The Association Between Hypermobility Ehlers–Danlos Syndrome and Other Rheumatologic Diseases

Research has shown hypermobility Ehlers–Danlos syndrome (hEDS) to be associated with some complicated rheumatologic disease. In this feature paper, the authors discuss the prevalence and pathophysiology of rheumatologic conditions, specifically ankylosing spondylitis and rheumatoid arthritis, in patients with hEDS. Furthermore, the authors discuss possible reasons for the association of hEDS with these rheumatologic diseases.

Clinical and Molecular Features of Anti-CENP-B Autoantibodies

Centromeric proteins are the foundation for assembling the kinetochore, a macromolecular complex that is essential for accurate chromosome segregation during mitosis. Anti-centromere antibodies (ACAs) are polyclonal autoantibodies targeting centromeric proteins (CENP-A, CENP-B, CENP-C), predominantly CENP-B, and are highly associated with rheumatologic disease (lcSSc/CREST syndrome). CENP-B autoantibodies have also been reported in cancer patients without symptoms of rheumatologic disease. The rise of oncoimmunotherapy stimulates inquiry into how and why anti-CENP-B autoantibodies are formed. In this review, we describe the clinical correlations between anti-CENP-B autoantibodies, rheumatologic disease, and cancer; the molecular features of CENP-B; possible explanations for autoantigenicity; and, finally, a possible mechanism for induction of autoantibody formation.

Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1

Somatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported in patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations and unique bone marrow (BM) features in 16 patients with VEXAS. All patients were male and had a history of severe autoinflammatory and rheumatologic manifestations and a somatic UBA1 mutation (p.Met41). Ten patients had hematologic disorders: myelodysplastic syndrome (MDS; 6 of 16), multiple myeloma (2 of 16), monoclonal gammopathy of undetermined significance (2 of 16), and monoclonal B-cell lymphocytosis (2 of 16), and a few of those patients had 2 co-existing clonal processes. Although macrocytic anemia (100%) and lymphopenia (80%) were prevalent in all patients with VEXAS, thrombocytopenia and neutropenia were more common in patients with progression to MDS. All BMs in VEXAS patients had prominent cytoplasmic vacuoles in myeloid and erythroid precursors. In addition, most BMs were hypercellular with myeloid hyperplasia, erythroid hypoplasia, and varying degrees of dysplasia. All patients diagnosed with MDS were lower risk (low blast count, very good to intermediate cytogenetics) according to standard prognostic scoring with no known progression to leukemia. In addition, 10 of 16 patients had thrombotic events, including venous thromboembolism and arterial stroke. Although VEXAS presents symptomatically as a rheumatologic disease, morbidity and mortality are associated with progression to hematologic disease. Given the increased risk of developing MDS and multiple myeloma, surveillance for disease progression is important.

Still Disease is Still Hard to Diagnosis: A Case Report

Adult-onset Still Disease (AOSD) is a rare rheumatologic condition with unrecognized etiology. Spiking fevers, joint involvement (arthralgia or arthritis), rashes, lymphadenopathy, abnormal liver function test data, and leukocytosis are the main features of this disease. Yamaguchi’s criteria with the sensitivity and specificity of 96.2% and 92.1%, respectively, is the most beneficial tool for the diagnosis of AOSD, as a rare disease. The uncommon features of the still disease remain confusing for clinicians. about the present study reported a 27-year-old patient who was referred to our hospital with an unknown diagnosis, because of the rare features of Still disease. The explored characteristics of rashes, fever, and para-clinical data, as well as laboratory and imaging data, are described in detail; such features have led to long hospitalization to confirm the diagnosis in this patient. The positive family history of the rheumatologic disease and dramatic response to low dose corticosteroids were other outstanding features of our case. This report highlighted the necessity of conducting randomized clinical trials to address the management of AOSD. Besides, the present study signified the need for providing further awareness among clinicians to prevent long hospitalization.

Impact of rapid infliximab infusions on access at a large academic tertiary medical center

Purpose Infliximab promotes remission in patients with inflammatory bowel disease (IBD) and rheumatologic disease (RD). Rapid infliximab infusions (RI) reduce infusion time from 2 hours to 1 hour and can enhance access to care, as defined by capacity, safety, and patient characteristics. Our hypothesis for the study described here was that use of RI can enhance access for patients. Methods Data on all patients receiving infliximab for IBD or RD at our outpatient infusion center from February 2016 to August 2017 were retrospectively analyzed. Demographic and clinical information were collected. Results Of 348 patients who received infliximab, 205 had IBD and 143 had RD. In terms of capacity, 40% of patients received RI, resulting in a 16.1% decrease in average daily infusion time and a 9.8% increase in average daily available scheduled infusion chair time (P = 0.720). In terms of safety, 4 patients switched back to standard infusions after RI, after 3 specifically had reactions to RI. In terms of patient characteristics, more patients with RD versus IBD received RI (P = 0.020). Among the patients with RD, a lower proportion receiving RI were female (P = 0.043). For the patients with IBD, a higher proportion receiving RI were white (P = 0.048). Among both patients with RD and patients with IBD, a higher proportion receiving RI had private insurance (P = 0.016 and P = 0.018, respectively). Conclusion RI were safe and increased available chair time. Females with RD, patients of non-White race with IBD, and patients with public insurance were less likely to receive RI. Future directions include patient surveys and evaluation of implicit bias against patient factors that may impact access to RI.

Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases

Objective To compare baseline characteristics, clinical presentations, and outcomes of patients with rheumatic conditions requiring hospitalization for COVID-19 who received chronic hydroxychloroquine to those who did not receive chronic hydroxychloroquine. Methods We identified all patients with a rheumatologic disease who were admitted with COVID-19 to two hospitals in New York City between March 3-April 30 2020. Patients who received chronic hydroxychloroquine prior to admission were matched 1:2 (±10 years of age) to patients who did not receive chronic hydroxychloroquine. We compared demographics, comorbidities, hydroxychloroquine dosages, concurrent medications, presentations, and outcomes between the groups. Results There were 14 patients receiving hydroxychloroquine and 28 matched control subjects. The median age of cases was 63 years (IQR 43–73) and 60 years (IQR 41–75) for controls. Control subjects had a higher prevalence of pulmonary diseases (42.8%), diabetes (35.7%), and obesity (35.7%) than their case counterparts (28.6%, 14.3%, and 7.1%, respectively). A higher proportion of case than control subjects (50% vs.s 25%) reported usage of prednisone for their rheumatic conditions prior to admission. Despite these differences in baseline characteristics, univariate logistic regression revealed no statistically significant differences in the need for mechanical ventilation (OR 1.5; 95% CI: 0.34–6.38) or in-hospital mortality (OR 0.77; 95% CI: 0.13–4.56). Conclusion Hydroxychloroquine therapy in individuals with rheumatic conditions was not associated with less severe presentations of COVID-19 among hospitalized patients compared with individuals with rheumatic conditions not receiving hydroxychloroquine.