Comparison of Relapsing Polychondritis Patients with and Without Respiratory Involvement Based on Chest Computed Tomography: A Retrospective Cohort Study

Background Relapsing polychondritis (RP) patients with tracheal cartilage involvement are different from other patients. The objectives of this study were to compare the clinical features and disease patterns between respiratory involvement subgroup and non-respiratory involvement subgroup according to chest computed tomography. Method We performed a retrospective cohort study collected RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 - August 2021. Results The incident of costochondritis was more frequent in RP patients with respiratory involvement(p=0.03), the incidence of inflammatory eye disease(p=0.001) and auricular chondritis(p=0.001) was less frequent in RP respiratory involvement patients, compared with those of RP patients without respiratory involvement. Correlation analysis showed that a negative correlation between respiratory involvement and auricular chondritis (r=-0.58, p < 0.01), and between respiratory involvement and inflammatory eye disease (r=-0.45, P < 0.01). Auricular chondritis was positively correlated with inflammatory eye disease (r=0.49, P < 0.01). Compared with non-respiratory involvement subgroup, the incidence of pulmonary infection marginally increased in respiratory involvement subgroup(p=0.06). Inflammatory indexes except for CAR were significantly higher in respiratory involvement subgroup, subgroup analysis found that there was no significant relationship between inflammatory indexes and pulmonary infection. Conclusion RP patients with respiratory involvement was characterized by higher rate of costochondritis and pulmonary infection, fewer inflammatory eye disease and auricular chondritis compared to non-respiratory involvement. Increase inflammatory indexes may suggested that patients with respiratory involvement had a higher disease activity index of RP. The probability of survival was not significant between two subgroups.

F-18 FDG PET/CT in Relapsing Polychondritis Patients with Initial Respirotory Symptoms: Imaging Features and Association with Pulmonary Function and Disease Activity

Background: To summarize F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging features of relapsing polychondritis (RP) and to evaluate the feasibility of imaging parameters in the estimation of pulmonary function and disease activity in a cohort of RP patients with airway involvement.Methods: Thirty RP patients with respiratory symptoms who underwent PET/CT scans before corticosteroid treatment were included. Six patients underwent another post-therapeutic PET/CT scan. Imaging features were described by consensus, and FDG uptake values (SUVmax, PET FDG Burden Score (PETFBS) and PETCTindex) either for global cartilages or for the airway were calculated to correlate with clinical symptoms, pulmonary functional parameters and serological inflammatory markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).Results: Laryngo-tracheo-bronchial involvement was detected by PET/CT for all patients with increased FDG uptake in 28/30 patients. The incidence of positive PET was higher in segments with wall thickening (52.68% vs. 15.48%) but was not associated with calcification or stenosis. A total of 46.7% (14/30) of patients presented with sole respiratory symptoms, while PET/CT revealed additional abnormalities in addition to laryngo-tracheo-bronchia. FDG uptake values negatively correlated with disease duration but not with fever. All FDG uptake values showed a positive correlation with FEV1/FVC, with the highest coefficient for SUVmax in the airway (rs =0.628). CRP and ESR were negatively correlated with PETFBS and PETCTindex but not with SUVmax. The largest Spearman correlation coefficient resulted in PETFBS in the airway (rs =0.67). Re-examination PET/CT in 6 patients revealed partial therapeutic response (n = 4), stable disease (n = 1) and progressive disease (n = 1).Conclusion: PET/CT is a valuable tool for assessing RP with airway involvement, especially for patients who present with sole respiratory symptoms. SUVmax and PETFBS have distinct advantages in the clinical evaluation of RP with respect to pulmonary function and disease activity.

