Morvan syndrome and related disorders associated with CASPR2 antibodies
Jan. 18, 2022
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Temporal arteritis is the most common form of systemic vasculitis in the elderly. The etiology is unknown. Temporal arteritis can result in systemic, neurologic, and ophthalmological complications. When it presents as arteritic ischemic optic neuropathy, it becomes a true visual emergency, as the other eye may become involved within days if not treated promptly. In addition, if left untreated, these patients are at increased risk for ischemic stroke. High-dose corticosteroids are the mainstay of acute and chronic treatment. Other adjunctive immunosuppressants are also used as steroid-sparing agents. In this update, the author reviews advances in diagnosis and treatment for temporal arteritis.
• Temporal arteritis is a systemic vascular disease in which inflammation, usually with giant cells, affects the internal elastic lamina, adventitia, and adjacent media of medium and large arteries with a predilection for those in the head and neck.
• It is a disease almost exclusively in the elderly (older than 60 years) and usually presents with headache along with manifestations of ischemia in tissues of the head including most commonly pain, ulceration, and necrosis involving the scalp and oral mucosa.
• Ischemia of the temporalis and masseter muscles produces a distinctive syndrome called jaw claudication with crescendo pain in the mandibular region while chewing solid food and gradual relief after cessation of muscular activity in the involved muscles.
• The most common serious complication is vision loss from ischemic optic neuropathy or central retinal artery occlusion.
• Ischemic stroke can occur secondary to emboli from involved extracranial carotid and vertebral arteries.
• Serious complications can be prevented by treatment with systemic corticosteroids in adequate doses over prolonged periods.
Credit for the earliest complete description of temporal arteritis must be accorded to Horton and colleagues from the Mayo Clinic. The following is their succinct clinical description derived from examining 2 patients:
Both patients were admitted to the Clinic in the spring of 1931 because of fever, weakness, anorexia, loss of weight, anemia, mild leukocytosis, and painful, tender areas over the scalp and along temporal vessels. These manifestations had been present for 4 weeks to 6 weeks. Temporal artery biopsy in these 2 cases yielded granulomatous arteritis and periarteritis (25).
Since this report, temporal artery biopsy has remained as the mainstay of pathologic diagnosis.
Another painful syndrome, now called "polymyalgia rheumatica," shares with temporal arteritis the strong predilection for the elderly and the association with signs and symptoms of systemic illness (04). In the mid-1950s, the concept that temporal arteritis and polymyalgia rheumatica are 2 clinical manifestations of the same basic disease process was introduced (41). Hamrin and Ostberg both provided landmark publications, the former reporting his series of 93 cases of polymyalgia rheumatica with analysis of the relationship with temporal arteritis and underlying vascular pathology, and the latter reporting an autopsy study that revealed the link between the clinical syndrome called "polymyalgia rheumatica and giant cell arteritis of the aorta and its main branches" (21; 40).
According to the American College of Rheumatology 1990 criteria, patients must meet 3 of the following 5 criteria to qualify for diagnosis of giant cell arteritis: (1) age over 50 years; (2) new onset of localized headache; (3) temporal artery tenderness or decreased temporal artery pulse; (4) erythrocyte sedimentation rate greater than or equal to 50 mm/hour; or (5) positive temporal artery biopsy (26). A study of a cohort of 112 patients was performed to determine whether these criteria can accurately establish the diagnosis of giant cell arteritis without performing temporal artery biopsy (37). The authors concluded that temporal artery biopsy is indicated in all patients suspected of having giant cell arteritis.
New headache or dramatic change in pattern of longstanding headache in an elderly patient is the most common presentation of temporal arteritis. The pain may have a local component along the temporal and other external carotid branches, but often the character of the headache is nonspecific (20). Severity of the headache can be variable. Some patients describe "head pains" rather than headache, indicating the relatively superficial character of the discomfort (41).
