Colchicine Effectiveness and Safety in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis

Introduction: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common fever syndrome in childhood. High disease activity (DA) dramatically impacts the health-related quality of life. Thus, effective and safe treatment is crucial. Colchicine might be effective, but data are still lacking. Study aimed to assess colchicine safety and effectiveness in PFAPA.Methods: This single center study was conducted between 03/2012 and 05/2021 in PFAPA patients without variants in genetic panel testing aged ≤ 18 years fulfilling Marshall criteria and classification criteria of Gattorno et al. Exclusion criteria were elevated liver enzymes, impaired kidney function, celiac disease, lactose intolerance, previous/ongoing biologics, known colchicine-intolerance. Demographics, clinical characteristics, treatment, DA, colchicine effectiveness and safety were recorded at baseline, first and last visit. Colchicine was started at 0.5–1.0 mg/day. DA was captured by physician (PGA) and patient/parent (PPGA) global assessment on a 10 cm visual analog scale, categorized as mild (<2), moderate (2–4), and high (≥5). Adverse event (AE) monitoring included gastrointestinal symptoms, liver enzyme/creatinine elevation, leukopenia, neutropenia. Primary outcome included response (R; composite of PPGA + PGA decrease ≥2) at last follow-up. Secondary outcomes were partial response (PR; PGA decrease = 1 + PPGA decrease ≥1), no response (NR; unchanged/worsened PGA/PPGA), colchicine safety, flare characteristics.Results: Twenty-seven PFAPA patients were included, 52% were female, median age was 5.8 years (1–10.75), median follow-up time was 13 months. At baseline, median PPGA was high; median PGA moderate. All patients had febrile flares. Median flare frequency was every 4–5 weeks; median duration 5–6 days. Nine patients were pre-treated with corticosteroids, increasing flare frequency in 8/9. Primary Outcome: 17 patients (63%) were responders. Secondary outcomes: PR was achieved in 15%; NR in 22% at last follow-up. DA decreased significantly (p <0.0001). At last follow-up, 52% reported no flares, median flare duration decreased to 1–2 days. At first follow-up, 22% reported mild abdominal pain/diarrhea. Moderate abdominal pain/diarrhea occurred with ≥1 mg/day. Mild asymptomatic liver enzyme elevation or leucopenia were rare; no severe AE or colchicine discontinuation were observed.Conclusion: Colchicine seems to be safe, well-tolerated, and effective in PFAPA patients. It can be considered in children with moderate/high DA even those without corticosteroid-benefit.

Kepler-411 Star Activity: Connection between Starspots and Superflares

Stellar magnetic activity, just like that of the Sun, manifests itself in the form of flares and spots on the surface of the star. In the solar case, the largest flares originate from large active regions. In this work, we present a study of the activity of the star Kepler-411, including spot modeling from planetary transits. Our goal was to search for a connection between the area of starspots with the energy of superflares produced by this star. Kepler-411 is a K2V-type star with an average rotation period of 10.52 days, radius of 0.79 R ⊙, and a mass of 0.83 M ⊙, which was observed by the Kepler satellite for about 600 days. Transit mapping allowed for the characterization of 198 starspots with estimates of their radius and temperature. Kepler-411 starspots had an average radius of (17 ± 7) × 103 km and a mean temperature of 3800 ± 700 K. Visual inspection of the light curves of Kepler-411 yields the identification of 65 superflares. The detected superflares lasted from 8 to 260 minutes and their energy varied from 1033–1035 ergs. The power-law index of the flare frequency distribution as a function of energy is (−2.04 ± 0.13) for the flare on Kepler-411. A positive correlation between the area of starspots and the energy of superflares was found when considering the averages taken every 16–35 days, with the highest correlation occurring for averages every 21 days. This timing is probably related to the lifetime of the Kepler-411 spots.

