Back
Seronegative lupus nephritis (LN) has been used to describe patients with typical renal histology of LN but without clinical nor serological evidence of systemic lupus erythematosus (SLE). Possible causes include hepatitis B and C, cryoglobulinemic GN, infection associated GN, C1q nephropathy, IgA nephropathy or idiopathic. Furthermore, the possibility of seronegative SLE should not be ruled out, implying that SLE diagnosis may occur even up to 10 years after histopathological findings. We present a seronegative patient with proliferative LN pattern where the diagnosis and the treatment are a challenge.
A 52-year-old male patient with a recent diagnosis of type 2 diabetes mellitus (DM), and obesity (BMI: 35), was admitted with a one-week history of fever and right knee pain. Initial laboratory test showed leukocytosis of 21,960/mm³ with a predominance of neutrophils, an elevated erythrocyte sedimentation rate of 105 mm/h, a C-reactive protein level of 24 mg/dl, normal creatinine level without proteinuria. Septic arthritis was diagnosed with isolation of methicillin-sensitive Staphylococcus aureus and the patient underwent treatment with cephalexin and joint drainage.
Two weeks later developed nephrotic syndrome associated with KDIGO III acute kidney injury, requiring renal replacement therapy (RRT). Laboratory results revealed a hematocrit (HCT) of 28.8 %, creatinine of 4.5 mg/dl, negative cryoglobulins, negative antinuclear antibodies (ANA), negative DNA antibodies, negative ANCA p-c, a C3 level of 106, C4 level of 33, negative HIV, negative HBV, negative HCV, proteinuria of 10 gr/d, polyclonal hypergammaglobulinemia with hypoalbuminemia (1.8 g/dl). Urinalysis showed, dysmorphic red blood cells, acanthocytes with hematic and muddy brown granular casts.
A renal biopsy was performed, which showed 18 glomeruli, with 4 of them with global sclerosis, 6 with epithelial crescents, double contour membranes, mesangial expansion, focal ATN, tubular atrophy and interstitial fibrosis 25%. Arterioles displayed moderate hyalinosis. Immunofluorescence (IF) indicated deposits of IgG+++, IgA+, IgM+, C3++, and C1q++ in the form of granules in the mesangium and capillary basement membranes. Electron microscopy (EM) showed subepithelial and subendothelial deposits, as well as subendothelial tubuloreticular structures. The diagnosis was made as glomerulonephritis with a diffuse MP pattern by immunocomplex. Treatment included corticosteroid and cyclophosphamide pulses, followed by maintenance therapy with mycophenolate. Renal replacement therapy (RRT) was continued for 2 months, and the patient's renal function improved, allowing discontinuation of hemodialysis.
The MP pattern associated with immune complexes is linked to various etiologies, including SLE. The histopathological features in our patient, in terms of optic microscopy, IF findings and the presence of tubuloreticular structures on EM, are characteristic but not specific to LN.
Therefore, a diagnostic dilemma results in this case from between infection associated GN and seronegative LN. However, in the face of diagnostic uncertainty and a poor clinical course, and after completing antibiotic treatment, immunosuppressive therapy was initiated, as it could potentially improve the prognosis if administered promptly.