Direct detection of free vitamin D as a tool to assess risk conditions associated with chronic plaque psoriasis


free vitamin D
direct immunoassay
cross-sectional study


Introduction.Psoriasis is a major public health problem that results in high social and health costs. New approaches and methods are required to identify any conditions related to the disease and comorbidity development. The vitamin D deficiency is associated to psoriasis and could play an important role in its pathogenesis. However, the serum level of vitamin D is currently measured as total vitamin D, which is affected by wide variability. Therefore, the determination of the free form could be more significant, since it is independent of confounding factors. A cross-sectional study was performed to assess the association between chronic plaque psoriasis and serum level of free vitamin D, detected by a direct analytical method.

Methods.The levels of bioavailable vitamin D, total vitamin D and other metabolic parameters whose homeostasis is regulated by vitamin D were evaluated in 72 psoriasis patients and in 48 healthy controls. A direct immunoassay method was used to directly measure serum free vitamin D level. Analysis of covariance was performed to calculate estimated marginal means (EMM) and 95% confidence interval (CI), after adjustment for age, sex and BMI, within the two groups.

Results.Patients showed an EMM of 5.526±0.271pg/ml, 95% CI 4.989-6.063; while controls an EMM of 6.776±0.271 pg/ml, 95% CI 6.115-7.437.

Conclusions.Chronic plaque psoriasis patients exhibited a serum level of free vitamin D lower than controls. The direct immunoassay method could represent a useful tool to assess vitamin D status and identify a risk condition associated with the onset of the pathology.


