Autosomal dominant pathogenic variants in PLCG2 are associated with autoinflammation and PLCG2–associated antibody deficiency and immune dysregulation (APLAID), characterized by immunological abnormalities and multi-system inflammation. Descriptions of associated neurological manifestations and vascular anomalies are limited. We describe three patients with APLAID, vasculopathies, neuroinflammation, and cerebral vascular tortuosity. These cases highlight underrecognized and clinically important manifestations of APLAID. All three patients had de novo variants in PLCG2 and early systemic inflammatory and immunodeficiency findings within the spectrum of APLAID (e.g. immune laboratory abnormalities, skin and gastrointestinal inflammation, and frequent infections). Additionally, they had notable neurological and vascular findings. Patient #1 (PLCG2 c.3420T > A; p.Asp1140Glu) is a female who had focal seizures at 16 months old. Magnetic resonance imaging (MRI) revealed right parietal leptomeningeal enhancement with white matter changes. MR angiography (MRA) showed cerebrovascular tortuosity and stenoses without evidence of vasculitis. She had extensive veno-lymphatic malformation in the thorax, abnormal renal vasculature, inferior vena cava (IVC) atresia, and bilateral pulmonary vein stenosis (PVS). Patient #2 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at four years old had an episode of status epilepticus. MRI revealed a right parietal infarct with surrounding leptomeningeal enhancement and MRA demonstrated abnormal caliber of the right middle cerebral artery (MCA), arterial tortuosity, and carotid aneurysms. His course was complicated by aortic root dilation and bilateral PVS. Patient #3 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at 16 months had a right sided focal motor seizure. MRI demonstrated infarct with associated sulcal enhancement predominantly in the left cerebral hemisphere. MRA found excessive vascular tortuosity and fenestrations. He has a dilated aortic root and ventricular septal defect (VSD). We present three cases of APLAID complicated by significant cerebrovascular tortuosity and seizure and two with cerebral ischemia. The etiology of stroke and/or seizures in these patients is unclear, but vasculopathy leading to perfusion deficits, neuroinflammation, or thrombosis due to underlying thrombotic diathesis or abnormal vascular anatomy may have contributed. We recommend all patients with APLAID undergo monitoring for neurologic manifestations. Additionally, we highlight important vasculopathic findings such as PVS, where early recognition for directed treatment is critical.

OBJECTIVE:To explore congruence between child self-reported and caregiver-proxy-reported health-related quality of life (HRQOL) over time in juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematosus (cSLE), and to identify factors associated with the level of congruence. METHODS:Data were from an observational, longitudinal cohort study conducted to validate the Patient-Reported Outcomes Measurement Information System (PROMIS) measures. HRQOL was assessed at baseline, 6, and 12 months. Four hundred fifty-one children (8-17 years) diagnosed with JIA or cSLE and their caregivers completed the PROMIS Pediatric and Parent Proxy measures, respectively. A 1-way random-effects model was used to estimate the intraclass correlation coefficient (ICC) for congruence between child and caregiver reports, and multivariable mixed-effect models were used to identify associated demographic and clinical factors. RESULTS:The study cohort (87.1% JIA) had a mean age of 13.8 years and were 71.4% female. Across all HRQOL domains, child self-reported and caregiver-proxy-reported mobility, physical activity, fatigue, pain interference, depressive symptoms, and psychological stress had moderate associations (ICC 0.50-0.68), whereas child self-reported and caregiver-proxy-reported family relationships and anxiety were weakly associated (ICC 0.34-0.42). Older children had higher congruence with their caregivers on symptom domains (0.25 to 0.75 points) than younger children; female children had higher congruence with their caregivers on psychological symptoms (-2.20 to -1.98 points) than male children. CONCLUSION:Caregivers provide complementary information on the physical aspects of HRQOL, with a tendency to estimate worse symptoms and decreased functioning. Child self-report remains the gold standard for understanding HRQOL in pediatric populations with rheumatic diseases.

