preskas procalcitonin

SERUM PROCALCITONIN FOR DIFFERENTIATING BACTERIAL INFECTION FROM DISEASE FLARES IN PATIENTS WITH

SYSTEMIC LUPUS ERYTHEMATOSUS

Evie Rosa Widyawanti N

Evidence Based Case Report

INTRODUCTION

• Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with clinical features of multi-system damages and infection is one of the major causes of death.

• Increased risk of infection due to intrinsic disturbances of immune responses and the use of immunosuppressive drugs.

• Infections may mimic exacerbations of SLE, leading to confusion over the diagnosis and appropriate treatment.

• A reliable biomarker that provides high sensitivity and specificity for the early discrimination of bacterial infection from disease flare in patients with autoimmune diseases was needed.

CLINICAL SCENARIO

•A 30 year old female came with progressive shortness of breath 3 days prior to admission that was continuous and aggravated by physical activities.

•She also had high fever and productive cough since 1 month.•She had been diagnosed with SLE, 7 months before and had been

taking 4 mg of methyl prednisolone three times a day.

Anamnesis

•BP :130/90 mmHg, HR: 120 bpm, RR: 36 tpm and T: 38.5 0C. •Anemic conjunctiva, JVP was 5+2 H2O•Chest examination revealed decreased vesicular sound on right lung

with crackle both of lung. •Pitting edema on both legs

Physical Examinatio

n

•Hb of 8.7 g/dl (normocytic normochromic anemia) ,Ht: 25.2, WBC: 18.700/µl, Diff Count : 0/0/89/6/3/2 , PLT: 258000/µl, ANA positive, C3 and C4= 57 mg/dl and 13 mg/dl, Ur and Cr =179.2 mg/dl and 5.77 mg/dl.

Lab Results

•Chest x-ray infiltrate on both lungs with right pleural effusion, cardiomegaly.

•ECG test result was sinus rhythm and low voltage.•Echocardiography decreased LV function with EF of 39% and

moderate pericardial effusion

Radiology

•Her main symptom worsened and the fever persisted. Her respiratory was failure and her was intubated.

•Hb: 5.9 g/dl, Ht: 18.4 %, WBC: 11430/µl Diff count 0/0/95,9/2/ 2,1, PLT: 186000/µl and PCT: 63.47 ng/ml, Anti ds DNA 684.5.

2 Days in ward

•Sepsis, HCAP, functional class IV CHF with moderate pericardial effusion, SLE flare SLEDAI score12 with serositis, hematological and renal involvements, acute on CKD.

•Patient underwent hemodialysis and was administered meropenem 2x500 mg, methyl prednisolone 2x62.5 mg

•Sputum culture and resistance was Enterococcus sp and Candida albicans ampicillin sulbactam 3x3 g and fluconazole 2x200 mg IV, also Mycophenolate 2x180 mg as imunosuppresant

DIAGNOSIS AND

TREATMENT

CLINICAL QUESTION

Can procalcitonin be uses to differentiate bacterial infection and disease flare on patient with systemic lupus erythematosus?

METHODS

PUBMED

0 articles12 articles

“Procalcitonin AND Infection AND (Systemic Lupus Erythematosus OR SLE

Flare)”

COCHRANE

3 articles

Limited articles within 2004-2014 only.

Review articles and those that were not specific for SLE were excluded

CRITICAL APPRAISAL

Variable Wei Li Ho et al KM Bador et al Jinquan Yu et al

Sensitivity and Specifity

Sens: 89,5%Spec: 100%

I. Sens SLE : 80%Spec SLE : 78%

II. Sens SLE Flare : 83%Spec SLE : 71%

Sens : 74,5%Spec: 95,5%

Likelihood Ratio

(+) = ~(-) = 0,1

I. (+) = 3,6/(-) 0,2II. (+)= 2,8/(-) 0,2

(+)= 16,5(-)= 0,2

IMPORTANCE


Participants

49 SLE with febrile- 30 SLE flare without

infection - 19 SLE with bacterial

infection

68 SLE - 6 infected with SLE

flare- 4 infected SLE without

flare- 24 non infected with

SLE flare- 34 non infected SLE

without flare

114 SLE flare patients- 47 with bacterial

infection- 67 without infection

Study Design

Retrospective study Cross sectional study Retrospective studyHo W-L, Lan J-L, Chen D-Y, Chen Y-H, Huang W-N, Hsieh T-Y. Procalcitonin may be a potential biomarker for distinguishing bacterial infection from disease activity in febrile patients with systemic lupus erythematosus. Formosan

