CMAJ Practice CME

Decisions A 34-year-old man with refractory and intermittent to solids

Hoang Pham MSc, William H. Yang MD

A 34-year-old man presents to his family physi- tion, whereas those with esophageal dysphagia Competing interests: None cian after completing a two-month trial of a may complain of food sticking.3 The next step is declared. proton pump inhibitor for heartburn. The to determine whether dysphagia is to solids, liq- This article has been peer heartburn, which had begun three months ear- uids or both. Dysphagia to only solids increases reviewed. lier, has not responded to the treatment. The the likelihood of a mechanical lesion of the esoph- The clinical scenario is patient describes experiencing intermittent dif- agus rather than a neuromuscular disorder.3 fictional. ficulty solids (e.g., bread and steak) The onset and frequency of dysphagia, partic- Correspondence to: and has tried to compensate by chewing food ularly whether it has been intermittent or progres- Hoang Pham, slowly and washing meals down with liquids to sive, provides further clues. Rapidly progressive [email protected] prevent food from sticking in his throat. He has dysphagia is more worrisome for a growing CMAJ 2016. DOI:10.1503​ not experienced weight loss and is not aware mass.3 Other worrisome features of possible /cmaj.150786 of food hypersensitivities. He has environmen- malignant disease causing mechanical obstruc- tal allergies to tree pollens. tion in the include age over 50 and unexplained weight loss.3 What diagnoses should be considered? Several features on history-taking may fur- In the context of heartburn-dominant dyspepsia, ther increase a clinical suspicion of eosinophilic dysphagia to solids is an alarm feature because it esophagitis. According to a systematic review, may indicate the presence of esophageal steno- patients with usually sis, strictures, rings, webs or malignant disease.1 have dysphagia to solids and elaborate coping However, eosinophilic esophagitis should also mechanisms for the dysphagia.2 They may de- be considered in an atopic man less than 50 years liberately avoid highly textured foods such as of age who has a history of intermittent dysphagia meat, and bulky foods such as bagels. Other to only solids with associated chronic heartburn.2 strategies include mincing food into small Eosinophilic esophagitis is a chronic immune/​ pieces, prelubricating­ foods with liquids or antigen-mediated disease characterized by eosin- butter before eating, meticulous chewing with ophilic inflammation of the esophageal epithe- prolonged meal durations and washing food lium, resulting in esophageal dysfunction and down with liquids. Any history of long-lasting fibrosis if left untreated.2 The pathogenesis is dysphagia that resulted in food impaction re- not fully understood yet but seems to be mixed quiring emergent intervention (e.g., endoscopic in terms of both immunoglobulin E–mediated removal) substantially increases the likelihood processes and delayed Th2 inflammation.2 of eosinophilic esophagitis.2 In addition to intermittent dysphagia, the What questions should this patient patient in our case was also experiencing symp- be asked? toms of gastrointestinal reflux disease (GERD) History-taking plays an important role in charac- refractory to treatment with a proton pump terizing dysphagia and narrowing the differential inhibitor. Eosinophilic esophagitis is uncommon diagnosis, as per the Canadian Association of in refractory GERD in the absence of dysphagia dysphagia algorithm.3 The first or food impaction. Two prospective studies (n = step is to ask patients with dysphagia whether 68–105) showed that there was a low prevalence they have difficulty initiating a swallow (suggest- of eosinophilic esophagitis (0.9%–8.8%) among ing ) or completing a adults with symptoms of refractory GERD.4 swallow (suggesting esophageal dysphagia). Although about one-quarter of adults with Patients with oropharyngeal dysphagia may report eosinophilic esophagitis have symptoms consis- a history of coughing, choking or nasal regurgita- tent with GERD, dysphagia (93%) and food