RELA-related disease is a rare, autosomal-dominant condition presenting with immune dysregulation and immunodeficiency. RELA encodes the p65 subunit, a component of the canonical NFκB pathway. The underlying pathogenesis, at least in part, involves impaired NFκB activation, increased susceptibility to TNFα-induced apoptosis, and hyperinflammation. To date, only a modest number of cases have been documented worldwide, and the full clinical and functional spectrum of disease remains incompletely defined. This study represents a large global cohort identified with RELA variants, comprising 40 patients from 30 institutions, expanding our previous report of a single large kindred (1). The clinical spectrum includes arthritis, mucocutaneous ulcers, uveitis, dermatitis, irritable bowel disease, recurrent infections, lymphopenia, hypogammaglobulinemia, recurrent fevers, and susceptibility to neoplasia. The patients represent 36 kindreds with 28 unique RELA variants, of which 15 are missense, 7 nonsense, and 6 frameshift variants. Fifteen are in the Rel homology domain, 7 in the transcriptional activation domain, and 6 in the C-terminal region proximal to TAD (Fig. 1). Functional studies assessed the canonical NFκB pathway in 27% of the cohort (n = 11; healthy controls = 40). Patient peripheral blood mononuclear cells (PBMCs) were used to quantify total and phosphorylated p65 (ph-p65, Ser529) by flow cytometry after stimulation with PMA (100 ng/ml) and ionomycin (1 uM). In 8 patients, we assessed the kinetics of IκBα degradation, required for p65 phosphorylation and nuclear translocation of p65/p50. All patients tested had decreased total p65, while 64% had decreased ph-p65 with altered phosphorylation kinetics. Nearly 45% had impaired IκBα degradation. One patient (P4) demonstrated increased IκBα degradation and ph-p65, while a related proband (P1) had decreased ph-p65. Additionally, P4 did not have the same mucocutaneous clinical phenotype as P1 despite sharing the same RELA variant. This could reflect the effect of other genetic modifiers, epigenetic, environmental, or stochastic variations, which could lead to variable expressivity and/or incomplete penetrance. All patients appeared to have haploinsufficiency, as none had normal levels of p65. This study expands the clinical and genetic spectrum of RELA-related disease and provides mechanistic insights into the impact of these variants on p65 phosphorylation and downstream function, resulting in variable expressivity.Figure 1.RelA protein structure. Represents unique variant locations and categories, key domains, and phosphorylation sites. Source: UniProt. Adapted from (2). BioRender.

OBJECTIVE:To assess the validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric measures in patients with chronic nonbacterial osteomyelitis (CNO). METHODS:Within the longitudinal patient registry of CNO, English-speaking patients aged 8 years and older self-reported PROMIS Pediatric measures of fatigue, pain interference (PI), pain behavior (PB), mobility, upper extremity (UE), physical activity (PA), and strength impact (SI), and external validation measures. Log-transformed linear mixed-effects models with random patient intercepts were used to assess PROMIS T-score changes. Wilcoxon signed-rank test was performed to determine the PROMIS T-score changes among the improved, worsened, and unchanged groups. Spearman rank correlation test determined the relationship of PROMIS T-scores with disease status reported by patients/families. RESULTS:More than 1,000 clinical visits from 184 patients included PROMIS Pediatric measures entries. All PROMIS T-scores correlated significantly (P < 0.01) with patient-reported variables and physician global assessment (PHGA). The correlation between function and mobility, PB, and PI was good (r = 0.4-0.6). The correlation of patient-reported disease status was strong with PHGA (r = 0.75); moderate with mobility, PB, and PI; and weak with fatigue, SI, UE, and PA. The changes of PROMIS T-scores over time for mobility, PB, PA, and PI compared with the self-reported status change were significant (P < 0.05). After effective treatment, when clinical disease activity score improved by at least three points (n = 18), the change of PROMIS T-scores for mobility, PB, PI, and UE were significant (P < 0.05). CONCLUSION:This study provided evidence supporting the use of PROMIS Pediatric mobility, PB, and PI measures for CNO clinical disease monitoring.

