Anxiety in Childhood Onset Lupus: Longitudinal Anxiety Symptom Screening

Abstract

Objective:

Mental health conditions, including anxiety, are common in childhood onset systemic lupus erythematosus (cSLE) and impact disease management and quality of life. This study evaluates the prevalence of anxiety symptoms and association of anxiety screening results with baseline and longitudinal demographic, clinical, treatment, and social features in cSLE.

Methods:

Patients ≥ 12 years of age diagnosed with cSLE were included. Demographic information, disease characteristics, disease activity, medications, provider-assessed medication adherence, and patient-reported outcomes of pain, physical function, anxiety, depression, suicidality and social determinants of health were extracted from the electronic health record. Anxiety symptoms, measured using the Generalized Anxiety Disorder (GAD) 7, were considered significant if score ≥ 10. The associations between GAD-7 scores and clinical, patient-reported, and social characteristics were evaluated longitudinally.

Results:

Among 76 cSLE patients with 196 visits, 47% and 21% had at least one GAD-7 of mild, and moderate or severe anxiety, respectively. Baseline clinical features including history of lupus nephritis and glucocorticoid dose were not associated with GAD-7 scores. The Deprivation and Community Index, which estimates socioeconomic disadvantage within geographic areas, did not vary by anxiety status. In multivariate longitudinal analysis, there was an association with depression and clinically significant GAD scores.

Conclusion:

Anxiety symptoms were common in this cohort of cSLE, and anxiety and depression were significantly associated. In multivariate longitudinal analysis, there was no association between anxiety and disease activity, steroid use, pain, physical function, or social factors. Results support the need for routine anxiety screening in children and adolescents with lupus.

Introduction:

According to the 2022 National Survey of Children’s Health (NSCH), in the United States, approximately 10.6% of children and adolescents experience anxiety disorders¹. Anxiety is more prevalent in adolescence and in the setting of chronic medical conditions¹, and specifically in childhood-onset systemic lupus erythematosus (cSLE), the prevalence of anxiety symptoms is reported to be as high as 50%^{2, 3}. Anxiety in childhood predicts future anxiety and depression, and negatively impacts health care quality of life, medication adherence, disease activity, pain and functional status^4–6. Thus, it is crucially important to identify and treat anxiety to promote best outcomes for children and adolescents with cSLE. The American Academy of Pediatrics and United States Preventive Services Task Force recommend annual anxiety screening for all children starting at age ≥ 10 years and ≥ 8 years, respectively^{7, 8}. Recently, the American College of Rheumatology has recommended at-least annual anxiety screening for youth ages 12 and up who are in established pediatric rheumatology care⁹. In children, available anxiety screening tools include the Generalized Anxiety Disorder-7 (GAD-7), Beck Youth Inventories-Anxiety Inventory, Screen for Childhood Anxiety Related Emotional Disorders (SCARED), State-Trait Anxiety Inventory for Children, and Patient-Reported Outcomes Information Measurement System (PROMIS). Although these screening tools are widely available and feasible to implement in pediatric rheumatology clinics¹⁰, anxiety screening is not performed universally for youth with SLE. Much remains unknown concerning the prevalence and clinical associations of anxiety symptoms in children and adolescents with SLE. To address these gaps in knowledge, this study aimed to evaluate the prevalence of anxiety symptoms in cSLE and the longitudinal association of anxiety with demographic, treatment, clinical, and social variables.

Methods:

Setting:

This retrospective study included patients with cSLE who were evaluated at a quaternary care pediatric rheumatology center between 2022 and 2024. This study was approved by the Nationwide Children’s Institutional Review Board (STUDY00002913).

Inclusion Criteria:

Patients were identified from the electronic health record and included if they had 1) a diagnosis of systemic lupus erythematosus (International Classification of Diseases – Clinical Modifier (ICD-CM) (ICD-10-CM M32.*), on the history or problem list, 2) a cSLE diagnosis confirmed on manual chart review, 3) were ≥ 12 years of age, and 4) completed at least one GAD-7 questionnaire in the rheumatology clinic.

