A 32-year-old Irish man was referred to our eye emergency department with a myriad of symptoms which included jaw pain, right-sided headache, scalp discomfort, and sudden-onset painless right visual loss over a duration of 3 days. He denied any significant antecedent trauma event as a lucid historian but cited pain following eye movement. He was initially and incorrectly managed by a medical team as suspected giant cell arteritis (GCA) with oral steroid therapy initiated. The jaw pain and scalp discomfort created a clinical picture suggestive of GCA, but this differential was weakened by the young age profile of the man. His right-sided visual acuity was reduced to “counting fingers” from a previous baseline of 6/6, while his left-sided visual acuity remained intact with 6/6 documented. Medical history included psoriatic arthritis that had been managed medically with monoclonal antibody therapy in the form of adalimumab administered via the subcutaneous route at a dose of 40 mg every 2 weeks. His family history was noncontributory. He worked as a hotel manager and is a nonsmoker. He was initially treated with oral prednisolone 60 mg once daily, for which he received 7 days of treatment.
Clinical findings
Family and personal history were unremarkable for any ophthalmic pathology. His intraocular pressures lay within an acceptable range bilaterally. Significant pain on eye movement that was most pronounced on lateral gaze was recognized during the physical examination. Clinical examination revealed blot hemorrhages observed superiorly in the right retina accompanied by gross optic nerve swelling with a flat retina. The left eye examination did not relevant significant pathology. The anterior segment findings were noncontributory in relation to both eyes examined. The anterior chamber was deep and quiet bilaterally. There was no evidence of flare or fibrin in each eye. The optical coherence tomography (OCT) macula scan was unremarkable bilaterally.
Timeline
Initially, the patient was admitted to hospital and treated as atypical optic neuritis, using intravenous methylprednisolone therapy. A thorough set of radiological and immunological tests were requested. The timeline for definitive diagnosis and treatment is illustrated in Table 1. Here, the treatment paradigm shifts amid the knowledge of an evolving diagnosis.
Diagnostic assessment
A battery of tests were requested on admission to hospital. Admission blood work illustrated a significant elevation in white cell count and neutrophils in addition to elevated inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Initial white cell count was shown to be 17.0 × 10⁹/L alongside an elevated neutrophil count of 14.21 × 10⁹/L. A CRP of 59 mg/L and ESR of 58 mm/hour were reported by the hospital laboratory. Additional immunology testing revealed the patient to be negative for the following tests: quantiferon, anti-cyclic citrullinated peptide (anti-CCP), antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), and antimitochondrial antibody.
Given the significant rise in acute inflammatory markers, a blood-borne viral screen was sent in addition to a complete infectious disease panel. Treponema pallidum was later detected, and the remaining screen was noncontributory. Serum protein electrophoresis was normal alongside normal immunoglobulin reports. The man was HIV negative on serological investigation. Liver autoantibody profile testing was also reassuring. The anti-parietal cell, anti-smooth muscle antibody, and anti-liver–kidney microsomal (anti-LKM) antibody results were negative. A lumbar puncture was performed and was proven to be noncontributory.
The urea and electrolytes and liver function tests all lay within an acceptable range. Rheumatological panel testing was reported as normal. The patient was negative for myelin oligodendrocyte glycoprotein (MOG) antibodies and neuromyelitis optica (NMO) antibodies. Relevant imaging included an erect chest x-ray and magnetic resonance imaging (MRI) orbits including contrast. Radiological investigations were reported as entirely unremarkable. There were no financial concerns in relation to ordering tests owing to the level 4 nature of the clinical site. Additionally, the native English-speaking nature of the patient removed any language barriers.
Differential diagnosis
The ophthalmology team initially treated this case as an atypical optic neuritis presentation. The significant pain following eye movement accompanied with monocular visual loss rendered optic neuritis a reasonable differential and important component of the clinical workup. Reassuring optical coherence tomography (OCT) scans of the disc accompanied with normal retinal nerve fiber layers rendered optic neuritis an unlikely cause for pathology. MRI orbit with contrast was noncontributory and accompanied by negative blood test results for MOG antibodies and NMO antibodies, making this an unlikely cause for presentation.
A wide variety of other differentials were considered, including intermediate uveitis, white dot syndromes, macular choroiditis, acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), and Behçet’s disease. The history and clinical examination findings excluded these listed differentials systematically.
Laboratory tests revealed positive syphilis serology with detectable Treponema pallidum antibodies (TPHA) and rapid plasma reagin (RPR) at a titer of 1:128. In the aforementioned clinical context, this result was suggestive of ocular syphilis. At this point, the infectious disease team were invited for their expert oversight.
Therapeutic intervention
This man faced initial medical management with oral prednisolone 60 mg taken once daily for a duration of 7 days, prior to the timely referral to ophthalmology colleagues. A clinical decision was made to treat the patient on an inpatient basis. He was subsequently commenced on intravenous methylprednisolone therapy 1 g once daily for a period of 3 days. The intravenous methylprednisolone therapy provided analgesic effect but no change from presenting visual acuity. In total, the patient received 7 days of oral steroid therapy and 3 days of intravenous prior to antibiotic commencement.
The visual acuity prior to antibiotic was “counting fingers.” Knowledge of the specific blood results prompted a shift toward intravenous antibiotic therapy in the form of intravenous benzylpenicillin 2.4 g four times daily, as advised by the infectious diseases team. A significant improvement in visual acuity was demonstrated following benzylpenicillin therapy with a visual acuity of 6/15 noted in the clinic review 3 weeks subsequently. He completed a 14-day course of intravenous benzylpenicillin and was later switched to a tapering course of oral steroids alongside this. He was discharged from hospital following completion of pharmacotherapy and reviewed in the outpatient clinic setting thereafter.
Follow-up and outcomes
He recorded right-sided visual acuity of 6/15 without any aid amid uncompromised color vision at the 2-month follow-up following his planned discharge. The OCT macula scan did not show signs of evolution, however the right-sided OCT disc highlighted issues related to ganglion cell loss and retinal nerve fiber layer decay, consistent with the infectious disease process.
Follow-up clinical examination excluded right-sided papilledema. This represented a departure from the initial assessment. The formative pain following eye movement had subsided during the hospital admission. A gradual decline in symptom severity had been cited by the patient throughout the treatment course.
At the 2-month follow-up, the patient was entirely asymptomatic. Right-sided visual acuity had stabilized to a revised baseline of 6/15 from an initial visual acuity of “counting fingers.” The RPR test revealed a titer of 16 at the follow-up review with an initial RPR titer of 128 noted. This reduction is an important marker for disease resolution.
The most recent follow-up revealed a right visual acuity of 6/12 unaided with no improvement with pinhole test. His intraocular pressure stood at 15 mmHg in the right eye and 16 mmHg in the left eye. Optos wide-field imaging revealed a decrease in disc edema in the right eye consistent with clinical improvement in his condition. The patient had completed relevant antibiotic therapy and is being monitored by the infectious disease and ophthalmology team. This man will continue to be followed up by the ophthalmology clinical service on an annual basis.