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Rheumatology Advance Access originally published online on December 20, 2008
Rheumatology 2009 48(2):158-159; doi:10.1093/rheumatology/ken437
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Procalcitonin at the onset of giant cell arteritis and polymyalgia rheumatica: the GRACG prospective study

J. Schmidt1, P. Duhaut1, A.M. Bourgeois2, V. Salle1, A. Smail1, D. Chatelain3, F. Betsou4, J.C. Mazière2, J.P. Ducroix1 and members of the Groupe de Recherche sur l’Artérite à Cellules Géantes (GRACG)

1Department of Internal Medicine and RECIF, 2Laboratory of Biochemistry, 3Department of Pathology and 4Biobank of Picardie, Amiens University Hospital, Amiens, France.

Correspondence to: J. Schmidt, Department of Internal Medicine, Place Victor Pauchet, Amiens University Hospital, 80000 Amiens CEDEX 1, France. E-mail: schmidt.jean{at}chu-amiens.fr


   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Objectives. An epidemic pattern has been reported for GCA and PMR. Immunological studies have shown that an unknown antigen activates the dendritic cells of the adventitia and the type 4 toll-like receptors. Procalcitonin (PCT) is an early marker of bacterial infection. The goal of the study was to assess the level of PCT in GCA and PMR at the onset of the disease.

Methods. Patients diagnosed during the 2002–06 period were randomly selected. All the 46 patients fulfilled the ACR or the Hunder criteria, and all blood samples were taken before steroid therapy.

Results. PCT was normal in all patients. PCT was slightly increased in men (0.087 ± 0.023 µg/l) compared with women (0.066 ± 0.027 µg/l) (P = 0.009), and in PMR (0.092 ± 0.027µg/l) compared with GCA (0.068 ± 0.026 µg/l) (P = 0.018). There was no significant correlation with inflammation markers.

Conclusions. These results are not in favour of a bacterial trigger for GCA or PMR. Increased PCT levels in patients with inflammatory syndrome, GCA–PMR symptoms and negative temporal artery biopsy may rule out the diagnosis of GCA and PMR.

KEY WORDS: Giant cell arteritis, Polymyalgia rheumatica, Procalcitonin, Infectious trigger


   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 References
 
GCA is a vasculitis of unknown origin, associated in 40% of the cases with PMR [1]. However, an epidemic pattern has been suggested in epidemiological studies [2], some authors have suggested that bacteria could trigger the disease [3], and toll-like receptors usually activated by bacterial agents are also activated at the early stages of the GCA and PMR inflammatory process, as well as the adventitial dendritic cells [4, 5]. Determination of procalcitonin (PCT) level is routinely performed in severe pneumonia, pancreatitis, meningitis and post-operative fever as a marker of bacterial infection and/or severity. In these conditions, sensitivity has been assessed as medium (± 70%) and specificity as good or excellent (± 90%) [6, 7]. A mild increase of PCT level has been described in various active inflammatory diseases such as Behçet's disease and Wegener's granulomatosis [8]. Moreover, Okada et al. [9] found elevated PCT levels during the acute phase of Kawasaki disease, which affects large- and medium-size arteries (mean ± S.D.: 2.3 ± 3.0 ng/ml), but not during the subacute phase.

Whether a mild increase reflects disease activity, the non-specific inflammatory syndrome, or an associated infection remains unknown, but could be of interest for the clinician before beginning high-dose steroids or immunosuppressive agents. Serum inflammatory markers such as CRP increase in atherosclerosis [10]. A mild increase in PCT levels has been demonstrated in patients with coronary artery disease [11].

PCT may be elevated in GCA, a medium- and large-size artery vasculitis of the elderly (in which atherosclerosis is frequent) [12].

The aim of this study was to assess PCT levels in GCA and PMR patients, at the onset of the disease, before steroid treatment.


   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 References
 
Patients
Newly diagnosed GCA and/or PMR patients were included on pre-determined diagnostic criteria. Inclusion and exclusion criteria have been previously described [13]. Patients included in the present study were randomly selected over the 2002–06 period, in the Internal Medicine Department of the Amiens University Hospital. All GCA patients fulfilled the ACR criteria, and all PMR patients the Hunder criteria (age of 50 yrs or older; bilateral aching and stiffness for 1 month or more and involving two of the following areas: neck or torso, shoulders or proximal regions of the arms, and hips or proximal aspects of the thighs; ESR >40 mm/h; exclusion of all other diagnoses except GCA [14]). Clinical characteristics of patients were collected at the onset of the disease with a pre-established questionnaire. All blood samples were collected before steroid treatment. A temporal artery biopsy (TAB) was performed in all patients. Peripheral arterial disease was defined as a non-palpable or murmuring large-size artery at the time of diagnosis.

