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Aim: To study the clinical presentation, radiological findings, and therapy responsiveness of patients with biopsy-proven immunoglobulin G4 (IgG4)-related neurological disease. Methods: The study was conducted between January 2016 and March 2018 from the Department of Neurology and Pathology of Nizam's Institute of Medical Sciences. Patients with neurological symptoms and biopsy suggestive of IgG4-related disease (IgG4-RD) were included. These patients were studied for their demographic pattern and clinical presentation. The presence of serological markers such as vasculitic profile and IgG4 levels was analyzed. Radiological findings were studied in detail. Therapeutic agents used and the response to therapy were assessed. Results: There were six cases with IgG4-related neurological disease which were all hypertrophic pachymeningitis. The age ranged from 35 to 64 (mean = 46) years. The clinical presentation was acute in one, subacute in two, and chronic in three patients. The most common presenting symptom was headache (4), followed by gait and/or urinary disturbances (2), paraparesis (1), and diplopia (1). IgG4 levels were elevated in 50% of them. Pseudotumor-like mass and sinovenous thrombosis, not described previously, were seen in one patient. All the patients were treated with oral or intravenous steroid. Rituximab was given in three patients; azathioprine was the steroid-sparing agent in one patient. Those with acute/subacute onset of presentation had an excellent response to steroids. All the patients with a chronic duration of their symptoms received empirical anti-tuberculous therapy before a definitive diagnosis of Ig G4-RD was made. Conclusions: The characterization of patients with IgG4-related neurological disease based on the understanding of the clinical spectrum increases the confidence in the clinician to resort to early immunosuppression, thereby having prognostic implications.

SummaryIgG4-related kidney disease (IgG4-RKD) occasionally progresses to chronic renal failure and is pathologically characterized by IgG4-positive lymphoplasmacyte-rich tubulointerstitial nephritis with storiform fibrosis (bird's-eye pattern fibrosis). Although radiology reveals a heterogeneous distribution of affected areas in this disease, their true distribution within the whole kidney is still unknown because of difficulty in estimating this from needle biopsy samples. Using 5 autopsy specimens, the present study histologically characterized the distribution and components of interstitial inflammation and fibrosis in IgG4-RKD. Interstitial lymphoplasmacytic infiltration or fibrosis was observed in a variety of anatomical locations such as intracapsular, subcapsular, cortical, perivascular, and perineural regions heterogeneously in a patchy distribution. They tended to be more markedly accumulated around medium- and small-sized vessels. Storiform fibrosis was limited to the cortex. Immunostaining revealed nonfibrillar collagens (collagen IV and VI) and fibronectin predominance in the cortical lesion, including storiform fibrosis. In contrast, fibril-forming collagens (collagen I and III), collagen VI, and fibronectin were the main components in the perivascular lesion. In addition, α-smooth muscle actin–positive myofibroblasts were prominently accumulated in the early lesion and decreased with progression, suggesting that myofibroblasts produce extracellular matrices forming a peculiar fibrosis. In conclusion, perivascular inflammation or fibrosis of medium- and small-sized vessels is a newly identified pathologic feature of IgG4-RKD. Because storiform fibrosis contains mainly nonfibrillar collagens, “interstitial fibrosclerosis” would be a suitable term to reflect this. The relation between the location and components of fibrosis determined in whole kidney samples provides new clues to the pathophysiology underlying IgG4-RKD.

IgG4 related disease is a fibro-inflammatory condition with involvement of renal and extra renal organs, characterized by lymphoplasmacytic infiltration with organ dysfunction. We describe three cases of IgG4 related renal disease from a tertiary care hospital in south India.