Disease Modification in Gout: A Qualitative Study of Gout Expert Rheumatologists

Objective To examine healthcare provider views of disease modification in gout to potentially derive a provisional set of domains for disease modification in gout. Methods We performed a qualitative nominal group (NG) study with 20 gout experts (15 were authors/expert panel members of the 2012 and/or 2020 ACR gout guidelines, and/or 2015 ACR/EULAR gout classification criteria) about what constitutes “disease modification” in gout – “What sorts of things do you think constitute a change in the course of disease in gout? (positive); What are all the ways in which gout as a disease can be modified?” Results Decrease in gout flares was rated #1 rank in all six NGs as indicative of disease modification in gout, followed by serum urate (SU) lowering, which was rated #1 rank in 1 of the 6 NGs (tied score with flares in one NG). Other components of gout disease modification were to improve quality of life/productivity; restore function; reduce/eliminate pain; reduce tophi burden; and joint preservation or resolution of joint damage. Potential additional components that were not ranked in the top 3 votes within each NG were: Decrease healthcare cost/utilization; cardiovascular/renal morbidity/mortality reduction; and stop urate crystals formation. Conclusion This qualitative study provides a provisional set of domains for disease modification in gout. Future studies for the development of thresholds for disease modification domains, and wider consensus on this definition are needed.

Association of Hidradenitis Suppurativa (HS) with Autoimmune Disease and Autoantibodies

Objective There is thought to be an association between Hidradenitis Suppurativa (HS) and autoimmune diseases. This retrospective longitudinal cohort study looked to identify whether certain autoimmune diseases or autoantibody specificities are more closely associated with HS than others and, whether such associations are related to severity of HS. Methods Patients were identified using the SlicerDicer search tool in Epic from January 1, 2010 through August 15, 2020. Search criteria included HS diagnosis by ICD-10 code and at least one visit in dermatology. Charts were reviewed to determine HS disease severity, treatment modalities, presence of autoimmune disease, and autoantibody positivity. Results 627 patients were identified. Most patients were females (75.3%) and had obese BMIs (71.1%), but there were no significant demographic differences between HS patients with and without autoimmune diseases. 101 (16.1%) patients in the total cohort had at least one autoimmune disease, most commonly, thyroid disease, lupus, psoriasis, and inflammatory bowel disease (IBD). 212 patients were also tested for the presence of autoantibodies. The most common positive autoantibody, found in 54 patients (28.4%), was antinuclear antibody (ANA). 54 patients with more severe HS disease manifestations required biologic medications to treat their HS. Neither HS severity nor biologic treatment was associated with presence of autoimmune disease or positive autoantibodies. Conclusion In a large cohort of patients with HS followed longitudinally, autoimmune disorders (especially lupus, psoriasis and IBD) and presence of autoantibodies were more commonly observed than expected in the normal population.

Pneumocystis pneumonia and rheumatic disease: diagnostic potential of circulating microbial cell-free DNA sequencing

Objectives This study aimed to explore the clinical utility of circulating microbial cell-free DNA (cfDNA) sequencing as a non-invasive approach for diagnosing Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients with rheumatic disease (RD). Methods The study included 72 RD patients with suspected lung infections admitted to Renji hospital. Eighteen individuals were diagnosed with PJP, and 54 patients without PJP were enrolled as control group. All patients had undergone pulmonary computed tomography scans, and blood and respiratory tract specimens had been subjected to metagenomic next-generation sequencing (mNGS) and conventional microbiological tests. The clinical and laboratory parameters were collected and efficacy of circulating microbial cfDNA of PJP was evaluated. Results Of the 18 patients with PJP, the average age was 53.0 years and the median time between RD diagnosis and PJP presentation was 126 days (IQR 84.0–176.3). Low circulating CD4+ cell counts and a lack of PJP prophylaxis were observed in the patients. Metagenomic NGS of circulating microbial cfDNA was performed in 69 patients including 15 cases with PJP and 54 controls. Twelve (80%) of 15 analysed blood samples contained Pneumocystis jirovecii (PJ) sequences in PJP group with PJ not detected among controls. There was a significant difference between PJP and non-PJP groups (p < 0.001) with a sensitivity of 83.3% and specificity of 100% when using plasma cfDNA sequencing. Higher β-D-glucan levels were found in patients with positive results for PJ in plasma cfDNA sequencing. Conclusion Metagenomic NGS of circulating microbial cfDNA is a potential tool for diagnosing PJP in RD patients.

Therapeutic efficacy of denosumab for rheumatoid arthritis: a systematic review and meta-analysis

Objectives Denosumab is used for osteoporosis, as it inhibits osteoclast maturation and suppresses bone resorption. Although denosumab is expected to inhibit the bone erosion in rheumatoid arthritis (RA), its therapeutic efficacy is not well established. The aim of this study was to estimate the effects of denosumab on RA through a meta-analysis. Methods A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Web of Science and Scopus were searched for original studies providing information on bone mineral density (BMD), joint destruction and disease activity in denosumab-treated RA. A random-effects model was used in the meta-analysis. Results Of the 367 studies identified, 18 met the selection criteria. The BMDs of the lumbar spine, total hip and femoral neck at 12 months after denosumab treatment increased by 5.27% (95% confidence interval: 4.37–6.18), 2.82% (2.46–3.18) and 3.07% (2.66–3.48), respectively. In the sensitivity analysis, age and gender tended to influence the effect of denosumab therapy on the variation rate of BMD, but not glucocorticoid use. The changes in the modified total sharp, erosion and joint space narrowing scores at 12 months after denosumab treatment were significantly smaller with denosumab than with placebo, although the disease activity score did not change after denosumab treatment. Conclusion Although denosumab has an inhibitory effect on the bone resorption in RA, its effects may be influenced by age and gender of RA, but not glucocorticoid use.

Validation of the Southend Giant Cell Arteritis Probability Score in a Scottish single centre fast-track pathway

Objective To externally validate the Southend GCA Probability Score (GCAPS) in patients attending a GCA Fast-Track Pathway (GCA FTP) in NHS Lanarkshire. Methods Consecutive GCA FTP patients between November 2018 and December 2020 underwent GCAPS assessment as part of routine care. GCA diagnoses were supported by USS +/- TAB and confirmed at 6 months. Percentages of patients with GCA according to GCAPS risk group, performance of total GCAPS in distinguishing GCA/non-GCA final diagnoses, and test characteristics using different GCAPS binary cut-offs, were assessed. Associations between individual GCAPS components and GCA, and the value of USS and TAB in the diagnostic process, were also explored. Results 44/129 patients were diagnosed with GCA, including 0/41 GCAPS low risk patients (GCAPS <9), 3/40 medium risk (GCAPS 9–12), and 41/48 high risk (GCAPS >12). Overall performance of GCAPS in distinguishing GCA/non-GCA was excellent [ROC AUC 0.976 (95% CI 0.954–0.999)]. GCAPS cut-off ≥10 had 100.0% sensitivity and 67.1% specificity for GCA. GCAPS cut-off ≥13 had highest accuracy (91.5%), with 93.2% sensitivity and 90.6% specificity. Several individual GCAPS components were associated with GCA. Sensitivity of USS increased by ascending GCAPS risk group (nil, 33.3%, 90.2% respectively). TAB was diagnostically useful in cases where USS was inconclusive. Conclusion This is the first published study describing application of GCAPS outside the specialist centre where it was developed. Performance of GCAPS as a risk stratification tool was excellent. GCAPS may have additional value for screening GCA FTP referrals and guiding empirical glucocorticoid treatment.