Top

Published in:

01-08-2021 | Kawasaki Disease | Observational Research

The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon

Authors: Katarzyna Kapten, Krzysztof Orczyk, Elzbieta Smolewska

Published in: Rheumatology International | Issue 8/2021

Abstract

Raynaud phenomenon (RP) may be the first manifestation of a systemic connective tissue disease (SCTD). Early detection of dysfunction of small vessels called microangiopathy is essential for the diagnostic process. The focus of this single-center, retrospective study was to investigate the potential dependencies between microvascular image and laboratory markers measured in children with RP. The study analyzed the nail-fold video-capillaroscopy (NVC) findings and laboratory results of 81 children between the ages 6 and 17 who were referred to pediatric rheumatologist with a suspicion of SCTD. Out of 52 patients presenting with RP at the time of evaluation, abnormalities in capillary microscopic imaging were found in 34. NVC findings were then compared to levels of specific biomarkers in serum. Vitamin D3 serum levels have been significantly decreased in patients with RP (23.4 ng/mL ± 8.76 vs. 30.0 ng/mL ± 12.66, P = 0.0148). There were positive significant correlations between levels of vitamin D3 and acute-phase reactants in serum, such as C-reactive protein (P = 0.0292). Furthermore, free thyroxine levels (fT4) in patients with both RP (P = 0.0126) and micro-angiopathy (P = 0.05496) persisted in the lower range of the normal limit (< 1.0 ng/dL). Regular oral supplementation of vitamin D3 should be always considered in children with RP if deficiency is found. Additionally, low fT4 level (< 1.0 ng/dL) should be considered as an indication to perform NVC in patients suspected of SCTD even when they do not present RP.

Temprano KK (2016) A review of Raynaud’s disease. Mo Med 113:123–126PubMedPubMedCentral

Walecka I, Malewska A, Roszkiewicz M, Wieczorek M, Lagun Z, Szymanska Z (2017) Raynaud’s phenomenon—the clinical picture, treatment and diagnostics. Acta Angiologica 23:29–33. https://doi.org/10.5603/AA.2017.0003CrossRef

Sulli A, Soldano S, Pizzorni C, Montagna P, Secchi ME, Villaggio B, Seriolo B, Brizzolara R, Cutolo M (2009) Raynaud’s phenomenon and plasma endothelin: correlations with capillaroscopic patterns in systemic sclerosis. J Rheumatol 36:1235–1239. https://doi.org/10.3899/jrheum.081030CrossRefPubMed

Latuskiewicz-Potemska J, Chmura-Skirlinska A, Gurbiel RJ, Smolewska E (2016) Nailfold capillaroscopy assessment of microcirculation abnormalities and endothelial dysfunction in children with primary or secondary Raynaud syndrome. Clin Rheumatol 35:1993–2001. https://doi.org/10.1007/s10067-016-3340-8CrossRefPubMed

Musa R, Qurie A (2020) Raynaud disease. StatPearls (Internet). StatPearls Publishing, Treasure Island

Piotto DG, Hilário MO, Carvalho NS, Len CA, Andrade LE, Terreri MT (2013) Prospective nailfold capillaroscopy evaluation of Raynaud’s phenomenon in children and adolescents. Acta Reumatol Port 38:114–121PubMed

Litonjua AA (2019) Vitamin D and childhood asthma: causation and contribution to disease activity. Curr Opin Allergy Clin Immunol 19:126–131. https://doi.org/10.1097/ACI.0000000000000509CrossRefPubMedPubMedCentral

Martineau AR, Jolliffe DA, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Janssens W, Jensen ME, Kerley CP, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S, Stelmach I, Kumar GT, Urashima M, Camargo CA, Griffiths CJ, Hooper RL (2019) Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess 23:1–44. https://doi.org/10.3310/hta23020CrossRefPubMedPubMedCentral

Xu WR, Jin HF, Du JB (2017) Vitamin D and cardiovascular risk in children. Chin Med J (Engl) 5(130):2857–2862. https://doi.org/10.4103/0366-6999.215500CrossRef

10.

