Temporal arteritis

Prognosis and complications
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By James Goodwin MD

Although the patient is often most interested in pain relief, the possibility of an ischemic complication is, for the physician, the most compelling component of temporal arteritis. Because it is impossible to know when an ischemic event might occur, it is necessary to make the diagnosis and initiate corticosteroid treatment quickly.

The most common ischemic complications of temporal arteritis involve the eye and vision. In an earlier review of large series, I found that visual loss occurs in a third to half of patients (Goodwin 1980). Sudden total binocular blindness has been reported, and in many cases the second eye becomes involved only hours to days after the first ischemic event. The threat of rapid progression to binocular blindness constitutes the emergency in treatment of temporal arteritis. Some clinicians believe that simultaneous occurrence of ischemic optic neuropathy and central retinal artery occlusion in the same eye or in opposite eyes is pathognomonic for temporal arteritis. Multiple attacks of amaurosis fugax alternating between eyes are also a strong indicator of temporal arteritis and do not often occur in atherosclerotic carotid artery disease. Most ischemic visual events occur after several weeks of symptoms, but usually less than 6 months from onset of symptoms.

Font and colleagues found that among 146 patients with biopsy proven temporal arteritis, 23 (15.75%) had visual loss (Font et al 1997). All of the patients who lost vision had had classic symptoms of temporal arteritis for an average of 1.3 months or of polymyalgia rheumatica for an average of 10.8 months prior to vision loss. Also, it is important to note that 65.2% of these patients had had premonitory visual symptoms for an average of 8.5 days prior to permanent vision loss. These statistics provide support for the urgency of correct diagnosis and prompt initiation of treatment in temporal arteritis and in polymyalgia rheumatica.

In a study of 90 biopsy-positive cases of temporal arteritis, univariate analysis showed that the most common risk factors for progressive visual loss were older age, elevated C-reactive protein, and disc swelling (Loddenkemper et al 2007).

The most frequent cause of blindness in temporal arteritis is anterior ischemic optic neuropathy, but central retinal artery occlusion accounts for a significant number of blind eyes, sometimes in conjunction with anterior ischemic optic neuropathy. In 1958 Wagener and Hollenhorst studied 100 affected eyes in 58 patients at the Mayo Clinic and found anterior ischemic optic neuropathy in 64% of the eyes and ischemic changes in the distribution of the central retinal artery in 7% (Wagener and Hollenhorst 1958). In that series a total of 54 of 122 (44%) had visual impairment from temporal arteritis. Thirty years later, Caselli and colleagues found permanent visual loss in only 14 of 166 (8.4%) of biopsy-positive patients in the Mayo Clinic cohort, of whom 12 lost vision in 1 eye and 2 in both (Caselli et al 1988). The incidence of visual complications was assessed in a population-based study of temporal arteritis in Denmark (Fledelius and Nissen 1992). Ten of 264 (3.8%) patients with temporal arteritis from a county sample and a hospital-based series had significant visual impairment. The authors acknowledged that the rate of visual impairment is lower than in published series from other parts of the world. They also speculate that the diagnosis is made earlier in Denmark and that early steroid treatment may be preventing permanent complications in more patients than elsewhere.

