Frequency Of Flares Research Articles

Risk factors and diagnostic value for ultrasound-detected tendon monosodium urate crystal deposition in patients with gout

OBJECTIVE To evaluate frequency and patterns, risk factors of MSU (monosodium urate) crystal deposition at lower extremity tendon by ultrasonography in gout patients, and to explore diagnostic value by ultrasonography. METHODS Patients diagnosed with gout and age matched healthy controls had ultrasound scanning of both feet and knees including joints and tendons (achilles, quadriceps, and patellar tendon). Readers who scored the ultrasound scans for MSU crystal deposition were blinded to the patients' clinical diagnoses. Clinical characteristics were compared between positive and negative crystal deposition groups by US, and risk factors of MSU deposition in tendons were analyzed. Diagnostic values of MSU deposition were evaluated by ultrasonography according with positive MSU crystal in synovial fluid or tophi by polarized microscopy. RESULTS Eighty patients and eighty healthy controls were included. Thity-three patients (47.5%) had tophi by physical examination. The achilles tendon was the most commonly involved tendon site 41(51.2%), followed by the quadriceps tendons 22(27.5%), and patella tendon 10(12.5%). There were no MSU deposition in healthy control group at tendon by ultrasonography. Compared with negative MSU deposition at tendon site by ultrasonography, tendon MSU positive patients had longer mean gout duration [(87.3±40.9) months vs. (7.7±2.6) months, P=0.001];higher frequency of gout flare [2(1, 2) /year vs. 1(1, 1) /year, P=0.001]; higher BMI [(26.3±2.5) kg/m2vs. (23.3±2.1) kg/m2, P=0.05]. Also, the mean serum uric acid and creatinine levels were higher in tendon MSU positive group [(584.6±87.6) μmol/L vs. (460.4±96.7) μmol/L, P=0.001] and [(90.9±33.3) μmol/L vs. (70.6±40.2) μmol/L, P=0.02] separately. Logistic regression analysis showed gout duration and flare frequency were independent risk factors for MSU deposition at tendon by ultrasonography (P < 0.01). Joint or tophi aspirations were performed in all the eighty gout patients, and positive MSU crystals in synovial fluid analysis by polarized microscopy were defined as the golden standard of gout diagnosis. When compared with the golden standard, the sensitivity and specificity were 94.0% and 78.0% separately for MSU deposition at tendon by ultrasonography. CONCLUSION Tendon involvement at the lower extremity tendons in gout is very common. Long gout disease duration and high frequency of gout flare are both independent risk factors of tendon MSU deposition by ultrasonography. Ultrasonography had good sensitivity and specificity for detecting tendinous tophi and aggregates.

Surface and Oceanic Habitability of Trappist-1 Planets under the Impact of Flares

The discovery of potentially habitable planets around the ultracool dwarf star Trappist-1 naturally poses the question: could Trappist-1 planets be home to life? These planets orbit very close to the host star and are most susceptible to the UV radiation emitted by the intense and frequent flares of Trappist-1. Here, we calculate the UV spectra (100-450 nm) of a superflare observed on Trappist-1 with the K2 mission. We couple radiative transfer models to this spectra to estimate the UV surface flux on planets in the habitable zone of Trappist-1 (planets e, f, and g), assuming atmospheric scenarios based on a prebiotic and an oxygenic atmosphere. We quantify the impact of the UV radiation on living organisms on the surface and on a hypothetical planet ocean. Finally, we find that for non-oxygenic planets, UV-resistant life-forms would survive on the surface of planets f and g. Nevertheless, more fragile organisms (i.e., Escherichia coli) could be protected from the hazardous UV effects at ocean depths greater than 8 m. If the planets have an ozone layer, any life-forms studied here would survive in the habitable zone planets.

