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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We were highly interested in the editorial &#8220;<span class="elsevierStyleItalic">Vitamina D y enfermedades autoinmunes reum&#225;ticas</span>&#8221; &#40;&#8220;Vitamin D and autoimmune rheumatic disease&#8221;&#41;&#44; published recently in <span class="elsevierStyleSmallCaps">Reumatolog&#237;a Cl&#237;nica</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> At the present time&#44; it is well-known that vitamin&#47;hormone D has an essential role in the regulation of the immune system&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and that its deficiency is related to the presence of inflammation&#44; autoimmunity&#44; cancer and atherosclerosis&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> This is especially interesting&#44; when we learn that the levels of vitamin D are substantially reduced in western countries and in the Spanish population in particular&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">As the authors of the editorial do point out&#44; the deficiency or insufficiency of vitamin D is related not only to the coexistence of autoimmune diseases like systemic lupus erythematosus or rheumatoid arthritis &#40;RA&#41;&#44; but also to the activity of some of these diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#8211;7</span></a> The role that vitamin&#47;hormone D may have in other chronic inflammatory diseases&#44; like ankylosing spondylitis &#40;AS&#41; or psoriatic arthritis &#40;PsA&#41;&#44; is less well-known&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Recently&#44; we published the baseline data on cardiovascular morbidity and levels of vitamin&#47;hormone D in patients included in the CARMA &#40;&#8220;CARdiovascular in rheuMAtology&#8221;&#41; project&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> The proposal is a prospective Spanish study&#44; promoted by the Sociedad Espa&#241;ola de Reumatolog&#237;a &#40;SER&#41;&#44; in which we evaluate the risk of developing a fatal cardiovascular event after 10 years in patients with RA&#44; AS and PsA&#44; compared to a cohort of patients with no inflammatory diseases&#44; followed in rheumatology clinics of 67 Spanish hospitals&#46; The study includes a total of 2234 patients&#58; 775 RA&#44; 738 AS and 721 PsA&#44; in addition to 677 noninflammatory individuals&#44; with degenerative or soft tissue diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In the baseline analysis&#44; we found that the patients with inflammatory diseases had a more marked deficiency of D &#40;25-OH-vitamin D<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#44; than the noninflammatory patients &#40;40&#46;5&#37; in RA&#59; 40&#37; in AS&#59; 41&#37; in PsA&#59; and 26&#46;7&#37; in the control group&#59; &#91;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#93;&#41;&#46; The mean levels of 25-OH-vitamin D were&#58; 20&#46;4<span class="elsevierStyleHsp" style=""></span>ng&#47;mL in RA&#59; 20&#46;9<span class="elsevierStyleHsp" style=""></span>ng&#47;mL in AS&#59; 20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL in PsA&#59; and 24&#46;8<span class="elsevierStyleHsp" style=""></span>ng&#47;mL in the control group&#46; We should point out that the controls included&#44; mostly&#44; patients with osteoarthritis&#44; osteoporosis&#44; low back pain or soft tissue disease&#44; in which vitamin&#47;hormone D is usually reduced&#44; as we confirmed&#44; although with fewer percentage points of deficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">With respect to the activity and severity&#44; the bivariate study demonstrated a significant association between the vitamin&#47;hormone D deficiency and certain parameters for aggressive disease&#46; This association disappeared in the adjusted model&#44; although there persisted a certain associative trend between the vitamin&#47;hormone D deficiency and the presence of anti-cyclic citrullinated peptide antibodies &#40;adjusted odds ratio &#91;OR&#93;&#58; 1&#46;45&#59; 95&#37; confidence interval &#91;CI&#93;&#58; 0&#46;99&#8211;2&#46;12&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;056&#41; and Bath AS Functional Index &#40;adjusted OR&#58; 1&#46;08&#59; 95&#37; CI&#58; 0&#46;99&#8211;1&#46;17&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;070&#41;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> in RA and AS&#44; respectively&#46; However&#44; we also point out that patients with inflammatory diseases are closely controlled in hospital rheumatology units&#44; and between 40&#37; and 47&#46;4&#37; are receiving biologic therapy&#44; with activity reduced to their inclusion in the study &#40;disease activity score 28 joints&#8211;erythrocyte sedimentation rate of 3&#46;2 in RA and 3&#46;0 in PsA&#59; Bath AS Disease Activity Index 3&#46;5 in AS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Although our work has certain limitations and there are still doubts concerning supplementation in patients with vitamin&#47;hormone D deficiency&#44; in particular&#44; those with chronic inflammatory diseases&#44; as to&#44; whether&#44; it improves their health and reduces inflammatory activity&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> We feel&#44; like the authors of the editorial&#44; that it is important to monitor and supplement these patients&#44; especially those with a moderate&#47;serious deficiency&#44; because of the possible pathogenic role that vitamin&#47;hormone D may have in the course and comorbidity of their underlying disease&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Finally&#44; it must still be determined whether the maintenance of low vitamin D levels increments the incident of cardiovascular events in our cohort&#46; This is one of the objectives of the CARMA study&#44; and is to be analyzed in the next few years&#46;</p></span>"
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Journal Information
Vol. 12. Issue 6.
Pages 356-357 (November - December 2016)
Vol. 12. Issue 6.
Pages 356-357 (November - December 2016)
Letter to the Editor
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Vitamin D and Autoimmune Rheumatic Diseases
Vitamina D y enfermedades reumáticas
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4391
María A. Martín-Martíneza, Santos Castañedab, Ana Urruticoechea-Aranac, Miguel A. González-Gayd,e,
Corresponding author
miguelaggay@hotmail.com