Momentary stabbing or ice pick headache accompanying new-onset persistent headache in an elderly person may be a useful indicator of temporal arteritis as the cause (45). Incidence of headache in temporal arteritis was about 80% in a large series, reinforcing that one cannot dismiss the diagnosis entirely in the absence of headache.
Diffuse tenderness of the scalp, face, or oral mucosa results from ischemia secondary to widespread arteritic involvement of extracranial vessels. Patients should be asked if they are experiencing new tenderness when they comb their hair, or if a hat or the temple pieces of their glasses are causing new pain in 1 or both temples.
Pain and ulceration of the oral mucosa tongue or scalp is an especially useful sign favoring temporal arteritis. Scalp necrosis and ulceration can be mistaken for herpes zoster. Ischemia of the tongue can be misdiagnosed as glossitis with beefy enlargement and loss of taste sensation.
Jaw claudication is nearly pathognomonic for temporal arteritis. Both the internal and external carotid systems must be affected together to produce jaw claudication, as each system provides collateral flow to the other when occlusive disease involves only 1 system. Jaw claudication must be distinguished from other causes of pain around the lower face and dentition. The pain of claudication builds progressively with the muscular activity of chewing rather than occurring with the pressure of biting down, whereas dental pain occurs even with the first bite and pain occurs with any jaw movement with pathology in the temporomandibular joint. As with claudication elsewhere, the pain is relieved with rest and usually requires at least a few seconds to dissipate when the patient stops chewing. Careful history taking is the only way to elicit these fine points and correctly identify claudication or ischemia as the mechanism of pain.
Visual loss is usually unilateral and occurs within weeks to less than 6 months from onset of symptoms. In an earlier review of a large series, it was found that visual loss occurs in a third to half of patients (17).
Involvement of the contralateral eye can happen within days to weeks, and hence there is urgency of timely treatment with systemic corticosteroid therapy to prevent vision loss in the contralateral eye. Giant cell arteritis can rarely present as simultaneous bilateral loss of vision.
Multiple attacks of transient vision loss amaurosis fugax can precede permanent loss of vision, and particularly alternating between eyes are a strong indicator of temporal arteritis, as they do not often occur in atherosclerotic carotid artery disease.
The most common cause of vision loss is arteritic anterior ischemic optic neuropathy, which presents with sudden, severe visual loss, and pale swelling of the optic nerve head. Posterior ischemic optic neuropathy can also occur. Central retinal artery occlusion can also cause vision loss in temporal arteritis. Early examinations of the retina are classically described as "cherry red spot'' appearance and later exams show retinal pallor and loss of capillaries. 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.
Occasionally, ischemic complications can appear before any of the systemic signs or symptoms of illness, making diagnosis extremely difficult. Some authors have called this type of presentation "occult temporal arteritis" (08). Twenty percent of patients with permanent vision loss had no constitutional symptoms of giant cell arteritis (07).
Uncommonly, giant cell arteritis may present with dilated pupil (42) or diplopia as a result of ischemia of the oculomotor nerves, or ocular ischemic syndrome that may be refractory even to corticosteroid treatment (27).
Many patients with temporal arteritis have low-grade fever, leukocytosis, or mild anemia either at presentation or during the course of the illness. Depression, listlessness, and general malaise are common complaints among the elderly, but increased intensity of 1 or more of these symptoms may signal the onset of temporal arteritis. Nonspecific complaints like these have been shown to precede the more specific symptoms, even for several months, in up to half the patients. Weight loss, weakness, and inanition may be profound in the occasional patient. Lower back pain can be the presenting symptom of abdominal aortic giant cell arteritis and 18 FDG-PET is useful to identify the aortic involvement in this setting (12).