© 2016 Joule Inc. or its licensors CMAJ, September 6, 2016, 188(12) 893 Practice

impaction (62%) are far more common.5 Two field) restricted to the esophagus that persist after prospective studies involving about 300 partici- a two-month trial of a proton pump inhibitor.7 pants reported that up to 15% of adults present- Histology is required because no endoscopic­ fea- ing with refractory GERD and dysphagia may tures are considered pathognomonic.7 However, have eosinophilic esophagitis, with the preva- the authors of a clinical prediction tool for this lence of the condition increasing to 48% among condition prospectively enrolled 81 patients with those with food impaction.4 A small prospective eosinophilic esophagitis and 144 controls with study involving 150 participants with refractory GERD and dysphagia symptoms into a validation GERD reported that independent predictors of study. Certain clinical factors (age < 50 yr, male eosinophilic esophagitis in the six patients with sex, presence of dysphagia and food allergies) diagnosed eosinophilic esophagitis were age less combined with specific endoscopic features (pres- than 45 years, dysphagia and atopy.4 ence of esophageal rings, furrows and plaques, Given the patient’s age, history of atopy, and absence of hiatal ) predicted eosino- intermittent dysphagia and lack of response to philic esophagitis with a sensitivity of 84%, speci- treatment with a proton pump inhibitor, eosino- ficity of 97% and accuracy of 92%.8 An online philic esophagitis is strongly suspected. calculator developed by the University of North Carolina’s Center for and Should this patient be referred Swallowing is available to help predict the proba- for endoscopy? bility of this condition (https://gicenter.med.unc. The patient should be referred for expedited edu/cedas/eoe_clinical_calculator.html). ­endoscopy. The Canadian Association of Gastro- enterology suggests that endoscopy be avoided Given the high likelihood of eosinophilic for dyspepsia without alarm symptoms in patients esophagitis, what information about its less than 55 years of age (Box 1).6 However, dys- management should be discussed? phagia should be considered an alarm feature if Diet modification can be considered as an initial difficulty swallowing solids is the primary symp- step in the management of eosinophilic esophagi- tom and it fails to respond to a two- to four-week tis.7 A meta-analysis of 33 studies involving 1317 trial of a proton pump inhibitor with once or twice patients with the condition found that a six-food daily standard dosing.1 Dysphagia unresponsive­ elimination diet (milk, soy, egg, nuts, seafood to even longer courses of proton pump inhibi- and wheat) was likely the best dietary approach tors should prompt generalists to refer for an ex- for motivated adults.9 This approach balances the pedited endoscopy.1 lower effectiveness of this diet (71.9% in adults) Endoscopy is helpful for investigating a clinical against the major disadvantages of a more effec- history suspicious for mechanical obstruction, with tive elemental diet (e.g., no table food, unpleasant the added benefit of being able to obtain biopsies.3 taste, high cost, extremely limiting socially).9 A diagnosis of eosinophilic esophagitis re- There have been more liberal elimination diets quires symptoms of esophageal dysfunction plus developed, such as a four-food elimination diet histologic evidence of predominantly eosinophilic­ (milk, wheat, egg and soy), a milk elimination inflammation (≥ 15 eosinophils per high-power diet and elimination diets directed by allergy testing, but they are less effective and less well Box 1: Choosing Wisely Canada studied.9 However, they may be considered for recommendation on endoscopy for patients who desire a less restrictive diet or are dyspepsia by the Canadian Association of having difficulty adhering to the six-food elimi- 6 Gastroenterology nation diet. Avoid performing an endoscopy for dyspepsia Evidence from a recent systematic review and without alarm symptoms for patients under the meta-analysis of seven randomized controlled tri- age of 55 years. als involving 226 patients suggests that the use of • Endoscopy is an accurate test for diagnosing swallowed inhaled steroids for an initial duration dyspepsia, but organic pathology that does not respond to acid suppression or of eight weeks serves as first-line pharmacother- Helicobacter pylori eradication therapy is apy, after an initial trial of a proton pump inhibi- rare under the age of 55. Most guidelines tor.10 Options include fluticasone 440–880 μg therefore recommend as the first-line twice daily or budesonide 1 mg twice daily in approach for managing dyspepsia either 7 empirical proton pump inhibitor therapy or adults. Fluticasone should be puffed directly into a noninvasive test for H. pylori and then the mouth without inhaling or using a spacer and offering therapy if the result is positive. If then dry swallowed. Budesonide can be swal- the patient has alarm features such as lowed as an oral viscous solution or nebulized progressive dysphagia, or weight mixture. Food and drink should be avoided for 30 loss, endoscopy may be appropriate. minutes after administration of swallowed topical

