Andrea M. Knight
VerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 1989–2026
About
Andrea M. Knight, MD MSCE, is an Adjunct Assistant Professor of Pediatrics (Rheumatology) and a Faculty Scholar at PolicyLab at The Children's Hospital of Philadelphia. She is affiliated with the University of Pennsylvania Department of Pediatrics. Her clinical research focuses on pediatric neuropsychiatric lupus, psychosocial health and outcomes of youth with lupus and other rheumatologic diseases, and healthcare utilization and disparities in pediatric lupus. Dr. Knight specializes in the diagnosis and management of pediatric autoimmune diseases, including systemic lupus erythematosus, juvenile idiopathic arthritis, juvenile dermatomyositis, and vasculitic syndromes. Her educational background includes a BSc in Human Biology from the University of Toronto, an MD from Columbia College of Physicians & Surgeons, and an MSCE from the University of Pennsylvania.
Research topics
- Medicine
- Internal medicine
- Psychiatry
- Pediatrics
- Cardiology
Selected publications
Lupus Science & Medicine · 2026-01-01
articleOpen accessSenior authorOBJECTIVE: This study examined serum brain injury markers and their associations with disease features, cytokines associated with microglial activation in lupus and cognitive dysfunction (CD) in adolescents with childhood-onset SLE (cSLE). METHODS: We used cross-sectional data from cSLE patients (aged 12-17 years) and age-matched, sex-matched healthy controls. Serum levels of brain injury markers (serum neurofilament light, glial fibrillar acidic protein (GFAP), Tau), interferon (IFN)-α, IFN-γ and interleukin-6 (IL-6) were quantified using Simoa assays. cSLE features included disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000), damage (Systemic Lupus International Collaborating Clinics damage index) and glucocorticoid (GC) exposure. A neurocognitive battery assessed executive function, attention and working memory, and CD was determined using standardised scores. We compared brain injury marker levels between cSLE and controls, and those with and without CD using Wilcoxon rank-sum tests. We calculated correlations between injury markers, disease features and cytokines and examined differences in disease features between those with and without high-level brain injury markers (>90th percentile) (using Bonferroni correction). RESULTS: Participants included 56 cSLE patients (median disease duration=10.6 months (IQR 2.0-14.1), one with neuropsychiatric lupus) and 43 controls. Levels were higher in cSLE versus controls for GFAP (z=-3.97, p<0.001), Tau (z=-2.10, p=0.035), IFN-α (z=-4.80, p<0.001), IFN-γ (z=-2.42, p=0.015) and IL-6 (-3.09, p=0.002). Severe CD (≥2 SD from standardised mean) was present in 31% cSLE versus 9% controls (chi2=6.69, p=0.01), associated with higher Tau levels for cSLE (z=-3.94, p<0.001). High-level brain injury markers were observed in 13 (23%) cSLE patients associated with higher SLEDAI-2K, IL-6 levels and current GC dose. CONCLUSION: Brain injury marker levels were high and associated with disease activity and CD in this cSLE adolescent cohort, suggesting a link between systemic inflammation and clinically under-detected neuronal/glial injury. Larger, longitudinal studies should explore the potential clinical utility of brain injury markers for clinical assessment of brain involvement in cSLE.