Polymyalgia, like temporal arteritis, almost exclusively affects persons over the age of 50 years. The clinical picture consists of pain and stiffness in the shoulder or pelvic girdles. Pain and limited motion of the axial skeleton including the cervical and thoracic spine are common. Pain and stiffness are often worse on arising in the morning, with some improvement of mobility as the day proceeds. Onset may be insidious or acute. Severity of symptoms can be asymmetric, but the disorder is invariably bilateral. There may be mild swelling of the shoulders and even distal joints in the extremities, but as a rule no articular deformity is manifest either clinically or by radiographic examination. In fact, there is considerable overlap between polymyalgia rheumatica and seronegative rheumatoid arthritis. Polymyalgia rheumatica may have a range of atypical presentations including peripheral synovitis, mild weakness, and normal sedimentation rate.
The duration of polymyalgia has ranged in various reports from 6 months to as long as 14 years, but most patients are ill with it for 1 to 3 years and it is not uncommon for patients with polymyalgia to develop additional symptoms of temporal arteritis after they have had the original illness for some time, sometimes years.
Although the signs and symptoms of temporal arteritis are variable, once they have begun, they are usually continuous or progressive until effective treatment is established. Visual prognosis is poor once the visual pathway is involved.
Relapses occur predominantly in the first 2 years of treatment. In patients with relapses, 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 when compared to those without relapse (01).
Epidemiologic studies indicated that life expectancy of patients with temporal arteritis is not significantly less than that of age-matched controls (34). The exception was the development of aortic dissection, which markedly increased mortality (39). Death from ischemia in temporal arteritis is rare and has been reported from vertebral artery occlusion and brainstem infarction or from coronary occlusion and myocardial infarction (49; 13). Being on a statin drug reduced the incidence of cardiovascular hospitalizations among these temporal arteritis patients (43).
The incidence of aortic aneurysm is dramatically increased in patients with temporal arteritis as compared with an age-matched general population. 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 (16). Surgical repair of these arteritic aortic aneurysms is extremely hazardous but can be carried out successfully (03).
A 78-year-old woman presented with a 2-month history of malaise, poor appetite, and unintentional weight loss. During the past 2 weeks, she also had frequent vertex headaches that were often severe and kept her from sleeping. In addition, she had trouble combing her hair in the morning because it caused pain in the scalp.
She consulted her dentist because chewing caused pain in the mandibular area, but he could find no dental cause for this. On further questioning she specified that the pain in her jaw would start a few seconds after she began to chew solid food and grow in severity over another 10 to 20 seconds to the point that she would have to stop chewing, after which the pain would subside over another 5 to 15 seconds. She was also having pain in the hips and stiffness of the legs that made walking difficult.
On the day of her office visit she had experienced a brief episode of visual loss in her left eye that she described as a "shade being pulled down" over the upper half of the visual field. For about 20 seconds she lost all vision in the left eye, and then sight returned first in the lower half of the field and then the upper half, with full return of vision within 1 to 2 minutes. No pain was associated with this episode.
Examination revealed a frail-looking elderly woman in mild distress. There was evidence of recent weight loss, and she had trouble rising from the waiting room chair to enter the office. Blood pressure was 180/95 taken from her right arm and 140/80 from the left arm. There was a loud left subclavian bruit. An ulcer was noted in the buccal mucosa next to the left lower teeth. There were no localizing findings on neurologic examination. Her gait appeared painful and stiff, and she held her head rigidly in the straight-ahead position as she walked. When asked to bend her neck forward or back or to turn her head to either side she winced with pain. The examiner was able to move her head and neck in all directions passively, but it required slow steady movement to avoid causing pain. Active and passive flexion of either leg caused pain in the hips and upper thighs.
There was no subjective red desaturation either eye on viewing a red bottle cap with either eye singly. Visual fields were full to confrontation testing (finger counting in each quadrant). Eye movement motility was full.
Complete blood count revealed moderate normochromic, normocytic anemia, and the Westergren erythrocyte sedimentation rate was 89 in the first hour. Carotid Duplex blood flow examination showed insignificant stenosis on either side, but ocular plethysmography showed reduced pulse amplitude in both eyes. Left temporal artery biopsy was performed, and methylprednisolone 1 gram daily was infused intravenously immediately afterward. She was instructed to return for an additional infusion of intravenous methylprednisolone 1 gram for the next 2 days, after which she was placed on oral prednisone at a dose of 80 mg each morning.
