NDT Advance Access originally published online on July 5, 2005
Nephrology Dialysis Transplantation 2005 20(9):2014-2015; doi:10.1093/ndt/gfh959
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Development of Graves' disease during cyclosporin treatment for severe Henoch–Schönlein nephritis
Sir,A 10-year-old girl presented with palpable purpura and abdominal pain. Routine laboratory tests were normal, but urinalysis revealed microscopic haematuria [5–10 red blood cells/highpower field (RBCs/HPF)]. A skin biopsy demonstrated leukocytoclastic vasculitis. A diagnosis of Henoch–Schönlein purpura (HSP) was made, and oral prednisolone was started, with rapid improvement. One month later, she was admitted to our hospital for macroscopic haematuria and heavy proteinuria (2.3 g/day). She had no significant past medical history but her mother had Graves’ disease. Her blood pressure was 100/60 mmHg and the physical examination was unremarkable. Laboratory findings showed a serum albumin of 4.0 g/dl, and C3 and serum IgA levels were normal. A renal biopsy revealed diffuse mesangial proliferative glomerulonephritis with 12% crescents and deposits of IgA, C3 and IgG. She was commenced on prednisolone (48 mg once qod) and cyclosporin (75 mg twice daily). Cyclosporin was given for 10 months with the desired level of 100–200 ng/ml, and prednisolone was tapered during cyclosporin therapy. Her proteinuria resolved (0.05 g/day) within 2 months of cyclosporin therapy, but microscopic haematuria persisted at 2 year follow-up.
At 6 months after onset of the HSP, she developed a goitre and mild exophthalmos. A clinical diagnosis of Graves’ disease was given and she was immediately started on propranolol at a dose of 20 mg twice daily (1 mg/kg/day). Subsequently her thyroid-stimulating hormone level was found to be 0.04 µIU/ml (normal 0.34–3.5 µIU/ml), free thyroxine 2.6 ng/dl (normal 0.73–1.95 ng/dl) and triiodothyronine 270.27 ng/dl (normal 80–220 ng/dl). Thyroglobulin and microsomal antibodies were raised at 427.9 IU/ml (negative: <60 IU/ml) and 1086.3 IU/ml (negative: <60 IU/ml), respectively. She was commenced on propylthiouracil at a dose of 100 mg twice daily (5 mg/kg/day) and thyroid function became normal over 7 months.
There have been some reports that HSP is associated with autoimmune thyroiditis or transient hyperthyroidism [1]. However, the association between HSP and Graves’ disease has not been reported previously in children. Graves’ disease is a multifactorial disease which is caused by genetic susceptibility and environmental triggers. It has been suggested that HLA-DR3 and cytotoxic T-lymphocyte antigen 4 increase the risk for Graves’ disease in both the sporadic and familial forms [2]. However, additional genes which contribute to the aggregation of Graves’ disease within families have not been identified yet.
Renal involvement in thyroid diseases is rare, but immune complex glomerulonephritis such as membranous nephropathy has been reported in association with Graves’ disease [3]. Activation of the complement cascade can take place in 
40% of patients with Graves’ disease, and IgG, IgA and C3 immune complex depositions in the extrathyroidal tissues are possible as the manifestations of Graves’ disease [4]. In the present case, immunofluorescence demonstrated mesangial depositions of IgG, IgA and C3 consistent with an immune complex glomerulonephritis, suggesting common immunological mechanisms may be implicated between HSP nephritis and Graves’ disease.
Both prednisolone and cyclosporin are used as the treatment of Graves’ ophthalmopathy by inhibiting T-cell function. In contrast, these drugs can cause the development of Graves’ disease in a transplant recipient by abnormal modulation of the immune system [5]. Although there have been no reports describing the development of Graves’ disease during immunosuppressive treatment in patients with other autoimmune diseases, a familial tendency to Graves’ disease in our patient may affect the subsequent expression of Graves’ disease.
In conclusion, the sequential occurrence of HSP and Graves’ disease in our patient suggests a possible immunological link between two diseases, and a familial predisposition and immunosuppression by cyclosporin may have been triggering factors in the development of Graves’ disease. Clinicians should pay more attention to the use of immunosuppressants in susceptible patients with Graves’ disease.
Conflict of interest statement. None declared.
1 Department of Paediatrics2 Department of Pathology The Institute of Kidney Disease Yonsei University College of Medicine Seoul Korea Email: jsyonse{at}yumc.yonsei.ac.kr
References
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[Abstract/Free Full Text] - Becker BA, Fenves AZ, Breslau NA. Membranous glomerulonephritis associated with Graves’ disease. Am J Kidney Dis 1999; 33: 369–373[Medline]
- Antonelli A, Palla R, Casarosa L, Fallahi P, Baschieri L. IgG, IgA and C3 deposits in the extra-thyroidal manifestations of autoimmune Graves’ disease: their in vitro solubilization by intravenous immunoglobulin. Clin Exp Rheumatol 1996; 14 [Suppl]: S31–S35
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