Lupus Science & Medicine · 2026-01-01
articleOpen accessSenior authorOBJECTIVE: To investigate the relationship between adverse childhood experiences (ACEs) and health outcomes in childhood-onset SLE (cSLE). METHODS: We conducted a retrospective cohort study of cSLE outpatients aged 9-18 years at a Canadian tertiary centre from July 2018 to June 2020. ACEs data were collected from electronic medical records, categorised according to the US Centers for Disease Control-Kaiser framework and in relationship to time of cSLE diagnosis. Primary outcomes included disease activity, disease damage and comorbid psychiatric diagnoses (not attributable to cSLE). Secondary outcomes included neuropsychiatric SLE (NPSLE), lupus nephritis and arthritis. Regression models examined the relationship between (1) presence (yes/no) and (2) timing of ACEs (none vs before vs after cSLE diagnosis) and the outcomes. Covariates included sex, ethnicity, age at diagnosis, disease duration, nephritis/NPSLE and glucocorticoid use. RESULTS: Of 224 patients with cSLE, 41% had documented ACEs. The presence of ACEs was associated with NPSLE (adjusted OR=3.40, 95% CI 1.55 to 7.78, p=0.003). ACEs occurring before diagnosis were associated with disease damage (adjusted OR 3.10, 95% CI 1.21 to 8.04, p=0.018) and NPSLE (adjusted OR=2.67, 95% CI 1.02 to 6.98, p=0.043). ACEs occurring after cSLE diagnosis were associated with comorbid psychiatric diagnosis (adjusted OR=5.01, 95% CI 1.20 to 21.12, p=0.025). ACEs were not associated with disease activity, nephritis or arthritis. CONCLUSION: ACEs exposure was prevalent in this cSLE cohort, associated with NPSLE diagnosis, disease damage and comorbid psychiatric diagnoses. These findings suggest that early-life stressors may contribute to cSLE morbidity, particularly neuropsychiatric features, emphasising the importance of addressing psychosocial issues in the context of medical care.
The Journal of Rheumatology · 2025-05-20
articleOpen accessSenior authorO005 / #41 Topic: AS18 - Pediatric SLE SCIENTIFIC HYBRID SESSION: CLINICAL TRACK PRESENTATIONS - OUTSTANDING ABSTRACT PRESENTATIONS 23-05-2025 9:00 AM - 10:00 AM Background/Purpose Adolescents with childhood-onset systemic lupus erythematosus (cSLE) typically experience higher prevalence of brain involvement when compared to adult-onset patients. They are vulnerable to neuropsychiatric syndromes (NPSLE) that may strike during neurodevelopment and could alter the functioning of brain networks that are crucial for cognition and behavior. Brain alterations in functional connectivity (FC) can be examined with resting-state functional magnetic resonance imaging (rs-fMRI) and have been observed in adults with lupus. However, FC abnormalities in relation to disease characteristics have been understudied in cSLE. We aimed to examine differences in brain FC between adolescents with cSLE and healthy controls (HC) utilizing rs-fMRI, and to evaluate if FC is associated with disease duration, activity and glucocorticoid use in cSLE. Methods Patients with cSLE aged 11-17 years and age and sex-matched HC underwent T1-weighted MRI and rs-fMRI at 3T. Disease activity was evaluated with the time-adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2K (SLEDAI-AMS), calculated as the area under the curve over 1 year before the MRI scan. Cumulative glucocorticoid use was calculated as prednisone equivalent dose in grams. Brain networks were parcellated with independent component analysis, thresholded, and transformed into regions of interest (ROIs). Group FC differences between all ROIs and regional volumes from structures with abnormal FC were evaluated with age-adjusted general linear models. In the cSLE group, regression analyses evaluated associations between FC and disease duration, activity and cumulative prednisone dose. All connections were family wise error (FWE) corrected with Threshold Free Cluster Enhancement (TFCE, p-FWE < 0.05). Results Participants included 60 patients with cSLE (52 females; age – median, IQR: 16, 3 years; 3 with NPSLE diagnosis) and 59 HC (49 females; age – median, IQR: 15, 2 years). For patients, median disease duration was 0.9 (IQR = 1.2) years, 45% had active disease (SLEDAI-AMS ≥ 4) in the year prior to study visit (median, IQR: 2.7, 5.4), and 73% were exposed to prednisone (cumulative prednisone dose – median, IQR: 1.9, 6.0 grams). Patients with cSLE had lower FC compared to HC in a cluster of frontoparietal connections (TFCE = 66.42, p-FWE = 0.00001; Figure 1). Lower right superior frontal cortex volumes were observed in patients with cSLE compared to HC (T = -2.34, p = 0.021). In the cSLE group (Figure 2), lower FC in superior frontal and cerebellar regions was associated with higher disease activity (TFCE = 55.10, p-FWE = 0.004) and higher cumulative prednisone dose (TFCE = 49.53, p-FWE = 0.013). Figure 1. Figure 2. Conclusions Patients with cSLE, compared to HC, exhibited decreased FC and, to a lesser extent, atrophy in frontoparietal regions known to associate with somatosensory and visuospatial functions. Moreover, higher cSLE disease activity and prednisone exposure may dysregulate the functioning of fronto-cerebellar networks involved in sensory information processing. Further longitudinal studies are needed to investigate the effect of cSLE and its treatment on brain function and development over time.