Understanding flare in axial spondyloarthritis: novel insights from daily self-reported flare experience

Objectives Our objective was to explore daily self-reported experience of axial spondyloarthritis (axSpA) flare based on data entered into the Project Nightingale smartphone app (www.projectnightingale.org), between 5th April 2018 - 1st April 2020. Methods Paired t-tests were conducted for mean_flare_on and mean_flare_off scores for each recorded variable. Mean estimated difference between flare and non-flare values for each variable was calculated with 95% confidence intervals (CI). Mean, standard deviation (SD) and range were reported for flare duration and frequency. Participants with ≥10 days of data entry were included for affinity propagation cluster analysis. Baseline characteristics and mean flare on versuss flare off values were reported for each cluster. Welch’s t-test was used to assess differences between clusters. Results 143/189 (75.7%) participants recorded at least 1 flare. Each flare lasted a mean of 4.30 days (SD 6.82 days, range 1–78 days), a mean frequency of once every 35.32 days (SD 65.73, range 1–677 days). Significant relationships were identified between flare status and variable scores. Two clusters of participants were identified with distinct flare profiles. Group 1 experienced less severe worsening of symptoms during flare in comparison to Group 2 (p < 0.01). However, they experienced significantly longer flare duration (7.2 versuss 3.5 days, p < 0.01); perhaps indicating a prolonged, yet less intense flare experience. Groups were similar in terms of flare frequency and clinical characteristics. Conclusions Two clusters of participants were identified with distinct flare experiences, but similar baseline clinical characteristics. Smartphone technologies capture subtle changes in disease experience, not currently considered in clinical practice.

Simultaneous Multiwavelength Flare Observations of EV Lacertae

We present the first results of our ongoing project conducting simultaneous multiwavelength observations of flares on nearby active M dwarfs. We acquired data of the nearby dM3.5e star EV Lac using five different observatories: NASA’s Transiting Exoplanet Survey Satellite (TESS), NASA’s Neil Gehrels Swift Observatory (Swift), NASA’s Neutron Interior Composition Explorer (NICER), the University of Hawaii 2.2-meter telescope (UH88), and the Las Cumbres Observatory Global Telescope (LCOGT) Network. During the ∼25 days of TESS observations, we acquired three simultaneous UV/X-ray observations using Swift that total ∼18 ks, 21 simultaneous epochs totaling ∼98 ks of X-ray data using NICER, one observation (∼3 hr) with UH88, and one observation (∼3 hr) with LCOGT. We identified 56 flares in the TESS light curve with estimated energies in the range log E T (erg) = (30.5–33.2), nine flares in the Swift UVM2 light curve with estimated energies in the range log E UV (erg) = (29.3–31.1), 14 flares in the NICER light curve with estimated minimum energies in the range log E N (erg) = (30.5–32.3), and 1 flare in the LCOGT light curve with log E L (erg) = 31.6. We find that the flare frequency distributions (FFDs) of TESS and NICER flares have comparable slopes, β T = −0.67 ± 0.09 and β N = − 0.65 ± 0.19, and the FFD of UVOT flares has a shallower slope (β U = −0.38 ± 0.13). Furthermore, we do not find conclusive evidence for either the first ionization potential (FIP) or the inverse FIP effect during coronal flares on EV Lac.

Influence of climate factors on pediatric alopecia areata flares in Philadelphia, Pennsylvania

Patients with alopecia areata (AA) may experience episodic disease flares characterized by increasing hair loss that follow a seasonal pattern. However, no studies have examined whether specific climate factors contribute to the seasonal pattern of AA flares. Using Spearman rank correlation analyses, we assessed the association between climate variables and AA flare frequency per month in 336 children with AA in Philadelphia, Pennsylvania. Region-specific monthly values for average ambient temperature, air pressure, cloudiness, hours of sunlight, relative humidity, number of days with sun, number of days with rain, volume of precipitation, wind gust, wind speed, and UV index from January 2015 to December 2017 were obtained from World Weather Online. We found significant (P < 0.05) correlations between AA flare frequency and UV index (R = − 0.66), precipitation (R = − 0.66), number of days with rain (R = − 0.70), number of days with sun (R = 0.62), and air pressure (R = 0.80). Stratified analyses showed even stronger associations with UV index and precipitation in patients with an atopic comorbidity. New significant correlations appeared with temperature, wind speed, and UV index of the prior month. However, in patients who did not have atopic comorbidities, we generally observed weaker and non-significant correlations between climate and AA flare frequency. This study suggests that certain climate factors may mediate the seasonal pattern of AA flares and may contribute to AA pathogenesis. Atopic AA patients may be more susceptible to the influence of climate compared to those with no history of atopy.

