Elderly man presents with bilateral injection, pain, tearing and photosensitivity
Click Here to Manage Email Alerts
A 92-year-old Asian man was seen in the uveitis ophthalmology clinic due to 2 weeks of bilateral eye injection, pain, tearing and photosensitivity. He denied flashes, floaters, diplopia or metamorphopsia.
A complete systemic review was negative for cough, shortness of breath or joint pain. His ocular history was significant for exudative age-related macular degeneration in his right eye, nonexudative AMD in his left eye and bilateral dense cataracts. He was recently diagnosed and treated for recurrent bilateral bacterial conjunctivitis. Baseline visual acuity was 20/400 in the right eye and 20/70 in the left eye. His medical history was significant for hypertension, hypercholesterolemia and high-grade papillary urothelial carcinoma of the bladder. His medications included amlodipine 2.5 mg, metoprolol succinate XL 50 mg, aspirin 81 mg and atorvastatin 80 mg, and he recently completed six cycles of intravesical bacillus Calmette-Guérin (BCG). He had no pertinent surgical or family history and no known allergies.
Examination
Upon examination, best corrected visual acuity was counting fingers at 3 feet in the right eye and 20/100 in the left eye. IOPs were within normal limits. Both pupils were minimally reactive to light without afferent pupillary defect. Extraocular eye movements were full and painless, and confrontation visual field was full bilaterally. Anterior segment slit lamp examination was notable for bilateral bulbar hyperemia and chemosis without follicles, papillae or exudate. No keratic precipitates were seen. There was fibrin in both anterior chambers, posterior synechiae, fine iris hyperemia and symmetric dense age-related cataracts.
Dilated fundus examination was limited due to the dense cataracts in both eyes. There was no obvious vitritis in the right eye and a healthy nerve with sharp margins and chronic subfoveal scarring with surrounding hemorrhage. The vessels were normal in course. There was no view to the periphery. There was a limited view to the posterior pole in the left eye.
Imaging
B-scan ultrasonography of both eyes was conducted due to dense cataracts and revealed no obvious vitreous opacities or retinal detachment. OCT of the macula demonstrated significant subretinal hemorrhage vs. fibrosis in the right eye, and there was parafoveal drusen and an epiretinal membrane in the left eye.
What is your diagnosis?
See answer below.
Conjunctivitis, anterior uveitis
The patient developed both presumed conjunctivitis and anterior uveitis within 6 weeks of his last intravesical BCG cycle. It is likely the patient experienced an autoimmune reaction secondary to the intravesical BCG.
Workup and management
One day after his last dose of intravesical BCG, the patient developed what was thought to be bacterial conjunctivitis. Conjunctival cultures at that time were negative, and there was no evidence of anterior uveitis. He was started on ofloxacin drops with minimal improvement. Prednisolone was added to the treatment regimen, resulting in a full resolution of symptoms. Within a week of the conjunctivitis, the patient was additionally started on diclofenac by his primary care doctor for “vague lower extremity pain.”
The patient presented 6 weeks later with recurrent bilateral eye pain, photosensitivity and injection and was found to have recurrent conjunctival hyperemia and chemosis in the right eye. He was restarted on a short prednisolone taper with resolution of the hyperemia. Two weeks later at his follow-up visit, the patient complained of persistent photosensitivity. There was now fibrin in the anterior chamber, posterior synechiae and iris hyperemia in both eyes. Fortunately, no obvious vitritis was seen on initial B-scan. The patient was restarted on prednisolone in both eyes along with cyclopentolate in both eyes and referred to the uveitis clinic.
On our initial evaluation, the patient appeared to be improving on prednisolone with no obvious anterior chamber reaction and less anterior chamber fibrin in both eyes. The iris hyperemia appeared to be improving. While there was mild concern for potential mycobacterial endophthalmitis, an aqueous tap was not performed as there was no evidence of vitritis and the patient appeared to be clinically improving on topical therapy.
