Table 2. Vasculitis with positive ANCA induced by TNF- inhibitors.
ANCA: Anti-Neutrophilic Cytoplasmic Antibody; TNF-i: Tumor Necrosis Factor inhibitor; CD: Crohn’s Disease; GN: Glomerulonephritis; Hb: Hemoglobin; CRP: C-Reactive Protein; RBC: Red Blood Cell; PR-3: Proteinase-3; IV: Intravenous; MP: Methylprednisolone; RA: Rheumatoid Arthritis; UPC: Urine Protein Creatinine; ANA: Anti-Nuclear Antibody; dsDNA: double stranded Deoxyribonucleic Acid; anti-GBM: anti-Glomerular Basement Membrane; HCQ: Hydroxychloroquine; MTX: Methotrexate; HD: Hemodialysis; ESR: Erythrocyte Sedimentation Rate; RF: Rheumatoid factor; MPO: Myeloperoxidase; SS: Sjogren’s Syndrome; CrCl: Creatinine Clearance; PO: Per Oral; TMP: Trimethoprim; AZA: Azathioprine; RTX: Rituximab; Cr: Creatinine.
| Patient No. | Age/Sex | TNF-i | Indication for TNF-i | Time of onset after starting TNF-i (months) | Clinical presentation | Labs | ANCA type | Other serologies | Pathology | Previous/Concomitant drugs | Treatment | Outcome |
| 54/M | Adalimumab | CD | 30 | Fever, asthenia, lower extremity edema, inflammatory arthritis, polyneuropathy and optic neuritis, anemia, GN | Hb: 9 gm/dl, CRP: 7.9 mg/dl, Urine studies: 1.2 gm protein/day >50 RBCs/hpf Granular casts | C-ANCA PR3 | - | Pauci-immune extracapillary GN (Kidney) | - | IV MP, IV CYC | Persistent renal dysfunction C-ANCA negative | |
| 62/F | Adalimumab | RA | 48 | Malaise, weight loss nasal stuffiness, visual blurring, rash, GN | Urine studies: 3+ blood 3+ protein UPC 5.9 g | C-ANCA PR3 | (+) ANA1:640 (-) dsDNA (-) anti-GBM (-) anti- Cardiolipin, Normal complements | Pauci-immune mild segmental sclerosis with no tubuloreticular lesions (Kidney) | HCQ, Sulfasalazine, MTX | IVMP, Plasma exchange, 1 HD PO prednisone, CYC | Improved UPC Persistent renal dysfunction Improved C-ANCA | |
| 67/F | Etanercept | RA | 3 | Painful, erythematous ulcerated nodules, nasal congestion, peripheral neuropathy, polyarthritis, scleritis, GN pulmonary parenchymal nodules, chronic sinusitis on CT | Hb 13 gm/dl, ESR 111 mm/hr, CRP 15.3 mg/dl, Urine Studies: Hematuria | C-ANCA | (+) RF (45 IU/ml) (+) ANA 1:320 homogenous | Leukocytoclastic (Skin) | MTX, Prednisolone | IVMP pulses, CYC 750/month Steroid taper | Good clinical response | |
| 33/F | Infliximab | RA | 16 | Synovitis anemia GN | Hb 8.8 gm/dl, Cr 0.6 mg/dl (CrCl 82.5 ml/min), ESR 56 mm/hr, CRP 2.5 mg/dl, Urine Studies: 3+ protein 3+ occult blood, 24 hr urine protein: 1.2 gm/day | MPO PR3 | (-) Anti-DNA (-) Anti-GBM Normal IgG, IgA, IgM Normal complement | IgM deposition (weak intensity) IgG, IgA, C3, C1q and kappa and Lambda chains (-)- Necrotizing GN (Kidney) | MTX, Sulfasalazine, Bucillamine, Cyclosporine | IVMP, PO prednisone | Good clinical response | |
| 31/M | Infliximab | RA | 8 | Synovitis rash GN | Cr 3.4 mg/dl (CrCl 54 ml/min), CRP 9.1 mg/dl, Urine Studies: 3+ blood 24 hr Urine protein 1.5 gm | C-ANCA PR3 | (+) ANA 1:320 (homogenous) (-) dsDNA (+) RF (-) HepB and C serology (-) Cryoglobulin Normal complement | Pauci-immune crescentic GN (Kidney), Non diagnostic (Skin) | MTX, Cyclosporine Sulfasalazine, HCQ leflunomide | TMP, 1 gm IVMP for 3 days, Oral CYC 2 mg/kg daily. AZA | Good clinical response Decreased PR3 | |
| 58/F | Adalimumab | RA | 48 | Asymptomatic rapidly progressive GN Alveolar hemorrhage with pulmonary biopsy showing pauci-immune vasculitis anemia | Hb 6.2 gm/dl, CRP < 10 mg/dl, Urine Studies: RBCs+, 2.47 gm spot urine protein | P-ANCA MPO | (-) GBM (-) dsDNA (+) RF (+) ANA 1:640 homogeneous (+) SS-A & SS-B | Pauci-immune necrotizing GN-extracapillary necrotizing GN (Kidney) | D-penicillamine, Gold, MTX, steroids | IVMP, PO prednisone, Plasma exchanges-7 over 2 weeks, IV CYC six courses HD, AZA | Persistent renal dysfunction | |
| 55/M | Etanercept | RA | 4 | Alopecia maculopapular rash lower extremity sensory neuropathy GN | Cr. 3 mg/dl, Urine Studies: 1+ protein >5 RBCs/hpf 5 WBCs/hpf no casts 24 hr urinary protein - 1 gm/day | P-ANCA | (+) ANA 1:320 (-) anti-dsDNA Normal C3 and C4 | Pauci-immune focal, segmental, necrotizing and crescentic GN (Kidney) | MTX | IV CYC | Died | |
| 52/F | Adalimumab | RA | 3 | Gross hematuria and acute renal failure, GN | Urine Studies: 3+ protein >20 RBC/hpf granular casts 3.8 gm proteinuria | Atypical ANCA | (+) RF (+) ANA 1:640 homogenous, (+) dsDNA 1:25 IgG (-) cryoglobulin Decreased C3 and C4 | Focal proliferative lupus nephritis (class 3) (Kidney) | Prednisone, MMF, Infliximab, MTX, HCQ Penicillamine, Gold | Pulse IVMP PO steroids for 1 month | Persistent renal dysfunction | |
| 65/F | Etanercept | AS | 36 | Worsening cervical pain Severe and extensive aortitis on CTA chest and abdomen | Hb 9 mg/dl, ESR > 100 mm/hr, CRP 23.9 mg/dl | C-ANCA MPO | Borderline ANA (-) RF Normal complements | IVMP 1 g for 3 days, RTX, Prednisone | Good clinical response |