Lung ultrasound in the assessment of interstitial lung disease in patients with connective tissue disease: Performance in comparison with high-resolution computed tomography.

OBJECTIVE: To investigate clinical relevance of performing lung ultrasound (LUS) in patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) in comparison with high-resolution computed tomography (HRCT). METHODS: This single-centre study enrolled eligible patients with CTD-ILD from the prospective LUS registry. Total B-lines were detected by assessment at 14 sites via LUS. Forced vital capacity, diffusing lung capacity for carbon monoxide (DLCO), DLCO/alveolar volume, 6-minute walking distance, and the ILD-GAP index were used as ILD prognostic parameters. Correlations were examined using single and multiple regression analyses. RESULTS: Sixty-seven patients were enrolled, including 29 with idiopathic inflammatory myopathy or anti-synthetase syndrome, 25 with systemic sclerosis (SSc), 10 with rheumatoid arthritis, and 3 with mixed connective tissue disease. The total number of B-lines correlated with ILD extent on HRCT in patients with CTD-ILD (r = 0.66; P < 0.001), particularly in patients with SSc-ILD (r = 0.78; P < 0.001). Total B-lines and ILD extent on HRCT showed comparable correlations with prognostic parameters, while multiple regression analysis revealed the limited benefit of performing LUS in addition to HRCT in predicting correlations with prognostic factors. CONCLUSIONS: LUS serves as an alternative tool for assessing the severity and prognosis of patients with CTD-ILD.

Delayed adverse events following COVID-19 vaccination in patients with systemic sclerosis and other autoimmune diseases: a substudy of the COVAD-2 cohort.

Data on short-term safety of COVID-19 vaccination in patients with systemic sclerosis (SSc) were explored previously in the first COVID-19 vaccination in autoimmune diseases (COVAD) survey conducted in 2021. However, delayed adverse events (ADEs) (occurring > 7 days post-vaccination) are poorly characterized in these patients with SSc. In this study, we analysed delayed COVID-19 vaccine-related ADEs among patients with SSc, other systemic autoimmune and inflammatory disorders (SAIDs) and healthy controls (HCs) using data from the second COVAD study conducted in 2022. The COVAD-2 study was a cross-sectional, patient self-reported global e-survey conducted from February to June 2022. Data on demographics, SSc/SAID disease characteristics, COVID-19 infection history, and vaccination details including delayed ADEs as defined by the Centre for Disease Control were captured and analysed. Among 17,612 respondents, 10,041 participants fully vaccinated against COVID-19 were included for analysis. Of these, 2.6% (n = 258) had SSc, 63.7% other SAIDs, and 33.7% were HCs. BNT162b2 Pfizer (69.4%) was the most administered vaccine, followed by MRNA-1273 Moderna (32.25%) and ChadOx1 nCOV-19 Oxford/AstraZeneca (12.4%) vaccines. Among patients with SSc, 18.9% reported minor, while 8.5% experienced major delayed ADEs, and 4.6% reported hospitalization. These frequencies were comparable to those of the ADEs reported by other patients with SAIDs and HCs. However, patients with SSc reported a higher frequency of difficulty in breathing than HCs [OR 2.3 (1.0-5.1), p = 0.042]. Patients with diffuse cutaneous SSc experienced minor ADEs [OR 2.1 (1.1-4.4), p = 0.036] and specifically fatigue more frequently [OR 3.9 (1.3-11.7), p = 0.015] than those with limited cutaneous SSc. Systemic sclerosis patients with concomitant myositis reported myalgia more frequently [OR 3.4 (1.1-10.7), p = 0.035], while those with thyroid disorders were more prone to report a higher frequency of joint pain [OR 5.5 (1.5-20.2), p = 0.009] and dizziness [OR 5.9 (1.3-27.6), p = 0.024] than patients with SSc alone. A diagnosis of SSc did not confer a higher risk of delayed post-COVID-19 vaccine-related ADEs overall compared with other SAIDs and HCs. However, the diffuse cutaneous phenotype and coexisting autoimmune conditions including myositis and thyroid disease may increase the risk of minor ADEs. These patients may benefit from pre-vaccination counselling, close monitoring, and early initiation of appropriate care in the post-COVID-19 vaccination period.

