Background: Psoriasis is a common inflammatory dermatological condition and affects 2–3% population worldwide. Psoriasis area and severity index (PASI) and body surface area (BSA) are two commonly used scales used to measure disease severity in psoriasis patients. However, these scales are plagued by weaknesses as inter-observer variation and insufficient evaluation of micro-vascular inflammation. Thus, it is necessary to have an objective and simple measure of the severity of inflammation. The ratio of neutrophils-to-lymphocytes (NLR) and platelets-to-lymphocytes (PLR) are simple and inexpensive markers of systemic inflammatory response that can be measured as part of a complete blood count and are already used in the setting of inflammatory diseases. The utility of the NLR and PLR in psoriasis however, remains relatively unexplored. Aims and Objectives: The present study was undertaken to assess if NLR, PLR and C-reactive protein were altered in chronic plaque psoriasis patients as compared to controls and also to determine correlation of NLR and PLR values with disease severity as measured by PASI. Methods: This case control study consisted of equal numbers (45 each) chronic plaque psoriasis patients and control subjects. The subjects were evaluated by way of history taking, clinical and blood examination. Thereafter, the results were tabulated and examined statistically. Results: Our study results indicate that psoriasis patients tended to have a higher neutrophil count, lymphocyte count, NLR and C-reactive protein in comparison the control subjects (P < 0.05). Conclusion: We concluded that such easily available and low cost indices of systemic inflammation are raised in psoriasis patients and are positively correlated with the severity of involvement. They can thus not only be used to monitor the effect of systemic drugs in psoriasis.
Keywords: Neutrophils-to-lymphocytes ratio, platelets-to-lymphocytes ratio, psoriasis severity
Psoriasis is a common inflammatory dermatological condition with significant comorbidities and it afflicts 2–3% population worldwide.[1] Psoriasis severity is too complicated for a single tool to assess. One of the most commonly used scales in identifying psoriasis severity is the Psoriasis area and severity index (PASI), which includes symptoms as erythema, desquamation (scaling) and induration/infiltration according to anatomic localisation. Body surface area (BSA) distribution percentage is a simple scale that can also be used.
However, the scopes of PASI and BSA are limited by inter-observer variation, lack of objective evaluation criteria and insufficient evaluation of chronic microvascular inflammatory conditions underlying the disease. Thus, it is necessary to have a simple and objective measure of the severity of inflammation in psoriasis, not only for estimation of the severity of disease but also for evaluation of the benefit of systemic anti-inflammatory treatment.
The ratio of neutrophils-to-lymphocytes (NLR) and platelets-to-lymphocytes (PLR) are simple and inexpensive markers of the systemic inflammatory response that can be measured as part of a complete blood count and is commonly used in the setting of chronic inflammatory diseases.[2] Previous studies investigated the use of NLR and PLR in diabetes mellitus, acute coronary syndrome, atrial fibrillation, ischemic stroke, ulcerative colitis, end-stage renal disease, tuberculosis, rheumatoid arthritis, cirrhosis and systemic inflammation in familial Mediterranean fever.[3],[4],[5],[6],[7] There are studies which propose NLR and PLR be used to determine prognoses also in cancer patients.[8]
In the Indian context however, the utility of the N/L and P/L ratio in psoriasis remains relatively unexplored besides a handful of studies.[9],[10],[11] The existing inadequacies in the knowledge in this field prompted us to undertake the present study.
Aims and objectives
The study aimed to find if neutrophil-to-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and C-reactive protein (CRP) are altered in chronic plaque psoriasis patients as compared to controls (primary objective) and determine if these markers correlated with disease severity (secondary objective).
Materials and MethodThe study was conducted in the Department of Dermatology, of a tertiary level hospital in eastern India. Recruitment of patients and study was done during January 2019 to March 2020. It was an institution based, case control study. Patients presenting with chronic plaque psoriasis, fulfilling the inclusion criteria, who expressed consent for participating in the study were included in the study and a group of healthy subjects was included as control. Prior institutional ethics committee clearance was obtained and the Code of Ethics of the World Medical Association (Declaration of Helsinki) was adhered to.
Calculation of sample size was done based on the results of a previous study,[12] where the mean ± SD of NLR in psoriasis and control groups were 2.78 ± 1.74 and 1.75 ± 0.55, respectively, and P = 0.0001. We calculated a minimum sample size of 45 in the case and control groups with a power of 0.8 and alpha of 0.05. Consecutive sampling of all psoriasis patients either attending the outdoor department or admitted in the in-patient department was done and recruited in the study as cases. Healthy subjects of same age and sex were included as control. Patients were included as all consecutive patients of any age group suffering from clinically diagnosed chronic plaque psoriasis. Controls were obtained from hospital staff, students and healthy relatives of patients without psoriasis or chronic inflammatory diseases (inclusion criteria).
Subjects on immunomodulatory systemic drugs, associated co-morbidities such as active infections, cancer, diabetes mellitus, and systemic inflammatory diseases, pregnant women and otherwise immunocompromised patients were excluded (Exclusion criteria).