Microscopic examination of the temporal artery tissue revealed areas of intimal proliferation, fragmentation of the internal elastic lamina, and adjacent to disrupted segments of the elastic lamina, the media was infiltrated with lymphocytes, plasma cells, epithelioid cells, and multinucleated giant cells.
Within 48 hours of treatment onset she was free of pain, and within 2 weeks her body weight and strength had returned to premorbid status. After 3 weeks the prednisone dosage was gradually tapered in decrements of 5 mg/day each month.
The cause and pathogenesis are unknown, but considerable attention has been focused on the immunologic characteristics of the cellular infiltrate, which is dominated by mononuclear cells and multinucleated giant cells (31). Studies indicate that 2 distinct pathogenetic mechanisms can be distinguished in temporal arteritis (55; 10). One, mediated by Th17 T-cells that produce interleukin 17, serves systemic inflammation with manifestations such as fever, malaise, anorexia, and headache and is corticosteroid responsive. The other, mediated by Th1 T-cells that produce interferon-gamma, mediates vascular wall inflammation and is corticosteroid resistant.
There has been speculation about the role a virus might play in the pathogenesis of giant cell arteritis. Earlier work had showed varicella zoster virus antigen and DNA in localized patches of the arteries that were called “skip areas” in pathologically-negative temporal artery specimens and reexamination of the virus-positive segments demonstrated typical pathologic findings of temporal arteritis (38), and this larger study also found the virus in isolated patches or “skip areas.” A role of varicella zoster virus in temporal arteritis was the subject of an extensive study that found varicella zoster virus antigen in 61 of 82 (74%) of temporal arteritis pathologically positive temporal artery specimens and in only 1 of 13 (8%) of normal arteries (15).
Analysis of epidemiologic studies in temporal arteritis is hindered by the variability of diagnostic criteria and differences in population bases in the various studies. In general the incidence is relatively high in northern regions including the United States, Scandinavia, and European countries, whereas a much lower incidence is reported in southern European countries. Genetic factors are probably important in view of the predilection of temporal arteritis to occur in Caucasians and the association with the HLA-DR4 genotype.
In the Olmsted County population-based temporal arteritis study by Chen and colleagues, the population-based age- and sex-adjusted annual incidence of vision loss from arteritic ischemic optic neuropathy from temporal arteritis among persons aged at least 50 years was 1.3 per 100,000 population (07). The authors think that this high incidence reflects the population of Olmsted County, which is 90.3% Caucasian. Eighty percent of patients with permanent vision loss were females, which is in concordance with the overall female predominance of their study (79% of the cases). The highest incidence figures come from South Norway, where the annual incidence of temporal arteritis in persons aged 50 years or older was 29.0 per 100,000 (39.9 in women and 16.3 in men).
Although there are no known means of primary prevention of temporal arteritis, prevention of vision loss in 1 or both eyes with high dose steroids is the mainstay of management of patients with temporal arteritis. Following acute treatment, slow steroid taper and consideration for steroid sparing agents should be given.
Other disorders that present with headaches along with systemic symptoms include primary and metastatic tumors involving the brain, meninges, and skull, and a variety of infections and other inflammatory diseases. MRI and CT should be performed to evaluate for tumors. Lumbar puncture and CSF examination may be needed to rule out inflammatory (granulomatous), infectious, and neoplastic meningeal infiltrative diseases. Rarely, paranasal sinus infection might mimic both the local and systemic symptoms of temporal arteritis, but this will be identified by cranial imaging studies.
Focal symptoms caused by temporal arteritis each have their own differential diagnosis including nonarteritic ischemia.
