Visual loss in giant cell arteritis 3 weeks after steroid initiation

Abstract

Giant cell arteritis (GCA) is the most common vasculitis in adults and blindness is a common complication if left untreated. Oral glucocorticoids are the mainstay of treatment and if started promptly, loss of vision can usually be prevented. We present the case of a 77-year-old man who developed irreversible bilateral blindness after a confirmed diagnosis of GCA and oral steroid treatment. The roles of diagnostic delay, steroid dosing, significance of visual symptoms at diagnosis and after commencing oral glucocorticoids, and interpretation of ophthalmological signs are reviewed.

Background

Giant cell arteritis (GCA) is the most frequent vasculitis in adults and blindness is a common complication if left untreated. Major efforts have been made to increase the awareness of the disease and to emphasise the importance of prompt diagnosis and treatment initiation, especially in cases with ophthalmological involvement, as this is the most effective measure to avoid sight loss.^1–9

Current guidelines recommend prednisolone 40 mg/day in uncomplicated GCA and 60 mg/day or 500–1000 mg intravenous methylprednisolone in GCA complicated by visual or large artery involvement.^{3 4} It is well recognised that once treatment is initiated, symptoms and inflammatory markers should respond rapidly; if not, alternative diagnoses must be considered.^1–4

Our case is notable for the poor outcome with bilateral blindness.

Learning points are

1. The danger of a delayed GCA diagnosis.

2. The development of blindness after diagnosis and steroid initiation.

3. The significance of visual symptoms without ophthalmological signs in GCA.

Case presentation

A 77-year-old man with prior history of hypertension, coronary vein grafting and bladder cancer presented to the Accident & Emergency department with a 10-day history of worsening fronto-temporal headache, shoulder and neck stiffness, left jaw claudication, scalp tenderness and one episode of diplopia. He had consulted his general practitioner (GP) 4 days earlier who had sent him to a physiotherapist but had not noted any improvement.

He denied fever or weight loss. Physical examination with neurological and ophthalmological examinations and funduscopy were unremarkable. Head CT was normal; erythrocyte sedimentation rate was 75 mm/hour and C-reactive protein (CRP) was 295 mg/L. He was admitted to hospital and commenced on prednisolone 60 mg/day (equal to 1 mg/kg, given that the patient’s weight was 60 kg) for a suspicion of GCA with ophthalmological involvement. Following rheumatological and further normal ophthalmological examination, prednisolone was reduced to 40 mg/day (equal to 0.67 mg/kg) on the following day. Two days later, he complained of persistent headache and worsening eye symptoms with intermittent diplopia and blurred vision, 3–4 times per day, lasting for 30–60 min and disappearing at rest.

A third ophthalmological review found no signs of anterior ischaemic optic neuropathy (AION): with normal vision, ocular movements, colour vision, confrontation of visual fields and funduscopy. CRP fell to 136 mg/L and the patient was discharged on prednisolone 40 mg/day. A temporal artery biopsy (TAB) was requested.

Four days later, he experienced constant blurred vision and a darkening curtain over his right upper visual field that was progressing downwards from day to day and had started to appear on the left eye. Moreover, he reported three episodes of complete visual loss in the right eye and one in the left eye. He was advised to liaise with his optician as prior ophthalmological explorations had been unremarkable; however, oral prednisolone was increased to 60 mg/day. Hospital emergent review after another 4 days objectified vision loss and a CRP of 12 mg/L. Visual acuity was 6/9 in both eyes with an Ishihara score of 0/17 on the right and 4/17 on the left eye, a sluggish papillary reaction but a normal funduscopy with healthy discs, no swelling or haemorrhages. A TAB reported features of active GCA with multinucleated giant cells, a fibrous thickened intima and an almost obliterated lumen (figure 1). At this point, the patient was referred to the Vasculitis Service and started on intravenous methylprednisolone 500 mg/day for 3 days and intravenous cyclophosphamide 600 mg. CRP became normal. His vision continued to deteriorate to complete visual loss. Repeated funduscopy found no signs of AION.

Figure 1.

Left temporal artery biopsy. An H&E stained micrograph objective ×10 of a muscular artery showing focal chronic inflammation in media (black triangle), with intimal thickening (yellow line), stenosed lumen (black arrow), disrupted internal elastic lamina (blue arrow) and multinucleated giant cell (red arrow).

A summary of the evolution of his inflammatory markers, visual symptoms and the received steroid dose is depicted in figure 2.

Figure 2.

Chronological evolution of the inflammatory markers, the visual symptoms and the received steroid dose. Visual impairment is subjectively labelled as follows: 10%—intermittent diplopia once daily; 20%—intermittent diplopia and blurred vision 2–3 times daily; 40%—intermittent sight loss; 70%—sight loss of 70%; 80%—unable to read; 85%—needs help for dressing and bathing; 95%—distinguishes only rough shapes from one eye. Steroid dose is indicated in the subsequent horizontal bar. Intravenous doses are stressed with vertical arrows.

Investigations

Given the unusual ophthalmological presentation, an autoimmune screen, a head and neck magnetic resonance angiography (MRA) and an echocardiography were performed. The autoimmune screen was negative. The MRA was performed to exclude vascular occlusions in other territories and did not report any carotid or intracranial artery occlusion, intracerebral infarct, sign of restricted diffusion or microhaemorrhages, but reported focal stenosis of both vertebral arteries. The transthoracic echography was normal.

Differential diagnosis

• Other causes of artery occlusion: atherosclerotic, thromboembolic, dissection.

• Other types of vasculitis affecting the temporal artery: polyarteritis nodosa, granulomatosis with polyangiitis, cerebral vasculitis.

