Symptom Flares Research Articles

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.

Assessment of Toxic Effects Associated With Dose-Fractionated Radiotherapy Among Patients With Cancer and Comorbid Collagen Vascular Disease

The adoption of alternative fractionated radiotherapy regimens for the treatment of patients with cancer and comorbid collagen vascular disease (CVD) is controversial among oncologists because of concerns about potentially severe toxic effects; however, the association between fractionated radiotherapy and toxic effects in the modern era has not been well studied. To compare acute and late toxic effects among patients with cancer and comorbid CVD who received dose-fractionated radiotherapy. This retrospective cohort study examined 197 adult patients with cancer and CVD who received radiotherapy at a single-institution tertiary academic center over a 12-year period (February 1, 2007, to April 30, 2019), with a median follow-up of 23 months (range, 0-108 months). Data were analyzed from February 1 to August 31, 2020. Three dose-fractionated radiotherapy regimens: conventional fractionation (CF; ≤2 Gy per fraction), moderate hypofractionation (MH; >2 Gy to <5 Gy per fraction), and ultrahypofractionation (UH; ≥5 Gy per fraction). The main outcomes were the incidence and severity of acute and late radiotherapy-associated toxic effects, which were assessed separately by dose-fractionation regimen. Toxic effects occurring within 90 days after radiotherapy completion were considered acute, and toxic effects occurring after that 90-day period were considered late. Secondary goals were to identify covariates associated with toxic effects and to characterize the incidence of CVD symptom flares (defined as worsening clinical symptoms and/or worsening results [transient or permanent] on associated blood tests compared with baseline, as documented by managing physicians) after radiotherapy. Of 197 patients with cancer and comorbid CVD (mean [SD] age, 69 [12] years; 134 women [68.0%]; and 149 White participants [75.6%]), 80 patients (40.6%) received CF radiotherapy, 55 patients (27.9%) received MH radiotherapy, and 62 patients (31.5%) received UH radiotherapy. The most common CVD diagnoses were rheumatoid arthritis (74 patients [37.6%]), psoriasis (54 patients [27.4%]), systemic lupus erythematosus (34 patients [17.3%]), and scleroderma (8 patients [4.1%]). The most common radiotherapy sites were the breast (48 patients [24.4%]), thorax (25 patients [12.7%]), central nervous system (24 patients [12.2%]), and prostate (23 patients [11.7%]). Data on acute toxic effects were available for 188 patients (95.4%) and missing for 9 patients (4.6%). Data on late toxic effects were available for 142 patients (72.1%) and missing for 55 patients (27.9%). Over 12 years, the unadjusted incidences of severe acute toxic effects associated with CF, MH, and UH radiotherapy were 5.4% (95% CI, 0.3%-10.5%), 7.4% (95% CI, 0.4%-14.4%), and 1.7% (95% CI, 0%-5.0%), respectively. The incidences of severe late toxic effects associated with CF, MH, and UH radiotherapy were 8.3% (95% CI, 1.3%-15.3%), 0%, and 2.2% (95% CI, 0%-6.4%), respectively. No significant associations were found between severe acute or late toxic effects by dose fractionation regimen. In the multivariable analysis, MH radiotherapy was associated with a lower likelihood of developing late toxic effects (odds ratio [OR], 0.21; 95% CI, 0.05-0.83; P = .03) compared with CF radiotherapy. Those who received UH radiotherapy had a lower likelihood of experiencing late toxic effects (OR, 0.22; 95% CI, 0.04-1.21; P = .08). A total of 19 of 80 patients (23.8%), 15 of 55 patients (27.3%), and 10 of 62 patients (16.1%) experienced CVD symptom flares after receiving CF, MH, and UH radiotherapy, respectively (P = .33). In this study, the incidences of unadjusted severe toxic effects over 12 years were less than 10% and were not significantly associated with dose fractionation. When clinically indicated, patients with cancer and comorbid CVD may not require immediate exclusion from the receipt of currently used hypofractionated radiotherapy regimens.

Treatment adherence and disease status among children with rheumatological diseases during COVID-19 pandemic: A cross-sectional study from a tertiary care center

