Purpose The efficiency of [18F]FDG PET/CT using volume-based indices was evaluated to assess the disease activity and response to therapy in patients with immunoglobulin G4-related disease (IgG4-RD). Methods A total of 17 patients with IgG4-RD were examined with [18F]FDG PET/CT before and during treatment. The lesion boundary was determined using a fixed threshold of standardized uptake value (SUV) ≥ 2.5. The highest maximum SUV (SUVmax) among all affected lesions was calculated for individual patients. We summed metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of each affected lesion to generate a total MTV and total TLG. PET results were compared with those of serum IgG4 and soluble interleukin-2 receptor (sIL-2R) levels. Results The mean number of involved organs per patient was 3.8 as determined by [18F]FDG uptake. The number of involved organs, total MTV and total TLG were significantly correlated with IgG4 (P = 0.046, < 0.001, < 0.001, respectively) and sIL-2R (P < 0.001, = 0.031, 0.031, respectively). According to the clinical assessments for therapy response, all patients were classified as improved. The SUVmax, total MTV, and total TLG during therapy were all significantly lower than those before therapy (all P < 0.001). Conclusion [18F]FDG PET/CT is valuable for assessing the extent of multi-organ involvement before therapy and monitoring subsequent therapy in patients with IgG4-RD. [18F]FDG PET/CT using volumetric indices correlated with serum IgG4 and sIL-2R levels.
Objectives We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants. Methods SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA. Results S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with ( n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement ( n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers. Conclusion HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.
Background Muscle enzymes are the major noninvasive diagnostic parameters useful in polymyositis/dermatomyositis (PM/DM). Few studies have yet correlated findings on 18 F-FDG PET with disease activity in patients with PM/DM. Purpose We evaluated 18 F-FDG muscle uptake in patients with PM/DM compared with non-muscular diseases and correlated the results with serum muscle enzymes. Methods A total of 28 patients with untreated PM/DM and 28 control patients with non-muscular diseases were examined with 18 F-FDG PET/CT. 18 F-FDG uptake was evaluated in 9 proximal skeletal muscle regions bilaterally. The uptake was scored as follows: 0 = less than that of the mediastinal blood vessels, 1 = greater than or equal to that of the mediastinal blood vessels, and 2 = greater than or equal to that of the liver. A score 1 or 2 was considered positive. The mean and maximum standardized uptake values (SUV) were calculated in each muscle and were averaged for all muscle regions. PET findings were correlated with serum muscle enzymes. Results 18 F-FDG uptake was observed in 82% of patients with PM/DM and 7% of control patients. The number of positive regions, total score, mean SUVmean, and mean SUVmax in patients with PM/DM were significantly higher than those in the control patients (all P < 0.001). The total score of 2 was the best cut-off value that could discriminate patients with PM/DM from control patients. The total score, mean SUVmean, and mean SUVmax showed significant correlations with creatine kinase ( P = 0.047, 0.002, 0.010, respectively) and aldolase ( P = 0.036, 0.005, 0.038, respectively). Conclusion 18 F-FDG PET/CT using visual and SUV methods demonstrated its usefulness by discriminating PM/DM from non-muscular diseases and correlating with serum muscle enzymes in patients with PM/DM.
Background This study aimed to investigate the effect of glucocorticoid doses on adverse pregnancy outcomes (APOs) in women complicated by systemic lupus erythematosus (SLE). Methods We investigated 74 pregnancies complicated by SLE or SLE-dominant mixed connective tissue disease. The pregnancies were managed from conception to delivery in our institution. We retrospectively evaluated whether the mean glucocorticoid dose during pregnancy is associated with APOs, including preterm birth (PB), low birth weight (LBW), and light-for-date (LFD). We also calculated the cut-off dose of glucocorticoid that affected APOs. Results All APOs occurred in 35 (50.7%) patients, with 14 cases of PB, 23 cases of LBW, and 10 cases of LFD. Patients with all APOs or PB had a higher dose of glucocorticoid during pregnancy than patients without all APOs or with full-term birth (P = 0.03, P < 0.01, respectively). Logistic regression analysis for all APOs and PB showed that the cut-off values of the mean glucocorticoid dose were 6.5 and 10.0 mg/day, respectively. Patients who delivered LBW or LFD newborns showed no significant difference in the glucocorticoid dose used during pregnancy than patients without LBW or LFD newborns. Patients who delivered LBW newborns were more likely to have used glucocorticoids during pregnancy (P < 0.01). Conclusions In pregnancies complicated by SLE, a relatively lower dose of glucocorticoid than previously reported is significantly related to APOs, especially PB. Therefore, the disease activity of patients with SLE should be managed with the appropriate lower dose of glucocorticoid during pregnancy.
