The First Reported Case of Juvenile Dermatomyositis in an Adolescent with Down Syndrome and the Clinical Considerations for Therapy

Background: Down Syndrome (DS) is one of the most common birth conditions in the United States of America, with approximately 5300 births annually, resulting in an estimated birth prevalence of 12.6 per 10,000 live births and a population prevalence in the USA since 2010 of 6.7 per 10,000 inhabitants. Children with DS have complex medical challenges that present due to changes in their immune system that results in increased rates of infection, malignancy, and autoimmune disease. Juvenile Dermatomyositis (JDM) is a rare, autoimmune disease, and the most common inflammatory myopathy of childhood. Reports suggest an increased incidence of arthritis in children with DS, but there have been no reports of JDM in children with DS. Additionally, those with DS pose unique challenges with an increase in adverse effects and ineffectiveness of immunosuppressive therapy. Case : We describe the first case of an adolescent female with DS who developed JDM with a positive anti-p155/140 antibody and characteristic clinical phenotype. We discuss increased awareness of autoimmune disease in adolescents with DS and clinical considerations for therapy with immunosuppression. Conclusion: Adolescents with DS are at increased risk for autoimmune disease, including JDM. Awareness, early recognition of the signs and symptoms of autoimmune disease in those with DS is important, so appropriate therapy can be implemented.

COVID-19 Prevalence and Outcomes among Individuals with Rheumatoid Arthritis and Systemic Lupus Erythematosus Taking Hydroxychloroquine; A Retrospective Analysis

Introduction: The SARS-CoV-2 global pandemic has resulted in a universal search for potential treatments of Coronavirus Disease 2019 (COVID-19). Initial reports of the therapeutic potential of chloroquine (CQ) and hydroxychloroquine (HCQ) and early non-randomized non-controlled studies were followed by subsequent trials refuting such properties. The use of CQ and HCQ in diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), prompted us to examine the prevalence of COVID-19 and proposed prophylactic and therapeutic properties of HCQ in this population. Methods: A total of 103 patients with RA and SLE aged 18 to 75 diagnosed with COVID-19 were identified. The patients were categorized as those taking HCQ (cases) and those not on HCQ (controls) for at least 6 months. Primary (mechanical ventilation, length of stay, death) and secondary outcomes were defined, data were collected, and results were compared and statistically analyzed between cases and controls. Results: No statistical difference was observed in demographic features, baseline comorbidities, and medications. Primary outcomes’ statistical analysis did not reveal any differences between cases and controls. Statistical analysis of secondary outcomes revealed that cases had a statistically higher chance of being tachypneic (p 0.034). D-Dimer (p 0.017) and LDH levels (p 0.044) were found to be significantly lower in cases versus controls. Conclusion: This study highlights the lack of clinical prophylactic and therapeutic efficacy of HCQ against COVID-19 when taken at regular doses for patients with RA and SLE. It also shows that the prevalence of COVID-19 was similar in RA and SLE patients regardless of baseline consumption of HCQ.

Does Disease Activity Influence the Levels of Uric Acid in Psoriatic Arthritis?

Background: Hyperuricemia is not only associated with the development of gout but also with renal and vascular dysfunction. The prevalence of this condition has already been studied in psoriasis, but there are a few studies that have been carried out in psoriatic arthritis (PsA). Some studies have shown an association with metabolic syndrome, while others with the extent of cutaneous involvement, but there are no studies that have evaluated the disease activity with compound indexes. Objective: The aim of the study was to determine if disease activity, measured by different composite scores, influences the levels of uric acid. Method: This was a cross-sectional, observational study, which included 52 PsA patients. Clinical assessments included dactylitis, tender and swollen joint counts, Psoriasis Area and Severity Index, Leeds Enthesis Index, Minimal Disease Activity and Disease Activity for Psoriatic Arthritis. Hyperuricemia was defined as serum uric acid levels ≥ 6mg/dL in females and ≥ 7mg/dL in males. Results: Among the 52 included patients, 55.76% were female. The mean age was 54.9 ± 11.6 years. Hyperuricemia occurred in 26.92%. Demographic data, diet, comorbidities and medication were similar between patients with and without hyperuricemia. Patients with hyperuricemia had higher waist circumference (p <0.0046). There was no difference in disease activity between groups, either in the isolated items or in the composite indexes. There was a significant difference in uric acid levels according to the classification of chronic kidney disease by estimated glomerular filtration rate (p=0.0016). Individuals using leflunomide had significantly lower levels of uric acid than those who were not using (p=0.0071). Conclusion: This study supports the notion that, in PsA, hyperuricemia is more related to metabolic factors than to disease activity.