Introduction: There is a reallocation of health-care services across the world in view of the COVID-19 pandemic. This has resulted in the disruption of routine care to children with chronic rheumatological diseases. We studied the treatment adherence and disease status of these children during the COVID-19 pandemic.Methods: We did a cross-sectional observational study of children (<16 years) with rheumatological diseases. Parents of seventy consecutive children with rheumatological diseases were interviewed through the telephone to assess the treatment adherence and disease status from April 2020 to July 2020.Results: In our study cohort, 44.3' (n = 31) had juvenile idiopathic arthritis (JIA), 52.9' (n = 37) had childhood lupus childhood-onset systemic lupus erythematosus (cSLE), 1.4' (n = 1) had juvenile scleroderma, and 1.4' (n = 1) had childhood vasculitis. About 38.6' (n = 27) had poor compliance due to reasons like difficulty in transportation (88.6') (n = 24), financial constraints (88.6') (n = 24), fear of acquiring COVID-19 by attending the study center (55.5') (n = 15), and fear of taking immunosuppressive drugs (18.5') (n = 5). Thirty percent (n = 21) respondents reported flare of symptoms. Common flare symptoms reported were joint pain (25.7') (n = 18), skin rashes (1.4') (n = 1), and oral ulcers (1.4') (n = 1). One patient with cSLE required admission for acute pancreatitis. Nearly 4.3' (n = 3) experienced influenza like illness. One patient with cSLE developed swab-positive mild COVID-19 illness. cSLE patients experienced significantly less flare symptoms compared to patients with other rheumatological illness (P = 0.03, odds ratio = 0.32, confidence interval = 0.1–0.9). Almost 98.6' (n = 68) of parents were not aware of electronic consultation portals.Conclusion: Although COVID-19 causes less symptomatic disease in children, this study highlights the indirect effects of pandemic like financial constraints and parental misconceptions on children with rheumatological diseases. Furthermore, the awareness about electronic portals in consultation needs to be increased.

Longitudinal Autonomic Nervous System Measures Correlate With Stress and Ulcerative Colitis Disease Activity and Predict Flare.

Differences in autonomic nervous system function, measured by heart rate variability (HRV), have been observed between patients with inflammatory bowel disease and healthy control patients and have been associated in cross-sectional studies with systemic inflammation. High HRV has been associated with low stress. Patients with ulcerative colitis (UC) were followed for 9 months. Their HRV was measured every 4 weeks using the VitalPatch, and blood was collected at baseline and every 12 weeks assessing cortisol, adrenocorticotropin hormone, interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein (CRP). Stool was collected at enrollment and every 6 weeks for fecal calprotectin. Surveys assessing symptoms, stress, resilience, quality of life, anxiety, and depression were longitudinally collected. Longitudinally evaluated perceived stress was significantly associated with systemic inflammation (CRP, P = 0.03) and UC symptoms (P = 0.02). There was a significant association between HRV and stress (low-frequency to high-frequency power [LFHF], P = 0.04; root mean square of successive differences [RMSSD], P = 0.04). The HRV was associated with UC symptoms (LFHF, P = 0.03), CRP (high frequency, P < 0.001; low frequency, P < 0.001; RMSSD, P < 0.001), and fecal calprotectin (high frequency, P < 0.001; low frequency, P < 0.001; RMSSD, P < 0.001; LFHF, P < 0.001). Significant changes in HRV indices from baseline developed before the identification of a symptomatic or inflammatory flare (P < 0.001). Longitudinally evaluated HRV was associated with UC symptoms, inflammation, and perceived and physiological measures of stress. Significant changes in HRV were observed before the development of symptomatic or inflammatory flare.

Does Pollen Trigger Urological Chronic Pelvic Pain Syndrome Flares? A Case-Crossover Analysis in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network.

We sought to determine whether pollen triggers urological chronic pelvic pain syndrome flares. We assessed flare status every 2 weeks for 1 year as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain case-crossover analysis of flare triggers (NCT01098279). Flare symptoms, flare start date and exposures in the 3 days before a flare were queried for the first 3 flares and at 3 randomly selected nonflare times. These data were linked to daily pollen count by date and the first 3 digits of participants' zip codes. Pollen count in the 3 days before and day of a flare, as well as pollen rises past established thresholds, were compared to nonflare values by conditional logistic regression. Poisson regression was used to estimate flare rates in the 3 weeks following pollen rises past established thresholds in the full longitudinal study. Analyses were performed in all participants and separately in those who reported allergies or respiratory tract disorders. Although no associations were observed for daily pollen count and flare onset, positive associations were observed for pollen count rises past medium or higher thresholds in participants with allergies or respiratory tract disorders in the case-crossover (OR 1.31, 95% CI 1.04-1.66) and full longitudinal (RR 1.23, 95% CI 1.03-1.46) samples. We found some evidence to suggest that rising pollen count may trigger flares of urological chronic pelvic pain syndrome. If confirmed in future studies, these findings may help to inform flare pathophysiology, prevention and treatment, and control over the unpredictability of flares.

Patient-reported dermatomyositis and polymyositis flare symptoms are associated with disability, productivity loss, and health care resource use.

