Download PDF
Aktuelle Rheumatologie 2016; 41(06): 492-498
DOI: 10.1055/s-0035-1545308
Originalarbeit
Georg Thieme Verlag KG Stuttgart · New York

Vitamin D Status in Egyptian Patients with Rheumatoid Arthritis

Vitamin D Status bei ägyptischen Patienten mit rheumatoider Arthritis
R. M. Gamal
1   Rheumatology and Rehablitation, Assiut University Hospital, Assiut, Egypt
,
W. Gaber
2   Rheumatology and Rehabilitation Department, Cairo University Hospital, Cairo, Egypt
,
S. Sayed
2   Rheumatology and Rehabilitation Department, Cairo University Hospital, Cairo, Egypt
,
A. M. Mohey
3   Clinical Pathology, Cairo University Hospital, Cairo, Egypt
,
S. H. Goma
1   Rheumatology and Rehablitation, Assiut University Hospital, Assiut, Egypt
,
M. S. E. Mohamed
4   Microbiology and Immunology Department, Faculty of Medicine, Assuit University, Assiut, Egypt
› Author Affiliations
Further Information

Publication History

Publication Date:
18 March 2015 (online)

Also available at
    Permissions and Reprints

Abstract

Background: Vitamin D is a potent regulator of calcium homeostasis and may have immunomodulatory effects. The influence of vitamin D on human autoimmune disease has not been well defined. The aim of this cross sectional study was to estimate the prevalence and determinants of vitamin D deficiency in patients with rheumatoid arthritis as compared to healthy controls and to analyze the association between 25-hydroxyvitamin D with disease activity.

Methods: The study includes 55 consecutive rheumatoid arthritis patients and 25 healthy controls, not on vitamin D supplements. Together with parameters of disease activity, all patients had serum 25-hydroxyvitamin D [25(OH)D] measured by ELISA kit in a centralized laboratory. Disease activity in rheumatoid arthritis was assessed by Disease Activity Score 28 (DAS28) and Health Assessment Questionnaire (HAQ). According to activity indexes, patients were divided into subgroups with high activity of the disease (DAS28>5.1), moderate activity of the disease (3.2<DAS28≤5.1), low activity of disease (2.6≤DAS28≤3.2) and remission (DAS28<2.60). Associations between serum levels of 25(OH)D and age, disease duration and activity were assessed.

Results: 25-hydroxyvitamin D deficiency, insufficiency and sufficiency were found in 16.00, 4.00 and 80.00% of controls, respectively, while, 25(OH)D insufficiency and sufficiency were found in 21.80 and 78.20% of rheumatoid arthritis patients, respectively with no significant difference between groups (P<0.918). According to DAS28 scoring, 9.10% of patients showed remission (DAS28<2.6), 7.30% showed low disease activity (2.6≤DAS28≤3.2), 63.60% showed moderate activity (3.2<DAS28≤5.1) and 20.00% showed high disease activity (DAS28>5.1). Disease duration was significantly longer in patients with moderate disease activity vs. those with low and high disease activity (P< 0.026 and P<0.001, respectively). 25(OH)D levels were lower in moderate disease activity vs. those with remission (P<0.014). DAS28 and HAQ were significantly higher in patients with high disease activity than remission, low disease activity and moderate disease activity. DAS28 and HAQ were significantly higher in patients with moderate disease activity than remission and those with low disease activity. A significant negative correlation was found in rheumatoid arthritis patients between 25(OH)D and ESR.

Conclusions: In rheumatoid arthritis patients, vitamin D deficiency is quite common, but similar to that found in control subjects; disease activity (expressed as ESR) is inversely related to 25(OH)D levels.

Zusammenfassung

Hintergrund: Vitamin D ist ein potenter Regulator der Kalzium Hämostase und hat möglicherweise immunmodulatorische Effekte. Der Einfluss von Vitamin D auf Autoimmunerkrankungen ist nicht gut untersucht. Ziel dieser Querschnittsstudie war die Einschätzung der Prävalenz und die Determinanten des Vitamin D Mangels bei Patienten mit rheumatoider Arthritis im Vergleich zu gesunden Kontrollen sowie die Analyse der Assoziation zwischen 25-Hydroxyvitamin D und der Krankheitsaktivität.