Purpose: Safety flag (SF) protocols are increasingly used in adolescent substance use research to protect of minor participants. This report examines the relationship between different thresholds for reporting participant substance use and study attrition. Methods: Data were analyzed from 2 concurrent adolescent studies that used an identical SF protocol with the exception of the threshold for heavy episodic drinking (HED). The first study recruited participants from a primary care adolescent medical clinic and the threshold for clinical intervention for past 3-month heavy episodic drinking was 10+ drinks on a single occasion. The second study recruited youth with chronic medical conditions from subspecialty pediatric clinics and used a lower threshold of 3+ to 5+ drinks on a single occasion. Generalized estimating equations were used to assess associations between SF type and subsequent attrition. Results: The baseline analytic sample size was 921 (10+ threshold = 487, 3+ to 5+ threshold = 434). No significant relationship between SF type and attrition was observed in either cohort. Conclusion: Positive SFs were not associated with significant differences in participant attrition. These results suggest that researchers can use different SF thresholds to accommodate adolescent populations with varying levels of risk without compromising study goals.

OBJECTIVE:Multinational research is essential to improve recognition and management of systemic juvenile idiopathic arthritis (sJIA). Current cohorts vary in the clinical variables and outcome measures collected. Adult-onset Still disease (AOSD) and sJIA are widely considered to comprise a single disease spectrum; however, classification criteria and clinical tools differ between groups. This systematic literature review aimed to identify clinical features and outcome measures collected across sJIA and AOSD cohorts worldwide to guide the development of a minimal dataset for Still disease. METHODS:A literature search was conducted from 2000 to 2024 using Ovid MEDLINE, Embase, and Wiley Cochrane Library (Trials). Included articles were in English and described sJIA or AOSD cohorts of ≥ 20 patients, reporting patient characteristics, clinical and laboratory features, and outcome measures. RESULTS:A total of 240 articles were included (95 sJIA, 134 AOSD, 11 mixed), from 37 countries, describing 23,136 patients. International League of Associations for Rheumatology classification was used in 77.9% of sJIA studies, whereas 98.5% of AOSD studies used Yamaguchi criteria. There was no clear consensus on the definition of macrophage activation syndrome. Race and ethnicity were only reported in 11.7% of articles. Cohorts evaluated aligned on the most commonly collected laboratory items for both AOSD and sJIA, with some agreement among clinical features, whereas disease outcome measures used to evaluate and follow disease trajectory were variable. CONCLUSION:Data reporting across sJIA and AOSD cohorts for clinical characteristics and outcome measures is widely heterogeneous. Consensus on the identification of a standardized minimal dataset for Still disease cohorts is needed to foster future collaboration and improve patient outcomes.

OBJECTIVES:To create definitions for minimal disease activity (MDA), flare, and minimal clinically important difference (MCID) for chronic nonbacterial osteomyelitis (CNO). It is necessary to establish these criteria before starting clinical effectiveness trials for therapies in CNO. METHODS:Three separate cohorts' samples from an international observational CNO registry were presented to a panel of 20 experts in CNO, including 7 patients/caregivers via online and in-person voting using the group consensus voting technique to define MDA, flare, and MCID, respectively. Experts classified the cases in each cohort as meeting the state for that specific cohort, ie, MDA or not, or flare or not, or meeting MCID or not. A consensus of ≥80% was required. RESULTS:General surveys identified the most important variables to include to define MDA, flare, and MCID. Clinical improvement of ≥30% in these critical parameters and improvement of the CNO Clinical Disease Activity Score by at least 3 were considered meaningful by providers and consensus data. CONCLUSIONS:This study provides the preliminary definitions of MDA, disease flare, and MCID in CNO, which can serve as targets and potential outcomes from treatments. These definitions must now be validated in other cohorts and tested in clinical trials.

OBJECTIVE:Children and adolescents living with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematosus (cSLE) frequently experience mental health comorbidities. This study evaluated sex differences in symptoms of depression, anxiety, and psychological stress in JIA and cSLE. METHODS:This multicenter, prospective cohort study recruited children and adolescents from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Disease activity and Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric self-report measures of Depressive Symptoms and Anxiety were collected at 3 timepoints over 12 months, and Psychological Stress was collected at baseline. Differences by sex were tested using chi-square and Wilcoxon rank-sum tests. Linear mixed effect models (LMMs) were created for each PROMIS measure to evaluate differences by sex. The prespecified α was 0.05. RESULTS:Among 393 children/adolescents with JIA and 58 children/adolescents with cSLE, Depressive Symptoms, Anxiety, and Psychological Stress scores were higher (indicating poorer mental health symptoms) for girls than boys. At baseline, approximately 1 in 3 girls with JIA and 1 in 2 girls with cSLE had moderate-to-severe Depressive Symptoms and Psychological Stress, compared to approximately 1 in 6 boys with JIA or cSLE. LMMs showed significantly higher scores (indicating poorer symptoms) for girls than boys, generally exceeding the minimally important difference threshold. CONCLUSION:Girls self-reported worse symptoms of depression, anxiety, and psychological stress compared to boys. Significant sex differences persisted after adjusting for rheumatic disease activity, time, and other pertinent variables. Mental health screening, management, and interventions may need to be tailored by sex.

