Journal of Immunology Research

Journal of Immunology Research / 2019 / Article

Research Article | Open Access

Volume 2019 |Article ID 8171373 | 8 pages | https://doi.org/10.1155/2019/8171373

Relationship between the Degrees of Itch and Serum Lipocalin-2 Levels in Patients with Psoriasis

Academic Editor: Ilaria Roato
Received04 Jul 2018
Accepted29 Nov 2018
Published21 Jan 2019

Abstract

Background. Lipocalin-2 (LCN2), a protein secreted mainly by activated neutrophils, has been associated with neurodegeneration, obesity, and inflammatory responses. Serum LCN2 concentration has been reported elevated in patients with psoriasis, but lower in patients with atopic dermatitis (AD). Spinal astrocyte-derived LCN2 was found to be involved in enhancement of itch in a mouse model of AD. However, the relationship between LCN2 and itch in patients with psoriasis has not been determined. Objective. This study examined the correlation between serum LCN2 levels and the degrees of itch in patients with psoriasis. Methods. Serum LCN2 concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in patients with psoriasis and AD and in healthy controls. The degree of itch was assessed using a visual analog scale (VAS), and disease severity was determined by measuring psoriasis area and severity index (PASI) and scoring atopic dermatitis (SCORAD). Correlations among serum LCN2 level, VAS, PASI, and SCORAD were analyzed statistically. We further examined the serum LCN levels in psoriasis patients before and after biological treatment. Results. Serum LCN2 concentrations were significantly higher in patients with psoriasis and AD than those in healthy controls. In patients with psoriasis, serum LCN2 concentrations were significantly correlated with VAS, but not with PASI. In contrast, serum LCN2 concentrations did not correlate with VAS or SCORAD in patients with AD. Serum LCN2 levels in psoriasis patients significantly decreased after the biological treatment along with improvement of VAS. Conclusion. Serum LCN2 concentration is associated with the degree of itch in patients with psoriasis, suggesting that serum LCN2 may be a useful clinical marker for itch in psoriasis.

1. Introduction

Itch is defined as an unpleasant sensation inducing a desire to scratch. Psoriasis is a chronic inflammatory skin disease accompanied by itch in about 60-90% of patients [16]. Possible mediators of itch in psoriasis include histamine, opioids, interleukin- (IL-) 31, and brain natriuretic peptide (BNP) [7, 8]. Itch causes distress in patients with psoriasis, not only by impairing quality of life but also by aggravating exanthema due to scratching (Koebner phenomenon) [6, 7, 9]. Despite the importance of controlling itch in patients with psoriasis, effective treatment for itch in psoriasis has not yet been established. Lipocalin-2 (LCN2), also known as 24p3 and neutrophil gelatinase-binding lipocalin (NGAL), is a protein secreted mainly by activated neutrophils [10]. LCN2 has been associated with neurodegeneration, cancer metastasis, insulin resistance, obesity, and inflammatory responses [1113]. In addition, LCN2 derived from spinal astrocytes has been found to enhance itch in a mouse model of atopic dermatitis (AD) [14]. Serum LCN2 concentration has been reported higher in patients with psoriasis, but lower in patients with AD, than that in healthy controls [15, 16]. LCN2 may contribute to the pathogenesis of psoriasis by modulating neutrophil activities, including neutrophil infiltration [17, 18], migration [19], and activation, inducing neutrophils to release proinflammatory mediators [19]. LCN2 may therefore be a potential target for the treatment of psoriasis [19]. In addition, LCN2 may be involved in the tendency of patients with psoriasis to develop metabolic syndrome [20]. To date, however, the relationship between LCN2 and itch in patients with psoriasis remains unclear. Therefore, the aim of this study was to investigate the correlations among serum LCN2 levels and the degrees of itch and skin inflammation in patients with psoriasis and AD.

2. Materials and Methods

2.1. Subjects

The study cohort comprised 153 subjects (86 men, 67 women), with age years (range, 18 to 88 years). These subjects were divided into three groups: 59 patients with psoriasis (47 men;12 women; age years); 47 patients with AD (19 men, 28 women; age years), and 47 healthy controls (20 men, 27 women, age years). Patients with psoriasis were diagnosed based on clinical features and/or histopathological findings. Patients with AD were diagnosed as described previously [21].