Evaluation of patients included history taking, clinical examination with PASI score estimation in psoriasis patients. Both patients and controls were subjected to complete haemogram, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, CRP estimation. The absolute counts of lymphocyte, neutrophil and platelet were used to calculate each ratio.
Statistical analysis
Quantitative variables were described as Mean ± S.D., parametric data as frequencies (no of cases), relative frequencies (percentages). Quantitative variables were compared using t-test (continuous variable), Mann-Whitney test; while for categorical data, Chi-square test was used. Medcalc® v 19 was used for analysis and the P value for significance was set at 0.05.
ResultsThis study was conducted over a period of 16 months and consisted of chronic plaque psoriasis patients (n1 = 45) and control subjects (n2 = 45). The findings are as stated below.
The groups were comparable with respect to sex ratio (P value = 0.34, Chi-square test). The age of psoriasis patients was significantly greater than that of the controls, (P value = 0.004, t-test).
In the psoriasis population, patients belonging to the age group of 21 to 40 years were most commonly affected followed by 41 to 60 years. Mean age was 38.11 ± 14.90 years. There was statistically significant positive correlation between age of the psoriasis population and PASI score. (ŕ =0.39, P Value = 0.006).
The mean disease duration was 6.16 years (±5.54). Twenty nine (64.44%) psoriasis patients had disease duration of 1 to 5 years, 11 (24.44%) patients had 6 to 10 years and 2 (4.44%) patients had duration of greater than 20 years. The range of disease duration was 2 to 25 years.
There was statistically significant positive correlation between disease duration in study population and PASI score (Spearman's coefficient) ŕ =0.27, P value = 0.04.
Family history
Fourteen (31%) patients had a positive family history.
Psoriasis area and severity index score (PASI)
The mean PASI score was 10.46 ± 5.45. Patients were classified as mild psoriasis (PASI <10); moderate psoriasis (PASI ≥10 <20) or severe psoriasis (PASI ≥20). It was observed that 25 (55%) patients had mild psoriasis, 17 (38%) patients had moderate psoriasis and 3 (7%) severe psoriasis.
History of joint involvement (pain and/or deformity)
The joint involvement in all involved patients included the small joints of hand (distal interphalangeal joints of hands). Joint pain was found in 11 (25%) patients while joint deformity was seen in 1 (2%) patient.
Koebnerization was noted in 23 (51%) patients.
Blood count
There was no significant difference found in haemoglobin levels between the patient and control groups (P = 0.19, T-test) as well as in the total white blood cell count (P = 0.62, Mann-Whitney test). The neutrophil count was higher in the patient group; difference in neutrophil count between the patient and control groups was statistically significant (P = 0.03, Mann-Whitney test).
The lymphocyte count was higher in the control group and the difference in the groups was statistically significant (P = 0.04, Mann-Whitney test). The NLR was higher in the patient group (2.06) than controls (1.71). This difference was statistically significant (P = 0.04, Mann-Whitney test).
There difference in platelet count between the patient and control groups was not statistically significant (P = 0.5, Mann-Whitney test).
There was no statistically significant difference found in PLR between the patient and control groups (P = 0.30, Mann-Whitney test).
Blood biochemistry
CRP level was more in psoriasis patients (mean value = 7.2 mg/dl) than in controls (mean value = 2.7 mg/dl). The difference of CRP between the groups was highly significant (P < 0.0001).
The clinical characteristics and laboratory investigations of each group were compared and are summarised in [Table 1].
Table 1: Comparison of demography and haematology and biochemistry parameters of patient and control groupsNL ratio, PL ratio, CRP, PASI score in joint involvement vs. non-involved patients
We found that NLR, PLR, CRP and PASI was higher in patients with joint involvement than those without, the difference however was not significant (Mann-Whitney test P = 0.2814, 0.5961, 0.5961 and 0.3213, respectively).
Nail involvement
Presence of nail involvement was noted in 23 (51%) patients; of whom, 16 (70%) patients had ridging and 13 (57%) had onychodystrophy. There was positive correlation between onychodystrophy and PASI score in chronic plaque psoriasis patients (P < 0.0001, Mann-Whitney test). When compared with patients with no nail changes, all the values were higher in the “nail change present” group as compared to the “no nail change” group. Statistically, there was no difference in NLR and PLR among the groups (Mann-Whitney test P = 0.80 and 0.22, respectively). The difference in PASI score and CRP was highly significant (Mann-Whitney test P < 0.0001 and 0.0009, respectively).
Correlation of disease severity with NL ratio
Among the psoriasis patients, mean NLR was 2.27 ± 1.30; range was 0.85 to 8.70. There was no significant correlation found in terms of PASI score and NLR [Spearman's coefficient (ŕ) = -.218. P value = 0.15].
Correlation of disease severity with platelet-to-lymphocyte ratio
Among the psoriasis patients, mean PL ratio was 7.71 with standard deviation of 3.30. There was statistically significant positive correlation found in terms of PASI score and PL ratio [Spearman's ŕ =0.27, P Value = 0.04].
Among the study population, CRP ranged from 1.23 to 20.40 with mean of 7.86 ± 4.9.
PASI score was positively correlated with CRP (Spearman's rho) =0.41, P value = 0.004.