Flare Properties of A-type Stars in Kepler Data

Abstract We analyzed the long-cadence (LC) light curves of 5435 stars with effective temperatures of 7000–10,500 K in Data Release 25 of Kepler to extend the samples of A-type flare stars and study their flare properties. A total of 103 flare stars are detected, of which 72 have the Large Sky Area Multi-Object fiber Spectroscopic Telescope spectral types, resulting in 51 A-type stars, including 17 new and 34 known. A total of 352 flares are detected from the 51 stars. The flare durations, amplitudes, and energies in the Kepler band are calculated, with medians of 2.5 hr, 2.1 mmag, and 1035.8 erg, respectively. We give the flare frequency distribution (FFD) of the A-type stars. Within the same energy range, the flare rates of our FFD are lower than those in previous research, which was also based on Kepler LC data, and the FFD slope is consistent with that in the research. The activity–rotation relation of the A-type flare stars is shown for the first time, in which the flare activity decreases as the rotation period increases. The relation is similar to that of the late-type stars in previous studies. For the two relatively bright A-type flare stars, KIC 5360548 and KIC 9468475, three high-resolution spectra are observed on different nights for each of them, and radial velocities are calculated and compared with that of the previous research. The comparisons suggest that there is no evidence of the KIC 5360548 companion, and KIC 9468475 could have a low-mass companion.

Flare Rates, Rotation Periods, and Spectroscopic Activity Indicators of a Volume-complete Sample of Mid- to Late-M Dwarfs within 15 pc

Abstract We present a study of flare rates, rotation periods, and spectroscopic activity indicators of 125 single stars within 15 parsecs and with masses between 0.1 and 0.3 M ⊙ observed during the first year of the TESS mission, with the goal of elucidating the relationship between these various magnetically connected phenomena. We gathered multiepoch high-resolution spectra of each target, and we measured equivalent widths of the activity indicators helium I D3, Hα, and the calcium infrared triplet line at 8542.09 Å. We present 18 new rotation periods from MEarth photometry and 19 new rotation periods from TESS photometry. We present a catalog of 1392 flares. After correcting for sensitivity, we find the slope of the flare frequency distribution for all stars to have a standard value of α = 1.98 ± 0.02. We determine R 31.5, the rate of flares per day with energies above E = 3.16 × 1031 ergs in the TESS bandpass. We find that below a critical value of Hα EW = −0.71 Å, log R 31.5 increases linearly with increasing Hα emission; above this value, log R 31.5 declines rapidly. The stars divide into two groups: 26% have Hα in emission, high flare rates with typical values of log R 31.5 = −1.30 ± 0.08, and have Rossby numbers &lt;0.50. The remaining 74% show little to no Hα in emission and exhibit log R 31.5 &lt; −3.86, with the majority of these stars not showing a single flare during the TESS observations.

Activity–rotation in the dM4 star Gl 729

Aims. Recently, new debates about the role of layers of strong shear have emerged in stellar dynamo theory. Further information on the long-term magnetic activity of fully convective stars could help determine whether their underlying dynamo could sustain activity cycles similar to the solar one. Methods. We performed a thorough study of the short- and long-term magnetic activity of the young active dM4 star Gl 729. First, we analyzed long-cadence K2 photometry to characterize its transient events (e.g., flares) and global and surface differential rotation. Then, from the Mount Wilson S-indexes derived from CASLEO spectra and other public observations, we analyzed its long-term activity between 1998 and 2020 with four different time-domain techniques to detect cyclic patterns. Finally, we explored the chromospheric activity at different heights with simultaneous measurements of the Hα and the Na I D indexes, and we analyzed their relations with the S-Index. Results. We found that the cumulative flare frequency follows a power-law distribution with slope ~−0.73 for the range 1032–1034 erg. We obtained Prot = (2.848 ± 0.001) days, and we found no evidence of differential rotation. We also found that this young active star presents a long-term activity cycle with a length of about 4 yr; there is less significant evidence of a shorter cycle of 0.8 yr. The star also shows a broad activity minimum between 1998 and 2004. We found a correlation between the S index, on the one hand, and the Hα the Na I D indexes, on the other hand, although the saturation level of these last two indexes is not observed in the Ca lines. Conclusions. Because the maximum-entropy spot model does not reflect migration between active longitudes, this activity cycle cannot be explained by a solar-type dynamo. It is probably caused by an α2-dynamo.