Psoriasis disease severity was assessed by measuring psoriasis area and severity index score (PASI; 0-72 points) [22], whereas AD disease severity was determined by scoring atopic dermatitis index (SCORAD; 0-103 points) for AD [23]. When was defined as severe, 40 patients with psoriasis had mild to moderate and 19 had severe disease. When points was defined as severe, 34 patients with AD had mild to moderate and 13 had severe disease. The degree of itch during the previous two weeks was assessed with a visual analog scale (VAS; 0-100%) [24]. VAS was measured at the same day of blood sampling.

Peripheral blood samples were obtained from all study subjects. The blood samples were allowed to clot for 30 minutes before centrifugation for 15 minutes at 1000×. Serum samples were collected and assayed immediately or stored at ≤−20°C.

All subjects provided written informed consent. All procedures were approved by the ethics committees of The Jikei University and Juntendo University Urayasu Hospital. This study was conducted according to the principles of the Declaration of Helsinki.

2.2. Enzyme-Linked Immunosorbent Assay (ELISA)

Serum LCN2 concentrations were measured in all study subjects using specific ELISA kits (R&D Systems, Minneapolis, MN, USA), according to the manufacturer’s instructions.

2.3. Statistical Analysis

All statistical analyses were performed using GraphPad Prism 7 (GraphPad Software Jolla, CA, USA). Data were evaluated by Dunnett’s or Bonferroni’s multiple comparison tests and Student’s -test and correlation coefficients () by Spearman’s rank correlation test. Correlations were deemed weak for from 0.2 to 0.4 and moderate for from above 0.4 to 0.7, with indicating statistical significance.

3. Results

3.1. Degree of Itch and Serum LCN2 Concentrations in Patients with Psoriasis and AD

Of the 59 patients with psoriasis, 43 had itch while 16 did not (). Similarly, of the 47 patients with AD, 46 had itch, while only one did not (Table 1).


HCPSOAD

Age
Mean
Range21 to 6421 to 8818 to 60
Sex (patient number)
Male204719
Female271228
Itch (patients number)
With4346
Without161
Disease severity (patient number)
Mild to moderate4034
Severe1913

ELISA measurements showed that serum LCN2 concentrations were significantly higher in patients with psoriasis ( ng/ml) and AD ( ng/ml) than those in healthy controls ( ng/ml, each), but there was no significant deference in serum LCN2 levels between psoriasis and AD patients (Figure 1). Serum LCN2 levels were also significantly higher in psoriatic patients with than without itch ( ng/ml vs.  ng/ml, ) (Figure 2(a)), but there was no correlation between serum LCN2 levels and disease severities (PASI or SCORAD) (Figures 2(b) and 2(c)).

3.2. Correlations among Serum LCN2 Level, Itch, and Skin Inflammation

Serum LCN2 concentrations in patients with psoriasis were significantly correlated with VAS scores ( ) (Figure 3(a)), but not with PASI (Figure 3(b)). In AD patients, serum LCN2 levels were not correlated with VAS scores or SCORAD (Figures 4(a) and 4(b)).

3.3. Comparison of Serum LCN2 Level with Psoriasis Patients between Pre- and Posttreatment

We also compared serum LCN2 levels before and after biologic treatment with 14 psoriasis patients. Four patients were treated with adalimumab, 6 patients with secukinumab, 3 patients with brodalumab, and one with infliximab. There was not a statistical significance but a tendency that serum LCN2 levels and VAS scores were lower in psoriasis patients without itch after biologic treatment (Figures 5(a) and 5(b)). PASI improved significantly after biological treatment ( points vs. points, ) (Figure 5(c)).

Next, we divided the patients into two groups by the presence and absence of itch before biological treatment and compared the change of serum LCN2 levels. Serum LCN2 levels were significantly decreased in psoriasis patients with itch after biological treatment ( ng/ml vs. ng/ml, ) (Figure 6(a)), but there was no significant difference in serum LCN2 levels with psoriasis patients without itch after treatment (Figure 6(b)). Furthermore, to examine whether the serum LCN2 level represents itch sensation, the patients were divided into two groups by the therapeutic effects of itch with the biological treatment. We defined the patients with improved VAS scores as an improved group, while the others with unchanged or increased VAS scores as a nonimproved group. In the improved group, VAS scores and serum LCN2 levels after treatment were significantly decreased than before treatment (% vs. %, ) ( ng/ml vs. ng/ml, ) (Figures 7(a) and 7(b)). In the nonimproved group, there was no significant change in serum LCN2 levels between before and after treatment (Figure 7(c)).

