**3. Conclusion**

Anti-thyroid drugs are a common and widespread treatment for Graves' disease and the other forms of hyperthyroidism. It is a safe and efficacy treatment, and it is the treatment of choice in patients refusing radioactive iodine as definitive treatment or during pregnancy and breast-feeding.

However, this treatment has been associated with several side effects and among them, vasculitis, with a wide-range of severity and clinical presentations.

Vasculitis are more commonly reported in PTU-treated patients, with a long duration of treatment, and with positivity for ANCA autoantibodies.

Thionamides-related vasculitis usually recover after discontinuation of therapy, although rare cases of fatalities have been also reported.

### **4. References**

388 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

Clinical and serological data from idiophatic and anti-thyroid drug-induced ANCA positive vasculitis were compared in a 11-year retrospective study. In this cohort (Bonaci-Nikolic et al., 2005), both groups of patients showed a similar high frequency of arthralgia and myalgia, whereas skin involvement, especially represented by urticaria and urticaria-like vasculitis, was more common in patients treated with anti-thyroid drugs, with histological evidence of leucocytoclastic vasculitis. Furthermore, patients with idiophatic systemic vasculitis showed more frequently fever, weight loss, renal and respiratory manifestations, pulmonary-renal syndrome, ear/nose and nervous system

As for serological profile, patients with drug-induced vasculitis, showed positivity for ANAs and antihistone antibodies, and had high levels of IgM anticardiolipin antibodies

Hence, drug-induced vasculitis seem to have a milder course and a better long-term prognosis, since the withdrawal of anti-thyroid drugs usually leads to the resolution of

Thus, the prognosis of anti-thyroid-induced ANCA-associated vasculitis is usually good as long as the drug is discontinued. However, early recognition of clinical symptoms is very important because of the potential risk of life-threatening injury, such as pulmonary-renal syndrome, with pulmonary hemorrhage and renal failure. In these patients, additional treatment with steroids and/or immunosuppressive agents should be recommended. In a retrospective study of fifteen patients with PTU-induced ANCA-associated vasculitis, Gao et al. investigated treatment protocols and outcomes of patients, suggesting that immunosuppressive therapy should be administrated only in those patients with vital organ involvement, such as lung and kidney vasculitis, in order to prevent progression to

Interestingly, unlike what is normally found in patients with primary ANCA-associated vasculitis (Hogan et al., 2005), none of the patients with drug-induced vasculitis experienced relapse after the discontinuation of immunosuppressive therapy at follow-up (Gao et

Moreover, immunosuppressive therapy may be administered only for a shorter period of time, usually 6-12 months, than in primary ANCA-associated vasculitis, without any further

Anti-thyroid drugs are a common and widespread treatment for Graves' disease and the other forms of hyperthyroidism. It is a safe and efficacy treatment, and it is the treatment of choice in patients refusing radioactive iodine as definitive treatment or during pregnancy

However, this treatment has been associated with several side effects and among them,

Vasculitis are more commonly reported in PTU-treated patients, with a long duration of

Thionamides-related vasculitis usually recover after discontinuation of therapy, although

vasculitis, with a wide-range of severity and clinical presentations.

treatment, and with positivity for ANCA autoantibodies.

rare cases of fatalities have been also reported.

cryoglobulinemia and low C4 values (Wiik et al., 2005; Bonaci-Nikolic et al., 2005).

clinical manifestations in the vast majority of cases.

manifestations.

irreversible disease.

maintenance therapy (Gao et al., 2008).

al.,2008).

**3. Conclusion** 

and breast-feeding.

AACE Thyroid Guidelines. (2002*). Endocrine Practice*, Vol. 8, No. 6, pp. 457-69.


thyroid medication. *European Journal of Endocrinology*, Vol. 142, No. 6, pp. 587-590, ISSN 0804-4643

Thionamides-Related Vasculitis

972X

1011-1013

pp. 80-84

100, No. 11, pp. 772-775

in Autoimmune Thyroid Disorders: Review of Current Literature and Case Reports 391

Sato, H.; Hattori, M.; Fujieda, M.; Sugihara, S.; Inomata, H.; Hoshi, M. & Miyamoto, S.