The Journal of Rheumatology · 2025-05-20
articleOpen accessPV168 / #462 Poster Topic: AS18 - Pediatric SLE Background/Purpose Symptoms of depression and anxiety are common among patients with childhood-onset systemic lupus erythematosus (cSLE). In recent years, screening for depression and anxiety using validated self-report tools is increasingly part of routine clinical care. Comparing prevalence of mood disorders over time amid evolving perspectives on mental health requires retrospective chart review. However, identifying patients with depression and anxiety by retrospective chart review is challenging and requires consideration of both clinical documentation and patient-reported symptoms. This study aims to investigate the prevalence of clinical and self-reported diagnoses of depression and anxiety among children and adolescents diagnosed and followed for cSLE in the SickKids Lupus Clinic, using retrospective clinical chart review and self-report screening tools. Methods We completed a retrospective study of children and adolescents aged ≤ 18 years seen in a tertiary care Lupus Clinic between January 1, 2000, to December 31, 2023. All patients met ≥4 American College of Rheumatology (ACR) and/or Systemic Lupus International Collaborative Clinics (SLICC) criteria for SLE with data prospectively collected in a dedicated Lupus database. Additional information such as age of SLE diagnosis, sex, ancestry, and disease activity were extracted from the database. Symptoms and diagnoses of depression and/or anxiety and use of psychotropic medication, before and after cSLE diagnosis, were extracted from clinical charts in ChartMaxx and EPIC. We identified patients with depression and/or anxiety as those with medical chart documentation of 1) a diagnosis and 2) persistent depression and/or anxiety symptoms over a course of at least 2 months. Self-reported depression and anxiety were identified by the Children’s Depressive Inventory (CDI, CDI-2) and Multidimensional Anxiety Scale for Children (MASC, MASC-2), completed as clinical screening measures for patients seen by psychiatry. We classified individuals as positive for self-reported depression based on a total score >13 on the CDI and CDI-2, and for self-reported anxiety based on a total score >60 on the MASC and MASC-2, appropriate for referral to mental health services. We included patients who completed at least 1 self-report screen for depression or anxiety and retained the most severe score in analyses. Descriptive statistics were used for cohort demographics and cSLE features. Results We reviewed 491 patient clinical charts and identified 135 patients who completed at least 1 self-report questionnaire. The majority were females (86%) and the median age of cSLE diagnosis was 13 years (IQR 12-15) (Table 1). Most patients were of European (33%) and East Asian (24%) ancestry. The majority of patients completed the CDI (64%) and/or the MASC (25%), followed by MASC-2 (6%) and/or CDI-2 (5%) (Table 2). Of the 93 patients who completed a self-report screen for depression, 41 (44%) screened positive for depression; the majority who screened positive (68%) did not receive a diagnosis of depression (Table 3). Of the 42 patients who completed a self-report screen for anxiety, 18 (43%) screened positive for anxiety; the majority who screened positive (55%) did not receive a diagnosis of anxiety. Psychotropic medication was initiated in 34% of patients after screening positive for depression and/or anxiety. Table 1. Demographic and clinical features of reviewed cSLE cohort (n = 135) Table 2. Number of patients who completed the CDI, CDI-2, MASC, and/or MASC-2 Table 3. Number of patients who screened positive for depression on the CDI or CDI-2, and/or anxiety on the MASC or MASC-2 Conclusions We found self-reported depression and anxiety to be prevalent among youth with cSLE. Future directions include examining scores for the Patient Health Questionnaire-4 (PHQ-4), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder 7-item scale (GAD-7). Concordance between clinical diagnosis and self-reported depression and anxiety will be assessed using chi-square statistics for categorical values and Wilcoxon rank-sum test for continuous variables.