BACKGROUND: Flare activity or worsening symptoms are not well defined for myositis. OBJECTIVES: To (a) characterize dermatomyositis (DM) and polymyositis (PM) flares from the patient perspective and (b) report the corresponding disability and rate of unplanned medical encounters. METHODS: Online survey data were collected from volunteer patients from The Myositis Association and Johns Hopkins Myositis Center. Flare frequency; Health Assessment Questionnaire Disability Index (HAQ-DI), HAQ-Pain Index, Work Productivity and Activity Impairment (WPAI) scales; emergency department/urgent care (ED/UC) visits; and hospital admissions during the past year were examined. RESULTS: 564 individuals with selfreported diagnoses of DM/PM were surveyed between December 2017 and May 2018. Recall of symptom flares was reported by 524 respondents (78.1% were female, mean age of 55 years). Among the respondents, 378 (72.1%) reported ≥ 1 flare in the past year. The pattern of flare frequency was similar for DM and PM respondents. The most common symptoms were muscle weakness (83%), extreme fatigue (78%), and muscle pain/discomfort (64%). Increasing flare frequency was associated with significantly (P < 0.01) greater mean HAQ-DI and HAQ-Pain scores, myositis-related ED/UC visits, hospital admissions, WPAI work productivity loss (among those employed), and WPAI nonwork activity impairment. CONCLUSIONS: DM/PM-related flares are common with exacerbations of muscle weakness and fatigue being the most common flare symptoms. Flare frequency was associated with greater disability, pain, work productivity loss, nonwork activity impairment, and increased ED/UC utilization. Higher frequency of patient-reported flares may serve as a marker of worsening physical functioning and intensifying health care needs and, therefore, suggests their importance in the clinical assessment of patients with DM/PM. DISCLOSURES: This study was supported by Mallinckrodt Pharmaceuticals (Bedminster, NJ) via grants to Vedanta Research and The Myositis Association. Christopher-Stine has received compensation from previous Mallinckrodt Advisory Board meetings, unrelated to this subject matter. Wan is an employee of Mallinckrodt Pharmaceuticals and is a stockholder of the company. Reed and Bostic received grant support from Mallinckrodt Pharmaceuticals for data collection and analysis. McGowan is an employee of The Myositis Foundation, which received grant funding to support study data collection. Kelly has no conflicts to disclose. This study was presented, in part or full, at the 2019 Annual American College of Rheumatology and Association of Rheumatology Professional Meeting (November 8-13, 2018; Atlanta, GA) and at the Third Global Conference on Myositis (March 27, 2019; Berlin, Germany).

November 2020 Imaging Case of the Month: Cause and Effect?

No abstract available. Article truncated after 150 words. Clinical History: A 36 -year-old woman with Crohn’s disease and ulcerative colitis diagnosed approximately 1 year earlier, was initially treated with adalimumab, but later switched to prednisone and budesonide when subcutaneous nodules and migraines were attributed to this medication. Subsequently a flare of gastrointestinal symptoms prompted hospitalization with colonoscopy which showed severe pancolitis consistent with ulcerative colitis. One month following hospital discharge, the patient then presented to the Emergency Department with continued complaints of nausea, diarrhea, abdominal pain, intermittent fever (self-measured to 101º F), joint pain, and a pruritic rash all over her body. These symptoms had occurred following her hospitalization 2 months earlier. She also complained of 25 lbs. weight loss over the previous year. In addition to prednisone and budesonide, the patient’s medications included hydroxyzine, famotidine, vitamin C, and hydrocodone-acetaminophen. The patient denies allergies and did not smoke nor use drugs. Physical examination showed the patient to be …

S2241 Familial Mediterranean Fever Mimicking Crohn's Disease

INTRODUCTION: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent episodes of fever and polyserosal inflammation. The non-specific symptoms of FMF can mimic a large variety of diseases, particularly Crohn’s disease (CD), as both diseases affect the digestive tract, skin, and joints. This manuscript presents a case of FMF with clinical symptoms that closely resemble CD. CASE DESCRIPTION/METHODS: A 28-year-old female with Melkerson-Rosenthal syndrome presented to the Wake Forest Digestive Health Clinic after genetic testing revealed a mutation in the MEFV (Mediterranean fever) gene. The patient reported a thirteen-year history of recurrent episodes of facial and labial edema, erythema and pain, a two year history of severe episodic abdominal pain, and high fever accompanying her symptomatic flares. Skin biopsy demonstrated granulomatous inflammation suspicious for cutaneous CD. Prior to her presentation, she had five colonoscopies and two esophagogastroduodenoscopies with macroscopically and microscopically unremarkable findings. She also had a normal CT enterography and a negative inflammatory bowel disease (IBD) gene panel. Due to the patient’s lack of GI findings and failure to respond to Humira, cutaneous CD became an unlikely diagnosis. The patient was treated with colchicine, resulting in dramatic symptomatic improvement. Given that her symptoms and response to colchicine met Livneh diagnostic criteria for FMF, FMF was the most likely diagnosis. DISCUSSION: FMF may be easily mistaken for IBD especially in young adult patients. Typical FMF histopathologic findings include esophagitis, gastritis, duodenitis, ileitis, or colitis. Imaging findings typically include ileus, hepatosplenomegaly, ascites, focal peritonitis, or mesenteric adenopathy. This case is one of the only cases in the literature of FMF mimicking CD with entirely unremarkable findings on endoscopy and imaging. Genetic analysis of the MEFV mutation should be considered when patients who are suspected to have CD do not have typical endoscopy findings or respond appropriately to CD treatment.