Methoden: Die Studie inkludierte 55 konsekutive Patienten mit rheumatoider Arthritis und 25 gesunde Kontrollen, die kein Vitamin D einnahmen. Zusätzlich zu Krankheitsaktivitätsparametern erhielten alle Patienten Serum 25-Hydroxyvitamin D [25(OH)D] Analysen anhand eines ELISAs in einem zentralen Labor. Die Krankheitsaktivität der rheumatoiden Arthritis wurde anhand des Disease Activity Score 28 (DAS28) und des Health Assessment Questionnaire (HAQ) gemessen. Entsprechend ihrer Aktivitätsindizes wurden die Patienten in Subgruppen mit hoher (DAS28>5,1), moderater (3,2<DAS28≤5,1), und niedriger Krankheitsaktivität (2,6≤DAS28≤3,2)sowie Remission (DAS28<2,60) eingeteilt. Die Assoziation zwischen Serum Werten von 25(OH)D und Alter, Krankheitsdauer und Aktivität wurden analysiert.

Ergebnisse: Eine 25-Hydroxyvitamin D Defizienz, ein Mangel und ein suffizienter Spiegel wurden bei 16,00, 4,00 und 80,00% der Kontrollen gefunden, während ein 25(OH)D Mangel und ein suffizienter Spiegel bei 21,80 und 78,20% der rheumatoiden Arthritis Patienten gefunden wurden, was nicht signifikant unterschiedlich in der Gruppenanalyse war (P<0,918). Entsprechend dem DAS28 Score, waren 9,10% der Patienten in Remission (DAS28<2,6), 7,30% hatten eine niedrige Krankheitsaktivität (2,6≤DAS28≤3,2), und 63,60% zeigten eine moderate Aktivität (3,2<DAS28≤5,1) und 20,00% hatten eine hohe Krankheitsaktivität (DAS28>5,1). Die Krankheitsdauer war signifikant länger bei Patienten mit moderater Krankheitsaktivität als bei solchen mit niedriger und hoher Aktivität (P< 0,026 und P<0,001). Die 25(OH)D Werte waren niedriger bei moderater Krankheitsaktivität als bei Patienten in Remission (P<0,014). DAS28 und HAQ waren signifikant höher bei Patienten mit hoher Krankheitsaktivität als in Remission, niedriger oder moderater Krankheitsaktivität. DAS28 und HAQ waren signifikant höher bei Patienten mit moderater Krankheitsaktivität im Vergleich zu Remission und niedriger Krankheitsaktivität. Eine signifikant negative Korrelation zwischen 25(OH)D Werten und der BSG wurde bei Patienten mit rheumatoider Arthritis gefunden.

Schlussfolgerung: Bei Patienten mit rheumatoider Arthritis ist ein Vitamin D Mangel relativ häufig, aber ähnlich häufig wie bei Kontrollpersonen, die Krankheitsaktivität (dargestellt als BSG) ist invers mit den 25(OH)D Werten korreliert.

