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Lyme Disease-Associated Uveitis: A Case Report and Review Emphasizing the Importance of Travel History and Geographic Considerations

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Title: Lyme Disease-Associated Uveitis: A Case Report and Review Emphasizing the Importance of Travel History and Geographic Considerations

Authors: Andrew DesLauriers, BA; Marissa Larochelle, MD

Photographer: Rich Ordonez

Date: 08/09/2023

Keywords/Main Subjects: lyme disease, intermediate uveitis, anterior uveitis, travel history

Diagnosis: Lyme Disease-Associated Intermediate and Anterior Uveitis

Description of Case:

Introduction:

Lyme disease, caused by the Borrelia genus of bacteria transmitted through Ixodes ticks, is primarily reported in the Northeast and Mid-Atlantic regions of the United States, as well as in certain parts of Europe and Japan.1,2 Ocular involvement can occur at any stage of the disease, presenting with diverse manifestations, including uveitis. Early identification of Lyme-associated uveitis is crucial to initiate appropriate treatment and prevent long-term complications. Lyme-associated uveitis should be considered in the differential diagnosis of patients with new-onset uveitis and a history of travel to endemic areas.

Case Presentation:

In early August, a 10-year-old male presented to the Moran Eye Center in Utah with sharp, bilateral eye pain, blurred vision, and increased redness for three days. He reported a history of mild, intermittent eye redness without pain for three months prior to presentation. Additionally, one month before the increase in ocular symptoms, the patient experienced a brief generalized illness with fevers, headache, and cervical/post-cervical and submandibular lymphadenopathy, initially attributed to a self-limited viral illness. The patient, who had recently been diagnosed with autoimmune thyroiditis and a strong family history of autoimmune diseases, reported no previous ocular history. The patient’s mother reported that he regularly interacts with several stray cats near their home, but there were no instances of reported bites or scratches. Additionally, the patient and his family had vacationed in Vermont, a Lyme disease endemic area, three months prior to his presentation at the Moran Eye Center, though no tick bites were reported during their trip.

Examination and Diagnosis:

On examination, the patient had 1-2+ mixed cells in the anterior chamber and 1+ cell and 2+ vitreous haze bilaterally with notable vitreous debris. Fluorescein angiography revealed mild diffuse vascular leakage in both eyes. Based on the clinical picture, the patient was diagnosed with bilateral, simultaneous anterior and intermediate uveitis. Initial laboratory workup was significant for positive Bartonella IgM (1:256) but negative Bartonella IgG. Consequently, the patient was treated for presumed Bartonella infection with doxycycline and rifampin, along with topical prednisolone, cyclopentolate, and an oral prednisone taper to manage inflammation and prevent complications. The patient was referred to Infectious Disease clinic and further history taking revealed hiking in Lyme-endemic Vermont, so Lyme serology was added to the lab work up.

Treatment and Follow-Up:

Two weeks later, additional lab results indicated a positive Lyme ELISA and Immunoblot assay. While the initial Bartonella IgM had been elevated, a repeat Bartonella IgM test was negative (1:64), and two Bartonella IgG assays were also both negative, indicating that the initial positive IgM was likely a false-positive. Fortunately, doxycycline is effective in the treatment of both Bartonella and Lyme Borreliosis, so the patient had already been started on an effective regimen. Rifampin was discontinued, and the patient continued doxycycline for an additional 6 weeks. Following a two-month course of doxycycline with an oral prednisone taper, the patient’s symptoms had completely resolved, and a clinical examination showed no remaining signs of intraocular inflammation. The patient remained symptom-free, with no intraocular inflammation or recurrences at 11 months after the initial presentation.

Lyme Disease Overview:

The Borrelia genus of bacteria, transmitted through a bite from an Ixodes tick, cause Lyme disease, which progresses through three clinical stages. Stage 1 is characterized by a bulls-eye rash (Erythema Migrans) at the infection site in around 80% of patients, accompanied by constitutional flu-like symptoms in some cases. Stage 2 involves hematogenous spread to organs, leading to a variety of sequalae, including meningitis, neuropathies, and acute carditis. Stage 3 presents months to years post-inoculation with chronic manifestations, most commonly oligoarticular arthritis. Notably, 2-3% of Lyme disease patients present with Stage 2 or Stage 3 sequelae within days of exposure.3 Infection with Borrelia tends to peak during the late spring or early summer in endemic areas.3

Ocular Involvement in Lyme Disease:

Ocular involvement, typically bilateral, can occur at any disease stage.4 The most common ocular symptom associated with Lyme disease is a follicular conjunctivitis, occurring in approximately 11% of patients most commonly during Stage 1 of disease.5 Stages 2 and 3 of Lyme disease are associated with a variety of symptoms including all types of uveitis, retinal vasculitis, neuroretinis, episcleritis, keratitis, papillitis, optic neuritis, and cranial nerve palsies of nerves III, V, VI, and VII.4,6