The Journal of Rheumatology · 2025-09-01
articleSenior authorObjective This study investigates individual and socioecological resilience and its relationship with sociodemographic and disease characteristics, as well as psychosocial patient-reported outcome measures (PROMs) in childhood-onset systemic lupus erythematosus (cSLE). Methods We conducted a cross-sectional study of patients with cSLE, ages 11-22 years, at a Canadian tertiary center from October 2021 to July 2024. The 10-item Connor-Davidson Resilience Scale (CD-RISC-10) assessed individual resilience. The Child and Youth Resilience Measure–Revised (CYRM-R) assessed socioecological resilience. Linear regression models examined associations between resilience with sociodemographic (eg, health literacy, adverse childhood experiences [ACEs]) and disease factors (eg, age of onset, duration, disease activity). Pearson correlations determined relationships between resilience and patient-reported depressive and anxiety symptoms, executive functioning, pain interference, and fatigue. Results Of 49 participants, the mean score for individual psychological resilience was 26.0 (SD 7.1; CD-RISC-10), and the mean score for socioecological resilience was 73.4 (SD 9.1; CYRM-R). Higher resilience on CD-RISC-10 (β 0.99, 95% CI 0.45-1.55, P < 0.01) and CYRM-R (β 0.84, 95% CI 0.13-1.55, P = 0.02) was associated with better health literacy on the communication subscale. Lower CYRM-R scores were associated with higher number of ACEs (β −1.02, 95% CI −1.88 to −0.17; P = 0.02). For PROMs, lower scores for both individual and socioecological resilience correlated with worse depressive symptoms ( r −0.44, P = 0.003 for CD-RISC-10; r −0.55, P = 0.001 for CYRM-R) and executive functioning ( r −0.49, P = 0.002 for CD-RISC-10; r −0.56, P = 0.002 for CYRM-R). Conclusion Greater resilience was associated with fewer ACEs and better health-related communication, patient-reported mental health, and executive functioning. Findings highlight the importance of fostering resilience to improve outcomes in youth with cSLE.
UNC Libraries · 2025-09-05
articleOpen accessOBJECTIVE: There is a pressing need for high-quality, comprehensive research to describe the natural history, best treatments, access to care and disparities in care for patients with childhood-onset SLE (cSLE). Building on a previously published survey study of cSLE clinicians and researchers to describe research priorities in cSLE, the primary objective of this study was to conduct expert interviews to define high-priority areas for cSLE research. METHODS: Individuals with identified multidisciplinary expertise in cSLE were recruited worldwide using purposive sampling technique. Experts participated in open-ended, semistructured qualitative interviews. Interviews were designed to elicit expert perspectives on research priorities, optimal research approaches, and factors that facilitate and hinder advancing cSLE research. Interviews were digitally recorded, transcribed and de-identified for analysis. Analysis for underlying themes of cSLE expert perspectives was performed using a constant comparative approach. RESULTS: Twenty-nine experts with diverse clinical and research backgrounds participated. Themes emerged within five domains: (1) expanding disease knowledge; (2) investigator collaboration; (3) partnering with patients and families; (4) improving care to optimise research; and (5) overcoming investigator barriers. Choosing a singular area of focus was difficult; experts identified many competing priorities. Despite the numerous priorities that emerged, experts described several existing and potential opportunities for advancing cSLE research. CONCLUSIONS: In addition to the priorities identified by cSLE experts in this study, the opportunities for advancing cSLE research and care that were proposed should be used as a foundation for creation of a cSLE research agenda for both research and funding allocation.