Clinical Characteristics:

Demographics, disease duration, history and class of lupus nephritis, mental health diagnosis were extracted from the electronic health record using ICD-CM codes, including anxiety (F40.*, F41.*), depression (F32.*, F33.*), mood disorder (F43.*), seizure disorder (G40.*) and confirmed by manual chart review. Neuropsychiatric lupus was defined as documentation of one or more of the following findings during manual chart review: aseptic meningitis, cerebrovascular disease, demyelinating syndrome, lupus headache, chorea, myelopathy, seizures attributed to lupus, acute confusional state, cognitive dysfunction, or psychosis. The diagnosis of SLE was established by the primary clinician using either the American College of Rheumatology/ European League Against Rheumatism or Systemic Lupus International Collaborating Clinics classification criteria^{11, 12}.

Medications and Adherence:

Current medications, number of pills per week, and number of injections and infusions per month were ascertained from manual chart review. Glucocorticoid dose was transformed to oral prednisone equivalents in mg/kg/day at the time of the visit. Physician rating of medication adherence was estimated by the question at each visit, “How frequently was the patient taking hydroxychloroquine in the last month” with a 0–100% of the time response options.

Patient Reported Outcomes:

The following patient reported outcomes were collected as part of standard of care for all patients with cSLE at all clinic visits: 1) Patient-reported pain related to rheumatology disorder over past week on a 0–10 ordinal scale, 2) Physical function measured by self-reported Childhood Health Assessment Questionnaire (CHAQ) on a 0–3 scale with higher scores indicating worse function.

Mental Health Screening Tools:

In this clinic, since 2022, as part of routine clinical care, all patients with cSLE are asked to complete at each pediatric rheumatology clinic visit an electronic questionnaire on a tablet that includes the Generalized Anxiety Disorder −7 (GAD-7), Patient Health Questionnaire (PHQ-8), and Ask Suicide-Screening Questions (ASQ) questionnaires. In the event of positive screen on the PHQ-8 (score ≥10) and/or ASQ (endorsement of “yes” to any question), the physician and other providers documenting in the medical record receive an interruptive alert that facilitates linking the patient to a mental health specialist during the visit. If an acute positive response to the ASQ is elicited (e.g., answer of “yes” to the item, “Are you having thoughts of killing yourself right now?”), 1:1 staff supervision of patient is initiated until full suicide risk evaluation is completed. A silent in-basket message is also sent to the mental health specialist team, including a psychologist and social worker, who are tasked with completing suicide risk assessment, engaging in safety planning, and reviewing or connecting the patient with crisis resources as indicated. In the event of positive screen on the GAD-7 (GAD-7 ≥ 10), the physician and other providers entering the medical record receive a hard stop to ensure that the patient is linked with behavioral health support and otherwise, are prompted to place behavioral health referral for anxiety management.

Anxiety screening tool:

This study utilized the GAD-7 questionnaire, a self-reported anxiety screening tool well validated children and adolescents ≥ 12 years of age which can be completed by patient or caregiver¹³. In our clinic, patients ≥ 12 years (rather than caregivers) are instructed to complete the questionnaire. This questionnaire includes 7 items and takes ≤ 5 minutes to complete with scores ranging from 0–21. Scores of 0–4, 5–9, 10–14, >15 indicate none, mild, moderate, and severe anxiety symptoms, respectively. For the purposes of this study, a clinically significant score for anxiety symptoms was defined as GAD-7 ≥ 10.

Depression screening tool:

The PHQ-8 is a self-reported depression screening tool that is well validated for use in children ≥ 12 years of age¹⁴. This questionnaire includes 8 items and takes ≤ 5 minutes to complete with scores ranging from 0–24. Scores of 0–4, 5–9, 10–14, 15–19 and ≥ 20 indicate no/minimal, mild, moderate, moderately severe, and severe depression symptoms, respectively.

Suicide risk screening tool:

The ASQ tool is a tool validated to screen for suicide risk in children (≥ 8 years of age) and adults, includes 4 items, and takes < 1 minute to complete¹⁵. Any answer of “yes” to any question is considered positive and warrants further evaluation.

