Cranial arteritis, also called "giant cell arteritis" or "temporal arteritis" is a vasculitis primarily affecting older adults. Like polymyalgia rheumatica, it occurs more often in women than men. Cranial arteritis involves medium- and large-sized arteries in which all three portionsaeadventitia, media, and intimaaeare involved.
Giant cells are characteristically found but are not essential for diagnosis. Cranial arteritis can present with myriad features including polymyalgia rheumatica, vision loss, and aortic dissection. Although the etiology has not been elucidated, the pathogenesis is an immunologically mediated inflammatory disease. Most clinical manifestations respond to glucocorticoids, but once vision loss occurs, it is usually irreversible.
In the second of this two-part article, the authors review the diagnosis and management of cranial arteritis and discuss co-existing polymyalgia rheumatica and cranial arteritis. As mentioned in part 1, both articles represent the authors' experience with more than 2,000 people diagnosed with polymyalgia rheumatica and more than 450 people with biopsy-proven cranial arteritis.
Clinical view of cranial arteritis
The most characteristic presentation of cranial arteritis is a severe headache. It may be diffuse or localized to the temples or occiput. The pain may be severe and unrelenting. Typically, the headache is quite different from the patient's usual headache. It may be accompanied by scalp tenderness and, at times, obvious swelling of the temple artery. "Jaw claudication" is characteristic but not very common. With jaw claudication, the patient has difficulty chewing as the masseter and temporalis muscles tighten after the patient takes a few bites. The patient must stop eating for a few seconds before continuing. The symptom is usually relieved by rest.
Most often, the patient also feels systemically ill, with fever or malaise. Typical polymyalgia rheumatica is found in approximately 30 to 40% of patients with cranial arteritis. Swelling of the joints may occur, but it is not usually a prominent or common feature of the disease. Intermittent claudication of both the upper and lower extremities may occur.
Rarely, skin rashes are seen. A few patients have exhibited gangrene of the face, tongue, and temple.
A "malignoid" syndrome may occur with fever and weight loss mimicking infection or malignancy. Weakness of the upper extremity may occur. Fever unaccompanied by other symptoms is sometimes seen. Chest pain and shortness of breath may occur, particularly if cranial arteritis results in aortic dissection or coronary artery occlusion.
Vision loss is a serious complication of cranial arteritis. Vision loss may be sudden in some patients, but in others it is preceded by double vision, amaurosis fugax, or scotomas. At times, ocular pain may occur. Vision loss, with the exception of amaurosis fugax, is usually permanent and rarely reversed by treatment.
Cerebrovascular accidents involving the anterior and posterior cerebral circulation can occur, but are not common. Confusion and organic brain syndrome are uncommon.
Physical examination may be unrevealing. Patients often have swollen, tender, and pulseless temporal arteries, but for some patients, examination of the temporal arteries is normal. The patient also may appear chronically or acutely ill, depending on symptoms. Weight loss, at times extreme, may be present.
Patients with diffuse arteritis may exhibit loss of pulses in the upper and lower extremities. Although lower extremity atherosclerosis is common in older adults, the absence of pulses in the upper extremities in an older person should alert the clinician to the presence of cranial arteritis, particularly if the patient is systemically ill. The examination may reveal bruits over large vessels.
Swelling of the joints may be found but is not common. Usually there is no muscle weakness. Exceptions are if the patient has had a stroke or a motor neuropathy.
If the patient has not experienced vision loss, the eye exam is not helpful, except to rule out other problems. Once vision loss has occurred, it is most often due to ischemic optic neuropathy caused by involvement of the posterior ciliary vessels. Central retinal artery occlusion is rarely present. Vision problems are diagnosed through careful examination by an ophthalmologist. We have seen one patient who had vision loss secondary to an occipital infarct due to involvement of the posterior cerebral circulation.
There are no specific laboratory findings associated with cranial arteritis. The laboratory examination usually reflects the presence of inflammation. Elevation of sedimentation rate and C-reactive protein are almost always present, but there are exceptions: We saw two patients with biopsy-proven cranial arteritis who lost vision yet never had an elevated sedimentation rate.
Severe normocytic anemia is often present. We have seen at least one patient who had a hemoglobin of 6 grams with no other symptoms except for those related to anemia. The diagnosis was made based on temporal artery biopsy, corticosteroid treatment was given, and the anemia resolved.