Conditions that may mimic PMR or GCA (infectious disease, recent malignancy, RA, SLE, PAN) were excluded [15].

The study has been approved by the local ethical committee, and patients have given their written consent.

Measurements
PCT level was assessed by automated immunofluorometric assay (Brahms, Saint Ouen, France). Rates <0.5 µg/l were considered as normal in our laboratory, and the lowest limit of detection was 0.02 µg/l.

Statistical analysis
Statistical analysis was performed with SAS (Statistical Analysis System, SAS Institute, Cary, NC, USA). Quantitative variables were expressed as mean ± S.D. when the distribution was normal, and as median and extremes when it was not. A Wilcoxon rank sum test was performed for quantitative variables, and a Spearman coefficient was computed for correlations.


   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 References
 
Forty- six patients entered the study, 31 women (mean age 75 ± 7 yrs) and 15 men (mean age 74 ± 10 yrs). There were 36 GCA and 10 ‘pure’ PMR without GCA. Among the GCA patients, 22 had positive TAB, 14 negative TAB. All PMR had negative TAB.

PCT was low and normal in all patients, and never exceeded 0.124 µg/l. Classical inflammation markers were elevated, such as ESR (75 ± 23 mm) or CRP (89 ± 57 µg/l).

PCT was slightly increased in men (0.087 ± 0.023 µg/l) compared with women (0.066 ± 0.027 µg/l, P = 0.009), and in PMR compared with GCA (0.092 ± 0.027 vs 0.068 ± 0.026 µg/l, P = 0.018). However, these small variations within normal range may not have any clinical or physiopathological relevance. PCT levels did not differ between biopsy-positive and biopsy-negative GCA (0.065 ± 0.027 vs 0.074 ± 0.024 µg/l, P = 0.06).

We found no correlation between PCT levels and ESR (P = 0.76), CRP (P = 0.87), haptoglobin (P = 0.99), fibrinogen (P = 0.46), ferritin (P = 0.55) or platelet count (P = 0.34).

Since smoking increases inflammation markers levels [16], we compared PCT levels in smokers (n = 17) and non-smokers (n = 29): PCT levels did not significantly differ (0.081 ± 0.025 vs 0.067 ± 0.028 µg/l, P = 0.1). Also, PCT levels were similar in patients with (n = 6) and without (n = 40) clinically pre-existent peripheral artery disease (0.075 ± 0.028 vs 0.071 ± 0.028 µg/l, P = 0.4).


   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
References
 
PCT levels are normal and low in all 46 GCA and PMR patients at diagnosis. Delèvaux et al. [17] published consistent results in 13 GCA patients (PCT median level: 0.1 ng/ml). Such negative results may be helpful for clinicians in diagnosing GCA and PMR: increased PCT levels in suspected GCA–PMR patients lead to consider another diagnoses or a simultaneous bacterial infection.

PCT levels <0.5 µg/l are usually considered as normal. However, a mild increase in PCT level has been observed in active inflammatory disease without infection [18]. So the PCT level useful to discriminate between infectious and non-infectious aetiology of fever is difficult to determine. According to Delèvaux et al. [17], bacterial infection should be considered for PCT levels >1.2 µg/l. However, Quintana et al. [18] described a patient with active SLE and without infection, with a PCT level at 3.18 µg/l, and this illustrates the difficulty of assessing a PCT rate cut-off.

As for Kawasaki disease, affecting large- and medium-size arteries, infectious agents have been suspected in GCA. Unlike Kawasaki, however, PCT levels do not increase even at the onset of the disease: our data may argue against the bacterial trigger hypothesis. However, one cannot exclude that the rapid kinetics of PCT elevation could explain PCT normality after a transient rise. Also, elevated PCT is rather seen in invasive or severe bacterial infections, which certainly is not the case in GCA even in the hypothesis of a bacterial trigger.

Some clinical differences between biopsy-proven, and biopsy-negative GCA patients (diagnosed with GCA, and fulfilling the ACR classification criteria) have been described; more particularly, there may be a decreased incidence of severe ischaemic complication in TAB-negative patients at diagnosis [19, 20]. In our study, PCT levels did not differ between biopsy-positive and biopsy-negative GCA (0.065 ± 0.027 vs 0.074 ± 0.024 µg/l, P = 0.06).

Conclusion
PCT levels are normal and low in all patients diagnosed with GCA and/or PMR at the onset of the disease, before steroid therapy. PCT levels are not likely to be modified by the already known risks factors for the disease. These results are not in favour of a bacterial trigger for GCA or PMR. Increased PCT levels in patients with inflammatory syndrome, GCA–PMR symptoms and negative temporal artery biopsy may rule out the diagnosis of GCA and PMR.

Formula

Disclosure statement: The authors have declared no conflicts of interest.


   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Submitted 6 August 2008; revised version accepted 17 October 2008.
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