On the other hand, temporal arteritis may masquerade as other diseases and be missed as the underlying cause. Ascending aortic aneurysm has been shown histologically to be caused by underlying temporal arteritis (19). Myocardial infarction can complicate known temporal arteritis or may rarely be the presenting feature of the disease (13). Temporal arteritis presenting as subclavian artery stenosis has also been described (47). Cases of temporal arteritis presenting as orbital inflammatory pseudotumor (09) and panuveitis (44) have been recorded as well. Temporal arteritis was found to be the most frequent specific multisystem disease in an elderly population presenting as fever of unknown origin (52).
The most frequently used tests for the diagnosis of temporal arteritis include Westergren erythrocyte sedimentation rate, C-reactive protein, complete blood count, and temporal artery biopsy. Mild anemia is common, as are various degrees of leukocytosis, sometimes with a left shift.
Marked elevation of the erythrocyte sedimentation rate is the most characteristic laboratory abnormality in patients with temporal arteritis. However, this is not specific. The laboratory criteria most strongly suggestive of temporal arteritis included C-reactive protein above 2.45 mg/dl and erythrocyte sedimentation rate of 47 mm/hr or more, in that order. C-reactive protein was more sensitive (100%) than erythrocyte sedimentation rate (92%) for detection of temporal arteritis. The combination of C-reactive protein and erythrocyte sedimentation rate above the cutoff values gave the best specificity (97%) (23). However, a normal erythrocyte sedimentation rate does not rule out the diagnosis when other features are highly suggestive.
The degree of erythrocyte sedimentation rate elevation in temporal arteritis and polymyalgia rheumatica is often extreme (greater than 100 mm in the first hour). Unfortunately, other conditions, some of which produce systemic symptoms similar to temporal arteritis, also elevate the erythrocyte sedimentation rate. A review of the literature showed that the sedimentation rate is nonspecific and has been found to be elevated in a wide variety of clinical conditions unrelated to temporal arteritis, even some noninflammatory conditions such as stroke, coronary artery disease, and prostate cancer.
Studies have sought to find better biological markers for clinical activity of the disease and markers to differentiate temporal arteritis from other rheumatological conditions. Elevation of anticardiolipin antibodies were found in approximately 50% of patients with temporal arteritis or polymyalgia rheumatica. However, there was no significant correlation between the presence of antiphospholipid antibody and ischemic events (11).
Demonstration of the inflammatory granulomatous lesion of temporal arteritis has made temporal artery biopsy a mainstay in establishing the diagnosis with assurance. The typical lesion is a granulomatous inflammatory reaction concentrated at the innermost part of the vascular media near zones of fragmented and reduplicated internal elastic lamina with adjacent intimal proliferation, sometimes to the point of occluding the lumen. Multinucleated giant cells are classically present but are not necessary for the diagnosis.
There are many cases of active temporal arteritis in which an entire temporal artery or segments of the artery are not involved; these were called "skip lesions" by Klein and colleagues (28). To compensate for the patchy nature of the pathologic process, these authors suggested that the length of the biopsy segment should measure at least 2.5 cm, and if frozen section of samples from that specimen are all normal, that the other temporal artery be biopsied at the same surgical session. On the other hand, Chakrabarty and colleagues suggested that "routinely examining a temporal artery biopsy at multiple levels does not increase the diagnostic yield of the test, although selective further examination may be indicated in some cases" (06).
Allison and Gallagher presented evidence suggesting that corticosteroid treatment prior to biopsy results in a significant reduction in the rate of positive results (02). A large survey of U.S. specialists in the fields of ophthalmic plastic and reconstructive Surgery (n=127), neuro-ophthalmology (n=119), rheumatology (n=799), and other (n=28) was carried out in 2010 and reported in 2013 (48). Sixty-six percent of respondents favored initial unilateral temporal artery biopsy, 18% bilateral biopsy in all cases, and 16% unilateral or bilateral biopsy depending on the degree of clinical suspicion. Rheumatologists were 4.5 times more likely to favor initial bilateral biopsy than the other 2 groups. Most believed that biopsy results were not rendered falsely negative with immunosuppressive treatment for up to 2 weeks.