Frequency, severity and costs of flares increase with disease severity in newly diagnosed systemic lupus erythematosus: a real-world cohort study, United States, 2004–2015

ObjectiveTo evaluate frequency, severity and costs of flares in US patients with newly diagnosed SLE.MethodsAdults diagnosed with SLE between January 2005 and December 2014 were identified from US commercial claims data linked to electronic medical records. Disease and flare severity during 1 year after diagnosis were classified as mild, moderate or severe using a claims-based algorithm. Study outcomes included frequency and severity of flares stratified by disease severity during the 1-year post-diagnosis period and all-cause healthcare costs of flares by severity at 30, 60 and 90 days after flare.ResultsAmong 2227 patients, 26.3%, 51.0% and 22.7% had mild, moderate and severe SLE, respectively. The overall annual flare rate was 3.5 and increased with disease severity: 2.2, 3.7 and 4.2, respectively, for mild, moderate and severe SLE (p<0.0001). Patients with severe SLE had a higher annual severe flare rate (0.6) compared with moderate (0.1) or mild SLE (0; p<0.0001). Mean total all-cause costs at 30, 60 and 90 days after flare were $16 856, $22 252 and $27 468, respectively, for severe flares (mild flares: $1672, $2639 and $3312; moderate flares: $3831, $6225, $8582; (p<0.0001, all time points)). Inpatient costs were the primary driver of the increased cost of severe flares.ConclusionsFlare frequency and severity in newly diagnosed patients with SLE increase with disease severity. After a flare, healthcare costs increase over the following 90 days by disease severity. Preventing flares or reducing flare rates and duration may improve outcomes and reduce healthcare costs.

What represents treatment efficacy in long-term studies of gout flare prevention? An interview study of people with gout

Objective The patient experience of gout flares is multidimensional with several contributing factors, including pain intensity, duration and frequency. There is currently no consistent method for reporting gout flare burden in long-term studies. This study aimed to determine which factors contribute to patient perceptions of treatment efficacy in long-term studies of gout flare prevention. Methods This study involved face-to-face interviews with people with gout using visual representations of gout flare patterns. Participants were shown different flare scenarios over a hypothetical 6-month treatment period portraying varying flare frequency, pain intensity and flare duration. The participants were asked to indicate and discuss which scenario they believed was most indicative of successful treatment over time. Quantitative data relating to the proportion of participants selecting each scenario were reported using descriptive statistics. A qualitative descriptive approach was used to code and categorize the data from the interview transcripts. Results Twenty-two people with gout participated in the semi-structured interviews. All three factors of pain intensity, flare duration and flare frequency influenced participants' perception of treatment efficacy. However, a shorter flare duration was the most common indicator of successful treatment, with half of participants (n = 11, 50%) selecting the scenario with a shorter flare duration over those with less painful flares. Conclusion Flare duration, flare frequency, and pain severity are all considered by patients with gout when considering treatment efficacy over time. Long term studies of gout should ideally capture all of these factors to better represent patients' experience of treatment success.

K2 Ultracool Dwarfs Survey – VI. White light superflares observed on an L5 dwarf and flare rates of L dwarfs

ABSTRACT $Kepler\, K2$ long cadence data are used to study white light flares in a sample of 45 L dwarfs. We identified 11 flares on 9 L dwarfs with equivalent durations of (1.3–198) h and total (UV/optical/IR) energies of ≥0.9 × 1032 erg. Two superflares with energies of &gt;1033 erg were detected on an L5 dwarf (VVV BD001): this is the coolest object so far on which flares have been identified. The larger superflare on this L5 dwarf has an energy of 4.6 × 1034 erg and an amplitude of &gt;300 times the photospheric level: so far, this is the largest amplitude flare detected by the Kepler/K2 mission. The next coolest star on which we identified a flare was an L2 dwarf: 2MASS J08585891+1804463. Combining the energies of all the flares which we have identified on 9 L dwarfs with the total observation time which was dedicated by Kepler to all 45 L dwarfs, we construct a composite flare frequency distribution (FFD). The FFD slope is quite shallow (−0.51 ± 0.17), consistent with earlier results reported by Paudel et al. for one particular L0 dwarf, for which the FFD slope was found to be −0.34. Using the composite FFD, we predict that, in early- and mid-L dwarfs, a superflare of energy 1033 erg occurs every 2.4 yr and a superflare of energy 1034 erg occurs every 7.9 yr. Analysis of our L dwarf flares suggests that magnetic fields of ≥0.13–1.3 kG are present on the stellar surface: such fields could suppress Type II radio bursts.