Cutaneous Leukocytoclastic Vasculitis Induced by Apixaban and/or Rivaroxaban With Seronegative Anti-Neutrophil Cytoplasmic Antibody (ANCA) Titers: A Case Report and Literature Review.

A 45-year-old man presented with a diffuse petechial rash and a non-blanching palpable purpura, mainly on his lower extremities, some of which had coalesced, blistered, and ulcerated. The patient had a history of hypercoagulability and was chronically on anticoagulant medication. The rash appeared a week after starting apixaban 5 mg twice daily by mouth. Prior to that, he was receiving rivaroxaban. The rash was biopsied, which demonstrated cutaneous leukocytoclastic vasculitis (LCV). Serum anti-neutrophil cytoplasmic antibody (ANCA) titers were negative. Complement levels of C3, C4, and CH50 were normal. Hepatitis C antibodies were negative. HIV antibodies were non-reactive. Titers for Lyme disease and Rocky Mountain spotted fever were nonreactive. It is unusual for a drug to induce cutaneous LCV with negative ANCA titers. Although rare, it usually requires aggressive therapy. Our case resolved after the discontinuation of apixaban and rivaroxaban and the initiation of warfarin for hypercoagulability in conjunction with a short course of steroids. As the use of apixaban and rivaroxaban increases, we may see a consequent increase in cutaneous LCV that is specifically ANCA-negative.

Antitubular Basement Membrane Antibody Disease Associated with Nivolumab Infusion and Concomitant Acute Pyelonephritis Leading to Acute Kidney Injury : a Case Report and Literature Review.

Antitubular basement membrane (anti-TBM) antibody disease is an extremely rare disorder. It may be idiopathic or secondary to exposure of the proximal tubular basement membrane, triggered by tubular injury due to acute pyelonephritis, acute allergic interstitial nephritis, or kidney allograft rejection. The histopathology of anti-TBM antibody disease is characterized by strong linear deposits of IgG with complement C3 along the proximal tubular cell basement membranes. The staining is restricted to proximal tubules. Currently, a kidney biopsy with these pathognomonic findings is the only diagnostic method. Serological testing and titers for anti-TBM antibodies are not clinically standardized. Our patient had pyelonephritis and possibly acute allergic interstitial nephritis as a result of nivolumab infusion. The kidney biopsy demonstrated dense interstitial infiltrates of neutrophil-rich interstitial inflammation, neutrophilic casts, and neutrophilic tubulitis consistent with acute pyelonephritis, as well as areas of mixed inflammation with lymphocytic tubulitis suggesting concurrent acute interstitial nephritis. The presence of linear IgG staining along proximal but not distal tubular basement membranes was diagnostic of anti-TBM antibody disease, favored to be due to both triggers. The patient was treated with discontinuation of nivolumab, intravenous antibiotics, and corticosteroids and was supported with hemodialysis. After 6 weeks, the patient's kidney function recovered enough to discontinue hemodialysis and had significant renal improvement.