EG/EoD IS
UNDERDIAGNOSED

DIAGNOSIS OF EOSINOPHILIC GASTRITIS AND/OR EOSINOPHILIC DUODENITIS (EG/EoD) IS OFTEN MISSED, and EG/EoD may be more common than other gastrointestinal (GI) conditions such as ulcerative colitis and Crohn’s disease1-4

POTENTIAL CONTRIBUTORS TO UNDERDIAGNOSIS

Endoscopy with systematic biopsy collection may not be routinely performed to investigate functional symptoms unless more serious signs are present5,6

In about half of EG/EoD cases, gastric and duodenal mucosae appear deceptively normal on endoscopy, which may discourage the necessary diagnostic step of biopsy collection7

Systematic counting of eosinophils in gastric and duodenal biopsies may not be performed as part of the histopathologic evaluation8

MISDIAGNOSIS IS COMMON1,8

In a prospective study evaluating 405 patients with nonspecific GI symptoms1:

PRIOR TO DEFINITIVE DIAGNOSIS OF EG/EoD 93% OF PATIENTS HAD BEEN DIAGNOSED WITH ANOTHER GI CONDITION

Functional dyspepsia (FD)
Gastroesophageal reflux disease (GERD)
Irritable bowel syndrome (IBS)
Other functional GI disorder
  • The nonspecific clinical presentation of EG/EoD—symptoms such as abdominal pain, diarrhea, early satiety, and nausea/vomiting—overlaps with other GI conditions8-10
  • Patients are often misdiagnosed with a functional GI disorder such as IBS or FD, and thus may not undergo esophagogastroduodenoscopy (EGD) with biopsy8

MISSED OR DELAYED DIAGNOSIS FREQUENTLY OCCURS1

Patients endured an 11-year diagnostic delay on average from symptom onset until they were diagnosed with EG/EoD1,a

Premature diagnosis with a functional GI disorder may preclude or delay upper endoscopy with biopsy and histopathologic evaluation, steps required for definitive diagnosis of EG/EoD8

Diagnosis is often missed on initial endoscopy—38% of patients with EG/EoD were not diagnosed on index EGD8,b

  • a Multicenter, prospective study of 405 patients with GI symptoms for ≥6 months without an organic cause, who underwent EGD with biopsy, from 20 sites in the United States.1
  • b Retrospective observational study of 4108 patients with EG/EoD from a representative US administrative claims database from 2008-2018.8

PATIENT CASES: EXAMPLES OF DIAGNOSTIC DELAY

CASE 1: 36-YEAR-OLD FEMALE

This patient was misdiagnosed repeatedly, including with functional dyspepsia, delaying her definitive diagnosis of EG/EoD until 8 years after initial presentationc

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CASE 2: 45-YEAR-OLD FEMALE

This patient endured 6 years of worsening GI symptoms and visited multiple healthcare providers prior to her definitive diagnosis of EG/EoDc

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Patient presented to primary care with 4-month history of abdominal pain and bloating. Empirically diagnosed with noninfectious gastroenteritis.

Clinical Presentation

Patient presented to primary care with 4-month history of abdominal pain and intermittent bloating refractory to OTC probiotics and H2 antagonist

Evaluation

Patient empirically diagnosed with noninfectious gastroenteritis

Management Approach

Treatment with PPI initiated

Missed Opportunities

  • Limited diagnostic evaluation
  • No referral to a gastroenterologist
  • Incomplete characterization as noninfectious gastroenteritis

Year

1

MISSED DIAGNOSIS

Patient referred to gastroenterologist due to more frequent abdominal pain and new-onset heartburn. Diagnosed with gastroesophageal reflux.

Clinical Presentation

Patient experienced persistent symptoms; referred to gastroenterologist due to more frequent abdominal pain now associated with heartburn

Evaluation

No additional tests performed by gastroenterologist. Patient diagnosed with gastroesophageal reflux.

Management Approach

Increased dose of PPI

Missed Opportunities

  • No EGD or other diagnostic workup to identify or rule out possible cause of symptoms

Year

3

MISSED DIAGNOSIS

Patient returned with worsening abdominal pain and bloating, now with nausea and early satiety. EGD with biopsy performed but gastric and duodenal eosinophils not counted. Patient diagnosed with functional dyspepsia.

