|Year : 2023 | Volume
| Issue : 1 | Page : 3
Giant cell arteritis: Is there a link between ocular and systemic involvement?
Mariana G Portela1, Marta R Correia1, Margarida L Baptista1, Carolina P Bruxelas1, Daniel Pinto2, João M Costa1
1 Department of Ophthalmology, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
2 Department of Pathology, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
|Date of Submission||30-Nov-2022|
|Date of Decision||12-Dec-2022|
|Date of Acceptance||14-Dec-2022|
|Date of Web Publication||19-Feb-2023|
Mariana G Portela
Rua da Junqueira, 126, 1349-019 Lisbon
Source of Support: None, Conflict of Interest: None
Introduction: Giant cell arteritis (GCA) is a systemic disease that may cause severe visual loss. Our purpose was to determine which factors contribute to ocular manifestations (OMs) in patients with temporal artery biopsy-proven GCA.
Methods: This was a retrospective review of all cases diagnosed in our center from 2010 to 2021 (>6 months follow-up). We analyzed demographic data, comorbidities, type and duration of symptoms before diagnosis, ocular features, and systemic and laboratory findings.
Results: Out of 51 patients (60.8% females, mean age 74.8 ± 13.5), 32 (63%) had OM, of whom 28% had transient visual loss, 69% had permanent visual loss, and 9% had diplopia. Apart from scalp tenderness (P = 0.039), OM did not correlate with other ischemic symptoms such as jaw claudication or headache and were even significantly associated with the absence of fever (P = 0.026). Patients with OM also showed lower values of C-reactive protein (CRP) (P = 0.045).
Conclusion: In our sample, visual involvement was not significantly associated with any systemic symptom apart from scalp tenderness, which highlights the importance of having a high index of suspicion for GCA in an ophthalmology setting, especially in older patients with visual loss. Furthermore, OMs were significantly associated with the absence of fever and lower values of CRP which may suggest a lower inflammatory state may in these patients.
Keywords: Amaurosis fugax, anterior ischemic optic neuropathy, biopsy, giant cell arteritis, temporal arteries
|How to cite this article:|
Portela MG, Correia MR, Baptista ML, Bruxelas CP, Pinto D, Costa JM. Giant cell arteritis: Is there a link between ocular and systemic involvement?. Pan Am J Ophthalmol 2023;5:3
|How to cite this URL:|
Portela MG, Correia MR, Baptista ML, Bruxelas CP, Pinto D, Costa JM. Giant cell arteritis: Is there a link between ocular and systemic involvement?. Pan Am J Ophthalmol [serial online] 2023 [cited 2023 Mar 21];5:3. Available from: https://www.thepajo.org/text.asp?2023/5/1/3/369998
| Introduction|| |
Giant cell arteritis (GCA) is the most common idiopathic systemic vasculitis affecting large- and medium-sized arteries in adults over the age of 50 years., The estimated incidence for people over 50 is 3.2 to 5.8/100,000, but it varies according to region, gender, and age., This condition is typically characterized by a systemic presentation, including headache, jaw claudication, scalp tenderness, and constitutional symptoms., However, it may also be accompanied and sometimes preceded by ophthalmologic manifestations such as visual loss., Furthermore, 20% of GCA cases with permanent visual loss do not present with systemic symptoms. When left untreated, it may lead to severe consequences, including visual loss of the other eye or even death.,, Thereby, the ophthalmologist's prompt recognition of this disease may avoid bilateral ocular involvement and improve general systemic prognosis. A clear connection between ocular and systemic manifestations has not been demonstrated, and if existing, it could help clinicians to be more aware of possible ophthalmologic involvement in some instances.
Our purpose was, therefore, to determine if and which factors contribute to, or are associated with, ocular manifestations (OMs) in patients with temporal artery biopsy (TAB)-proven GCA.
| Methods|| |
This was a comparative retrospective study performed between 2010 and 2021. In collaboration with the pathology department, we collected and reviewed the medical records of all patients diagnosed with a GCA proved by TAB. Patients with a follow-up inferior to 6 months or a GCA diagnosis based on other diagnostic methods were excluded. Two subgroups were then created and compared: patients with GCA with OM and patients with GCA without OM.
