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

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.

Concurrent presentation of IgG4-related tubulointerstitial nephritis and ANCA MPO crescentic glomerulonephritis

“…Concurrent subacute presentation of IgG4-related kidney disease with ANCA-associated MPO crescentic glomerulonephritis is uncommon, with cases reporting these simultaneously presenting diagnoses only surfacing over recent years ( Table 1 ) [ 9 , 10 , 11 , 12 , 13 , 14 ]. In 2017, Su et al [ 10 ] reported the first case of concurrent IgG4-related tubulointerstitial nephritis with ANCA-associated MPO crescentic glomerulonephritis in a 42-year-old Chinese man.…”

Acute tubulointerstitial nephritis associated with antineutrophil cytoplasmic antibody following cimetidine treatment: a case report

“…These cases have mostly been related to drugs or systemic disease [ 6 – 8 ]. Although certain drugs, such as propylthiouracil, may play a role in the pathogenesis of AAV [ 9 , 10 ], the relationship between most drugs and ATIN associated with ANCA is tentative and the pathological mechanisms are unknown. Most cases of drug-induced AAV improve after withdrawal of the suspected drug, but in severe cases, steroids may be required [ 11 ].…”

An unsuspected histopathological finding —concomitant IgA nephropathy in a patient with ANCA-associated vasculitis: a case report and literature review

“…Drugs may also trigger AAV and IgAN (2,36). Galante et al described the coexistence of AAV and IgAN triggered by propylthiouracil (19). According to the authors' hypothesis, propylthiouracil-induced AAV resulted in an infiltration of IgG4rich cells in the tubulointerstitial tissue as well as epiphenomena of anti-GBM antibody production.…”