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29 April 2023: Articles  USA

Neuroretinitis: There Is More to Cat Scratch Disease than Meets the Eye

Challenging differential diagnosis

Raina Saxena12ADEF*, Nishan Gajjar13ADE, Bernard Karnath3ADEF, You Zhou4BCDEF

DOI: 10.12659/AJCR.938380

Am J Case Rep 2023; 24:e938380

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Abstract

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BACKGROUND: Cat scratch disease (CSD) is a self-limited infection caused by Bartonella henselae that causes lymphadenitis, fevers, skin changes at the inoculation site, headache, nausea, and ocular symptoms. Bartonella neuroretinitis is a form of CSD that presents with ocular symptoms, such as a central scotoma, rather than the typical lymphadenopathy of CSD. Bartonella neuroretinitis is the most common cause of infectious neuroretinitis leading to painless vision loss. Symptoms can mimic the more common optic neuritis, which can lead to under-diagnosis. Early diagnosis of Bartonella neuroretinitis and initiation of appropriate treatment is crucial to prevent vision loss and shorten recovery time.

CASE REPORT: A 47-year-old man presented to the Emergency Department with nonspecific symptoms of headache, fevers, and visual changes. He was noted to have adopted a cat 2 months prior to presentation. A dilated fundus examination revealed grade 3 optic disc edema with small disc hemorrhages bilaterally without lymphadenopathy, and Bartonella henselae serologies returned positive for the disease. The patient was treated with doxycycline and rifampin at discharge. At his follow-up outpatient ophthalmology visit, the patient had symptomatically improved vision, with dilated fundus examination supporting reduced optic disc edema in the right eye.

CONCLUSIONS: Early recognition and treatment of Bartonella neuroretinitis is essential to prevent vision loss and shorten recovery time. The current standard of treatment is doxycycline and rifampin for 4 to 6 weeks, and a growing body of literature indicates the supplementation of corticosteroids with these antibiotics.

Keywords: Bartonella henselae, Cat-Scratch Disease, Retinitis, Humans, Bartonella, doxycycline, Rifampin, papilledema

Background

Bartonella neuroretinitis is an atypical presentation of cat scratch disease (CSD), a gram-negative bacterial infection caused by Bartonella henselae. Transmission occurs when fleas lay their stool on cats, who serve as natural reservoirs. The infection can be transmitted to humans via a cat scratch. The typical manifestation of CSD is a self-limited lymphadenitis with skin lesions at the site of inoculation [1]. In some patients, infection can disseminate to other organ systems, with the eye being the most common site of dissemination through the lymphatic system. Ocular complications from CSD include optic neuritis and neuroretinitis. Prompt recognition of Bartonella neuroretinitis is crucial to prevent vision loss. Because sending specimens out to serology laboratories can delay recognition of the disease, it is important for clinicians to include CSD as a differential diagnosis in atypical presentations of painless vision loss to avoid delay of empiric antibiotic treatment [2].

Case Report

A healthy 47-year-old man with no significant past medical history presented to the Emergency Department with a 2.5-week history of fever, night sweats, intractable headaches, and gradual left ocular vision loss. The patient reported having a COVID-19 infection 1 month prior to presentation. He had mild symptoms of COVID-19, including a fever, that lasted for 2 weeks but did not require hospitalization. After being asymptomatic for 1 week, he developed recurrent fevers and constant headaches 1 week prior to admission. At home, he took over-the-counter acetaminophen and ibuprofen, which temporarily alleviated his symptoms. After retesting for COVID-19 with a negative result, the patient visited his primary care provider, who suggested his symptoms were related to post-COVID-19 syndrome. On his drive back from the primary care provider, the patient experienced abrupt painless vision loss with an associated inferonasal field defect in the left eye. This was complicated by photophobia and left eye pain with extraocular movement. He also experienced an onset of throbbing headaches that were associated with fever, nausea, and vomiting. He denied neck stiffness, weakness, numbness, tingling, or rashes. One week after fever onset, he arrived at the University of Texas Medical Branch’s Emergency Department after experiencing abrupt painless vision loss in his left eye. Initial evaluation with a complete blood count, comprehensive metabolic panel, COVID-19 rapid test, influenza A/B test, urinalysis, Epstein Barr virus test, and PCR respiratory panel was unremarkable. Chest X-ray and computed tomography of the head were unremarkable. He was admitted to the inpatient neurology service for headaches and vision loss. Besides a recent COVID-19 infection, the patient was previously healthy, with no sick contacts. He previously lived in North Texas and California before moving to Galveston, TX. There was no relevant family medical history. He did not take any prescription medications and had no known allergies. He was a former smoker who quit 6 years ago, with an indeterminate pack-year smoking history. He denied alcohol or other recreational drug use but reported that he occasionally used marijuana and vaped e-cigarettes. He had adopted a cat 2 months prior to admission and noted his cat would frequently scratch his arms. On admission, the patient was afebrile, his blood pressure was 134/84 mmHg, his pulse rate was 78 beats per min, and his respiratory rate was 18 breaths per min. On ophthalmic examination, the patient’s visual acuity was 20/25 and 20/100, without correction, in the right and left eye, respectively. Intraocular pressures were 8 mmHg bilaterally, and pupillary examinations were within the normal limits. A confrontational visual field examination demonstrated an inferonasal field defect in the left eye. Aside from the presence of trace cells (indicating inflammation) in the anterior chamber of the left eye, the slit lamp examination was unremarkable bilaterally, including the absence of anterior chamber inflammation in the right eye. A dilated fundus examination revealed grade 3 optic disc edema with small disc hemorrhages bilaterally.