894 CMAJ, September 6, 2016, 188(12) Practice steroids. The most common adverse effect was an References increased risk of asymptomatic esophageal candi- 1. Armstrong D, Marshall JK, Chiba N, et al. Canadian Consensus 10 Conference on the management of gastroesophageal reflux disease diasis responsive to antifungal therapy. Use of in adults — update 2004. Can J Gastroenterol 2005;19:15-35. systemic steroids (e.g., prednisone 1 mg/kg daily) 2. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esopha- 2,7 gitis: updated consensus recommendations for children and should be reserved for more severe cases. adults. J Allergy Clin Immunol 2011;128:3-20.e6. Based on large case series, endoscopic esoph- 3. Cockeram AW. Canadian Association of Gastroenterology prac- ageal dilation may be considered in symptomatic tice guidelines: evaluation of dysphagia. Can J Gastroenterol 1998;12:409-13. adults with strictures refractory to diet and 4. García-Compeán D, González-Cervera JA, Marrufo García CA, pharmacotherapy.7 et al. Prevalence of eosinophilic esophagitis in patients with refractory gastroesophageal reflux disease symptoms: a prospec- An allergy consultation may be helpful in tive study. Dig Dis 2011;43:204-8. optimizing diet therapies and comorbid atopic 5. Sgouros SN, Bergele C, Mantides A. Eosinophilic esophagitis in adults: a systematic review. Eur J Gastroenterol Hepatol 2006;​ conditions, which may contribute to the immu- 18:211-7. nopathogenesis of this condition.2,7 6. Canadian Association of Gastroenterology: Five things physicians and patients should question. Ottawa: Choosing Wisely Canada; 2014. Eosinophilic esophagitis is a chronic disease Available: www.choosingwiselycanada.org/recommendations/​ with frequent symptom recurrence after initial gastroenterology-2/ (accessed 2015 Dec. 4). 7. Dellon ES, Gonsalves N, Hirano I, et al. ACG clinical guideline: treatment. Patients should be counselled on the evidenced based approach to the diagnosis and management of possible need for maintenance therapy (diet or esophageal eosinophilia and eosinophilic esophagitis (EoE). Am pharmacotherapy) for controlling symptoms J Gastroenterol 2013;108:679-92. 8. Dellon ES, Rusin S, Gebhart JH, et al. A clinical prediction tool and preventing complications. Indications for identifies cases of eosinophilic esophagitis without endoscopic maintenance therapy include narrow esophagus, biopsy: a prospective study. Am J Gastroenterol 2015;110:1347-54. 9. Arias Á, González-Cervera J, Tenias JM, et al. Efficacy of prior stricture requiring repeated dilations, prior dietary interventions for inducing histologic remission in emergent endoscopy for food impaction, prior patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology 2014;146:1639-48. esophageal perforation, prior Boerhaave syn- 10. Chuang MY, Chinnaratha MA, Hancock DG, et al. Topical steroid drome, severe or ongoing symptoms and patient therapy for the treatment of eosinophilic esophagitis (EoE): a sys- 7 tematic review and meta-analysis. Clin Transl Gastroenterol preference. 2015;6:e82-9. A collaborative care model between the pa- tient, consultant and primary care physician Affiliations: Faculty of Medicine (Pham, Yang), University is important in the long-term management of of Ottawa; Ottawa Allergy Research Corporation (Yang), ­eosinophilic esophagitis, because the condition Ottawa, Ont. requires continuing patient education, monitor- Contributors: Hoang Pham drafted the manuscript, which ing of adherence to and adverse effects of treat- both authors revised. Both authors approved the final version to be published and agreed to act as guarantors of the work. ment, and monitoring for complications.

Case revisited The patient was referred for upper endoscopy, and eosinophilic esophagitis was diagnosed after biop- Decisions is a series that focuses on practical evi- sies showed esophageal eosinophilia. Swallowed dence-based approaches to common presentations inhaled steroid therapy with fluticasone was pre- in primary care. The articles address key deci- scribed. Because the patient wanted to follow the sions that a clinician may encounter during initial least restrictive diet modification strategy, allergy assessment. The information presented can usu- testing helped guide his dietary choices. The aller- ally be covered in a typical primary care gist also helped optimize his environmental aller- appointment. Articles should be no longer than gies with nasal cortico­steroids, antihistamines and 650 words, may include one box, figure or table subcutaneous immunotherapy. At one-year follow- and should begin with a very brief description (75 up, the patient’s symptoms had improved consid- words or less) of the clinical situation. The deci- sions addressed should be presented in the form erably, which motivated him to continue with his of questions. A box providing helpful resources diet and flu­ticasone treatment to minimize mild for the patient or physician is encouraged. ongoing symptoms.

CMAJ, September 6, 2016, 188(12) 895