Lyme-Associated Uveitis:

Lyme uveitis, an uncommon manifestation of Stage 2 and Stage 3 Lyme disease, comprises up to 4.3% of all uveitis cases at referral centers in endemic areas; however, the reported prevalence varies widely and is much lower in non-endemic areas.4,7 Patients typically present with symptoms such as eye pain, redness, blurred vision, new floaters, and photophobia. The most common presentation is an intermediate uveitis; however, cases of anterior, posterior, and panuveitis have also been reported.4 Uveitis is commonly accompanied by retinal vasculitis. The uveitis can be granulomatous or non-granulomatous in nature.8 Published reports have described varied clinical findings of Lyme uveitis in different patients, with some demonstrating choroidal neovascularization and others showing multifocal white dots in the posterior pole, resembling white dot syndromes such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE).9,10,11

Diagnosis and Management:

Lyme-associated uveitis should be considered in any patient presenting with new-onset uveitis after travel to a Lyme-endemic area. A detailed history should focus on possible exposure and any symptoms outside of eye-related issues, though ocular involvement can be the sole manifestation of Lyme infection, meaning patients may not have other systemic symptoms.4,6 Particular attention should be paid to patients who report spending any amount of time outdoors in an endemic region, engaging in activities such as hiking, gardening, hunting, or forestry work.3

Tissue biopsies are seldom useful in the detection of ocular Borrelia infection.4 Routine screening for Lyme disease in all uveitis patients isn’t recommended due to the low incidence of Lyme-associated uveitis. However, in the right clinical context and with a history of travel to Lyme-endemic areas, serum antibody testing can be used to confirm the diagnosis. Lyme-associated uveitis management should include regular surveillance, and multi-modal imaging is useful for monitoring progression and treatment response.11

Treatment:

Borrelis burgdorferi, the species of bacteria causing Lyme disease in the United States, is typically sensitive to tetracyclines and many B-lactam antibiotics. Doxycycline, ceftriaxone, and amoxicillin can treat any stage of disease, with ceftriaxone preferred for CNS involvement.3,4 These medications are also effective in treating ocular disease, with some studies suggesting use of a cephalosporin for better ocular penetration.12 Steroid treatment alone does not worsen disease but is insufficient in resolving ocular complications.4 Lyme-associated uveitis typically requires a combined approach of both antibiotic treatment and management of inflammation.

Discussion:

This case illustrates the importance of maintaining a high suspicion for Lyme disease in patients with uveitis if there is a report of recent travel to Lyme-endemic areas. Conversely, it is important to note that Lyme disease is a less likely cause of uveitis in patients without exposure to an endemic region, for example, residents of Utah who have not travelled out of the state. While there are small populations of ticks in Utah that could potentially carry Lyme disease, tests conducted on samples of these ticks have not detected the presence of Borrelia bacteria.13 Even in endemic areas, Lyme disease is an uncommon cause of uveitis, however it should be considered in patients with the appropriate risk factors such as a history of time spent outdoors and additional clinical symptoms. Please see the geographic distributions of reported Lyme disease included in the resources section below to help guide risk stratification based on travel history.

Lyme-associated uveitis can present in various forms, making it crucial to include this infectious etiology in the differential diagnosis when risk factors are present and perform appropriate antibody testing for confirmation. In this case, the patient’s travel to an endemic area in late spring placed him at risk of Lyme exposure. His intermittent eye redness preceding the acute uveitis episode was likely attributable to the follicular conjunctivitis often reported in Lyme disease’s Stage 1. Furthermore, the febrile illness he experienced one month prior to presenting at the Moran Eye Center was likely a systemic manifestation of Lyme disease. Early identification allows for timely treatment and prevents vision-threatening complications.14 Untreated Lyme uveitis, although rare, can result in complete loss of vision and phthisis bulbi.15

Conclusion:

Lyme-associated uveitis, though uncommon, can lead to serious complications. This case report emphasizes the significance of clinical acumen in diagnosing and treating vision-threatening diseases related to Lyme borreliosis. Awareness of Lyme disease’s geographic distribution and risk factors can guide risk stratification based on travel history, helping to identify cases promptly and initiate appropriate management. Clinicians in non-endemic areas should maintain a high index of suspicion for Lyme uveitis in patients with relevant travel history, particularly in the setting of characteristic systemic symptoms.