Objectives To create definitions for minimal disease activity (MDA), flare, and minimal clinically important difference (MCID) for chronic nonbacterial osteomyelitis (CNO). It is necessary to establish these criteria prior to starting clinical effectiveness trials for therapies in CNO. Methods Three separate cohorts samples from an international observational CNO registry were presented to a panel of twenty experts in CNO, including 7 patients/caregivers via online and in-person voting using nominal group technique to define MDA, flare, and MCID, respectively. Experts classified the cases in each cohort as meeting the state for that specific cohort, ie. MDA or not, or flare or not, or meeting MCID or not. A consensus of ⩾80% was required. Results General surveys identified the most important variables to include to define MDA, flare, and MCID. Clinical improvement of 30% or more in these critical parameters and improvement of CNO Clinical Disease Activity Score (CDAS) by at least 3 were considered meaningful by providers and consensus data. Conclusions This study provides the preliminary definitions of MDA, disease flare, and MCID in CNO which can serve as targets and potential outcomes from treatments. These definitions must now be validated in other cohorts and tested in clinical trials. Key Messages WHAT IS ALREADY KNOWN ON THIS TOPIC Measurements of minimal disease activity (MDA), worsening disease activity (‘flare’), and minimally clinically important differences (MCID) in CNO are not well-established. For successful execution of clinical trials to identify effective treatment strategies in patients with CNO, standardized definitions of these terms are necessary. WHAT THIS STUDY ADDS Using data from an international real-world registry of CNO patients, we developed and validated quantitative definitions for MDA, flare, and MCID. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY Definitions of MDA, flare, and MCID will serve as potential outcomes in future clinical trials to study effectiveness of therapies in CNO.

Lupus erythematosus panniculitis (LEP) is a rare variant of chronic cutaneous lupus erythematosus that commonly affects the face, upper arms, thighs and buttocks. It is distinguished by its potential to cause irreversible scarring, lipoatrophy and disfigurement. Even in patients with a known diagnosis of LEP, monitoring for ongoing disease activity can be challenging as overlying erythema and evolving subcutaneous nodularity and/or atrophy can be subtle. To our knowledge, we report the first case of a patient with facial LEP monitored longitudinally using three-dimensional stereophotogrammetry.

We describe radiological and symptomatic improvement in two patients with dermatomyositis with recalcitrant muscle disease following off-label treatment with anifrolumab, a monoclonal antibody targeting type I interferon receptor recently approved by the FDA and EMA for the treatment of systemic lupus erythematosus.

ObjectiveTo assess whether demographic characteristics, referral patterns, nomenclature, anatomic features, and/or socioeconomic factors of patients with Craniofacial Scleroderma (CS) are related to delays in diagnosis or referral for reconstructive surgery.DesignA retrospective review of patients with CS from 1980 to 2022.SettingThe study was conducted at a tertiary care pediatric hospital.PatientsPatients were identified by medical record search for terms "Parry-Romberg," "hemifacial atrophy," "localized scleroderma," "progressive facial atrophy," "craniofacial morphea," "craniofacial scleroderma," "linear morphea," and "en coupe de sabre." Patients were excluded if the diagnosing specialist, age of onset, or age of diagnosis were unknown.Main Outcomes MeasuredAge of onset, diagnosis, sex, nomenclature, anatomic variation, Fitzpatrick skin type, median income, ethnicity, language, travel-distance, referral sequence, and operative interventions were recorded. Two-sample t-tests, one-way analysis of variance, and logistic regression were used to measure association between these variables with delays in diagnosis or referrals to plastic surgery.ResultsOf 124 patients identified, 104 met inclusion criteria (62% female, average age of onset 6.4 ± 4.4 years and diagnosis 9.5 ± 5.4 years). Dermatology most often diagnosed CS (64%). Thirty-five patients (33%) were evaluated by plastic surgery; of these, 45% underwent reconstructive procedures. Age of onset, income, and travel-distance were not statistically associated with delays in diagnosis.ConclusionsTimely diagnosis for patients with CS minimizes disease impact; however, we found that many patients experience years of symptoms before being diagnosed and may not be fully informed of potential reconstructive options. Interdisciplinary care and awareness of treatment options is critical to ensure patients receive prompt and comprehensive care. Recommendations for interdisciplinary care are proposed.