S3194 Metformin: A Therapeutic Adjunct for Patients With Inflammatory Bowel Disease?

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are known to have gut dysbiosis, where disease progression has been correlated with decreased commensal bacterial diversity. Various bacterial species promote gut homeostasis including Akkermansia muciniphilia, a mucin producing bacteria that constitutes 1–4% of adult enterobiota. Recent studies have demonstrated an increase in Akkermansia in both animal and human subjects treated with metformin. We present a retrospective analysis comparing patients with IBD who were also taking metformin, against IBD patients who were not, in an effort to determine if metformin therapy results in lower incidence of IBD symptom flares. METHODS: We utilized a Mann-Whitney U Test to determine if there was a significant difference in the number of symptom flares, between patients with IBD over a 2 year span, who were taking metformin compared to those patients who were not. Groups consisted of 52 patients with Ulcerative colitis, and 45 patients with Crohns disease. RESULTS: The mean number of flares was significantly lower (P = 0.022) in Metformin users 0.33 ± 0.65 compared to the non-metformin users 1.3 ± 1.42 in Ulcerative colitis. No significant difference (P = 0.13) was noted between Metformin users 0.6 ± 0.89 compared to non-metformin users in Crohn's disease 3.1 ± 6.1. The overall mean of both groups were significantly lower (P = 0.003) in Metformin users 0.41 ± 0.71 compared to the non-metformin users 2.2 ± 4.49. CONCLUSION: Patients with IBD have relatively low proportions of gut-beneficial microbes such as Firmicutes and Bacterioides and higher proportions of Enterobacteriacae and Actinobacteria. Metformin leads to increases in gut Akkermansia via up regulation of mucin producing goblet cells, which act as substrates promoting Akkermansia growth. This is especially important in IBD associated dysbiosis, which results in greater proportions of mucolytic bacterial species such as Ruminococcus gnavas and Ruminococcus torques. Crohns disease and Ulcerative colitis, differ in terms of the areas of the alimentary tract they most commonly affect. Disease location may impact therapeutic efficacy, as Akkermansia predominates in the large intestine and rectum as opposed to the small bowel. The relative benefit of metformin may differ in patients receiving concurrent therapies which also impact gut flora. Anti-TNF therapy for example, promotes the abundance of Faecalibacterium prausnitzzi, which exerts anti-inflammatory effects in anti-TNF responsive patients.Figure 1Figure 2Figure 3

S0698 More Pathogens, Less Insight: Comparing Extended Stool PCR Panels to Basic Stool PCR Panels

INTRODUCTION: Stool Polymerase Chain Reaction (PCR) panels can be used to rapidly detect specific pathogens responsible for gastrointestinal (GI) infections. This is particularly important in patients with inflammatory bowel diseases (IBD) as the symptoms of IBD flare often overlaps with those of GI infections. While the increased risk of Clostridioides difficile (C. difficile) among IBD patients is well established, the risk of other gastrointestinal pathogens is less well studied. Our study compares the utility of two stool PCR panels that tests for 22 pathogens in IBD patients hospitalized for gastrointestinal symptoms. METHODS: We retrospectively reviewed the electronic medical records of adult patients with IBD hospitalized at a southeastern New England hospital between January 1, 2017 and April 1, 2019. Patients were included if they had a stool PCR panel test and symptoms consistent with an IBD flare or infectious gastroenteritis. Patients with positive C. difficile stool PCR or culture were excluded. Statistical analysis with generalized linear mixed modeling was used to compare the utility of the basic verses extended stool PCR panels. RESULTS: A total of 770 IBD patients (82.5% Caucasian, 56.6% female; mean age 49.51 years, SD = 19.42) with 1,189 hospitalizations were included in the study. The basic stool PCR panel yielded positive results (13/1651, 0.79%) slightly more often than the extended stool PCR panel (14/2354, 0.59%) (Table 1). In general, the most common pathogens detected were Enteropathogenic Escherichia Coli (2.38%), Norovirus (2.38%), and Sapovirus (2.38%) (Table 1). On linear mixed modeling (Table 2), none of the factors were associated with a significantly increased utility of performing an extended stool PCR panel over a basic panel except when comparing patients on IBD medication (P = 0.0433) or those who presented with nausea (P = 0.0477). Participants who identified as Asian were more likely to have a positive test result compared to participants who identified as white for both tests (basic, P = 0.0147; extended, P = 0.0969). CONCLUSION: Our study identified no advantage when ordering the extended stool PCR panel over the basic stool PCR panel in hospitalized IBD patients. While the extended stool PCR stool panel identified some unique bacteria/viruses, these cases were extremely rare and without clinical predictors. Clinicians should be judicious when ordering extended stool PCR panels for IBD patients as they have low positive rates and may not change medical management.Table 1.: Detection rate of non-C. difficile pathogens using the basic stool PCR panel verses the extended stool PCR panel among hospitalized IBD patientsTable 2.: Model Results Estimating Probability of a Positive Test

