Abstract: SA-PO272
Immune Checkpoint Inhibitor (ICI) Induced Necrotizing Granulomatous Arteritis, Interstitial Nephritis, and Dermatitis
Session Information
- Trainee Case Reports - VI
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 103 AKI: Mechanisms
Authors
- Mohan, Sneha, All India Institute of Medical Sciences (AIIMS), New Delhi, India
- Garg, Gunjan, University of Michigan, Ann Arbor, Michigan, United States
- Farkash, Evan A., University of Michigan, Ann Arbor, Michigan, United States
- Perlman, Rachel, University of Michigan, Ann Arbor, Michigan, United States
Introduction
With emergence of ICIs as potent agents against melanoma, there has been a rapid surge in use of drugs like ipilimumab, targeted against cytotoxic T lymphocyte associated antigen 4(CTLA-4), and nivolumab, targeted against programmed death 1(PD-1) protein. Immune related adverse events (IRAE), including skin lesions and AKI, have been reported with use of ICIs. Nivolumab has been associated with sarcoidal pattern of granulomatous dermatitis while both drugs have been associated with acute interstitial nephritis (AIN). We present a case of skin and renal complications following concomitant nivolumab and ipilimumab therapy.
Case Description
A 67 yo man diagnosed with melanoma 9mos ago, on 3rd cycle of ipilimumab and nivolumab presented with fever, skin rash and AKI. Serum creatinine (Cr) was 2.65 mg/dL (baseline 0.8 mg/dL). Skin biopsy (Bx) showed granulomatous dermatitis compatible with granuloma annulare. Renal Bx showed necrotizing granulomatous arteritis with interstitial fibrosis and tubular atrophy (Fig). ANA and ANCA were negative. Mycobacterial and fungal causes were excluded. Given the suspicion of ICIs related cutaneous and renal side effects, both drugs were stopped and 80mg daily oral prednisone was initiated for 1mo followed by slow taper. Rash improved rapidly and Cr returned to baseline.
Discussion
These findings describe another pathological manifestation of ICIs. We suspect that synergistic effects of anti-CTLA-4 and anti-PD1 therapy triggered the granulomatous arteritis. With increasing use of ICIs for melanoma and other cancers, it is important to be vigilant of their side effects. Steroid therapy, initiated early, appears to have utility in reversing IRAEs.
Renal Bx showing obliteration of an intralobular artery by granulomatous inflammation with multinucleated giant cells, accompanied by interstitial hemorrhage and AIN. H&E, 200x