To reveal which disease activity parameters affect low Apgar scores of newborns, which is considered as a predictive parameter for neurological development. We examined retrospectively the data from 42 newborns who were delivered from systemic lupus erythematosus (SLE) mothers from 2006 to 2019. We evaluated whether the disease activity parameters, such as the achievement ratio of lupus low disease activity state (LLDAS), SLE disease activities index (SLEDAI), complement level, titer of anti-double stranded DNA (anti-dsDNA) antibody, therapeutic agents were related with low Apgar scores of newborns. In 42 newborns, adverse pregnancy outcomes, especially preterm birth (16.7%), low birth weight (31.0%) light-for-date (11.9%) were associated with disease activity parameters or prednisolone dose. Apgar scores at 1 minute were related with unachieved LLDAS and the titer of anti-dsDNA antibody at first and third trimester, SLEDAI score and complement level at third trimester, mean prednisolone dose. Apgar scores at 5 minutes were also associated with the titer of anti-dsDNA antibodies at first and third trimester and mean prednisolone dose. Multivariate analysis showed only high titer of anti-dsDNA antibody was significantly associated with low Apgar score at both one minute and 5 minutes. In our retrospective study, high titer of anti-dsDNA antibodies at first and third trimester was a risk factor for low Apgar scores of newborns born to SLE mothers. We considered that high titer of anti-dsDNA antibody influenced on childrens neurological development, therefore, there is a need for long-term follow-up study of SLE offsprings.
Objective To investigate the serum total antibody (immunoglobulin M and immunoglobulin G) titre against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain following BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination in Japanese rheumatic disease patients undergoing immunosuppressive therapy. Methods The serum antibody titre against SARS-CoV-2 spike protein was analysed in 123 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers who had received 2 doses of the BNT162b2 mRNA vaccine with at least 14 days elapsing since the second dose. Results The antibody titre in rheumatic disease patients was significantly lower than that in healthy subjects (p<0.0001). The antibody titres of the 41 patients who received biologics or Janus kinase inhibitors and the 47 patients who received conventional immunosuppressive agents were significantly lower than those of the 35 patients who did not receive immunosuppressive agents (p<0.0001 and p<0.0001, respectively). In addition, the mean antibody titre of the 43 patients on methotrexate was significantly lower than that of the 80 patients not on methotrexate (p=0.0017). Conclusion Immunogenicity to the BNT162b2 mRNA COVID-19 vaccine in rheumatic disease patients was found to be reduced under immunosuppressive treatment. In particular, methotrexate seems to be associated with a decreased antibody response.
Objective Hydroxychloroquine (HCQ) has been prescribed in Japan only relatively recently and is recommended for the treatment of skin lesions, arthritis and renal lesions according to the Japanese Guideline for the Management of systemic lupus erythematosus (SLE) (2019). However, the associations between the efficacy and safety and the HCQ dose in Japanese SLE patients remain unclear. We investigated the efficacy and safety of different HCQ doses in Japanese SLE patients with a low disease activity who were not receiving immunosuppressants. Methods The disease activity was evaluated using the SELENA-SLEDAI 2011 criteria, the Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum biomarkers. Safety was evaluated via the frequency of adverse events over a period of three months. Results We enrolled 61 SLE patients treated with HCQ and no additional immunosuppressive therapy for more than 3 months. HCQ was administered to 46 patients at the usual dose and to 15 cases at a lower than usual dose. Although the CLASI activity scores decreased significantly in both groups, the magnitude of this decrease was larger in the usual-dose HCQ group than in the low-dose HCQ group. SLEDAI scores and immunological activity were significantly improved only in the usual-dose HCQ group. In addition, changes in the serum complement levels in the usual-dose HCQ group were more dramatic than in the low-dose HCQ group six months after the initiation of HCQ administration. Adverse events were more frequent in the usualdose HCQ group than in the low-dose HCQ group (30.4% and 13.3%, respectively). Conclusion HCQ therapy is effective for maintenance therapy of SLE patients. The usual dose of HCQ may have some advantage in ameliorating low complement levels.
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