The Journal of Rheumatology · 2025-05-20
articleOpen accessSenior authorO069 / #96 Topic: AS18 - Pediatric SLE ABSTRACT CONCURRENT SESSION 12: PEDIATRIC SLE – ADVANCES IN DISEASE OUTCOMES AND MENTAL HEALTH 24-05-2025 10:40 AM - 11:40 AM Background/Purpose Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease characterized by multiorgan inflammation, alongside high frequencies of mood disorders and cognitive impairment. Adverse Childhood Experiences (ACEs) quantify traumatic childhood events, which have been linked to altered immune response and increased chronic disease risk. Prior studies indicate that those with ≥ 4 ACEs, including adults with SLE, face higher risk of worse health outcomes. Limited research exists on ACEs in cSLE. We aimed to describe the prevalence of ACEs among cSLE patients and investigate associations with i) disease activity, ii) patient-reported outcome measures, and iii) self-reported executive function. Methods This cross-sectional study analyzed prospective data from cSLE patients aged 13-19 years at the time of assessment. The Pediatric ACEs and Related Life Events Screener (PEARLS) measured self-reported ACEs. Disease activity over the time since diagnosis was measured by the adjusted mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K). The Patient Reported Outcomes Information System (PROMIS) Pediatric-37 Profile assessed patient-reported anxiety, depression, and fatigue. The Behavior Rating Inventory of Executive Function (BRIEF-2) Global Executive Composite score measured executive function. The frequency of ACEs types was tabulated, and patients were classified into high-risk (≥ 4 ACEs) and low-risk (≤ 3 ACEs) groups. Associations between ACEs risk group and the outcomes were examined using regression analyses with generalized linear models, adjusted for age. Results Of 48 cSLE patients (mean age 15.23 ± 1.87 years, 85% female), 73% reported at least 1 ACE, and 30% reported ≥ 4 ACEs (Table 1). The most common ACEs were caregiver verbal abuse, emotional neglect, and separation, as well as community violence (Figure 1). Being in the high-risk ACEs group compared to low risk, was significantly associated with worse scores for PROMIS anxiety (p<0.001), depression (p<0.001), and fatigue (p=0.001), alongside poorer executive function scores (p<0.001) (Figure 2). No significant associations were observed for disease activity (p=0.987). Table 1. Patient Demographics, Disease Characteristics, and Outcome Measures Figure 1. Self-Reported Adverse Childhood Experiences (ACEs) in Patients with cSLE: Frequency and Types Note . Figure 1 illustrates the distribution of 19 reported adverse childhood experiences (ACEs) types within our cSLE cohort (n=48). Among the total ACEs (n=134) self-reported on the patient PEARLS questionnaire, the most commonly reported ACEs were caregiver verbal abuse (n=18), community violence (n=14), emotional neglect (n=14), and caregiver separation/divorce (n=14). Figure 2. Relationship between ACEs and Self-Reported cSLE Outcomes Note . Figure 2 contains 4 sets of boxplots depicting differences in mean outcome scores between the high-risk and low-risk ACEs groups. Associations show beta coefficients, confidence intervals, and p-values from regression analyses. Regression analyses showed significant associations for worse PROMIS anxiety (p<0.001), depression (p<0.001), and fatigue (p=0.001) scores alongside poorer executive function (p<0.001) within the high-risk group. The p-value threshold used for significance was p<0.05. Acknowledgments: Lupus Research Alliance, U.S. Department of Defense Conclusions Within our cSLE cohort, ACEs were substantially prevalent, with almost a third of patients having experienced ≥ 4 ACEs. The high-risk group (≥ 4 ACEs) had significantly worse patient-reported outcomes across anxiety, depression, fatigue, and executive function. These results underscore the impact of ACEs on patient well-being, emphasizing the need for integrated medical and mental health care approaches. Future research should examine these associations within larger cohorts.
The Journal of Rheumatology · 2025-05-20
articleOpen accessPV154 / #267 Poster Topic: AS17 - Miscellaneous Background/Purpose Neonatal lupus erythematosus (NLE) is a passively acquired autoimmune condition. The antibody-mediated neonatal heart disease of NLE is associated with a high risk of mortality and adverse health outcomes. Prenatal treatment can slow progression from incomplete to complete heart block and improve neonatal survival. However, the impacts of postnatal immunosuppressant treatment have not been described. This study aimed to describe the outcomes of children with antibody-mediated cardiac NLE treated with postnatal therapy. Methods We reviewed patients consented from the NLE clinic in a tertiary pediatric center, born between January 1, 1997 – June 10, 2024. We identified patients with cardiac manifestations who received postnatal