We analyzed the following data: patient demographics (gender, age at diagnosis, and race); previous medical history, including diabetes mellitus, arterial hypertension, obesity, chronic obstructive pulmonary disease, chronic kidney disease, obstructive sleep apnea, thyroid disease, and cardiovascular disease; type and duration of ocular and systemic symptoms before diagnosis; ocular examination at the time of diagnosis and after at least six months of follow-up including best corrected visual acuity (BCVA), slit-lamp and ocular fundus examination, color perception test, intraocular pressure, relative afferent pupillary defect, optical coherence tomography, and visual field testing; and systemic and laboratory findings at the time of diagnosis including body temperature, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and hemoglobin levels, and platelet count.
Systemic symptoms of GCA included headache, localized or diffuse scalp tenderness, jaw or tongue claudication, fatigue, fever (reported by the patient), weight loss, anorexia, and complaints of polymyalgia rheumatica, such as shoulder pain or stiffness, pelvic pain or stiffness, and bilateral aching neck. Body temperature was measured at diagnosis and registered. Fever was defined as an oral or axillary temperature above 37.6°C or an ear temperature above 38.1°C.
The following were considered OMs of GCA: episodes of amaurosis fugax with no other apparent cause, such as carotid or cardioembolic disorders, migraine, occipital seizure, papilledema, optic disc drusen, or intermittent angle-closure glaucoma; visual loss or visual field defects secondary to arteritic anterior ischemic optic neuropathy, posterior ischemic optic neuropathy, central retinal artery occlusion, ocular ischemic syndrome, cilioretinal artery occlusion, or choroidal infarction; and diplopia.
| Results|| |
We included 51 patients diagnosed with a TAB-proven GCA. Among these, 60.8% were females, 92.2% were white, and the mean age was 76.37 ± 8.22 years. Thirty-two patients (62,7%) presented with OMs related to GCA. On average, patients with ocular involvement were 3.53 years older (P = 0.143). In addition, both groups had no difference regarding sex (P = 0.514) or race (P = 0.205). Demographic data are summarized in [Table 1].
Previous medical history
The previous medical history of all patients is summarized in [Table 2]. Arterial hypertension was the most common systemic comorbidity in both groups, followed by diabetes mellitus and dyslipidemia. There was no significant difference in the prevalence of systemic comorbidities between both groups.
|Table 2: Previous medical history of all patients with giant cell arteritis|
Click here to view
Temporal headache was the most common systemic symptom at presentation in both the groups, followed by jaw claudication. Scalp tenderness was reported significantly more frequently by patients with OM (P = 0.028). There was no difference between the two groups in terms of the prevalence of other systemic symptoms. [Table 3] summarizes these findings.
|Table 3: Systemic symptoms at presentation of all patients with giant cell arteritis|
Click here to view
The average time between the appearance of the first symptom and the diagnosis of GCA was 22.6 days (median 5.5 days) for patients with OM and 39.8 days (median 30 days) for patients without OM (P = 0.194).
Laboratory and systemic findings
CRP levels were 13.35 mg/mL higher on average in patients without OM (P = 0.045). Other laboratory findings revealed no significant differences. Furthermore, significantly more patients without OM presented with a fever (P = 0.026). [Table 4] compares the laboratory and systemic results of the two groups.
Ocular symptoms and findings
Permanent visual loss was the most common ocular symptom among patients with OM, followed by transient visual loss. Three patients reported diplopia, and three more reported a visual field defect. Most patients with permanent visual loss presented with a BCVA of less than 20/125 (n = 21, 95.5%), and in no case did it improve during follow-up. At the fundoscopic examination, the most common diagnosis was anterior ischemic optic neuropathy (n = 20, 62.5%). Posterior ischemic optic neuropathy was diagnosed in 2 cases, and both initially presented with a normal fundoscopy that evolved to optic atrophy during follow-up. Another three patients had a central retinal artery occlusion, which was diagnosed based on fundoscopic appearance with retinal whitening and a cherry red spot that later progressed to inner retina atrophy. There was no patent cilioretinal artery in any of these cases, and all had a BCVA of less than 20/100. Finally, one patient was identified as having ocular ischemic syndrome. In this case, Doppler ultrasound imaging excluded hemodynamically significant internal carotid artery stenosis. [Table 5] describes the visual symptoms and fundoscopic diagnosis of all patients with OM.
Six patients had bilateral OM (19%) either with an initial bilateral presentation or a documented sequential bilateral involvement (n = 2). In all cases of initial bilateral presentation, the fundoscopic examination revealed that one eye had been affected first, presenting in most cases with an already established optic nerve atrophy.