Outcome and follow-up

Subsequent cyclophosphamide infusions were contraindicated by lymphopaenia and thrombocytopaenia. After a short course of methotrexate, tocilizumab was commenced. Prednisolone dose was slowly reduced and was 30 mg/day 6 weeks after initial presentation. The patient remained almost blind, being only able to distinguish vague shades with his left eye, without other symptoms of GCA or inflammatory disease.

Discussion

High physician awareness, prompt diagnosis and treatment initiation in GCA are important to avoid disease-related damage, especially visual impairment.^1–10 Blindness continues to occur in 20% of GCA cases, although this rate is lower with early diagnosis.⁸ Our case was notable for the appearance of blindness despite repeated normal visual explorations and the fact that this occurred 3 weeks after diagnosis and initiation of prednisolone. Review of the patient’s course has identified several learning points that merit emphasis and may have influenced his outcome.

Diagnostic delay occurs because patients fail to seek medical advice or because their symptoms are not interpreted as suggesting GCA. Systems to support early GCA detection exist and this diagnosis should be considered in any patient with headache, temporal tenderness, polymyalgia or jaw claudication.^1–4 Oral prednisolone should be commenced and investigations ordered. Diagnosis should be confirmed by either TAB or temporal artery ultrasound.^1–4

Our patient had visual symptoms at diagnosis and these persisted after treatment initiation. Unfortunately, they were discounted due to repeated normal ophthalmological examinations. Ophthalmological nerve damage can occur in GCA without visual signs and with normal funduscopy. Once blindness occurs, treatment intensification is usually unsuccessful at restoring vision.^11–14 Going blind while on steroids is unusual in GCA although it has been described in up to 10% of GCA-associated eye damage.5–9 15–18 The patient presented with all the risk factors for GCA with ocular ischaemic complications, namely visual symptoms, jaw claudication, mild general symptoms, cardiovascular risk factors and an ESR on arrival between 70 and 100 mm/hour.11 17 19–22 Of note, amaurosis fugax is an important predictor of permanent visual loss, and hypertension is a risk factor for blindness and for other ischaemic complications such as stroke or large vessel involvement.^{23 24} Higher initial prednisolone doses should be considered in this setting, even in the absence of objective visual abnormalities on ophthalmological examination.

Management guidelines from the European League Against Rheumatism (EULAR) and British Society of Rheumatology (BSR) recommend oral prednisolone 60 mg/day or intravenous methylprednisolone 500–1000 mg/day for 3 days in GCA with visual signs or symptoms and moderate doses of 40 mg/day of prednisolone in uncomplicated GCA.^{3 4} It is important to stress that visual symptoms alone justify treatment with high-dose steroids. The results of ophthalmological assessment should not influence the therapeutic plan in patients with evolving visual symptoms.

Aspirin that has been associated with a reduced risk of ischaemic complications is now widely recommended as adjunctive treatment to steroids and was given in our patient.3 4 21 25–27

Cyclophosphamide, methotrexate and tocilizumab have been shown to reduce relapse risk and help steroid tapering but have not yet been shown to have additional benefit in initial disease treatment.1–4 28–31 Heparin at therapeutic doses has been reported in few case reports to be able to resolve ischaemic complications resistant to high-dose steroid treatment; however, larger studies or pathophysiological arguments for thrombosis in GCA are lacking.^{26 32 33}

In GCA, blindness is secondary to AION in more than 90% of the cases. This condition is diagnosed by a pale and swollen disc on funduscopy and choroidal hypoperfusion with fluorescein angiography. However, visual loss can be secondary to occlusion of the central artery of the retina, to an occipital stroke or, even more rarely, to posterior ischaemic optic neuropathy (PION).^11–14 Those latter cases also present with progressive vision alteration but are difficult to diagnose because funduscopy is normal in the initial setting and will only show a pale disc 4–8 weeks after the onset of visual symptoms. Signs seen at earlier stages are delayed afferent pupillary reaction (as in our case) and visual field abnormalities that sometimes can be subtle and missed on confrontation visual fields, hence need exploration with Goldmann perimeter testing. The management of GCA-related PION is similar to that of AION and prompt high-dose steroid treatment is mandatory to avoid further vision deterioration.^11–14 In the light of all these findings, a diagnosis of PION seems the most plausible for our patient.

In conclusion, our case demonstrates some of the complexities of GCA, in particular, the dissociation of visual symptoms from ophthalmological signs and the progression of visual loss despite prednisolone treatment. Detailed review of the patient’s course has identified several learning points relevant to GCA management.

Patient’s perspective.

Losing my eyesight so rapidly and completely has had a devastating effect and changed every aspect of my life. This is very challenging.

Why didn’t my GP follow NICE Guidelines for suspected GCA when I presented with all the typical symptoms? Should I have been given intravenous steroids rather than oral and should the steroid treatment have commenced sooner? Why were my concerns with regards to the ongoing deterioration of my eyesight not taken seriously? The fact that the eye clinic had refused to see me on two occasions and had repeatedly told me my eyes were fine left me reluctant to seek further medical help.

I hope that lessons can be learnt and that no one else has to go through the same ordeal.

Learning points.

• Prompt recognition of the symptoms of giant cell arteritis (GCA) is important to minimise diagnostic delay.

• Visual symptoms, even without signs, are a risk factor for permanent visual loss in GCA and should never be ignored.

• Risk factors for visual loss include visual symptoms, jaw claudication and cardiovascular risk factors.

• If a patient is at risk of visual complications, prednisolone 60 mg/day or intravenous methyl prednisolone is indicated and aspirin should be considered.

• Visual loss can occur after prednisolone initiation.

• Expert opinion should be sought when symptoms, signs or laboratory markers indicate ongoing active disease after initiation of prednisolone.