4. Discussion

The present study demonstrated that serum LCN2 levels were higher in patients with psoriasis and AD than those in healthy controls and that only the degree of itch in psoriasis correlated with serum LCN2 levels. LCN2 is an antimicrobial protein [25] mainly secreted by activated neutrophils and associated with neurodegeneration, cancer metastasis, inflammatory responses, insulin resistance, obesity, and atherosclerotic disease [1113, 26]. Serum LCN2 concentration was shown to be higher in psoriatic patients [15] and LCN2 was found to contribute to the pathogenesis of psoriasis by modulating neutrophil function to enhance T-helper 17-type responses [19, 27]. LCN2 was found to be upregulated in spinal astrocytes in a mouse model of AD, indicating itch sensitization at the spinal level. Although the precise mechanism by which LCN2 induces itch in psoriasis has not been determined, the results of our study suggest that LCN2 enhances itch centrally in psoriasis by a mechanism similar to that in the mouse model of AD.

In addition to its central effect, LCN2 may have peripheral effects, inducing neutrophil infiltration, migration, and activation, all of which have been associated with the pathologic development of psoriasis [19, 27]. Although the relationship between neutrophils and itch has not been fully determined, neutrophil activities have been associated with several pruritogens such as tumor necrosis factor (TNF-α) and substance-P (SP). TNF-α produced by epidermal keratinocytes is required in the expression of acute and chronic itch in mice [28]. Moreover, SP may be associated with multiple cellular responses, including neutrophil activation [29]. SP has been shown to increase the cutaneous concentration of leukotriene B4 (LTB4) [30], an endogenous mediator of itch in the skin [31]. LCN2 was also found to be overexpressed in the lesional skin of psoriatic patients [19]. LCN2 may be derived from keratinocytes as well as from neutrophils in certain conditions. Epidermal keratinocytes also produce endogenous pruritogens such as TNF-α, LTB4, nitric oxide (NO), and thymic stromal lymphopoietin (TSLP) [28, 3234]. In addition, injection of LCN2 into psoriasiform skin induced by imiquimod increased the levels of mRNA encoding various cytokines and chemokines, including IL-17A, IL-17F, IL-22, IL-12p40, IL-23p19, and CCL20 mRNAs, as well as TNF-α and CXCL1 mRNAs [27]. CXCL1 can also induce itch via transient receptor potential vanilloid type 1 (TRPV1) [35]. Taken together, these findings suggest that LCN2 induces the production of pruritogens from neutrophils and epidermal keratinocytes and that LCN2 may be involved indirectly in the pathogenesis of psoriatic itch at the periphery.

Consistent with an earlier study [15], our study found that serum LCN2 levels did not correlate with PASI (). In contrast, another study reported a positive correlation between LCN2 and PASI [20]. These discrepancies may be due to factors such as disease duration and severity and previous medical history and treatment.

We also found that serum LCN2 concentrations were significantly increased in AD patients, despite the lack of correlation between the degree of itch and serum LCN2 level. This finding may be explained by differences in the local and systemic effects of LCN2 in the patients with psoriasis and AD. In contrast to psoriasis, LCN2 expression was not increased in AD skin [36], suggesting that the local effect of LCN2 on itch is limited in AD. In addition, LCN2 has been identified as an adipokine [37]. Serum LCN2 concentrations were found to be increased in patients with metabolic syndrome, with a significant correlation between LCN2 and measures of insulin resistance [37]. Obesity and psoriasis were found to be strongly associated, whereas AD and LCN2 were not [38]. LCN2 may have systemic effects in psoriasis but not in AD. These differences may explain the lack of correlation of serum LCN2 concentration with itch and disease severity in patients with AD.

