Predictors of rapidly progressive interstitial lung disease and mortality in patients with autoantibodies against melanoma differentiation-associated protein 5 dermatomyositis.

OBJECTIVE: Anti-melanoma differentiation-associated protein 5 (MDA5)-positive DM is associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This multicentre retrospective study aimed to identify predictors of mortality and RP-ILD. METHODS: Anti-MDA5-positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System. Clinical characteristics were reviewed. Risk factors for mortality and RP-ILD were identified. RESULTS: Among the 116 recruited patients, 100 (86.2%) had ILD, 47 (40.5%) had RP-ILD and 44 (37.9%) patients died. Cox regression analysis revealed RP-ILD [hazard ratio (HR) 9.735 (95% CI 3.905, 24.272)], age >52 years [HR 4.750 (95% CI 1.692, 13.333)], ferritin level >2800 pmol/l [HR 3.042 (95% CI 1.323, 6.997)] and lactate dehydrogenase (LDH) >400 IU/l [HR 2.290 (95% CI 1.009, 5.198)] were independent predictors of mortality. With regard to RP-ILD, analyses showed that potential predictors at baseline included age >50 years [HR 2.640 (95% CI 1.277, 5.455)], LDH >300 IU/l [HR 3.189 (95% CI 1.469, 6.918)], fever [HR 1.903 (95% CI 0.956, 3.790)] and neutrophil:lymphocyte ratio >7.0 [HR 1.967 (95% CI 0.942, 4.107)]. We proposed a prediction model based on fever, LDH, age and white cell count (FLAW) to stratify the risk of development of RP-ILD. The probability of RP-ILD in a patient with a score of 4 was 100%. A small internal validation cohort showed the odds of RP-ILD with FLAW scores of 0, 1, 2 and 3 were 0%, 0%, 42.9% and 75%, respectively. CONCLUSIONS: Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates. The FLAW model maybe useful to predict the development of RP-ILD.

Cancer risk and chemoprevention in Chinese inflammatory bowel disease patients: a population-based cohort study.

Background and aim: Role of 5-aminosalicylic acid (5-ASA), statin and aspirin in reducing cancer risks in inflammatory bowel disease (IBD) remains controversial. We aimed to examine chemo-preventive effects of these drugs in all cancers in IBD in population-based setting.Methods: IBD patients diagnosed between 2000 and 2016 were identified from the Hong Kong IBD Registry and followed from IBD diagnosis until first cancer occurrence. Primary outcome was cancer development ≥6 months after IBD diagnosis. Adjusted hazard ratio (aHR) with 95% confidence interval (CI) was estimated with Cox proportional hazards model. Additional effects of statin and aspirin on chemoprevention were also assessed.Results: Amongst 2103 IBD patients (857 Crohn's disease, 1246 ulcerative colitis; mean age 40.0 ± 15.6; 60.3% male) with 16,856 person-years follow-up, 48 patients (2.3%) developed cancer. The 5-r, 10-r and 15-year (95% CI) cumulative incidence of cancer were 1% (0.6 - 1.5%), 2.8 (2.0 - 3.9%) and 4.8 (3.4 - 6.5%), respectively. Total 1891 (89.9%) and 222 (10.6%) patients have received one or more prescriptions of 5-ASA and statin respectively. In multivariable analysis adjusted for age, gender, smoking status, IBD type and use of other medications, use of 5-ASA or statin was not associated with a reduced risk of cancer development (5-ASA: aHR 1.22, 95% CI: 0.60-2.48, p = .593; statin: aHR 0.48, 95% CI: 0.14-1.59, p = .227). Adding aspirin was not associated with a lowered cancer risk (aHR 1.18, 95% CI: 0.32-4.35, p = .799).Conclusion: Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit.Key summaryInflammatory bowel diseases (IBD) including Crohn's disease and ulcerative colitis are associated with increased risk of both intestinal and extra- intestinal cancers.Various medications including 5-aminosalicylate acid (5-ASA), statins and aspirin have been studied for their chemoprevention effects. However, most studies focused on colorectal cancer only and showed conflicting evidence. No studies so far looked at the effects of these medications on all cancer development in IBD.The 5-, 10- and 15-year (95% confidence interval) cumulative incidence of cancer in Chinese IBD patients were 1 (0.6-1.5%), 2.8 (2.0-3.9%) and 4.8 (3.4-6.5%), respectively.Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit.

Spondyloarthritis: How far are we from precision medicine?

