Our findings validated that four clinical phenotypes of IgG4-RD patients shared different demographic and serological features. As for therapeutic response, most patient achieve remission with GC monotherapy or combination therapy. GC withdrawal, GC monotherapy and higher score of ACR/EULAR IgG4-RD Classification Criteria were associated with disease relapse.
In our cohort, the median age of onset in our cohort was 63 years old, and the ratio of male to female was 2.62:1, which was basically consistent with previous studies by other Chinese authors (median age:53.1,M:F=2.3:1).17The most common affected organ was pancreas which was different from some research.8,17This difference may attribute to the fact that our center has advantages of subject in gastroenterology.
Patients with multiple organ involvement had higher level of baseline serum IgG and IgG4. It suggests that we should consider the possibility of multiple organ involvement if we observe the patients with significant increase of IgG4 or IgG4.
Our study revealed that patients from head and neck limited group were more likely to be female. Mikulicz syndrome with systemic involvement group had the highest serum globulin, IgG and IgG4 level. These findings were in line with an Italian cohort and two international cross-sectional cohorts.15,18 It also validated that some demographics and serological features were quite different between each clinical phenotype. 15It may provide physicians a new insight to this clinical classification of IgG4-RD.
Our result demonstrated that 97.4% patients(n=74) response to glucocorticoids therapy, only 2 patients did not achieve remission. 6 patients with milder degree of pancreas enlargement achieved remission without GC treatment and the rest of 10 patient who did not take GC therapy were failed to achieve remission. It is widely accepted that glucocorticoids is the treatment of choice for IgG4-RD and effective for most patients.4 Several studies had reported that patients with IgG4-RD who are not treated with GC are less likely to achieve remission.19,20 Our finding indicated that majority of IgG4-RD patients with moderate-severe and/or multiple organ involvement may not benefit from the “Watchful waiting” strategy. 4
In this study, the relapse rate was 20.3% which was consistent with some researches. 8,9 Cox regression showed that GC withdrawal, GC monotherapy and higher score of ACR/EULAR IgG4-RD Classification Criteria were independent prognostic factors for relapse. It is accepted that GC withdrawal is associated with disease relapse.9,21,22In our cohort, 7 patients relapsed within median 4.3 months after glucocorticoids withdrawal. (OR 3.189, 95% CI 1.571–6.474, P=0.001).
So far, the role of combination therapy in relapse still remains controversial. Several studies have reported that combination therapy associated with a lower relapse rate.9,11,23 Our study also revealed that patients who took GC+IM therapy were less likely to relapse than GC monotherapy group (OR 0.12, 95% CI 0.02-0.94, P=0.04). On the contrary, a recently cohort shown that GC+IM therapy was not the risk factor of relapse.8 This doubt may attribute to different types and maintenance period of IM between medical centers. Standardized immunosuppressive agent treatment are urgently needed for IgG4-RD patients in the future.
Our univariate analysis shown that higher score of ACR/EULAR IgG4-RD Classification Criteria was also associated with disease relapse (OR 1.10, 95% CI 1.02-1.99, P=0.01). It seems that patients with higher score of ACR/EULAR IgG4-RD Classification Criteria are likely to relapse and should own more attention. Score of ACR/EULAR IgG4-RD Classification Criteria was calculated as the sum of several weighted criteria including clinical findings, serological results, radiological assessments and pathological interpretations.12 Higher score implied patients may have more organ involvement, higher serum IgG4 level or baseline IgG4-RD RI score. Some of those components (more organ involvement, higher serum IgG4 level) were reported as the risk relapse factors. 9,24 It may explain the relationship between higher score of ACR/EULAR IgG4-RD Classification Criteria and relapse.
Our study has several limitations. Firstly, this is a single-center and retrospective study. Large sample size and long duration follow-up studies are required to define the prognosis of the condition. Secondly, our cohort have different spectrum of organ involvement; therefore, a multicenter study might help us better recognize the disease.
In conclusion, GC withdrawal, GC monotherapy were the risk factor of relapse. For the first time, this study described that higher score of ACR/EULAR IgG4-RD Classification Criteria may associated with relapse.