White blood cell count is usually normal in patients with cranial arteritis. Platelet counts may be increased as a reflection of ongoing inflammation.
Serologies such as rheumatoid factor, antinuclear antibodies, and anti-neutrophil cytoplasmic antibodies (ANCAs) are not typically present in cranial arteritis. Their frequency is similar to that of older patients who do not have cranial arteritis.
Chemistries are usually normal, with the exception of alkaline phosphatase elevation, which may be mild to moderate. Occasionally, elevations of serum aspartate transaminase (AST) or alanine transferase (ALT) are seen. With the rarest of exceptions, renal disease is absent and urine analysis is normal.
There have been a number of patients with cranial arteritis who have demonstrated the laboratory features of the syndrome of inappropriate antidiuretic hormone production (SIADH). These patients manifest a low serum sodium level.
Radiographs are usually not helpful, and the skeletal changes seen are typical of those found in an older population. Aortic aneurysm, if present, may be seen on chest x-ray. If aneurysm occurs it is most commonly in the ascending aorta. If aneurysm is suspected, special imaging to include CT, MRI, or MRA can be helpful. When pulseless disease is present, MRA can outline the extent of the disease. In contrast to some arteritides, in which small blood vessels are involved and require contrast angiography for diagnosis, cranial arteritis involves larger vessels and usually does not require arteriography.
Doppler ultrasound of the temporal arteries has been suggested as a possible diagnostic modality. The typical "halo" that has been described was found to be highly sensitive and specific in one study. (1) Subsequent studies, however, suggested this technique to be no more precise than careful physical examination. (2) PET scanning may prove useful in diagnosing cranial arteritis, but at this time is still investigational.
Most important to the diagnosis of cranial arteritis is a high suspicion for its presence. Many patients may present with the typical headache and polymyalgia rheumatica, however, others may not. Although the incidence of cranial arteritis is unknown, it probably exceeds the estimated annual incidence of 11.7 per 100,000 people over age 50 that has been reported. (3)
In Malmo, Sweden, where all deaths are investigated by autopsy, investigators examined a section of the aorta and two specimens of temporal arteries and found that 1.6% of patients had arteritis. (4) On the basis of that study, it was estimated that arteritis (without specifying what type) may occur in as much as 2% of the general population. Confirming this observation is a histologic exam of 1,169 consecutive pre-surgery patients with aortic aneurysm. Nineteen patients had giant cell arteritis that was not clinically suspected or manifested at the time of surgery. (5) Since older patients with cranial arteritis may present with various symptoms, the clinician must be mindful of this possible diagnosis, particularly when patients who do not have evidence of either infection or malignancy present with fever of unknown origin, anemia, and weight loss.
The gold standard for diagnosis of cranial arteritis is histopathologic examination, usually of the temporal artery. The temporal artery is a readily accessible site for biopsy. If the artery is tender, swollen, or indurated, the likelihood of a positive biopsy is increased, although an artery that is clinically normal may, on microscopic examination, demonstrate typical changes of cranial arteritis. Usually the biopsy is performed on the side where symptoms are most apparent or clinical findings occur. Some clinicians advocate the use of bilateral temporal artery biopsy. Studies have revealed that bilateral biopsy increases the positive yield by approximately 5%. (6)
Full discussion of the histopathology of cranial arteritis is outside the realm of this article. It should be noted, however, that it is important for the surgeon to obtain a large enough sample so that multiple sections can be examined if needed. Also, to make the diagnosis, a cellular infiltrate should be present in the blood vessel wall. Mere disruption of the internal elastic membrane is not adequate for diagnosis. The presence of giant cells is helpful but not necessary for diagnosis. In addition, arteritides other than cranial arteritis can be found on temporal artery biopsy. Thus polyarteritis, Churg-Strauss arteritis, Wegener's granulomatosis, and eosinophilic arteritis, can be found in temporal artery biopsies.
In our experience, approximately 20% of patients who have a characteristic clinical picture of cranial arteritis have negative biopsies of the temporal artery. This may be a result of the patchy distribution of the inflammatory lesions. The patient in whom a clinical diagnosis of cranial arteritis is made should be treated the same as the patient with a positive biopsy. However, the physician must also consider other conditions that may cause a similar clinical picture.