Social Determinants of Health:

As part of routine clinical care, patients complete annual social determinant of health screening across four domains: resource strain^{16, 17}, transportation needs¹⁸, food insecurity¹⁹, and housing stability²⁰. For each patient, the Distressed Community Index (DCI) was calculated using baseline data. The DCI is a tool which estimates socioeconomic disadvantage using patient zip codes. Scores range from 0–100 with higher score indicating more distress²¹. Using the DCI, communities are grouped into quintiles: prosperous, comfortable, mid-tier, at risk, and distressed.

SLE Disease Activity:

Lupus disease activity is measured each visit in our clinic as part of routine care using the SLE Disease Activity Score 2000²² (SLEDAI-2K), a 24 item score containing 16 clinical and 8 laboratory criteria with scores ranging from 0 to 105, with higher scores indicating increased disease activity.

Statistical Analysis:

Differences in baseline demographics and clinical characteristics were evaluated using the Wilcoxon signed-rank test for continuous variables, Chi square and Fisher’s exact for categorical variables, as appropriate. Median and interquartile range (IQR) and count (percent) are reported.

Model development:

Our primary outcome was a clinically significant GAD-7 score. We tested the association of clinical, patient-reported, and social characteristics with the GAD-7 score over time using logistic regression. Subject was a random effect in all models. Variables with p<0.20 in univariate analysis were included in a multivariable model. Supplemental analysis was completed using GAD-7 as a continuous variable and evaluated over time using mixed effects linear regression with random intercepts, and subject was a random effect in all models.

Results:

We identified 76 patients who met the inclusion criteria and were included in the analyses. These patients attended 196 rheumatology clinic visits (median of 2 visits [IQR 1, 3]) during the study period. Individual patient GAD-7 and PHQ-8 trajectories are shown in Figures 1a and 2a, respectively. The median age at first GAD-7 screening was 17 years, the majority (84%) were female, and the sample was racially diverse (25% Black, 35% White, and 24% Multi-racial, and 16% Asian) (Table 1). The median duration of disease was 19 months [IQR 6, 49] and 7% had a history of neuropsychiatric lupus. Thirty-six percent of patients had a history of lupus nephritis, distributed as follows: class I (2 patients), class II (3 patients), class III (7 patients), class IV (11 patients), class V (3 patients), and class VI (1 patient). A pre-existing anxiety diagnosis was present, ascertained by ICD-CM codes, in 1% and depression diagnosis in 11%. Overall lupus disease activity was low with median SLEDAI of 2 [IQR 0, 4]. Medication burden was high with median number of pills per week of 54 [IQR 35, 76]; median daily prednisone dose was 0.02 mg/kg/day [IQR 0, 0.2]. Adherence with hydroxychloroquine use was reported to be high (90–100%) by providers. Resource strain, transportation needs, food insecurity or housing instability were reported in 13%, and the median Distressed Community Index was 49 [IQR 11, 74], with 7 (10%) mid-tier, 15 (21%) at-risk, and 16 (21%) distressed.

Figure 1a:

Spaghetti plots demonstrating individual patient GAD-7 scores over time. Abbreviations: GAD-7: Generalized Anxiety Disorder-7 Scale.

Figure 2a:

Spaghetti plots demonstrating individual patient PHQ-8 scores over time. Abbreviations: PHQ-8: Patient Health Questionnaire- 8.

Table 1:

Baseline Characteristics and Comparison of Groups with and without at Least Moderate Anxiety Symptoms (GAD-7 ≥ 10)