Role of rituximab in the treatment of systemic sclerosis: A literature review.

This literature review aimed to evaluate the effectiveness of rituximab (RTX) in patients with systemic sclerosis (SSc). PubMed was searched for articles, published through 31 March 2022, on any controlled studies using RTX in the treatment of SSc. Of 85 identified articles, 9 were selected by title/abstract screening and full text examination. All nine articles reported outcomes of forced vital capacity (%FVC), and seven reported those of modified Rodnan skin scores (mRSS). The results showed that among the seven controlled studies evaluating skin lesions in patients with SSc, four showed a significant improvement of mRSS by RTX when compared with a control group, whereas three showed no significant effect. Among the nine controlled studies evaluating lung lesions, five showed a significant improvement of %FVC compared with a control group, whereas four showed no significant effect. In conclusion, RTX may be effective in the treatment of skin and lung lesions in patients with SSc. The profiles of SSc patients for whom RTX was indicated were unclear, although patients with diffuse cutaneous SSc and those positive for anti-topoisomerase I antibody were considered potential targets. Additional studies are needed to assess the long-term effectiveness of RTX in the treatment of patients with SSc.

Outcomes in patients with systemic sclerosis undergoing early vs delayed intervention with potential disease-modifying therapies.

OBJECTIVE: To examine whether early therapeutic intervention, compared with delayed intervention, is beneficial for patients with early SSc. METHODS: This is a single-centre, retrospective cohort study of SSc patients who received CYC, MMF, MTX or tocilizumab for diffuse cutaneous SSc (dcSSc) or interstitial lung disease (ILD) within 6 years after disease onset. The patients were divided into early and delayed intervention groups based on the disease duration of ≤18 and >18 months at treatment introduction, respectively. Clinical worsening was defined as the development of any original or revised ACR Composite Response Index in SSc (CRISS) step 1 event or progressive fibrosing ILD (PF-ILD). RESULTS: There was no difference in baseline characteristics between the early (n = 25) and delayed (n = 21) intervention groups except forced vital capacity, which was better in the early vs delayed intervention groups. The early intervention group less frequently had stable pulmonary function over 1 year than did the late intervention group (odds ratio 0.087, 95% CI: 0.0079, 0.51; P = 0.003). The active disease was significantly decreased from 79% to 42% in the early intervention group (P = 0.007), but the change in the delayed intervention group was not statistically significant (68% to 42%; P = 0.11). Cumulative rates free from clinical worsening events defined by revised ACR-CRISS and PF-ILD were significantly higher in the early vs delayed intervention groups (P = 0.03 and 0.003, respectively). CONCLUSION: A therapeutic 'window of opportunity' might exist in SSc patients.

Infection with capsular genotype K1-ST23 hypervirulent Klebsiella pneumoniae isolates in Japan after a stay in East Asia: Two cases and a literature review.

Disseminated community-acquired infections caused by the hypervirulent Klebsiella pneumoniae (hvKp) among relatively healthy individuals in East Asia have been reported in recent years. Isolate of the capsular genotype K1, belonging to sequence type (ST) 23, is the most common causative agent of this disease. We experienced two cases of K1-ST23 infection with a travel history in East Asia, and hvKp infection was diagnosed after entering or returning to Japan. Case 1 was a 45-year-old Myanmar seaman with a history of ischemic heart disease who developed a fever on board and was transported to Japan via Shanghai and Taiwan. He had multiple disseminated lesions due to K. pneumoniae; other symptoms included liver abscess, intraocular inflammation, intraventricular thrombosis, brain abscess, and bloodstream infection. Along with antimicrobial treatment, drainage of liver abscesses and surgery for intraocular inflammation and intraventricular thrombosis were required. The patient was discharged 93 days after admission, with little improvement in the visual acuity. Case 2: A 29-year-old Japanese man with no underlying disease developed a prostate abscess and bloodstream infection caused by K. pneumoniae after a trip to Korea. However, he improved only with antimicrobial treatment. K. pneumoniae in both cases were identified to have the rmpA gene, with capsular genotypes K1 and ST23. Further, both cases were considered to have been infected with hvKp during their stay in East Asia. In conclusion, it is important to suspect disseminated disease and perform a systemic search, taking into account that hvKp may be present in cases of Klebsiella infection acquired from East Asia.