Steroids in Pediatric Eosinophilic Esophagitis

Swallowed fluticasone and oral viscous budesonide are effective first-line therapies for eosinophilic esophagitis in children. Side effects are minimal without evidence of Cushing syndrome, as seen in treatment with systemic corticosteroids. New studies on alternative delivery systems and different corticosteroids (eg, ciclesonide) are encouraging. As knowledge of corticosteroids in eosinophilic esophagitis expands, newer questions continue to arise concerning dose, delivery, and choice of corticosteroids; long-term adverse effects; and maintenance therapies.

Key points

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Topical corticosteroids (CSs) (eg, swallowed fluticasone propionate [FP] and oral viscous budesonide [OVB]) are effective first-line therapies for pediatric eosinophilic esophagitis.
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Topical CSs have minimal known side effects when used for treatment of eosinophilic esophagitis.
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Systemic CSs have significant adverse effects and are now reserved for urgent situations where topical CSs are not effective or in patients who require rapid improvement in symptoms.

The goals for treatment of eosinophilic esophagitis (EoE) are improvements in symptoms and esophageal eosinophilic inflammation with the ideal endpoint complete resolution of the latter. Once a diagnosis of proton pump inhibitor (PPI)-nonresponsive EoE is confirmed, treatment options include pharmacologic agents and/or dietary elimination. If pharmacologic therapy is chosen, topical CSs are effective and considered first line. Although these medications are currently not Food and Drug Administration approved for EoE, the 2 commonly used options are swallowed aerosolized FP and OVB. Systemic CSs (ie, prednisolone and methylprednisolone) may be useful if topical steroids are not effective or in patients who require rapid improvement in symptoms.

This article discusses the use of topical and systemic CSs for induction of remission and as maintenance treatment of pediatric EoE. The risks and benefits of these agents are outlined and some important and clinically relevant questions discussed.

Topical corticosteroids for induction

In 1998, Faubion and colleagues described 4 children with eosinophilic inflammation isolated to the esophagus who improved clinically and histologically by swallowing aerosolized CSs (FP and beclomethasone) from an inhaler without use of a spacer. Over time, FP has become the topical CS used most often in EoE, although other agents are also used (discussed later). We will review prospective and randomized studies involving topical steroids used in pediatric eosinophilic esophagitis ( Table 1 ). Adult studies are discussed elsewhere in this issue.

Table 1

Topical steroids in pediatric eosinophilic esophagitis, prospective and randomized controlled trials

Study	Type of Study	Control Group (n)	Histologic Criteria	Drug (n)	Dose (μg)	Length of Treatment	Primary Outcomes	Drug Efficacy ^a(%)	Control Group Response (%)	Other Outcomes	Adverse Events	Comments
Teitelbaum et al, 2002	Prospective	NA	>15 eos/hpf, superficial layering, and/or eosinophil microabscesses	FP (13)	2–4 yo: 88 BID 5–10 yo: 220 BID ≥11 yo: 440 BID	8 wk	Clinical improvement/resolution of symptoms	100	NA	70% Still had abnormal endoscopy (loss of vascular pattern, thickened longitudinal folds), but improved histology	18% With esophageal candidiasis, 9% (n = 1) symptomatic	8-wk PPI trial before diagnosis. Normal 24-h continuous pH monitoring; 9 of the patients who responded clinically to FP had failed allergy testing–based diet restriction.
Konikoff et al, 2006	Randomized, double- blind, placebo-controlled	Placebo (15)	>24 eos/hpf in any ×400 HPF and epithelial hyperplasia	FP (21)	440 BID	3 mo	Complete response: <1 eos/hpf	50	9	All FP responders: resolved distal furrowing, epithelial hyperplasia, and vomiting	Incidental esophageal candidiasis in 9% of FP pts (1/11)	Prior acid suppression therapy was not necessary for diagnosis. FP response higher in nonallergic individuals. FP response negatively correlates with patient age, height, and weight.
Konikoff et al, 2006	Randomized, double- blind, placebo-controlled	Placebo (15)	>24 eos/hpf in any ×400 HPF and epithelial hyperplasia	FP (21)	440 BID	3 mo	Partial response: 1–24 eos/hpf	15	9		Incidental esophageal candidiasis in 9% of FP pts (1/11)
Schaefer et al, 2008	Randomized, comparator controlled	Prednisone 1 mg/kg/d (40)	≥15 eos/hpf with negative pH probe studies	FP (40)	1–10 yo: 220 QID 11–18 yo: 440 QID	4-wk Induction	Complete histologic resolution	50	81	97% FP group had resolution of symptoms. 100% of prednisone group had resolution of symptoms.	Incidental esophageal candidiasis in 15% of FP patients; hyperphagia, weight gain in 40% of prednisone patients.	Symptom relapse in 44% of FP patients, 45% of prednisone 12 wk after treatment stopped.
Schaefer et al, 2008	Randomized, comparator controlled	Prednisone 1 mg/kg/d (40)	≥15 eos/hpf with negative pH probe studies	FP (40)	1–10 yo: 220 QID 11–18 yo: 440 QID	4-wk Induction	Improvement in biopsy grade (score based on basal cell zone % and # eos/hpf)	94	94
Dohil et al, 2010	Randomized, double- blind, placebo-controlled	Placebo (9)	Peak eos/hpf ≥20	OVB (15)	<5 ft Tall: 1000/d ≥5 ft Tall: 2000/d	3 mo	Responders: <6 eos/hpf	87	0	Endoscopy score improved more in OVB vs placebo. Symptom score improved in OVB but not placebo group.	Oral candidiasis that responded to nystatin. Serum cortisol unchanged	All patients received PPI during drug period. <10 yo: Lansoprazole 15 mg BID; ≥10 yo: lansoprazole 30 mg BID. Placebo and PPI did not improve eosinophilia at any level.
							Partial responders: 7–19 eos/hpf	6.7	11
							Nonresponders ≥20 eos/hpf	6.7	89
Boldorini et al, 2013	Prospective	NA	>15 eos/hpf	FP (34)	750 TID	6 wk	Responders: ≤6 eos/hpf	74	NA	All children had symptomatic improvement irrespective of histologic results. Responders had more severe inflammation (higher median peak eos/hpf, higher likelihood of eosinophilic microabscesses, and peak mast cells/HPF).	No adverse events seen	All children were nonresponders to PPI or 24-h pH monitoring was negative for gastroesophageal reflux. 4 Children had celiac disease, 3 were responders 1 was not. Age, weight, and height, did not affect response.
							Borderline: 7–20 eos/hpf	0
							Nonresponders: >20 eos/hpf	26