Stagi S, Rigante D, Lepri G, Cerinic MM, Falcini F (2016) Severe vitamin D deficiency in patients with Kawasaki disease: a potential role in the risk to develop heart vascular abnormalities? Clin Rheumatol 35:1865–1872. https://doi.org/10.1007/s10067-015-2970-6CrossRefPubMed

11.

Chen YL, Wang JL, Li WQ (2014) Prediction of the risk of coronary arterial lesions in Kawasaki disease by serum 25-hydroxyvitamin D3. Eur J Pediatr 173:1467–1471. https://doi.org/10.1007/s00431-014-2346-yCrossRefPubMedPubMedCentral

12.

Di Rosa M, Malaguarnera G, De Gregorio C, Palumbo M, Nunnari G, Malaguarnera L (2012) Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages. Cell Immunol 280:36–43. https://doi.org/10.1016/j.cellimm.2012.10.009CrossRefPubMed

13.

Tabatabaeizadeh SA, Avan A, Bahrami A, Khodashenas E, Esmaeili H, Ferns GA, Abdizadeh MF, Ghayour-Mobarhan M (2017) High dose supplementation of vitamin D affects measures of systemic inflammation: reductions in high sensitivity C-reactive protein level and neutrophil to lymphocyte ratio (NLR) distribution. J Cell Biochem 118:4317–4322. https://doi.org/10.1002/jcb.26084CrossRefPubMed

14.

Liefaard MC, Ligthart S, Vitezova A, Hofman A, Uitterlinden AG, Kiefte-de Jong JC, Franco OH, Zillikens MC, Dehghan A (2015) Vitamin D and C-reactive protein: a Mendelian randomization study. PLoS ONE 6(10):e0131740. https://doi.org/10.1371/journal.pone.0131740CrossRef

15.

Tao RX, Zhou QF, Xu ZW, Hao JH, Huang K, Mou Z, Jiang XM, Tao FB, Zhu P (2015) Inverse correlation between vitamin D and C-reactive protein in newborns. Nutrients 10(7):9218–9228. https://doi.org/10.3390/nu7115468CrossRef

16.

Park YC, Kim J, Seo MS, Hong SW, Cho ES, Kim JK (2017) Inverse relationship between vitamin D levels and platelet indices in Korean adults. Hematology 22:623–629. https://doi.org/10.1080/10245332.2017.1318334CrossRefPubMed

17.

Hélou J, Moutran R, Maatouk I, Haddad F (2013) Raynaud’s phenomenon and vitamin D. Rheumatol Int 33:751–755. https://doi.org/10.1007/s00296-012-2445-xCrossRefPubMed

18.

Szymańska-Kałuża J, Biernacka-Zielińska M, Stańczyk J, Smolewska E (2013) Vitamin D level in children with juvenile idiopathic arthritis and its correlation with clinical picture of the disease. Reumatologia 51:271–276. https://doi.org/10.5114/reum.2013.37250CrossRef

19.

Saggese G, Vierucci F, Boot AM, Czech-Kowalska J, Weber G, Camargo CA Jr, Mallet E, Fanos M, Shaw NJ, Holick MF (2015) Vitamin D in childhood and adolescence: an expert position statement. Eur J Pediatr 174:565–576. https://doi.org/10.1007/s00431-015-2524-6CrossRefPubMed

20.

Shagan BP, Friedman SA (1976) Raynaud’s phenomenon in hypothyroidism. Angiology 27:19–25. https://doi.org/10.1177/000331977602700104CrossRefPubMed

21.

Lateiwish AM, Fehér J, Baraczka K, Rácz K, Kiss R, Gláz E (1992) Remission of Raynaud’s phenomenon after L-thyroxine therapy in a patient with hypothyroidism. J Endocrinol Invest 15:49–51. https://doi.org/10.1007/BF03348657CrossRefPubMed

22.

Shagan BP, Friedman SA (1980) Raynaud’s phenomenon and thyroid deficiency. Arch Intern Med 140:832–833CrossRef

23.