	All patients (N=76)	Never clinically positive anxiety screening (N=60)	Ever clinically positive anxiety screening (N=16)	p-value
Age (years), median [IQR]	17 [15, 19]	17 [15, 19]	16 [14, 19]	0.67
Female sex	64 (84%)	48 (80%)	16 (100%)	0.06
Race				0.25
Asian	12 (16%)	12 (20%)	0 (0%)
Black	19 (25%)	14 (23%)	5 (31%)
Multi-racial	18 (24%)	13 (22%)	5 (31%)
White	27 (35%)	21 (35%)	6 (38%)
Hispanic ethnicity	11 (14%)	8 (13%)	3 (19%)	0.58
Primary language				0.36
English	66 (87%)	50 (83%)	16 (100%)
Spanish	6 (8%)	6 (10%)	0 (0%)
Other	4 (5%)	4 (7%)	0 (0%)
Public insurance	33 (43%)	24 (40%)	9 (56%)	0.24
Disease duration in months, median [IQR]	19 [6, 49]	17 [7, 43]	31 [1, 90]	0.82
History of
Lupus nephritis	27 (36%)	20 (34%)	7 (47%)	0.36
Neuropsychiatric lupus	5 (7%)	3 (5)	2 (13%)	0.28
Anxiety disorder	1 (1%)	1 (2%)	0 (0%)	1.00
Depressive disorder	9 (11%)	6 (10%)	3 (18%)	0.39
Mood disorder	3 (4%)	3 (5%)	0 (0%)	1.00
Seizure disorder	4 (5%)	2 (3%)	2 (13%)	0.19
SLEDAI, median [IQR]	2 [0, 4]	2 [0, 4]	2 [1, 8]	0.46
Number of pills prescribed per week, median [IQR]	54 [35, 76]	49 [32, 73]	70 [61, 130]	0.01
Prednisone (mg/kg/day), median [IQR]	0.02 [0, 0.2]	0 [0, 0.2]	0.1 [0, 0.6]	0.38
Medication adherence	100 [90, 100]	100 [90, 100]	90 [90, 100]	0.14
Any positive social risk screeninga	13 (17%)	8(13%)	5 (13%)	0.13
Resource strain	11 (15%)	6 (10%)	5 (31%)	0.03
Transportation needs	2 (3%)	0 (0%)	2 (6%)	0.04
Food insecurity	8 (11%)	3 (5%)	5 (31%)	<0.01
Housing instability	4 (5%)	2 (3%)	2 (13%)	0.19
Distressed Community Indexb
Prosperous	25 (34%)	23 (39%)	2 (14%)	0.18
Comfortable	10 (14%)	7 (12%)	3 (22%)
Mid-Tier	7 (10%)	5 (8%)	2 (14%)
At Risk	15 (21%)	10 (17%)	5 (36%)
Distressed	16 (21%)	14 (24%)	2 (14%)

Legend: IQR: interquartile range. SLEDAI: Systemic Lupus Erythematosus Disease Activity Index 2000.

^aScreening is not mutually exclusive.

^bAvailable in 73 patients.

When comparing those who had at least one clinically significant GAD-7 score during the study period to those who did not, the groups did not differ by age, sex, race, disease duration, disease activity, or steroid dose. Provider-reported adherence to hydroxychloroquine was high overall but was lower in those who had at least one clinically significant GAD-7 score. Unmet social needs of resource strain, transportation needs, and food insecurity were more frequently reported in those who had at least once clinically significant GAD-7 score (all p<0.05).

At baseline, no/minimal anxiety symptoms were present in 66%, mild symptoms in 21%, moderate symptoms in 10%, and severe symptoms in 3% (Table 2). Clinically significant depressive symptoms (PHQ-8 ≥10) were present in 12% at baseline, and 8% had positive ASQ screens indicating risk for suicidality. Thirty-six (47%) had at least one GAD-7 score > 4. While an anxiety diagnosis was identified in the electronic medical record in only 1%, one in eight youth had clinically significant anxiety symptoms on screening. Of the 16 (21%) patients with a clinically significant GAD-7 (score ≥ 10) screening during the study period, baseline depression scores were none (33%), mild (27%), moderate (27%), moderately severe (7%), and severe (7%). Among patients who had ever reported clinically significant GAD scores across all visits, the simultaneous PHQ-8 depression scores were as follows: 6 with none, 8 with mild, 4 with moderate, 2 with moderately severe, and 3 with severe depression. There were higher baseline pain and worse physical function scores in patients who had at least one clinically significant GAD-7 score during the study period (all p<0.05).

