test : In patients with idiopathic retroperitoneal fibrosis (iRPF), inflammation and fibrosis may be a manifestation of IgG4-related disease. As such, serum IgG4 levels may be of value as parameter of IgG4-related inflammation and in predicting treatment response.

Design: Prospective, observational study of 29 consecutive iRPF patients who were seen at our tertiary care referral centre from September 2010 through November 2013.

Measurements: Clinical, laboratory and radiological investigation was performed at presentation and at repeated follow-up. All but 2 patients were treated with tamoxifen. Treatment success was defined as such satisfactory clinical, laboratory and radiological response to tamoxifen during follow-up that there was no need to alter therapy. Treatment outcome analysis included patients who had at least 4 months of follow-up and who underwent at least the first CT scan follow-up. Second-line treatment consisted of corticosteroids, either alone or combined with other immunosuppressants.

Results: Overall, 13 patients (44.8%) had IgG4 levels above the normal range of 1.4 g/L. In patients with elevated IgG4 levels, locoregional lymphadenopathy (53.8% vs. 18.8%; P <0.01) and to lesser extent atypical mass localisation (30.7% vs. 6.3%; P=0.14) was observed more frequently compared to that in patients with normal range levels. Fibrotic mass thickness did not differ between patients with normal range or elevated IgG4 levels (median 28.0 [IQR 21.5-43.5] mm vs. 34.5 [IQR 16.5-50.3] mm; P=0.72). Males tended to have higher IgG4 levels compared to females (1.66 [0.7-4.1] g/L vs. 0.53 [0.4-1.3] g/L; P=0.09). Eleven of 24 patients (45.8%) who received tamoxifen eventually switched to second-line treatment. Success rate in tamoxifen-treated patients with normal range or elevated baseline IgG4 levels did not differ. However, non-responders to tamoxifen had higher baseline IgG4 levels compared to patients who responded satisfactorily to tamoxifen (1.31 g/L [0.7-7.3] g/L vs. 0.64 [0.3-1.7] g/L, P=0.05). All patients (100%) who had treatment failure were men, compared to 57% of patients with treatment success (P=0.02). In patients who had treatment failure with tamoxifen, IgG4 levels did not decrease until after switch to second-line treatment (∆IgG4 0.55 [0.1-2.5] before switch vs. 1.86 [0.6-7.2] after switch, P=0.01). Eleven of 13 patients had success of second-line therapy.

Conclusions: iRPF patients with elevated IgG4 levels may present more often with atypical mass localisation and particularly locoregional lymphadenopathy. Non-responders to tamoxifen had higher IgG4 levels than responders. Females seem to respond better to tamoxifen therapy, which might be explained by their lower IgG4 levels.