Additionally, small, discrete white choroidal lesions were present in close proximity to the nerve, without evidence of obvious macular edema or macular star formation. A non-ophthalmic examination did not reveal any skin changes or the presence of lymphadenopathy. His liver enzyme levels were elevated, with an aspartate transaminase level of 79 U/L (reference range: 13–40 U/L) and alanine aminotransferase level of 146 U/L (reference range: 5–50 U/L). He also presented with an elevated erythrocyte sedimentation rate of 41 mm/h (reference range: 0–10 mm/h) and elevated C-reactive protein level of 8.1 (reference range: <0.8). The initial differential diagnosis was concerning for meningitis owing to nonspecific symptoms of high fevers, headache, and nausea, with venous sinus thrombosis and other inflammatory causes. The patient was empirically started on intravenous vancomycin, ceftriaxone, and acyclovir initially for concerns of meningitis. A computed tomography angiogram of the head revealed 2 internal carotid artery aneurysms up to 4 mm and 7×5 mm. Lumbar puncture results demonstrated an elevated white blood cell count of 10 (reference range: 0–5/mm3). The meningitis panel, Gram stain from the lumbar puncture, and cryptococcal antigen test were negative. The syphilis IgG/IgM test was positive, but his rapid plasma reagin test was nonreactive, and his treponema pallidum particle agglutination test was negative. Infectious work-up was obtained, including typhus, cytomegalovirus, toxoplasmosis, West Nile virus, hepatitis B/C, and Bartonella, but results were not immediately available. The patient continued to have fevers and ocular symptoms with no clear cause. Suspicion for a Bartonella infection grew given his clinical picture, recent adoption of a cat causing transmission via cat scratches, and otherwise negative workup, including negative typhus serologies. Consequently, his antibiotics were changed to intravenous doxycycline and oral rifampin. The patient’s headaches and fever gradually improved as a result; however, his vision loss remained unchanged. His Bartonella henselae serologies eventually returned with elevated IgG of >1: 1024 (reference value: <1: 64), and IgM of 1: 128 (reference value: <1: 16), supporting a diagnosis of Bartonella neuroretinitis. The patient was discharged on 6 weeks of oral doxycycline 100 mg every 12 h and oral rifampin 300 mg twice a day. The patient was relatively adherent to the antibiotics, missing a total of 5 to 7 doses. At his ophthalmology follow-up visit 5 weeks after discharge, he stated his headaches and fever remained resolved, with some improvement in his visual field loss. A visual acuity examination determined stable vision of 20/25 in the right eye and showed improvement of his vision from 20/100 to 20/30 in the left eye. Intraocular pressures were 12 and 13 mmHg in the right and left eye, respectively. The slit lamp examination remained unremarkable. A dilated fundus examination showed improving optic disc edema in the right eye (grade 1) and resolved disc edema with pallor in the left eye. The previously noted white choroidal lesions were replaced by chorioretinal scars. No macular edema or macular star formation was noted. Humphrey visual field testing (Figure 1) showed a left infero-nasal quadrantanopia with concomitant temporal and supero-temporal thinning on optical coherence tomography of the optic nerve (Figure 2). Optical coherence tomography imaging of the macula was unremarkable bilaterally (Figure 3). Neither fluorescein angiography nor fundus photo imaging were performed.