Savige, J.; Davies, D.; Falk, R.J.; Jennette, J.C. & Wiik, A. (2000). Antineutrophil cytoplasmic

Sève, P.; Stankovic, K.; Michalet, V.; Vial, T.; Scoazec, J.Y. & Broussolle, C. (2005).

Sera, N.; Ashizawa, K.; Ando, T.; Abe, Y.; Ide, A.; Usa, T.; Tominaga, T.; Ejima, E.;

Stankus, S.J. & Johnson, N.T. (1992). Propylthiouracil-induced hypersensitivity vasculitis presenting as respiratory failure. *Chest*, Vol. 102, No. 5, pp. 1595-1596 Streetman, D.D. & Khanderia, U. (2003). Diagnosis and treatment of Graves disease. *Annals* 

Ten Holder, S.M.; Joy, M.S. & Falk, R.J. (2002). Cutaneous and systemic manifestation of drug-induced vasculitis. *Annals of Pharmacotherapy*, Vol. 36, No. 1, pp. 130-147 Tripodi, P.F.; Ruggeri, R.M.; Campennì, A.; Cucinotta, M.; Mirto, A.; Lo Gullo, R.; Baldari, S.;

Tsai, M.H.; Chang, Y.L.; Wu, V.C.; Chang, C.C. & Huang, T.S. (2001). Methimazole-induced

Van der Wonde, F.J.; Rasmussen, N.; Lobatto, S.; Wiik, A.; Permin, H.; van Es, L.A.; van der

Vanek, C. & Samuels, M.H. (2005). Central nervous system vasculitis caused by

Wada, N.; Mukai, M.; Kohno, M.; Notoya, A.; Ito, T. & Yoshioka, N. (2002). Prevalence of

Wiik, A. (2005). Clinical and laboratory characteristics of drug-induced vasculitic

syndromes. *Arthritis Research & Therapy*, Vol. 7, No. 5, pp. 191-192

Wegener's granulomatosis. *Lancet*, Vol. 1, No. 8426, pp. 425-429

*Endocrine Journal*, Vol. 49, No. 3, pp.329-334

stomach. *Journal of Internal Medicine*, Vol. 258, No. 2, pp. 191-195

*Kidney International*, Vol. 57, No. 3, pp. 846-862

Graves' disease. *Thyroid*, Vol. 10, No. 7, pp. 595-599

*of Pharmacotherapy*, Vol. 37, No.7-8, pp. 1100-1109

(2000). High prevalence of antineutrophil cytoplasmic antibody positivity in childhood onset Graves' disease treated with propylthiouracil. *Journal of Clinical Endocrinology and Metabolism*, Vol. 85, No. 11, pp. 4270-4273, ISSN 0021-

antibodies and associated disease: a review of the clinical and laboratory features.

Carbimazole induced eosinophilic granulomatous vasculitis localized to the

Yokoyama, N. & Eguchi, K. (2000). Treatment with propylthiouracil is associated with appearance of antineutrophil cytoplasmic antibodies in some patients with

Trimarchi, F.; Cucinotta, D. & Russo, G.T. (2008). Central nervous system after starting methimazole in a woman with Graves' disease. *Thyroid,* Vol. 18, No. 9, pp.

pulmonary haemorrhage associated with antimyeloperoxidase-antineutrophil cytoplasmic antibody: a case report. *Journal of the Formosan Medical Association*, Vol.

Giessen, M.; van der Hem, G.K. & The, T.H. (1985). Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in

propylthiouracil therapy: a case report and literature review. *Thyroid*, Vol. 15, No. 1,

serum anti-myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) in patients with Graves' disease treated with propylthiouracil and thiamazole.