Images or video:

Figure 1: Lyme Disease Map

Figure 1: Lyme Disease Map. Distribution of reported lyme disease cases in the United States in 2021. Each green dot represents a case of Lyme Disease reported to the CDC in 2021. States shaded with light blue are regarded as “high incidence states” by the CDC. States shaded in grey are considered low incidence. Lyme Disease Map acquired from the CDC website: https://www.cdc.gov/lyme/datasurveillance/lyme-disease-maps.html

Figure 2 (Top Image) - FA .035, Lyme-Associated Uveitis

Figure 2 (Bottom Image) - FA 5.24, Lyme-Associated Uveitis

Figure 2. Fluorescein angiography images of the patient’s right eye that were taken upon presentation. The images captured at 0:35 (top) and 5:24 (bottom) after infusion reveal mild diffuse vascular leakage.

Summary of the Case:
Lyme disease, caused by the Borrelia genus of bacteria and transmitted by Ixodes ticks, can lead to a variety of ocular complications including uveitis. Transmission typically occurs in endemic regions with the appropriate ecological factors to allow for bacterial reproduction and transmission. A 10-year-old male presented with eye pain, redness, and blurred vision after vacationing in a Lyme-endemic region, although he had no reported tick bites. His examination and subsequent tests revealed Lyme-associated uveitis. The importance of early identification and treatment is underscored, as untreated cases can result in severe vision complications. Clinicians in non-endemic regions should maintain vigilance for Lyme uveitis in patients with relevant travel history in order to ensure prompt and effective management.

Format: Case Report, Literature Review

References

  1. Lyme Disease Map | Lyme Disease | CDC. Accessed August 1, 2023. https://www.cdc.gov/lyme/datasurveillance/lyme-disease-maps.html
  2. Overview | Johns Hopkins Lyme and Tickborne Diseases Dashboard. Accessed August 1, 2023. https://www.hopkinslymetracker.org/overview/
  3. Steere AC, Strle F, Wormser GP, et al. Lyme borreliosis. Nature Reviews Disease Primers. 2016;2(1):16090. doi:10.1038/nrdp.2016.90
  4. Bernard A, Seve P, Abukhashabh A, et al. Lyme-associated uveitis: Clinical spectrum and review of literature. Eur J Ophthalmol. 2020;30(5):874-885. doi:10.1177/1120672119856943
  5. Steere AC, Bartenhagen NH, Craft JE, et al. The early clinical manifestations of Lyme disease. Ann Intern Med. 1983;99(1):76-82. doi:10.7326/0003-4819-99-1-76
  6. Lesser RL. Ocular manifestations of Lyme disease. The American Journal of Medicine. 1995;98(4, Supplement 1):60S-62S. doi:10.1016/S0002-9343(99)80045-X
  7. Mikkilä H, Seppälä I, Leirisalo-Repo M, Immonen I, Karma A. The etiology of uveitis: The role of infections with special reference to Lyme borreliosis. Acta Ophthalmologica Scandinavica. 1997;75(6):716-719. doi:10.1111/j.1600-0420.1997.tb00637.x
  8. Mikkilä HO, Seppälä IJT, Viljanen MK, Peltomaa MP, Karma A. The expanding clinical spectrum of ocular lyme borreliosis. Ophthalmology. 2000;107(3):581-587. doi:10.1016/S0161-6420(99)00128-1
  9. Kılıç Müftüoğlu İ, Aydın Akova Y, Gür Güngör S. A Case of Lyme Disease Accompanied by Uveitis and White Dot Syndrome. Turk J Ophthalmol. 2016;46(5):241-243. doi:10.4274/tjo.25991
  10. Amer R, Brannan S, Forrester JV. Inflammatory choroidal neovascular membrane in presumed ocular Lyme borreliosis. Acta Ophthalmol. 2009;87(3):346-348. doi:10.1111/j.1755-3768.2007.01160.x
  11. Ferro Desideri L, Rosa R, Forte P, et al. Multimodal imaging for the management of Lyme-associated uveitis: A case report from an Italian tertiary center. European Journal of Ophthalmology. Published online January 29, 2023:11206721231154172. doi:10.1177/11206721231154172
  12. Lindström BE, Skogman BH, Lindström AK, Tallstedt L, Nilsson K. Borrelia Ocular Infection: A Case Report and a Systematic Review of Published Cases. Ophthalmic Res. 2022;65(2):121-130. doi:10.1159/000521307
  13. Richardson K, Davis R, Ramirez R. Ticks and Tick-Borne Diseases of Utah. Utah State University Extension and Utah Plant Pest Diagnostic Laboratory; 2023.
  14. Copeland RAJ. Lyme uveitis. Int Ophthalmol Clin. 1990;30(4):291-293. doi:10.1097/00004397-199030040-00019
  15. Kauffmann DJ, Wormser GP. Ocular Lyme disease: case report and review of the literature. British Journal of Ophthalmology. 1990;74(6):325-327. doi:10.1136/bjo.74.6.325

Faculty Approval by: Marissa Larochelle, MD

Copyright: Andrew DesLauriers, ©2023. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/

Identifier: Moran_CORE_126899