Discussion

It is important to recognize Bartonella neuroretinitis early to prevent damage to the eye and vision loss. CSD-induced Bartonella neuroretinitis is diagnosed based on visual symptoms, headache, history of cat exposure, and positive serology. Although CSD is most commonly associated with lymph-adenopathy, multiple case series and case reports have shown that patients with the clinical manifestation of neuroretinitis and the serologic confirmation of CSD can present without the typical lymphadenopathy [2,3]. Specifically, Tsuneoka and Tsukahara found that up to 16% of patients with the serological diagnosis of CSD can present without the typical lymphadenopathy [4]. Although Bartonella neuroretinitis is a common ocular complication of CSD, the lack of classic lymph-adenitis makes Bartonella neuroretinitis an underdiagnosed condition, especially in the setting of solely visual and headache symptoms [2,5]. Bartonella neuroretinitis also mimics the more common optic neuritis [6]. On ocular fundus examination, Bartonella neuroretinitis presents with optic disc edema, subretinal fluid, exudates, discrete white retinal or choroidal lesions (as seen in this patient), or exudates presenting in a classic macular star formation [7,8]. It is important to note that CSD is the leading cause of infectious neuroretinitis, and 5% to 10% of patients with CSD present with ocular symptoms [7]. Of note, the most common presentation of SCD in the eye is parinaud oculoglandular syndrome, which is present in about 4% of patients, but was not seen in our patient [9]. A previous study found that 64.3% of patients initially diagnosed with neuroretinitis tested positive for Bartonella henselae titers, suggesting past or current infection [10]. Bartonella neuroretinitis should be kept high on the differential diagnosis when a patient presents with fevers, headaches, and visual symptoms. Studies have shown that early administration of targeted antibiotics like doxycycline and rifampin can shorten the infection course and provide rapid visual recovery [2,11]. Early literature has suggested a controversial role of systemic steroids in Bartonella neuroretinitis. These studies indicate that there is no difference between patients that were treated with or without corticosteroids [7]. However, more recent literature has begun to favor the supplementation of corticosteroids to the treatment regimen, stating that patients can yield better outcomes regarding visual recovery [11,12]. Future research is needed to determine if combination treatment of antibiotics with corticosteroids is more effective on regaining visual acuity than antibiotics alone.

Conclusions

Here we present a case of a patient presenting with nonspecific symptoms of headache, fevers, and visual changes who was found to have optic disc edema without lymphadenopathy and was eventually diagnosed with Bartonella neuroretinitis. It is important to keep a Bartonella infection in the differential diagnosis when a patient presents with fevers and visual changes, as Bartonella can cause painless vision loss and is the leading cause of infectious neuroretinitis. Early recognition and treatment of this condition are essential to preventing vision loss and shortening recovery time.

References:

1.. Jacomo V, Kelly PJ, Raoult D: Clin Diagn Lab Immunol, 2002; 9(1); 8-18

2.. Gan JJ, Mandell AM, Otis JA: Arch Neurol, 2011; 68(1); 122-26

3.. Celiker H, Kazokoglu H, Eraslan M: Jpn J Infect Dis, 2018; 71(6); 397-401

4.. Tsuneoka H, Tsukahara M, Analysis of data in 30 patients with cat scratch disease without lymphadenopathy: J Infect Chemother, 2006; 12(4); 224-26

5.. Salicio-Bermejo Y, Cilla-Eguiluz G, Blanco-Esteban A: Enferm Infecc Microbiol Clin (Engl Ed), 2021; 39(9); 451-53

6.. Yap SM, Saeed M, Logan P, Healy DG: Pract Neurol, 2020; 20(6); 505-6

7.. Ksiaa I, Abroug N, Mahmoud A: J Curr Ophthalmol, 2019; 31(3); 254-61

8.. Tey MY, Govindasamy G, Vendargon FM, The clinical spectrum of ocular bartonellosis: A retrospective study at a tertiary centre in Malaysia: J Ophthal Inflamm Infect, 2020; 10; 31

9.. Baranowski K, Huang B, Cat scratch disease. [Updated 2022 Jun 21]: StatPearls [Internet] Jan, 2022, Treasure Island (FL), StatPearls Publishing Available from: https://www.ncbi.nlm.nih.gov/books/NBK482139/

10.. Suhler EB, Lauer AK, Rosenbaum JT, Prevalence of serologic evidence of cat scratch disease in patients with neuroretinitis: Ophthalmology, 2000; 107(5); 871-76

11.. Reed JB, Scales DK, Wong MT: Diagnosis, management, and sequelae. Ophthalmology, 1998; 105(3); 459-66

12.. Habot-Wilner Z, Trivizki O, Goldstein M, Cat-scratch disease: Ocular manifestations and treatment outcome: Acta Ophthalmol, 2018; 96(4); e524-e32

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923