Efficacy and Outcomes of a Novel Telephone-based Gout Disease Management Program

Objective: Gout is the most common inflammatory arthritis in the United States. Despite published guidelines, management remains suboptimal, leading to unnecessary morbidity and increased cost of care. We have designed the gout disease management program (GDMP) to improve outcomes, increase patient satisfaction, and decrease healthcare utilization. Methods: Gout patients were seen at their usual rheumatology clinical visit and offered participation in the GDMP. Data were collected between April 2017 and November 2019. Serum uric acid (SUA) levels were measured at the initial outpatient encounter, at the entrance to GDMP, and every 4 weeks until SUA was at the goal of ≤6 mg/dl. Through telephonic encounters, gout-related recent hospitalizations, and ER or urgent care visits since the last encounter were ascertained. Self-reported gout medication usage and adherence were also determined. Patient satisfaction with GDMP was surveyed using a 5-point Likert scale. Results: A total of 158 patients were enrolled, of which 112 had ≥ 1 telephone encounter and were included in our analyses. During the telephone phase, 79 patients (70%) achieved the SUA goal of ≤6.0 mg/dl. Only 3 patients (2.6%) required hospitalization or visits to an ER or urgent care center due to gout flare, and 98% rated their encounter as a 5 on the 5-point Likert scale. Conclusion: Our telephone-based management program for gout led to improved clinical outcomes as defined by the ACR guidelines, decreased healthcare visits, and had high patient satisfaction. Significance and Innovations: • First telephone-based, rheumatology providers-led study to manage gout • Additional evidence to confirm the feasibility and benefit of telemedicine in common diseases • First study to show excellent patient satisfaction

Effect of Low-Dose Corticosteroid Use on HBV Reactivation in HBsAg-positive Rheumatoid Arthritis Patients

Background: It is well known that the use of corticosteroids (CS) results in increased viral replication and elevated alanine aminotransferase in hepatitis B virus (HBV) patients. However, only a few studies have investigated the effect of low-dose CS on HBV reactivation. In addition, there are few studies on the effects of synthetic disease-modifying anti-rheumatic drugs on HBV reactivation. Objective: We investigated the reactivation of HBV in rheumatoid arthritis (RA) patients treated with long-term low-dose corticosteroids. In addition, we analyzed factors affecting HBV reactivation, including disease-modifying anti-rheumatic drugs. Methods: We retrospectively reviewed medical records and analyzed the incidence of HBV reactivation in RA patients who were hepatitis B surface antigen (HBsAg) positive and who were receiving ≤10 mg of prednisolone over 4 weeks. Logistic regression analysis was performed to investigate the factors that increase the risk of HBV reactivation. Results: A total of 141 patients were included in the study, out of which 24 (17.0%) patients had HBV reactivation. The administration of low-dose corticosteroids did not affect HBV reactivation in HBsAg-positive RA patients (odds ratio: 0.807, 95% confidence interval: 0.143–4.546, p = 0.808), nor did the duration of corticosteroid administration, average daily corticosteroid dose, and cumulative corticosteroid dose. Administration of leflunomide was found to significantly increase the risk of HBV reactivation (odds ratio: 3.851, 95% confidence interval: 1.026–14.459, p = 0.046). Conclusion: The administration of low-dose corticosteroids did not affect the rate of HBV reactivation, suggesting that it can be used safely. Leflunomide may increase the risk of HBV reactivation; therefore, HBV patients should be carefully monitored when receiving this drug.

The Protein Tyrosine Phosphatase Non-receptor Type N22 (PTPN22) Gene Functional Polymorphism (1858T) is not Associated with Rheumatoid Arthritis in Kuwaiti Patients