Table 2:

Baseline Mental Health and Patient-Reported Outcome Screening with and without at Least Moderate Anxiety Symptoms (GAD-7 ≥ 10)

	All patients (N=76)	Never clinically positive anxiety screening (N=60)	Ever clinically positive anxiety screening (N=16)	p-value
GAD-7 score				<0.01
No anxiety (0–4)	50 (66%)	47 (78%)	3 (19%)
Mild (5–9)	16 (21%)	13 (22%)	3 (19%)
Moderate (10–14)	8 (10%)	0 (0%)	8 (50%)
Severe (≥ 15)	2 (3%)	0 (0%)	2 (12%)
PHQ-8 scorea				<0.01
No depression (0–4)	51 (69%)	46 (78%)	5 (33%)
Mild (5–9)	14 (19%)	10 (17%)	4 (27%)
Moderate (10–14)	7 (10%)	3 (5%)	4 (27%)
Moderately severe (15–19)	1 (1%)	0 (0%)	1 (7%)
Severe (20–24)	1 (1%)	0 (0%)	1 (7%)
Positive ASQb	4 (8%)	1 (2%)	3 (33%)	0.02
Pain score, median [IQR]	0 [0, 3]	0 [0, 1]	3 [0, 8]	<0.01
CHAQ score, median [IQR]	0 [0, 0.13]	0 [0, 0]	0.13 [0, 0.78]	0.01

Legend:

^aavailable in 74 subjects.

^bavailable in 50 subjects.

ASQ: Ask Suicide Questionnaire. CHAQ: Childhood Health Assessment Questionnaire. IQR: interquartile range.

In longitudinal univariate analysis, a clinically significant GAD-7 score was significantly associated with disease duration, SLEDAI score, pills per week, PHQ-8 score, positive ASQ, pain score, CHAQ score, and food insecurity (Table 3). There were no associations with race, presence of lupus nephritis or neuropsychiatric lupus, prednisone dose, medication adherence, or Distressed Community Index.

Table 3:

Longitudinal Associations of Clinically Significant GAD-7 Scores in Logistic Regression Modeling

	Univariate Analysis		Multivariate Analysis
	Odds Ratio (95% CI)	p-value	Odds Ratio (95% CI)	p-value
Age	0.99 (0.74, 1.36)	0.99	--	--
Female sex	--	--	--	--
Race
White	Reference	--	Reference	--
Asian	--	--	--	--
Black	1.23 (0.18, 8.55)	0.83	--	--
Multi-racial	0.09 (0.13, 7.63)	0.99	--	--
Hispanic ethnicity	0.92 (0.09, 9.43)	0.95	--	--
Primary language
English	Reference	--	--	--
Spanish	--	--	--	--
Other	--	--	--	--
Public insurance	4.10 (0.81, 20.69)	0.09	4.56 (0.34, 61.10)	0.25
Disease duration in months	1.01 (1.00, 1.02)	0.04	1.01 (0.99, 1.02)	0.24
History of
Lupus nephritis	1.41 (0.24, 8.17)	0.70	--	--
Neuropsychiatric lupus	2.46 (0.11, 53.46)	0.57	--	--
Anxiety disorder Depressive disorder	1.03 (−1.28, 3.34)	0.38	--	--
Mood disorder	--	--	--	--
Seizure disorder	3.37 (0.13, 86.87)	0.46	--	--
SLEDAI score	1.22 (1.03, 1.44)	0.02	1.19 (0.92, 1.55)	0.18
Pills per week	1.02 (1.00, 1.04)	0.01	1.03 (1.00, 1.07)	0.06
Injections per month	1.10 (0.77, 1.59)	0.55	--	--
Infusions per month	1.03 (0.14, 7.35)	0.98	--	--
Prednisone (mg/kg/day)	0.51 (0.04, 6.00)	0.59	--	--
Mediation adherence	1.00 (0.97, 1.02)	0.70	--	--
PHQ-8 score	1.82 (1.27, 2.62)	<0.01	1.43 (1.04, 1.96)	0.03
Positive ASQ	141.17 (2.02, 9865.52)	0.02	2.43 (0.11, 55.60)	0.57
Pain score	1.74 (1.18, 1.84)	<0.01	1.06 (0.70, 1.61)	0.77
CHAQ score	3.51 (1.02, 12.02)	0.05	0.34 (0.01, 8.39)	0.51
Positive social risk screening	2.62 (0.46, 14.67)	0.28	--	--
Resource strain	7.39 (0.88, 61.90)	0.07	1.47 (0.02, 99.31)	0.86
Transportation needs	6.98 (0.19, 253.91)	0.29	--	--
Food insecurity	9.58 (1.41, 64.88)	0.02	3.27 (0.04, 258.08)	0.60
Housing instability	2.45 (0.13, 45.53)	0.55	--	--
Distressed Community			--	--
Index
Prosperous	Reference	--	Reference	--
Comfortable	6.42 (0.38, 108.86)	0.20	0.54 (0.02, 13.75)	0.71
Mid-Tier	6.37 (0.24, 165.50)	0.27	0.15 (0.01, 6.36)	0.32
At Risk	10.90 (0.89, 133.44)	0.06	0.06 (0.01, 2.36)	0.13
Distressed	3.03 (0.20, 45.03)	0.42	0.05 (0.01, 7.10)	0.24

