By Richard L. Rabin, MD, Sara Khandan, MD, and Nicholas P. Byrne, MD
Edited by Ahmad A. Aref, MD, MBA
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After a week of worsening fatigue and nausea, John Jones,* a 74- year-old triathlete, visited his primary care physician. During that examination, he noted that when his symptoms first began, he experienced pain when he opened his jaw wide while yawning, but the pain resolved after a couple days.
His physician was concerned that he might have temporal arteritis and ordered same-day blood work. The results revealed an erythrocyte sedimentation rate (ESR) of 29 mm/hr (normal: 0-37 mm/hr) and a platelet count of 188,000/μL (normal: 150,000 to 450,000/μL). His C-reactive protein (CRP) was not measured.
Two days later, Mr. Jones called his primary care physician complaining of new-onset double vision. He was promptly referred to our ophthalmology clinic for a same-day evaluation.
We Get a Look
Mr. Jones had an unremarkable past ocular history. He had hypertension that was well-controlled through diet and exercise, and he took no medication. He stated that his double vision resolved after he placed an eye patch over either eye. However, he had difficulty characterizing the direction of his diplopia, and he noted that he experienced intermittent mild frontal headaches over his brows that started three days prior. He did not have a headache when we saw him.
Previously, Mr. Jones had enjoyed exercising and weightlifting at least six days per week, but recently his appetite had decreased, and he was still experiencing nausea. He told us about “pain in the muscles that move the eyes.” He said that he hadn’t been experiencing any temple pain, pain with combing his hair, or jaw fatigue with chewing. Aside from the double vision, he had no vision changes.
On examination, no temporal tenderness was noted. Mr. Jones’ BCVA was 20/40 in his right eye and 20/40 in his left, consistent with media opacities from cataracts. An afferent pupillary defect was absent, and his confrontational fields were normal. The posterior segment exam was unremarkable, and the optic nerves were pink and sharp with 0.3 cups in both eyes.
Identifying the Problem
Though Mr. Jones’ extraocular movements appeared normal, the Parks-Bielschowsky three-step-test revealed a left hypertropia that was worse in left gaze and worse on right head tilt. These findings were consistent with a left inferior rectus palsy.
His extraocular movements were rechecked with attention paid to the left eye. On downgaze, a left eye inferior duction weakness was noted only after the upper eyelids were lifted.
Temporal arteritis came to mind as the most immediate and serious issue to rule out, given his age, vague history of jaw pain with other systemic symptoms, and isolated left inferior rectus palsy. The lack of diabetes or significant hypertension increased the likelihood of a secondary cause. Because an isolated infraduction deficit would not fit with a cranial nerve 3, 4, or 6 palsy, it seemed less likely that the palsy was due to a microvascular ischemic event.
Differential Diagnosis
We considered the following: orbital tumor due to metastatic or primary cancer, temporal arteritis (even though ESR testing two days prior was normal), myasthenia gravis, thyroid eye disease, and orbital pseudotumor.
Diagnosis and Treatment Course
Friday: a trip to the ED. After discussing Mr. Jones’ eye movements with him, we immediately referred him—despite his objections—to the emergency department (ED) for a repeat ESR test, CRP testing, and initiation of IV methylprednisolone for treatment of presumed temporal arteritis. At this point, Mr. Jones’ ESR was 18 mm/hr, and his CRP was 68 mg/L (normal: 0-9.9 mg/L).
Neurology was consulted at 2:00 p.m. that day and recommended that Mr. Jones discontinue steroid treatment due to lack of “temporal tenderness or temporal headaches or other signs of giant cell arteritis [GCA].” That evening, after we spoke to the in-patient care team about our differential, which included temporal arteritis, steroids were restarted. In addition, Mr. Jones was admitted for magnetic resonance imaging (MRI). MRI of the brain and temporal arteries with and without contrast did not show any acute abnormalities. The temporal artery MRI report stated, “The left superficial temporal artery demonstrates no mural thickening and no mural enhancement (score 0). The right superficial temporal artery demonstrates no mural thickening, but slight mural enhancement, which is likely physiologic, score 1 … No evidence of temporal arteritis.”
Saturday: discharged. On Saturday, Mr. Jones’ ESR had increased to 52 mm/hr. He was discharged on oral prednisone 80 mg/day by mouth and scheduled for an outpatient temporal artery biopsy in two days (Monday).
Monday: back to the ED. Two days later, on Monday morning, we were informed that Mr. Jones had returned to the ED because of three episodes of amaurosis fugax in his left eye.
As it turned out, Mr. Jones never went to the pharmacy to pick up his oral prednisone and canceled his biopsy because he did not believe that he had temporal arteritis, given his overall good physical fitness.
In the ED, IV steroids were restarted, and he was placed in a hyperbaric oxygen chamber. By midday Monday, Mr. Jones’ vision had deteriorated to no light perception (NLP) in his left eye, and he was having episodes of amaurosis fugax in the right eye. These episodes eventually resolved as the steroid treatment was initiated. At this point, his CRP was elevated at 81 mg/L, and his ESR was 10 mm/hr.
