Unusual association of a positive pANCA pauci-immune extracapillary glomerulonephritis in a lupus patient

Sir,

We report a case of pauci-immune proliferative and crescentic glomerulonephritis in a 22-year-old female with systemic lupus erythematous (SLE) who was admitted because of a rapidly progressive glomerulonephritis syndrome. On admission, the patient had generalized edema, a blood pressure of 130/80 mmHg and anuria. There were no extra-renal signs.

Investigations showed a serum creatinine of 15.2 mg/ dl, hemoglobin of 6.9 g/dl, a lymphopenia (900/cumm), low serum complement C₃ concentration of 20 (50- 120 mg/ dl), positive antinuclear antibodies at 1/640 with homogenous fluorescence, and positive anti-DNA antibodies >300 UI/ml.

Renal histology included 23 glomeruli, there was extracapillary proliferation with circumferential crescents in 13 glomeruli and one obsolescent glomerulus [Figure 1].

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Figure 1

Circumferential extracapillary crescent with flocculus crushing (H and E, ×400)

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Immunofluorescence (IF) examination of the kidney biopsy did not reveal any significant deposit of immunoglobulins and complement. Anti-myeloperoxidase (MPO) antibodies were positive at 212 UI/ml by enzyme-linked immunosorbent assay (ELISA).

Immunosuppressive treatment included corticosteroids and intravenous cyclophosphamid. The renal evolution was characterized by a persistent anuria for 45 days. A progressive amelioration of renal function led to a serum creatinine of 1.7 mg/dl one year after initial treatment with a persistent proteinuria of 2. 4 g/24 hours.

Approximately 20% of patients with SLE have antineutrophil cytoplasmic autoantibodies (ANCA) positivity by indirect IF (IIF), mainly with a perinuclear pattern (p-ANCA).[1] ANCA seropositivity by ELISA is less frequent and the target antigens are most commonly lactoferrin, cathepsin G, and MPO.[1]

There are conflicting reports on the significance of ANCA positivity in patients with SLE.[1] SLE and lupus nephritis (LN) may promote neutrophil degranulation and facilitate ANCA autoantibody formation.[2] Diffuse proliferative LN that contains little or no sub-endothelial deposits is rare.[3] Underlying vasculitic lesions induced by ANCA antibodies were recently incriminated in the pathogenesis of these forms.[4]

Nasr et al. reported 10 cases of LN with ANCA-associated glomerulonephritis,[2] the evolution of these patients after the treatment by corticosteroids and cyclophosphamid was marked by lethal infectious complications in three patients, complete remission in six patients with a relapse in one case and resistance to treatment in one patient.

Nasr et al. evoked the probability of an overlap between lupus nephropathy and ANCA extracapillary glomerulonephritis and suggested to search systematically the positivity of ANCA by ELISA test in a lupus patient whenever renal histology shows extensive necrotizing lesions with a non-significant endocapillary proliferation and rare sub-endothelial deposits.[2]