We examined the change in serum LCN2 levels with psoriasis patients between before and after biologic treatment. The results showed that serum LCN2 levels decreased after treatment in psoriatic patients with itch. In the VAS improved group, there was significantly lower in serum LCN2 levels before than after treatment. Disease severity improved in all patients, but there was no significant difference in the serum LCN2 levels between pre- and posttreatment. Based on our results, we can assume that the decrease of serum LCN2 levels represents the improvement of itch by biologics and serum LCN2 level may be a useful clinical marker for the evaluation of itch in psoriasis patients.

5. Conclusion

In conclusion, the present study showed a close relationship between the degree of itch and serum LCN2 level in patients with psoriasis. Serum LCN2 level may represent not only disease severity but also itch intensity. Thus, serum LCN2 level may be a useful clinical marker for itch in patients with psoriasis.

Data Availability

The individual serum LCN2 levels, disease severity, itch intensity, sex, and age data used to support the findings of this study are restricted by the ethics committees of The Jikei University and Juntendo University Urayasu Hospital in order to protect patient privacy. Data are available from Norie Aizawa (Department of Dermatology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan h19ms-aizawa@jikei.ac.jp), for researchers who meet the criteria for access to confidential data.

Conflicts of Interest

A. A. and Y. U. have received consultant and/or speaker fees from Maruho, AbbVie, Eisai, Mitsubishi Tanabe Pharma, Janssen Pharmaceutical, Kyowa Hakko Kirin, Torii Pharmaceutical, and Eli Lilly Japan. H. N. has received honoraria and/or grant funding as an advisor, consultant, and/or speaker fees from Maruho, AbbVie, Eisai, Mitsubishi Tanabe Pharma, Janssen Pharmaceutical, Kyowa Hakko Kirin, Torii Pharmaceutical, and Leo Pharma. All other authors declare no conflicts of interest associated with this manuscript.

Acknowledgments

This work was partly supported by a grant of Strategic Research Foundation Grant-aided Project for Private Universities from MEXT (S1311011).

