Serum procalcitonin

What is a serum procalcitonin (PCT) and how should it be interpreted in the setting of autoimmune disease?

PCT is a propeptide of calcitonin and is produced in the thyroid gland. Virtually all PCT in the thyroid is converted to calcitonin; therefore, serum levels are undetectable or very low in healthy individuals (0.05 ng/mL). In bacterial infections, PCT levels are significantly elevated. The source of production in this setting is thought to lie outside the thyroid gland, although the exact site of production and the biologic function of elevated PCT are unknown. The clinical utility of the PCT test has been most extensively studied in bacterial infections among the general population, with data supporting a role for PCT in the decision of when to start and/or stop antibiotic therapy (common cut-off level ≥ 0.5 ng/mL).

The potential utility of PCT in differentiating infection from disease flare in patients with autoimmune disease has been examined in small retrospective and prospective cohort analyses. Disease activity in RA and SLE is associated with minor elevations in PCT levels, but values ≥ 0.5 ng/mL retain a high specificity for bacterial infection. Additional studies have suggested a potential role for PCT in differentiating septic arthritis from other causes of inflammatory arthritis. Of importance, some forms of vasculitis (granulomatosis with polyangiitis, Goodpasture’s disease, and Kawasaki disease), and adult-onset Still’s disease have been associated with elevated PCT in the absence of bacterial infection. Nonrheumatic conditions that have been associated with elevated PCT in the absence of infection include surgery, trauma, cardiogenic shock, pancreatitis, and some forms of cancer such as small-cell lung carcinoma.

Bacterial infections associated with a systemic inflammatory response are most commonly associated with elevated PCT levels, whereas viral infections are not associated with elevated PCT levels. Of interest, tumor necrosis factor-α (TNFα) and other cytokines have been identified as potential upregulators of PCT production. As such, there is theoretical concern about the clinical accuracy of PCT in patients on immunosuppressive medication. Limited data suggest that steroid therapy does not impair PCT levels in patients with concurrent bacterial infection. In addition, studies have shown similar rates of positive PCT values (≥ 0.5 ng/mL) among infected patients with autoimmune disease, regardless of whether they were on biologic therapy or not. Further investigation of this area is needed.

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