A repeat review of symptoms after the diagnosis was established revealed no history of headache or jaw claudication.

 

Treatment with one low-dose aspirin per day should be started to reduce the risk of cranial ischemic complications of giant-cell arteritis. In addition, calcium and vitamin D should be prescribed to prevent glucocorticoid-induced bone loss.

 

Treatment with prednisone and aspirin was started, with subsequent resolution of the fevers, sweats, and thigh pain and normalization of the alkaline phosphatase level. Calcium and vitamin D supplements were also recommended. The patient remains well on a slowly tapered dose of prednisone 6 months after the initiation of glucocorticoid therapy.

Commentary

 

Temporal arteritis is a large-vessel vasculopathy that preferentially involves the aorta and the extracranial branches of the carotid artery.1 It typically affects patients older than 50 years of age and is characterized by nonspecific systemic features, including anorexia, weight loss, fatigue, and fever. Headache is the most common chief symptom. 1 High fever is present in 10% of patients and may be the presenting or only manifestation of giant-cell arteritis,2 occasionally accompanied by rigors and sweats mimicking sepsis. Other clinical manifestations depend on the ischemic vessels involved. An elevated erythrocyte sedimentation rate often triggers a suspicion of temporal arteritis, but this finding is nonspecific.

 

Polymyalgia rheumatica, a closely related syndrome reported in 40 to 60% of patients with giant-cell arteritis, is characterized by aching and stiffness in the neck, shoulder, and pelvic girdle. Of particular concern with giant-cell arteritis is the risk of sudden, permanent loss of vision, but glucocorticoid treatment appears to reduce this risk. Delays in the diagnosis and treatment of giant-cell arteritis can have devastating consequences. This patient presented without the characteristic cranial or ocular signs and symptoms of giant-cell arteritis but with an isolated elevation in the alkaline phosphatase level and fever. The typical symptoms of giant-cell arteritis, such as jaw claudication and temporal headache, are present in only 34% and 52%, respectively, of patients with biopsy-proven arteritis,3 which makes the diagnosis more challenging. Atypical features include fever of unknown origin and respiratory, cardiovascular, central nervous system, and gastrointestinal symptoms and findings.4 The asymptomatic elevation in the alkaline phosphatase level in this patient indicated hepatic involvement, which has been observed in up to one third of cases of temporal arteritis.5 In most patients with temporal arteritis or polymyalgia rheumatica, liver-biopsy specimens are normal or show minor, nonspecific changes; however, arteritis of the portal tract and septal vessels with cholangitis in adjacent bile ducts6,7 and granulomatous hepatitis8 have been reported. Liver involvement does not appear to affect the prognosis for patients with giant-cell arteritis,9 and with the prompt initiation of glucocorticoid therapy, liver-enzyme levels tend to normalize quickly, as occurred in this case.

 

Case reports have suggested an association between tetracycline use and the development of cholangiopathy,10 including progressive cholestasis, known as the vanishing bile duct syndrome, which can occur up to 1 year after discontinuation of the drug. Medications from almost every pharmacologic class have been implicated in hypersensitivity and leukocytoclastic vasculitis; however, we are not aware of a link between medications and giant-cell arteritis. Therefore, any role of minocycline in precipitating this patient's rheumatic symptoms remains speculative.

 

The thigh pain and associated soft-tissue, interfascial, and muscle edema detected on MRI were initially presumed to be related to the same condition that was causing the fever and elevated alkaline phosphatase level. Although bursitis, joint and periarticular synovitis, and edema at extracapsular sites adjacent to the joint capsule or in the soft tissues have been reported in patients with polymyalgia rheumatica,11,12 to our knowledge, the specific MRI findings in this case have not been described previously in association with either giant-cell arteritis or polymyalgia rheumatica and thus cannot necessarily be attributed to either condition.

 

The elevated alkaline phosphatase level and unexplained fever, despite normal findings on hepatobiliary imaging, prompted a liver biopsy, which eventually led to the correct diagnosis. A liver biopsy is indicated in patients with abnormal liver-enzyme levels when the serologic workup has been inconclusive and the biliary tree is not dilated.13 In this case, the diagnosis of giant-cell arteritis was subsequently confirmed with a temporal-artery biopsy.

 

The frequency of visual complications in patients with giant-cell arteritis has substantially decreased since the introduction of glucocorticoid therapy, and the risk of visual loss appears to be low after therapy has been initiated.14 Although data from randomized trials are lacking to guide the use of prednisone for this condition, high-dose prednisone (approximately 1 mg per kilogram) is typically given for 2 to 4 weeks and is then gradually tapered (e.g., by 10% of the total dose every 2 weeks) until a maintenance dose of 7.5 to 10.0 mg per day has been reached, followed by a slower subsequent taper, and in most cases eventual discontinuation. Although most of the clinical manifestations of giant-cell arteritis respond rapidly to glucocorticoids, vision generally does not improve if there was visual loss before the start of treatment. Retrospective studies suggest that the risk of cranial ischemic complications is reduced in patients with giant-cell arteritis who are treated with aspirin, so aspirin is often prescribed adjunctively. 15

 

This case represents an unusual presentation of giant-cell arteritis, a diagnosis that is commonly considered in patients who present with cranial symptoms such as headache and jaw claudication. The single giant cell fortuitously detected in the liver-biopsy specimen provided a critical clue to the diagnosis and, in this case, demonstrated that the arteritis was not all in the patient's head.