Demographics

Forty-six patients fulfilled the 2020 Revised Comprehensive Diagnostic Criteria for IgG4-RD as either definite, probable, or possible disease [17]. Twenty-eight males and eighteen females in the total patient population were divided into cardiovascular and non-cardiovascular subgroups, depending on the presence or absence of IgG4-RD lesions in the heart, blood vessels, or pericardium.

Thirty-eight patients of which twenty males and eighteen females formed the non-cardiovascular subgroup, while the cardiovascular subgroup composed of 8 male patients (Table 1). This difference in gender was statistically significant (p = 0.015), while the difference in distribution of ethnicities was not (p = 1.00). The mean age of diagnosis was higher in the cardiovascular subgroup at 60.9 years compared to 58.2 years, though this was identified to not be statistically significant (p = 0.262).

Table 1 Demographics of patients with IgG4-RD in cardiovascular and non-cardiovascular subgroupsInitial clinical presentation

Out of these 46 patients, the most common presentation was lacrimal gland or orbital swelling in 18 patients (39.1%), followed by salivary gland swelling in 8 patients (17.3%) (Fig. 1). Notably, 8 patients (17.3%) did not have symptoms related to IgG4-RD and were identified incidentally during radiological or histopathological evaluation for other diseases. Within the cardiovascular subgroup, IgG4-related disease was most often detected incidentally (37.5%) with no patients in this subgroup presenting with chest pain, dyspnoea, or other cardiovascular symptoms.

Fig. 1

Initial presenting complaints of all patients diagnosed with IgG4-related disease. The most common presentation in all patients with IgG4-related disease was lacrimal gland or orbital gland swelling, followed by salivary gland swelling. Two patients presented with both lacrimal and salivary gland swelling.

Initial imaging and histopathological findings

Initial 2-[18F]FDG PET/CT scans identified 36 sites of organ involvement amongst the 8 patients in the cardiovascular subgroup, and 73 sites of organ involvement amongst 38 patients in the non-cardiovascular subgroup (Table 2).

Table 2 Sites of disease involvement in cardiovascular and non-cardiovascular subgroup

Cardiovascular involvement was identified based on lesions in the pericardium (n = 2), coronary arteries (n = 5), as well as aorta and other vessels (n = 4) (Table 3). In descending order of frequency, the sites of involvement in arteries are abdominal aorta (n = 3), iliac arteries (n = 3), followed by hepatic arteries, descending aorta, coeliac artery, renal artery, and right sided mesenteric vessels (n = 1 each). Patients with cardiovascular involvement had more extensive disease with a higher mean number of organs involved at 4.625 ± 3.20 compared to patients from the non-cardiovascular subgroup at 1.89 ± 1.20 (p = 0.049). In both groups, lymph nodes were the most frequently identified site.

Table 3 Cardiovascular manifestations of IgG4-related disease

Multiple organ involvement, defined as at least two organs with suspected IgG4-related disease, was more frequent in patients within the cardiovascular subgroup (75.0%) than in the non-cardiovascular population (52.6%).

Comparing inflammatory biomarkers

For each patient, paired values of serum immunoglobulins (IgG4, or total serum IgG), inflammatory biomarkers (CRP, ESR), and semi-quantitative parameters on 2-[18F]FDG PET/CT (SUVmax, MTV, TLG) were compared. TBR values were also compared for cardiovascular lesions. Spearman’s rho identified no strong correlation between these variables (Table 4), though there was a moderate correlation between total IgG and ESR (p < 0.001) for all patients. For patients with cardiovascular disease, correlations between IgG4 and TBR, and between total IgG and TBR were not significant (p > 0.05).

Table 4 Correlation between serum immunoglobulins vs inflammatory markers and semi-quantitative parametersComparing cardiovascular and non-cardiovascular subgroups

For cardiovascular and non-cardiovascular subgroups, Shapiro–Wilk test identified that all 7 variables were not normally distributed (p < 0.001 to 0.001). Therefore, to compare the extent of similarity between these two subgroups, the Mann–Whitney U test was applied. The two subgroups were significantly different for total serum IgG (U = 0.024), MTV (U = 0.006), and TLG (U = 0.006) but were not significantly different for IgG4 (U = 0.120), CRP (U = 0.940), ESR (U = 0.072), and SUVmax (U = 0.467).

Comparing radiological findings pre- and post-treatment

Ten patients identified had repeat 2-[18F]FDG PET/CT scan following the initiation of treatment.. This group of 10 patients consisted of 5 patients with cardiovascular involvement, and 5 patients without cardiovascular involvement. Immunosuppressive therapies administered include, in order of decreasing popularity: prednisolone, mycophenolate mofetil, methotrexate, and rituximab.

All patients had a decrease in TLG after starting immunosuppressive therapy, with median treatment duration of 284 days. Representative images of the PET/CT scans are shown in the appendix (Additional file 1: Fig. S1, Additional file 2: Fig. S2, Additional file 3: Fig. S3), demonstrating a notable decrease in 2-[18F]FDG uptake following therapy. Overall, there was a marked decrease in TLG from a mean of 1066.61 ± 1265 in the pre-treatment group to 53.24 ± 39.1 in the post-treatment group (p = 0.0193). Similar statistically significant decreases were also observed across other semi-quantitative measures of SUVmax (p = 0.001), MTV (p = 0.019), and number of involved organs (p = 0.002), across both cardiovascular and non-cardiovascular subgroups (Table 5). Within the cardiovascular subgroup, there was a significant decrease in TBR before and after treatment (p = 0.002). While semi-quantitative measures reflected this change, laboratory indicators such as total IgG (p = 0.058) and ESR (p = 0.243) did not demonstrate a statistically significant change before and after treatment. There were insufficient post-treatment data for CRP and IgG4 to analyse their utility in reflecting response to treatment.

Table 5 Comparisons of semi-quantitative parameters and radiological findings before and after treatment