Background/Aims: Vitiligo is considered to be an autoimmune disease and is known to be associated with other autoimmune diseases, particularly affecting the thyroid. In children and adolescents this association has been reported in only a few studies, with varying results. The aim of this study was to examine thyroid function and prevalence of thyroid autoimmunity in children and adolescents with vitiligo and to investigate the utility of screening. Methods: Two hundred and sixty patients with vitiligo were enrolled. Plasma TSH, FT4 and anti-thyroid peroxidase (TPO) antibody concentrations were measured. The prevalence of thyroid dysfunction and autoimmunity were compared to the general healthy paediatric population. Results: Autoimmune thyroiditis (AIT) with thyroid hormone disturbances was diagnosed in 16 patients (6.2%). This is significantly higher than the prevalence reported in the general healthy paediatric population. Increased levels of anti-TPO antibodies (= 30 kU/l), without thyroid hormone disturbances, were found in 27 patients (10.5%). Conclusion: The prevalence of AIT in children and adolescents with vitiligo is significantly higher than in the general population. It may be advantageous to screen thyroid function and antibody levels in all paediatric patients with non-segmental vitiligo. To strengthen recommendations on screening, research on the burden for patients and cost-effectiveness is needed.

Keywords:
Adolescents, Autoimmune thyroid disease, Screening, Vitiligo
1.
Lerner AB: Vitiligo. J Invest Dermatol 1959;32:285-310.
2.
Majumder PP, Nordlund JJ, Nath SK: Pattern of familial aggregation of vitiligo. Arch Dermatol 1993;129:994-998.
3.
Janniger CK: Childhood vitiligo. Cutis 1993;51:25-28.
4.
Jaisankar TJ: Vitiligo in children. Int J Dermatol 1992;31:621-623.
5.
Hu Z, Liu JB, Ma SS, Yang S, Zhang XJ: Profile of childhood vitiligo in China: an analysis of 541 patients. Pediatr Dermatol 2006;23:114-116.
6.
Linthorst Homan MW, de Korte J, Grootenhuis MA, Bos JD, Sprangers MA, van der Veen JP: Impact of childhood vitiligo on adult life. Br J Dermatol 2008;159:915-920.
7.
Naughton GK, Eisinger M, Bystryn JC: Antibodies to normal human melanocytes in vitiligo. J Exp Med 1983;158:246-251.
8.
Kemp EH, Waterman EA, Gawkrodger DJ, Watson PF, Weetman AP: Identification of epitopes on tyrosinase which are recognized by autoantibodies from patients with vitiligo. J Invest Dermatol 1999;113:267-271.
9.
van den Boorn JG, Konijnenberg D, Dellemijn TA, van der Veen JP, Bos JD, Melief CJ, Vyth-Dreese FA, Luiten RM: Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J Invest Dermatol 2009;129:2220-2232.
10.
Hann SK, Lee HJ: Segmental vitiligo: clinical findings. J Am Acad Dermatol 1996;35;671-674.
11.
Betterle C, Caretto A, De Zio A, Pedini B, Veller-Fornasa C, Cecchetto A, Accordi F, Peserico A: Incidence and significance of organ-specific autoimmune disorders (clinical, latent or only autoantibodies) in patients with vitiligo. Dermatologica 1985;171:419-423.
12.
Hegedus L, Heidenheim M, Gervil M, Hjalgrim H, Hoier-Madsen M: High frequency of thyroid dysfunction in patients with vitiligo. Acta Derm Venereol 1994;74:120-123.
13.
Daneshpazhooh M, Mostofizadeh GM, Behjati J, Akhyani M, Robati RM: Anti-thyroid peroxidase antibody and vitiligo: a controlled study. BMC Dermatol 2006;10:3.
14.
Boelaert K, Newby PR, Simmonds MJ, Holder RL, Carr-Smith JD, Heward JM, Manji N, Allahabadia A, Armitage M, Chatterjee KV, Lazarus JH, Pearce SH, Vaidya B, Gough SC, Franklyn JA: Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med 2010;123:183-189.
15.