Analysis of arthritis flares after achievement of inactive disease with methotrexate monotherapy in juvenile idiopathic arthritis

To investigate the frequency of arthritis flare and factors affecting occurrence of flare in children with juvenile idiopathic arthritis (JIA) who achieved inactive disease (ID) with methotrexate (MTX) monotherapy. A total of 217 patients were included. The modality of treatment discontinuation, time of MTX withdrawal, and disease course were examined retrospectively. For each patient, the first episode of ID after MTX start was evaluated. Patient follow-up was censored at occurrence of flare or at last visit with persistent ID. 170 patients (78.3%) had arthritis flare after a median of 1.6 years, whereas 47 (21.7%) maintained ID until last visit, after a median of 3 years. 54.2% of patients had discontinued MTX after ID, whereas 45.8% were still receiving MTX at the time of study censoring. Among patients who had MTX withdrawn, the median interval between ID and MTX stop was 1.5 years. Occurrence of flare was more common in patients who were still receiving MTX at study censoring than in those who had discontinued MTX (p<0.001). Most patients (78.8%) had MTX tapered over time by increasing the interval between doses. Tapering modality was comparable between patients with flare and persistent ID. Only 7.7% of the patients had a biologic DMARD started at the time of flare. Our results confirm that children with JIA who achieve ID with MTX monotherapy have a high risk of arthritis flare. The risk of flare was independent of withdrawal strategy. Most flare episodes were not treated with biologic therapy.

Stellar flares versus luminosity: XUV-induced atmospheric escape and planetary habitability

ABSTRACT Space weather plays an important role in the evolution of planetary atmospheres. Observations have shown that stellar flares emit energy in a wide energy range (1030–1038 erg), a fraction of which lies in X-rays and extreme ultraviolet (XUV). These flares heat the upper atmosphere of a planet, leading to increased escape rates, and can result in atmospheric erosion over a period of time. Observations also suggest that primordial terrestrial planets can accrete voluminous H/He envelopes. Stellar radiation can erode these protoatmospheres over time, and the extent of this erosion has implications for the planet’s habitability. We use the energy-limited equation to calculate hydrodynamic escape rates from these protoatmospheres irradiated by XUV stellar flares and luminosity. We use the flare frequency distribution of 492 FGKM stars observed with TESS to estimate atmospheric loss in habitable zone planets. We find that for most stars, luminosity-induced escape is the main loss mechanism, with a minor contribution from flares. However, flares dominate the loss mechanism of ∼20 per cent M4–M10 stars. M0–M4 stars are most likely to completely erode both their proto- and secondary atmospheres, and M4–M10 are least likely to erode secondary atmospheres. We discuss the implications of these results on planetary habitability.

A Case Series: The Novel Use of Emapalumab and Ruxolitinib in Acquired Malignancy-Associated HLH in Pediatric Patients

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory syndrome that is classified into primary and acquired forms. Primary-HLH has genetic components related to defects in cytotoxic T and NK cells. The acquired form of HLH is classified based on the underlying triggers of immune dysregulation through malignancy, infections, and/or autoimmune processes. The standard of care is established with etoposide and dexamethasone, but there are currently no guidelines for refractory HLH or cases with confounding presentations with infection or malignancy. We describe cases of malignancy-associated HLH (m-HLH) in pediatric patients to discuss the intricacies in the initial diagnostic considerations, the balance of therapeutic regimens and their toxicities, and the novel use of emapalumab and ruxolitinib in refractory patients. We discuss a 16-year-old female with NK/T-cell lymphoma of the nasopharynx who presented in septic shock with pancytopenia and DIC. Diagnostic considerations included progressive lymphoma, bacteremia, and EBV viremia as possible explanations for her shock physiology. HLH was a consideration on admission given her presentation, but she did not meet criteria until HD#7 with ferritin of 740ng/mL (ref 10-291ng/mL), soluble IL-2 receptor (CD25) of 10,600pg/mL (ref &amp;lt;1033pg/mL), sCD163 of 5,636ng/mL (ref 387-1,785ng/mL) and an abnormal NK cell function. Standard treatment with etoposide and dexamethasone showed minimal effect, as did the introduction of rituximab. Gemcitabine and oxaliplatin were started as treatment for her lymphoma as the driver of her HLH, but she developed acute decompensation with hemodynamic instability and multi-organ system failure. Her systemic inflammation worsened as evidenced by a rise in her ferritin to 15,462ng/mL and sIL-2 receptor to 28,700pg/mL. Her CXCL9, a downstream chemokine and marker of IFN-gamma activity shown to be elevated in HLH, had a dramatic increase to 106,918 pg/mL (ref &amp;lt;121pg/mL). A decision to hold treatment for her lymphoma was made to reduce toxicities and better manage her HLH. Compassionate use of emapalumab, an IFN-gamma inhibitor indicated in primary HLH, led to dampening of her systemic inflammatory processes with resolution of fevers and signs of recovery of her hepatobiliary, renal, and gastrointestinal systems. We also describe a 17-year-old male who presented with T-ALL and bacteremia who developed HLH during induction-chemotherapy with complications from bacterial sepsis and fulminant fungemia. He represented a diagnostic conundrum throughout his induction chemotherapy with persistent fevers despite appropriate treatment and improvement of his bacteremia and fungemia. It was not until HD#50 that he met criteria for HLH with the addition of a ferritin level of 6,073ng/mL. He had limited response to treatment and had multi-system toxicities from the therapies for his HLH, ALL, and fungemia that necessitated frequent adjustments to his treatment plans. The treatment for his HLH was not standard given the toxicities. Etoposide was never in consideration given concerns for myelosuppression and dexamethasone was not given at full doses due to intolerance but was given over a prolonged duration of months. His course included a waxing and waning response to a combination of steroids and IVIG with recurrent admissions for presumed HLH flares. A trial of ruxolitinib, a JAK inhibitor, demonstrated response with stabilization of his hyperinflammatory state. Although not curative, as evidenced by his persistent hyperferritinemia, the use of ruxolitinib has allowed him to better tolerate his chemotherapy and improve his overall quality of life with a decrease in frequency of flares and hospitalizations. These cases highlight the intricacies of the management of m-HLH in pediatric patients with the spectrum of disease severity and complex diagnostic evaluations one must consider at presentation. Due to the toxicity of treatment options for often concurrent processes of malignancy, infection, and HLH, novel therapeutics such as emapalumab and ruxolitinib are required and should be evaluated in larger studies. Furthermore, guidelines for the management of pediatric m-HLH are required with inclusion of adjustments to standard therapy based on toxicity, inciting factors, concurrent processes, and the incorporation of novel therapeutics to achieve improved outcomes. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Ruxolitinib and emapalumab for refractory acquired HLH in Pediatric patients.

