January 02, 2026
5 min read
A 29-year-old woman sought care at Tufts Medical Center for a puzzling case of bilateral uveitis—inflammation affecting both eyes—that hadn’t responded to standard treatments. It’s a diagnostic challenge, to say the least.
Unraveling a Complex Case of Uveitis
Table of Contents
Understanding the interplay of gastrointestinal symptoms, tattoos, and ocular inflammation is crucial for accurate diagnosis and effective treatment.
- The patient initially presented with irregular pupils and floaters, responding temporarily to steroid eye drops.
- Despite initial improvement, inflammation returned with each attempt to reduce steroid dosage.
- A thorough investigation revealed a surprising connection between her uveitis, recent weight loss, and a history of tattoos.
- Ultimately, a diagnosis of celiac disease and suspected tattoo-associated uveitis emerged, highlighting the importance of considering systemic conditions in ocular inflammation.
The patient’s journey began over a year prior when she noticed an unusual appearance to her pupils and experienced floaters in her vision. An initial diagnosis of bilateral anterior uveitis was made, and treatment with topical prednisolone acetate provided temporary relief. However, the inflammation stubbornly returned each time the steroid dosage was tapered, necessitating ongoing maintenance therapy with twice-daily applications.
Notably, she had no prior history of autoimmune or infectious diseases. A review of her medical history revealed more than four bowel movements daily, leading to unintentional weight loss of 10 pounds over the preceding six months. She denied any back pain, joint discomfort, oral or genital ulcers, shortness of breath, new skin rashes, or changes in urination. She owned a cat and had traveled to Europe within the past year. She also had tattoos, which appeared stable at the time of her initial presentation.
Initial tests for tuberculosis, syphilis, Lyme disease, Bartonella, and the HLA-B27 genetic marker were all negative. Angiotensin-converting enzyme levels were within normal limits. However, as the condition progressed and developed bilateral vitreous cell and cystoid macular edema in the right eye, she was referred to a uveitis specialist for further evaluation. (The patient provided verbal consent for the publication of this case.)
Examination Findings
Visual acuity was 20/20 in both eyes. Intraocular pressure (IOP) measured 20 mm Hg in the right eye and 18 mm Hg in the left eye using applanation tonometry. Pupil examination, visual field testing, and assessment of extraocular movements were normal in both eyes. Examination of the anterior segment revealed rare cells in the right eye and trace cells in the left eye. No keratic precipitates or posterior synechiae were observed. A dilated fundus exam showed trace anterior cells in both eyes, with no evidence of haze, snowballs, snowbanks, retinal vasculitis, or choroiditis.
Imaging Results
Optical coherence tomography (OCT) of the macula showed no cystoid macular edema and normal retinal architecture. Fluorescein angiography revealed nonspecific peripheral leakage in both eyes, with patchy areas of delayed choroidal filling observed in the left eye (Figure 1).
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Undifferentiated Bilateral Uveitis: A Broad Differential
The broad differential diagnosis for bilateral anterior and intermediate uveitis with retinal vasculitis included infectious, autoimmune, neoplastic, and idiopathic causes.
While initial infectious disease screening—including tests for tuberculosis, syphilis, and Lyme disease—came back negative, Whipple disease was considered due to the patient’s uveitis and recent diarrhea with weight loss. However, she did not exhibit the polyarthritis and central nervous system effects commonly associated with Whipple disease. Inflammatory conditions like inflammatory bowel disease related to HLA-B27 remained on the differential, prompting further investigation with a gastroenterology consultation.
Other inflammatory possibilities included sarcoidosis and tubulointerstitial nephritis and uveitis (TINU) syndrome—particularly relevant given the patient’s age and gender. Tattoo-associated uveitis was also considered, though deemed less likely in the absence of tattoo swelling. A neoplastic etiology, such as lymphoma, was considered less probable due to the patient’s younger age and immunocompetent status. It’s important to remember that up to 50% of uveitis cases remain idiopathic (Maghsoudlou et al.).
Further Workup and Management
Repeat syphilis testing using treponemal antibodies was negative. Additional lab tests for rheumatoid factor, antinuclear antibody (ANA), and Whipple PCR were also negative. Beta-2 microglobulin, which is elevated in TINU, was within normal limits. Lysozyme levels were normal, and a chest X-ray showed no signs of sarcoidosis. Both perinuclear antineutrophil cytoplasmic antibody (P-ANCA) and cytoplasmic antineutrophil cytoplasmic antibody (C-ANCA) were negative.
