A Pediatric Case of a D-Penicillamine Induced ANCA-associated Vasculitis Manifesting a Pulmonary-Renal Syndrome

Abstract

D-penicillamine has been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting as rapidly progressive glomerulonephritis or pulmonary-renal syndrome mostly in adults. We report a pediatric case of D-penicillamine induced ANCA-associated vasculitis that manifests as a pulmonary-renal syndrome with a mild renal manifestation. A 13-year-old girl who has been taking D-penicillamine for five years under the diagnosis of Wilson disease visited the emergency room because of hemoptysis and dyspnea. She had diffuse pulmonary hemorrhage, microscopic hematuria, and proteinuria. Myeloperoxidase ANCA was positive, and a renal biopsy revealed pauci-immune crescentic glomerulonephritis. Under the diagnosis of D-penicillamine-induced ANCA-associated vasculitis, D-penicillamine was switched to trientine, and the patient was treated with plasmapheresis, glucocorticoid, cyclophosphamide, and mycophenolate mofetil. Pulmonary hemorrhage improved rapidly followed by the disappearance of the hematuria and proteinuria five months later.

Autoantibodies in Wilson disease: Impact on clinical course

“…Some case reports documented that D‐penicillamine treatment induced ANCA‐associated vasculitis and glomerulonephritis in patients with WD. 12 , 30 , 32 Our analysis showed elevated prevalence of ANCA in WD patients in comparison to healthy individuals, but with no association with disease manifestation. Vasculitis is not a part of pathomorphological features of WD known from postmortem brain examinations.…”

“…28 D-penicillamine is associated with increased risk of autoimmune diseases, with drug-induced lupus, vasculitis, myasthenia gravis, glomerulonephritis, epidermolysis bullosa acquisita noted in many case reports. 12,[29][30][31][32][33] In 235 WD patients, coexisting autoimmune disorders were found in 8.1% of the patients, with 5.5% having preexisting autoimmune diseases and 2.6% developing an autoimmune condition while receiving long-term D-penicillamine treatment. 15 In our study, clinically overt autoimmune diseases were rare (4 cases) and appeared unrelated to treatment type.…”

“… 8 , 9 , 10 D‐penicillamine is one such drug that can induce autoantibody production, including antinuclear antibodies (ANA), anti‐neutrophil cytoplasmic antibodies (ANCA), anti‐muscle‐specific tyrosine kinase antibodies and anti‐acetylcholine receptor antibodies. 11 , 12 , 13 Moreover, multiple liver diseases, including autoimmune hepatitis, influence the immune system and lead to increased serum autoantibody production. 14 Consequently, due to liver injury, as well as D‐penicillamine treatment, we may expect elevated prevalence of autoantibodies in patients with WD.…”

Proteinuria in a 6‐year‐old girl with Wilson disease: Lessons learnt

“…The spectrum of histopathological changes in penicillamine‐induced nephropathy includes membranous nephropathy (80%), lupus nephritis, tubulointerstitial nephritis, minimal change disease, crescentic glomerulonephritis, Goodpasture syndrome and renal‐limited vasculitis 4 . Penicillamine‐induced anti‐neutrophil cytoplasmic antibody–associated vasculitis in children has also been described 5 …”

“…4 Penicillamine-induced antineutrophil cytoplasmic antibody-associated vasculitis in children has also been described. 5 DIL is an autoimmune condition that results from drug exposure and presents with clinical features of SLE. However, DIL is less severe than SLE and poses a diagnostic dilemma because both the conditions are similar in their clinical presentations.…”