S2292 Gastrointestinal Manifestations in Patients With Inflammatory Bowel Disease and Novel Coronavirus Infection

INTRODUCTION: There has been speculation about the level of risk and severity of symptoms in patients with Inflammatory Bowel Disease (IBD). Studies have shown that patients with Crohn’s disease and Ulcerative Colitis (UC) have increased expression of Angiotensin-converting Enzyme 2 (ACE 2) in their inflamed guts.2 SARS-CoV-2 uses ACE2 on the host receptor to enter into cells.1 The utilization of immunosuppressants or immunomodulators is another consideration that needs to be made for patients with IBD. We present a case series of 2 patients with different forms of IBD as well as differing forms of management. CASE DESCRIPTION/METHODS: Case 1: 64-year-old AA female with a PMH of CD, DM2, HTN, and Breast Cancer presented to the ER with fevers, cough, and myalgias for 5 days. SARS-CoV-2 PCR was collected. The patient was admitted five days later due to worsening symptoms of dyspnea, fevers, and diarrhea. Her physical exam was within normal limits. Initial management included initiation of broad spectrum intravenous antibiotics, cessation of immunosuppressant Azathioprine, continuation of Cholestyramine, and Hydroxychloroquine. RNA PCR returned positive for Sars-Cov-2. Stool studies collected during hospitalization were significant for lactoferrin and osmolality (390 mOsm/kg). Stool infectious studies were negative. Case 2:50-year-old AA female with PMH of UC presented with symptoms of fevers and dyspnea. SARS-CoV-2 PCR collected and she was discharged. The patient returned to the ER with 1 week worsening GI symptoms. Symptoms of previous flares were sharp hypogastric pain associated with increased frequency of hematochezia and tenesmus different from the symptoms experienced during this admission. DISCUSSION: This is the first case series of patients with IBD on immunomodulators who developed gastrointestinal manifestations of COVID-19. A dilemma faced in both of the patients presented was whether their symptoms were secondary to COVID-19 or IBD flare. ACE2 is ubiquitously expressed in the gastrointestinal tract with upregulation in IBD. Specific guidance on Covid-19 infected patients has been published for patients with IBD stratified by risk. IBD medication management varied drastically in our two cases. Studies have shown an increased risk of viral infection in clinically active IBD with exposure to thiopurines and so Azathioprine was held in Patient 1. In contrast it was felt appropriate to continue 5-Aminosalicylic acid in patient 2. Both IBD patients had extended clinical courses but positive outcomes.Table 1Table 2

S2301 COVID-19 and Ulcerative Colitis in Pregnancy

INTRODUCTION: Impacts of the novel Coronavirus (SARS-CoV-2) are widespread, range in severity, and vastly unknown. Inflammatory bowel disease (IBD) patients are often treated with immunosuppressive medications which can increase risk of viral infections and associated morbidity and mortality. We present a case of a pregnant patient with pan-colonic ulcerative colitis (UC) who was infected with SARS-CoV-2. CASE DESCRIPTION/METHODS: A 29-year-old female with pan-colonic UC, at 22 weeks’ gestation, presented with bloody diarrhea, fecal urgency, and incontinence. She was diagnosed in 2015 and established care with us in 2018 while on balsalazide. During initial attempt to stage her UC with a colonoscopy, she became pregnant but unfortunately had a miscarriage. Her colonoscopy revealed Mayo 1 activity in the left colon with decreased vascular pattern (Figures 1 and 2). She had a disease flare 1 year ago which resolved with transrectal 5-mesalamine. During a pre-conception planning IBD visit, given her clinical course (disease flares, lack of complete mucosal healing with moderate histological activity), targeted immune-modifying biologic was recommended. After much discussion, she elected to stay the course with close surveillance. Her current presentation was consistent with another disease flare. Evaluation revealed fecal calprotectin of 700.4mcg/gm and CRP of 14.4mg/L with negative C. diff testing. She was started on budesonide 9mg daily, however due to persistent symptoms 2 weeks later, was switched to prednisone 40mg daily with clinical response within 72 hours. One week later, she developed rhinorrhea and myalgias and tested positive for SARS-CoV-2. As she was clinically stable, she was advised to self-quarantine without need for hospitalization. Prednisone dose was immediately decreased to 20mg daily with a 4-week taper. The UC flare symptoms resolved and her viral symptoms improved after 3 weeks. She is currently back to her baseline health with no known adverse effects to her pregnancy, which is currently at 38 weeks’ gestation. With collaboration with her obstetrics team, the decision was made to proceed with vedolizumab after delivery. DISCUSSION: Pre-pregnancy IBD control is predictive of IBD-related pregnancy outcomes. Our case demonstrates treatment of an intrapartum UC exacerbation in the setting of maternal infection with SARS-CoV-2. Cautious treatment of maternal IBD is necessary. A multidisciplinary approach between IBD gastroenterology and Obstetrics is critical in safely managing these patients.Figure 1.: Decreased vascular pattern seen in the rectum on white light (left) and narrow-band imaging (right).Figure 2.: Mucosal erythema demonstrated in the sigmoid colon.