Gastroenterology workup for infectious causes of diarrhea was negative. However, fecal calprotectin levels were elevated at 220 µg/g (normal 0-120), indicating nonspecific stool inflammation. Endoscopic biopsies of the upper gastrointestinal tract and colon revealed lymphocytosis with preserved intestinal architecture. With an HLA-DQ2 haplotype and elevated levels of deaminated gliadin IgG, transglutaminase IgG, and IgA, the patient was diagnosed with celiac disease. She subsequently adopted a gluten-free diet.
During the systemic workup, the patient returned with worsening uveitis symptoms. Treatment was switched from topical prednisolone to difluprednate, and an oral prednisone taper was initiated. One month into the taper, she reported that her tattoos had gradually become indurated, swollen, and painful (Figure 2). Her intraocular inflammation also worsened during this period. The concurrent tattoo inflammation and uveitis led to a presumed diagnosis of tattoo-associated uveitis.
Discussion: Tattoo-Associated Uveitis and Beyond
Tattoo-associated uveitis is characterized by cutaneous inflammation of tattoos accompanied by concurrent intraocular inflammation. Differentiating it from sarcoidosis can be challenging due to a similar granulomatous inflammatory process (Ghalibafan et al.). A thorough lab workup and imaging are essential, as tattoo-associated uveitis is often a diagnosis of exclusion. Some theories suggest it may be a localized form of sarcoidosis affecting the skin and eyes, while others propose a delayed-hypersensitivity reaction to tattoo ink (Carvajal Bedoya et al.).
As seen in this case, patients typically present with bilateral anterior uveitis. Vitritis and cystoid macular edema are also common findings. Larger tattoos and black ink are more frequently implicated. A recent systematic review found that 89% of patients experience skin inflammation that precedes or coincides with ocular inflammation. Symptom onset can range from days to years after tattooing (Ghalibafan et al.).
Inflammation is typically managed with steroids or immunosuppression. In rare cases, excisional removal of small tattoos has led to complete resolution of inflammation (Carvajal Bedoya et al.). Laser tattoo removal is generally not recommended due to concerns that increased immune system exposure to pigment could amplify the inflammatory response (Izikson et al.).
While tattoo-associated uveitis is rare, its incidence is believed to be rising due to the increasing prevalence of tattoos. In the United States, tattoo prevalence has doubled in 20 years, with approximately 30% of adults having at least one. Therefore, inquiring about tattoos is a valuable component of the review of systems when evaluating a patient with uveitis, especially in bilateral cases.
Celiac disease is not typically considered in the differential diagnosis of uveitis. However, several cases of noninfectious uveitis have been linked to celiac disease (Krifa et al.; Saleem et al.). Larger-scale studies have also suggested an increased risk of uveitis in patients with biopsy-proven celiac disease (Boustany et al.; Mollazadegan et al.). This area warrants further investigation.
Tattoo-associated uveitis remains a diagnosis of exclusion. Given the concurrent celiac disease, which could also contribute to uveitis, a definitive diagnosis of tattoo-associated uveitis in this patient is uncertain. However, the association with tattoos is more compelling given that the uveitis flared despite adherence to a gluten-free diet. It’s known that uveitis related to celiac disease often responds to a gluten-free diet (Krifa et al.).
Clinical Course and Outcome
The patient experienced overall improvement in intraocular inflammation with topical difluprednate, which is currently being tapered. On her most recent visit, there was one cell per high-powered field in the anterior chamber and trace old-appearing cells in the vitreous bilaterally. Two months prior, the patient experienced a steroid-induced elevation in IOP, which has been controlled with timolol-dorzolamide. Upon completion of the oral prednisone taper, she was transitioned to methotrexate with folate supplementation. She has no plans for pregnancy. Rheumatology is providing support with medication management. Her tattoos have become less edematous (Figure 3). Since eliminating gluten from her diet, her diarrhea has resolved.
- For more information:
- Lianna Valdes, MD, is with New England Eye Center, Tufts University School of Medicine.
- Ke Zeng, MD, of New England Eye Center, Tufts University School of Medicine, can be reached at [email protected].