Systemic corticosteroid therapy was administered to all patients.
| Discussion|| |
Our study identified 51 patients with GCA, proved by a positive TAB. Among these, 32 individuals (63%) presented with OM. Patients without OM were younger, which is consistent with the literature., The influence of sex, however, is still contradictory. In our sample, we did not find significant differences between both groups. Male sex has, nevertheless, been proposed as both a risk factor 15 and a protective factor for cranial ischemic complications in GCA.
The link between OM and systemic diseases in GCA has yet to be established. All of the systemic disorders we investigated had no increased prevalence in any group, including diseases associated with increased cardiovascular risk, such as arterial hypertension, diabetes, and dyslipidemia.
In our work, patients with OMs were more likely to complain of scalp tenderness (P = 0.028). Other systemic symptoms have been associated with higher probability of ocular involvement such as headache and our sample demonstrated a similar trend. Other constitutional symptoms were not significantly different between groups, supporting the need to suspect possible ocular involvement in all cases of GCA.
Patients without OM had significantly higher levels of CRP (P = 0.045) and a greater chance of having a fever (P = 0.026). High CRP level has been associated with a reduced risk of permanent visual loss in other works., The absence of fever has also been associated with an increased risk of cranial ischemic complications. The association of lower inflammatory markers with the absence of OM may lie within the tendency of patients without OM being younger, thus having more ability to mount an inflammatory response. In the sample from Hayreh et al., patients without OMs had higher levels of ESR, which the same reason may explain.
We also found that patients with OM sought medical care faster. This is probably due to the panic felt by patients with vision loss. In future studies, it could be interesting to understand if patients with OM have a better systemic prognosis.
In our sample, the permanent visual loss was mainly caused by anterior ischemic optic neuropathy. This is still a significant cause of visual loss in GCA. Despite systemic corticosteroid therapy, no patient improved their BCVA during follow-up. However, we believe that high-dose corticosteroids should be urgently started when the suspicion of GCA arises without waiting for the TAB results. Furthermore, nine patients presented with transient visual loss, and six patients demonstrated a normal retina and optic nerve at fundoscopy, although later having a positive TAB. Cases such as these support that amaurosis fugax is a threatening symptom commonly associated with GCA and often progresses to permanent visual loss.,
Furthermore, TAB is still considered the gold standard for diagnosing GCA. However, other diagnostic methods, such as Doppler ultrasonography of the temporal artery, magnetic resonance, computed tomography angiography, and 18F-fluorodeoxyglucose positron-emission tomography, may be helpful in the diagnosis of large-vessel vasculitides, such as GCA.,, By choosing to exclude patients that had not been submitted to TAB, we probably failed to include some individuals that had had the disease. Furthermore, there is evidence in previous studies that the likelihood of receiving a positive TAB is higher in patients with OM, which could also bias our results.,
To conclude, GCA remains an essential diagnosis in the ophthalmology clinic with devastating symptoms and signs and often with a poor prognosis. The ophthalmologist must have a high index of suspicion for this entity, even in the absence of characteristic systemic features. OMs of GCA vary widely and may associate with misleading findings such as lower values of CRP and the absence of fever. Raising awareness for this disorder among ophthalmologists is decisive.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bengtsson BA, Malmvall BE. The epidemiology of giant cell arteritis including temporal arteritis and polymyalgia rheumatica. Incidences of different clinical presentations and eye complications. Arthritis Rheum 1981;24:899-904.
Carroll SC, Gaskin BJ, Danesh-Meyer HV. Giant cell arteritis. Clin Exp Ophthalmol 2006;34:159-73.
Dunstan E, Lester SL, Rischmueller M, Dodd T, Black R, Ahern M, et al.
Epidemiology of biopsy-proven giant cell arteritis in South Australia. Intern Med J 2014;44:32-9.
Catanoso M, Macchioni P, Boiardi L, Muratore F, Restuccia G, Cavazza A, et al.
Incidence, prevalence, and survival of biopsy-proven giant cell arteritis in Northern Italy during a 26-year period. Arthritis Care Res (Hoboken) 2017;69:430-8.
Kawasaki A, Purvin V. Giant cell arteritis: An updated review. Acta Ophthalmol 2009;87:13-32.
