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Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-002148International development of a lupus-specific instrument to assess cognitivesymptoms in patients with SLE: LupusBrain Fog Severity Scale (LBFSS) studyLaurent Arnaud ,1 Matteo Piga ,2 Guillermo J Pons-Estel ,3 Yurilis J Fuentes-Silva,4 Hervé Devilliers,5 Raquel Faria ,6,7 Ali Duarte-Garcia ,8 Daniel Guimarães de Oliveira,9,10,11 Marina Scolnik,12 Sander van Leuven,13 Eve Smith,14 Simone Appenzeller,15 Ivan Padjen,16,17 Michelle A Petri ,18 Alessandra Bortoluzzi,19 Ioannis Parodis ,20,21 Meggan Mackay,22 Faisal Parlindungan,23 Odirlei A Monticielo,24 Antonis Fanouriakis ,25 Catherine Kleitz,26 Andrea M Knight ,27,28,29 Nathalie Philippi,26 Alberta Hoi ,30 Zoe Karakikla- Mitsakou,31 Sofia Silva Ribeiro,32 Annemarie Sluijmers,31 Aldevina Sturiene,31 Zahi Touma 33To cite: Arnaud L, Piga M, Pons- Estel GJ, et al. International development of a lupus- specific instrument to assess cognitive symptoms in patients with SLE: Lupus Brain Fog Severity Scale (LBFSS) study.Lupus Science & Medicine2026;13:e002148. doi:10.1136/ lupus-2026-002148► Additional supplemental material is published online only. To view, please visit the journal online (https:// doi. org/ 10. 1136/lupus- 2026- 002148). Received 7 May 2026 Accepted 23 June 2026 For numbered affiliations see end of article.Correspondence toPr Laurent Arnaud; laurent.arnaud@ chru- strasbourg. frCo- morbidities© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.ABSTRACTIntroduction Cognitive symptoms such as ‘brain fog’ are frequent and disabling in patients with SLE. We aimed to develop and validate the Lupus Brain Fog Severity Scale (LBFSS), the first patient-reported outcome measure (PROM) for cognitive symptoms in SLE.Methods The LBFSS was developed using a multi-step international approach involving healthcare professionals and patients with SLE. Patients provided free-text descriptions of brain fog, generating candidate domains through thematic analysis (step 1). Domains were rated for relevance (step 2) and those retained converted into self-assessable items (step 3). The pilot LBFSS was iteratively refined (step 4). The finalised LBFSS was validated (step 5) in a large international SLE cohort. Psychometric evaluation included internal consistency, exploratory factor analysis and assessment of construct, convergent, known-groups and criterion-related validity.Results In step 1, 147 SLE participants across 39 countries generated 21 domains for cognitive symptoms, of which 13 were retained in consensus (step 2), converted into self-assessable items (step 3) and iteratively refined using patient and physician feedback. In step 5, validation of the LBFSS instrument in 378 patients from 36 countries demonstrated high internal consistency (Cronbach’s α=0.95) and a unidimensional structure explaining 62.2% of variance. LBFSS scores were significantly higher in participants reporting brain fog (p<0.0001), confirming known-group validity. Construct validity was supported by significant correlations with functional impact and symptom severity (ρ=0.46–0.65, p<0.0001), strong convergent validity with the Perceived Deficits Questionnaire-20 (ρ=0.84, p<0.0001) while the discriminative performance for presence versus absence of self-reported brain fog was high (area under the curve=0.85).Conclusion The LBFSS is a new, valid and feasible PROM to assess brain fog and cognitive symptoms in SLE.INTRODUCTIONSLE is a heterogeneous autoimmune disease1 with potential involvement of the central and peripheral nervous systems, collectively termed neuropsychiatric SLE (NPSLE). NPSLE encompasses a broad spectrum of neurological and psychiatric manifestations, among which objectively measurable cogni- tive dysfunction is one of the most frequently reported features.2 This dysfunction typically affects domains such as memory, attention, processing speed and executive function.3 In parallel, individuals with SLE frequently report subjective cognitive symptoms that impact daily functioning and quality of life.4 These patient-reported experiences are not restricted to those with NPSLE and do not consistently correlate with objective measuresWHAT IS ALREADY KNOWN ON THIS TOPIC⇒ Brain fog and other cognitive symptoms can signifi- cantly impair daily functioning and quality of life in SLE.WHAT THIS STUDY ADDS⇒ The Lupus Brain Fog Severity Scale (LBFSS) is the first validated patient-reported outcome measure to assess cognitive symptoms in SLE.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY⇒ Developed through an international, patient-centred approach, the LBFSS shows strong reliability and high discriminative performance for cognitive symp- toms in SLE. ### Page 2 Arnaud L, et al. Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-0021482Lupus Science & Medicineof cognitive dysfunction. Among these symptoms, ‘brain fog’ has emerged as a common and clinically relevant concern,5 6 often described as mental clouding, slowed thinking or reduced clarity of thought. Despite its apparent frequency, brain fog remains poorly charac- terised, with no universally accepted definition or stan- dardised assessment approach. Efforts to link subjective cognitive symptoms, including brain fog, with objective cognitive impairment or markers of central nervous system involvement7 have produced inconsistent results.8 This dissociation underscores the difficulty of capturing patient-perceived cognitive diffi- culties using conventional clinical or neuropsychological tools. The Lupus Brain Fog Severity Scale (LBFSS) study was therefore designed to address this unmet need by devel- oping a self- administered, patient-reported outcome measure (PROM) specifically aimed at quantifying the severity of subjective cognitive symptoms in individuals with SLE. Such a tool, if shown to be reliable and valid, could enhance clinical care by improving the recognition and longitudinal monitoring of cognitive issues, while also providing a standardised outcome measure for research, including clinical trials.METHODS Study designThe LBFSS study was conducted over a 12-month period and followed a five-step mixed-methods approach to develop and validate a self-administered PROM targeting perceived cognitive symptoms in SLE. The process combined sequential input from patients and health- care professionals (HCPs) and included domain genera- tion, domain prioritisation, item development, cognitive debriefing and psychometric evaluation.Steering committee and participantsThe study was guided by an international steering committee comprising 21 physicians with expertise in SLE and neuropsychiatric involvement, alongside a neurolo- gist with specialisation in cognitive disorders, a neuropsy- chologist, a clinical psychologist, a methodologist and three patient representatives affiliated with Lupus Europe and Agrupación Lupus Chile. Across the different phases, participants with a self-reported, medically-confirmed diagnosis of SLE were recruited through social media and patient organisations.Development and validation processThe five- step methodology underpinning the LBFSS (figure 1) was largely based on the European Refer- ence Network (ERN) ReCONNET ELICIT framework, developed within the European Reference Networks to address the issue of poorly defined constructs in rare and complex connective tissue diseases. This approach relies on broad stakeholder engagement, initial crowdsourcing of concepts, structured thematic analysis and iterative consensus-building. In the present study, the first two steps focused on identifying and prioritising domains reflecting the patient experience of ‘brain fog’ and cognitive symptoms, whereas subsequent steps addressed LBFSS questionnaire construction and validation.Step 1: identification of domains (patient crowdsourcing)Patients with SLE were recruited between April and June 2025 to participate in an online crowdsourcing exercise. Participants responded to an open-ended prompt inviting them to describe all aspects of their experience of ‘brain fog’ including symptom characteristics (frequency, dura- tion, intensity) and impact on daily life. For all subsequent analyses, only responses from participants who reported a medically confirmed diagnosis of SLE were retained. Responses were submitted in English but participants could translate their contributions from their native language when necessary, using back-translation to ensure that the translation reflected the intended meaning. Individual submissions were reviewed, with duplicate orFigure 1 Flowchart of the LBFSS study. HCPs, healthcare professionals; LBFSS, Lupus Brain Fog Severity Scale. ### Page 3 Arnaud L, et al. Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-002148 3Co- morbiditiesoverlapping concepts removed. The remaining content was coded and organised into domains using thematic analysis by the first author (LA), according to the ERN ReCONNET ELICIT methodology.Step 2: domain prioritisationA multidisciplinary panel of HCPs and patient repre- sentatives evaluated the domains identified in Step 1. Each domain was rated for relevance on a 9-point scale (1=lowest relevance; 9=highest relevance). Domains with a median score ≥7 were retained for further development.Step 3: item generation and refinementRetained domains were translated into questionnaire items to create a preliminary version of the LBFSS. Initial wording was drafted in English and iteratively refined with input from patient representatives and HCPs a web- based review process. Participants could endorse or suggest revisions to each item, with the aim of improving clarity, interpretability and cross-cultural applicability.Step 4: questionnaire debriefing and feasibilityThe pilot instrument was tested in an independent sample of patients with SLE from Europe and Latin America. Participants completed the questionnaire and provided structured feedback on clarity, relevance, ease of comple- tion, response options and overall burden. Completion time was recorded. Minor revisions were made based on this feedback before finalising the instrument.Step 5: psychometric validationThe finalised LBFSS was administered to a large