A 65-year-old man comes to the emergency department with a 3-day history of headaches localized to the right temporal region. The headaches are accompanied by intermittent blurring of vision in both eyes. He has also felt fatigued for the past week, with stiffness in his shoulders and hips. On examination, temperature is 37.5 C (99.5 F). There is tenderness on palpation of the right temporal region with enlargement of the underlying artery, as shown in the exhibit.

Funduscopic examination reveals edematous optic discs in both eyes. The patient has limited active abduction of the shoulder joints bilaterally. Laboratory studies show an erythrocyte sedimentation rate of 115 mm/hr. Which of the following is the most important mediator of this patient's current condition?

Question

A 65-year-old man comes to the emergency department with a 3-day history of headaches localized to the right temporal region.  The headaches are accompanied by intermittent blurring of vision in both eyes.  He has also felt fatigued for the past week, with stiffness in his shoulders and hips.  On examination, temperature is 37.5 C (99.5 F).  There is tenderness on palpation of the right temporal region with enlargement of the underlying artery, as shown in the exhibit.

Funduscopic examination reveals edematous optic discs in both eyes.  The patient has limited active abduction of the shoulder joints bilaterally.  Laboratory studies show an erythrocyte sedimentation rate of 115 mm/hr.  Which of the following is the most important mediator of this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3b63_7db5_9249_1f7e59a37eae_MD0001_00 This patient with headaches, visual and muscular symptoms, an enlarged temporal artery, and elevated erythrocyte sedimentation rate has typical features of giant cell arteritis ([GCA] temporal arteritis) with associated polymyalgia rheumatica. GCA is the most common systemic vasculitis in persons of Northern European descent and occurs almost exclusively in patients age >50. Although both humoral and cellular immune mechanisms have been implicated in the pathogenesis of GCA, cell-mediated processes are of primary importance. The inflammatory infiltrate in affected vessels is composed of lymphocytes (predominantly CD4-positive T cells) and macrophages and frequently contains multinucleated giant cells. The production of cytokines, in particular interleukin-6 (IL-6), appears to closely correlate with the severity of the disease; a monoclonal antibody against IL-6 (tocilizumab) is effective in treating GCA. (Choices A and B) Antibodies to myeloperoxidase and proteinase-3 are involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides such as microscopic polyangiitis and granulomatosis with polyangiitis. (Choice C) B cell-activating factor (BAFF) is a cytokine belonging to the tumor necrosis factor ligand family. Inadequate levels of BAFF will lead to immunodeficiency, whereas excess levels can cause autoimmune diseases (eg, systemic lupus erythematosus). (Choice E) Matrix metalloproteinases are enzymes capable of degrading various extracellular matrix proteins and processing a number of bioactive molecules. They may be involved in cytokine inactivation but do not play a direct role in the pathogenesis of GCA. Educational objective: Cell-mediated immunity is the primary mechanism underlying giant cell arteritis. The production of cytokines, in particular interleukin-6, is an important driver of this process and closely correlates with the severity of symptoms. __________ References: Pathogenesis of giant cell arteritis: new insight into the implication of CD161+ T cells. (http://www.ncbi.nlm.nih.gov/pubmed/23663684) Pathogenesis of giant cell arteritis: more than just an inflammatory condition? (http://www.ncbi.nlm.nih.gov/pubmed/20457278) New treatment strategies in large-vessel vasculitis. (http://www.ncbi.nlm.nih.gov/pubmed/23114585)

A 65-Year-Old Man Comes to the Emergency Department with a 3-Day