Journal of Rheumatology. 2009; 23: 52–8.

Bador KM , Intan S, Hussin S, Gafor AH . Serum procalcitonin has negative predictive value for bacterial infection in active systemic lupus erythematosus. Lupus. 2012; 21(11): 1172 – 7.

Jinquan Y, Bingling X, 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(3): 457-63.


Exclusion Criteria

Not available - Already on antibiotics- Had acute myocardial

infarction,acute pancreatitis, thyroid or bronchial carcinoma or a < 7 days history of severe trauma or surgery

- With no activity (SLEDAI score = 0)

- With non bacterial infection (viral and/or fungal infection) or mycobacterium tuberculosis infection

Intervention

PCT level was measured PCT level was measured PCT was measured


Comparison

Positive cultures in SLE patients with infection

Positive result from blood culture, urine, stool or other specimens in SLE patients with infection

Positive culture of the blood, urine and sputum

Outcome - PCT level in SLE patients with and without infection

- Sensitivity and specificity of PCT

- PCT level in SLE flare with and without infection

- PCT level in SLE with and without infection


- Positive predictive value

- Negative predictive value

- PCT level in SLE flare with and without infection


- Positive predictive value

- Negative predictive value

RESULT

Wei Li Ho et al study

Levels of serum PCT in the bacterial infection group (median 7.11 ng/mL, IQR 1.38-42.83) were higher when compared to the SLE disease flare group (median 0.06 ng/mL, IQR 0.05-0.20, p<0.001)

Sensitivity (89.5%), and Specificity (100%) of PCT at the 0.74 ng/mL cutoff

value

KM Bador et al study

Procalcitonin was significantly higher in patients SLE with bacterial infection compared to without infection (0.19 vs 0.06 ng/ml, p=0.003)

SLE patients without infection, PCT was higher in those with active disease (p<0.001). No correlation between SLEDAI score and PCT (r =0.158, p = 0.236)

Among infected patients there was no significant difference in PCT (p=0.088) levels between flare and remission patients

Among flare patients only, showed that PCT (0.33 versus 0.08 ng/ml, p= 0.019) was higher with infection

A cut-off value of 0.12 ng/ml for PCT sensitivity (80%) and specificity (78%) with PPV (38%) and NPV (96%)

A PCT cut-off value of 0.17 ng/ml sensitivity (83%) and

specificity (71%) to detect infection in lupus flare

patients with NPV (94%) and PPV (42%)

Jinquan yu et all study

The cutoff value 0.38 ng/ml had the best combination to compare SLE flare with and without infection sensitivity (74.5%) and specificity (95.5%), while the PPV and NPV were 92.1% and 84.2%, respectively

DISCUSSION

• Procalcitonin (PCT) is a 116-amino-acid residue peptide with molecular weight of about 13 kDa

• PCT was first described by Le Moullec et al. in 1984• PCT produced by the C cells of the thyroid gland as a precursor protein of

calcitonin• Synthesis and secre tion during infections extra-thyroi dal (the lung, liver,

pancreas, colon, and other organs)• Liliana simon et al, from the systematic reviews and meta-analysis serum PCT

and CRP as markers for bacterial infection, found that PCT level was more sensitive (88% vs. 75%) and more specific (81%vs. 67%) than CRP level for differentiating bacterial from non-infective causes of inflammation.• Serum PCT is normally undetectable (< 0.05 ng/mL) PCT levels > 0.5

ng/mL are used to distin guish infections from non-infectious inflammationHatzistilianou M . Diagnostic and prognostic role of procalcitonin in infections. Scientific World Journal. 2010; 10: 1941 – 6.