Nationwide cross-sectional survey of patients with relapsing polychondritis in 2019 demonstrates reduction of airway involvement compared with that in 2009

We conducted retrospective cohort studies of patients with relapsing polychondritis (RP) twice in 2009 and 2019, using a physician questionnaire. We compared the patients’ clinical statuses between the years. Age and gender were comparable between the two surveys. Mean disease duration was longer in 2019 survey (8.3 years) than that in 2009 survey (4.8 years, P < 0.001). The mortality rate declined in 2019 survey compared with those in 2009 survey (from 9.2 to 1.6%, P < 0.001). Incidence of airway involvement decreased in 2019 survey compared with that in 2009 survey (from 49 to 37%, P = 0.012). In 2019 survey, we found more frequent use of biological agents and immunosuppressants in patients with airway involvement. When we focused on RP patients with airway involvement, physicians in 2019 chose methotrexate and calcineurin inhibitors preferentially, compared with azathioprine and cyclophosphamide. Of note is that increased use of infliximab was observed in RP patients with airway involvement, but not in those without. Reduction of airway involvement and mortality in patients with RP was observed in 2019 survey. The reduction may associate with the frequent use of biologics including infliximab in RP patients with airway involvement.

Clinical characteristics and disease patterns of patients with relapsing polychondritis: a retrospective cohort

Background Relapsing polychondritis (RP) is a rare autoimmune disease affected various cartilage, Patients with tracheal cartilage involvement are different from other patients. The objectives of this study were to allocated RP patients into two subgroups by chest computed tomography (CT) and compare the clinical features and disease patterns of each group.Methods A retrospective cohort study collected RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 - August 2021. Patients were divided into two groups: respiratory involvement group and non-respiratory involvement group according to chest CT.Results In our study, respiratory involvement found in 59.7% (n=43) patients, which had higher rate of costochondritis, fewer rate of Inflammatory eye disease and auricular chondritis than those in non-respiratory involvement. Compared with non-respiratory involvement subgroup, The incidence of pulmonary infection marginally increased and those inflammatory indexes except for CAR were significantly higher in respiratory involvement subgroup, further subgroup analysis found that there was no significant relationship between inflammatory indexes and pulmonary infection. Finally, 5 patients died during the follow-up in this cohort with a median follow-up time of 6 years (range 3-8 years).Conclusion 59.7% of patients had respiratory involvement according to chest CT findings in our cohort, which had a strong inverse relationship between respiratory and auricular, ocular involvement. Increase inflammatory indexes were not correlated with pulmonary infection, suggesting that patients with respiratory involvement had a higher disease activity index of RP. The probability of survival was not found significant in two subgroups.

A high-throughput amplicon screen for somatic UBA1 variants in Cytopenic and Giant Cell Arteritis cohorts

Somatic mutations in the gene encoding the major E1 ubiquitin ligase, UBA1, were recently identified as a cause of VEXAS, a late-onset acquired auto-inflammatory syndrome. Differential diagnoses for patients subsequently found to have VEXAS include relapsing polychondritis, Sweet’s syndrome, myelodysplastic syndrome (MDS), giant cell arteritis (GCA) and undifferentiated systemic autoinflammatory disease (uSAID). We therefore sought to screen DNA from individuals with a non-diagnostic cytopenia or GCA, for known VEXAS-associated mutations. To this end, we developed a multiplexed UBA1 amplicon sequencing assay, allowing quick screening of large cohorts while also providing sufficient sequencing depth to identify somatic mutations to an allele frequency <1%. Using this assay, we screened genomic DNA from 612 males diagnosed with GCA, and bone marrow DNA from 1,055 cases with an undiagnosed cytopenia. No GCA cases were found to have UBA1 mutations, however 4 different mutations in the cytopenic cohort were identified in 7 individuals. Furthermore, we describe a female case identified in the screen with a UBA1 mutation and all VEXAS-associated phenotypes, but without Monosomy X. Our study suggests that, despite the overlap in clinical features, VEXAS is rarely misdiagnosed as GCA, but identified in 1.0% of males with an undiagnosed cytopenia. The identification of a UBA1 variant in a female case adds further evidence that VEXAS should not be ruled out as a differential diagnosis in females with VEXAS-like symptoms.Key points-Mutations in UBA1 exon 3 have been associated with VEXAS syndrome-UBA1 exon 3 was screened in 1650 patients with cytopenia or GCA by amplicon sequencing.-6 males were identified from the non-diagnostic cytopenia cohort (1.0%) with UBA1 mutations.-A female with a somatic UBA1 mutation was identified without Monosomy X