interna- tional online cohort of adults with self-reported, medi- cally confirmed SLE. Participants reported demographic characteristics, indicated whether they had experienced brain fog within the preceding 10 days and completed the LBFSS. Specifically, brain fog was assessed over the preceding 10 days to align with the timeframe used in established SLE assessment instruments, including earlier versions of the SLE Disease Activity Index.9 In addition, we aimed to keep the recall period relatively short to minimise recall bias and to capture fluctuations in symp- toms that are characteristic of brain fog while remaining practical for participants completing the questionnaire. Convergent validity was assessed using the Perceived Deficits Questionnaire-20 (PDQ- 20), a validated generic self- report measure of perceived cognitive symptoms in daily functioning.10 Participants also rated brain fog severity and its impact on daily life, relationships and work or study using 0–10 numerical rating scales. These measures were used to examine construct validity and criterion- related associations.Statistical analysisContinuous variables are reported as median and IQR (25th–75th percentile) and categorical variables as counts and percentages. Comparisons between groups were performed using the χ² test for categorical variables and the Mann-Whitney U test for continuous variables. Internal consistency of the LBFSS was assessed using Cronbach’s alpha and standardised Cronbach’s alpha. The dimensionality of the instrument was evaluated using exploratory factor analysis (EFA) with maximum likeli- hood extraction applied to all 13 items. The number of factors retained was determined based on: eigenvalues >1 and scree-plot inspection. Factor loadings ≥0.40 were considered acceptable. The proportion of variance explained by the retained factor(s) was reported. The distribution of LBFSS scores was examined to iden- tify floor or ceiling effects. Known-groups validity was evaluated by comparing LBFSS scores between partici- pants reporting versus not reporting brain fog. Construct validity was assessed using Spearman correlation coef- ficients between LBFSS scores and patient-reported brain- fog severity and its impact on daily life, relationships and work/study capacity. Convergent validity was eval- uated by examining correlations between LBFSS scores and PDQ- 20 scores. Criterion-related validity was assessed using receiver operating characteristic (ROC) curve anal- ysis, with the area under the curve (AUC) used to quantify the ability of the LBFSS to discriminate between partici- pants with and without brain fog during the previous 10Table 1 Main thematic domains of brain fog, reported during step 1 (as the proportion of all comments)Main dimensions of brain fog in SLE n (%)Forgetfulness—memory issue 76 (30.9) Cognitive slowness 23 (9.4) Word- finding difficulties 23 (9.4) Lightheadedness (or heaviness or fogginess, or any other abnormal sensation in the head, except headache) 22 (8.9) Thought flow disruption—mental block 21 (8.5) Concentration and focus difficulty 20 (8.1) Feelings of disorientation 11 (4.5) Derealisation—dreamstate 7 (2.8) Dizziness 7 (2.8) Learning impairment (difficulty registering new information) 7 (2.8) Fatigue 5 (2) Mental fatigue 5 (2) Sensory overload 4 (1.6) Executive task difficulty 3 (1.2) Headache 3 (1.2) Visual and spatial perception issues (eg, blurry vision) 3 (1.2) Depersonalisation (out of the body experience) 2 (0.8) Decision- making difficulty 1 (0.4) Emotional detachment 1 (0.4) Emotional lability 1 (0.4) Irritability 1 (0.4) ### Page 4 Arnaud L, et al. Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-0021484Lupus Science & MedicineTable 2 Median (IQR) meaningfulness scores for inclusion of potential brain fog domains into the LBFSS on the 1 (least relevant) to 9 (most relevant) scaleBrain fog domains All participants (n=35) HCPs (n=25) Patient-representatives (n=10) P value*Forgetfulness—memory issue Having trouble remembering things. 9 (8–9) 9 (7.5–9) 9 (7.75–9) 0.62 Word- finding difficulties Struggling to recall the right words, particularly when speaking. 8 (7–9) 8 (7–9) 8.5 (7–9) 0.97 Cognitive slowness Feeling slowed down in the head, thoughts are coming in slow motion. 8 (7–9) 9 (8–9) 8 (7–9) 0.20 Lightheadedness Head feeling empty or heavy or clouded or buzzing (excludes headache—shown separately). 7 (6–8) 6 (6–8) 8 (5.75–9) 0.30 Thought flow disruption—mental block Difficulty maintaining a continuous flow of thoughts. Feeling stuck with no new thought coming in the head. 8 (7–9) 8 (7.5–9) 8 (6–9) 0.58 Concentration and focus difficulty Finding it hard to pay attention or stay focused on tasks or conversations. 9 (7–9) 9 (7–9) 8 (8–9) 0.97 Feelings of disorientation Feeling lost or unsure of where you are or what you are doing. 7 (6–8) 7 (6–8) 8 (6.75–8.25) 0.35 Derealisation—dreamstate feeling Feeling like the world around you is not real or seems dreamlike. 7 (5–8) 6 (5–7) 8 (6.75–8) 0.02 Dizziness Feeling the world spinning around you, feeling faint, woozy, weak or wobbly. 