Each physician must deal with negative biopsy results based on the adequacy of the specimen submitted and the intensity with which the biopsy material is studied. Also, the strength of the clinical presentation must be weighed, and if the signs and symptoms are typical and fairly specific (jaw claudication, tender arteries) then patients should not be denied prompt treatment based on negative biopsy results.
Another addition to the armamentarium for diagnosing vascular inflammation is 3-Tesla MRA, which can demonstrate not only segmental areas of lumen narrowing, but wall thickening and enhancement that are characteristic of large vessel vasculitis (05).
Hauenstein and colleagues found high-resolution MRI and color-coded duplex sonography of the temporal arteries to be more sensitive than temporal artery biopsy in diagnosing temporal arteritis and that their sensitivity rapidly declined during the first few days after initiation of steroid treatment (22).
A European multicenter prospective study found contrast enhanced magnetic resonance imaging of superficial cranial arteries to be 78.4% sensitive and 90.4% specific in diagnosing temporal arteritis and that diagnostic accuracy declined after 5 days of steroid treatment (29).
Ultrasound and PET can be used to demonstrate arteritis in the large arteries of the chest and neck in patients with temporal arteritis. Both procedures agree on the distribution of these changes in patients with large-vessel giant cell arteritis and these changes are most often clinically silent. Hypoechoic halo around arteries indicating mural edema is the most useful ultrasound feature (Schmidt and Blockmans 2005; 18).
Most recently, a prospective, double-blink, cross-sectional study evaluated the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) of the head, neck, and chest for determining a diagnosis of giant cell arteritis (46). Compared to temporal artery biopsy, the sensitivity of PET/CT for a diagnosis of giant cell arteritis was 92% and specificity was 85%. The negative predictive value was 98%. Compared to clinical diagnosis, PET/CT had a sensitivity of 71% and specificity of 91%. The authors suggested that the high diagnostic accuracy of this PET/CT protocol would support its use as a first-line test for giant cell arteritis. The negative predictive value of 98% indicates the particular utility of this test in ruling out the condition in patients considered to be at lower risk of giant cell arteritis. They also concluded that PET/CT had benefit over temporal artery biopsy in detecting vasculitis mimics and aortitis (46).
In cases with visual pathway involvement, ophthalmic imaging can be helpful. Specifically, fluorescein angiography can demonstrate involvement of multiple vascular territories in support of a diagnosis of temporal arteritis. There has been interest in the diagnostic utility of measuring choroidal blood flow using either newly developed methods for noninvasive measurement, such as ocular plethysmography or timed fluorescein angiography.
Since the introduction of high-dose corticosteroid therapy for temporal arteritis in the 1950s by Shick and colleagues (50), new visual loss has only infrequently been reported in patients who had been taking the recommended high initial dose for at least 7 days. The classic recommendation for initial treatment of temporal arteritis has been to commence with prednisone at a dosage of 40 to 80 mg/day, though 60 mg/day or above has been more commonly described than lower doses. This relatively high dose is usually maintained for 3 to 4 weeks, following which the dose is gradually reduced over many weeks to months, watching for reemergence of clinical symptoms (headache, jaw claudication, etc.) or rising erythrocyte sedimentation rate. Sometimes side effects require that the dose be reduced earlier than 4 weeks but this must be individualized to suit each patient's special needs. Patients with polymyalgia rheumatica but no headache or other specific signs of temporal arteritis can be safely managed with prednisone 15 mg/day or less from the onset and seem not to be liable for ischemic complications.
There have been proponents of intravenous pulse methylprednisolone therapy at doses of 1 to 2 g/day to initiate treatment in temporal arteritis in cases where visual loss has occurred in 1 or both eyes. Occasional cases have demonstrated marked visual return with this type of treatment, although a secondary goal is simply to prevent visual involvement of the second eye (35). A randomized, double-blind, placebo-controlled study showed highly significant long-term benefit for the group that received pulse IV methylprednisolone (15 mg/kg of ideal body weight/day) initially (36). In addition, this group also had a higher number of sustained remissions after discontinuation of treatment and a lower median daily dose of prednisone at 78 weeks.
