Fluticasone

In 2002, a prospective study using swallowed FP in children cited its ease of administration, low systemic absorption, and rapid first-pass metabolism by the liver to limit systemic side effects. These children had symptoms of esophageal dysfunction (ie, chest pain, food impaction, dysphagia, feeding refusal, and vomiting), eosinophilic esophageal infiltration, normal 24-hour continuous monitoring of intraesophageal pH (pH probe), and lack of clinical response to an 8-week trial of PPI. FP dosing was age dependent, with a maximum of 880 μg/d divided twice daily. Four patients had no food allergens identified by history, radioimmunosorbent assay, or skin prick testing and were started directly on swallowed FP. Eleven patients were started on dietary restriction and nutritional counseling based on abnormal allergy testing or history; however, none of these patients had clinical improvement and 9 were subsequently treated with swallowed FP. All 13 patients who received FP had resolution of their presenting symptoms, and all 11 patients with post-treatment endoscopy showed improvement in histology with similar decreases in eosinophilia in proximal and distal esophageal biopsies.

A subsequent randomized, double-blind, placebo-controlled trial in children showed that 50% of FP-treated patients achieved complete histologic remission (≤1 eosinophil [EOS] per high-power field [HPF]) with a standard dose, regardless of patient age and/or size, of 880 μg/d divided twice daily. Patient factors predictive of histologic resolution in this study included shorter stature and younger age. Unlike the previous study, proximal esophageal biopsies were more improved than those from the distal esophagus. Another randomized controlled trial comparing swallowed FP to oral prednisone (880–1760 μg/d based on age and 1 mg/kg/d to a maximum of 30 mg twice daily, respectively) showed complete histologic resolution in 50% of patients in FP group versus 81% in prednisone group at week 4; partial improvement in histologic grade was recorded in 94% of patients in both groups. As expected, symptomatic improvement was seen more often compared with histologic reversal; 97.2% of FP patients and 100% of prednisone patients had resolution of presenting symptoms with therapy although symptoms recurred in approximately 45% of patients 12 weeks after treatment was stopped ( Fig. 1 A).

( A ) Proportion of symptom-free patients with prednisone and swallowed fluticasone. Patients received induction dose × 4 weeks, were weaned over 8 weeks, and were clinically monitored for next 12 weeks. ( B ) Recurrence of esophageal eosinophilia after withdrawal of swallowed fluticasone (220 μg twice daily).

( From [ A ] Schaefer ET, Fitzgerald JF, Molleston JP, et al. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol 2008;6:165–73, with permission; and [ B ] Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 2005;3:1202, with permission.)

A recent prospective Italian study in children using a higher dose of FP (2250 μg/d) for 6 weeks reported higher likelihood (73.5%) in reaching post-treatment peak esophageal eosinophils of less than 6 eos/hpf and suggested that more severe esophageal inflammation (higher median peak eos/hpf, presence of eosinophilic abscesses, and peak mast cells/HPF) was associated with higher response rate to FP treatment. Age and height did not affect response in this study.

Improvement in incidental gastric eosinophilic inflammation (≥10 eos/hpf) in patients otherwise similar to EoE patients was noted with FP. Therefore, mild gastric eosinophilia should not exclude FP as a possible therapeutic option for esophageal eosinophilia.

The results of the first double-blind, randomized, placebo-controlled trial of FP (1760 μg/d) in children and adults are awaited. Further studies are needed to determine ideal dosing regimen but current recommendations are listed in Table 2 .

Budesonide

Budesonide is another topical steroid with proved efficacy for EoE. OVB was initially developed to help patients who were developmentally unable to perform the puff and swallow technique required for FP. The first studies to evaluate its efficacy mixed aqueous budesonide (0.5 mg/2 mL suspension, Budesonide Respules [Pulmicort], Astra-Zeneca, Wilmington, DE) with sucralose (see Table 2 for recipe) to create a thickened slurry. A randomized, double-blind, placebo-controlled trial in children showed significant improvement in symptoms, endoscopic findings, and esophageal eosinophilia compared with placebo. Patients less than 1.5 meters (5 feet) tall received 1 mg daily; patients greater than or equal to 5 feet tall received 2 mg daily for 3 months. Patients in both groups also received twice-daily lansoprazole (15 mg twice daily if less than 10 years old and 30 mg twice daily if greater than 10 years old). Peak eosinophil counts in the OVB group improved from 66.7 to 4.8 eos/hpf, with significant reductions in proximal, mid-, and distal esophageal eosinophilia.

No studies to date have compared FP and OVB in children.

Ciclesonide

Two small case series report a total of 8 children treated with ciclesonide, a topical CS also used in asthma, allergic rhinitis, and allergic conjunctivitis. Six of the 8 patients showed histologic improvement; the 2 who did not respond had previous poor response to OVB as well. In asthma, inhaled ciclesonide seems to have similar effectiveness compared with inhaled FP and nebulized budesonide. Larger randomized, drug-controlled studies are needed to see if this is the case in EoE.