5 (5–7) 5 (3.5–6) 7 (5.75–8.25) 0.003 Learning impairment Trouble absorbing new information or skills. 8 (7–9) 8 (7–9) 8 (7–9) 0.77 Mental fatigue Feeling mentally tired or exhausted, even after little mental effort. 8 (7–9) 8 (7–9) 8.5 (7.75–9) 0.23 Sensory overload Feeling overwhelmed by too much sensory input like lights, sounds, conversations. 7 (5–8) 6 (5–7) 7 (5.75–8) 0.27 Executive task difficulty Struggling with planning, organising or completing tasks. 8 (7–9) 8 (7–9) 8 (5.75–8) 0.25 Decision- making difficulty Finding it hard to choose or make decisions, even simple ones. 7 (6–8) 7 (6–8) 7.5 (6–8.25) 0.74 Headache Experiencing pain in the head. 4 (2–6) 3 (1.5–5) 7.5 (5.75–8) 0.0004† Visual perception issues Feeling of blurry vision or tunnel- vision. 5 (3–6) 3 (2.5–5.5) 7 (6–7.25) 0.0005† Depersonalisation Feeling detached from yourself, as if you are outside your body or not fully connected to yourself. 6 (4–7) 6 (3–7) 8 (7–8) 0.01 Emotional lability Experiencing change in the mood and emotional status. 5 (4–7) 5 (3–6) 7 (5–8.25) 0.02 *P value comparing meaningfulness scores between HCPs and patient-representatives. †These p values remain significant after Bonferroni correction for multiple testing. HCPs, healthcare professionals; LBFSS, Lupus Brain Fog Severity Scale. ### Page 5 Arnaud L, et al. Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-002148 5Co- morbiditiesdays. A two-sided p value <0.05 was considered statistically significant. All analyses were performed using JMP V.13.0 (SAS Institute, Cary, USA).RESULTSIn step 1, 147 SLE participants (143 (97.3%) women), with a median age of 43 (IQR: 34–53) years, residing in 39 countries (online supplemental table 1) were asked to describe the main characteristics of ‘their brain fog’, as well as the frequency, duration, intensity and severity of typical brain fog episodes (online supplemental table 2). Thematic analysis yielded a total of 21 potential cognitive symptom domains (table 1). Following discus- sions between steering committee members, fatigue was merged with mental fatigue given the broader context of cognitive symptoms, and three domains (emotional detachment, emotional lability and irritability) were regrouped.In step 2, the panel of 25 HCPs from the steering committee and 10 patients with SLE and patient-representatives were asked to review the potential brain fog domains collected during step 1, and to assess their relevance on a 1 (lowest) to 9 (highest) relevance scale, with the instruction that domains with a median score≥7 would be included in the final LBFSS instrument (table 2). This yielded a final list of 13 domains. Of note, the general assessment of relevance was similar between HCPs and patient- representatives for each of these domains, except for ‘headache’ and ‘visual perception issues’, which were given a significantly higher relevance score by patients (table 2).In step 3, each of the 13 domains retained after step 2 was transformed into a self-assessable questionnaire items for patients. A total of 23 HCPs and seven other patients (or patient representatives) provided feedback on each question of the pilot LBFSS instrument, leading to several important changes in the wording of four questions (online supplemental table 3).In step 4, the pilot LBFSS was presented to 12 patients with lupus (online supplemental table 4), and a cognitive debriefing was conducted to gather additional insights about the instrument. Patient feedback supported the feasibility and acceptability of the pilot LBFSS, as the instrument was considered clear in its instructions, items and response scale, culturally relevant, easy to complete and of appropriate length with a median completion time of 6.5 min (IQR: 3.75–9.25). However, one partici- pant highlighted that items 7 (‘Q7. How much have you been feeling disoriented, for example unsure of where you are or what you are doing?’) and 8 (‘How much have you been feeling as if the world around you is not real or if you are living in a dream’) may trigger psychi- atric stigma in Latin American patients. Following addi- tional discussions with patient-representatives, these two items were subsequently adjusted to as ‘How much have you felt lost in familiar places or about what you are doing?’ and ‘How often have you felt like things around you were feeling unreal, as in a dream?’, respec- tively. Finally, the HCP panel unanimously confirmed the content validity of the final LBFSS (table 3), judging the instrument to be clear, easy to understand, cultur- ally relevant and appropriate for assessing brain fogTable 3 Lupus Brain Fog Severity Scale (LBFSS) The following LBFSS questionnaire is designed to find out how severe your lupus brain fog is. Please carefully read each statement and then tick the single closest answer to how you have felt DURING THE LAST 10 DAYS BECAUSE OF YOUR LUPUS BRAIN FOG, considering the IMPACT ON YOUR LIFE of the intensity and/or frequency of each statement.Please answer all the following questions Not at all A little Moderately A lot ExtremelyQ1. How much have you been forgetting things, recent events or information that you should