An important long-term prospective study of 170 patients between 1973 and 1995 was reported by Hayreh. Fifty percent of the patients presented with visual symptoms, of which 97.7 had vision loss, 30% amaurosis fugax, and 6% diplopia. Of those with vision loss, the etiology was anterior ischemic optic neuropathy in 81%, central retinal artery occlusion in 14%, cilioretinal artery occlusion in 22% (12 of 55 patients with fluorescein angiogram), posterior ischemic optic neuropathy (disc not swollen) in 7%, and ocular ischemia in 1 patient (Hayreh et al 1998). Retabulation of 114 eyes in 84 consecutive patients from the same clinic between 1974 and 1999 indicated anterior ischemic optic neuropathy in 91%, central retinal artery occlusion in 10.5%, cilioretinal artery occlusion in 10%, and posterior ischemic optic neuropathy (no disc edema acutely) in 4% either alone or in different combinations (total >100) (Hayreh et al 2002). Galor and Lee provide a well-documented case of slowly progressive blindness in 1 eye secondary to choroidal ischemia in a 93 year old man with biopsy positive giant cell temporal arteritis who happened to be on Coumadin for atrial fibrillation. After a month, vision in that eye had dropped to finger counting but returned to 20/50 a day after treatment with IV solumedrol (methylprednisolone) was begun. The authors suggest the rate of visual progressive loss may have been slowed because of the Coumadin and cite other references suggesting a beneficial effect of anticoagulation for visual loss in temporal arteritis (Galor and Lee 2006).

The incidence of visual complications in any cohort of patients with temporal arteritis is subject to tremendous potential bias from many factors. For instance, a review of 47 patients with biopsy positive temporal arteritis done at an ophthalmologic hospital in Switzerland found vision loss in 33 patients (70%). Obviously, the denominator in their fraction, the patients referred to an eye hospital are likely to include an inflated percent with eye complications. Of the 33 patients with vision loss, 22 (66%) had anterior ischemic optic neuropathy and 7 (21%) had central retinal artery occlusion, consistent with earlier series.

Anterior ischemic optic neuropathy presents with sudden visual loss, commonly with "altitudinal" or upper and lower-half loss of visual field and pale swelling of the optic nerve head. A rare posterior ischemic optic neuropathy presents with the same visual deficit but with no optic disc edema.

The physiologic cup is a normal depression in the central surface of the optic disc that is typically enlarged in glaucoma (cupping of the disc). Various reports have described cupping as a late manifestation of anterior ischemic optic neuropathy. In a review of fundus photographs, the size of the physiologic cup was compared between 2 groups of patients with anterior ischemic optic neuropathy: 92 patients with arteritic anterior ischemic optic neuropathy and 102 patients with nonarteritic anterior ischemic optic neuropathy. Cupping was present in 92% of eyes with arteritic disease and in only 2% of eyes with nonarteritic disease (Danesh-Meyer et al 2001).

Central retinal artery occlusion is characterized by sudden loss of visual function, either with total blindness or with predilection for the upper or lower altitudinal half visual field, as in ischemic optic neuropathy. During the first few minutes blood flow may cease in the arteries, leaving only the appearance of white threadlike "ghost" vessels until flow is reestablished, usually within just a few minutes. The fundus may then appear normal despite ongoing blindness or dense visual field loss. Within 12 to 24 hours the infarcted inner retinal layers develop edema that appears white and opaque, obscuring retinal vessel segments and underlying structures. The edema is often most apparent at the fovea, which appears unnaturally red against the surrounding abnormally white retina. This is because the retina is thin at the fovea and the whiteness is much less intense there. This appearance has been called the relative cherry red spot. Within 2 to 3 weeks the retinal edema fades, leaving the fundus looking relatively normal again. Within a few months Wallerian degeneration of axons in the retinal nerve fiber layer reaches the optic nerve head, causing pallor and loss of capillaries that accompany atrophy of the neural tissue.

Temporal arteritis may cause ischemia of the entire globe, either unilateral or bilateral; this may be refractory, even to intensive treatment with pulse intravenous methylprednisolone followed by high-dose oral prednisone treatment (Hwang et al 1999).

