Giant Cell Arteritis

A Curious Headache
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Diagnosis and reasoning

A new onset headache in a patient over 50 years of age should be considered to be due to a secondary cause until proven otherwise. Important possibilities to consider include giant cell arteritis (GCA), primary or metastatic cerebral tumor, and subdural hematoma; note also that headache due to prescription medications is extremely common in this age group and often overlooked. A detailed history and examination is essential; this reveals a recent episode of blurring of vision - an ominous finding which strongly favors GCA. An important clinical point is that visual disturbances in a patient with GCA are a herald of impending irreversible vision loss. This may occur at any point in time - even on the day of presentation itself. Thus, the next step in her workup should be urgent estimation of her erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) levels; if possible, she should be requested to remain in the emergency department until the results become available. Note the presence of elevated inflammatory markers - particularly the ESR of 60 mm/1h; when considered along with the age of the patient and the new-onset headache, this satisfies the 1990 classification criteria for giant cell arteritis (GCA), as laid down by the American College of Rheumatology (ACR). A temporal artery biopsy should be obtained as well; however, several days may be required for the results to become available. Neuroimaging is not indicated right now; nor is there good justification for a lumbar puncture. GCA is an neuro-ophthalmic emergency; it is essential to administer high-dose corticosteroids as soon as the diagnosis has been made; this should never be delayed pending temporal artery biopsy results. The current consensus is that patients with visual disturbances should receive high-dose intravenous (IV) corticosteroid therapy (typically IV methylprednisolone) for 3 days, followed by conversion to an oral formulation (such as prednisolone). As she will subsequently require long-term high-dose steroid therapy, osteoporosis prophylaxis is also essential. IV antibiotics are not indicated in her current management; nor is referral to a neurosurgeon.