[1] Di Cesare A, Di Meglio P. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol 2009;129(6):1339-50.
[2] Boehncke WH, Schön MP. Psoriasis. Lancet 2015;386(9997):983-94.
[3] International Federation of Psoriasis Associations. World Psoriasis Day 2015. Available at: [Accessed on 21/01/2020].
[4] Prignano F, Rogai V, Cavallucci E, Bitossi A, Hammen V, Cantini F. Epidemiology of psoriasis and psoriatic arthritis in Italy – a systematic review. Curr Rheumatol Rep 2018;20: 43.
[5] Gudjonsson JE, Elder JT. Psoriasis. Reference Module in Biomedical Sciences 2014.
[6] Di Costanzo L, Fattorusso V, Mozzillo E, Patrì A, Di Caprio R, De Nitto E, Balato N, Franzese A. Psoriasis in children with type 1 diabetes: A new comorbidity to be considered? Acta Diabetol 2017;54:803.
[7] Langley RG, Krueger GG, Griffiths CE. Psoriasis: Epidemiology, clinical features, andquality oflife. Ann Rheum Dis 2005;64(2):ii18-ii23.
[8] Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis D, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA 2006; 296: 1735-41.
[9] Helmick CG, Lee-Han H, Hirsch SC, Baird TL, Bartlett CL. Prevalence of psoriasis among adults in the US: 2003–2006 and 2009–2010 National Health and Nutrition Examination Surveys. Am J Prev Med 2014;47(1):37-45.
[10] Seremet S, Genc B, Tastan A, Akyildiz ZI, Nazli C, Ozcelik S, Afsar FS, Solak A, Emren V. Are all patients with psoriasis at increased risk for coronary artery disease? Int J Dermatol 2015;54: 355-61.
[11] Kim N, Thrash B, Menter A. Comorbidities in psoriasis patients. Semin Cutan Med Surg. 2010;29:10-5.
[12] Yeung H, Takeshita J, Mehta NN, Kimmel SE, Ogdie A, Margolis DJ, Shin DB, Attor R, Troxel AB, Gelfand JM. Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol 2013;149:1173-9.
[13] Kimball A, Guerin A, Tsaneva M, Yu A, Wu E, Gupta S, Bao Y, Mulani P. Economic burden of comorbidities in patients with psoriasis is substancial. J Uur Acad Dermatol Venereol 2011;25(2):157-163.
[14] Feldman SR, Zhao Y, Shi L, Tran MH, Lu J. Economic and comorbidity burden among moderate-to-severe psoriasis patients with comorbid psoriatic arthritis. Arthritis Care Res (Hoboken). 2015;67:708-17.
[15] Soleymani T, Hung T, Soung J. The role of vitamin D in psoriasis: a review. Int J Dermatol 2015;54(4)383-92.
[16] Umar M, Sastry KS, Al Ali F, Al-Khulaifi M, Wang E, Chouchane AI. Vitamin D and the pathophysiology of inflammatory skin diseases. Skin Pharmacol Physiol 2018;31(2)74-86.
[17] Mason A, Mason J, Cork M, Hancock H, Dooley G. Topical treatments for chronic plaque psoriasis: an abridged cochrane systematic review. J American Acad Dermatol 2013;69(5)799-807.
[18] Scott LJ, Dunn CJ, Goa KL. Calcipotriol ointment: A review of its use in the management of psoriasis. Am J Clin Dermatol 2001;2(2)95-120.
[19] Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 2016;96(1)365-408.
[20] Tsuprikov O, Chen X, Hocher CF, Skoblo R, Yin L, Hocher B. Why should we measure free 25(OH) vitamin D? J Steroid Biochem Mol Biol 2018;180:87-104.
[21] Gisondi P, Rossini M, Di Cesare A, Idolazzi L, Farina S, Beltrami G, Peris K, Girolomoni G. Vitamin D status in patients with chronic plaque psoriasis. Br J Dermatol 2012;166(3):505-10.
[22] Ricceri F, Pescitelli L, Tripo L, Prignano F. Deficiency of serum concentration of 25-hydroxyvitamin D correlates with severity of disease in chronic plaque psoriasis. J Am Acad Dermatol 2013;68(3):511-2.
[23] Lee YH, Song GG. Association between circulating 25-hydroxyvitamin D levels and psoriasis, and correlation with disease severity: a meta-analysis. Clin Exp Dermatol 2018;43(5):529-35.
[24] World Health Organization (WHO). Physical status: The use and interpretation of anthropometry, 1995. Available at: [Accessed on 10/02/2019].
[25] Fredriksson T, Pettersson U. Severe psoriasis-oral therapy with a new retinoid. Dermatologica 1978;157(4):238-44.
[26] Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R. Vitamin-D binding-protein and vitamin D status of black Americans and white Americans. N Engl J Med 2013;369(21):1991-2000.
[27] Soleymani T, Tracy H, Jennifer S. The role of vitamin D in psoriasis: a review. Int J Dermatol 2015;54(4):383-92.
[28] Barrea L, Savanelli MC, Di Somma C, Napolitano M, Megna M, Colao A, Savastano S. Vitamin D and its role in psoriasis: An overview of the dermatologist and nutritionist. Rev Endocr Metab Disord 2017;18(2):195-205.
[29] Schwartz JB, Lai J, Lizaola B, Kane L, Weyland P, Terrault NA, Stotland N, Bikle D. Variability in free 25(OH) vitamin D levels in clinical populations. J Steroid Biochem Mol Biol 2014;144:156-8.
[30] van Hoof HJ, de Sévaux RG, van Baelen H, Swinkels LM, Klipping C, Ross HA, Sweep CGJ. Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding. Eur J Endocrinol 2001;144(4):391-6.
[31] Grymonprez A, Proesmans W, Van Dyck M, Jans I, Goos G, Bouillon R. Vitamin D metabolites in childhood nephrotic syndrome. Pediatr Nephrol 1995;9(3):278-81.
[32] Lambert PW, De Oreo PB, Fu IY, Kaetzel DM, von Ahn K, Hollis BW, Roos BA. Urinary and plasma vitamin D3 metabolites in the nephrotic syndrome. Metab Bone Dis Relat Res 1982;4(1):7-15.
[33] Aloia J, Mikhail M, Dhaliwal R, Shieh A, Usera G, Stolberg A, Ragolia L, Islam S. Free 25(OH)D and the vitamin D paradox in African Americans. J Clin Endocrinol Metab 2015;100(9):3356-63.
[34] Płudowski P, Karczmarewicz E, Bayer M, Carter G, Chlebna-Sokół D, Czech-Kowalska J, Dębski R, Decsi T, Dobrzańska A, Franek E, Głuszko P, Grant WB, Holick MF, Yankovskaya L, Konstantynowicz J, Książyk JB, Księżopolska-Orłowska K, Lewiński A, Litwin M, Lohner S, Lorenc RS, Łukaszkiewicz J, Marcinowska-Suchowierska E, Milewicz A, Misiorowski W, Nowicki M, Povoroznyuk V, Rozentryt P, Rudenka E, Shoenfeld Y, Socha P, Solnica B, Szalecki M, Tałałaj M, Varbiro S, Żmijewski MA. Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe—recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Endokrynol Pol 2013;64(4):319-27.
[35] Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008;87(4):1080S-6S.
[36] Cashman KD, Sheehy T, O’Neil CM. Is vitamin D deficiency a public health concern for low middle income countries? A systematic literature review. Eur J Nutr 2019;58(1):433-53.
[37] Chun NRF, Nielson CM. Free vitamin D: Concepts, assays, outcomes, and prospects. In: Feldman D, Pike JW, Bouillon R, Giovannucci E, Goltzman D, Hewison M, editors. Vitamin D. 4th edition. San Diego: Elsevier Press; 2017. pp. 925-37.
[38] Jassil NK, Sharma A, Bikle D, Wang X. Vitamin D binding protein and 25-hy-droxyvitamin D levels: emerging clinical applications. Endocr Pract 2017;23(5):605-13.
[39] Bikle DD, Siiteri PK, Ryzen E, Haddad JG, Gee E. Serum protein binding of 1, 25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab 1985;61(5):969-75.
[40] Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 1986;63(4):954-9.
[41] Schwartz JB, Lai J, Lizaola B, Kane L, Markova S, Weyland P, Terrault NA, Stotland N, Bikle D. A comparison of measured and calculated free 25(OH) vitamin D levels in clinical populations. J Clin Endocrinol Metab 2014;99(5):1631-7.
[42] Weinstein SJ, Stolzenberg-Solomon RZ, Kopp W, Rager H, Virtamo J, Albanes D. Impact of circulating vitamin D binding protein levels on the association between 25-hydroxyvitamin D and pancreatic cancer risk: a nested case-control study. Cancer Res 2012;72(5):1190-8.
[43] Heureux N, Lindhout E, Swinkels L. A direct assay for measuring free 25-hydro-xyvitamin D. J AOAC Int 2017;100(5):1318-22.