Confirmation and outcome. Mr. Jones underwent an inpatient temporal artery biopsy (Figs. 1 and 2); it was positive for temporal arteritis. He was discharged on oral prednisone three days later.
The vision in Mr. Jones’ left eye has remained at NLP. The vision in the right eye also remained unchanged.
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BIOPSY. (1A) Histologic cross-section with low-power view of the temporal artery demonstrates diffuse inflammatory infiltration involving the tunica intima, media, and adventia. Mural chronic inflammation, including histiocytes and multinucleated giant cells, is evident at the level of the internal elastic lamina. (1B) High-power view of the temporal artery is notable for the presence of multinucleated giant cells in the adventia (HE stain). (2A) Temporal artery reveals fragmentation of the internal elastic lamina and mural inflammatory infiltrate. (2B) Intact area of internal elastic lamina and mural inflammatory infiltrate from the same patient for reference. (Elastin/EVG stain for 2A and 2B).
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About the Disease
Temporal arteritis, also known as GCA, is a potentially blinding and life-threatening systemic vasculitis that primarily affects medium and large arteries of the aorta and its extracranial branches.1-3
Signs and symptoms. This vasculitic disease can present with a variety of clinical manifestations, including headache, scalp tenderness, jaw claudication, fever, malaise, anorexia, weight loss, diplopia, amaurosis fugax, pallid disc edema, arteritic ischemic optic neuropathy, central retinal artery occlusion, cilioretinal artery occlusion, stroke, transient ischemic attack, decreased temporal artery pulse and tender palpable temporal artery, distal musculoskeletal pain, and aortic disease.
Who’s at risk? Risk factors for GCA include Northern European descent, polymyalgia rheumatica, and advanced age.4
Diagnosis. Diagnostic tools include laboratory markers, MRI, ultrasonography, and temporal artery biopsy. Laboratory markers include ESR, CRP, and platelet counts.
Color duplex ultrasonography of the temporal artery may demonstrate abnormalities including occlusion, stenosis, or a dark halo sign (thought to be secondary to edema in the vascular wall).5 The gold standard for diagnosing temporal arteritis is a temporal artery biopsy with histopathological confirmation of the disease.
Histopathology typically demonstrates presence of multinucleated giant cells, inflammatory cells, reduced arterial lumen size, and fragmented internal elastic lamina.6
Treatment. As GCA is considered an ophthalmic emergency, treatment should not be delayed. Treatment consists of intravenous methylprednisolone 1g/day for three days followed by oral prednisone 1mg/kg body weight per day.7 A confirmatory temporal artery biopsy can be performed up to two weeks after the initiation of steroid treatment.
Corticosteroid treatment typically does not improve the vision in the affected eye but is thought to prevent involvement of the contralateral eye.8 In the presence of an unremarkable biopsy, despite high clinical suspicion, a contralateral biopsy can be performed. Corticosteroid treatment is tapered slowly in coordination with a rheumatologist while carefully monitoring inflammatory laboratory markers and clinical signs. Tocilizumab, an interleukin-6 receptor antagonist, may be used to reduce the corticosteroid burden long-term but is not a substitute for steroids acutely.
Conclusion
GCA is a large vessel vasculitis that affects multiple organ systems. Ophthalmic manifestations—including transient diplopia or amaurosis fugax—may be some of the first presenting symptoms.
Laboratory markers are a good screening tool, but this case underlines the importance of maintaining a high clinical suspicion for this potentially blinding disease even in the face of normal inflammatory markers. Temporal artery biopsy with histopathologic confirmation is the gold standard for diagnosing the condition.
While you await biopsy confirmation, corticosteroid treatment must not be delayed in order to prevent blindness and contralateral involvement.
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* Patient’s name is fictitious.
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1 Salvarani C et al. N Engl J Med. 2002;347(4):261-271.
2 Salvarani C et al. Lancet. 2008;372(9634):234-245.
3 Restuccia G et al. Medicine (Baltimore). 2016;95(19):e3524.
4 Weyand CM, Goronzy JJ. N Engl J Med. 2014;371(1):50-57.
5 Schmidt WA et al. N Engl J Med. 1997;337(19):1336-1342.
6 Naumovska M et al. Scand J Rheumatol. Published online May 13, 2022.
7 Ness T et al. Dtsch Arztebl Int. 2013;110(21):376-385.
8 Bengtsson BA, Malmvall BE. Arthritis Rheum. 1981;24(7):899-904.
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Dr. Rabin is at Walnut Creek Eye Care in Walnut Creek, Calif.; Dr. Khandan is at Kaiser Permanente in Santa Clara, Calif.; and Dr. Byrne is a pathologist at John Muir Medical Center in Walnut Creek, Calif. Financial disclosures: None.