Key words

vitamin D deficiency - rheumatoid arthritis - disease activity

Schlüsselwörter

Vitamin D Mangel - rheumatoide Arthritis - Krankheitsaktivität
 

  • References

  • 1 Firestein GS. Etiology and pathogenesis of rheumatoid arthritis. In: Harris ED, Budd RC, Sargent JS, Sledge CB, Ruddy S. (eds.) Kelley’s textbook of rheumatology. Elsevier Saunders; Philadelphia: 2005: 996-1042
    Google Scholar
  • 2 Sokka T. Rheumatoid arthritis databases in Finland. Clin Exp Rheumatol 2005; 23 (Suppl. 39) 201-204
    PubMedGoogle Scholar
  • 3 Cantorna MT, Zhu Y, Froicu M et al. Vitamin D status, 1, 25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004; 80: 1717-1720
    PubMedGoogle Scholar
  • 4 Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 2005; 26: 662-687
    CrossrefPubMedGoogle Scholar
  • 5 Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new etiological and therapeutic considerations. Ann Rheum Dis 2007; 66: 1137-1142
    CrossrefPubMedGoogle Scholar
  • 6 D’Ambrosio D, Cippitelli M, Cocciolo MG et al. Inhibition of IL-12 production by 1,25-dihydroxy-vitamin D3. Involvement of NF-kappa B down regulation in transcriptional repression of the p40 gene. J Clin Invest 1998; 101: 252-262
    CrossrefPubMedGoogle Scholar
  • 7 Hayes CE, Nashold FE, Spach KM et al. The immunological functions of the vitamin D endocrine system. Cell Mol Biol 2003; 49: 277-300
    PubMedGoogle Scholar
  • 8 Zitterman A. Vitamin D in preventive medicine: are we ignoring the evidence?. BJN 2003; 89: 552-572
    CrossrefPubMedGoogle Scholar
  • 9 Cantorna MT, Hayes CE, DeLuca HF. 1,25-dihydroxyvitamin D inhibits the progression of arthritis in murine models of human arthritis. J Nutr 1998; 128: 68-72
    PubMedGoogle Scholar
  • 10 Cantorna MT, Hayes CE, DeLuca HF. 1,25-dihydroxyvitamin D reversibly blocks the progression of relapsing encephalomyelitis. Proc Natl Acad Sci USA 1996; 93: 7861-7864
    CrossrefPubMedGoogle Scholar
  • 11 Tetlow LC, Smith SJ, Mawer EB et al. Vitamin D receptors in the rheumatoid lesion: expression by chondrocytes, macrophages and synoviocytes. Ann Rheum Dis 1999; 58: 118-121
    CrossrefPubMedGoogle Scholar
  • 12 Inaba M, Yukioka K, Furumitsu Y et al. Positive correlation between levels of IL-1 or IL-2 and 1,25(OH)2D/25-OH-D ratio in synovial fluid of patients with rheumatoid arthritis. Life Sci 1997; 61: 977-985
    CrossrefPubMedGoogle Scholar
  • 13 Merlino LA, Curtis J, Mikuls TR et al. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum 2004; 50: 72-77
    CrossrefPubMedGoogle Scholar
  • 14 Nielen MMJ, van Schaardenburg D, van de Stadt RJ et al. Vitamin D deficiency does not increase the risk of rheumatoid arthritis. Arthritis Rheum 2006; 11: 3719-3724
    PubMedGoogle Scholar
  • 15 Costenbader KH, Feskanich D, Holmes M et al. Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women. Ann Rheum Dis 2008; 67: 530-535
    CrossrefPubMedGoogle Scholar
  • 16 Patel S, Farrager T, Berry J et al. Association between serum vitamin D metabolites levels and disease activity in patients with early inflammatory polyarthritis. Arthritis Rheum 2007; 56: 2143-2149
    CrossrefPubMedGoogle Scholar
  • 17 Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315-324
    Google Scholar
  • 18 Prevoo MLL, Van’t Hof MA, Van Leeuwen MA et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38: 44-48
    CrossrefPubMedGoogle Scholar
  • 19 Van Gestel AM, Haagsma CJ, Van Riel PLCM. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 1998; 41: 1845-1850
    CrossrefPubMedGoogle Scholar
  • 20 Fries J, Spitz P, Kraines RG et al. Measurement of patient outcome in arthritis. Arthritis Rheum 1980; 23: 137-145
    CrossrefPubMedGoogle Scholar
  • 21 Wolfe F, Michaud K, Pincus T. Development and validation of the Health Assessment Questionnaire II: a revised version of the Health Assessment Questionnaire. Arthritis Rheum 2004; 50: 3296-3305
    CrossrefPubMedGoogle Scholar
  • 22 Lips P, Wiersinga A, van Ginkel FC et al. The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab 1988; 67: 644-650
    CrossrefPubMedGoogle Scholar
  • 23 Webb AR, Pilbeam C, Hanafin N et al. An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston. Am J Clin Nutr 1990; 51: 1075-1081
    PubMedGoogle Scholar