Caselli and colleagues analyzed the neurologic complications in 166 consecutive cases of biopsy-proven temporal arteritis at the Mayo Clinic and found that overall 31% of the patients followed for a median of 17 months (ranging from 15 to 19 months) had some form of neurologic impairment, either transient or permanent (Caselli et al 1988). They found a total of 5 (3%) patients who had brain infarction, 3 in the carotid artery distribution and 2 vertebrobasilar. The authors comment that this hardly exceeds the expected rate of cerebral infarction from atherosclerosis in the age group of the cohort, and that the relation to arteritis remains unproved. Large-artery disease, defined as the presence of bruit or diminished pulse amplitude, was found in 54 patients. The carotid arteries were affected in 31, upper limb arteries in 29, and lower limb arteries in 15. This relative frequency follows closely the distribution of arterial involvement demonstrated in an autopsy study of patients with polymyalgia rheumatica reported by Ostberg (Ostberg 1973) and in the accompanying clinical analysis by Hamrin (Hamrin 1972). A retrospective analysis of stroke among 98 patients with giant cell arteritis at a single hospital found that stroke had occurred at initial presentation in 6 patients, 3 of which involved the vertebrobasilar territory, and there were no additional strokes during follow-up of these patients (Zenone and Puget 2013).

Pupillary dilatation is sometimes encountered in temporal arteritis, usually from ischemia involving the third cranial nerve. Prasad and colleagues describe isolated pupillary mydriasis in an 85-year-old man who had biopsy-positive temporal arteritis with the development of denervation supersensitivity with meiosis in response to 0.125% pilocarpine. The patient also had segmental pupillary sphincter involvement, and the overall picture was most consistent with tonic pupil. The authors favor ischemia of the ciliary ganglion or the postganglionic parasympathetic fibers as the etiology (Prasad et al 2009).

The Mayo Clinic group studied the patterns of tissue-specific inflammatory response in a group of 23 patients with typical inflammatory lesions in temporal artery specimens (Weyand et al 1997). They found that those with ischemic complications expressed higher concentrations of IFN gamma mRNA (P=0.008) and IL-1 beta mRNA (P=0.02). Formation of giant cells was associated with local synthesis of IFN gamma (P=0.003). Tissue from patients with concomitant polymyalgia rheumatica had higher levels of IL-2 mRNA transcripts (P=0.001). In a preliminary way, this work shows that the characteristics of the inflammatory lesion may, in the future, allow patients to be chosen for more intense treatment based on patterns of inflammatory response that indicate a higher likelihood of developing ischemic complications. Along these same lines, a study of a group of 36 patients with temporal arteritis from Barcelona found relatively higher expression of interleukin-1beta, tumor necrosis factor alpha and interleukin-6 mRNA in temporal arteries from patients who went on to have longer time to first remission on steroids, higher steroid dose requirements, and longer required duration of steroid treatment (Hernandez-Rodriguez et al 2004).

Various measures of neovascularization or ischemia induced angiogenesis in patients with temporal arteritis have shown that higher levels of this response to ischemia correlated significantly with having fewer ischemic complications. This suggests that the capacity to mount vigorous new vessel formation may be an effective compensatory mechanism in temporal arteritis (Cid et al 2002).

Death from ischemia in temporal arteritis is rare but has been reported on occasion, usually from vertebral artery occlusion and brainstem infarction or from coronary occlusion and myocardial infarction (Sheehan et al 1993; Freddo et al 1999). A particularly dramatic death was reported secondary to aortoduodenal fistula that developed in a patient with temporal arteritis (Lagrand et al 1996). Though death from temporal arteritis is dramatic and usually precipitates a case report, an epidemiologic study indicated that life expectancy of patients with temporal arteritis is not significantly less than that of age-matched controls (Matteson et al 1996). An analysis of the Mayo Clinic series of patients with temporal arteritis followed over the past 50 years found 46 incident cases of large-artery complications among 168 patients in the cohort. These complications included 30 cases of aortic aneurysm and 21 cases of large artery stenosis (Nuenninghoff et al 2003a). In general, the survival in this group of temporal arteritis patients with large vessel complications was not different from the total group of temporal arteritis patients. The exception was the development of aortic dissection, which markedly increased mortality (Nuenninghoff et al 2003b).