Muller Beat, Kenneth L. Procalcitonin: how a hormone became a marker and mediator of sepsis. Swiss Med Wkly. 2001; 131: 595-602.

Maruna P, Nedelnikova K. Physiology and genetics of procalcitonin. Physiol. Res. 2000; 49: S57-S61.

Christ Mirjam, Muller beat. Procalcitonin in bacterial infections – hype, hope, more or less?. Swiss Med Wkly. 2005; 1 3 5 : 4 5 1 – 4 6 0.

Ramanujam M, Davidson A. Targeting of the immune system in systemic lupus erythematosus. Expert reviews in molecular medicines. 2008; 10: 1-27.

NONINFECTIOUS CONDITIONS THAT MAY INCREASE PCT LEVELS

• Newborns (physiologically) during first days of life • Acute respiratory distress syndrome • Acute attacks of plasmodium falciparum malaria • Severe mechanical trauma • Following surgical trauma • Severe burns and heat strokes • Patients with medullary thyroid cancer, small cell cancer of the lung, carcinoid,

tumours with paraneoplastic hormone production• Treatment with interleukins, TNF-α, and other drugs stimulating the release of

proinflammatory cytokines

Hatzistilianou M . Diagnostic and prognostic role of procalcitonin in infections. Scientific World Journal. 2010; 10: 1941 – 6.

Christ Mirjam, Muller beat. Procalcitonin in bacterial infections – hype, hope, more or less?. Swiss Med Wkly. 2005; 1 3 5 : 4 5 1 – 4 6 0.

• Systematic reviews and meta-analysis by Jiunn-yih wu “The use of serum procalcitonin to detect bacterial infection in patients with autoimmune disease” sensitivity of 0.75 (95% CI 0.63–0.84) and specificity was 0.90 (95% CI 0.85–0.93) compared to CRP, sensitivity 0.77 (95% CI 0.67–0.85) and specifity was 0.56 (95% CI 0.25–0.83).

• The positive likelihood ratio (7.28 [95% CI 5.10–10.38]) as a rule-in diagnostic tool

• The negative likelihood ratio (0.28 [95% CI 0.18–0.40]) low to qualify procalcitonin as a reliable rule-out diagnostic tool

Joo K ,Park W ,Lim MJ ,Kwon SR ,Yoon J. Serum Procalcitonin for Differentiating Bacterial Infection from Disease Flares in Patients with Autoimmune Diseases. J Korean Med Sci. 2011; 26(9):

1147– 51.

We Li Ho et all study Significantly higher levels of serum PCT were noted in the bacterial infection group compared with the SLE disease flare group a good sensitivity of 89.5% and a specificity of 100 % serum PCT could be used as biomarker for detecting

bacterial infection in patients with SLE

KM Bador et all study negative predictive values were greater than positive predictive values suggesting that PCT may be a

better tool to rule out infection in SLE flare patients

• Jinquan yu et al study Specifity 95,5% and positive predictive value of PCT was up to 92.1%, indicating the

excellent ability of PCT test in diagnosing bacterial infection in SLE Flare patients.

The result differences may be influenced by the number of the subject in studies, prevalence of bacterial infection case with

SLE flare, and the procalcitonin cut-off value used in the studies

CONCLUSION

• Procalcitonin has a lower sensitivity but higher specificity with high PPV in one study and with high NPV in the other study so can be used to rule in or rule out bacterial infection in SLE flare patients.• Procalcitonin can be used as a biomarker to differentiate bacterial

infection and disease flare in patients with systemic lupus erythematosus with cut off PCT in 0,17 ng/ml and 0,38 ng/ml.• Further prospective study with serial measurement of PCT would

present more comprehensive evidences

Thank you

preskas procalcitonin

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