Giant cell arteritis as the cause of chronic fever of unknown origin

Giant cell arteritis (GCA) is an inflammatory disease affecting medium and large arteries. Its incidence is 15 to 25 per 100 000 population, and it usually affects individuals older than 50 years of age (typically in their seventh or eighth decade of life).^1,2 The etiopathogenesis involves proinflammatory and autoimmune mechanisms.³ Patients present with symptoms related to an ongoing inflammatory process (fever, malaise) and ischemia of tissues supplied by the affected vessels. These symptoms may not occur simultaneously. Some patients may display one predominant symptom (eg, fever), which complicates the diagnosis. A common comorbidity in GCA is polymyalgia rheumatica. The diagnosis is based on ultrasonography (which reveals the characteristic hypoechoic halo sign around the artery lumen), computed tomography (CT), magnetic resonance imaging, and positron-emission tomography / computed tomography (PET-CT).^4,5

A 64-year-old man was admitted to the Department of Internal Medicine after 2 months of empiric antibiotic therapy due to sustained subfebrile temperature. He reported headache, depressive disorders, and weight loss (6 kg over 3 months). On admission, enlarged neck and axillary lymph nodes with ultrasound features of reactive lymph node enlargement, tooth decay, and left knee bursitis were noted. The patient did not consent to lymph node biopsy.

We did not observe arthritis or symptoms of polymyalgia rheumatica. Laboratory tests showed high levels of inflammatory markers (C-reactive protein, 114 mg/l; erythrocyte sedimentation rate, 120 mm/h), anemia of chronic disease, and thrombocytosis. Multiple blood and urine culture tests were negative. Protein electrophoresis did not show increased γ-globulin and monoclonal protein levels. Typical infections were excluded (hepatitis B and C, HIV, cytomegalovirus, mononucleosis, toxoplasmosis, Lyme disease, and influenza). Antinuclear, proteinase 3, myeloperoxidase, β₂-microglobulin, and antiphospholipid antibodies were negative. Chest X-ray showed no inflammatory lesions. Abdominal ultrasound revealed kidney stones, gallbladder polyp, and hepatic cyst. Endoscopy showed no abnormalities. Due to suspicion of malignancy, imaging studies were performed, including chest, abdominal, and pelvic CT. They revealed enlarged lymph nodes (up to 9 mm) in the mediastinum and lesser curvature (up to 12 × 18 mm), aortic atherosclerosis, kidney stones, hepatic cyst, and a metallic foreign body in the left eye (which precluded head magnetic resonance imaging). Chest CT did not reveal features of sarcoidosis. Following a dental consultation, 6 teeth were extracted as a possible source of systemic inflammation. Broad-spectrum antibiotic therapy was started (metronidazole, trimethoprim / sulfamethoxazole, clindamycin). However, subfebrile temperature and the levels of inflammatory markers were not reduced. The patient was referred for PET-CT to a nuclear medicine unit. The examination showed increased glucose metabolism in the aorta and its branches (figure 1A and 1B). Based on the clinical presentation and extensive workup, GCA was diagnosed. Treatment with intravenous methylprednisolone (0.5 g for 3 days) was administered. Then, oral glucocorticoids were continued at the initial daily prednisone dose of 60 mg. Additionally, methotrexate at a titrated dose of up to 25 mg/wk was administered. The patient’s general condition improved, with a reduction in the body temperature and levels of inflammatory markers.

We presented a complex case of fever and malaise due to vasculitis. The wide differential diagnosis and numerous recommended imaging studies were inconclusive.^3,5 The cause of nonspecific symptoms and persistently elevated levels of inflammatory markers was ultimately identified by PET-CT, which has high sensitivity and specificity for early GCA diagnosis.⁴