Corresponding author.
a Unidad de Investigación, Sociedad Española de Reumatología, Madrid, Spain
b Servicio de Reumatología, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid, Madrid, Spain
c Sección de Reumatología, Hospital Can Misses, Ibiza, Balearic Islands, Spain
d Servicio de Reumatología, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Cantabria, Spain
e Grupo de Investigación en Epidemiología, Genética y Aterosclerosis de las Enfermedades Inflamatorias Sistémicas, Instituto de Investigación Sanitaria Marqués de Valdecilla (IDIVAL), Santander, Cantabria, Spain
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To the Editor,

We were highly interested in the editorial “Vitamina D y enfermedades autoinmunes reumáticas” (“Vitamin D and autoimmune rheumatic disease”), published recently in Reumatología Clínica.1 At the present time, it is well-known that vitamin/hormone D has an essential role in the regulation of the immune system,2 and that its deficiency is related to the presence of inflammation, autoimmunity, cancer and atherosclerosis.3 This is especially interesting, when we learn that the levels of vitamin D are substantially reduced in western countries and in the Spanish population in particular.4

As the authors of the editorial do point out, the deficiency or insufficiency of vitamin D is related not only to the coexistence of autoimmune diseases like systemic lupus erythematosus or rheumatoid arthritis (RA), but also to the activity of some of these diseases.5–7 The role that vitamin/hormone D may have in other chronic inflammatory diseases, like ankylosing spondylitis (AS) or psoriatic arthritis (PsA), is less well-known.

Recently, we published the baseline data on cardiovascular morbidity and levels of vitamin/hormone D in patients included in the CARMA (“CARdiovascular in rheuMAtology”) project.8,9 The proposal is a prospective Spanish study, promoted by the Sociedad Española de Reumatología (SER), in which we evaluate the risk of developing a fatal cardiovascular event after 10 years in patients with RA, AS and PsA, compared to a cohort of patients with no inflammatory diseases, followed in rheumatology clinics of 67 Spanish hospitals. The study includes a total of 2234 patients: 775 RA, 738 AS and 721 PsA, in addition to 677 noninflammatory individuals, with degenerative or soft tissue diseases.8,9

In the baseline analysis, we found that the patients with inflammatory diseases had a more marked deficiency of D (25-OH-vitamin D<20ng/mL), than the noninflammatory patients (40.5% in RA; 40% in AS; 41% in PsA; and 26.7% in the control group; [P<.001]). The mean levels of 25-OH-vitamin D were: 20.4ng/mL in RA; 20.9ng/mL in AS; 20ng/mL in PsA; and 24.8ng/mL in the control group. We should point out that the controls included, mostly, patients with osteoarthritis, osteoporosis, low back pain or soft tissue disease, in which vitamin/hormone D is usually reduced, as we confirmed, although with fewer percentage points of deficiency.9

