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Glomerulonephritis (GN) is typically classified based on histological patterns, the clinical and research utility of this classification has recently been called into question. Anders et al proposed an immunopathogenesis-based classification. The clinical and histological characteristics of this case demonstrates the utility of the immunopathogenesis-based classification.
Case presentation: A 62-year-old female presented with a 2 week history of rash, periorbital swelling, weakness, dyspnea on exertion and lower back pain. Past medical history was relevant for chronic axillary and cervical lymphadenopathy compatible with reactive follicular hyperplasia, type 2 diabetes, hypercholesterolemia, irritable bowel syndrome, depression and asthma. At the time of presentation she was taking: pantoprazole, naproxen, chlordiazepoxide/clidinium, bupropion, duloxetine and rosuvastatin. Laboratory work up revealed an increase in serum creatinine from 0.7 to 1.9 mg/dL, proteinuria 3 gr/day in 24-hour collection and microscopic hematuria. Further work up was relevant for positive p-ANCA, and normal CRP, C3-C4, SPEP and TSH.
A renal biopsy was performed:
Renal biopsy report:
*PLA2R negative stage 1 membranous nephropathy with peritubular deposits and early focal necrotizing lesions with early crescent, focal acute tubular injury with focal interstitial nephritis.
*1/17 glomeruli globally sclerosed.
*Moderate interstitial fibrosis and tubular atrophy.
*Moderate arteriolar hyalinosis and arterial sclerosis.
Discussion: According to the autoimmune-mediated mechanism: electron microscopy findings in the glomerular basement membrane (membranous) were compatible with a single hit process taking into consideration drug-induced autoimmune membranous with tubulointerstitial nephritis and tubular basement membrane immune complexes; however, it does not justify the early crescentic lesions which together with positive p-ANCA antibodies account for the extra capillary proliferation.
The differential diagnoses included ANCA-associated vasculitis (AAV) over imposed to IgG4-related disease (IgG4RD) vs drug-induced tubulointerstitial nephritis with tubular basement membrane immune complexes.
We consider IgG4 in glomeruli and tubules as a manifestation that unifies histological patterns through autoimmunity. Regarding IgG4-RD, the classification criteria proposed by ACR/EULAR in 2019 consider the presence of positive ANCA autoantibodies as an exclusion criteria (mimicker), however, in the same year Ma et al described 92 AAV patients with renal biopsy results, among them 10 met both AAV and IgG4-RD criteria (concomitant group) and found that patients with AAV showed elevated serum IgG4 levels even if they did not met IgG4-related disease criteria and that IgG4 subclass of ANCA, but not IgG1, IgG2 or IgG3 subclasses, was specifically elevated in the concomitant group. Moreover, IgG4 subclass of ANCA has been reported to be pathogenic.
To sum up this patient can be considered with an overlap AAV and IgG4-RD, the common pathogenic pathway involving IgG4 in this overlap syndrome represents an area for future research.