Serum Procalcitonin as a Potential Marker for Differential Diagnosis of Acute Gouty Attack and Bacterial Infection

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Serum Procalcitonin as a Potential Marker for Differential Diagnosis of Acute Gouty Attack and Bacterial Infection
Key Take-Away: 

Serum procalcitonin (PCT) levels found to be significantly lower in patients with the acute gouty attack than in patients with bacterial infection.

The acute gouty attack is an inflammatory response in which monosodium urate crystals get deposited in joints. It is characterized by redness, tenderness, swelling, and heat over inflamed joints, and systemic fever.

ABSTRACT: 
Background: 

The acute gouty attack is an inflammatory response in which monosodium urate crystals get deposited in joints. It is characterized by redness, tenderness, swelling, and heat over inflamed joints, and systemic fever.  The differential diagnosis between acute gouty attack and bacterial infections is occasionally difficult due to the resemblance between clinical features and laboratory findings including leukocytosis and increase in levels of the serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Hyperuricemia is used to distinguish between acute gouty attack and bacterial infection. However, in some instances, serum uric acid increases in bacterial infection and not in the acute gouty attacks making the diagnosis tricky.

Procalcitonin (PCT) is a 13-kDa protein produced by C cells of the thyroid gland in the form of a calcitonin precursor, but during a bacterial infection, PCT production occurs in other organs as well. It can also function as an acute-phase reactant during bacterial infection as reported by some studies. Therefore, it can be regarded as an important biomarker for the early diagnosis of sepsis in critically ill patients.

Rationale behind research

  • There is lack of data available that can report the role of PCT in acute gouty attack
  • This study was carried out to determine the effectiveness of PCT to function as a marker for differential diagnosis between acute gouty attack and bacterial infection.

Objective

To determine the differences in PCT levels between the two inflammatory conditions, acute gout, and bacterial infections, and evaluating the ability of serum PCT to function as a clinical marker for differential diagnosis between gouty attack and bacterial infection.

Methods: 

 

Study outcomes

  • For acute gouty attack patients: Included measurements of PCT, ESR, CRP, complete blood count, uric acid, blood urea nitrate, creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), in addition to other laboratory tests. A test to measure PCT was performed before the administration of drugs for the gouty attack, such as NSAIDs.
  • For patients with bacterial infection: Clinical and laboratory data were taken from the medical records at the day when the serum PCT was measured. A fluorescent enzyme immunoassay was used to measure serum PCT levels according to the manufacturer's recommendations. The assays were performed in duplicates, and the detection limits of serum PCT varied between 0.05 ng/mL and 200 ng/mL.
Results: 

 

Baseline: No considerable baseline differences between the groups were observed

Study outcomes:

  • No significant difference found between ESR levels, CRP levels and WBC count between acute gout group and bacterial infection group.
  • In patients with acute gouty attacks, serum uric acid levels were found to be higher as compared to bacterial infections (7.62±2.03 mg/dL vs. 5.19±2.36 mg/dL, p<0.001) (Fig-1).
  • PCT levels were higher in patients with bacterial infections as compared to acute gout patients (4.94±13.763 ng/mL vs. 0.096±0.105 ng/mL vs., p=0.001) (Fig-2)

Figure 1: Serum Uric acid levels in patients with acute gout and bacterial infections

Figure 2: Serum PCT levels in patients with acute gout and bacterial infection

  • When ROC (Receiver-operating characteristic) analysis was carried out to assess ability of PCT levels in differentiating acute gout and bacterial infectious group, the areas under the curves (AUCs) of serum PCT, uric acid, and CRP were 0.857 [95% confidence interval (CI), 0.798–0.917, p<0.001], 0.808 (95% CI, 0.738–0.878, p<0.001), and 0.638 (95% CI, 0.544–0.731, p=0.005), respectively.
  • No considerable differences in ESR and white blood cell count were observed between these two conditions.
  • With a cut-off value of 0.095 ng/mL, the sums of sensitivity and specificity of PCT were the highest (81.0% and 80.6%, respectively).
Conclusion: 

It is not easy for the clinicians to distinguish between acute gout attacks and bacterial infections as they possess similarities in their symptoms. A precise diagnosis between acute gouty attack and infectious diseases is essential, as the management methods for these conditions are distinct. Particularly, glucocorticoid or canakinumab use in patients with bacterial infection can lead to serious adverse events. In this study, the ability of PCT levels to be used as a serological marker in discrimination of acute gout attacks and bacterial infections has been evaluated. This study is the first report to show the utility of serum PCT levels in the diagnosis of acute gout patients.

The different markers used for diagnosis of these diseases like serum ESR or CRP levels and leukocytosis shows no significant differences in these two conditions, but PCT levels and serum uric acid levels can be used to distinguish between acute gout and bacterial infections. PCT levels were found to be <0.05 ng/mL or are undetectable in healthy individuals, but the PCT levels are significantly increased in patients with bacterial infections as compared to patients with gout attacks. This may be due to the production of microbial endotoxins and indirectly by many pro-inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 in various tissues, including lung, liver, kidney, and adipose tissue. PCT levels do not increase significantly in gouty attack patients; however, the reason remains unexplained. It is suspected that in acute gout patients there may be some cytokines produced that inhibit PCT.

In conclusion, serum PCT is expected to be a useful serologic marker for differential diagnosis between acute gout arthritis and bacterial infection. The best cut-off PCT value to distinguish between infection and gout was 0.095 ng/mL, with a sensitivity of 81.0% and a specificity of 80.6%.

Yonsei Med J 2016 Sep;57(5):1139-1144

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