Harper, L.; Chin, L.; Daykin, J.; Allahabadia, A.; Heward, J.; Gough, S.C.; Savage, C.O. &

Hogan, S.L.; Falk, R.J.; Chin, H.; Cai, J.; Jennette, C.E.; Jennette, J.C. & Nachman, P.H. (2005).

Jennette, J.C. & Falk, R.J. (1997). Small vessel vasculitis. *New England Journal of Medicine*,

Jennette, J.C. & Falk, R.J. (2007). The role of pathology in the diagnosis of systemic

Kallenberg, C.G. & Heeringa, P. (1998). Pathogenesis of vasculitis. *Lupus*, Vol. 7, No. 4, pp.

Kawaki, Y.; Nukaga, H.; Hoshito, M.; Iwata, M. & Otsuka, F. (1995). ANCA associated

Laurberg, P. (2006). Remission of Graves' disease during anti-thyroid drug therapy. Time to

Laurberg, P.; Andersen, S. & Karmisholt, J. (2006). Antithyroid drug therapy of Graves'

Lee, E.; Hirouchi M.; Hosokawa, M.; Sayo, H.; Kohno, M. & Kariya, K. (1988). Inactivation of

Leger, J.M.; Dancea, S.; Brunet, P. & Hauw, JJ. (1984). Polyneuropathy during treatment with

Morita, S.; Ueda, Y. & Eguchi, K. (2000). Anti-thyroid drug-induced ANCA-associated

Nakamura, H.; Noh, J.Y.; Itoh, K.; Fukata, S.; Miyauchi, A. & Hamada, N. (2007).

Ozduman Cin, M.; Morris, Y.; Tiryaki Aydintug, O.; Kamel, N. & Gullu, S. (2007).

carbimazole. *Revue Neurologique (Paris)*, Vol. 140, No. 11, 652-656

*Experimental Dermatology*, Vol. 20, No. 4, pp. 345-347

*Endocrinology & Metabolism*, Vol.1, pp. 91-102

ISSN 0804-4643

9, pp. 621-631

S52-56

280-284

*Endocrinology*, Vol. 60, No. 6, pp. 671-675

Vol.337, No. 21, pp. 1512-1523

783-786, ISSN 0804-4643

No. 11, pp.2151-2153

4, pp. 467-470

No. 6, pp. 2157-2162

*Practice,* Vol. 63, No. 2, pp. 299-302

thyroid medication. *European Journal of Endocrinology*, Vol. 142, No. 6, pp. 587-590,

Franklyn, J.A. (2004). Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves' disease. *Clinical* 

Predictors of releapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. *Annals of Internal Medicine*, Vol. 143, No.

vasculitis. *Clinical and Experimental Rheumatology,* Vol. 25, No. 1 supp 44, pp.

vasculitis and lupus like syndrome caused by methimazole. *Clinical and* 

reconsider the mechanism? *European Journal of Endocrinology*, Vol. 155, No. 6, pp.

hyperthyroidism: realistic goals and focus on evidence. *Expert Review of* 

peroxidase of rat bone marrow by repeated administration of propylthiouracil is accompanied by a change in the heme structure. *Biochemical Pharmacology*, Vol. 37,

vasculitis: a case report and review of the literature*. Endocrine Journal*, Vol. 47, No.

Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease*. Journal of Clinical Endocrinology and Metabolism*, Vol. 92,

Prevalence and clinical significance of antineutrophil cytoplasmic antibody in Graves' patients treated with propylthiouracil. *International Journal of Clinical* 


Yazisiz, V.; Ongut, G.; Terzioglu, E. & Karayalcin, U. (2010). Clinical importance of antineutrophil cytoplasmic antibody positivity during propylthiouracil treatment. *International Journal of Clinical Practice*, Vol. 41, No. 1, pp. 19-24

**Part 4** 

**Pathogenesis & Underlying Mechanisms** 