Blood work was obtained looking for common causes of anterior uveitis, including a complete blood count, basic metabolic panel, HLA-B27, syphilis antibodies, serum lysozyme and angiotensin converting enzyme (ACE) levels, and a QuantiFERON Gold assay. All were negative except for a positive QuantiFERON Gold and borderline elevation in ACE levels. A chest X-ray demonstrated no focal consolidations or hilar lymphadenopathy. The patient was continued on prednisolone with close follow-up.
Discussion
Intravesical BCG is routinely used as an adjunctive immunotherapy treatment for several types of bladder cancer. While it is typically safe and effective, approximately 5% of patients experience serious systemic complications. Ocular manifestations include conjunctivitis, anterior uveitis, posterior uveitis and infectious endogenous endophthalmitis. It is theorized that a cell-mediated hypersensitivity reaction in response to elevated cytokine and interleukin levels or via antigenic mimicry response may be responsible for the autoimmune complications.
Ocular autoimmune complications typically arise between four to six cycles of intravesical BCG and respond to steroids. Conjunctivitis is by far the most common ocular manifestation, seen in more than 80% of ocular complications. It is typically associated with Reiter’s syndrome, a type of reactive inflammatory response affecting the joints (arthritis), eyes (conjunctivitis) and mucosa (urethritis). Approximately 50% of patients with Reiter’s syndrome secondary to intravesical BCG may only experience conjunctivitis as their presenting symptom. In our patient, what was thought to be bacterial conjunctivitis was likely a hypersensitivity reaction. There was a strong temporal relationship to the sixth BCG cycle and symptoms resolved only when topical prednisolone was initiated. Additionally, the patient experienced simultaneous “vague lower extremity pain,” prompting the patient’s primary care doctor to prescribe diclofenac. While most patients who develop Reiter’s syndrome are HLA-B27 positive, it is not required for diagnosis and only aids in predicting treatment response.
Of the ocular manifestation, uveitis is exceedingly rare, comprising only 5% of all cases. Our patient had presumed anterior uveitis; despite no anterior chamber cell, there was evidence of an anterior chamber reaction given the fibrin, posterior synechiae and iris hyperemia. Fortunately for our patient, there was no posterior involvement. Topical steroids are usually a sufficient treatment for anterior uveitis. Any evidence of posterior uveitis will likely require the addition of anti-tuberculosis treatment and systemic steroids, potentially requiring surgical intervention if inflammation is too dense. Refraining from further intravesical BCG is the definitive treatment.
This case highlights the importance of attempting to identify one underlying diagnosis connecting many vague symptoms and previous diagnoses. Drug-induced uveitis is a diagnosis of exclusion and can be challenging to make. A thorough workup should always be conducted to exclude more common causes of uveitis. Physicians should consider systemic medications, illnesses and drug side effects when patients present several times with recurrent diseases despite standard medical treatment.
Case resolution
Six weeks later, the patient had been successfully tapered off prednisolone without recurrence of conjunctivitis or uveitis. He did not receive another cycle of intravesical BCG. He has now been free of any signs of ocular inflammation for more than a year with continuous monitoring.
- References:
- Agarwal M, et al. Indian J Ophthalmol. 2020;doi:10.4103/ijo.IJO_816_20.
- Al-Shakarchi F. Iraqi Postgraduate Med J. 2015;14(1):91-95.
- Alkan S, et al. Semin Ophthalmol. 2022;doi:10.1080/08820538.2021.1974060.
- Anis O, et al. Autoimmun Rev. 2023;doi:10.1016/j.autrev.2023.103329.
- Freixa M, et al. Eur J Case Rep Intern Med. 2020;doi:10.12890/2020_001448.
- Liu Y, et al. J Oncol. 2019;doi:10.1155/2019/6230409.
- Spratt A, et al. J Pediatr Ophthalmol Strabismus. 2008;doi:10.3928/01913913-20080701-15.
- Wertheim M, et al. Br J Ophthalmol. 2002;doi:10.1136/bjo.86.6.706.
- For more information:
- Edited by William W. Binotti, MD, and Julia Ernst, MD, PhD, of New England Eye Center, Tufts University School of Medicine. They can be reached at william.binotti@tuftsmedicine.org and julia.ernst@tuftsmedicine.org.
Collapse
Read more about
Click Here to Manage Email Alerts