Infections are one of the most common cause of morbidity and mortality in rheumatic diseases. Autoimmune disease and immunosuppression makes a patient more susceptible. Differentiating a disease flare from infection has always remained a challenge even with addition of more and more armamentorium. The two may have similar clinical and laboratory features, beside the fact that the infections may precipitate underlying rheumatic disease flare, adding to the dilemma. It may not always be possible to wait for cultures as the patient may not give enough time and the management of an infection versus disease flare is poles apart.

Procalcitonin, a 116 amino acid protein and a precursor of calcitonin, produced by parafollicular C cells of thyroid gland, usually undetectable in healthy individuals, for unknown reasons, is increased in patients with infections [1] Bacterial infections resulting in increased endotoxin and IL-1 beta stimulates PCT secretion whereas IFN- gamma tends to decrease it [4] Procalcitonin rises within 4 hours, peaks after 6 hours and plateaus between 8 to 24 hours. PCT has a half-life time of approximately 24 hours, independent of renal function [2].

Does severity correlate with the serum levels ? Studies have revealed mixed results but generally it tends to be highest in Septic shock > Sepsis > SIRS and higher in patients with bacteremia and in infections with gram negative organisms when compared to gram positive patients [7,8] It may aid in differentiating septic shock from cardiogenic or due to adrenal insufficiency. However it is not a good tool to pick up viral or fungal infections or tuberculosis though it may be increased in parasitic infections like malaria. It can serve as a guide to antibiotic therapy [Procalcitonin Algorithm] [9]

A number of studies have tried analysing PCT in rheumatic diseases including its comparison to CRP with various cut off set in different diseases [Table 1 and 2] Some of the rheumatic diseases like AAV, AOSD, Kawasaki disease can have higher PCT during active disease [6,10]. Most of the studies in lupus mention PCT to be more specific than CRP with better positive likelihood ratio but a study by Bador et al, with 68 lupus patients (15% with infection) highlights CRP as a better differentiating tool in lupus patients in remission [11]. A case series on 7 patients with Neurobehcet showed PCT to be less than < 0.1 ng/ml and a good biomarker to differentiate it from bacterial meningitis. There is dearth of data on PCT in sarcoidosis and studies looking at TB and sarcoidosis found no difference in serum levels. A metaanalysis on septic arthritis which also included patients with RA underlined the utility of PCT as a differentiating tool [13].

Though various cut off have been defined but it needs to be prospectively assessed in larger group of patients particularly in non lupus CTD. The cutoff level also depends on the sensitivity on the testing system and definition of infection/sepsis [3]. The heterogeneity in defining these terms has been one of the difficulties faced in most studies/metanalysis.

PCT levels, thus maybe a useful tool, particularly when clubbed with a thorough history and physical examination, combined with appropriate immunological, microbiological, radiological, and histological data. Serial assessment will serve as a better guide considering the kinetics of this biomarker. It may be a good ‘rule in’ test but is not recommended as ‘rule out’ test for infections.

References

[1] Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515–8.

[2] Yu J, Xu B, Huang Y et al. Serum procalcitonin and C-reactive protein for differentiating bacterial infection from disease activity in patients with systemic lupus erythematosus. Mod Rheumatol 2014;24:45763.

[3] J Y Wu et al, Use of Serum Procalcitonin to Detect Bacterial Infection in Patients With Autoimmune Diseases, A and R, 201

2 [4] Linscheid P et al.: In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. Endocrinology 2003; 144: 5578-84.

[5] G G song et al, Diagnostic accuracies of procalcitonin and C-reactive protein for bacterial infection in patients with systemic rheumatic diseases: a meta-analysis, Clinical and Experimental Rheumatology, 2015;33: 166-173.

[6] Chen DY et al, Diagnostic value of procalcitonin for differentiation between bacterial infection and noninfectious inflammation in febrile patients with active adult-onset Still’s disease. Ann Rheum Dis 2009; 68: 1074-5.

[7] Bell K, Wattie M, Byth K, et al: Procalcitonin: A marker of bacteraemia in SIRS. Anaesth Intensive Care 2003; 31:629–636

[8] Giamarellou H, Giamarellos-Bourboulis EJ, Repoussis P, et al: Potential use of procalcitonin as a diagnostic criterion in febrile neutropenia: Experience from a multicentre study. Clin Microbiol Infect 2004; 10: 628–633

[9] Bouadma L, Use of Procalcitonin to Reduce Patients' Exposure to Antibiotics in Intensive Care Units (PRORATA Trial): A Multicentre Randomised Controlled Trial, Lancet 2010

[10] Moosig F, Csernok E, Reinhold-Keller E, Schmitt W, Gross WL. Elevated procalcitonin levels in active Wegener’s granulomatosis.J Rheumatol 1998;25(8):1531-3.

[11] K M bador et al, Serum procalcitonin has negative predictive value for bacterial infection in active systemic lupus erythematosus, Lupus 2012;12:1172-1177

[12] S koido et al, Clinical significance of serum procalcitonin in patients with ulcerative colitis, World J Gastroenterol 2013 Dec 7; 19(45): 8335–8341

[13] Shen et al. The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis, European Journal of Clinical Microbiology & Infectious Diseases, June 2013, Volume 32, Issue 6, pp 807–814

Dr Pravin Hissaria, Royal Adelaide Hospital, Adelaide

Dr Avinash Jain, DM Resident, SGPGIMS, Lucknow