Background:Juvenile Localized Scleroderma (jLS) is a rare pediatric inflammatory disease of skin and underlying tissues that may cause significant functional impairment and disfigurement. Management approaches vary and an optimum treatment regimen is lacking. In 2012, a group of jLS researchers of Childhood Arthritis and Rheumatology Research Alliance (CARRA) proposed consensus treatment plans (CTPs), aimed to streamline the approach to care for jLS patients.Objectives:This study aimed to evaluate a large jLS patient cohort seen over a 21-year period in a single tertiary care pediatric hospital in the USA, in order to examine treatments utilized and determine parameters for systemic therapy initiation.Methods:This retrospective cohort study included jLS patients with disease onset in childhood (≤18-years of age) who were seen in rheumatology, dermatology, or combined rheumatology-dermatology clinics from 1999-2020, with ≤ 3 years of follow-up. Data on demographics, disease characteristics, therapies prescribed, and treatment trends were analyzed.Results:Of the 270 jLS patients identified, 101 fulfilled the inclusion criteria. The primary reason for exclusion was <3 years of follow-up. Selected demographic data and disease characteristics of patients are shown in Table 1. There were no statistically significant differences in most patient and disease characteristics between patients who received systemic treatment and those who did not. There were no significant differences in baseline laboratory values. The group treated with systemic therapy did have higher rates of extracutaneous involvement and had a higher proportion of patients with a generalized morphea phenotype.Table 1.Demographic and Disease CharacteristicsAll Patients(n=101)On Systemic Therapy(n=63)No Systemic Therapy(n=38)p valueAge-onset (Y), median (IQR)7.5 (6.4)9 (6)7 (4)NSAge-diagnosis(Y), median (IQR)9 (7.9)10 (6.7)9 (3.7)NSDiagnostic delay(M), median (IQR)10 (2.9)12 (13)7.5 (17)NSFollow-up (M), median (IQR)74 (69.3)65 (44.5)78 (47.7)NSSubtype Linear563917NS Face29209NS Circumscribed23419<0.0001 Mixed220NS Generalized201820.004Extracutaneous Involvement191810.001Clinic type Dermatology29227<0.0001 Rheumatology211920.003 Combined51429<0.0001The majority of patients who were on systemic immunomodulatory therapy were treated with methotrexate (59/63, 93.6 %) and/or systemic corticosteroids (21/63, 33 %). 5 patients were treated with hydroxychloroquine, 2 of which were also on methotrexate. 6 patients on methotrexate were either switched to or had mycophenolate mofetil added as concomitant therapy. The most common adverse effects observed in methotrexate-treated patients were gastrointestinal complaints (12/61, 19.7%) and fatigue (7/61, 11.5%). The median treatment duration was 50 months (IQR: 33.5). Patients were more likely to receive systemic therapy if they were followed in rheumatology or combined rheumatology-dermatology clinics as compared to dermatology clinics. Finally, 78% of patients with jLS received systemic treatment after 2013 (a year after publication of the CARRA jLS CTP) as compared to 55% of patients prior to 2013 (p < 0.05).Conclusion:This jLS cohort is one of the largest reported from a single center and reflects an increase in the use of systemic therapy since publication of CARRA CTPs in 2012. Further studies on long-term treatment outcomes and therapeutic approaches utilized when first-line treatment failures occur are warranted.References:[1]Li SC, Torok KS, Pope E, et al. Development of consensus treatment plans for juvenile localized scleroderma: a roadmap toward comparative effectiveness studies in juvenile localized scleroderma. Arthritis Care Res (Hoboken). 2012;64(8):1175-1185.Disclosure of Interests:Bugra Egeli: None declared, Johnathan Dallas: None declared, Edwin Anderson: None declared, Michelle Min: None declared, Daniel Mazori: None declared, Stephen Gellis: None declared, Mary Beth Son: None declared, Robert Sundel: None declared, Ruth Vleugels: None declared, Fatma Dedeoglu Consultant of: Novartis