References

  1. J. C. Szepietowski and A. Reich, “Pruritus in psoriasis: an update,” European Journal of Pain, vol. 20, no. 1, pp. 41–46, 2016. View at: Publisher Site | Google Scholar
  2. B. Amatya, G. Wennersten, and K. Nordlind, “Patients’ perspective of pruritus in chronic plaque psoriasis: a questionnaire-based study,” Journal of the European Academy of Dermatology and Venereology, vol. 22, no. 7, pp. 822–826, 2008. View at: Publisher Site | Google Scholar
  3. S. E. Chang, S. S. Han, H. J. Jung, and J. H. Choi, “Neuropeptides and their receptors in psoriatic skin in relation to pruritus,” The British Journal of Dermatology, vol. 156, no. 6, pp. 1272–1277, 2007. View at: Publisher Site | Google Scholar
  4. G. Stinco, G. Trevisan, F. Piccirillo et al., “Pruritus in chronic plaque psoriasis: a questionnaire-based study of 230 Italian patients,” Acta Dermatovenerologica Croatica, vol. 22, no. 2, pp. 122–128, 2014. View at: Google Scholar
  5. J. C. Szepietowski, A. Reich, and B. Wisnicka, “Pruritus and psoriasis,” The British Journal of Dermatology, vol. 151, no. 6, pp. 1284–1284, 2004. View at: Publisher Site | Google Scholar
  6. G. Yosipovitch, A. Goon, J. Wee, Y. H. Chan, and C. L. Goh, “The prevalence and clinical characteristics of pruritus among patients with extensive psoriasis,” The British Journal of Dermatology, vol. 143, no. 5, pp. 969–973, 2000. View at: Publisher Site | Google Scholar
  7. A. Reich and J. C. Szepietowski, “Mediators of pruritus in psoriasis,” Mediators of Inflammation, vol. 2007, Article ID 64727, 6 pages, 2007. View at: Publisher Site | Google Scholar
  8. K. Taneda, M. Tominaga, O. Negi et al., “Evaluation of epidermal nerve density and opioid receptor levels in psoriatic itch,” The British Journal of Dermatology, vol. 165, no. 2, pp. 277–284, 2011. View at: Publisher Site | Google Scholar
  9. J. C. Szepietowski, A. Reich, and B. Wiśnicka, “Itching in patients suffering from psoriasis,” Acta Dermatovenerologica Croatica, vol. 10, no. 4, pp. 221–226, 2002. View at: Google Scholar
  10. L. Kjeldsen, D. Bainton, H. Sengelov, and N. Borregaard, “Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils,” Blood, vol. 83, no. 3, pp. 799–807, 1994. View at: Google Scholar
  11. G. Ding, J. Fang, S. Tong et al., “Over-expression of lipocalin 2 promotes cell migration and invasion through activating ERK signaling to increase SLUG expression in prostate cancer,” The Prostate, vol. 75, no. 9, pp. 957–968, 2015. View at: Publisher Site | Google Scholar
  12. A. M. Nelson, W. Zhao, K. L. Gilliland, A. L. Zaenglein, W. Liu, and D. M. Thiboutot, “Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human sebaceous gland cells,” The Journal of Clinical Investigation, vol. 118, no. 4, pp. 1468–1478, 2008. View at: Publisher Site | Google Scholar
  13. G. Wang, N. Ma, L. Meng, Y. Wei, and J. Gui, “Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation,” Molecular and Cellular Biochemistry, vol. 410, no. 1-2, pp. 207–213, 2015. View at: Publisher Site | Google Scholar
  14. M. Shiratori-Hayashi, K. Koga, H. Tozaki-Saitoh et al., “STAT3-dependent reactive astrogliosis in the spinal dorsal horn underlies chronic itch,” Nature Medicine, vol. 21, no. 8, pp. 927–931, 2015. View at: Publisher Site | Google Scholar
  15. M. Kamata, Y. Tada, A. Tatsuta et al., “Serum lipocalin-2 levels are increased in patients with psoriasis,” Clinical and Experimental Dermatology, vol. 37, no. 3, pp. 296–299, 2012. View at: Publisher Site | Google Scholar
  16. H. El-Hadidi, N. Samir, O. G. Shaker, and S. Otb, “Estimation of tissue and serum lipocalin-2 in psoriasis vulgaris and its relation to metabolic syndrome,” Archives of Dermatological Research, vol. 306, no. 3, pp. 239–245, 2014. View at: Publisher Site | Google Scholar
  17. M. K. Jha, S. Jeon, M. Jin et al., “The pivotal role played by lipocalin-2 in chronic inflammatory pain,” Experimental Neurology, vol. 254, pp. 41–53, 2014. View at: Publisher Site | Google Scholar
  18. V. Wieser, P. Tymoszuk, T. E. Adolph et al., “Lipocalin 2 drives neutrophilic inflammation in alcoholic liver disease,” Journal of Hepatology, vol. 64, no. 4, pp. 872–880, 2016. View at: Publisher Site | Google Scholar
  19. S. Shao, T. Cao, L. Jin et al., “Increased lipocalin-2 contributes to the pathogenesis of psoriasis by modulating neutrophil chemotaxis and cytokine secretion,” The Journal of Investigative Dermatology, vol. 136, no. 7, pp. 1418–1428, 2016. View at: Publisher Site | Google Scholar
  20. J. Romaní, A. Caixàs, V. Ceperuelo-Mallafré et al., “Circulating levels of lipocalin-2 and retinol-binding protein-4 are increased in psoriatic patients and correlated with baseline PASI,” Archives of Dermatological Research, vol. 305, no. 2, pp. 105–112, 2013. View at: Publisher Site | Google Scholar
