NDT Advance Access originally published online on December 22, 2007
Nephrology Dialysis Transplantation 2008 23(5):1768; doi:10.1093/ndt/gfm885
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reply
Correspondence and offprint requests to: E-mail: Alex.Woywodt{at}lthtr.nhs.ukSir,
We read with interest the article by Lionaki et al. on thyroid disease and vasculitis [1]. We would like to take issue with their conclusion that ‘the association [of vasculitis] with thyroid disease was not driven by use of anti-thyroid agents and these agents are unlikely to account for many cases in the general population’ [1].
ANCA positivity as well as clinical and/or histological evidence of vasculitis in conjunction with anti-thyroid medication has been described repeatedly, and propylthiouracil (PTU) has been implicated in the majority of cases. A current PubMed query for ‘anti-thyroid’ and ‘vasculitis’ yields as many as 106 papers on this subject. In 2000, Gunton et al. reported ANCA positivity in 26.7% of patients in a small cohort of patients of anti-thyroid drugs [2], and listed 32 cases of vasculitis in association with anti-thyroid drugs from the literature [2]. In a more recent cross-sectional study of ANCA development in 607 patients with thyroid disease, ANCA positivity was observed in 33.3% of PTU-treated patients, 15.9% of carbimazole-treated patients but only 3.8% of thionamide-naïve patients [3]. In another recent study, Slot et al. from the Netherlands detected ANCA in 6% of 207 patients with hyperthyroidism; they also observed a strong association with anti-thyroid drugs (odds ratio 11.8) [4]. Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis induced by PTU has been demonstrated in cats by Waldhauser and Uetrecht, and the same authors reported that PTU is oxidized in the presence of myeloperoxidase (MPO) to form reactive intermediates [5]. The latter observation may offer a clue as to the pathogenesis of vasculitis after thionamide exposure.
In their study, Lionaki et al. relied mainly on telephone interviews to ascertain the presence of thyroid disease and anti-thyroid medication. Medical charts were available in only 52% of patients, and a proxy interview had to be conducted for 29 patients. We very much appreciate the work by Lionaki et al. [1] and believe that their data show an association of vasculitis and thyroid disease. However, we doubt whether their methodology is sufficient to question the apparently well-documented association between anti-thyroid drugs and vasculitis. Clinical experience indicates that patients and relatives often forget or confuse medication. This may be particularly true when the disease or treatment in question occurred years ago. Intriguingly, Slot et al.'s data suggest that ANCA positivity and vasculitis may occur years after treatment with thionamides [4]. Finally, Lionaki and colleagues report use of anti-thyroid drugs in only 2 out of 31 patients (6.45%) who recalled thyroid disease. The expected ratio of thionamide exposure in Lionaki's study population is difficult to gauge, but we think it is rather unlikely that so few patients in their study were truly thionamide naïve.
Conflict of interest statement. None declared.
Consultant Renal Physician, Renal Unit, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK
References
- Lionaki S, Hogan SL, Falk RJ, et al. Association of thyroid disease and its treatment with ANCA small-vessel vasculitis: a case control study. Nephrol Dial Transplant (2007) 22:3508–3515.
[Abstract/Free Full Text] - Gunton JE, Stiel J, Clifton-Bligh P, et al. Prevalence of positive anti-neutrophil cytoplasmic antibody (ANCA) in patients receiving anti-thyroid medication. Eur J Endocrinol (2000) 142:587.[Abstract]
- Harper L, Chin L, Daykin J, et al. Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves’ disease. Clin Endocrinol (Oxf) (2004) 60:671–675.[CrossRef][Medline]
- Slot MC, Links TP, Stegeman CA, et al. Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs: a long-term followup study. Arthritis Rheum (2005) 53:108–1013.[CrossRef][Web of Science][Medline]
- Waldhauser L, Uetrecht J. Oxidation of propylthiouracil to reactive metabolites by activated neutrophils. Implications for agranulocytosis. Drug Metab Dispos (1991) 19:354–359.[Abstract]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||