Legend: GAD-7: Generalized Anxiety Disorder-7 Scale; SLEDAI 2K: Systemic Lupus Erythematosus Disease Activity Score 2000. PHQ: Patient Health Questionnaire. CHAQ: Childhood Health Assessment Questionnaire.

In longitudinal multivariate analysis, clinically significant GAD-7 scores were associated with higher PHQ-8 score. Insurance status, disease duration, SLEDAI score, pills per week, patient-reported measures of pain and physical function, food insecurity, and Distressed Community Index scores were not associated with clinically significant GAD-7 scores.

When evaluating individual patient GAD-7 scores across time, there is a tendency for scores to decrease over time for most patients, but there can be sharp fluctuations across visits (Figure 1a). For those with any GAD-7 scores <10 during the study period, anxiety symptoms tended to remain stable (Figure 1b). However, there was a trend of improvement in GAD scores for those whose initial GAD-7 scores were ≥ 10.

Figure 1b:

Trajectory of median GAD-7 scores over time, comparing individuals with at least one clinically significant score to those without. Abbreviations: GAD-7: Generalized Anxiety Disorder-7 Scale.

When evaluating individual patient PHQ scores across time, there is a tendency for scores to improve over time, but individual trajectories vary widely (Figure 2a).Similarly, PHQ scores decreased over time in those who ever had PHQ-8 scores ≥ 10 (Figure 2b).

Figure 2b:

Trajectory of median PHQ-8 scores over time, comparing individuals with at least one clinically significant score to those without. Abbreviations: GAD-7: Generalized Anxiety Disorder-7 Scale; PHQ-8: Patient Health Questionnaire- 8.

When evaluating GAD-7 scores in longitudinal univariate linear regression, higher GAD-7 scores were associated with female sex, SLEDAI score, pills per week, PHQ-8, ASQ, pain, resource strain, and food insecurity; Asian race was protective (Supplemental Table). When evaluating GAD-7 scores in longitudinal multivariate linear regression, higher GAD-7 scores were associated with seizure disorder and PHQ-8, and Asian race was protective.

Discussion:

In this single center cohort of 76 children and adolescents with lupus who completed anxiety screening as part of routine care over a two-year period, anxiety was prevalent at baseline: 21% experienced mild anxiety symptoms (GAD-7 score of 5–9) and 13% had clinically significant, moderate to severe anxiety symptoms (GAD-7 score ≥ 10). Almost half (47%) experienced at least mild anxiety on one or more clinic visits. These estimates of anxiety symptom prevalence as measured by GAD-7 are higher than what is described in the general pediatric population and are similar to published results from the Toronto cohort which showed that in 146 children and adolescents with lupus undergoing routine anxiety screening using GAD-7, 20% had mild and 13% moderate to severe anxiety symptoms¹⁰. In adult SLE studies, the pooled prevalence of anxiety using a range of methods was 26% among 38 studies and 4439 patients²³.

In our univariate longitudinal analysis, the presence of clinically significant anxiety symptoms was independently related to higher disease duration, SLEDAI score, number of pills per week, pain score, PHQ-8 score, positive ASQ screening, and food insecurity. However, in multivariate longitudinal analysis, only higher PHQ-8 score was independently associated with higher GAD-7 score.