Correlation of NLR with mild and moderate to severe psoriasis:
We classified patients into “mild disease” if PASI ≤10 and “moderate to severe disease” if PASI >10. The range of NLR in these groups was 0.85–0.94 and 8.7–6.08, respectively. The median NLR was 2.06 and 1.88, respectively.
There was no statistically significant difference found in NLR between mild and moderate versus severe psoriasis patients. (P = 0.44, Mann-Whitney test).
PLR and NLR values compared in “mild” and “moderate to severe” psoriasis [Table 2]:
Table 2: PLR and NLR values compared in “mild” and “moderate to severe” psoriasisAmong the study population, there was no statistical difference found in terms of PLR between mild and moderate to severe group of psoriasis patients. (P = 0.15, Mann-Whitney test).
There was no correlation found between CRP and NLR [Spearman's coefficient (rho) =0.02, P value = 0.8].
Correlation of C-reactive protein with platelet-to-lymphocyte ratio
There was no statistically significant correlation found between CRP and PLR Spearman's coefficient (rho) =0.11, P value = 0.43}.
DiscussionThis case control study was aimed at comparing markers of systemic inflammation in psoriasis patients versus healthy controls. This was done using simple parameters like neutrophil: lymphocyte ratio (NLR) and platelet: lymphocyte ratio (PLR) and CRP. The study also determined relationship between these ratios and PASI. Results obtained in the current study is compared and contrasted with previous studies.
Kim et al.[9] in their study found significant difference in white blood corpuscle (WBC) count, neutrophil count, ESR, CRP and NLR between psoriasis and control groups. However no significant difference was found in lymphocyte and platelet count, haemoglobin and PLR values. Our study mostly agreed with the former.
PASI was positively correlated with platelet count, NLR and PLR, but not with CRP, neutrophil count, disease duration or joint and nail involvement. The current study found PASI score to be positively correlated with PLR and CRP but not with NLR.
In the same study, when patients were compared based on their PASI score (<10 and ≥10) the platelet count, NLR and PLR were all significantly higher in moderate to severe psoriasis group (PASI ≥10) as compared to the mild psoriasis (PASI <10) group. On similar analysis, we found significant difference in CRP but no difference in NLR and PLR. (P = 0.01, 0.44, 0.15, respectively). Thus except for NLR values, the current study seemed to agree with the previous study. The deviation in NLR may be attributed to population differences.[13]
Yurtdas et al.[14] hypothesised that systemic inflammation could provide an explanation of the increased cardiovascular risk observed in psoriasis patients. It was hypothesised that NLR and PLR are prospective predictors of subclinical atherosclerosis in psoriasis. They found significantly raised NLR in psoriasis patients compared to controls (P = 0.005). Thus, NLR and PLR are simple and inexpensive measurements of systemic inflammation as well as coronary risks in psoriasis patients. Our study did not measure cardiac indices as in the former study but observed increased NLR in psoratic patients as compared to controls.
Cerman et al.[15] compared NLR and mean platelet volume in 49 psoriasis patients (19 female, 30 male) with 47 control subjects. They found statistically significant difference in NLR (P < 0.001) but no significant difference in mean platelet volume (P = 0.06). The present study agrees with Cerman in this respect; platelet volume estimation was however not done in the current study.
In a Turkish study, (Polat et al.)[12] involving 46 each of psoriasis patients and healthy subjects, statistically significant difference in leukocyte, platelet, and neutrophil, NLR and PLR between the patient and control groups was found. However, no significant difference was found in haemoglobin, WBC count and CRP values (P = 0.08, 0.4, 0.53, respectively). Our study agreed with the former study by finding significant difference in neutrophil and NLR and no difference in haemoglobin level, and leucocyte counts. However, we differed in respect to higher CRP level in patient group but indifferent WBC count, platelet count and PLR in the groups.
Sen et al.[11] found that the patients with psoriasis had significantly higher neutrophil counts (P < 0.01) and lower lymphocyte counts (P < 0.01) than controls. The present study agrees with the former in these regards. In agreement to their findings, the N/L ratios and high sensitivity C-reactive protein (hs-CRP) levels in our study were significantly higher in psoratic patients. They found the PASI score to be positively correlated with N/L ratios and hs-CRP levels. Our study agreed with the former regarding CRP and PLR but found no significant correlation with PLR.
Limitations of the study
The sample size, though statistically adequate was modest. Consistent with disadvantages of case control studies, patient follow up was not done whereby sizeable information about disease evolution was missed. Also, all confounding variables were not brought into account during analysis.
Thus, in summary, our study results indicate that psoriasis patients tended to have a higher neutrophil count, lymphocyte count, NLR and CRP in comparison the control subjects. Both NLR and PLR had a positive correlation with the severity of psoriasis; however, the same was statistically significant with NLR only.
We could demonstrate that easily available and low cost indices of systemic inflammation are raised in psoriasis patients and are positively correlated with the severity of involvement. They can thus not only be used to monitor the effect of systemic drugs in psoriasis but also predict inflammation related comorbidities in them.
Acknowledgements
We would like to congratulate and thank all patients and controls who agreed to take part in the study.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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