Australian patient perspectives on the impact of gout.

To explore the perceptions of patients toward the impacts of gout, in an Australian context. Semi-structured interviews were conducted with Australian patients with gout (n=17). Interviews focused on the impacts of gout on patients' day-to-day lives. The interviews were audio-recorded, transcribed verbatim and analyzed thematically by 2 independent reviewers. Patients with gout reported variable but significant impacts of gout on their daily lives. Patients were primarily concerned with the pain and poor mobility associated with gout flares. Participants also reported significant social impacts related to their inability to attend events and the need for family and friends to look after them. Productivity was also negatively affected due to pain and poor mobility, and emotional wellbeing was reduced both by the symptoms of gout flares and anxiety between flares. Diet, daily planning, hobbies, exercise, sleep and selection of attire were also reported as being impacted by their gout. In Australia, gout has significant and preventable impacts beyond the physical symptoms of gout flares, across a variety of domains. By identifying patients' key concerns, this can potentially aid clinicians to tailor gout education and encourage medication adherence, in order to improve gout management.

Gut microbial transcytosis induced by tumor necrosis factor-like 1A-dependent activation of a myosin light chain kinase splice variant contributes to IBD.

Inflammatory bowel disease (IBD) is characterized by abnormal host-microbe interactions. Proinflammatory cytokine IFNγ and a novel TNF superfamily member, TL1A, have been implicated in epithelial barrier dysfunction. The divergent regulatory mechanisms of transcellular versus paracellular hyperpermeability remain poorly understood. Intestinal epithelia express two splice variants of long myosin light chain kinase (MLCK), of which the full-length MLCK1 differ from the shorter isoform MLCK2 by a Src kinase phosphorylation site. The aim was to investigate the roles of MLCK splice variants in gut barrier defects under proinflammatory stress. Upregulated expression of TL1A, IFNγ, and two MLCK variants was observed in human IBD biopsy specimens. The presence of intraepithelial bacteria preceded tight junction (TJ) damage in dextran sodium sulfate-treated and TL1A-transgenic mouse models. Lack of barrier defects was observed in long MLCK(-/-) mice. TL1A induced MLCK-dependent terminal web (TW) contraction, brush border fanning, and transepithelial bacterial internalization. The bacterial taxa identified in the inflamed colonocytes included Escherichia, Enterococcus, Staphylococcus,and Lactobacillus. Recombinant TL1A and IFNγ at low doses induced PI3K/Akt/MLCK2-dependent bacterial endocytosis, whereas high-dose IFNγ caused TJ opening via the iNOS/Src/MLCK1 axis. Bacterial internalization was recapitulated in MLCK-knockout cells individually expressing MLCK2 but not MLCK1. Immunostaining showed different subcellular sites of phosphorylated MLC localized to the TJ and TW in the MLCK1- and MLCK2-expressing cells, respectively. In conclusion, proinflammatory cytokines induced bacterial influx through transcellular and paracellular routes via divergent pathways orchestrated by distinct MLCK isoforms. Bacterial transcytosis induced by TL1A may be an alternative route causing symptom flares in IBD.

The NFκB Expression on Apical Dental Granuloma: An Immunohistochemistry Analysis.

BackgroundEndodontic treatment on dental caries with dental granuloma on the periapical has the potential to flare. The symptoms of acute flare in dental granuloma are strongly related to the activation of macrophages that produce pro-inflammatory cytokine through nuclear factor kappa B (NFκB). However, the role of NFκB in dental granuloma has not been widely explained.PurposeTo compare NFκB expression in dental granuloma and dental nongranuloma in the periapical of dental caries.MethodsThe periapical lesion of dental granuloma and dental nongranuloma was obtained from patients with dental caries who were subjected to tooth extraction. The periapical lesion was confirmed by periapical radiography and then differentiated by histological and immunohistochemistry by analyzing the NFκB expression.ResultsMost dental granulomas were found in females (66.67%) between the ages 36 and 45 (61.11%). Dental granuloma showed higher NFκB expression compared to dental nongranuloma lesions in tooth caries (p=0.021).ConclusionThe dental granuloma tissue of dental caries showed an increase in NFκB expression. Understanding the role of NFκB might provide additional insights into the process of periapical lesion development.