Our findings are consistent with prior cross-sectional studies, which have not shown consistent relationships between anxiety symptoms and clinical features. In a Thai cohort of 91 patients with cSLE and similarly well controlled disease (median SLEDAI of 2), the prevalence of clinically significant, or moderate to severe, anxiety (SCARED score > 25) was 49% and higher SCARED scores correlated in multivariable logistic regression models with organ damage and pain score³. In a multicenter implementation of mental health screening in cSLE patients with mean SLEDAI of 5, a GAD-7 score of 5–10 was noted in 24%; 10–14 in 9% and > 15 in 8%; GAD 7 scores correlated with depression, anxiety and fatigue domains on the PROMIS-25 measure but not with demographic variables; multivariable modeling was not performed²⁴. In an adult study of 139 SLE patients, using PROMIS Emotional Distress: Anxiety Short Form measure, anxiety symptoms were more likely to occur in patients who reported Black race.²⁵

Longitudinally, anxiety levels were relatively stable in this study over time and no significant relationship between anxiety and SLE disease activity was observed in multivariable analysis. In our study, those with low anxiety demonstrated stable scores over time but those with at least one clinically significant anxiety score showed a trend of improvement, which could reflect effects of clinician response to anxiety screening results. However, individual patients had fluctuations in both their anxiety and depression scores over time, highlighting the need for regular screening in pediatric rheumatology clinics.

Symptoms of anxiety and depression are often comorbid in adults and children in the general population and in those with SLE, thus the relationship between PHQ-8 and GAD-7 scores is not surprising. Our study showed that glucocorticoid dose, disease activity, and presence of nephritis were not associated with anxiety symptoms when evaluated longitudinally. Prior adult and pediatric cross-sectional studies have shown mixed results regarding relationships between glucocorticoid treatment and disease activity. The median SLEDAI-2K for our patient population was low at 2 [0, 4] as was the baseline glucocorticoid dose (0.1 mg/kg/day). Low disease activity and steroid dose may have limited the ability to show an association between anxiety symptoms, disease activity, and steroid exposure. Our cohort of patients overall had a high medication burden (median of > 50 pills per week), and those with ≥ 1 clinically significant GAD had higher pill burden.

Our analysis of the longitudinal relationship between anxiety and resource strain trended towards significance, and food insecurity was significant in univariate, but neither were significant in multivariate analysis. Other studies have shown that low socioeconomic status is associated with poor renal and cardiovascular outcomes in lupus patients²⁶. In the general population, exposure to socioeconomic stress is linked to increased likelihood of mental health disorders^{27, 28}. This association raises the question as to whether the effects of anxiety on disease activity can be compounded and exacerbated by unmet social needs.

Our study has many strengths. To our knowledge this is the first study to assess longitudinal relationships between anxiety symptoms and clinical characteristics in cSLE. The measurements of interest in this study are routinely collected for every patient visit as a standard of care. This consistency of data collection reduces the risk for recall bias and missing data points, strengthening the power of our results.

However, this study must be interpreted considering its limitations. The cohort was limited to those who completed anxiety screenings, and it is possible that some patients did not complete the screening. Nonetheless, quality improvement efforts were underway at the site to promote routine mental health screening and missingness was mitigated through the routine administration of a standardized set of questionnaires at all clinic visits and has been previously described²⁹. The study included 76 patients and 196 visits from a single pediatric rheumatology center. As a result, it may not capture populations outside our clinic, could be underpowered to detect certain associations, and the multivariate model may be at risk of overfitting. Future multi-center studies are needed to validate these findings. Questionnaires were administered only in English which may have limited response for those with other primary languages. Additionally, not all anxiety screening results were further evaluated with clinical interview by a psychologist and/or psychiatrist, thus limiting our ability to confirm anxiety disorder diagnosis. Finally, response bias may have influenced reporting of anxiety symptoms across longitudinal surveys.

Conclusion:

In conclusion, this longitudinal study of anxiety screening results confirms the prevalence of anxiety in the cSLE population and, importantly, emphasizes that routine screening, particularly with the GAD-7, is feasible and warranted. Early detection and management of anxiety in cSLE through routine screening has the potential to improve significantly disease and mental health outcomes.

Data availability:

Data will be available upon request.