Anti-MDA5 autoantibodies associated with juvenile dermatomyositis constitute a distinct phenotype in North America.

Myositis-specific autoantibodies have defined distinct phenotypes of patients with juvenile myositis (JIIM). We assessed the frequency and clinical significance of anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody-associated JIIM in a North American registry. Retrospective examination of the characteristics of 35 JIIM patients with anti-MDA5 autoantibodies was performed, and differences from other myositis-specific autoantibody groups were evaluated. Anti-MDA5 autoantibodies were present in 35/453 (7.7%) of JIIM patients and associated with older age at diagnosis, and lower serum creatine kinase and aldolase levels. Patients with anti-MDA5 autoantibodies had more frequent weight loss, adenopathy, arthritis, interstitial lung disease (ILD), and less frequent falling compared with anti-transcriptional intermediary factor 1 (TIF1), anti-nuclear matrix protein 2 (NXP2)and myositis-specific autoantibody/myositis-associated autoantibody-negative patients. They had a different season of diagnosis and less frequent mechanic's hands and ILD compared with those with anti-synthetase autoantibodies. Anti-MDA5 patients received fewer medications compared with anti-TIF1, and corticosteroid treatment was shorter compared with anti-TIF1 and anti-nuclear matrix protein 2 autoantibody groups. The frequency of remission was higher in anti-MDA5 than anti-synthetase autoantibody-positive JIIM. In multivariable analyses, weight loss, arthritis and arthralgia were most strongly associated with anti-MDA5 autoantibody-positive JIIM. Anti-MDA5 JIIM is a distinct subset, with frequent arthritis, weight loss, adenopathy and less severe myositis, and is also associated with ILD. Anti-MDA5 is distinguished from anti-synthetase autoantibody-positive JIIM by less frequent ILD, lower creatine kinase levels and differing seasons of diagnosis. Anti-MDA5 has comparable outcomes, but with the ability to discontinue steroids more rapidly and less frequent flares compared with anti-TIF1 autoantibodies, and more frequent remission compared with anti-synthetase JIIM patients.

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).

