Psoriasis is a systemic disease: A proposed approach for infl ammation scale calculation

Psoriasis is a skin disease affecting 2.3% of the Iraqi population [1] and 1–3% globally [2]. The disease is characterized by a chronic natural history characterized by remission, relapse, and acute exacerbation [3]. Although psoriasis has an obscure etiology, previous studies have suggested that genetic, infectious, immunological, and environmental factors play a role in the induction of the disease [4,5]. Psoriasis is induced as a local dermatological disease with subsequent immuno-inflammatory and metabolic changes [6,7].


INTRODUCTION
Psoriasis is a skin disease affecting 2.3% of the Iraqi population [1] and 1-3% globally [2]. The disease is characterized by a chronic natural history characterized by remission, relapse, and acute exacerbation [3]. Although psoriasis has an obscure etiology, previous studies have suggested that genetic, infectious, immunological, and environmental factors play a role in the induction of the disease [4,5]. Psoriasis is induced as a local dermatological disease with subsequent immuno-inflammatory and metabolic changes [6,7].
The diagnosis of systemic inflammation with a mathematical model was previously reported for clinical conditions such as obstetric, acute multiple injuries, heart surgery, and sepsis [36,37]. Thus, this study proposed a mathematical model for the calculation of a scale that may be employed to diagnose the presence of systemic inflammation in psoriasis and to monitor treatment response of the disease.

Study Population
The present study included 211 subjects with psoriasis attending a dermatology clinic during the period from January 2012 till the end of May 2014.
A total of 163 subjects, sex-and age-matched controls, were included in the study.
The mean age of the patients was 37.85 (±14.81) years, and that of the control group was 36.76 (±10.92) years with no significant difference between the two groups. Additionally, the mean BMI was 25.83 (±6.41) in the patients with psoriasis and 25.90 (±13. 16) in the controls, with a nonsignificant difference. The gender frequency rate was not significantly different between the patients and controls ( Table 1). The study was approved by the ethical committee of Tikrit University College of Medicine and informed consent was taken from each subject included in the study. Individuals with liver disease, a family history of hyperlipidemia, diabetes, cardiovascular disease, hypertension, smoking, hypothyroidism, renal disease, connective tissue disease, and those using lipid-lowering drugs were excluded from the study.

Determination of Infl ammation
Inflammatory responses were determined with an approach by Zotova et al. [37], with some modifications.

Calculation of the coefficient of reactivity (CR)
[0-36] with the data extracted from Table 2. The sum of 7 (60%) largest RISs from the 11 factors used gave the CR scale. 3. Transformation of the CR scale (0-36) into the reactivity level scale (RLS) with 0-5 points (40) as shown in Table 3. 4. The Sequential Organ Failure Assessment (SOFA) scale was calculated with the serum level of bilirubin, creatinine, osteopontin, the platelet count, and the presence of sepsis and erythroderma. The SOFA scale was within the range of (0-4) ( Table 4). 5. The last step was the calculation of the Systemic Inflammation (SI) scale using the phenomenon described in Table 5.

Statistical Analysis
Variable values were presented as a mean ± standard deviation [SD]. The Student's t-test was used to determine the significant differences between the groups. A P value of less than 0.05 was regarded as significant.

RESULTS
There was no significant difference in the mean age and BMI between the psoriatic and control groups. However, there was a significantly higher mean serum value of IL-6, IL-8, IL-10, IL-23, lipoprotein (a), chemerin, TNF-α, hs-CRP, osteopontin, D-dimer, troponin I, creatinine, bilirubin, and the platelet count in the psoriatic patients than in the controls. Meanwhile, the serum mean values of adiponectin, paraoxonase, and cortisol were significantly lower in the psoriatic subjects than in the controls (Table 1).

DISCUSSION
The above biomarkers were selected to determine t h e l e v e l s o f i n f l a m m a t i o n b a s e d o n t h e reported association between psoriasis and these biomarkers [41]. Previous studies showed an increase in serum levels of IL-6, IL-8, IL-10, IL-23, lipoprotein (a), chemerin, TNF-α, hs-CRP, osteopontin, D-dimer, Troponin I, creatinine, bilirubin, creatinine, and the platelet count in patients with psoriasis, and a decrease in the serum levels of adiponectin, paraoxonase, and cortisol [21,32,. Serum osteopontin was selected as a biomarker for the calculation of the SOFA scale depending on its role as the bridging of adaptive and innate immunity in autoimmune diseases, including psoriasis [65]. Table 6 shows the data of the RI scale calculated as described in Table 2 with the information in Table 5. Then, CR was calculated by the sum of the 7 [60%] largest values of RIS and, thus, the CR value for the psoriatic patients was 32. According to the criteria presented in Table 3, the CR scale value was      transformed into the RL scale and, thus, for our study cohort, the RL scale was 5 (Table 3). Table 6, shows the SOFA scale calculated according to the criteria presented in Table 4 and, thus, the SOFA scale value for the psoriatic patients was 6. The systemic inflammation scale (SI) was determined with the criteria presented in Table 5 and, for the psoriatic patients, the SI scale was 7. The scale cut-off value that indicated systemic inflammation was equal to or above 5 points.
The mathematical model for the diagnosis of systemic inflammation was used previously in other clinical conditions, such as in obstetric, acute multiple injuries, heart surgery, and sepsis [36,37].

CONCLUSION
The mathematic model presented here is of predictive value in the determination of systemic inflammation and the discrimination between local and systemic inflammation.

Statement of Human and Animal Rights
All the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 2008 revision of the Declaration of Helsinki of 1975.

Statement of Informed Consent
Informed consent for participation in this study was obtained from all patients.