"Silent" giant cell arteritis.

Giant cell (temporal) arteritis (GCA) is a large and medium-sized blood vessel systemic vasculitis characterized by the granulomatous involvement of the aorta and its major branches, with predilection for the extracranial branches of the carotid artery. (1) GCA is the most common vasculitis in the elderly in white individuals. (2)

Classically, GCA patients present with clinical manifestations that are the result of vascular involvement. Among them, cranial ischemic complications, in particular irreversible visual loss, are the major sources of chronic disability in these patients. (1,3-5) They are the result of inflammation of the arterial wall, yielding a series of structural changes, such as intimal hyperplasia and fragmentation of internal elastic laminae, leading to luminal occlusion. (6)

In most cases, the diagnosis of GCA is relatively straightforward. However, a variable proportion of individuals may present without obvious vascular manifestations of this vasculitis. (7-11) In this regard, 18 (7.5%) of 240 patients diagnosed with biopsy-proven GCA in Lugo (Northwestern Spain) between January 1, 1981, and June 15, 2004, presented with subclinical ("silent") GCA. No overt ischemic manifestations of GCA were observed from the onset of symptoms until the time of disease diagnosis. (4) Eleven of them presented with polymyalgia rheumatica (PMR) features. Two fulfilled criteria for fever of unknown origin. The remaining 5 patients presented at the hospital because of asthenia, anorexia, weight loss, and/or anemia. Patients with "silent GCA" had lower mean hemoglobin values than those with typical cranial ischemic manifestations (11.0 g/dL versus 11.8 g/dL). (4)

In a variable proportion of cases, a temporal artery biopsy (TAB) taken from patients with isolated PMR, without any cranial manifestation related to vascular involvement in the setting of GCA, may yield typical inflammatory changes of GCA. (12,13) However, this frequency seems to be low in a series of unselected patients. (14) In Lugo, a TAB is generally considered in patients with isolated "pure" PMR if they have constitutional syndrome (asthenia anorexia and weight loss of at least 4 kg) and/or the erythrocyte sedimentation rate is greater than 80 mm/h. (15-17) Following this procedure, only 9% of the patients with isolated PMR were found to have positive biopsy results for GCA. (17,18) Also, in our experience, the potential development of cranial manifestations of GCA in those patients initially diagnosed as having isolated PMR generally occurs within the first two years after the onset of PMR symptoms. In the series from Lugo, only 2% of patients diagnosed as having isolated PMR, who did not exhibit symptoms of GCA within the first 2 years after the diagnosis of PMR, developed cranial ischemic features of GCA later over their extended follow-up. (17)

In this issue of the Southern Medical Journal, Kathula et al describe a patient with biopsy-proven GCA without clinically evident vascular involvement. (19) The patient presented with severe anemia, monoclonal gammopathy, high erythrocyte sedimentation rate, and significant weight loss. The authors support the fact that GCA may present with atypical manifestations and without the classic cranial ischemic manifestations of the disease. They also emphasize the importance of considering additional tools, such as 18F-fluorode-oxyglucose positron emission tomography (FDG-PET), to detect the presence of "silent" vascular involvement in GCA. Interestingly, they confirmed a diagnosis of GCA by a positive TAB. This procedure should be utilized by all clinicians as a positive TAB is the gold standard test for the diagnosis of GCA. (20)

FDG-PET has recently been assessed for its value in evaluating patients with large vessel inflammation. FDG-PET imaging may be helpful in the diagnosis of GCA of large arteries in patients with atypical manifestations of the disease and negative or unavailable TAB. (21) FDG-PET has the advantage of identifying all the sites of large vessel inflammation within one examination. However, this technique is less accurate in vessels of temporal artery size. FDG-PET uptake decreases following corticosteroid therapy, at a time when inflammatory parameters had normalized and patients had become asymptomatic. (21,22) This observation might suggest a potential role of FDG-PET in the follow-up of patients with GCA.

In conclusion, GCA may present without clinically evident vascular manifestations. A diagnosis of GCA must be considered in patients with unexplained fever, severe anemia, constitutional syndrome or PMR associated with severe inflammatory response, despite the absence of cranial ischemic manifestations of this vasculitis.