SAT0614-HPR IDENTIFYING AND OPTIMISING MULTIPLE INTERVENTION COMPONENTS AND THEIR DELIVERY WITHIN A SELF-MANAGEMENT SMARTPHONE APP FOR PEOPLE WITH SJÖGREN’S SYNDROME: A QUALITATIVE STUDY

Background:Sjögren’s syndrome (SS) is an autoimmune rheumatic disease with diverse symptoms including mental and physical fatigue, dryness, pain and sleep disturbances. These symptoms are interconnected and rarely occur in isolation. Improving symptoms and quality of life requires people with SS to navigate multiple interventions and engage in self-management. Smartphone applications (apps) can deliver multiple cognitive and behaviour-based interventions in users’ everyday daily lives and are readily accessible. However, delivering several therapeutic interventions together within a single coherent self-management app requires systematic and evidence-based selection of intervention components, and an understanding of existing self-management approaches and their associated challenges for those living with SS.Objectives:To identify theory-based intervention components for inclusion in a SS self-management app. To understand the self-management approaches and challenges of those living with SS to inform in-app component delivery.Methods:First, to identify intervention components within the app, existing interventions that target each symptom of fatigue, dryness, pain, sleep disturbance were identified through a literature search. Their content was coded by the research team using behaviour change techniques and the Theoretical Domains Framework1. The content was grouped to form five intervention components which target multiple symptoms.Second, to understand SS self-management approaches and challenges, 13 people living with SS took part in a series of qualitative focus groups (n=6) and design workshops (n=7). Focus groups involved participants discussing their own self-management experiences and approaches (e.g. when and how they employed a variety of techniques). In design workshops participants sketched metaphors to explain these experiences and used craft materials to create “Magic Machines”2addressing their self-management challenges. Focus groups and design workshops were audio-recorded, transcribed, thematically analysed as a single data set, and findings mapped to the self-determination theory3dimensions of capability, autonomy, and relatedness.Results:Intervention components identified were: i) SS psychoeducation, ii) relaxation techniques, iii) activity pacing and goal setting, iv) assertiveness and communication skills, and v) sleep and dryness tips. Participants tackled complex symptom patterns (i.e. symptom interrelatedness and flares) using different self-management approaches; reactively (focusing on the most severe symptom) or systematically (one symptom at a time). Knowing which intervention techniques to choose was felt to be challenging; however the availability of multiple interventions techniques provided a sense of optimism and motivation. Participants were enthusiastic about accessing several intervention techniques via an app, but warned that smartphones and technology can exacerbate mental fatigue and eye dryness. The invisible nature of symptoms, and highly visible nature of management techniques (e.g. applying eye drops), presented further self-management challenges relating to their interactions with other people.Conclusion:Promising components to include in an SS app were identified but should be tested in an optimisation trial. The in-app delivery of component modules should be designed to support diverse self-management approaches, choice and autonomy, yet provide module recommendations and guidance when needed, and be simple to use to reduce mental fatigue and dry eye symptoms. A self-management app should also be designed to enable users to share information about SS with other people.

Ciprofloxacin-Induced Reaction Imitating a Lupus Flare: A Case Report

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect almost any organ in the body. It usually runs a chronic course with systemic inflammation, and age at diagnosis varies from 15 to 44 years. Laboratory reports often show high anti-nuclear antibody (ANA) levels, increased anti-double-stranded deoxyribonucleic acid (anti-dsDNA) levels, and low complement levels. 'Lupus flare' is a term used for an acute exacerbation of previously existing SLE. It usually manifests as an acute worsening of clinical signs and symptoms, along with an abrupt change in typical laboratory values. Triggers for a lupus flare include viral or bacterial infections, acute stress, and various environmental factors such as ultraviolet (UV) light. Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic used for various bacterial infections. On rare occasions, ciprofloxacin can cause adverse effects in the body, which may resemble an acute flare of SLE symptoms in patients with previously controlled disease. We have presented such a case of ciprofloxacin-induced reactions mimicking a lupus flare in an SLE patient.