Withrington RH, Seifert MH (1981) Hypothyroidism associated with mixed connective tissue disease and its response to steroid therapy. Ann Rheum Dis 40:315–316. https://doi.org/10.1136/ard.40.3.315CrossRefPubMedPubMedCentral

24.

Ciaffi J, Ajasllari N, Mancarella L, Brusi V, Meliconi R, Ursini F (2020) Nailfold capillaroscopy in common non-rheumatic conditions: a systematic review and applications for clinical practice. Microvasc Res 131:104036. https://doi.org/10.1016/j.mvr.2020.104036CrossRefPubMed

25.

Ingegnoli F, Ughi N, Dinsdale G, Orenti A, Boracchi P, Allanore Y, Foeldvari I, Sulli A, Cutolo M, Smith V, Herrick AL, EULAR Study Group on Microcirculation in RheumaticDiseases (2017) An international SUrvey on non-iNvaSive tecHniques to assess the mIcrocirculation in patients with RayNaud’s phEnomenon (SUNSHINE survey). Rheumatol Int 37:1879–1890. https://doi.org/10.1007/s00296-017-3808-0CrossRefPubMed

26.

Tavakol ME, Fatemi A, Karbalaie A, Emrani Z, Erlandsson BE (2015) Nailfold capillaroscopy in rheumatic diseases: which parameters should be evaluated? Biomed Res Int 2015:974530. https://doi.org/10.1155/2015/974530CrossRef

27.

Schonenberg-Meinema D, Bergkamp SC, Nassar-Sheikh Rashid A, van der Aa LB, de Bree GJ, Ten Cate R, Cutolo M, Hak AE, Muller PCH, van Onna M, Kuijpers TW, Smith V, van den Berg JM (2021) Nailfold capillary abnormalities in childhood-onset systemic lupus erythematosus: a cross-sectional study compared with healthy controls. Lupus 30(5):818–827. https://doi.org/10.1177/0961203321998750CrossRefPubMedPubMedCentral

28.

Torrente-Segarra V, Hernández-Baldizón S, Mosquera JM, Antón J (2021) The importance of nailfold capillaroscopy in children with rheumatic diseases. Clin Exp Rheumatol 39(Suppl 128-1):35PubMed

29.

Okazaki R, Ozono K, Fukumoto S, Inoue D, Yamauchi M, Minagawa M, Michigami T, Takeuchi Y, Matsumoto T, Sugimoto T (2017) Assessment criteria for vitamin D deficiency/insufficiency in Japan: proposal by an expert panel supported by the Research Program of Intractable Diseases, Ministry of Health, Labour and Welfare, Japan, the Japanese Society for Bone and Mineral Research and the Japan Endocrine Society [Opinion]. J Bone Miner Metab 235:1–5. https://doi.org/10.1007/s00774-016-0805-4CrossRef

30.

Rossi D, Russo A, Manna E, Binello G, Baldovino S, Sciascia S, Roccatello D (2013) The role of nail-videocapillaroscopy in early diagnosis of scleroderma. Autoimmun Rev 12:821–825. https://doi.org/10.1016/j.autrev.2012.11.006CrossRefPubMed

31.

Tamez-Rivera O, Villarreal-Treviño AV, Castañeda-Macazaga T, Britton-Robles SC, Ramos-Gómez LI, Rubio-Pérez NE (2021) Abnormal nailfold capillaroscopy in a patient with multisystem inflammatory syndrome in children. Pediatr Infect Dis J 40(3):e113–e115. https://doi.org/10.1097/INF.0000000000003022CrossRefPubMed

32.

Sampaio-Barros MM, Takayama L, Sampaio-Barros PD, Bonfá E, Pereira RM (2016) Low vitamin D serum levels in diffuse systemic sclerosis: a correlation with worst quality of life and severe capillaroscopic findings. Rev Bras Reumatol Engl Ed 56:337–344. https://doi.org/10.1016/j.rbre.2016.05.006 (English, Portuguese)CrossRefPubMed

33.

