Prevalence and risk factors of monoclonal gammopathy in patients with autoimmune inflammatory rheumatic disease: A systematic review and meta-analysis.

OBJECTIVE: To systemically investigate the prevalence and risk factors of monoclonal gammopathy (MG) in patients with autoimmune inflammatory rheumatic disease (AIIRD). METHODS: A literature search was conducted using databases of PubMed, EMBASE, and Web of Science for relevant studies from inception to 31 July 2021. The pooled prevalence, odds ratio (OR), weighted mean difference (WMD), and 95% confidence interval (CI) were calculated with Stata 16.0 using a random or fixed effects model. RESULTS: In 17 included studies involving 6667 AIIRD patients, the pooled prevalence of MG in AIIRD patients was 7% (95%CI: 0.06-0.09). Compared to general populations, patients with Sjögren's syndrome (SS) possessed the highest risk for MG (OR 4.51; 95%CI: 3.39-5.74), followed by systemic lupus erythematosus (OR 3.99; 95%CI: 2.84-5.14), ankylosing spondylitis (OR 2.04; 95%CI: 1.11-2.97), and rheumatoid arthritis (OR 2.00; 95%CI: 1.79-2.22). Older age (WMD = 5.17 years; 95%CI: 0.68-9.66), higher erythrocyte sedimentation rate (WMD = 14.04 mm/H; 95%CI: 7.77-20.30), higher serum gammaglobulins level (WMD = 1.92 mg/dl, 95%CI: 0.51-3.32) were associated with a greater risk of MG in AIIRD patients. CONCLUSIONS: MG prevalence was higher in AIIRD patients, especially in SS patients. Older age, higher erythrocyte sedimentation rate, and hypergammaglobulins were risk factors for MG in AIIRD patients.

The efficacy and safety of tacrolimus on top of glucocorticoids in the management of IIM-ILD: A retrospective and prospective study.

Objective: To examine the efficacy of tacrolimus on top of glucocorticoids (GCs) in the management of idiopathic inflammatory myopathies-associated interstitial lung disease (IIM-ILD) and further assess the therapeutic benefit and safety of low-dose pirfenidone followed above treatments. Methods: The retrospective study comprised 250 patients with IIM-ILD hospitalized in Tongji Hospital from 2014 to 2020. Demographic data, survival outcomes, and recurrence rates over the 1-year follow-up period were retrospectively analyzed. These patients were divided into two groups based on treatment with tacrolimus alone or other conventional immunosuppressants. Endpoints were compared by adjusted Cox regression model using inverse probability of treatment weighting to minimize treatment bias and potential confounders. For the prospective study, IIM-ILD patients treated with tacrolimus alone or tacrolimus combined with low-dose pirfenidone were enrolled from 2018 to 2020. Clinical characteristics, survival outcomes and multifarious assessment scales were followed up at baseline, 3, 6 and 12 months. The primary endpoint was 12-month survival rate and the secondary endpoints included respiratory-related events, adverse events, exacerbation in HRCT findings and laboratory parameters during therapy courses, and changes in respiratory function. Results: For the retrospective study, tacrolimus group (n=93) had a significantly higher survival rate (weighted HR=0.330, p=0.002) and a lower relapse rate (weighted HR=0.548, p=0.003) compared with patients treated with other types of immunosuppressant (n=157) after adjustment. The prospectively enrolled 34 IIM-ILD patients were treated with tacrolimus (n=12) or tacrolimus combined with low-dose pirfenidone (n=22). After 12 months of treatment with tacrolimus, patients in the prospective cohort showed significant improvements in cardio-pulmonary function, disease activity, muscle strength, and mental scale from baseline. Subgroup analysis indicated that patients with tacrolimus and pirfenidone combination therapy showed lower chest HRCT scores (p=0.021) and lower respiratory-related relapse rates than those in tacrolimus monotherapy group (log-rank p=0.0029). The incidence rate of drug-associated adverse events (AEs) was comparable between two groups and none of the patients discontinued the treatment due to severe AEs. Conclusion: Tacrolimus is well-tolerated and effective in the treatment of IIM-ILD. Furthermore, low-dose pirfenidone add-on treatment seems result in favorable improvements in pulmonary involvements for IIM-ILD patients. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2100043595.

Clinical value of 18F-FDG PET/CT in IgG4-related disease.

OBJECTIVE: To investigate the clinical value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in IgG4-related disease (IgG4-RD). METHODS: Seventy two patients diagnosed with IgG4-RD who underwent PET/CT were included. Correlations between clinical variables and PET/CT findings were analyzed by Spearman's correlation test. Conventional radiology was compared to PET/CT to evaluate detection discrepancies. The detection ability of insidious organ involvement by PET/CT at disease onset was investigated. The utility value of PET/CT for the 2019 ACR/EULAR classification criteria was analyzed with the multivariate logistic analysis and ROC curve. RESULTS: SUVmax of main involved organ was positively correlated with IgG4-RD Responder Index (IgG4-RD RI), serum and tissue IgG4 levels and IgG4/IgG ratio, serum eosinophils counts and number of involved organs, while negatively correlated with serum IgM levels. PET/CT was superior in detecting organ/tissue involvements including prostate, gastrointestinal tract and lung compared with conventional imaging. For patients with pancreato-hepato-biliary or head-neck involvements at onset, PET/CT showed superiority in detecting insidious lesions. Multivariate analysis showed that disease duration, multiple-organ involvement, SUVmax of main involved organ and mean SUVmax of all involved organs were significantly associated with the fulfillment of the 2019 ACR/EULAR classification criteria. ROC curves indicated that the cut-off value for SUVmax of main involved organ and mean SUVmax of all involved organs for fulfillment of the 2019 ACR/EULAR classification criteria for IgG4-RD were 4.1 and 3.5, respectively. CONCLUSION: 18F-FDG PET/CT has potential capacity to monitor disease activity, evaluate organ involvements and assist in the classification criteria in IgG4-RD.

