|Year : 2007 | Volume
| Issue : 2 | Page : 73-75
Propylthiouracil-associated antineutrophil cytoplasmic antibody positive crescentic glomerulonephritis
R Bonu, V Siddini, K Babu, S Ballal
Manipal Institute of Nephrology and Urology, Manipal Hospital, Bangalore, Karnataka, India
Manipal Institute of Nephrology and Urology, Manipal Hospital, # 98, Rustom Bagh, Airport Road, Bangalore - 560 017, Karnataka
Source of Support: None, Conflict of Interest: None
The vasculitic syndromes of Wegeners granulomatosis, microscopic polyangitis, Churg-Strauss syndrome and renal limited variants are associated with antineutrophil cytoplasmic antibodies (ANCA). Positive ANCA are also seen in many viral infections, inflammatory bowel diseases and drugs. Drug-induced ANCA-associated renal disease is reported less frequently than drug-induced lupus nephritis. ANCA-positive crescentic glomerulonephritis due to propylthiouracil has been reported in children and adults especially in Japanese population. The renal outcome is better in propylthiouracil-associated ANCA-positive crescentic GN as compared with nondrug-induced crescentic GN. Propylthiouracil-associated ANCA-positive crescentic GN may or may not require steroid and cytotoxic therapy depending on the severity of renal failure. We report a case of propylthiouracil-associated ANCA-positive crescentic GN with severe renal failure; the renal function improved after steroid and cytotoxic therapy.
Keywords: Antineutrophil cytoplasmic antibodies, crescentic glomerulonephritis, myeloperoxidase, propylthiouracil, proteinase 3
|How to cite this article:|
Bonu R, Siddini V, Babu K, Ballal S. Propylthiouracil-associated antineutrophil cytoplasmic antibody positive crescentic glomerulonephritis. Indian J Nephrol 2007;17:73-5
|How to cite this URL:|
Bonu R, Siddini V, Babu K, Ballal S. Propylthiouracil-associated antineutrophil cytoplasmic antibody positive crescentic glomerulonephritis. Indian J Nephrol [serial online] 2007 [cited 2020 Feb 25];17:73-5. Available from: http://www.indianjnephrol.org/text.asp?2007/17/2/73/37026
| Introduction|| |
Pauci-immune crescentic glomerulonephritis (CSGN) is usually associated with antineutrophil cytoplasmic antibodies (ANCA). ANCA-associated CSGN is observed in Wegeners granulomatosis (WG) and microscopic polyangiitis (MPA).  C-ANCA is often observed in WG, whereas P-ANCA is often positive in MPA. Drug-induced CSGN with C-ANCA or P-ANCA has been reported with D-pencillamine, propylthiouracil (PTU) and hydraliazine. Rarely, diseases such as inflammatory bowel disease, rheumatoid arthritis, viral infections are also known to cause ANCA-positive CSGN.
We report an unusual case of P-ANCA-positive CSGN due to PTU.
| Case Report|| |
In June 2003, a 32-year-old female was diagnosed to have thyrotoxicosis and was started on PTU. Her thyroid functions became normal after 6 months of treatment, and she was continued on PTU till November 2004. In the first week of November, she presented with low-grade fever and malaise; a week later, she had nausea and vomiting. She discontinued PTU and her laboratory parameters revealed the following: Hb% - 10 gm/dl, total WBC count - 7000/mm 3 serum creatinine - 5.9 mg/dl, and BUN - 60 mg/dl; urine examination revealed 3 + protein and plenty of red blood cells/hpf. The ultrasonography of her abdomen revealed normal size kidneys and T3, T4, and TSH were normal.
Her clinical examination revealed anemia, pedal edema and proptosis, and the subsequent laboratory parameters revealed positive P-ANCA, normal serum complement C3, ANA and C-ANCA were negative. She received a dose of intravenous methyl prednisolone on the day of admission and was given dialysis for 2 days after which she underwent a renal biopsy. The renal biopsy revealed circumferential cellular crescents in 8 out of the 10 glomeruli, and there were no immune deposits on immunoflorescense [Figure - 1],[Figure - 2]. She totally received 4 gm of intravenous methyl prednisolone and was dialyzed for another 3 days. She was given one dose of 500 mg IV cyclophosphamide and subsequently started on oral cyclophosphamide 100 mg/day and continued on prednisolone 40 mg/day. After 4 weeks, her serum creatinine level decreased to 2.0 mg/dl; therefore, the dose of cyclophosphamide and prednisolone has been reduced to 75 mg/day and 20 mg/day, respectively. After another 4 weeks, the serum creatinine level decreased to 1.7 mg/dl. Immunosuppression was further tapered and discontinued later.
| Discussion|| |
Circulating ANCA is now regarded as a serological marker for pauci-immune necrotizing CSGN. The important vasculitic conditions that are commonly associated with ANCA are Wegeners granulomatosis, microscopic polyangitis and Churg-Strauss syndrome. ANCA can be positive in many other conditions, particularly infections such as HIV, parvovirus B 19, Hepatitis B and drugs - commonly D-pencillamine, PTU, hydralazine and rifampicin. 