OBJECTIVE:Disordered T peripheral helper (Tph)-B cell interactions have been implicated in several forms of inflammatory arthritis, including oligoarticular (oligo) juvenile idiopathic arthritis (JIA). We sought to evaluate the Tph-B cell axis in oligo JIA through an analysis of intra-articular B cells. METHODS:B cells from the blood and synovial fluid (SF) of 44 children with oligo JIA were compared to those from the blood and tonsils of controls. Flow cytometry, B cell receptor (BCR) repertoire analysis, and autoantibody profiling were used to characterize B cells. RESULTS:Memory B (Bmem) cells and heterogeneous subsets of CD21lo B cells were enriched in oligo JIA-SF versus blood of patients and controls. Compared to male patients, female patients with oligo JIA had greater proportions of intra-articular Tph cells that expressed B cell help factors as well as Bmem cells, plasmablasts, and age-/autoimmune-associated B cells. The sex differences in B cells were observed only in the joints and were not found in the blood or tonsil, nor were they explained by other disease features such as age at onset, antinuclear antibody status, or severity. Bmem cells in SF from female patients displayed characteristics of autoreactivity, including longer complementarity determining region 3 lengths and increased usage of autoreactive BCR gene segments, which were not found in blood Bmem cells. A diverse array of autoantibodies accumulated in the SF of female patients with oligo JIA compared to the blood of patients with JIA and controls. CONCLUSION:These findings demonstrate prominent B cell dysregulation in oligo JIA and implicate sex as an important biologic factor in B cell responses in this disease.

Introduction Chronic nonbacterial osteomyelitis (CNO) and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome are autoinflammatory bone diseases of unknown etiology that present with bone pain and varying degrees of extraosseous manifestations such as skin, intestinal and joint involvement. Currently, there are no validated outcome measurement sets that represent the input from all collaborating groups. Methods The OMERACT CNO & SAPHO working group performed a scoping review to identify domains previously used in CNO and SAPHO clinical studies. The list of potential domains was narrowed through a process of binning and winnowing. Results A scoping review included 260 observational studies published from 1978 -2020 and 220 domains were initially identified. Domains were reduced to 25 through a binning and winnowing process. Domains cover each of the OMERACT core with most domains mapped to life impact and pathophysiological manifestations. Conclusion We identified 25 potential domains covering health concepts of function, disease manifestations, pain, and impact on mental health and societal participation to be included in the final core domain set. The next step will be to reach a consensus on the final CNO & SAPHO core domain set and begin instrument selection.

Objectives Systemic autoinflammatory diseases (SAIDs) significantly impact patients’ and their families’ quality of life (QoL). This international study aimed to evaluate the extent of this burden by gathering patient-reported data on their SAIDs and its effects on daily living and well-being. Methods A 24-question online survey, developed by the Autoinflammatory Alliance and KAISZ/VAISZ in English and Dutch, was distributed internationally from 2017 to 2018. The survey included both closed-ended and open-ended questions addressing the SAID diagnosis and perceived impact on QoL. Participants were recruited through online social media platforms, and responses were collected using convenience sampling. Results A total of 371 responses were received. Most respondents were from the United States (64%). The most common diagnoses were undifferentiated SAIDs (24%); periodic fever, aphthous stomatitis, pharyngitis, adenitis (19%); and cryopyrin-associated periodic syndrome (12%). Participants saw an average of 6.5 doctors before diagnosis, with 7% seeing over 20 doctors. Common symptoms included headaches (94%), fatigue (86%), pain (80%), and fever (79%). Assessment of QoL revealed an average score of 61 of the 100 between flares, which dropped to 18 of the 100 during flares. Daily activities were severely limited during flares for 52.5% of participants; 81% of participants reported that SAIDs impacted their work, career, or education. Conclusions This study highlights the profound impact of SAIDs on QoL, emphasising the need for ongoing research and improved care for these rare conditions. Early diagnosis, targeted treatment, and psychosocial support can help mitigate the burden of these diseases.