Metformin as Adjunctive Therapy for Pediatric Patients With Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder seen in adolescents and adults characterized by abscesses, sinus tracts and scarring, typically affecting intertriginous skin. Treatments often provide suboptimal control of the disease, and there are limited reports of therapies utilized in the pediatric population. There are no published guidelines or consensus for the treatment of pediatric HS. To evaluate the clinical efficacy and safety of metformin as adjunctive treatment in adolescent patients with HS who have not responded to standard therapies at a single institution. Retrospective chart review identified 16 pediatric patients treated with metformin as adjunctive therapy for HS. Baseline scores were Hurley 1 in eleven (69%) and Hurley 2 in five (31%) patients. Follow-up visit data showed six (67%) patients were Hurley 1 and three (33%) patients were Hurley 2; five patients showed improvement on metformin with decreased frequency of flares, and five patients had no improvement. Six patients were lost to follow up or data was not available. Two patients discontinued metformin therapy due to side effects, including gastrointestinal distress and mood changes; the third patient discontinued due to lack of improvement. Two patients had mildly elevated liver transaminases prior to metformin initiation which improved while on metformin therapy. For some pediatric patients, metformin as an adjunctive therapy may help improve control of HS with minimal side effects. Adequately designed and controlled studies are needed to further evaluate the role of metformin, and efficacy, tolerability and safety in the pediatric HS patients. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5447.

Statistical properties of radio flux densities of solar flares

Short timescale flux variations are closely related to the energy release process of magnetic reconnection during solar flares. Radio light curves at 1, 2, 3.75, 9.4, and 17 GHz of 209 flares observed by the Nobeyama Radio Polarimeter from 2000 to 2010 are analyzed with a running smooth technique. We find that the impulsive component (with a variation timescale shorter than 1 s) of 1 GHz emission of most flares peaks at a few tens of solar flux unit and lasts for about 1 minute and the impulsive component of 2 GHz emission lasts a shorter period and peaks at a lower flux level, while at the three high frequency channels the occurrence frequency of flares increases with the decrease of the flux density up to the noise level of the corresponding background. However, the gradual components of these emissions have similar duration and peak flux density distributions. We also derive the power spectrum on different timescales and a normalized wavelet analysis is used to confirm features on short timescales. At a time resolution of 0.1 s, more than ∼60% of these radio light curves show significant flux variation on 1 s or shorter time scales. This fraction increases with the decrease of frequency and reaches ∼100% at 1 GHz, implying that short timescale processes are universal in solar flares. We also study the correlation between the impulsive radio flux densities and soft X-ray fluxes obtained with the GOES satellites and find that more than 65% of the flares with an impulsive component have their impulsive radio emission reach a peak value ahead of the soft X-ray fluxes and this fraction increases with the radio frequency.

Association of influenza infection with hospitalisation-related systemic lupus erythematosus flares: a time series analysis.

This study aimed to investigate whether the influenza annual outbreak in Korea is related to hospitalisation-related flares in systemic lupus erythematosus (SLE) patients. The weekly frequency of hospitalisation-related SLE flares (2012-2015) was collected from the Korean National Health Insurance claim database. The weekly laboratory-confirmed detection rate of influenza infection was obtained from the Korea Centers for Disease Control and Prevention database. A generalised linear model was used to examine the relative risks (RRs) of hospitalisation-related SLE flares associated with influenza infection, after adjusting for time trends and meteorological data. A total of 2,223 hospitalisation-related SLE flares were analysed. An interquartile range (24.5%) increase in influenza infection was associated with a 14.0% increase in hospitalisation-related SLE flares (RR, 1.14; 95% confidence interval [CI]: 1.04-1.25; p=0.006). In addition, influenza infections at lag 0-1 (over 2 weeks including concurrent and 1 previous week) and lag 0-2 (over 3 weeks including concurrent and 2 previous weeks) were associated with increase in hospitalisation-related SLE flares (RR, 1.14; 95% confidence interval [CI]: 1.03-1.26; p=0.014 and RR, 1.13; 95% CI: 1.02-1.26; p=0.023). Significant associations were especially observed in women (RR, 1.15; 95% CI: 1.15-1.16; p=0.006) and immunosuppressant (RR, 1.26; 95% CI: 1.26-1.27; p<0.001) or glucocorticoid recipients (RR, 1.17, 95% CI: 1.16-1.17; p=0.004). This study shows a significant association between seasonal influenza infection and flares in SLE patients, which suggests influenza can be a novel environmental risk factor for SLE flares.

