GCA and PR on NEJM

Weyand CM and Goronzy JJ. Giant-Cell Arteritis and Polymyalgia Rheumatica. N Engl J Med (2014) 371:50-57 July 3, 2014 DOI: 10.1056/NEJMcp1214825

Fazio S. Giant-Cell Arteritis and Polymyalgia Rheumatica. Now@NEJM. July 4, 2014.

The latest edition of the New England Journal features a major review on giant-cell arteritis (GCA) and polymyalgia rheumatica  (PR). Here we present the details in brief.

GCA and PR (which is 3-10 times more frequent) are beginning to look like different phases of the same disease. Both are now recognized as chronic conditions.

PR can present before, during, or after GCA. As a vignette in this review describes, it can appear while glucocorticoids are being tapered after an acute attack.

There are still no validated diagnostic criteria for either condition. GCA is suspected on the basis of patient demographics, history, clinical evaluation, and laboratory tests, and confirmed by biopsy. Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have high sensitivity but low specificity for GCA.

The classic temporal artery biopsy identifies 85-95% of GCA. Interpreting the negative temporal biopsies is difficult. False negatives arise when there is subclavian but not temporal artery involvement. Magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) can identify GCA in patients with negative biopsies.

Because wrongly interpreting biopsies as false negatives and treating these patients would expose them to the risk of unnecessary glucorticoid treatment, the authors believe that negative biopsies should be repeated.

Large-vessel vasculitis occurs in 25% of patients with giant-cell arteritis, and follows the aortic tree. MRA and CTA can identify those cases. Intramural leaky microvessels give rise to delayed enhancement of the artery wall, which is consistent with but not specific for inflammatory activity.

Glucocorticoid monotherapy is an effective treatment. Other treatments have weak evidence or marginal benefit, but are widely used nonetheless, the authors say. There is no data to support use of aspirin and statins.

This review generally follows the treatment recommendations of the British Society for Rheumatology, although the European League Against Rheumatism recommendations suggest a faster initial tapering.

Flares occur frequently during tapering, often manifested as polyarthritis rheumatica, and respond to small increases in glucorticoids. Inflammatory markers are monitored monthly during the first year, bimonthly during the second year, and at 3-6 months for long-term followup, consistent with the concept of chronic disease.

The latest molecular studies suggest that dendritic cells in the vessel wall start the pathogenic cascade and recruit T cells and macrophages to form the granulomatous infiltrates. The immune response includes T helper (Th) cells, interferon (IFN), and interleukin (IL). Two major pathways have been identified: One involving IL-6, Th17, IL-17 and IL-21, and the second involving IL-12, Th1, and IFN-γ. The first, but not the second, is suppressed with glucocorticoids.

These inflammatory processes target arterial endothelial cells, smooth muscle cells, and fibroblasts, leading to lumen-obstructive intimal hyperplasia. Further processes promote remodeling of the arterial wall, which results in the clinical manifestations.