immunosuppressants. The protocol typically included 1 dose of intravenous immunoglobulin (IVIG) 2g/kg, pulse corticosteroid of 30 mg/kg/day for 3 days, followed by 2 mg/kg/day for 4 weeks with tapering guided by troponin levels. We reviewed medical records with long-term outcomes supplemented by patient/parent questionnaires. We report the prevalence of features and outcomes using summary statistics. Results We reviewed 33 patients with cardiac manifestations of NLE and postnatal therapy. Of the total cohort, 28 (85%) mothers received prenatal immunosuppressive therapy with dexamethasone, IVIG and/or a beta agonist. The median duration of follow-up was 6.04 years (IQR: 2.47 – 11.36 years). The majority (70%) of patients presented with heart block at birth (first-degree/second-degree atrioventricular block [n=7], complete heart block [n=16]). The remaining 10 patients had extranodal manifestations of cardiac inflammation, including echogenic endocardium and valvular regurgitation. All the patients received corticosteroids, 17 with pulse and 28 received IVIG. Of the 7 patients with first or second-degree block at birth, 4 progressed to complete heart block within an average of 11 months. One patient with first-degree block had complete reversal to normal sinus rhythm. Of the 18 (70%) patients that required a permanent pacemaker, 83% were paced within the first year of life. Of all patients that developed complete heart block in their lifetime, 2 never required pacing (age at last follow-up 17.38 and 19.25 years). None of the patients required a heart transplant. Three patients developed device-associated or sternal wound infections an average of 1.1 months after birth. Mortality in the cohort was 9% with cause of death attributed to circulatory shock due to sepsis and an unrelated genetic syndrome. Conclusions We report on the outcomes of a large series of children with cardiac NLE who received postnatal immunosuppressive therapy. The vast majority of patients had good outcomes. The 9% mortality is improved upon historical reports ranging from 13-30%. Postnatal immunosuppressive therapy may be responsible for improved cardiovascular outcomes in children with antibody-mediated neonatal heart disease.
Cognitive Behavioral Therapy for Youth With Childhood‐Onset Lupus: A Randomized Clinical Trial
Arthritis Care & Research · 2025-12-15
articleOpen accessSenior authorObjective Our objective was to determine the feasibility and acceptability of the Treatment and Education Approach for Childhood‐Onset Lupus (TEACH), a six‐session cognitive behavioral intervention addressing depressive, fatigue, and pain symptoms, delivered remotely to individual youth with lupus by a trained interventionist. We expected that TEACH would be considered feasible and acceptable based on recruitment and retention rates. We also examined the effect of TEACH on youths’ depressive, fatigue, and pain symptoms compared to medical treatment as usual (TAU). Methods A pilot two‐arm longitudinal randomized controlled clinical trial was conducted. Adolescents (12–17 years) and young adults (18–22 years) with childhood‐onset systemic lupus erythematosus and elevated depressive, fatigue, and/or pain symptoms were recruited from six pediatric rheumatology sites across the United States and Canada from August 2020 to March 2023. Participants were randomized 1:1 to TEACH and TAU or TAU alone and reported symptom data at baseline and eight weeks later. Results Of the 200 youth approached, 97 consented to participate (48.5% recruitment). Among 64 eligible participants, 32 were randomized to TEACH and TAU and 32 to TAU alone. Retention was high (92.2%). At postassessment, the intervention group demonstrated reductions in depressive (C emm 7.88, 95% confidence interval 3.20–12.60; 14%) and fatigue (C emm 3.91, 95% confidence interval 0.44–7.39; 7%) symptoms but not pain (C emm 0.89, 95% confidence interval −0.06 to 1.84). Conclusion This remotely delivered cognitive behavioral intervention tailored to youth with lupus was feasible and associated with reduced depressive and fatigue symptoms compared with medical TAU. Further increasing accessibility by implementing TEACH in medical settings may improve uptake and patient outcomes. image
CAR T cell therapy for children with rheumatic disease: the time is now
Nature Reviews Rheumatology · 2025-07-02 · 10 citations
reviewOpen access
Recent grants
Frequent coauthors
- 167 shared
Tamar B. Rubinstein
Children's Hospital at Montefiore
- 167 shared
Alaina M. Davis
Vanderbilt University Medical Center
- 139 shared
David S. Mandell
May Institute
- 136 shared
Joyce C. Chang
Children's Hospital of Philadelphia
- 115 shared
Marisa S. Klein‐Gitelman
Children's Hospital of Philadelphia
- 110 shared
Zuleyha Cidav
University of Pennsylvania
- 106 shared
Hannah Katcoff
University of Pennsylvania
- 106 shared
Jennifer Faerber
Children's Hospital of Philadelphia
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