Spondyloarthritis (SpA) is a family of heterogenous diseases consisting of different phenotypes. The exact disease mechanism remains unclear but evidence shows the complex pathophysiology with interplay between genome, microbiome, and immunome. Biologic DMARDs have markedly improved patients' disease control and quality of life. However, treatment response varies among patients. There is a growing need to identify biomarkers for the diagnosis, prognosis, prevention, and treatment of SpA. Genomic studies have been the research focus in the past two decades and have identified important genes involved in SpA. In recent years, emerging evidence supports the link between gut and joint inflammation in SpA, in which the role of gut microbiome in SpA is of great interest. Herein, potential genetic and gut microbial biomarkers for predicting treatment response are discussed. Novel strategies targeting dysbiosis in SpA are also summarized. These results represent a significant step toward precision medicine for patients with SpA.

Seasonal Effect on Disease Onset and Presentation in Anti-MDA5 Positive Dermatomyositis.

OBJECTIVE: To investigate the seasonal variation of disease onset and presentation in an ethno-geographically homogeneous cohort of patients with anti-MDA5 positive dermatomyositis (DM). METHODS: This was a multi-centered, retrospective cohort study. Adult Chinese anti-MDA5 positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System from 2015 to 2020. Equal number of IIM patients without anti-MDA5 antibody were selected as controls. Line blot immunoassay was used to detect the autoantibodies. The onset of disease, presenting clinical features and subsequent complications were analyzed for any seasonality. RESULTS: A total of 110 patients with anti-MDA5 positive DM were studied. The mean age at diagnosis was 53.0 ± 12.3 years and the mean follow-up duration was 20.6 ± 23.1 months. Two third of the patients (66%) had the clinically amyopathic phenotype. Most patients (86%) had interstitial lung disease (ILD) and 42% developed rapidly progressive ILD (RP-ILD). The mortality was 40% and the commonest cause was RP-ILD. Chi-square test showed significantly less patients had symptom onset in July to September. However, no particular seasonal pattern was observed in the anti-MDA5 negative IIM controls. RP-ILD occurred more frequently in patients with disease onset in October to December. Anti-MDA5 positive DM patients with disease onset in warmer months (April to September) were more likely to have clinical muscle involvement. CONCLUSION: Apparent seasonal patterns were noted in our ethno-geographically identical anti-MDA5 positive DM patients, but not in IIM patients in general. Certain environmental factors, particularly infection, might be implicated.

Performance of the 2017 European Alliance of Associations for Rheumatology/American College of Rheumatology Classification Criteria in Patients With Idiopathic Inflammatory Myopathy and Anti-Melanoma Differentiation-Associated Protein 5 Positivity.

OBJECTIVE: This study aimed to evaluate whether the 2017 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) could appropriately classify the diagnosis in adult patients with anti-melanoma differentiation-associated protein 5 (anti-MDA-5)-positive IIM. In addition, this study sought to determine whether a status of anti-MDA-5 positivity could be incorporated into the EULAR/ACR IIM classification criteria set and whether the recently modified criteria based on the presence of myositis-specific autoantibodies (MSAs) could be used to appropriately classify the diagnosis in patients with anti-MDA-5-positive IIM. METHODS: Consecutive adult patients clinically diagnosed as having anti-MDA-5-positive IIM from 10 hospitals in Hong Kong were retrospectively recruited; patient characteristics were obtained from electronic medical records. We used a commercial line blot immunoassay to detect MSAs. We also determined a proposed set of phenotypic-serologic classification criteria specific for anti-MDA-5. RESULTS: In the patient cohort (n = 120; 31.7% with dermatomyositis, 68.3% with clinically amyopathic dermatomyositis [CADM]), the diagnosis could be classified with the EULAR/ACR criteria in 86 patients (71.7%) and with the Bohan and Peter criteria in 49 patients (40.8%). However, when combined with criteria specifically modified for CADM, the diagnosis could be classified by the Bohan and Peter criteria in 76.7% of patients. We observed that the sensitivity of the EULAR/ACR criteria could be improved to 98.3% if anti-MDA-5 antibody-positive status was considered as one of the criteria. The MSA-based criteria had 100% sensitivity. When we applied our proposed specific phenotypic-serologic criteria for the classification of patients with anti-MDA-5 antibodies, 97.5% of patients were able to be classified as having IIM. CONCLUSION: In this cohort of patients with anti-MDA-5-positive IIM, the diagnosis could not be classified by the EULAR/ACR criteria in almost 30% of patients. We suggest incorporating anti-MDA-5 antibody positivity as a criterion into existing criteria sets or developing specific criteria for patients with anti-MDA-5-positive IIM.