Prindaville B, Rivkees SA: Incidence of vitiligo in children with Graves' disease and Hashimoto's thyroiditis. Int J Pediatr Endocrinol 2011;2011:18.
16.
Laberge G, Mailloux CM, Gowan K, Holland P, Bennett DC, Fain PR, Spritz RA: Early disease onset and increased risk of other autoimmune diseases in familial generalized vitiligo. Pigment Cell Res 2005;18:300-305.
17.
Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA: Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their relatives. Pigment Cell Res 2003;16:208-214.
18.
Spritz RA: Shared genetic relationships underlying generalized vitiligo and autoimmune thyroid disease. Thyroid 2010;20:745-754.
19.
Santaguida MG, Del Duca SC, Virili C, Gargano L, Centanni M: The presence of non-segmental vitiligo modiefies intracellular cytokine subsets with chronic lymphocytic thyroiditis. Int J Immunopathol Pharmacol. 2010;23:1203-1209.
20.
Santaguida MG, Nardo S, Del Duca SC, Lococo E, Virili C, Gargano L, Lenti L, Centanni M: Increased interleukin-4-positive lymphocytes in patients with Hashimoto's thyroiditis and concurrent non-endocrine autoimmune disorders. Clin Exp Immunol 2011;165:148-154.
21.
Sinclair D: Clincal and laboratory aspects of thyroid autoantibodies. Ann Clin Biochem 2006;43:173-183.
22.
Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley-Evans J, Hasan DM, Rodgers H, Tunbridge F, et al: The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham study. Clin Endocrinol 1995;43:55-68.
23.
Biondi B, Cooper DS: The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008;29:76-131.
24.
Villar HC, Saconato H, Valente O, Atallah AN: Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev 2007;18:CD003419.
25.
Hoogendoorn EH, Heijer MD, Dijk AJ, Hermus AR: Subclinical hyperthyroidism: to treat or not to treat? Postgrad Med J 2004;80:394-398.
26.
Gawkrodger DJ, Ormered AD, Shaw L, Mauri-Sole I, Whitton ME, Watts MJ, Anstey AV, Ingham J, Young K: Guideline for the diagnosis and management of vitiligo. Br J Dermatol 2008;159:1051-1076.
27.
Taieb A, Picardo M: Vitiligo. N Engl J Med 2009;360:160-169.
28.
Vrijman C, Kroon MW, Limpens J, Leeflang MMG, Luiten RM, van der Veen JPW, Wolkerstorfer A, Spuls PI: The prevalence of thyroid disease in patients with vitiligo: a systematic review. Br J Dermatol 2012;167:1224-1235.
29.
Fernandes NC, Campos MM: Childhood vitiligo and thyroid disease. An Bras Dermatol 2009;84:200-202.
30.
Kurtev A, Dourmishev AL: Thyroid function and autoimmunity in children and adolescents with vitiligo. J Eur Acad Dermatol Venereol 2004;18:109-111.
31.
Kakourou T, Kanaka-Gantenbein C, Papadopoulou, Kaloumenou E, Chrousos GP: Increased prevalence of chronic autoimmune (Hashimoto's) thyroiditis in children and adolescents with vitiligo. J Am Acad Dermatol 2005;53:220-223.
32.
Cho SB, Kim JH, Cho S, Park JM, Park YK, Oh SH: Vitiligo in children and adolescents: association with thyroid dysfunction. J Eur Acad Dermatol Venereol 2011;25:64-67.
33.
Uncu S, Yayli S, Bahadir S, Okten A, Alpay K: Relevance of autoimmune thyroiditis in children and adolescents with vitiligo. Int J Dermatol 2011;50:175-179.
34.
Pagovich OE, Silverberg JI, Freilich E, Silverberg NB: Thyroid abnormalities in pediatric patients with vitiligo in New York city. Cutis 2008;81:463-466.
35.
Yang Y, Lin X, Fu W, Luo X, Kang K: An approach to the correlation between vitiligo and autoimmune thyroiditis in Chinese children. Clin Exp Dermatol 2010;35:706-710.
36.