Discussion

Giant Cell Arteritis (GCA), also termed Temporal Arteritis, is a systemic vasculitis that affects the aorta and its major branches; involvement of the ciliary artery can result in ischemic optic neuropathy and subsequent blindness, which is typically irreversible. The disease is most frequently encountered in individuals of Caucasian descent, although all racial groups may be affected; the mean age of onset is approximately 70 years of age, with the condition being rare in individuals younger than 50 years. Women are affected around 3 times as often as men. Approximately 50% of patients with GCA also have polymyalgia rheumatica (PMR), a closely related condition; conversely, around 15% of patients with PMR are found to have GCA as well. The disease process underlying GCA is a granulomatous inflammation which is typically positioned within the wall layers of medium and large arteries; these infiltrates are composed of CD4 T-cells and highly activated macrophages, often including multinucleated giant cells. The vascular wall, which is usually an immune-privileged site, responds to the attack with a response-to-injury program, which culminates in hyperplasia of the intimal layer, resulting in luminal compromise and vessel occlusion. In the majority of these patients, associated systemic inflammation is also present. Headache is the most common symptom of GCA, occurring in 90% of patients; many of them report that this does not feel like any other headache they have previously experienced, and thus, they may instead call it "head pain". The headache is usually constant and severe, often disturbing sleep. It is often temporal and bilateral, although it can be frontal, parietal, occipital, or may even spare the scalp and instead affect the eye, ear, face, jaw or neck; it may also be precipitated by brushing the hair. Scalp tenderness is common, particularly around the temporal and occipital arteries, and may disturb sleep. Jaw claudication is a fairly specific symptom encountered in 33% to 50% of cases; this is due to masseter ischemia secondary to stenosis of the maxillary artery. Note that this is different from temporomandibular dysfunction, which occurs with any jaw movement; jaw claudication occurs after a few minutes of mastication, and resolves rapidly with rest. Constitutional symptoms such as fever, night sweats, fatigue, malaise, and weight loss may also occur, and may be an early or even an initial finding. Visual disturbances such as diplopia, visual blurring, transient loss of part or all of the visual fields, visual hallucinations or photopsia occur in between 25% to 50% of patients; these are ominous, heralding irreversible vision loss in the near future, unless urgent treatment is initiated. Less common features include scalp or tongue necrosis, hemiparesis, peripheral neuropathy, deafness, depression, and confusion. Involvement of the coronary arteries may lead to myocardial infarction, while aortic regurgitation and congestive cardiac failure may also occur. Inflammatory markers such as erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and/or plasma viscosity (PV) are often elevated, and frequently markedly so. The full blood count may reveal anemia and/or thrombocytosis. Abnormalities of thyroid and liver function may also occur; serum alkaline phosphatase (ALP) is increased in many of these patients, while liver transaminases may also be mildly elevated; hyperthyroidism and/or thyrotoxicosis may accompany the disease, or may develop subsequently. Temporal artery biopsy is the most specific test for GCA, with the presence of mononuclear cell infiltration or granulomatous inflammation being diagnostic; these changes persist for even 1 to 2 weeks following initiation of steroid therapy. That said, it should be appreciated that GCA may manifest as 'skip' lesions (with the intervening areas being histopathologically normal); thus an adequate biopsy length (> 1cm) should be obtained. Ideally, the artery on the same side as the headache should be biopsied; in select patients, biopsy of both temporal arteries may be considered, as this increased the sensitivity by 13%. Ultrasonography of the temporal arteries has been explored as an alternative to biopsy; studies have shown that the presence of a temporal artery halo has a sensitivity of 82%, and a specificity of 92% if unilateral or 100% if bilateral. In addition, contrast enhanced magnetic resonance imaging (MRI) showing mural inflammation and thickening of temporal arteries has been shown to be 81% sensitive and 97% specific, while fluorodeoxyglucose (FDG)-positron emission tomography (PET) has a 56% sensitivity and 98% specificity for the diagnosis.In 1990, the American College of Rheumatology (ACR) established the following criteria for the classification of GCA: - Development of symptoms or findings at age 50 or older. - New onset localized headache or head pain. - Tenderness to palpation or decreased pulsation of the temporal arteries. - Erythrocyte sedimentation rate (ESR) of 50 mm/hour or more. - Abnormal artery biopsy showing vasculitis with mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells. Studies have shown that the presence of at least 3 of the above 5 criteria is 93.5% sensitive and 91.2% specific for the disease. That said, it is essential to appreciate that the above criteria were formulated for research purposes; the diagnosis of GCA should be based on the entirety of the patient's clinical findings and investigation results. Note that a new set of provisional ACR/European League Against Rheumatism (EULAR) classification criteria has recently been published, but are yet to be validated for diagnostic use in clinical practice. GCA is a neuro-ophthalmic emergency; urgent treatment is essential to prevent vision loss. Corticosteroids are mandatory, and dramatically relieve symptoms within a matter of days. Note that parenteral corticosteroid therapy is recommended in the setting of acute visual disturbances or visual loss. Methotrexate also appears to be effective, but does not have a rapid onset of action and cannot be recommended as a replacement for glucocorticoids at disease onset. Tumor necrosis factor (TNF) alpha inhibition is to some extent effective in longstanding, refractory GCA but is not effective in new onset GCA. While the use of low dose Aspirin has also been advocated as a means of reducing ischemic complications, this should be counterbalanced against the risk of gastrointestinal bleeding, especially with co-prescription of steroids. Note that many of these patients will require steroid therapy for months to years, and thus are at risk for serious treatment-related side effects; this is magnified by the fact that a significant number have comorbidities such as diabetes mellitus, hypertension and heart disease. Osteoporosis is a particularly important consideration; bisphosphonates, such as etidronate and alendronate, have been shown to be useful in retarding bone loss. Consideration should also be given towards screening these patients for extracranial disease, particularly given the fact that this is often clinically silent. Surgical treatment is usually reserved for management of aortic aneurysmal disease, clinically significant stenosis or occlusion of extracranial vessels that has failed corticosteroid treatment. Acute vision loss is the most feared complication of GCA, with only 5% to 7% of patients recovering visual acuity, even if promptly treated. Early diagnosis and aggressive management is essential for prevention of this.


Take home messages

  1. GCA is a neuro-ophthalmic emergency which can cause irreversible vision loss unless diagnosed and treated early.
  2. The diagnosis of GCA should be based on the entirety of the patient's clinical findings and investigation results.
  3. High dose corticosteroid therapy is single most important intervention and should be commenced as soon as the clinical diagnosis is made.
  4. IV corticosteroids are prefered over oral formulations in the acute treatment of patients with vision loss.

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