Background: Rheumatoid Arthritis (RA) is a chronic disorder characterized by an inflammation of synovial tissue in joints resulting in pain, deformities and affects the quality of life. The gene for protein tyrosine phosphatase non-receptor type 22 (PTPN22) encodes a lymphoid specific phosphatase (LYP), which serves as a negative regulator of T lymphocyte activation and is associated with a number of autoimmune/chronic diseases in various ethnic groups. Objective: This study was undertaken to investigate an association between PTPN22 gene functional polymorphism (C1858T; rs2476601) and rheumatoid arthritis (RA) in Kuwaiti Arabs. The frequency of this candidate locus was compared between Kuwaiti RA patients and the controls and with that reported from other populations. Methods: The study was carried out in 191 Kuwaiti RA patients and 214 healthy controls. The diagnosis of RA was carried out according to the guidelines of the American College of Rheumatology (ACR). The genotypes of PTPN22 gene (C1858T) polymorphism were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by DNA sequence analysis in RA patients and controls. Results: The TT genotype of PTPN22 gene functional polymorphism C1858T was found in 2/191 (1%) in RA patients compared to 2/214 (1%) in the controls (P = 1.0). In contrast, heterozygous CT genotype was detected in 3/191 (1.57%) RA patients compared to 32/214 (14.9%) in the controls. The CC genotype was detected in 186/191 (97.38%), RA patients while it was detected in 180/214 (84.1%) of the controls. The two RA patients who carried the homozygous variant (TT) genotype were both positive for rheumatoid factor (RF) and did not have any extra-articular manifestations. Amongst the Kuwaiti RA patients, 27% had a family history of RA. No correlation was found between the activity/severity of the disease and PTPN22 gene polymorphism genotypes. Conclusion: This study did not find an association between the PTPN22 gene functional polymorphism (C1858T) and clinical manifestation and activity/severity of RA in Kuwaiti Arabs. This is in sharp contrast to previous reports from Caucasian and some other populations in which a positive association of PTPN22 gene (C1858T) polymorphism with genetic susceptibility to RA has been reported.

Clinical, Radiologic, and Functional Outcomes Following Methotrexate Withdrawal in Etanercept-Treated Patients with Active Early Rheumatoid Arthritis: A Subanalysis of COMET Year 2 by Week 52 DAS28 Status

Introduction: This post-hoc analysis explored Methotrexate (MTX) withdrawal on clinical, radiographic, and functional outcomes in patients with early rheumatoid arthritis who previously received 52 weeks of Etanercept (ETN) + MTX treatment in the COMET study. Methods: Response at week 104 was analyzed based on the attainment of remission (28-joint disease activity score [DAS28] <2.6; Boolean); low disease activity (LDA; 2.6 ≤DAS28 ≤3.2); normal Health Assessment Questionnaire-Disability Index (HAQ-DI) score (≤0.5); or radiographic non-progression (change in modified Total Sharp Score ≤0.5). Results: Of 208 patients with baseline DAS28 scores at week 52, 105 received ETN + MTX and 103 received ETN over weeks 52-104 (Period 2). At week 104, rates of LDA (70% vs 67%), remission (59% vs 52%), and normal HAQ-DI (63% vs 61%) were similar in both arms; week 52 responders also had a higher response rate at week 104 irrespective of treatment during Period 2. Overall rates of radiographic non-progression were higher for ETN + MTX (90%) vs ETN (74%) at week 104; week 52 non-responders in the Period 2 ETN + MTX arm had a 21-27% higher rate vs ETN, while the treatment difference was 11-12% for week 52 responders. Conclusion: The data suggest that for responders to ETN + MTX at week 52, MTX may be safely withdrawn. For non-responders where de-escalation would not be considered, the continuation of the combination is advisable. Radiological outcome was numerically worse, but of uncertain clinical significance.

Gene Polymorphism of XRCC1 in Systemic Lupus Erythematous

Introduction: There are debates about the role of the X-ray repair cross-complementation group 1 (XRCC1) Arg399Gln gene in the pathogenesis of Systemic Lupus Erythematosus (SLE). Methods: The study was a case-control study carried out on 100 recently diagnosed SLE patients compared to 100 control subjects. The study of XRCC1 Arg399Gln polymorphism was performed by a polymerase chain reaction and restriction fragment length polymorphism. Results and Discussion: A higher frequency of ‘G’ allele in SLE (38.5%) versus control (32%) was noticed; however, this difference was not statistically significant (p = 0.174). Besides, a slightly higher frequency of G/G genotype was found in SLE (22%) vs. control (12%); again, this difference was not statistically significant (p = 0.157). A statistically significantly higher proportion of arthritis, serositis, and thrombocytopenia was observed in the A/A genotype (p = 0.010, 0.032, and 0.036, respectively). Furthermore, we noticed a statistically significant lower hemoglobin level in G/G genotype (p = 0.027). Otherwise, there was no statistically significant difference between the three genotypes regarding other parameters: photosensitivity, malar rash, oral ulceration, ANA, anti-dsDNA antibody, anemia, leucopenia, neurologic manifestations, and all lab parameters except hemoglobin level. Similar results were reported previously. According to genotype, in the study of Clinical and laboratory parameters in SLE patients, a statistically significantly higher proportion of arthritis, serositis, and thrombocytopenia was observed in the A/A genotype (p =0 .01, 0.032, and 0.036 respectively). Furthermore, we noticed a statistically significant lower hemoglobin level in G/G genotype (p = 0.027). These findings suggest a pathogenic connection between the seriousness of the defective DNA repair and the autoimmune severity; such connection is consistent with that found in several murine models. Additionally, negative regulation of the genes encoding the proteins involved in the NER pathway in SLE patients, specifically and XPC, has been found previously. Conclusion: The present study highlights the higher insignificant increase of G allele and GG genotype of XRCC1 399 gene in patients with SLE compared to healthy control. This increase was significantly associated with anemia in patients, which may reflect the aggravation of environmental risk factors to SLE associated with the reduced repair of DNA. Further longitudinal studies are required to validate the present findings.