Sub-classification of Hidradenitis suppurativa: a cross-sectional study

The typical Hidradenitis Suppurativa (HS) patient is a young woman with axillary and groin involvement, but the spectrum of the disease presentation is broad and no internationally acknowledged sub-classification of the disease exists to date. It is however speculated that different, yet unidentified, subtypes may respond differently to different treatments or carry a different prognosis. Classification according to self-reported clinically meaningful outcomes for patients offer practical advantages. Our objective was to build an empirical framework for sub-classification of HS patients based on the frequency of HS flares in various anatomic locations, using a cross-sectional questionnaire-based design. All patients with a clinically confirmed diagnosis of HS registered at our department until March 1, 2017 were invited to participate. The frequency of HS flares in various anatomic locations was used for identification of possible HS subtypes using Principal Component Analysis (PCA) and cluster analysis. A total of 524 (62%) of 845 invited patients answered the questionnaire; 402 (76.7%) were female. From the cluster analysis, we identified two possible subtypes of HS, labeled the "upper type" and the "lower type". The "upper type" was characterized by repeated outbreaks in axillary and mammary regions. Meanwhile, the "lower type" was characterized by outbreaks in the inguinal, genital, perianal, and gluteal regions. Our findings support the notion that HS can be sub-classified and imply that the pattern of where lesions are located may be an important element in future HS sub-classification systems.

Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity

Atopic dermatitis (AD) is a common skin disease affecting up to 20% of the global population, with significant clinical heterogeneity and limited information about molecular subtypes and actionable biomarkers. Although alterations in the skin microbiome have been described in subjects with AD during progression to flare state, the prognostic value of baseline microbiome configurations has not been explored. Our aim was to identify microbial signatures on AD skin that are predictive of disease fate. Nonlesional skin of patients with AD and healthy control subjects were sampled at 2 time points separated by at least 4 weeks. Using whole metagenome analysis of skin microbiomes of patients with AD and control subjects (n= 49 and 189 samples), we identified distinct microbiome configurations (dermotypes Aand B). Blood was collected for immunophenotyping, and skin surface samples were analyzed for correlations with natural moisturizing factors and antimicrobial peptides. Dermotypes were robust and validated across 2 additional cohorts (63 individuals), with strong enrichment of subjects with AD in dermotype B. Dermotype B was characterized by reduced microbial richness, depletion of Cutibacterium acnes, Dermacoccus and Methylobacterium species, individual-specific outlier abundance of Staphylococcus species (eg, S epidermidis, S capitis, S aureus), and enrichment in metabolic pathways (eg, branched chain amino acids and arginine biosynthesis) and virulence genes (eg, β-toxin, δ-toxin) that defined a pathogenic ecology. Skin surface and circulating host biomarkers exhibited a distinct microbial-associated signature that was further reflected in more severe itching, frequent flares, and increased disease severity in patients harboring the dermotype B microbiome. We report distinct clusters of microbial profiles that delineate the role of microbiome configurations in AD heterogeneity, highlight a mechanism for ongoing inflammation, and provide prognostic utility toward microbiome-based disease stratification.

Latent Class Growth Analysis of Gout Flare Trajectories: A Three-Year Prospective Cohort Study in Primary Care.

To investigate the existence of distinct classes of gout flare trajectories and compare their gout-specific, comorbid, and sociodemographic characteristics. In a prospective cohort study, adults with gout who were registered with 20 general practices self-reported the number of gout flares experienced at baseline and after 6, 12, 24, and 36 months via postal questionnaires. Latent class growth analysis (LCGA) was used to identify distinct gout flare trajectory classes. Statistical criteria and clinical interpretability were used to decide the optimal number of classes. Baseline comorbidities, medications, and sociodemographic and gout-specific characteristics of members of each class were described. A total of 1,164 participants (mean ± SD age 65.6 ± 12.5 years; 972 [84%] male) were included. Six latent gout flare trajectory classes were identified: "frequent and persistent" (n = 95), "gradually worsening" (n = 276), "frequent then improving" (n = 14), "moderately frequent" (n = 287), "moderately frequent then improving" (n = 143), and "infrequent" (n = 349). The "frequent and persistent" trajectory had the most class members classified as obese and, along with the "gradually worsening" class, the highest proportion who were socioeconomically deprived. The "frequent and persistent," "gradually worsening," and "frequent then improving" classes had the highest proportions of class members with an estimated glomerular filtration rate <60 ml/minute/1.73 m2 . The "infrequent" gout flare class was associated with more frequent allopurinol use and lower urate levels. Six distinct gout flare trajectories were identified. Infrequent flares were associated with allopurinol use and lower serum urate levels, supporting the use of urate-lowering therapy to reduce flare frequency. The characteristics of flare trajectory classes could help to target interventions and improve patient care.