Gut Microbiome and Its Interaction with Immune System in Spondyloarthritis.

Emerging evidence suggests there is a gut-joint axis in spondyloarthritis (SpA). In a study, subclinical gut inflammation occurred in nearly 50% of SpA. Chronic gut inflammation also correlated with disease activity in SpA. Trillions of microorganisms reside in the human gut and interact with the human immune system. Dysbiosis affects gut immune homeostasis and triggers different autoimmune diseases including SpA. The absence of arthritis in HLA-B27 germ-free mice and the development of arthritis after the introduction of commensal bacteria to HLA-B27 germ-free mice proved to be the important role of gut bacteria in shaping SpA, other than the genetic factor. The recent advance in gene sequencing technology promotes the identification of microorganisms. In this review, we highlighted current evidence supporting the link between gut and axial SpA (axSpA). We also summarized available findings of gut microbiota and its interaction with the immune system in axSpA. Future research may explore the way to modulate gut microorganisms in axSpA and bring gut microbiome discoveries towards application.

Incidence and clinical course of COVID-19 in patients with rheumatologic diseases: A population-based study.

OBJECTIVES: Patients with rheumatologic diseases might be more susceptible to COVID-19 and carry a poorer prognosis. The aim of this study is to examine the incidence and outcomes of all COVID-19 patients with rheumatologic conditions in Hong Kong. METHODS: This is a population-based retrospective study. All patients tested positive for SARS-CoV-2 by PCR with a previous diagnosis of rheumatologic diseases were reviewed. The incidence of COVID-19 in patients with rheumatologic conditions was calculated and compared to the general population in Hong Kong. Descriptive data of those rheumatologic patients with COVID-19 and the clinical course of the index infection were presented. RESULTS: Up till 27 May 2020, there were 1067 cases of COVID-19 diagnosed in Hong Kong which had a population of 7.5 million. Out of the 39,835 patients with underlying rheumatologic diseases, we identified 5 PCR confirmed COVID-19 cases. The estimated incidence of COVID-19 was 0.0126% patients with rheumatologic diseases, compared to 0.0142% in the general population. All 5 patients had inflammatory arthropathies. One patient was on hydroxychloroquine and sulphasalazine, and one was on methotrexate. None of the 3534 patients on b/tsDMARDs was infected. Four patients had leucopenia/lymphopenia and stool viral PCR was positive in 3 patients. All patients made uneventful recovery without complications or flare of underlying diseases. CONCLUSIONS: We found no alarming signals of increased frequency or severity of COVID-19 in patients with rheumatologic diseases, although extrapolation of the results to other populations with different infection control strategies should be made with caution.

Cancer Risk in 2621 Chinese Patients with Inflammatory Bowel Disease: A Population-based Cohort Study.

BACKGROUND: Studies on cancer risk in inflammatory bowel disease (IBD) have yielded inconsistent results. We conducted a population-based study to determine the risk of cancer in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Using a territory-wide IBD registry in Hong Kong, we identified 2621 patients with IBD and no history of cancer from 1990 to 2016. We followed them from diagnosis until either September 2016, cancer development, proctocolectomy, or death. Standardized incidence ratios (SIRs) of overall cancer and site-specific cancers were calculated. RESULTS: Of 2621 patients with IBD (1108 CD; 1603 UC; median age, 49 yr; 59.5% men) followed for 26,234 person-years, 88 patients developed cancer after IBD diagnosis. Patients with CD had an increased risk of anorectal cancers (SIR 4.11; 95% confidence interval (CI), 1.84-9.14) and hematological cancers (SIR 3.86, 95% CI, 1.61-9.27) including leukemia (SIR 5.98; 95% CI, 1.93-18.54). Nonmelanoma skin cancer was significantly increased in both CD and UC (CD: SIR 13.88; 95% CI, 1.95-98.51; UC: SIR 9.05; 95% CI, 2.26-36.19). Patients with CD had a higher risk of renal-cell carcinoma (SIR 6.89; 95% CI, 2.22-21.37), and patients with UC had a higher risk of prostate cancer (SIR 2.47; 95% CI, 1.24-4.95). CONCLUSIONS: In a population-based study, Chinese patients with CD are at an increased risk of anorectal cancers and hematological cancers compared with the general population. A higher risk of nonmelanoma skin cancer was also observed in CD and UC. Cancer surveillance should be considered.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy.

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.