang P. High prevalence of fastidious bacteria in 1520 cases of uveitis of unknown etiology. Medicine. 2008;87:167-176. FIG. 3. Case 2. A. Two weeks later, the right eye shows resolution of optic disc swelling and macular exudates. B. The optic disc in the left eye is now visible with peripapillary and macular exudates. Gulati et al: J Neuro-Ophthalmol 2012; 32: 243-245 245 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |