Sleep, Anxiety, Somatization, Quality of Life, and Resilience in Pediatric Patients With Eosinophilic Esophagitis

Abstract

INTRODUCTION:

Emerging evidence suggests a high burden of psychosocial comorbidities in patients with eosinophilic esophagitis (EoE), although factors associated with this burden have not been explored. We aimed to increase understanding of the psychosocial burden of EoE and assess factors that are associated with disease burden.

METHODS:

We conducted a cross-sectional study of patients with EoE (n = 87) recruited from a single-center, multidisciplinary pediatric eosinophilic gastrointestinal disorders clinic (2019–2021). Participants (aged 8–18 years) completed validated assessments during routine clinic visit to assess EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Score version 2.0), quality of life (Pediatric Quality of LIfe- Eosinophilic Esophagitis), anxiety state and trait (State-Trait Anxiety Score for Children), somatization (Child Somatic Symptoms Inventory 24), sleep disordered breathing (Pediatric Sleep Questionnaire) and, in a subset (n = 35), resilience (Connor Davidson Resilience Scale). Clinical and demographic data were collected.

RESULTS:

Participants were at a mean (SD) age of 12.8 (3.1) years, and 26% (n = 23) were female. Shorter disease duration (6–12 months) was associated with higher symptom burden (P = 0.03), somatization (P < 0.01), and anxiety (State-Trait Anxiety Score for Children Trait P < 0.01) scores. Participants with neurodevelopmental comorbidities had higher anxiety trait, somatization, sleep disordered breathing, and lower quality of life (P < 0.01 for all). Symptom burden was significantly associated with increased somatic symptoms (adjusted β [aβ] = 0.34; 95% confidence interval 0.23–0.45) and decreased quality of life (aβ = −0.42; 95% confidence interval −0.59 to −0.25) but not state anxiety, trait anxiety, or disordered sleep breathing.

DISCUSSION:

Pediatric patients with a recent diagnosis of EoE can experience higher EoE symptoms, somatization, and anxiety when compared with those with a longer-standing diagnosis. Patients earlier in their diagnosis and with neurodevelopmental disorders may experience increased somatization and anxiety that may warrant additional support services.

INTRODUCTION

Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease in children and adults characterized by inflammation of the esophageal mucosa and symptoms of dysphagia, chest pain, heartburn, and food impaction and is one of the most common conditions diagnosed during assessment of feeding problems in children (1). The incidence of EoE has increased dramatically over the previous 3 decades, and EoE is the most common of the eosinophilic gastrointestinal (GI) diseases (2,3). Despite the increase in incidence, the disease remains poorly understood, with much of the research focused on identifying and expanding therapeutic alternatives for disease treatment. Treatments include proton pump inhibitors, swallowed topical steroids, empiric and targeted dietary elimination approaches, and more recently, as of 2022, for children and adults 12 years of age or older, dupilumab (4). In the absence of noninvasive methods of disease monitoring and limited treatment options, patients undergo serial endoscopies to evaluate treatment response and disease progression. While studies have been conducted to evaluate the financial burden of repeat endoscopies, clinic visits, and medications for the treatment of EoE, the psychosocial burden of EoE and other patient-associated and disease-associated factors on the pediatric populations has had limited description (5–13). We sought to increase understanding of this burden by evaluating the psychosocial comorbidities of disordered sleep, anxiety, and somatization in a pediatric population with EoE. We further characterized the psychosocial burden in relation to patient demographic characteristics, disease-associated clinical factors and symptom burden, neurodevelopmental comorbidities, and measures of resilience, hypothesizing that both patient-associated and disease-associated factors would contribute to psychosocial comorbidities.

METHODS

Participant selection

Study participants were recruited during routine visits in the pediatric Eosinophilic Gastrointestinal Disorders clinic at Rady Children's Hospital, San Diego/University of California, San Diego between May 2019 and April 2021. The study was approved by the University of California, San Diego Institutional Review Board (Protocol 190374). Of the 105 patients approached, 7 (7%) declined to participate. All study participants provided written informed consent/assent. Our goal was to enroll 100 patients (50 patients aged 8–11 years and 50 patients aged 12–18 years). Patients were approached based on the flow of the clinic and the availability of the study coordinator. We excluded patients being seen for their initial visit and those with significant developmental delays that would have precluded them from completing the surveys. Of the 98 participants enrolled, 1 was excluded because of not having completed any of the surveys, and 10 were further excluded because of concurrent GI diseases such as inflammatory bowel or celiac disease, leaving 87 participants in the study. Participants who completed the study met the criteria of having been diagnosed with EoE per consensus guidelines (≥15 eosinophils per high-power field [eos/hpf] and symptoms consistent with esophageal dysfunction and exclusion of other causes of eosinophilia) (6).

Data collection

Patients (aged 8–18 years) enrolled in the study and completed validated assessments during a routine clinic visit, including EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Score version 2.0 [PEESSv2.0]), quality of life (Pediatric Quality of LIfe- Eosinophilic Esophagitis [PedsQL-EoE]), anxiety state and trait (State-Trait Anxiety Score for Children), somatization (Child Somatic Symptoms Inventory 24 [CSSI-24]), and sleep disordered breathing (Pediatric Sleep Questionnaire [PSQ]). Resilience measures (Connor Davidson Resilience Scale [CD-RISC]) were added to the protocol following study initiation and with the CD-RISC-10 completed by a subset of participants aged 12 years or older (n = 36). The PEESSSv2.0 assesses symptom burden in EoE. It includes 20 items with a maximum score of 100, with higher scores indicative of higher burden. The PedsQL-EoE was developed specifically for the assessment of quality of life among children diagnosed with EoE (14,15). It includes 33 items, with a total score of 100 for overall quality of life and a score of up to 100 for the domains of Worry, Communication, Treatment, Food Eating, Food Feelings, and Symptoms (I and II). Higher scores on the PedsQL-EoE are indicative of better health-related quality of life. The State-Trait Anxiety Score for Children assesses both State (transitory anxiety states) and Trait (anxiety proneness) anxiety and includes 20 items with a maximum possible score of 60 in each subscale and with higher scores indicative of higher anxiety (16). The CSSI-24 is a 24-item instrument assessing somatic symptoms with a maximum possible score of 96 (17). Higher scores on the CSSI-24 indicate higher somatization. The Sleep-Related Breathing Disorder Scale within the PSQ consists of 22 closed-response questions extracted from the PSQ and a total possible score of 1.0, with scores greater than 0.33 considered suggestive of high risk of a pediatric sleep-related breathing disorder (18). The CD-RISC-10 is a 10-item instrument used in children aged 12 years or older and was introduced at the study midpoint to support secondary analyses of potential protective factors for psychosocial comorbidity (19). The maximum possible score of the CD-RISC-10 is 40, with higher scores indicating higher resilience.

Age, sex, insurance status (private vs public), history of physician-diagnosed neurodevelopmental comorbidities (attention deficit hyperactivity disorder [ADHD] or autism), disease duration since diagnosis, number of encounters in the emergency department for food bolus impactions, number of endoscopies performed, time since most recent endoscopy, and endoscopic and histologic observations including disease activity state at the most recent endoscopy were all abstracted from the electronic health record (EHR). Participant sex was obtained by self-report from a patient-administered questionnaire and documented in the EHR. Participant body mass index from the associated clinic visit was also obtained from the EHR. Subject's disease activity status was determined using the endoscopy closest to the date of their completed surveys and grouped as endoscopies that took place less than 90 days, between 90 and 180 days, and greater than 180 days (approximately 6 months) from participation in the study. Those having <15 eos/hpf were considered to have “inactive” EoE. The EoE Endoscopic Reference Score (EREFS) (20) was calculated from review of endoscopy reporting in the patient electronic health record. Study questionnaire responses and clinical features were entered and managed in the REDcap electronic data capture platform hosted by the Altman Clinical Trial and Research Institute (ACTRI) at the University of California at San Diego (UCSD) (21,22).

Statistical analyses

We first examined the distribution of participant demographic and clinical factors in relation to EoE symptom severity scores and resilience and evaluated differences in symptom severity and resilience in relation to these factors. Next, we assessed demographic, clinical, and disease-associated factors and participant neurodevelopmental comorbidities in relation to quality of life, disordered sleep, state and trait anxiety, and somatization. We compared the total assessment score for disordered sleep, somatization, and quality of life and subscores for state and trait anxiety according to demographic, clinical, and disease-associated factors. Assessment of differences in distribution of scores according to demographic and clinical factors was performed using 1-way tests of analysis of variance. Next, using crude and adjusted linear regression models, adjusted for disease duration since diagnosis, we evaluated whether EoE symptom severity scores, obtained from the PEESSv2.0 assessment, were associated with less favorable scores for quality of life, sleep, somatization, and both state and trait anxiety. In a secondary analysis, using crude and adjusted linear regression models, we examined the association between EoE symptom burden and the individual domains of Worry, Communication, Treatment, Food Eating, Food Feelings, and Symptoms. Furthermore, noting that disease duration may influence assessment results, we examined disease duration as a continuous measure. We also examined the number of treatments in relation to assessment score change, specifically examining treatments according to none, 1, or multiple treatments and examining none or multiple in relation to assessment score. Finally, in an additional secondary analysis, and among the subset of participants completing the CD-RISC assessment, using crude and adjusted linear regression models, we assessed whether higher resilience was associated with more favorable quality of life, sleep, somatization, and anxiety scores. Adjusted models accounted for duration of disease since diagnosis.

RESULTS

Primary analyses

Participants were at a mean (SD) age of 12.8 (3.1) years, and 26% (n = 23) were female. Most subjects (n = 71; 82%) had been diagnosed with EoE at least 12 months earlier, and most of them (n = 52; 60%) were being treated with more than 1 treatment approach (including proton pump inhibitors, topical corticosteroids, and/or dietary elimination strategies). One-third (n = 29; 34%) of participants had undergone 7 or more esophagogastroduodenoscopy procedures, and nearly one-third (n = 27; 33%) had experienced a GI-related emergency department visit. Half (n = 44; 50%) had ≥15 eosinophils per high-power field on the biopsy most closely temporally associated with study participation (Table 1). Two-thirds (n = 58) of participants had private insurance and the remaining third (n = 29) had public insurance. Of the 87 participants, 3 had been diagnosed with autism and 10 with ADHD; thus, 14% had been diagnosed with a neurodevelopmental comorbidity (n = 1 participant had been diagnosed with both autism and ADHD).

Table 1.

Demographic and clinical characteristics in relation to EoE symptom severity

	n (%)	PEESSv2.0 (n = 85), mean (SD)	P
Overall	87	20.8 (15.7)	—
Sex
Male	64 (74)	20.3 (16.1)	0.57
Female	23 (26)	22.3 (15.6)
Age
15–18	27 (31)	21.0 (17.2)	0.80
12–14	26 (30)	19.1 (12.7)
8–11	34 (39)	21.8 (16.7)
Insurance
Private	58 (67)	22.0 (15.1)	0.30
Public	29 (33)	18.3 (16.7)
BMI
≤5th percentile	5 (6)	20.8 (24.4)	0.40
Percentile 6–94	72 (84)	21.4 (14.2)
Percentile ≥95	9 (11)	13.4 (22.1)
Neurodevelopmental comorbiditya
No	75 (86)	20.5 (15.7)	0.68
Yes	12 (14)	22.5 (16.1)
History of anaphylaxis
No	52 (60)	19.2 (15.6)	0.26
Yes	35 (40)	23.1 (15.7)
Disease duration
6–12 mo	16 (18)	28.5 (14.6)	0.03
>12 mo	71 (82)	19.1 (15.5)
Current treatmentb
None	12 (14)	32.6 (7.9)	0.78
PPI	10 (12)	32.1 (10.6)
TCS	5 (6)	30.4 (8.2)
Dietary elimination	8 (9)	28.0 (4.4)
Multipleb	52 (60)	31.3 (7.9)
No. of EGDs
1–3	29 (34)	26.1 (13.7)	0.09
4–6	28 (33)	17.6 (16.2)
7+	29 (34)	18.8 (16.4)
GI-related ED visits
No	60 (69)	20.6 (15.0)	0.90
Yes	27 (31)	21.1 (17.3)
Days since previous EGD
<90	69 (79)	21.0 (15.4)	0.33
90–180	10 (12)	14.9 (13.7)
180+	8 (9)	25.6 (20.0)
Active EoE (eos/hpf ≥15)
No	43 (49)	21.0 (14.8)	0.87
Yes	44 (51)	20.5 (16.7)
EREFSc
0–1	52 (60)	19.1 (13.7)	0.24
2–8	35 (40)	23.2 (18.2)

ADHD, attention deficit hyperactivity disorder; BMI, body mass index; ED, emergency department; EGD, esophagogastroduodenoscopy; EoE, eosinophilic esophagitis; eos/hpf, eosinophils per high-power field; EREFS, EoE Endoscopic Reference Score; GI, gastrointestinal; IQR, interquartile range; PEESSv2.0, Pediatric Eosinophilic Esophagitis Symptom Score version 2.0; PPI, proton pump inhibitor; TCS, topical corticosteroids.

^aIncludes n = 3 autism spectrum disorder and n = 10 ADHD.

^bIncludes PPI, TCS, dietary elimination, prednisone.

^cEREFS ranged between 0 and 6, with a median (IQR) score of 1 (0–2).

When examining EoE symptom severity in relation to participant demographic and clinical features, no differences in symptom burden were observed across any factors, except for disease duration. Participants with shorter disease duration, defined as 6–12 months since diagnosis, experienced higher symptom burden (P = 0.03) as indexed by their PEESSv2.0 score (Table 1).

Relative to those with private insurance, participants with public insurance had less favorable scores for sleep disordered breathing (P = 0.01). No other participant demographic factors examined were associated with differences in distribution of scores. When examining participant clinical factors in relation to somatization, state and trait anxiety, and quality of life, participants with neurodevelopmental comorbidities had significantly higher scores for somatic symptoms and trait anxiety and lower quality-of-life scores when compared with those without these comorbidities (P < 0.01 for all). They also had higher scores for sleep disordered breathing (P < 0.01). In addition, participants with shorter duration of disease since diagnosis had higher somatic symptoms (P < 0.01) and trait anxiety (P < 0.01) scores compared with those with longer disease duration (>12 months). Higher somatic symptom scores (P < 0.01) and state (P = 0.02) and trait (P = 0.03) anxiety scores were observed for those participants with fewer (1–3) EGDs. The median EREFS in this study sample was 1 (0–2). Participants with EREFS above the median experienced a less favorable EoE-PedsQoL score when compared with those below the median (scores 0–1) (P = 0.01). No other differences in score distribution was observed for any other clinical factors (Table 2).

Table 2.

Distribution of somatization, anxiety, disordered sleep, and quality-of-life scores according to participant demographic and clinical factors

	n (%)	CSSI-24 (n = 85), mean (SD)	P	STAI-C state (n = 87), mean (SD)	P	STAI-C trait (n = 87), mean (SD)	P	PSQ (n = 87), mean (SD)	P	EoE-PedsQL (n = 86), mean (SD)	P
Overall	87	11.6 (9.4)	—	29.6 (6.0)	—	31.2 (8.1)	—	0.24 (0.15)	—	80.5 (13.8)	—
Sex
Male	64 (74)	11.2 (8.9)	0.54	29.6 (5.9)	0.99	31.0 (8.0)	0.64	0.24 (0.15)	0.86	76.9 (15.9)	0.15
Female	23 (26)	12.7 (11.0)		29.6 (6.6)		31.9 (8.5)		0.23 (0.14)		81.8 (12.9)
Age, yr
15–18	27 (31)	13.8 (12.9)	0.33	30.6 (6.1)	0.12	33.3 (10.1)	0.25	0.22 (0.15)	0.10	80.2 (14.8)	0.31
12–14	26 (30)	10.1 (6.4)		30.8 (5.6)		30.8 (7.4)		0.20 (0.14)		83.7 (9.2)
8–11	34 (39)	11.0 (7.9)		27.9 (6.1)		29.9 (6.6)		0.28 (0.15)		78.1 (15.8)
Insurance
Private	58 (67)	12.1 (9.9)	0.44	30.1 (5.7)	0.26	31.9 (8.5)	0.27	0.21 (0.14)	0.01	81.7 (12.6)	0.23
Public	29 (33)	10.5 (8.5)		28.6 (6.6)		29.9 (7.0)		0.30 (0.16)		77.9 (16.0)
BMI
≤5th percentile	5 (6)	12.6 (15.2)	0.12	30.4 (1.1)	0.94	34.4 (3.3)	0.18	0.18 (0.1)	0.56	80.9 (21.3)	0.95
Percentile 6–94	72 (84)	12.0 (9.1)		29.5 (6.2)		31.3 (7.6)		0.24 (0.15)		80.7 (12.6)
Percentile ≥95	9 (11)	5.0 (4.3)		29.3 (6.6)		27.0 (9.9)		0.27 (0.17)		82.2 (16.5)
Neurodevelopmental comorbiditya
No	75 (86)	10.5 (8.3)	<0.01	29.3 (5.9)	0.29	30.3 (7.4)	<0.01	0.22 (0.15)	<0.01	82.0 (13.7)	<0.01
Yes	12 (14)	18.5 (13.3)		31.3 (6.6)		36.8 (9.9)		0.37 (0.10)		70.8 (10.9)
History of anaphylaxis
No	52 (60)	11.7 (9.4)	0.93	30.1 (5.8)	0.39	32.0 (8.9)	0.30	0.23 (0.16)	0.85	80.6 (15.0)	0.93
Yes	35 (40)	11.5 (9.7)		28.9 (6.4)		30.1 (6.6)		0.24 (0.14)		80.3 (12.3)
Disease duration
6–12 mo	16 (18)	17.6 (10.2)	<0.01	32.0 (7.9)	0.08	36.3 (10.5)	<0.01	0.25 (0.15)	0.44	74.2 (14.4)	0.08
>12 mo	71 (82)	10.3 (8.8)		29.1 (5.5)		30.1 (7.0)		0.21 (0.15)		81.7 (13.5)
Current treatmentb
None	12 (14)	15.0 (11.6)	0.55	30.2 (6.3)	0.73	32.6 (9.2)	0.78	0.30 (0.16)	0.39	74.6 (21.2)	0.41
PPI	10 (12)	14.0 (9.4)		30.8 (6.0)		32.1 (10.6)		0.21 (0.15)		81.8 (15.9)
TCS	5 (6)	7.8 (8.9)		26.2 (4.0)		30.4 (8.2)		0.16 (0.14)		88.6 (7.7)
Dietary elimination	8 (9)	11.8 (11.9)		29.8 (3.7)		28.0 (4.4)		0.26 (0.12)		80.2 (15.3)
Multipleb	52 (60)	10.8 (11.6)		29.5 (6.5)		31.3 (1.9)		0.24 (0.15)		80.8 (11.4)
No. of EGDs
1–3	29 (34)	16.7 (9.7)	<0.01	32.0 (7.2)	0.02	34.2 (9.1)	0.03	0.23 (0.13)	0.15	76.4 (14.4)	0.08
4–6	28 (33)	6.1 (5.3)		27.6 (3.7)		28.6 (6.8)		0.20 (0.15)		84.7 (12.6)
7+	29 (34)	11.8 (9.8)		28.9 (6.0)		30.9 (7.5)		0.28 (0.16)		80.4 (13.9)
GI-related ED visits
No	60 (69)	11.6 (8.5)	0.99	30.2 (6.6)	0.21	31.5 (8.0)	0.72	0.24 (0.14)	0.76	80.3 (12.8)	0.87
Yes	27 (31)	11.6 (11.5)		28.4 (4.5)		30.8 (8.3)		0.23 (0.17)		80.8 (16.2)
Days since previous EGD
<90	69 (79)	11.8 (9.3)	0.16	29.6 (6.0)	0.26	31.6 (8.5)	0.26	0.25 (0.15)	0.34	80.8 (13.7)	0.14
90–180	10 (12)	6.8 (4.3)		27.7 (3.7)		27.4 (4.5)		0.18 (0.14)		84.9 (8.2)
180+	8 (9)	15.4 (13.5)		32.4 (8.4)		32.8 (7.4)		0.27 (0.15)		72.2 (18.4)
Active EoE (eos/hpf ≥15)
No	43 (49)	12.6 (9.6)	0.32	30.6 (6.7)	0.12	32.4 (8.7)	0.18	0.25 (0.14)	0.60	81.3 (13.0)	0.58
Yes	44 (51)	10.6 (9.3)		28.6 (5.2)		30.1 (7.3)		0.23 (0.16)		79.6 (16.7)
EREFS at EGDc
0–1	52 (60)	11.1 (8.8)	0.54	29.8 (8.3)	0.18	30.0 (6.6)	0.47	0.25 (0.15)	0.43	83.5 (11.8)	0.01
2–8	35 (40)	12.4 (10.4)		29.8 (8.3)		29.0 (5.1)		0.22 (0.14)		76.0 (15.5)

ADHD, attention deficit hyperactivity disorder; BMI, body mass index; CSSI-24, Child Somatic Symptoms Inventory 24; ED, emergency department; EGD, esophagogastroduodenoscopy; EoE, eosinophilic esophagitis; eos/hpf, eosinophils per high-power field; EREFS, EoE Endoscopic Reference Score; GI, gastrointestinal; IQR, interquartile range; PPI, proton pump inhibitor; PSQ, Pediatric Sleep Questionnaire; STAI-C, State-Trait Anxiety Score for Children; TCS, topical corticosteroids.

^aIncludes n = 3 autism spectrum disorder and n = 10 ADHD.

^bIncludes PPI, TCS, dietary elimination, and prednisone.

^cEREFS ranged between 0 and 6, with a median (IQR) score of 1 (0–2).

Secondary analyses

Participant EoE-associated symptom burden was significantly associated with increased somatic symptoms (adjustedβ [aβ] = 0.34; 95% confidence interval [CI] 0.23–0.45) and decreased quality of life (aβ = −0.42; 95% CI −0.59 to −0.25) but not state anxiety, trait anxiety, or disordered sleep breathing (Table 3). In examining symptom burden in relation to quality-of-life domains, worry about food eating (Food Eating) and EoE-associated Symptoms were both associated with EoE-associated symptom burden (Table 4).

Table 3.

EoE symptom severity in relation to sleep, anxiety, somatization, and quality of life

	n	Crude β (95% CI)	Adjusteda β (95% CI)
Pediatric sleep Q (PSQ)	84	0.001 (−7.91 to 36.57)	0.002 (−0.01 to 0.004)
Anxiety (STAI-C state)	84	0.02 (−0.0001 to 0.003)	0.002 (−0.08 to 0.08)
Anxiety (STAI-C trait)	84	0.06 (−0.05 to 0.17)	0.002 (−0.09 to 0.13)
Somatic symptoms (CSSI-24)	82	0.37 (0.26 to 0.48)	0.34 (0.23 to 0.45)
Quality of life (EoE-PedsQL)	83	−0.44 (−0.61 to −0.27)	−0.42 (−0.59 to −0.25)

CI, confidence interval; CSSI-24, Child Somatic Symptoms Inventory 24; PSQ, Pediatric Sleep Questionnaire; STAI-C, State-Trait Anxiety Score for Children.

^aAdjusted for disease duration since diagnosis.

Table 4.

Symptom severity and quality-of-life domains

EoE-PedsQL domain	n	Crude β (95% CI)	Adjusteda β (95% CI)
Treatment	81	−0.07 (−0.37 to 0.23)	−0.09 (−0.40 to 0.22)
Worry	83	−0.24 (−0.49 to 0.02)	−0.20 (−0.45 to 0.06)
Communication	83	−0.27 (−0.54 to 0.004)	−0.24 (−0.51 to 0.04)
Food eating	56	−0.37 (−0.66 to −0.08)	−0.36 (−0.65 to −0.06)
Food feelings	58	−0.33 (−0.73 to 0.07)	−0.33 (−0.74 to 0.08)
Symptoms	83	−0.85 (−1.00 to −0.69)	−0.83 (−0.99 to −0.67)

CI, confidence interval.

^aAdjusted for disease duration since diagnosis.

When examining time since diagnosis among return visit patients, we observed that duration of disease was inversely associated with symptom score. Specifically, for each additional month since diagnosis, the symptom score decreased slightly as reflected by the PEESS score (β = −0.08; 95% CI −0.14 to −0.02). No statistically significant associations were observed between disease duration and anxiety, somatization, sleep, quality of life, or resilience (see Supplementary Table 1, Supplementary Digital Content 1, http://links.lww.com/CTG/B65). We observed no evidence of an association between number of treatments (0 vs 1; or multiple vs 1) and any of the assessment scores (see Supplementary Table 2, Supplementary Digital Content 1, http://links.lww.com/CTG/B65).

Higher resilience was associated with lower state (aβ = −0.66; 95% CI −1.01 to −0.32) and trait anxiety (aβ = −0.44; 95% CI −0.67 to −0.21) and somatization (aβ = −0.20; 95% CI −0.40 to 0.01). Resilience was not associated with EoE symptom burden or quality of life (Table 5).

Table 5.

Resilience in relation to sleep, anxiety, somatization, and quality of life

Assessment	n	Crude β (95% CI)	Adjusteda β (95% CI)
Somatic symptoms (CSSI)	35	−0.21 (−0.41 to −0.002)	−0.20 (−0.40 to 0.01)
Pediatric sleep Q (PSQ)	35	−9.68 (−25.53 to 6.17)	−11.34 (−27.12 to 4.51)
Anxiety (STAI-C state)	35	−0.68 (−1.02 to −0.33)	−0.66 (−1.01 to −0.32)
Anxiety (STAI-C trait)	35	−0.45 (−0.68 to −0.22)	−0.44 (−0.67 to −0.21)
EoE symptoms (PEESSv2.0)	34	−0.09 (−0.24 to 0.05)	−0.07 (−0.22 to 0.07)
Quality of life (PedsQL)	35	0.10 (−0.07 to 0.27)	0.09 (−0.09 to 0.26)

CI, confidence interval; CSSI-24, Child Somatic Symptoms Inventory 24; PEESSv2.0, Pediatric Eosinophilic Esophagitis Symptom Score version 2.0; PSQ, Pediatric Sleep Questionnaire; STAI-C, State-Trait Anxiety Score for Children.

^aAdjusted for disease duration since diagnosis.

DISCUSSION

In a sample of pediatric patients with EoE, we observed that those with more recent diagnosis may be at increased risk of experiencing EoE-associated and somatic symptoms. Patients with more recent diagnosis also had higher anxiety scores. For those with both EoE and neurodevelopmental comorbidity, we observed significantly higher scores for somatic symptoms, trait anxiety, and sleep disordered breathing and significantly lower quality-of-life scores when compared with those without neurodevelopmental comorbidity. These findings have clinical implications for the care of patients with EoE and suggest a need for assessing and mitigating anxiety and somatic complaints early in diagnosis. It has been reported that patients with EoE have higher rates of neurodevelopmental comorbidities, and our findings suggest that this subpopulation of children with EoE may need particular attention directed toward management of their somatic complaints, anxiety, and sleep disordered breathing patterns (23,24).

EoE symptom burden score was positively associated with somatic symptom score and inversely associated with quality of life, with symptoms and dietary eating factors contributing to this observed reduced quality of life. Among a subset of older (aged 12 years or older) patients administered the CD-RISC-10, resilience was inversely associated with both state and trait anxiety and somatic symptom burden. These findings support that integrated care models, designed to improve resilience in patients with EoE and their families, may reduce their EoE and somatic symptoms and increase their quality of life. Given that EoE is a chronic disease, early interventions targeted at improving coping with disease burden could be a helpful adjuvant therapy. Interventions designed to build resilience among patients in IBD have led to decreased emergency department utilization and reduced corticosteroid and opioid use (25,26).

Our observation that patients newer in their diagnosis reported higher anxiety and somatization is not surprising. Patients who are more recent in their diagnosis may be experiencing a higher degree of psychologic burden because they adjust to the reality of a new diagnosis and the potential of a lifelong health condition (27). Furthermore, experiences with the health care delivery system in terms of the need for repeated endoscopy with biopsy and anesthesia and recommendations for medication therapies that are often used off label may contribute. In addition, the elimination of foods as a therapeutic intervention and the risk of food exposure may elicit patient and family anxiety. As the disease becomes better managed and familiarity with health care procedures and treatments increases, anxiety and somatization may decrease. This phenomenon of conditioning to an illness has been observed in other conditions (27). The change in symptoms, somatization, and anxiety over the course of chronic illness is a particularly salient feature for clinical trial readiness because the same metrics and outcomes are assessed in patients enrolled in the same clinical trial but at different stages in their disease course. Indeed, symptom control has been a significant impediment for the approval of pharmacologic therapeutics in EoE, but the effect of disease duration on patient-reported outcomes has not been systematically studied or addressed.

Of interest, the distribution of scores for any of the assessments, including EoE symptom burden, did not differ according to those with active disease or inactive disease as defined by number of eosinophils per high power field (28). Increasing evidence suggests that assessment of EoE activity based on the isolated surrogate marker of tissue eosinophilia may not be adequate and that additional endoscopic, histologic, and disease complication parameters should be addressed to best gauge EoE activity and severity (29). This finding is also impactful on the best metrics used when judging the success or failure of a therapeutic intervention. In addition, our findings underscore that patients in the chronic phase of their disease, post initial diagnosis, may require additional patient-reported or functional outcome metrics for assessing therapeutic response.

In this study, we report that 3 of our 87 participants had a concurrent diagnosis of autism, as reflected in their EHR. This is a higher rate of autism than in the general population, but enrichment of autism among those with EoE has been previously reported (24,30). Ten participants had a diagnosis of ADHD, again, higher than that in the general population. ADHD and autism are both neurodevelopmental comorbidities and often co-occur, so the enrichment of ADHD in this sample is consistent with our finding of autism (31,32). However, to our knowledge, this has not been previously reported and merits additional research to determine what, if any, association exists between ADHD and EoE. This is particularly important because these children experience higher disease burden, as reflected by higher anxiety, somatic symptoms, and poorer quality of life. Additional and early interventions to mitigate unnecessary anxiety and somatization and assessment of sleep disordered breathing may be warranted in children with EoE and concurrent ADHD and/or autism.

Our study has several limitations. The study sample size was relatively small, thus limiting the ability to make inferences for smaller subgroups within the sample (e.g., those diagnosed with autism). Furthermore, this included patients with EoE only, thus precluding comparisons of responses to a general population of pediatric patients and limiting ability to provide context on the degree to which scores were higher or lower than those of the general population. Still, the variability in scores observed within the sample offers insight into those patients with EoE who may be experiencing a higher or lower degree of disease-associated burden. Finally, this study sample was not completely representative of the patient population with EoE. For example, we excluded those children with higher disability who would not have been able to complete study questionnaires and those with concomitant GI diseases such as inflammatory bowel disease. We also excluded patients early in their diagnosis, thus limiting our ability to assess very recent diagnosis in relation to study outcomes. The median (interquartile range) EREFS in this patient population was 1 (0–2) and perhaps indicative of a patient population with well-managed disease. Thus, these results may not be generalizable to all pediatric patients diagnosed with EoE. Finally, we performed numerous tests, and although these outcomes are correlated, and do not necessarily represent independent tests, there is a potential that any significant observations noted were due to chance.

Still, our study represents the most comprehensive study to date to examine psychosocial comorbidities in the pediatric patient population with EoE. We administered validated instruments assessing multiple psychosocial and patient-reported factors and abstracted detailed clinical data for examination of variability from within the patient sample with EoE. These results are likely to inform the development of future interventions designed to mitigate psychosocial burden in this patient population. For example, patients early in their diagnosis may need greater support from mental health providers. Increased screening for psychosocial comorbidities may be warranted, particularly in newly diagnosed and among those with neurodevelopmental comorbidities. Integrated care models, designed to build resilience among patients and their parents, may serve as an important adjuvant therapy. Last, the propensity toward sleep disordered breathing may need to be more carefully assessed, especially among those children with concurrent neurodevelopmental diagnoses.

In conclusion, our data show that pediatric patients with EoE may be at increased risk of experiencing higher psychosocial morbidities, especially early in their disease course or if they have autism or ADHD. Increased attention to patient psychosocial comorbidities may be warranted to bring more complete therapeutic relief to pediatric patients with EoE.

CONFLICTS OF INTEREST

Guarantor of the article: Seema S. Aceves, MD, PhD.

Specific author contributions: E.T.J.: contributed to study conception and led study analyses and manuscript drafting. K.C.: contributed to study conception, implementation, and manuscript drafting. O.A. and A.P.: contributed to the study conception, patient recruitment, and critical review of manuscript draft. S.S.A.: conceptualized the study, led study oversight, and contributed to study analyses and critical revisions of the manuscript drafts. All authors have reviewed the study manuscript and approved the final manuscript for submission.

Financial support: This study was supported by a grant from the UCSD Academic Senate and NIH K24 (AI135034) and partially supported UCSD ACTRI (UL1TR001442).

Potential competing interests: S.S.A. has funding from the NIAID and NIDDK, Implicit Biosciences and Bristol Meyer Squibb. S.S.A. is a disease state awareness speaker for Regeneron and Sanofi. S.S.A. is a consultant for Ferring and Sanofi. S.S.A. is a co-inventor of oral viscous budesonide, UCSD patent, Takeda license. The remaining authors have no disclosures to report.

Clinical trial registry name: Somatization, Anxiety and Disordered Sleep in Pediatric Eosinophilic Esophagitis.

Clinical trial identifier: NCT04309786.

Study Highlights.

WHAT IS KNOWN

• ✓ Eosinophilic esophagitis contributes significant symptom and health care burden.

• ✓ Patients experience significant psychosocial comorbidity, but factors contributing to this are unknown.

WHAT IS NEW HERE

• ✓ More recent diagnosis contributes to increased psychosocial burden.

• ✓ Patients with neurodevelopmental comorbidities are at increased risk of increased psychosocial burden.

• ✓ Patients with higher resilience experience lower symptom and psychosocial burden.

Supplementary Material

ct9-15-e00672-s001.pdf ^{(441.1KB, pdf)}

ct9-15-e00672-s002.docx ^{(13.9KB, docx)}