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Case Reports
. 2020 Jul 23;21(1):295.
doi: 10.1186/s12882-020-01964-w.

An unusual presentation of propylthiouracil-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate: a case report

J R Galante  1 , C P Daruwalla  2 , I S D Roberts  3 , R Haynes  2   4 , B C Storey  2 , M J Bottomley  2
Affiliations
Case Reports

An unusual presentation of propylthiouracil-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate: a case report

J R Galante et al. BMC Nephrol. .

Abstract

Background: A number of disease processes can culminate in rapidly progressive glomerulonephritis, including pauci-immune focal segmental necrotising glomerulonephritis, usually seen with positive serum antineutrophil cytoplasmic antibodies (ANCA). Propylthiouracil (PTU) has been associated with drug-induced ANCA-associated vasculitis (AAV), with antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) present individually and together having been recognised. 'Double-positive' vasculitis with ANCA and anti-glomerular basement membrane (GBM) antibodies has also been reported in association with PTU treatment. We present a case of PTU-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate.

Case presentation: A 51-year-old man presented 2 weeks after re-commencing propylthiouracil (PTU) treatment for Graves' disease, with a severe acute kidney injury and haemato-proteinuria. He demonstrated positive titres for autoantibodies to PR3 (76.9 IU/mL), MPO (28.8 IU/mL) and GBM (94 IU/mL). Renal biopsy demonstrated numerous glomerular crescents, widespread IgG4-positive lymphoplasmacytic infiltrate and mesangial positivity for IgA. PTU was stopped and he was treated with steroids, plasma exchange and cyclophosphamide with sustained improvement in his renal function.

Conclusions: This case of drug-induced AAV presented a unique and intriguing collection of serological and histological features. We propose that the PTU-induced AAV resulted in epiphenomena of anti-GBM antibody production and an IgG4-cell-rich tubulointerstitial infiltrate. It is uncertain whether the mesangial IgA deposition preceded or resulted from the AAV.

Keywords: Anti-GBM disease; Case report; IgA nephropathy; IgG4-related disease; NCA-associated vasculitis; Propylthiouracil.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Histology from renal biopsy at 40x magnification (a-e). Segmental necrosis with rupture of glomerular tuft and Bowman’s capsule (a; Jones silver-H&E stain). Large cellular crescent (b; Jones silver-H&E stain). Plasma cell rich tubulointerstitial infiltrate (c; H&E stain). Tubulointerstitial infiltrate rich in IgG4-positive cells (d; IgG4 immunohistochemical staining, IgG4-positive cells stained brown). Predominantly mesangial distribution of IgA (e; Immunoperoxidase staining for IgA). Electron microscopy at 6000x magnification showing paramesangial electron dense deposits (f) and subendothelial deposits associated with endocapillary hypercellularity (g) typical of IgA nephropathy
Fig. 2
Fig. 2
Timeline of admission and subsequent treatment overlaid on serum creatinine plot
See this image and copyright information in PMC

References

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