Hayreh SS, Podhajsky PA, Raman R, Zimmerman B. Giant cell arteritis: Validity and reliability of various diagnostic criteria. Am J Ophthalmol 1997;123:285-96.
Tovilla-Canales JL. Ocular manifestations of giant cell arteritis. Curr Opin Ophthalmol 1998;9:73-9.
Gordon LK, Levin LA. Visual loss in giant cell arteritis. JAMA 1998;280:385-6.
Chen JJ, Leavitt JA, Fang C, Crowson CS, Matteson EL, Warrington KJ. Evaluating the incidence of arteritic ischemic optic neuropathy and other causes of vision loss from giant cell arteritis. Ophthalmology 2016;123:1999-2003.
Danesh-Meyer H, Savino PJ, Gamble GG. Poor prognosis of visual outcome after visual loss from giant cell arteritis. Ophthalmology 2005;112:1098-103.
Graham E, Holland A, Avery A, Russell RW. Prognosis in giant-cell arteritis. Br Med J (Clin Res Ed) 1981;282:269-71.
Liu GT, Glaser JS, Schatz NJ, Smith JL. Visual morbidity in giant cell arteritis. Clinical characteristics and prognosis for vision. Ophthalmology 1994;101:1779-85.
Hayreh SS, Podhajsky PA, Zimmerman B. Ocular manifestations of giant cell arteritis. Am J Ophthalmol 1998;125:509-20.
Liozon E, Loustaud-Ratti V, Ly K, Soria P, Vidal E, Boutros-Toni F, et al.
Visual prognosis in extremely old patients with temporal (giant cell) arteritis. J Am Geriatr Soc 2003;51:722-3.
Salvarani C, Cimino L, Macchioni P, Consonni D, Cantini F, Bajocchi G, et al.
Risk factors for visual loss in an Italian population-based cohort of patients with giant cell arteritis. Arthritis Rheum 2005;53:293-7.
Nesher G, Berkun Y, Mates M, Baras M, Nesher R, Rubinow A, et al.
Risk factors for cranial ischemic complications in giant cell arteritis. Medicine (Baltimore) 2004;83:114-22.
Liozon E, Dalmay F, Lalloue F, Gondran G, Bezanahary H, Fauchais AL, et al.
Risk factors for permanent visual loss in biopsy-proven giant cell arteritis: A study of 339 patients. J Rheumatol 2016;43:1393-9.
Liozon E, Herrmann F, Ly K, Robert PY, Loustaud V, Soria P, et al.
Risk factors for visual loss in giant cell (temporal) arteritis: A prospective study of 174 patients. Am J Med 2001;111:211-7.
González-Gay MA, García-Porrúa C, Llorca J, Hajeer AH, Brañas F, Dababneh A, et al.
Visual manifestations of giant cell arteritis. Trends and clinical spectrum in 161 patients. Medicine (Baltimore) 2000;79:283-92.
Gonzalez-Gay MA. The diagnosis and management of patients with giant cell arteritis. J Rheumatol 2005;32:1186-8.
Schmidt WA, Kraft HE, Vorpahl K, Völker L, Gromnica-Ihle EJ. Color duplex ultrasonography in the diagnosis of temporal arteritis. N Engl J Med 1997;337:1336-42.
Bley TA, Reinhard M, Hauenstein C, markl M, Warnatz K, Hetzel A, et al.
Comparison of duplex sonography and high-resolution magnetic resonance imaging in the diagnosis of giant cell (temporal) arteritis. Arthritis Rheum 2008;58:2574-8.
Quinn KA, Ahlman MA, Malayeri AA, Marko J, Civelek AC, Rosenblum JS, et al.
Comparison of magnetic resonance angiography and (18) F-fluorodeoxyglucose positron emission tomography in large-vessel vasculitis. Ann Rheum Dis 2018;77:1165-71.
Robb-Nicholson C, Chang RW, Anderson S, Roberts WN, Longtine J, Corson J, et al.
Diagnostic value of the history and examination in giant cell arteritis: A clinical pathological study of 81 temporal artery biopsies. J Rheumatol 1988;15:1793-6.
Domínguez-Castellano A, Peña JM, Barbado FJ, González JJ, Madero R, León L, et al.
Usefulness of temporal artery biopsy: Analysis of 100 cases. Med Clin (Barc) 1989;92:81-5.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]