Trombetta AC, Smith V, Gotelli E, Ghio M, Paolino S, Pizzorni C, Vanhaecke A, Ruaro B, Sulli A, Cutolo M (2017) Vitamin D deficiency and clinical correlations in systemic sclerosis patients: a retrospective analysis for possible future developments. PLoS ONE 9(12):e0179062. https://doi.org/10.1371/journal.pone.0179062CrossRef

34.

Groseanu L, Bojinca V, Gudu T, Saulescu I, Predeteanu D, Balanescu A, Berghea F, Opris D, Borangiu A, Constantinescu C, Negru M, Ionescu R (2016) Low vitamin D status in systemic sclerosis and the impact on disease phenotype. Eur J Rheumatol 3:50–55. https://doi.org/10.5152/eurjrheum.2015.0065CrossRefPubMedPubMedCentral

35.

Gupta S, Goyal P, Feinn RS, Mattana J (2019) Role of vitamin D and its analogues in diabetic nephropathy: a meta-analysis. Am J Med Sci 357:223–229. https://doi.org/10.1016/j.amjms.2018.12.005CrossRefPubMed

36.

Shillo P, Selvarajah D, Greig M, Gandhi R, Rao G, Wilkinson ID, Anand P, Tesfaye S (2019) Reduced vitamin D levels in painful diabetic peripheral neuropathy. Diabet Med 36:44–51. https://doi.org/10.1111/dme.13798CrossRefPubMed

37.

Tecilazich F, Formenti AM, Giustina A (2020) Role of vitamin D in diabetic retinopathy: pathophysiological and clinical aspects. Rev Endocr Metab Disord 7:1–13. https://doi.org/10.1007/s11154-020-09575-4CrossRef

38.

Harris RA, Pedersen-White J, Guo DH, Stallmann-Jorgensen IS, Keeton D, Huang Y, Shah Y, Zhu H, Dong Y (2011) Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults. Am J Hypertens 24:557–562. https://doi.org/10.1038/ajh.2011.12CrossRefPubMed

39.

Molnár I, Czirják L (2000) Euthyroid sick syndrome and inhibitory effect of sera on the activity of thyroid 5′-deiodinase in systemic sclerosis. Clin Exp Rheumatol 18:719–724PubMed

40.

Gordon MB, Klein I, Dekker A, Rodnan GP, Medsger TA Jr (1981) Thyroid disease in progressive systemic sclerosis: increased frequency of glandular fibrosis and hypothyroidism. Ann Intern Med 95:431–435. https://doi.org/10.7326/0003-4819-95-4-431CrossRefPubMed

41.

De Martinis M, Sirufo MM, Ginaldi L (2018) Raynaud’s phenomenon and nailfold capillaroscopic findings in anorexia nervosa. Curr Med Res Opin 34:547–550. https://doi.org/10.1080/03007995.2017.1417828CrossRefPubMed

Title: The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon
Authors: Katarzyna Kapten
Krzysztof Orczyk
Elzbieta Smolewska
Publication date: 01-08-2021
Publisher: Springer Berlin Heidelberg
Keywords: Kawasaki Disease
Kawasaki Disease
Kawasaki Disease
Published in: Rheumatology International / Issue 8/2021
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-021-04919-y

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2021

Safety and efficacy of COVID-19 vaccines in pregnant women with rheumatic diseases: an immunologic perspective

COVID-19 pandemic and systemic autoinflammatory diseases management: a cross-sectional survey

Barriers to medication adherence and degree of nonadherence in a systemic lupus erythematosus (SLE) outpatient population

Antibody response to inactivated COVID-19 vaccine (CoronaVac) in immune-mediated diseases: a controlled study among hospital workers and elderly

Expanding the spectrum of reactive arthritis (ReA): classic ReA and infection-related arthritis including poststreptococcal ReA, Poncet’s disease, and iBCG-induced ReA

Sex hormones, autoimmunity and gender disparity in COVID-19

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page