know? ❑ ❑ ❑ ❑ ❑Q2. How much have you been having difficulties finding the right words when speaking or writing? ❑ ❑ ❑ ❑ ❑Q3. How much have you been feeling that your brain is working more slowly than usual? ❑ ❑ ❑ ❑ ❑Q4. How much have you been feeling that your head is empty, clouded or foggy? ❑ ❑ ❑ ❑ ❑Q5. How much have you been feeling that your thoughts are stuck or blocked? ❑ ❑ ❑ ❑ ❑Q6. How much have you been having difficulty staying focused on tasks or conversations? ❑ ❑ ❑ ❑ ❑Q7. How much have you felt lost in familiar places or about what you are doing? ❑ ❑ ❑ ❑ ❑Q8. How often have you felt like things around you were feeling unreal, as in a dream? ❑ ❑ ❑ ❑ ❑Q9. How much have you been having difficulties understanding new information or learning new skills? ❑ ❑ ❑ ❑ ❑Q10. How much have you been feeling mentally tired or exhausted, even after no or little mental effort? ❑ ❑ ❑ ❑ ❑Q11. How much have you been feeling overwhelmed by light or sound? ❑ ❑ ❑ ❑ ❑Q12. How much have you been having difficulties with planning, organising or completing tasks? ❑ ❑ ❑ ❑ ❑Q13. How much have you been finding it hard to choose or make decisions, even simple ones? ❑ ❑ ❑ ❑ ❑For the healthcare team only—LBFSS scoring: × 0 point × 1 point × 2 points × 3 points × 4 points 1. Count how many boxes are ticked in each column _ _ _ _ _ _ _ _ _ _ 2. Multiply the number of ticked boxes in each column, with the corresponding number of points = 0 = _ _ = _ _ = _ _ = _ _ 3. Sum the number of points across all columns to get the total LBFSS score LBFSS score = ### Page 6 Arnaud L, et al. Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-0021486Lupus Science & Medicinein patients with SLE, with items expected to be easily answerable by patients.In step 5, validation data for the LBFSS were collected from 378 English-speaking participants (352 women, with a median age of 45 (36–55) years) with SLE across 36 countries (table 4 and online supplemental table 5). Among these participants, 271 (71.7%) reported experi- encing brain fog within the preceding 10 days. The LBFSS demonstrated excellent internal consis- tency reliability, with both Cronbach’s alpha and stan- dardised Cronbach’s alpha equal to 0.95. Item response distributions across the five scale modalities for each of the 13 LBFSS items during the validation phase supported appropriate use of the full response range (online supple- mental table 6). EFA indicated a single dominant factor, with an eigenvalue >1, supporting the unidimension- ality of the 13-item LBFSS. All items loaded strongly (≥0.60) on this factor, which explained 62.2% of the total variance. The distribution of LBFSS scores showed no evident floor or ceiling effects (figure 2). The median score was 21 (IQR: 12–30), with a mean (±SD) of 21.4 (±11.6), covering the entire theoretical LBFSS range from 0 to 52. Known- groups validity was supported by significantly higher LBFSS scores among participants reporting brain fog (median: 25 (IQR: 17–33)), compared with those without brain fog (median: 10 (IQR: 3–17); p<0.0001). The limited overlap between the distributions further highlights the LBFSS ability to discriminate between participants with and without brain fog. Construct validity was further supported by moderate to strong correlations (figure 3) between LBFSS scores and self-reported impact of brain fog on daily life (Spear- man’s ρ=0.55, p<0.0001), personal relationships (ρ=0.53, p<0.0001) and ability to study or work (ρ=0.46, p<0.0001), as well as a strongly significant correlation with brain fog severity over the preceding 10 days (ρ=0.65, p<0.0001) as hypothesised. Convergent validity was demonstrated by a very strong correlation between LBFSS scores and the PDQ-20 (ρ=0.84, p<0.0001), a widely validated generic measure of perceived cognitive symptoms. Criterion-related validity was further supported by comparable discrim- inative performance of the LBFSS and the PDQ-20 for identifying presence versus absence of brain fog, as self-reported by patients, with similar areas under the ROC curve (AUCLBFSS=0.85; 20 AUCPDQ- 20=0.84).DISCUSSIONThe LBFSS study was designed to clarify how patients with SLE describe ‘brain fog’ and related cognitive symptoms with the goal to develop a patient-centred, self- administered instrument capable of quantifying the severity of cognitive symptoms in SLE. Importantly and as such, the LBFSS is intended to assess subjective cogni- tive experience and to complement, rather than substi- tute for, objective neuropsychological assessment, which is expected to be largely uncorrelated. The initial crowdsourcing phase yielded a wide range of patient descriptions, underscoring the heterogeneity of cognitive symptoms in SLE. Thematic analysis allowed these narratives to be organised into broader domains, highlighting the multidimensional nature of the construct. Subsequent prioritisation by both HCPs and patient representatives showed substantial agreement, supporting the relevance and clinical credibility of the selected domains. Translation of these domains into questionnaire items was iterative and informed by both