Adolescents\u2019 experiences of fluctuating pain in musculoskeletal disorders: a qualitative systematic review and thematic synthesis

BackgroundAdolescents with chronic musculoskeletal pain experience daily fluctuations in pain. Although not all fluctuations are bothersome, pain flares are a distinct type of symptom fluctuation with greater impact. Since literature on the experience of pain flares is non-existent, the aim of this review was to (i) synthesise the qualitative literature on adolescents’ experiences of fluctuating pain in musculoskeletal disorders in order to (ii) identify knowledge gaps to inform future research on pain flares.MethodsElectronic databases (CINAHL, MEDLINE, EMBASE, PsycINFO), grey literature and reference lists were searched from inception to June 2018 for qualitative studies reporting adolescents’ experiences of pain. Comprehensiveness of reporting was assessed using the Consolidated Criteria for Reporting Qualitative Health Research. Studies were analysed using thematic synthesis.ResultsOf the 3787 records identified, 32 studies (n = 536) were included. Principal findings were synthesised under three key themes: 1) symptom experience, 2) disruption and loss, and 3) regaining control. The first theme (symptom experience) describes adolescent’s perception and interpretation of pain fluctuations. The second theme (disruption and loss) describes the physical, social and emotional constraints faced as a result of changes in pain. The third theme (regaining control) describes coping strategies used to resist and accommodate unpredictable phases of pain. Each theme was experienced differently depending on adolescents’ characteristics such as their developmental status, pain condition, and the duration of the pain experience.ConclusionsAdolescents with chronic musculoskeletal pain live with a daily background level of symptoms which frequently fluctuate and are associated with functional and emotional difficulties. It was not clear whether these symptoms and challenges were experienced as part of ‘typical’ fluctuations in pain, or whether they reflect symptom exacerbations classified as ‘flares’. Further research is needed to explore the frequency and characteristics of pain flares, and how they differ from their typical fluctuations in pain. The review also highlights areas relating to the pain experience, symptom management and health service provision that require further exploration to support more personalised, tailored care for adolescents with chronic musculoskeletal pain.

S0780 Patient-Reported Disease Activity in a Large Sample of Ulcerative Colitis (UC) Patients Using Social Media-Delivered Questionnaires

INTRODUCTION: Therapy for IBD should have dual goals of improving symptoms and mucosal healing. PROs used for approval of UC treatments include number of bowel movements and bloody stools. Research highlights discordance between PROs and mucosal healing. The aim of this cross-sectional survey of UC patients is to understand patient perspectives on UC symptoms and disease burden. We hypothesized that UC patients experience disease activity despite treatment and current PROs fail to capture the full impact of disease on patients' lives. METHODS: IBD In America survey recruited patients via InflammatoryBowelDisease.net and associated social platforms in 2019. Patients self-reported an IBD diagnosis, were 18+, lived in U.S., and participated without monetary incentive. Survey questions addressed diagnosis, symptoms, QoL, treatment, demographics, etc. Survey terms were based on how patients discuss UC in the IBD online community. Remission was defined as “significant reduction of symptoms without an actual cure.” Flare was defined as “temporary intensification of symptoms.” Patients were categorized by disease activity based on number of flares and remission status during the past year. RESULTS: Of 487 patients with UC, mean age 45.6 (SD 16.0); 85% female; 89% moderate to severe; 78% diagnosed in past 5 years; and 51% taking 5ASAs, 37% biologics/JAKs, and 23% immunomodulators. Despite treatment, 46% experienced 15+ symptom days in past month. Fatigue was most frequent complaint (86%) followed by urgency to move bowels (80%), abdominal pain (76%), joint pain (67%), and bloating (66%). Daily pain was experienced by 32%; even patients in remission with no flares experienced pain at least once a month (55%). Difficulty completing daily tasks was reported by 37%, and 27% felt their UC was not controlled despite efforts to manage. 7% reported being in remission (past year) and no symptoms (past month). CONCLUSION: Most UC patients experience frequent symptoms and flares while on treatment. The most common symptoms are not considered in PROs nor addressed with current treatment. A more holistic approach to patient disease is needed.