Etiology and pathogenesis
The etiology of cranial arteritis is unknown. Theories about infectious or environmental causes remain speculative. Evidence has suggested that the vascular lesion results from an abnormal adaptive immune response in the artery, and that the systemic symptoms may result from an activated immune system. These hypotheses are actively being tested. (7,8)
Glucocorticoids are the mainstay of treatment for cranial arteritis. Although not yet studied in a systemic fashion, high-dose prednisone, [greater than or equal to]60 mg/d, is typically used as first-line treatment. Once the diagnosis is strongly suspected, treatment with high doses of oral corticosteroids should be instituted immediately while arrangements are being made for temporal artery biopsy. There is ample evidence that even a few weeks of high doses of glucocorticoids do not alter the histopathology of cranial arteritis or preclude the ability to make a pathologic diagnosis. Waiting for biopsy results before initiating treatment could place the patient at risk for vision loss, which in cranial arteritis is typically irreversible despite aggressive treatment.
Some authors recommend high doses of intravenous "pulse" methylprednisolone as initial treatment. However, there is no good data to support this approach. With rare exceptions, response to high-dose glucocorticoid treatment is dramatic and prompt, systemic symptoms usually regress in a matter of days, and markers of inflammation return to normal. High doses of glucocorticoids should be maintained for approximately 2 weeks before being slowly decreased. There is no formula for the rate of tapering. We usually taper prednisone by approximately 3 mg every 3 days after approximately 2 weeks of treatment, and then at a slower rate depending on the clinical condition.
Although some clinicians have advocated treating not only to control symptoms but also to normalize the sedimentation rate, we have not used this approach. Doing so could be dangerous as there are many reasons for an elevated sedimentation rate in older patients, and trying to decrease the sedimentation rate will often lead to excessive steroid treatment. Moreover, the clinical symptoms do not necessarily correlate with sedimentation rates, and older patients are particularly sensitive to steroid side effects.
Vision loss most often occurs early in cranial arteritis, and late vision loss rarely occurs. In our experience with more than 450 patients with biopsy-proven disease, only one patient had late vision loss and it was not clear that cranial arteritis was the cause. In the medical literature, late vision loss in cranial arteritis is quite unusual. (9,10) Should symptoms of fever, headache, severe myalgia, and vision loss occur, glucocorticoids must be maintained at a higher dose.
A recent retrospective study suggested that treatment with low-dose aspirin may be protective against ischemic complications of cranial arteritis. (11) This finding has not been confirmed in prospective controlled trials, but it would seem to be a reasonable approach if no contraindication to aspirin is present.
When starting treatment of cranial arteritis, it is important to screen patients for the presence of bone loss via DEXA scan. Calcium, 1,200 mg/d, and vitamin D, between 400 to 800 IU daily, is mandatory. A bisphosphonate should be added if necessary. Glucose and cholesterol levels should be monitored, as well as blood pressure and fluid retention.
Steroid myopathy is a common complication and manifests itself as muscle weakness, primarily in the hip flexors. The patient reports difficulty arising from a chair, getting off of a toilet seat, or out of a bathtub. Falling may occur. Steroid myopathy responds only to lowering the steroid dose.
Poor tissue healing and bruising are also a problem and only improve when the steroid dose is decreased. Hypertension, hyperglycemia, and hypercholesterolemia as well as fluid retention should be treated with standard agents.
Emotional lability may occur with high doses of steroids. Common symptoms are insomnia, restlessness, hypomania, and depression. These often recede with a decrease of the steroid dose, but, at times, psychotropic medication and psychiatric intervention are necessary.
Most patients can be tapered to a very low dose of corticosteroids in approximately 6 months, and some may be able to stop steroid treatment within a short period of time. Other patients, however, will have recurrence of clinical symptoms such as headaches, myalgia, fatigue, and fever, which respond only to increasing the steroid dose.
Side effects are common during long-term high-dose corticosteroid therapy. Particular problems include poor tissue healing, myopathy, osteoporosis, and depression. Attempts have been made to treat such patients with agents that may have a steroid-sparing effect, such as methotrexate. In two of three studies evaluating methotrexate for the treatment of cranial arteritis, no benefit was seen, (12,13) whereas in one study, some steroid-sparing effects were seen. (14) Nonsteroidal anti-inflammatory drugs, dapsone, hydroxychloroquine sulfate, azathioprine, and cyclophosphamide have also been tried, but the use of these agents is anecdotal. Nevertheless, when faced with a patient with clinical disease requiring an excessive amount of steroids, an empiric trial of these agents would be warranted even in the absence of convincing clinical trials.