patient and clinician input. Revisions primarily aimed to improve clarity and interpretability. The choice of a 10-day recall period was guided by consistency with existing SLE outcome measures,9 while limiting recall bias in a population where memory and attention may be affected.Table 4 Characteristics of the LBFSS validation population (378 participants)Main characteristics All participants (n=378)Sex, women, n (%) 352 (93.1) Age, years, median (IQR) 45 (36–55) Brain fog at least once during the last 10 days, n (%) 271 (71.7) Impact of brain fog*, median (IQR), 0–10 scaleOn ‘life in general’ 6 (4–7)On ‘personal relationships’ 5 (4–7)On ‘capacity to work or study’ 7 (5–8) Duration of brain fog episodes*A few seconds 33 (12.2%)A few minutes 77 (28.4%)Less than 1 hour 41 (15.1%)1 or 2 hours 40 (14.8%)More than 2 hours (several hours) 55 (20.3%)All day 25 (9.2%) Intensity of brain fog episodes*, median (IQR), 0–10 scale 6 (4–7) Previously tested for cognitive symptoms (neuropsychological tests)Yes 39 (14.4% of total)With abnormal results 14/39 (36.0%)With normal results 16/39 (41.0%)Does not know or is unsure 7/39 (17.9%)Prefer not to answer 2/39 (5.1%)No 217 (80.1%)Does not know or is unsure 15 (5.5%) *Data available in 100% of the 271 participants reporting brain fog at least once during the last 10 days. LBFSS, Lupus Brain Fog Severity Scale. ### Page 7 Arnaud L, et al. Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-002148 7Co- morbiditiesCognitive debriefing confirmed that the instrument was understandable, acceptable and feasible across different cultural settings. Wording adjustments were introduced, particularly to address concerns related to psychiatric connotations in Latin American participants. These refinements, grounded in direct patient feed- back, strengthened content and face validity prior to formal testing. Final review by the clinical panel further supported the relevance and clarity of the instrument. Psychometric evaluation provided consistent evidence supporting the validity of the LBFSS. Internal consistency was high, and response distributions indicated appro- priate use of the full scoring range, with negligible floor or ceiling effects. Factor analysis identified a single domi- nant dimension accounting for a substantial proportion of variance, supporting the use of a global summary score. Together, these findings suggest that the LBFSS captures a coherent underlying construct of perceived cognitive dysfunction. Construct validity was supported by significant associa- tions between LBFSS scores and patient-reported impact on daily functioning, interpersonal relationships and work or academic activities, as well as with overall brain fog severity. Known-groups validity was demonstrated by higher scores among participants reporting brain fog. Notably, score variability among those not explicitly reporting brain fog suggests that the instrument captures a broader spectrum of cognitive symptoms, a finding consistent with its unidimensional structure. Conver- gent validity was reinforced by a strong correlation with the PDQ-20, a widely used generic measure of perceived cognitive deficits. The LBFSS also showed comparable discriminative performance to the PDQ-20 in identifying brain fog, despite comprising substantially fewer items.10 This shorter format may reduce respondent burden while preserving measurement performance, which is particu- larly relevant for clinical studies and routine care. Beyond its measurement properties, the LBFSS is expected to have practical implications for both clinical care and research. In routine practice, cognitive issues in SLE are often under-recognised or insufficiently explored, despite their impact on daily functioning.5 6 The LBFSS is primarily intended to quantify the severity and diversity of cognitive symptoms, rather than to serve as a diagnostic tool for brain fog. In routine clinical practice, it could be used to systematically assess cognitive symptom burden in patients with SLE who report brain fog or cognitive difficulties. This structured approach may facilitate more focused discussions between patients and clinicians. This may help address a gap in care, where cognitive difficul- ties are frequently reported by patients but are not always fully taken into account or systematically assessed by clinicians.6 By providing a quantitative score, the LBFSS may serve as a first-line screening tool to identify patients who would benefit from targeted supportive measures, while the utility of systematic screening for cognitive symptoms in all patients with lupus remains to be further defined. Future research should explore how incorpo- rating the LBFSS into routine care could inform clinicalFigure 2 Distribution of LBFSS scores in total participants (n=378), as well as in those with (n=271) and without brain fog (n=107) during the previous 10 days. LBFSS, Lupus Brain Fog Severity Scale. ### Page 8 Arnaud L, et al. Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-0021488Lupus Science & Medicinedecision- making, identify patients who may benefit from comprehensive neurocognitive assessment and ulti- mately improve patient outcomes. In the research setting, the LBFSS offers a standardised approach to capturing patient-reported cognitive symptoms, an area that remains insufficiently addressed in SLE studies. Its rela- tively short format may facilitate inclusion in observational cohorts and clinical trials without substantially increasing participant burden. The availability of a disease-specific, patient-centred measure may also improve the assess- ment of treatment effects on cognitive outcomes, which are rarely included as primary or secondary endpoints. More broadly, its use could contribute to a better under- standing of the determinants and trajectories of cognitive symptoms in SLE. Several limitations should be considered. Psycho- logical factors such as anxiety and depression may influence cognitive symptoms which may also overlap with those observed in comorbid conditions such as fibromyalgia. Importantly, the LBFSS is a PROM designed to capture cognitive symptoms in patients with SLE, irrespective of aetiology. Further work is ongoing to better understand the role of contrib- uting factors, together with the association between subjective cognitive symptoms and cognitive dysfunc- tion. Recruitment through online platforms and patient organisations may introduce selection bias, although only participants reporting medically-confirmed SLE were included in the study, and there- fore no formal disease activity measure was available. Although participants to the validation step of the LBFSS represented a range of geographical regions, including Europe, Africa, Latin America, the Carib- bean and Asia, additional validation in larger and more ethnically diverse populations would further strengthen the assessment of the scale’s cross- cultural applicability and generalisability. The instrument was developed in English, and while the study popula- tion was geographically diverse, formal cross- cultural adaptation will be required for broader implemen- tation. Finally, test- retest reliability and responsive- ness were not evaluated in this study and should be addressed in future studies, particularly in longitu- dinal and interventional settings.Figure 3 Correlations between LBFSS and burden and severity of brain fog. Correlations between the LBFSS score and the impact of brain fog on life in general (A), personal relationships (B), capacity to work and study (C) and with the severity of brain fog during the 10 previous days (D). LBFSS, Lupus Brain Fog Severity Scale. ### Page 9 Arnaud L, et al. Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-002148 9Co- morbiditiesIn conclusion, the LBFSS is a PROM developed to assess brain fog and related cognitive symptoms in SLE. Its development followed a structured, multistep process integrating patient experience and clinical expertise. The instrument demonstrates good feasi- bility, strong internal consistency and multiple forms of validity. By capturing both brain fog and wider cognitive symptoms, it reflects the complexity of patient- reported cognitive symptoms in SLE. Further evaluation of reliability and sensitivity to change will help define its role in clinical practice and research.Author affiliations1Department of Rheumatology, National Reference Center for Autoimmune Diseases (RESO), Hôpitaux Universitaires de Strasbourg, INSERM UMR-S 1109, Strasbourg, France 2Rheumatology Unity, AOU Cagliari, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy 3Regional Center for Autoimmune and Rheumatic Diseases (GO-CREAR), Rosario, Argentina 4Departamento de Medicina, Universidad de Oriente, Ciudad Bolivar, Venezuela 5Internal Medicine and Systemic Diseases Unit, University Hospital Centre Dijon, Dijon, France 6Unidade de Imunologia Clínica – Unidade Local de Saúde Santo António; UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal 7ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal 8Division of Rheumatology, Mayo Clinic Minnesota, Rochester, Minnesota, USA 9UDAI – Autoimmune Diseases and Immunology Unit, Internal Medicine Department, ULS Tâmega e Sousa, Penafiel, Portugal 10Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal 11i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal 12Rheumatology Section, Hospital italiano de Buenos Aires, Buenos Aires, Argentina 13Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands 14School of Infection and Immunity, University of Glasgow, Glasgow, UK 15Departmento of Orthopedics, Rheumatology and Traumatology-Universidade Estadual de Campinas, Campinas, Brazil 16School of Medicine, University of Zagreb, Zagreb, Croatia 17Division of Clinical Immunology and Rheumatology, Referral Centre for SLE and Related Diseases, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia 18Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 19Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy 20Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine (CMM), Stockholm, Sweden 21Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden 22Feinstein Institutes for Medical Research, Northwell Health System, Manhasset, New York, USA 