Recent advances in the management and understanding of IgG4-related kidney disease (RKD) have emphasized the importance of urgent treatment in IgG4-related tubulointerstitial nephritis. On the other hand, to avoid long term glucocorticoid toxicity, strategies for early withdrawal of steroid or combination of immunosuppressants, such as rituximab, and the minimum dose of steroid have been pursued. However, disease recurrence after reducing or stopping steroid therapy hampers early withdrawal of glucocorticoid maintenance therapy. In addition, knowledge has accumulated in diagnostic approaches including differential diagnosis of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, idiopathic multicentric Castleman’s disease, and Rosai-Dorfman disease with kidney lesion, which leads to earlier and precise diagnosis of IgG4-RKD. This review summarizes recent progress in the differential diagnosis of IgG4-RKD and related treatment strategies, and recent topics of hypocomplementemia, membranous glomerulonephritis, and IgG4-related pyelitis and periureteral lesion.

Although several recent reports have discussed the similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE), the relationship between these conditions has not been established owing to the small number of patients investigated. In 1998-1999, an outbreak of Erythema infectiosum occurred close to our hospital, enabling us to investigate the clinical, hematological, and serological findings, including serum complement and antinuclear antibodies (ANA), in 22 patients with acute HPV-B19 infection. The principal symptoms included rash (86.3%), edema (59%), arthralgia (45.4%) and fever (31.8%). Lymphadenopathy was seen in three of the 22 cases. The laboratory findings showed high incidences of leukopenia (50%), hypocomplementemia (95%), and ANA (64.7%). At the time of disease onset, patients with acute HPV-B19 infection presented with features which were similar to those of SLE. The possibility of HPV-B19 infection should therefore be considered in patients presenting with SLE-like features.

BackgroundAlthough hypocomplementemia has been frequently reported in IgG4-related kidney disease (IgG4-RKD), few studies have investigated differences in the clinicopathological features of IgG4-RKD with and without hypocomplementemia in a relatively small cohort1,2).ObjectivesTo compare the clinicopathological features of Japanese patients with and without hypocomplementemia in IgG4-RKD.MethodsWe retrospectively examined the clinicopathological features of 60 patients with definitively diagnosed IgG4-RKD, collected from the institutions associated with the Japan IgG4-RKD working group between December 2010 and May 2019, with reference to the presence of hypocomplementemia.ResultsAmong the patients included, 42 (70%) had hypocomplementemia. In the latter group, serum levels of IgG and non-IgG4 IgG, calculated as total IgG minus IgG4, were significantly higher (mean IgG level, 3832 vs 2626 mg/dl, p=0.005, mean non-IgG4 IgG level, 2775 vs 1627 mg/ml, p =0.000). Renal function at diagnosis tended to be lower (mean eGFR level 42.4 vs 53.6 ml/min), although not to a significant degree (p=0.07). There were no significant inter-group differences in the levels of serum IgG4 and IgE, or in the number of extra-renal involved organs. Renal pathology specimens were obtained from 53 patients, 70% of whom had hypocomplementemia. In the hypocomplementemia group, light microscopy demonstrated a significantly broader extent of interstitial inflammatory cell infiltration (p=0.035), and immunofluorescence revealed a higher frequency of IgG or complement deposition on the renal tubular basement membrane (TBM) (p=0.048). C1q deposition on the TBM was evident only in the hypocomplementemia group. There was no significant inter-group difference in the presence of storiform fibrosis, the degree of interstitial fibrosis, the number of infiltrating IgG4-positive cells, or the frequency of membranous glomerulonephritis.ConclusionHypocomplementemia in IgG4-RKD is associated with elevated levels of IgG subclasses other than IgG4, and may be related to progression of renal inflammation.References[1]Wang R, et al. Role of complement system in patients with biopsy-proven immunoglobulin G4-related kidney disease. Hum Pathol. 2018;81:220-228.[2]Fujisawa Y, et al. Hypocomplementemia is related to elevated serum levels of IgG subclasses other than IgG4 in IgG4-related kidney disease. Mod Rheumatol. 2021;31(1):241-248.Disclosure of InterestsNone declared