References

1. Levine SM, Hellmann DB. Giant cell arteritis. Curr Opin Rheumatol 2002;14:3-10.

2. Gonzalez-Gay MA. Garcia-Porrua C. Epidemiology of the vasculitides. Rheum Dis Clin North Am 2001;27:729-749.

3. Huston KA, Hunder GG, Lie JT, et al. Temporal arteritis: a 25-year epidemiologic, clinical, and pathologic study. Ann Intern Med 1978;88:162-167.

4. Gonzalez-Gay MA, Barros S, Lopez-Diaz MJ, et al. Giant cell arteritis: disease patterns of clinical presentation in a series of 240 patients. Medicine (Baltimore) 2005;84:269-276.

5. Gonzalez-Gay MA, Garcia-Porrua C, Llorca J, et al. Visual manifestations of giant cell arteritis. Trends and clinical spectrum in 161 patients. Medicine (Baltimore) 2000;79:283-292.

6. Weyand CM, Goronzy JJ. Arterial wall injury in giant cell arteritis. Arthritis Rheum 1999;42:844-853.

7. Healey LA, Wilske KR. Presentation of occult giant cell arteritis. Arthritis Rheum 1980;23:641-643.

8. Calamia KT, Hunder GG. Giant cell arteritis (temporal arteritis) presenting as fever of undetermined origin. Arthritis Rheum 1981:24:1414-1418.

9. Desmet GD, Knockaert DC, Bobbaers HJ. Temporal arteritis: the silent presentation and delay in diagnosis. J Intern Med 1990;227:237-240.

10. Gonzalez-Gay MA, Garcia-Porrua C, Amor-Dorado JC, et al. Fever in biopsy-proven giant cell arteritis: clinical implications in a defined population. Arthritis Rheum 2004;51:652-655.

11. Gonzalez-Gay MA, Garcia-Porrua C, Amor-Dorado JC, et al. Giant cell arteritis without clinically evident vascular involvement in a defined population. Arthritis Rheum 2004;51:274-277.

12. Chuang TY, Hunder GG, Ilstrup DM, et al. Polymyalgia rheumatica: a 10-year epidemiologic and clinical study. Ann Intern Med 1982;97:672-680.

13. Healey LA. The spectrum of polymyalgia rheumatica. Clin Geriatr Med 1988;4:323-331.

14. Cantini F, Niccoli L, Storri L, et al. Are polymyalgia rheumatica and giant cell arteritis the same disease? Semin Arthritis Rheum 2004;33:294-301.

15. Gonzalez-Gay MA, Garcia-Porrua C, Vazquez-Caruncho M. Polymyalgia rheumatica in biopsy proven giant cell arteritis does not constitute a different subset but differs from isolated polymyalgia rheumatica. J Rheumatol 1998;25:1750-1755.

16. Gonzalez-Gay MA, Garcia-Porrua C, Vazquez-Caruncho M, et al. The spectrum of polymyalgia rheumatica in northwestern Spain: incidence and analysis of variables associated with relapse in a ten year-study. J Rheumatol 1999;26:1326-1332.

17. Gonzalez-Gay MA. Giant cell arteritis and polymyalgia rheumatica: two different but often overlapping conditions. Semin Arthritis Rheum 2004;33:289-293.

18. Gonzalez-Gay MA, Garcia-Porrua C, Rivas MJ, et al. Epidemiology of biopsy proven giant cell arteritis in northwestern Spain: trend over an 18 year period. Ann Rheum Dis 2001;60:367-371.

19. Kathula SK, Mantil J, Drehmer T, et al. Giant cell arteritis mimicking multiple myeloma, diagnosed by PET scan. South Med J 2006;99:1280-1281.

20. Gonzalez-Gay MA. The diagnosis and management of patients with giant cell arteritis. J Rheumatol 2005:32:1186-1188.

21. Schmidt WA, Blockmans D. Use of ultrasonography and positron emission tomography in the diagnosis and assessment of large-vessel vasculitis. Curr Opin Rheumatol 2005;17:9-15.

22. Gonzalez-Gay MA, Garcia-Porrua C, Miranda-Filloy JA. Giant cell arteritis: diagnosis and therapeutic management. Curr Rheumatol Rep 2006;8:299-302.

A sordid gain brigs no good in the end.
--Ovid

Miguel A. Gonzalez-Gay, MD, PhD, and Jose A. Miranda-Filloy, MD

From the Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain.

Reprint requests to Dr. Miguel A. Gonzalez-Gay, Division of Rheumatology, Hospital Xeral-Calde, c/o Dr. Ochoa s/n, 27004 Lugo, Spain. Email: [e-mail]