ANCA has been reported in Graves' disease because of the autoantibodies produced against the thyroid microsomal antibodies, and these antibodies mainly consist of thyroperoxidase that cross reacts with MPO.  PTU has been known to induce ANCA-positive vasculitis. It has been reported in adult patients as well as in children.  The pathogenesis of PTU-associated vasculitis is not clearly understood. PTU has been observed to accumulate in the neutrophils and bind to MPO, resulting in a change in the MPO structure. This alteration in the structure of MPO would result in inducing antineutrophil antibodies. , The prevalence of MPO-ANCA in PTU-induced vasculitis is not due to a cross-reactivity between MPO and thyroperoxidase because there is no correlation between MPO-ANCA titers and thyroperoxidase. 
PTU is an antithyroid drug that belongs to the thionamide group, and the common adverse effects are leucopenia agranulocytosis and the renal diseases are very rare. Most of the PTU-associated renal diseases have been reported in the Japanese population. Mikiya et al.  reported P-ANCA-associated pauci-immune CSGN patients with Graves' disease treated with PTU. PTU-associated renal disease is often found in females, whereas nondrug-induced CSGN is often observed in the male population. The possible explanation could be that thyrotoxicosis is more commonly observed in females than males. Most of the PTU-associated ANCA-positive vasculitis occurs in patients who were on PTU for a long time than those were on PTU for a shorter period of time.
PTU-associated renal disease often improves after discontinuing the drug, and most of the patients did not have relapse of Graves' disease even after the discontinuation of PTU. Another interesting observation is that the renal failure is usually less severe in PTU-associated ANCA-positive disease than those with nondrug-induced ANCA-positive disease.  However, severe renal failure has been reported to be associated with PTU. The discontinuation of the drug often results in improvement of the renal disease in PTU-associated renal disease, particulary in those patients with mild renal failure. Patients with severe renal failure may require steroid therapy with or without cyclophosphamide.
In summary, we report a young lady with CSGN who had been on PTU for Graves' disease. Her clinical presentation showed flu-like illness, which is typical of PTU-associated vasculitis CSGN; renal biopsy with positive P-ANCA and negative C-ANCA favor the diagnosis of PTU-associated renal disease. Her renal functions improved and remained stable with a short course of steroid and cyclophosphamide, which again would be in favor of PTU-associated renal disease rather than nondrug-induced renal diseases that usually require therapy for a longer period of time.
| Conclusion|| |
PTU- induced ANCA-positive renal disease is a rare form of disease than drug-induced lupus. In general, PTU-associated renal disease is often associated with P-ANCA. Prolonged therapy is an important risk factor for developing the disease. The clinical disease is often less severe than the nondrug-induced necrotizing GN. The discontinuation of the PTU alone results in the improvement of renal functions, particulary in those patients with mild renal failure. Patients with severe renal failure may require steroid with or without cyclophosphamide. The thyroid disease may not relapse after the discontinuation of PTU; however, a few patients would require either carbimazole or radioactive iodine if the disease relapses.
| References|| |
|1.||Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitides: Proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92. [PUBMED] |
|2.||Kitahara T, Hiromura K, Maezawa A, Ono K, Narahara N, Yano S, et al. Case of PTU-induced vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA): Review of literature. Clin Nephrol 1997;47:336-40. |
|3.||D'Cruz D, Chesser AM, Lightowler C, Comer M, Hurst MJ, Baker LR, et al. ANCA-positive CSGN associated with antithyroid drug treatment. Br J Rheumatol 1995;34:1090-1. [PUBMED] [FULLTEXT]|
|4.||Gunton JE, Stiel J, Caterson RJ, McElduff A. Clinical case seminar: Anti-thyroid drugs and antineutrophil cytoplasmic antibody positive vasculitis. A case report and review of the literature. J Clin Endocrinol Metab 1999;84:13-6. |
|5.||Fujieda M, Nagata M, Ito K, Yamaguchi Y. Anti-myeloperoxidase (MPO) antibodies associated CSGN with hyperthyroidism: A case report. Acta Paediatr Jpn 1993;97:2155-60. |
|6.||Tanemoto M, Miyakawa H, Hanai J, Yago M, Kitaoka M, Uchida S. Myeloperoxidase ANCA-positive CSGN complicating the course of Graves' disease: Report of three adult cases. Am J Kidney Dis 1995;26:774-80. [PUBMED] |
|7.||Dolman KM, Gans RO, Vervaat TJ, Zevenbergen G, Maingay D, Nikkels RE, et al. Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy. Lancet 1993;342:651-2. [PUBMED] |
|8.||Kawasaki Y, Suzuki J, Sike T, Isome M, Nozawa R, Suzuki S, et al. A pediatric case of myeloperoxidase-ANCA-related crescentic glomerulonephritis associated with propylthiouracil treatment for Graves' disease. Nippon Jinzo Gakkai Shi 1998;40:612-7. [PUBMED] |
|9.||Harper L, Cockwell P. Case of propylthiouracil-induced ANCA associated small vessel vasculitis. Nephrol Dial Transplant 1998;13:155-8. |
[Figure - 1], [Figure - 2]