  • 24 Gloth 3rd FM, Gundberg CM, Hollis BW et al. Vitamin D deficiency in homebound elderly persons. JAMA 1995; 274: 1683-1686
    CrossrefPubMedGoogle Scholar
  • 25 Thomas MK, Lloyd-Jones DM, Thadhani RI et al. Hypovitaminosis D in medical inpatients. N Engl J Med 1998; 338: 777-783
    CrossrefPubMedGoogle Scholar
  • 26 Craig SM, Yu F, Curtis JR et al. Vitamin D status and its associations with disease activity and severity in African Americans with recent-onset rheumatoid arthritis. J Rheumatol 2010; 37: 275-281
    CrossrefPubMedGoogle Scholar
  • 27 Turhanoğlu AD, Güler H, Yönden Z et al. The relationship between vitamin D and disease activity and functional health status in rheumatoid arthritis. Rheumatol Int 2011; 31: 911-914
    CrossrefPubMedGoogle Scholar
  • 28 Attar SM. Vitamin D deficiency in rheumatoid arthritis. Prevalence and association with disease activity in Western Saudi Arabia. Saudi Med J 2012; 33: 520-525
    PubMedGoogle Scholar
  • 29 Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006; 81: 353-373
    CrossrefPubMedGoogle Scholar
  • 30 Kröger H, Penttila IM, Alhava EM. Low serum vitamin D metabolites in women with rheumatoid arthritis. Scand J Rheumatol 1993; 22: 172-177
    CrossrefPubMedGoogle Scholar
  • 31 Rico H, Revilla M, Alvarez De Buergo M et al. Serum osteocalcin and calcitropic hormones in a homogeneous group of patients with rheumatoid arthritis: its implication in the osteopenia of the disease. Clin Exp Rheumatol 1993; 11: 53-56
    PubMedGoogle Scholar
  • 32 Oelzner P, Müller A, Deschner F et al. Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis. Calcif Tissue Int 1998; 62: 193-198
    CrossrefPubMedGoogle Scholar
  • 33 Aguado P, del Campo MT, Garces MV et al. Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density. Osteoporos Int 2000; 11: 739-744
    CrossrefPubMedGoogle Scholar
  • 34 Solomon DH, Finkelstein JS, Shadick N et al. The relationship between focal erosions and generalized osteoporosis in postmenopausal women with rheumatoid arthritis. Arthritis Rheum 2009; 60: 1624-1631
    CrossrefPubMedGoogle Scholar
  • 35 Harel M, Shoenfeld Y. Predicting and preventing autoimmunity, myth or reality?. Ann NY Acad Sci 2006; 1069: 322-345
    CrossrefPubMedGoogle Scholar
  • 36 Costenbader KH, Feskanich D, Benito-Garcia E et al. Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women. Ann Rheum Dis 2007; 31: 446-447
    PubMedGoogle Scholar
  • 37 Lange U, Teichmann J, Strunk J et al. Association of 1, 25 vitamin D3 deficiency, disease activity and low bone mass in ankylosing spondylitis. Osteoporosis Int 2005; 16: 1999-2004
    CrossrefPubMedGoogle Scholar
  • 38 Cutolo M, Otsa K, Laas K et al. Circannual vitamin D serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol 2006; 24: 702-704
    PubMedGoogle Scholar
  • 39 Andjelkovic Z, Vojinovic J, Pejnovic N et al. Disease modifying and immunomodulatory eVects of high dose 1 alpha (OH) D3 in rheumatoid arthritis patients. Clin Exp Rheumatol 1999; 17: 453-456
    PubMedGoogle Scholar
  • 40 Szodoray P, Nakken B, Gaal J et al. The complex role of vitamin D in autoimmune diseases. Scand J Immunol 2008; 68: 261-269
    CrossrefPubMedGoogle Scholar
  • 41 Mahon BD, Gordon SA, Cruz J et al. Cytokine proWle in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol 2003; 134: 128-132
    CrossrefPubMedGoogle Scholar
  • 42 Gullick NJL, Evans HG, Church LD et al. Linking power Doppler ultrasound to the presence of th17 cells in the rheumatoid arthritis joint. PLoS One 2010; 5 pii: e12516 DOI: 10.1371/journal.pone.0012516.
    PubMedGoogle Scholar
  • 43 Chen DYL, Chen YM, Chen HH et al. Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy. Arthritis Res Ther 2011; 13: R126 DOI: 10.1186/ar3431.
    CrossrefPubMedGoogle Scholar
  • 44 Wu C, Goodall JC, Busch R et al. Relationship of Cd146 Expression to Secretion of Interleukin-17, Interleukin-22, and Interferon-γ By Cd4+ T Cells in Patients with Inflammatory Arthritis. Clin Exp Immunol 2014; DOI: 10.1111/cei.12434. [Epub head of print]
    PubMedGoogle Scholar
  • 45 Ranganathan P, Khalatbari S, Yalavarthi S et al. Vitamin D deficiency, interleukin 17, and vascular function in rheumatoid arthritis. J Rheumatol 2013; 40: 1529-1534
    CrossrefPubMedGoogle Scholar