Experience of therapeutic plasma exchange in rheumatic diseases: Albumin may be a suitable substitute for plasma.

OBJECTIVES: In this study, we aimed to assess the value of therapeutic plasma exchange (TPE) in the treatment of rheumatic diseases and compare the safety of different replacement fluids used in TPE. PATIENTS AND METHODS: A total of 727 TPE procedures in 285 patients (57 males, 228 females; mean age: 39.7±15.4 years; range, 13 to 79 years) with rheumatic diseases between January 2011 and February 2019 were retrospectively analyzed. Data including demographic and clinical characteristics of the patients were recorded. Treatment response to TPE and adverse events were evaluated in all patients. RESULTS: Indications for TPE included 13 different disorders, with the majority being systemic lupus erythematosus (up to 50%). The mean number of TPE sessions was 2.55±1.00 per patient and the mean exchange plasma volume was 2,270±256 mL per session. Combined plasma and albumin was the most frequently used replacement fluid (69.5%), followed by albumin and plasma in 20.5% and 10.0% of episodes, respectively. Up to 73.7% (210/285) patients achieved clinical improvement after TPE treatment. Adverse events occurred in 15.1% (110/727) of all the procedures, and allergic reaction (34.5%) was the most common event. The overall incidence rate of complication was similar among the three types of replacement fluids (p=0.214). CONCLUSION: Based on our study results, TPE is an invasive, but safe, useful and, sometimes, essential tool with an acceptable risk/benefit ratio for most rheumatic diseases. Albumin can be used as a feasible substitute for plasma in case of shortage of blood resources.

Analysis of risk factors of interstitial lung disease and mortality rates in Chinese patients with idiopathic inflammatory myopathy.

AIM: To investigate the risk factors for interstitial lung disease (ILD) and prognosis in patients with idiopathic inflammatory myopathy (IIM). METHODS: A retrospective longitudinal study was performed in patients diagnosed with IIM between January 2012 and December 2018. RESULTS: The study cohort included 91 men and 195 women who were classified as having dermatomyositis (DM, n = 183), polymyositis (PM, n = 77), or clinical amyopathic DM (CADM, n = 26). ILD was identified in 46.5% (n = 133) of patients with IIM. The independent risk factors for ILD were age at disease onset, presence of anti-Ro-52 antibody, Gottron's papules, elevated serum immunoglobulin M levels and hypoalbuminemia. Older age at disease onset, ILD, malignancy, and increased serum aspartate aminotransferase and neutrophil-to-lymphocyte ratio (NLR) were identified as the independent predictors for mortality, whereas elevated serum albumin level was associated with a better prognosis. A total of 73 deaths (25.5%) occurred after a median follow-up time of 33 months. Infection (49.3%) was the leading cause of death. In the overall cohort, the 1-year, 5-year and cumulative survival rates were 83.2%, 74.2% and 69.4%, respectively. The receiver operating characteristic curve indicated that the optimal cut-off value of NLR for predicting death in IIM was 6.11. CONCLUSION: IIM patients have a poor prognosis with substantial mortality, especially in patients who have older age at onset, ILD, malignancy and higher NLR. Close monitoring and aggressive therapies are required in patients having poor predictive factors.

A medical mirroring: chronic myelomonocytic leukemia mimicking immunoglobulin G4-related disease.

Chronic myelomonocytic leukemia (CMML) can be complicated by autoimmune features associated with rheumatologic disorders, which have been commonly reported by more researches currently. The intrinsic correlation between CMML and autoimmune diseases can create significant pitfalls in differential diagnosis. CMML occasionally presents with clinical and histopathological manifestations that are similar to those of Immunoglobulin G4-related disease (IgG4-RD), a newly recognized systemic autoimmune disorder. Both CMML and IgG4-RD can have significant overlaps due to the common nature of these systemic disorders, especially when atypical clinical phenotypes are present. It is significant for physicians to accurately distinguish CMML and IgG4-RD because the therapy modalities could differ extremely between the two entities. Here we present a unique case of a 70-year-old female who had a condition that mimicked the onset of IgG4-RD not only in terms of clinical manifestations but also in serology and histopathology analyses. Following a series of rigorous examinations, this patient was ultimately diagnosed as having CMML. Herein, we discuss the aspects of IgG4-RD's differential diagnosis and the need for careful comparison of clinical and laboratory features as well as consideration of the pathogenesis of both IgG4-RD and CMML. We also stress a concept that the presence of autoimmune conditions cannot be the sole basis to exclude diagnosis of CMML, as these disorders can appear concomitantly.