SAT-500 Response to Tocilizumab Retreatment in Refractory Thyroid Eye Disease

Background: The current standard of care for moderate to severe thyroid eye disease (TED) is intravenous methylprednisolone (IVMP), though alternative immunosuppressive options are emerging. In a recent randomized trial, Tocilizumab (TCZ), an anti-IL-6 receptor antibody, demonstrated improved efficacy for corticosteroid-resistant TED compared to placebo. Clinical response to TCZ retreatment, however, has not been previously reported.Clinical case: A 64-year old man presented with progressive diplopia, eyelid retraction and edema and retrobulbar pain. Initial labs revealed TSH 0.221 uIU/mL, free thyroxine (FT4) 1.11 ng/dL, total T3 172 ng/dL and a thyroid stimulating immunoglobulin (TSI) index of 329 (normal < 140). The patient was a former cigarette smoker who had recently transitioned to e-cigarettes. He was treated with 12 weeks of IVMP with improvement in ocular redness and swelling. Three months following completion of treatment, he presented with worsening left sided proptosis, restrictive strabismus, and compressive optic neuropathy (CON) evidenced by deteriorating central acuity and color vision. He underwent urgent surgical decompression for CON with full restoration of visual acuity. He then received a second 12-week course of IVMP with concomitant orbital radiation. Of note, his hyperthyroidism was well controlled with methimazole. Two months after his second IVMP course, he had a third flare of ophthalmic symptoms. He was then treated with TCZ 8 mg/kg (800mg) IV monthly for six months. The patient’s Clinical Activity Score (CAS) improved from 4 to 2 and TSI index decreased from 610 to 92 (normal). He had significant improvement in periorbital edema, caruncle/plica swelling, and conjunctival injection. However, ten months following completion of the TCZ course he again complained of worsening diplopia and left proptosis. Of note, relapse of his TED symptoms was preceded by an increase in TSI from 92 to 300 two months prior. Orbital CT demonstrated progression of left orbitopathy and increased orbital apex crowding. Following these CT findings he was restarted on TCZ, of which he has now completed 5 additional infusions. His CAS has improved from 3 to 2 and TSI index has decreased from 284 to 100.Conclusion: This is the first reported case of response to successive courses of TCZ in relapsing, severe, corticosteroid-resistant TED. TCZ can be an effective option for refractory TED though retreatment may be necessary for recurrent inflammation. Further study of TCZ is required to determine its role in relapsing TED and the optimal duration of therapy needed.

Does weather trigger urologic chronic pelvic pain syndrome flares? A case-crossover analysis in the multidisciplinary approach to the study of the chronic pelvic pain research network.

To investigate whether meteorological factors (temperature, barometric pressure, relative humidity, ultraviolet index [UVI], and seasons) trigger flares in male and female urologic chronic pelvic pain patients. We assessed flare status every 2 weeks in our case-crossover study of flare triggers in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain 1-year longitudinal study. Flare symptoms, flare start date, and exposures in the 3 days preceding a flare or the date of questionnaire completion were assessed for the first three flares and at three randomly selected nonflare times. We linked these data to daily temperature, barometric pressure, relative humidity, and UVI values by participants' first 3 zip code digits. Values in the 3 days before and the day of a flare, as well as changes in these values, were compared to nonflare values by conditional logistic regression. Differences in flare rates by astronomical and growing seasons were investigated by Poisson regression in the full study population. A total of 574 flare and 792 nonflare assessments (290 participants) were included in the case-crossover analysis, and 966 flare and 5389 nonflare (409 participants) were included in the full study analysis. Overall, no statistically significant associations were observed for daily weather, no patterns of associations were observed for weather changes, and no differences in flare rates were observed by season. We found minimal evidence to suggest that weather triggers flares, although we cannot rule out the possibility that a small subset of patients is susceptible.

Effect of Lifestyle Factors on Outcomes in Patients With Inflammatory Bowel Diseases.

Various lifestyle factors including physical activity and obesity, stress, sleep, and smoking may modify the risk of developing inflammatory bowel diseases (IBDs). In patients with established IBD, these lifestyle factors may significantly impact the natural history and clinical outcomes. Recreational exercise decreases the risk of flare and fatigue in patients with IBD. In contrast, obesity increases the risk of relapse and is associated with higher anxiety, depression, fatigue, and pain and higher health care utilization. Obesity also modifies pharmacokinetics of biologic agents unfavorably and is associated with a higher risk of treatment failure. Sleep disturbance is highly prevalent in patients with IBD, independent of disease activity, and increases the risk of relapse and chronic fatigue. Similarly, stress, particularly perceived stress rather than major life events, may trigger symptomatic flare in patients with IBD, although its impact on inflammation is unclear. Cigarette smoking is associated with unfavorable outcomes including the risk of corticosteroid dependence, surgery, and disease progression in patients with Crohn's disease; in contrast, smoking does not significantly impact outcomes in patients with ulcerative colitis, although some studies suggest that it may be associated with a lower risk of flare. The effect of alcohol and cannabis use in patients with IBD is inconsistent, with some studies suggesting that cannabis may decrease chronic pain in patients with IBD, without a significant effect of biological remission. Although these lifestyle factors are potentially modifiable, only a few interventional studies have been conducted. Trials of structured exercise and psychological therapy including mindfulness-based therapies such as meditation and yoga and gut-directed hypnotherapy have not consistently demonstrated benefit in clinical and/or endoscopic disease activity in IBD, although may improve overall quality of life.