23Rheumatology Division, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Rumah Sakit Universitas Indonesia, Depok, Indonesia 24Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil 25Rheumatology and Clinical Immunology Unit, Attikon University Hospital, National Kapodistrian University of Athens Medical School, Athens, Greece 26Department of Neuropsychology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France 27Division of Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada 28Neurosciences and Mental Health Program, SickKids Research Institute, Toronto, Ontario, Canada 29Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada 30School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia 31Lupus Europe, Brussels, Belgium 32Center for Research and Social Intervention (CIS-Iscte), ISCTE-University Institute of Lisbon, Lisbon, Portugal 33Lupus Program at University Health Network, Schroeder Arthritis Institute, Krembil Research Institute, University of Toronto, Toronto Western Hospital, Toronto, Ontario, CanadaAcknowledgements The authors wish to thank Ms Katia Baumgaertner for her invaluable role in the preparation of the manuscript, acknowledge the contribution of Lupus Europe and Agrupacion Lupus Chile, and deeply thank all patients living with lupus who have contributed to the LBFSS study.Contributors LA, MP, GJP-E and ZT contributed to the design of the study. All authors contributed to the collection of study data. LA performed the statistical analysis. LA, MP and ZT prepared the draft manuscript. All authors revised the manuscript for significant intellectual content and approved the final version of the manuscript. The guarantor of the data is LA.Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for- profit sectors.Competing interests LA has acted as a consultant for AbbVie, AstraZeneca, Alpine, Biogen, BMS, Boehringer Ingelheim, Chugaï, GSK, Grifols, Janssen, Kezar, LFB, Lilly, Medac, Merck, Novartis, Pfizer, Roche and UCB. MP has received consultancy and speaker fees from AstraZeneca, GSK, Otsuka and Roche. GJP-E has grant support from AstraZeneca, GSK, Janssen and Roche, and he has been a speaker and/ or served on advisory boards for AstraZeneca, Biogen, GSK, Janssen, Novartis, Regeneron, Roche and Viatris. RF received lecture and consultancy fees from AstraZeneca and GSK. DGDO has received consultancy fees from AstraZeneca and speaker fees from GSK. MS has received consultancy and speaker fees from AstraZeneca and GSK. SA, National Council for Scientific and Technological Development (CNPq 305981/2023-4). IPad has acted as a consultant for AbbVie, AstraZeneca, Boehringer Ingelheim, Lilly, Medis, Novartis, Pfizer, Swixx Biopharma. AB reports honouraria/speaking fees from GSK and AstraZeneca. IPar has received research funding and/or honouraria from Amgen, Argenx, AstraZeneca, Aurinia, Biogen, BMS, Elli Lilly, Gilead, GSK, Janssen, Novartis, Otsuka, Roche, UCB and Viatris. MM has consulted for AbbVie Pharmaceuticals. OAM reports consulting fees from AstraZeneca, GSK, Janssen and Roche. Payment or honouraria for lectures, presentations, speakers bureau, manuscript writing or educational events: AbbVie, AstraZeneca, GSK, Janssen, UCB and Roche. AF reports consulting fees from Swixx, GSK, Boehringer Ingelheim and BMS and honouraria/speaking fees from GSK, AstraZeneca, Pfizer, Jannsen, Lilly, Novartis, Genesis, Amgen and UCB. AH has served as consultant and received speaker fee for AstraZeneca, GSK and Astellas. ZT consulted for AstraZeneca, GSK, AbbVie, Biogen BMS, Merck, Novartis, Roche, Viatris and UCB.Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.Patient consent for publication Not applicable.Ethics approval The study received approval from the Ethics Committee of Strasbourg University (approval #CE-2023-95). Participants gave informed consent to participate in the study before taking part.Provenance and peer review Not commissioned; externally peer reviewed.Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer- reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/. ### Page 10 Arnaud L, et al. Lupus Science & Medicine 2026;13:e002148. doi:10.1136/lupus-2026-00214810Lupus Science & MedicineORCID iDsLaurent Arnaud https://orcid.org/0000-0002-8077-8394 Matteo Piga https://orcid.org/0000-0002-1126-8315 Guillermo J Pons- Estel https://orcid.org/0000-0002-0647-929X Raquel Faria https://orcid.org/0000-0002-2956-1966 Ali Duarte- Garcia https://orcid.org/0000-0003-1749-5719 Michelle A Petri https://orcid.org/0000-0003-1441-5373 Ioannis Parodis https://orcid.org/0000-0002-4875-5395 Antonis Fanouriakis https://orcid.org/0000-0003-2696-031X Andrea M Knight https://orcid.org/0000-0003-4278-9049 Alberta Hoi https://orcid.org/0000-0002-9416-7383 Zahi Touma https://orcid.org/0000-0001-5177-2076REFERENCES1 Hoi A, Igel T, Mok CC, et al. Systemic lupus erythematosus. Lancet2024;403:2326–38.2 Rayes HA, Tani C, Kwan A, et al. What is the prevalence of cognitive impairment in lupus and which instruments are used to measure it? A systematic review and meta-analysis. 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