Rituximab for the Treatment of Common Variable Immunodeficiency (CVID) with Pulmonary and Central Nervous System Involvement

Background: Granulomatous and lymphocytic interstitial lung disease (GLILD) represents a typical form of pulmonary manifestation of CVID. Except for glucocorticoid- and immunoglobulin-administration, no standardized treatment recommendations exist. Objective: To investigate our CVID-patients with GLILD for the applied immunosuppressive regimen, with a focus on rituximab. Methods: A retrospective analysis of all CVID-patients for the manifestation and treatment of GLILD at a single German center was performed in this study. For the evaluation of treatment-response, CT-imaging and pulmonary function testing were used. Results: 50 patients were identified for the diagnosis of a CVID. 12% (n = 6) have radiological and/or histological confirmed diagnosis of a GLILD. Three patients received rituximab in a dose of 2 x 1000mg, separated by 2 weeks repeatedly. All patients showed radiological response and stabilization or improvement of the pulmonary function. Rituximab was used in one patient over 13 years with repeated treatment-response. Furthermore, the synchronic central nervous system-involvement of a GLILD-patient also responded to rituximab-treatment. With sufficient immunoglobulin-replacement-therapy, the occurring infections were manageable without the necessity of intensive care treatment. Conclusion: Rituximab might be considered as an effective and relatively safe treatment for CVID-patients with GLILD.

Self-Reported Symptoms in a Cohort of Rheumatoid Arthritis and Systemic Lupus Erythematosus during the COVID-19 Quarantine Period

Background: During the first three months of the COVID-19 pandemic in the Philippines, there was a supply shortage of hydroxychloroquine and methotrexate. Limited access to medication and the life changes resulting from the COVID-19 pandemic may predispose patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) to disease flares. Objective: This study aimed to investigate self-reported symptoms of disease flares among patients with rheumatoid arthritis or systemic lupus erythematosus during the COVID-19 pandemic. Methods: A total of 512 completed online surveys from patients with SLE or RA were collected. The data included sociodemographic characteristics, self-reported physical symptoms, health service utilization, and availability of hydroxychloroquine and methotrexate. Results: Seventy-nine percent of respondents had lupus, while 21% had RA. One-third of the cohort had contact with their attending physician during the two-month quarantine period prior to the survey. Eighty-two percent were prescribed hydroxychloroquine and 23.4% were prescribed methotrexate; but 68.6% and 65%, respectively, had “irregular” intake of these medicines due to unavailability. The current health status was reported as good by 66.2%; 24% had no symptoms during the two-week period prior to the survey. The most common symptoms experienced were joint pain (51%), muscle pain (35%), headache (26.8%), and skin rash (19.1%). Five percent had a combination of these four most common symptoms. Irregular supply of hydroxychloroquine among patients with SLE (n=323) was associated with more frequent occurrence of muscle pain (40.6% vs 27.9%, p=0.03) or rash (27.4% vs 11.7%, p<0.001). Irregular supply of methotrexate among RA patients prescribed hydroxychloroquine and methotrexate (n=36) was associated with more frequent occurrence of joint pains with or without swelling (73.9% vs 38.5%, p=0.04). Irregular supply of hydroxychloroquine was associated with less frequent occurrence of dizziness (0 vs 66.7%, p<0.001) among RA patients (n=18). Conclusion: In our cohort of RA and SLE, the majority reported at least one symptom that may indicate disease flare. There was a significant association between the irregular supply of hydroxychloroquine or methotrexate with the presence of muscle pain, rash, or joint pains during the 14-day period prior to the survey.