With respect to the activity and severity, the bivariate study demonstrated a significant association between the vitamin/hormone D deficiency and certain parameters for aggressive disease. This association disappeared in the adjusted model, although there persisted a certain associative trend between the vitamin/hormone D deficiency and the presence of anti-cyclic citrullinated peptide antibodies (adjusted odds ratio [OR]: 1.45; 95% confidence interval [CI]: 0.99–2.12; P=.056) and Bath AS Functional Index (adjusted OR: 1.08; 95% CI: 0.99–1.17; P=.070)9 in RA and AS, respectively. However, we also point out that patients with inflammatory diseases are closely controlled in hospital rheumatology units, and between 40% and 47.4% are receiving biologic therapy, with activity reduced to their inclusion in the study (disease activity score 28 joints–erythrocyte sedimentation rate of 3.2 in RA and 3.0 in PsA; Bath AS Disease Activity Index 3.5 in AS).9

Although our work has certain limitations and there are still doubts concerning supplementation in patients with vitamin/hormone D deficiency, in particular, those with chronic inflammatory diseases, as to, whether, it improves their health and reduces inflammatory activity.10 We feel, like the authors of the editorial, that it is important to monitor and supplement these patients, especially those with a moderate/serious deficiency, because of the possible pathogenic role that vitamin/hormone D may have in the course and comorbidity of their underlying disease.

Finally, it must still be determined whether the maintenance of low vitamin D levels increments the incident of cardiovascular events in our cohort. This is one of the objectives of the CARMA study, and is to be analyzed in the next few years.

Acknowledgements

All of the patients and participating centers, whose role in the follow-up and collection of clinical data is being fundamental for the development of the project. The list of participating centers and authors appears in the addendum of the respective publications. Likewise, we wish to thank the SER and Abbvie España for promoting and sponsoring the project.

References
[1]
M. García-Carrasco, J.L. Gálvez-Romero.
Vitamina D y enfermedades autoinmunes reumáticas.
Reumatol Clin, 11 (2015), pp. 333-334
[2]
A. Verstuyf, G. Carmeliet, R. Bouillon, C. Mathieu.
Vitamin D: a pleiotropic hormone.
Kidney Int, 78 (2010), pp. 140-145
[3]
M. Hewison.
An update on vitamin D and human immunity.
Clin Endocrinol (Oxf), 76 (2012), pp. 315-325
[4]
P. Aguado, M.V. Garcés, M.L. González Casaús, M.T. del Campo, P. Richi, J. Coya, et al.
High prevalence of vitamin D deficiency in postmenopausal women at a rheumatology office in Madrid. Evaluation of 2 vitamin D prescription regimens.
Med Clin (Barc), 114 (2000), pp. 326-330
[5]
M. Cutolo, K. Otsa, K. Laas, M. Yprus, R. Lehtme, M.E. Secchi, et al.
Circannual vitamin D serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe.
Clin Exp Rheumatol, 24 (2006), pp. 702-704
[6]
S. Patel, T. Farragher, J. Berry, D. Bunn, A. Silman, D. Symmons.
Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis.
Arthritis Rheum, 56 (2007), pp. 2143-2149
[7]
S. Zhao, S.J. Duffield, R.J. Moots, N.J. Goodson.
Systematic review of association between vitamin D levels and susceptibility and disease activity of ankylosing spondylitis.
Rheumatology (Oxford), 53 (2014), pp. 1595-1603
[8]
S. Castañeda, M.A. Martín-Martínez, C. González-Juanatey, J. Llorca, M.J. García-Yébenes, S. Pérez-Vicente, et al.
Cardiovascular morbidity and associated risk factors in Spanish patients with chronic inflammatory rheumatic diseases attending rheumatology clinics: baseline data of the CARMA Project.
Semin Arthritis Rheum, 44 (2015), pp. 618-626
[9]
A. Urruticoechea-Arana, M.A. Martín-Martínez, S. Castañeda, C.A. Piedra, C. González-Juanatey, J. Llorca, et al.
Vitamin D deficiency in chronic inflammatory rheumatic diseases: Results of the cardiovascular in rheumatology [CARMA] study.
Arthritis Res Ther, 17 (2015), pp. 211
[10]
E. Theodoratou, I. Tzoulaki, L. Zgaga, J.P. Ioannidis.
Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials.
BMJ, 348 (2014), pp. g2035

Please cite this article as: Martín-Martínez MA, Castañeda S, Urruticoechea-Arana A, González-Gay MA. Vitamina D y enfermedades reumáticas. Reumatol Clin. 2016;12:356–357.

Copyright © 2016. Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología
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