The major consequence of cranial arteritis is vision loss due to ischemic optic neuropathy. There are no clear data as to the true incidence of this problem in patients with cranial arteritis. In one report predating the availability of corticosteroids, 48% of patients with cranial arteritis had vision loss in at least one eye. The true incidence is probably much lower. If indeed the incidence of cranial arteritis in older adults is 2%, the frequency of vision loss in that disease may be quite low. Nevertheless, vision loss is a disastrous complication and must be considered when managing a patient with polymyalgia and cranial arteritis. As noted earlier, vision loss is most common early in the course of cranial arteritis, so initial treatment should be aggressive. Subsequent treatment should include the lowest steroid dose necessary to keep clinical disease under control.
Vision loss in cranial arteritis seems to be more common in men than in women, and when one eye is involved, there is a significant risk that the contralateral eye may become involved. In these patients, we often try to normalize the sedimentation rate, although we have no good evidence to support this approach. Symptoms such as double vision and scotomas are usually present early in the disease and tend to regress once corticosteroids are given.
Most patients with cranial arteritis who have not lost vision early in the disease have a good prognosis. Loss of vision later in the disease is rare, and longevity is not generally affected. Most patients can be tapered off steroids within 6 months to 2 years, although some require treatment for longer periods of time to control symptoms.
Some patients will exhibit residual steroid toxicity, particularly osteoporosis during and after treatment. Myopathy, poor tissue healing, and emotional problems tend to recede after steroids are discontinued. Disturbances in metabolism, such as elevated glucose and cholesterol levels, will also improve, although some patients will develop diabetes.
Any patient who has taken or is taking glucocorticoids should be informed about the need for "stress steroids" during medical or surgical stress. It is our policy to advocate "stress steroids" until a patient has been off glucocorticoids for 1 year.
Aortic aortitis may lead to aneurysm with rupture and dissection. Even years after having "active" disease, patients with a history of cranial arteritis are at increased risk of thoracic and abdominal aortic aneurysms compared with age-matched controls. (15) In epidemiologic studies comparing longevity in cranial arteritis to the general population, decreased life expectancy has not been demonstrated.
Link to polymyalgia rheumatica
Polymyalgia rheumatica and cranial arteritis are often regarded as the same entity. Approximately 30 to 40% of patients with cranial arteritis have polymyalgia rheumatica during the course of their illness. Often, the dosage of corticosteroids required to suppress polymyalgia rheumatica in these patients is greater than in polymyalgia rheumatica in the absence of concomitant cranial arteritis. Of those with polymyalgia rheumatica, cranial arteritis is eventually diagnosed in 5 to 30% of patients. However, in our experience with more than 2,000 patients with polymyalgia rheumatica without clinical evidence of cranial arteritis who respond to low doses of corticosteroids, the development of cranial arteritis is uncommon. Nevertheless, the patient and physician must be aware of the possible association, and any visual symptoms, severe headache, or jaw claudication must be immediately brought to the doctor's attention and, if necessary, the steroid dose should be increased and a temporal artery biopsy performed.
We do not routinely biopsy the temporal artery of patients with polymyalgia rheumatica who have no clinical evidence of cranial arteritis and who respond to small doses of corticosteroids. However, if the patient suspected of polymyalgia rheumatica does not respond to small doses of corticosteroids, alternative diagnoses are sought, including cranial arteritis.
It is likely that in some patients, polymyalgia rheumatica is a manifestation of cranial arteritis, but the majority of patients do not seem to be at risk for co-existent disease. The true incidence of cranial arteritis and polymyalgia rheumatica may be resolved if autopsy studies on patients with polymyalgia rheumatica could be performed.
Giant cell arteritis is a histopathologic entity with numerous clinical manifestations including vision loss and aortitis as well as polymyalgia rheumatica. If the clinician is aware of these entities, diagnosis can be established and effective treatment instituted.
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Spiera R, Spiera H. Inflammatory disease in older adults, part 2: Cranial arteritis. Geriatrics 2004; 59(12):00-00.
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Dr. Robert Spiera is associate professor of clinical medicine at the Albert Einstein College of Medicine, New York City.
Dr. Harry Spiera is professor of clinical medicine at the Mount Siani School of Medicine, New York City. Disclosure: Neither author has any real or apparent conflicts of interest relating to the subject presented here.
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