Practice Perfect 692
Procalcitonin – A Useful New Diagnostic Tool for the Lower Extremity Specialist

Modern infection medicine is an ever-improving process with new lab tests, classifications, and decision analysis aids. Whether it’s the UT classification, LRINEC score, SIRS/SOFA scores, or the use of lactate, providers have many options to acquire data to better inform and assist their patient care decisions. In my location procalcitonin, although present as a lab test since the 1970s, is not commonly used, and I was never trained in its use. Let’s explore procalcitonin with a high-yield review, and, if you’re not already using it, you can decide if it would be useful for your patients.

What is Procalcitonin?

Procalcitonin (PCT) is a 116 amino acid protein precursor molecule to calcitonin. PCT is produced in the parafollicular cells of the thyroid gland in response to multiple genetic and chemical markers in the blood with almost 100% conversion to calcitonin. Calcitonin is involved in the homeostasis of calcium and phosphorous and is secreted in response to elevated serum levels of calcium. Levels of procalcitonin in the blood are normally less than 0.05 ng/mL.1

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During inflammatory conditions, specifically bacterial septicemia, multiple organs (adipocytes, spleen, white blood cells, kidney, pancreas, colon, and brain) release PCT over a 2-6-hour time period, which peaks at 6-24 hours1 and has a half-life of 30 hours.2 PCT elevates rapidly during the onset of infection and disappears from the blood quickly (due to the short half-life) as sepsis resolves, making it a good biomarker for the diagnosis of bacterial infection and tracking the course of an infection when used in serial fashion. PCT release is blocked by interferon gamma, released during viral infections, which is why this is a good bacterial infection indicator.2 A meta-analysis found procalcitonin to have a sensitivity of 77% and specificity of 79%.3

Procalcitonin is a good biomarker for the diagnosis of bacterial infection and tracking the course of an infection when used in serial fashion.

How to Use Procalcitonin

PCT is easily ordered just as any other lab test such as ESR or CRP. Its cost is a little higher, but not very expensive, at about $25.4 It is recommended to use PCT as one test in a battery of labs rather than as an independent marker of infection.

Interpret PCT as follows:

Normal < 0.05 ng/ml

Sepsis 0.05 ng/ml – 2ng/ml

Severe sepsis 2ng/ml – 10ng/ml

Septic shock > 10ng/ml

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Keep in mind that false positives and negatives may be seen with procalcitonin. False positives occur during high stress events that cause inflammation such as trauma, surgery, burns, and pancreatitis. False negatives may be seen in localized infections such as abscesses or if drawn too early in the course of infection.2

Procalcitonin is highly useful to discriminate between infectious and noninfectious causes of inflammation.

Different algorithms for using procalcitonin levels exist, but for the purposes of the lower extremity specialist, the following may be used.1

< 0.1 ng/ml antibiotics are STRONGLY DISCOURAGED
0.1 – 0.25 ng/ml antibiotics are DISCOURAGED
0.25ng/ml – 0.5ng/ml antibiotics are ENCOURAGED
> 0.5ng/ml antibiotics are STRONGLY ENCOURAGED

What About “Special” Situations?

It’s important to keep in mind that recommendations for the use of the lab test, like many others, are made with the entire body in mind, including respiratory tract infections, which are less of an issue for podiatrists. However, some research has been done in situations that pertain to lower extremity infections. Let’s take a quick look at some.

Diabetic Foot Infections - Velissarius and colleagues recommend PCT along with CRP as a potentially useful diagnostic test with the cautionary note that localized infections will demonstrate lower levels than patients with systemic infections.5

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Necrotizing Fasciitis - Nova-Parra and colleagues found PCT to be a more accurate differentiator of early necrotizing fasciitis from cellulitis of the lower extremity than the LRINEC score in a retrospective case-control study.6 They defined risk of necrotizing fasciitis as low if the PCT was < 0.5ng/ml, moderate at PCT 0.5- 1.9 ng/ml, and high at > 2.0 ng/ml.

Osteomyelitis - Van Asten, et al found procalcitonin levels to be much higher in patients with osteomyelitis of the foot compared with those without (diagnosis based on bone culture and histopathology).7 The authors correctly caution that the results may be skewed due to the high pretest probability of osteomyelitis in their patient population (hospitalized patients with infections). Shen and colleagues, in a meta-analysis, determined PCT to be a better rule-in test than rule-out for bone and joint infections.8 They suggested that a lower cut-off value would improve the sensitivity of the test. We should interpret this information as increasing our concern for osteomyelitis in patients with high PCT levels.

Shen and colleagues determined PCT to be a better rule-in test than rule-out for bone and joint infections.8

Present Treasure Hunt 2020

As we close out this discussion, it’s important to point out that procalcitonin is highly useful to discriminate between infectious and noninfectious causes of inflammation. For example, an elevated PCT level discriminates well between cellulitis of the lower extremity versus DVT.9 It seems reasonably clear, then, that procalcitonin is a serum test we should be using more often than previously.

Best wishes.

Jarrod Shapiro, DPM
PRESENT Practice Perfect Editor
jarrod@podiatry.com
References
  1. Vijayan A L, Ravindran S, Saikant R, et al. Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy. J Intensive Care 2017 Aug 3,5:51
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  2. Rhee C. Using Procalcitonin to Guide Antibiotic Therapy. In Open Forum Nnfect Dis. 2016 Dec 7;4(1):ofw249.
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  3. Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013 May;13(5):426-435.
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  4. Procalcitonin Testing in Suspected Infection: Review. https://pulmccm.org/review-articles/procalcitonin-suspected-infection-review/. Last accessed 2/1/2020.
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  5. Velissarius D, Pantzaris ND, Platanaki C, et al. Procalcitonin as a diagnostic and prognostic marker in diabetic foot infection. A current literature review. Roman J Int Med. 2018 Mar 1;56(1):3-8.
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  6. Novoa-Parra CD, Wadhwani J, Puig-Conca MA, et al. Usefulness of a risk scale based on procalcitonin for early discrimination between necrotizing fasciitis and cellulitis of the extremities. Med Clín. 2019 Nov 15;153(9):347-350.
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  7. Van Asten SAV, Nichols A, La Fontaine J, Bhavan K, Peters EJG, Lavery LA. The value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis. Int Wound J. 2017 Feb;14(1):40-45.
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  8. Shen CJ, Wu MS, Lin KH.. The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis. Eur J Clin Microbiol Infect Dis. 2013 Jun;32(6):807-814.
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  9. Rast AC, Knobel D, Faessler L, et al. Use of procalcitonin, C‐reactive protein and white blood cell count to distinguish between lower limb erysipelas and deep vein thrombosis in the emergency department: a prospective observational study. J Dermatol. 2015 May 18;42(8):778-785.
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