A Case Report of Multiple Myeloma Associated With Myeloperoxidase and Proteinase-3 Antibodies Posing a Diagnostic Dilemma

Abstract

Multiple myeloma (MM) is a clonal proliferation of antibody-producing plasma cells that can precipitate renal injury through multiple mechanisms. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an inflammatory condition that can result in renal failure through mononuclear cell infiltration and consequent destruction of glomeruli. Several case reports have identified clinical situations where differentiating these entities has been challenging. Renal biopsy is an invaluable tool in differentiating between MM and AAV when clinical uncertainty exists. We report the case of an 85-year-old man who presented with a rapid decline in renal function and serologies positive for both MM and AAV. Renal biopsy findings confirmed the diagnosis of myeloma kidney and excluded vasculitis. This case highlights an unusual clinical scenario in which both proteinase-3 (PR-3) and myeloperoxidase (MPO) antibodies are positive. While these antibodies are both individually associated with ANCA vasculitis, they are seldom simultaneously positive. Our case would suggest that positive PR-3 and MPO antibodies should raise concern for an alternative diagnosis. Indeed, ANCA, PR-3, and MPO antibodies can all be positive in patients with monoclonal gammopathy in the absence of vasculitis. Our case underscores the value of renal biopsy in the setting of MM.

A Case of Myeloma Kidney with Perinuclear Anti-Neutrophil Cytoplasmic Antibody and Anti-Myeloperoxidase Positivity: The Importance of Determining the True Cause of Renal Impairment

“…We are aware of only one previous case which reports the presence of AKI resulting from MM with a concurrent positive ANCA ELISA. This report, however, did not identify a p-ANCA pattern on IIF and the patient demonstrated no features of AAV [12]. The differential diagnosis for AKI in our case initially included p-ANCA/anti-MPO positive AAV with renal involvement, MM and one of the many associated causes of renal impairment (as mentioned above), and tubulointerstitial nephritis resulting from recent non-steroidal anti-inflammatory medication use.…”

“…Several previous cases have been reported where AAV with renal involvement and a concurrent diagnosis of MM was identified [8][9][10][11]. To our knowledge, only one previous case of MM with renal involvement with positive anti-MPO and anti-PR3 serology has been identified [12], though that case did not demonstrate a positive ANCA titre.…”

The performance of the chemiluminescent immunoassay for measuring serum myeloperoxidase and proteinase 3 antibodies

“…Additionally, the clinical characteristics of non‐vasculitis patients with serologies positive MPO and PR3 antibodies were not significantly different from those without MPO and PR3 antibodies 25 . The serologies positive for MPO‐ANCA and/or PR3‐ANCA alone frequently failed to diagnosis as systemic vasculitis, might even cause diagnostic dilemma 26‐29 . Furthermore, CIA was highly correlated with ELISA.…”

Coexistence of double seropositivity for MPO antibody and anti-GBM antibody in ANCA-associated vasculitis concurrent with multiple myeloma: A case report

“…Despite the observation of ANCA-associated crescentic GN, none exhibited evidence of kidney involvement associated with MM. [ 19 ] Cheta and Binder [ 20 ] reported on 4 patients who exhibited monoclonal kappa/lambda immunoglobulin G positivity, suggesting a potential case of MM. Kidney histology analysis revealed pauci-immune glomerulonephritis in these patients.…”