  21. J. Hanifin and G. Rajka, “Diagnostic features of atopic dermatitis,” Acta Dermato-Venereologica, vol. 60, no. 92, pp. 44–47, 1980. View at: Google Scholar
  22. T. Fredriksson and U. Pettersson, “Severe psoriasis--oral therapy with a new retinoid,” Dermatologica, vol. 157, no. 4, pp. 238–244, 1978. View at: Publisher Site | Google Scholar
  23. J. F. Stalder, A. Taïeb, D. J. Atherton et al., “Severity scoring of atopic dermatitis: the SCORAD index: consensus report of the European task force on atopic dermatitis,” Dermatology, vol. 186, no. 1, pp. 23–31, 1993. View at: Publisher Site | Google Scholar
  24. A. Reich, M. Heisig, N. Q. Phan et al., “Visual analogue scale: evaluation of the instrument for the assessment of pruritus,” Acta Dermato-Venereologica, vol. 92, no. 5, pp. 497–501, 2012. View at: Publisher Site | Google Scholar
  25. T. H. Flo, K. D. Smith, S. Sato et al., “Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron,” Nature, vol. 432, no. 7019, pp. 917–921, 2004. View at: Publisher Site | Google Scholar
  26. V. Catalán, J. Gómez-Ambrosi, A. Rodríguez et al., “Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans,” Journal of Molecular Medicine, vol. 87, no. 8, pp. 803–813, 2009. View at: Publisher Site | Google Scholar
  27. C. S. Hau, N. Kanda, Y. Tada et al., “Lipocalin-2 exacerbates psoriasiform skin inflammation by augmenting T-helper 17 response,” The Journal of Dermatology, vol. 43, no. 7, pp. 785–794, 2016. View at: Publisher Site | Google Scholar
  28. X. Miao, Y. Huang, T.-T. Liu et al., “TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch in mice via peripheral and central mechanisms,” Neuroscience Bulletin, vol. 34, no. 1, pp. 42–53, 2018. View at: Publisher Site | Google Scholar
  29. M. Nakamura, M. Toyoda, and M. Morohashi, “Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors,” The British Journal of Dermatology, vol. 149, no. 4, pp. 718–730, 2003. View at: Publisher Site | Google Scholar
  30. T. Andoh and Y. Kuraishi, “Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice,” European Journal of Pharmacology, vol. 547, no. 1–3, pp. 59–64, 2006. View at: Publisher Site | Google Scholar
  31. T. Andoh and Y. Kuraishi, “Intradermal leukotriene B4, but not prostaglandin E2, induces itch-associated responses in mice,” European Journal of Pharmacology, vol. 353, no. 1, pp. 93–96, 1998. View at: Publisher Site | Google Scholar
  32. A. Köck, T. Schwarz, R. Kirnbauer et al., “Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light,” The Journal of Experimental Medicine, vol. 172, no. 6, pp. 1609–1614, 1990. View at: Publisher Site | Google Scholar
  33. T. Andoh and Y. Kuraishi, “Nitric oxide enhances substance P-induced itch-associated responses in mice,” British Journal of Pharmacology, vol. 138, no. 1, pp. 202–208, 2003. View at: Publisher Site | Google Scholar
  34. S. R. Wilson, L. Thé, L. M. Batia et al., “The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch,” Cell, vol. 155, no. 2, pp. 285–295, 2013. View at: Publisher Site | Google Scholar
  35. A. F. Deftu, A. Filippi, R. O. Gheorghe, and V. Ristoiu, “CXCL1 activates TRPV1 via Gi/o protein and actin filaments,” Life Sciences, vol. 193, pp. 282–291, 2018. View at: Publisher Site | Google Scholar
  36. S. J. Seo, J.-Y. Ahn, C.-K. Hong et al., “Expression of neutrophil gelatinase-associated lipocalin in skin epidermis,” The Journal of Investigative Dermatology, vol. 126, no. 2, pp. 510–512, 2006. View at: Publisher Site | Google Scholar
  37. Q. W. Yan, Q. Yang, N. Mody et al., “The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance,” Diabetes, vol. 56, no. 10, pp. 2533–2540, 2007. View at: Publisher Site | Google Scholar
  38. J. M. Carrascosa, V. Rocamora, R. M. Fernandez-Torres et al., “Obesity and psoriasis: inflammatory nature of obesity, relationship between psoriasis and obesity, and therapeutic implications,” Actas Dermo-Sifiliográficas, vol. 105, no. 1, pp. 31–44, 2014. View at: Publisher Site | Google Scholar

Copyright © 2019 Norie Aizawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


More related articles

1117 Views | 383 Downloads | 1 Citation
 PDF  Download Citation  Citation
 Download other formatsMore
 Order printed copiesOrder

Related articles

We are committed to sharing findings related to COVID-19 as quickly and safely as possible. Any author submitting a COVID-19 paper should notify us at help@hindawi.com to ensure their research is fast-tracked and made available on a preprint server as soon as possible. We will be providing unlimited waivers of publication charges for accepted articles related to COVID-19. Sign up here as a reviewer to help fast-track new submissions.