Iacovelli P, Sinagra JL, Vidolin AP, Marenda S, Capitanio B, Leone G, Picardo M: Relevance of thyroiditis and of other autoimmune diseases in children with vitiligo. Dermatology 2005;210:6-30.
37.
Rallison ML, Dobyns BM, Meikle AW, Bishop M, Lyon JL, Stevens W: Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults. 1991;91:363-370.
38.
Jaksic J, Dumic M, Filipovic B, Ille J, Cvijetic M, Gjuric G: Thyroid disease in a school population with thyromegaly. Arch Dis Child 1994;70:103-106.
39.
Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE: Serum TSH, T4, and thryroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489-499.
40.
Vanderpump MPJ, Ahlquist JAO, Franklyn JA, Clayton RN: Development of consensus for good practice and audit measures in the management of hypothyroidism and hyperthyroidism. BMJ 1996;313:539-544.
41.
Hefland M, Crapo LM: Screening for thyroid disease. Ann Intern Med 1990;112:840-849.
42.
Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA: Woeber KA, American Association of Clinical Endocrinologists and the American Thyroid Association Taskforce on Hypothyroidism in Adults: Clinical practice guidelines for hypothyroidism in adults. Thyroid 2012;22:1200-1235.
43.
Bettendorf M: Thyroid disorders in children from birth to adolescence. Eur J Nucl Med Mol Imaging 2002;2:439-446.
44.
Moore DC: Natural course of subclinical hypothyroidism in children and adolescence. Arch Pediatr Adolesc Med 1996;150:293-297.
45.
Wasniewska M, Salerno M, Cassio A, Corrias A, Aversa T, Zirilli G, Capalbo D, Bal M, Mussa A, De Luca F: Prospective evaluation of the natural course of idiopathic subclinical hypothyroidism in childhood and adolescence. Eur J Endocrinol 2009;160:417-421.
46.
Cerbone M, Bravaccio C, Capalbo D, Polizzi M, Wasniewska M, Cioffi D, Improda N, Valenzise M, Bruzzese D, De Luca F, Salerno M: Linear growth and intellectual outcome in children with long-term idiopathic subclinical hypothyroidism. Eur J Endocrinol 2011;164:591-597.
47.
Wu T, Flowers JW, Tudiver F, Wilson JL, Punyasavatsut N: Subclinical thyroid disorders and cognitive performance among adolescents in the United States. BMC Pediatrics 2006;6:12.
48.
Bona G, Prodam F, Monzani A: Subclinical hypothyroidism in children: natural history and when to treat. J Clin Pediatr Endocrinol 2012, E-pub ahead of print.
49.
Padberg S, Heller K, Usadel KH, Schumm-Draeger PM: One-year prophylactic treatment of euthyroid Hashimoto's thyroiditis with levothyroxine: is there a benefit? Thyroid 2001;3:249-255.
50.
Schmidt M, Voell M, Rahlff I, Dietlein M, Kobe C, Faust M, Schicha H: Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto's thyroiditis) treated with levothyroxine. Thyroid 2008;7:755-760.
51.
Prummel MF, Wiersinga WM: Thyroid peroxidase in euthyroid subjects. Best Pract Res Clin Endocrinol Metab 2005;19:1-15.
52.
Hutfless S, Matos P, Talor MV, Caturegli P, Rose NR: Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease. J Clin Endocrinol Metab 2011;96:1466-1471.
53.
Rallison ML, Dobyns BM, Keating FR, Rall JE, Tyler FH: Occurrence and natural history of chronic lymphocytic thyroiditis in childhood. J Pediatr 1975;86:675-682.
54.
Kroon MW, Joore IC, Wind BS, Leloup MA, Wolkerstorfer A, Luiten RM, Bos JD, Geskus RB, van der Veen JP: Low yield of routine screening for thyroid dysfunction in asymptomatic vitiligo patients. Br J Dermatol 2012;166:532-538.
55.
Wiersinga WM, Podoba J, Srbecky M, van Vessem M, van Beeren HC, Platvoet-Ter Schiphorst MC: A survey of iodine intake and thyroid volume in Dutch schoolchildren: reference values in an iodinesufficient area and the effect of puberty. Eur J Endocrinol 2001;144:595-603.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.