Temporal arteritis is usually active for at least 1 year but can remain active for an average of 3 to 4 years among various studies (30). Therefore, tapering prednisone too early commonly results in recurrence of headache and other symptoms that signal the threat of ischemic complications. Recurring symptoms can usually be brought under control by reestablishing the original high dose followed by another tapering interval. This is, however, cumbersome and does not provide full protection from ischemic complications. It is better to taper slowly and avoid reactivation of the disease. It is important to note that alternate-day steroid therapy has never been considered acceptable for these patients.
Long-term steroid use is not benign. One of the most serious side effects is osteoporosis. Various authors have generally recommended prophylactic treatment for osteoporosis using calcium and phosphate compounds, but there has been little proof of their effectiveness. Gabriel and others at the Mayo Clinic found that the risks for diabetes mellitus and various bone fractures were 2 to 5 times greater among the polymyalgia rheumatica patients as compared with age-matched controls (14). Proportional hazards modeling showed that the following 3 factors independently increased the number of adverse events: (1) higher age at diagnosis, (2) cumulative dose of prednisone greater than or equal to 1800 mg, and (3) female sex. Patients on corticosteroid doses typical for treatment of temporal arteritis should also receive antibiotic prophylaxis against PCP.
There has been interest in adding immunosuppressant drugs to the treatment regimen in an effort to reduce steroid dose requirements. A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate for treatment of temporal arteritis could not demonstrate any advantage for the drug over placebo in addition to corticosteroids (24).
Cyclophosphamide and azathioprine were studied in small cohorts of patients and their effectiveness as steroid-sparing agents was uncertain (32). Etanercept, a tissue necrosis factor inhibitor, was shown to reduce the cumulative dose of corticosteroid required to keep temporal arteritis in clinical remission over the course of a 1-year prospective, randomized, placebo-controlled study. However, the advantages of etanercept did not reach statistical significance (33).
It has been suggested that new therapeutic approaches to the steroid-resistant inflammatory process in the large vessels, possibly involving manipulation of specific inflammatory cytokines and other inflammatory mediators, are needed. Weyand and colleagues studied 25 patients with biopsy proven temporal arteritis prospectively and demonstrated plasma interleuken-6 (IL-6) to be a much more sensitive measure of disease activity than erythrocyte sedimentation rate. These authors also found that the IL-6 levels did not return to normal when all clinical indicators suggested favorable response; they suggested that incomplete suppression of arterial inflammation in most patients puts them at risk for progressive vascular disease (54).
The beneficial effects of tocilizumab, an IL-6 inhibitor, as a glucocorticoid-sparing intervention have been demonstrated in 2 clinical trials (53; 51). Stone and colleagues prospectively studied the efficacy of tocilizumab as an adjuvant treatment to systemic corticosteroids versus placebo in 251 patients with newly diagnosed or relapsing temporal arteritis (51). Sustained remission at week 52 was achieved in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P < 0.001). The tocilizumab groups were found to have lower cumulative median prednisone as compared with placebo group. Also, serious adverse events were less common in the tocilizumab groups. Anterior ischemic optic neuropathy developed in 1 patient in the group that received tocilizumab every other week. Tocilizumab was approved by the FDA in May 2017 to be the first FDA-approved medication to specifically treat temporal arteritis (51).
Whatever ultimate course of treatment is selected, it is important to emphasize the critical need to initiate effective treatment as soon after the diagnosis is suspected as possible to minimize blindness and other severe ischemic complications.
All of the patients are beyond their childbearing years.
There is no indication of particular interaction between temporal arteritis and any anesthetic agent. The risk for anesthesia should be evaluated based on overall comorbidities.
Yin Allison Liu MD PhD
Dr. Liu of University of California, Davis has no relevant financial relationships to disclose.See Profile
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