S0773 Association of Statins and NSAIDS With Flare of Inflammatory Bowel Diseases (IBD)

INTRODUCTION: In animal models, statins (Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors) have been shown to inhibit pro-inflammatory gene expression by blocking Nf-kB (Nuclear Factor kappa-light-chain-enhancer) signaling. Effect of statin on flare of Inflammatory bowel disease (IBD) has not been well studied. Statins also have antifibrotic activity which is unrelated to the anti-inflammatory effect of the drug. Previous studies on impact of Nonsteroidal anti-inflammatory drugs (NSAIDS) on IBD have shown increased as well as decreased flares. We aimed to look at whether use of statins and NSAIDS was associated with reduced rate of flares in patients of IBD, Ulcerative Colitis (UC) and Crohn’s Disease (CD). METHODS: We performed a retrospective cohort study on all patients in our IBD database after obtaining approval from Institutional review board (IRB). IBD patients exposed to statin and NSAIDS were compared to unexposed patients. Outcome was evaluated using Chi-square (X2) analysis. P < 0.05 was considered significant. RESULTS: Our study included 2978 patients. Of these, 1595 had UC, 1367 had CD and rest had IC (Indeterminate colitis). Six hundred sixty-eight patients had statin use and 2310 had no statin use. Statin use was associated with increased flare of IBD in general as well as strongly associated with UC flare (P = .042 and .005 respectively). There was no association between statin exposure and CD flare (P = .984). Exposure to NSAIDS was not associated with increased or decreased frequency of flares in IBD, including UC, CD, and IC (Table 1). CONCLUSION: Our observational analysis showed that statin use is associated with decreased flares of UC but not with CD. Anti-inflammatory effect of statin could be effective in reducing the inflammation seen in mucosa in UC. In CD, antifibrotic effect of the statins may help in prevention of transmural involvement of the gastrointestinal tract and reduce complications, including flares. NSAIDS exposure was not associated with flare of CD. Prospective and randomized control trial studies on effect of statins and NSAIDS on IBD are necessary in future.Table 1.: showing statin and NSAID exposure with IBD flares

S0671 The Association of Frailty With Mortality and Relapse Frequency in Inflammatory Bowel Disease

INTRODUCTION: Frailty represents a state of diminished physiologic reserve. While the influence of frailty on gut immune response, inflame-aging and microbiome composition is subject to ongoing investigation, limited data exists on clinical outcomes in frail inflammatory bowel disease (IBD) patients. We tested the hypothesis that a modified frailty index will predict mortality and propensity for more frequent flares of inflammatory bowel disease. METHODs: An observational analysis of a retrospectively collected data from a single center in patients with Ulcerative Colitis and Crohn's disease was performed. Study period was 2008–2019. A 7 factor IBD frailty index was modified from the Canadian Study of Health and Aging Frailty Index. For each patient a frailty score and a frailty index were calculated. A frailty index of >0.27 was used to define a frailty. Multivariate logistic regression analyses were conducted to assess the probability of mortality and >5 IBD flares in frail and non-frail patients, while controlling for potential comorbid confounders. The calibration of logistic models was tested via Hosmer-Lemeshow test; predictive capacity was assessed via a c-statistic obtained from receiver operating curves. RESULTS: A total of 2978 patients were included; 53.5% with Ulcerative colitis, 0.5% with indeterminate colitis and the rest with Crohn's. The prevalence of frailty was 32% in this population of patients with IBD. Frail patients with IBD were more frequently older, female, had a higher mean BMI and were more often smokers (P < 0.001 for all via two-tailed t-tests and chi-square analysis). The prevalence of mortality in frail patients was statistically higher than the mortality prevalence in the non-frail (11.42% vs 3.75%, P < 0.01). Similarly, a higher proportion of frail patients experienced >5 IBD flares than non-frail patients (35.6% vs 27.5%, P < 0.001) through the study period. On regression analysis (Figure 1), frailty was associated with highest odds for mortality in patients with IBD (odds ratio 1.52, confidence interval 1.07–2.16, P = 0.01). Frail status did not predict the odds of having >5 IBD relapses as compared to non-frail patients (odds ratio 1.20, confidence interval 0.99–1.45, P = 0.05). CONCLUSION: This study provides the first evidence of an association between frailty and mortality in patients with inflammatory bowel disease. Potential areas of further investigation include phenotypic assessments of frailty, rather than an index approach utilized herein, in patients with IBD.Figure 1.: The Impact of Frailty on IBD Mortality.Figure 2.: The Impact of Frailty on IBD Flare Frequency.