Dr. Greenbaum addresses an important question. What is the exact relation between giant cell arteritis and polymyalgia rheumatica? Our study [1] on tissue cytokines was designed to investigate whether and to what extent these diseases share pathogenetic mechanisms. In current clinical practice, polymyalgia rheumatica remains to some extent a diagnosis of exclusion. Because temporal artery vasculitis can be missed due to the patchy nature of the disease, we examine biopsy specimens from the contralateral temporal artery of patients suspected of having giant cell arteritis if cryosections of the first biopsy specimen are negative for the disease. Biopsy specimens from the bilateral temporal artery, combined with serial tissue sections, optimize the sensitivity of diagnosing vasculitis. Only a few patients who have biopsy specimens from both temporal arteries that are negative for giant cell arteritis present with or develop unequivocal clinical evidence for vasculitic involvement [2]. We do not routinely obtain biopsy specimens from patients with polymyalgia rheumatica, but the physicians examining the patients enrolled into our study believed that biopsy was appropriate, although no signs or symptoms of vasculitis were present.

Like Dr. Greenbaum, we are also interested in whether polymyalgia rheumatica is a heterogeneous disease. Indeed, we have examined the relation between polymyalgia rheumatica and giant cell arteritis using different methods, and all these studies have supported the model that these two diseases form a spectrum of disease. First, polymyalgia rheumatica and giant cell arteritis are genetically associated with the same HLA-DRB1 alleles [3, 4]. The strength of this association indicates that patients with polymyalgia rheumatica and giant cell arteritis are indistinguishable. Second, interleukin-6 concentrations are increased in patients with these diseases. So far, in untreated patients with either diagnosis, the extent of the increase in interleukin-6 levels has been very similar [5]. Third, patients with polymyalgia rheumatica and giant cell arteritis share a high frequency of activated circulating monocytes [5]. Fourth, patients with these diseases produce inflammatory cytokines in the temporal artery [1].

Features that distinguish polymyalgia rheumatica from giant cell arteritis include the formation of the histomorphologically detectable granulomatous infiltrate in the arterial wall and the local production of interferon- messenger RNA. We have hypothesized that patients with polymyalgia rheumatica have a characteristic immunoregulatory mechanism that protects most of them from progressing to full-blown vasculitis. Our studies also provide evidence that polymyalgia rheumatica is a heterogeneous entity. We are currently studying patients with polymyalgia rheumatica prospectively to define the full spectrum of the disease more completely.