The presence of traditional risk factors for atherosclerosis at the time of temporal arteritis diagnosis was found to significantly increase the risk of developing an ischemic complication, especially hypertension (Gonzalez-Gay et al 2004b).

The incidence of aortic aneurysm is dramatically increased in patients with temporal arteritis as compared with an age-matched general population. Gonzalez-Gay and colleagues found that 20 (9.5%) of 210 biopsy-proven temporal arteritis patients in northwestern Spain had aortic aneurysms (16 thoracic and 6 abdominal). The population incidence of aortic aneurysm and dissection in their region was 18.9 per 1000 person years at risk, which was similar to that in Olmsted County as published by the Mayo Clinic group. Hypertension and polymyalgia rheumatica with a marked inflammatory response at the time of diagnosis were the most predictive characteristics for later development of aortic disease (Gonzalez-Gay et al 2004a).

Another study from Spain involved a cohort of 54 patients with biopsy-proven giant cell arteritis who were screened for aortic structural damage, and significant damage was found in 12 patients (22.5%) after a median follow-up of 5.4 years after initial diagnosis (Garcia-Martinez et al 2008). Prospective follow-up of the 36 remaining patients from this original group of 54 giant cell arteritis patients was carried out with repeat aortic screening every 4 years for a median of 10.3 years (Garcia-Martinez et al 2013). Thirty-six patients were screened a second time, and 14 were available for a third screening at 8 years. Twelve (33.3%) of the 36 patients had developed aortic structural damage, all but one in the thoracic aorta at final screening. Ascending and descending aortic diameters significantly increased over time. One patient died from aortic dissection. The authors concluded that aortic structural damage is maximal within the first 5 years of diagnosis but continues over time, and dilatation continues, but without persistence of detectable disease activity. Surgical repair of these arteritic aortic aneurysms is extremely hazardous but can be carried out successfully (Atluri and Woo 2007).

Marie and co-workers reviewed records at the Internal Medicine Department of the University of Rouen and found 66 patients with nonatherosclerotic aortic complications, including aortitis, aortic ectasia, and aortic aneurysm; of these, 48 had associated temporal arteritis (Marie et al 2009). Seventy-seven percent of these arteritic cases were without symptoms referable to the aorta (no dysphagia, dyspnea, thoracic or abdominal pain, or back pain). Aortic helical computed tomography demonstrated either isolated aortitis manifest by circumferential thickening of the aortic wall in 41 cases, aortitis with aortic ectasia in 3 cases, and aortic thoracic aneurysm with thoracic and abdominal aortitis in another 3 cases. One case had both aortic abdominal aneurysm and aortitis. Aortitis was most commonly identified at the time of temporal artery diagnosis (41 cases) but was identified after initial diagnosis in 7 patients. After 6 months of treatment, 34 cases had repeat aortic helical computed tomography. This demonstrated complete disappearance of aortitis in nearly 9%, improved aortitis in 47%, unchanged findings in 41%, and deterioration of aortic thoracic aneurysm in 1 patient. Because of the high prevalence of potentially catastrophic aortic involvement, the authors recommend screening with aortic helical computed tomography on an annual basis.

An analysis of the prevalence, timing, and characteristics of relapses in patients with temporal arteritis in a cohort of 106 patients followed longitudinally for 7.8 ± 3.3 years (Alba et al 2014). Sixty-eight patients (64%) had at least 1 relapse, and 38 patients (36%) had 2 or more. First relapse was characterized as polymyalgia rheumatic in 51%, cranial symptoms in 31%, and systemic symptoms in 18%. Relapses occurred predominantly in the first 2 years of treatment. The time required to achieve maintenance prednisone dosages was significantly longer, and the cumulative prednisone dose required during the first treatment year was significantly higher in patients with relapses than those without.

In This Article

Historical note and nomenclature
Clinical manifestations
Clinical vignette
Pathogenesis and pathophysiology
Differential diagnosis
Diagnostic workup
Prognosis and complications
References cited