Clinical Presentation

Patient returned to gastroenterologist with abdominal pain and bloating, now with nausea and early satiety

Evaluation

EGD with gastric and duodenal biopsy performed; H. pylori and celiac disease ruled out. Patient diagnosed with functional dyspepsia.

Management Approach

Continued high-dose PPI, added probiotics and simethicone

Missed Opportunities

  • Gastric and duodenal eosinophils not counted during histopathologic evaluation
  • EG/EoD diagnosis not established on index EGD

Year

5

MISSED DIAGNOSIS

Patient returned with persistent symptoms and new-onset vomiting. Underwent abdominal imaging, with no relevant findings. Diagnosis unchanged.

Clinical Presentation

Patient returned to gastroenterologist with persistent symptoms and 3-month history of vomiting

Evaluation

Abdominal CT imaging performed with normal findings. Diagnosis unchanged from previous visit.

Management Approach

Continued high-dose PPI, simethicone and probiotics; added intermittent antiemetic

Missed Opportunities

  • No repeat EGD despite new and worsening symptoms

Year

7

MISSED DIAGNOSIS

Patient returned to gastroenterologist with persistent symptoms and underwent repeat EGD with biopsy. Histopathologic evaluation revealed ≥30 eosinophils per hpf.

Clinical Presentation

Patient returned to gastroenterologist with persistent symptoms

Evaluation

Repeat EGD with multiple gastric and duodenal biopsies. Histopathologic evaluation revealed 45 eosinophils per hpf. Patient diagnosed with EG/EoD.

Management Approach

Systemic steroid initiated, resulting in temporary symptomatic improvement

DEFINITIVE DIAGNOSIS OF EG/EoD

Year

8

DEFINITIVE DIAGNOSIS OF EG/EoD

Patient presented to primary care with 4-month history of diarrhea. Empirically treated with OTC probiotics and antidiarrheal.

Clinical Presentation

Patient presented to primary care with 4-month history of intermittent watery diarrhea without weight loss

Evaluation

Stool tests negative for leukocytes and ova and parasites

Management Approach

Empiric treatment with OTC probiotics and antidiarrheal initiated

Missed Opportunities

  • No referral to a gastroenterologist

Year

1

MISSED DIAGNOSIS

Patient returned to primary care for worsening diarrhea and new-onset upper abdominal pain. Abdominal ultrasound was negative.

Clinical Presentation

Patient returned to primary care with intermittent diarrhea and new-onset upper abdominal pain

Evaluation

Abdominal ultrasound performed with no abnormal findings

Management Approach

Treatment with PPI initiated

Missed Opportunities

  • No referral to a gastroenterologist despite new symptoms

Year

3

MISSED DIAGNOSIS

Patient referred to gastroenterologist for persistent diarrhea and abdominal pain and new-onset dysphagia, nausea, and vomiting. EGD with biopsy performed and patient diagnosed with eosinophilic esophagitis (EoE). No gastric or duodenal biopsies collected during EGD.

Clinical Presentation

Patient referred to gastroenterologist for persistent diarrhea and abdominal pain and new-onset dysphagia, nausea, and vomiting

Evaluation

EGD with esophageal biopsy performed and patient diagnosed with eosinophilic esophagitis (EoE). No gastric or duodenal biopsies collected during EGD.

Management Approach

Initiated swallowed topical steroid, resulting in improvement in dysphagia, but other symptoms persisted

Missed Opportunities

  • Gastric and duodenal biopsies not collected due to normal endoscopic appearance
  • EG/EoD diagnosis not established on index EGD

Year

5

MISSED DIAGNOSIS

Patient referred to another gastroenterologist for a second opinion on persistent symptoms. Repeat EGD performed with gastric and duodenal biopsy. Histopathologic evaluation revealed ≥30 eosinophils per hpf.

Clinical Presentation

Patient referred to another gastroenterologist for a second opinion on persistent symptoms

Evaluation

Repeat EGD performed with gastric and duodenal biopsy. Histopathologic evaluation revealed peak counts of 55 eosinophils per hpf. Patient diagnosed with EG/EoD.

Management Approach

Six-food elimination diet and enteric-coated topical steroid capsules initiated with some symptomatic improvement

DEFINITIVE DIAGNOSIS OF EG/EoD

Year

6

DEFINITIVE DIAGNOSIS OF EG/EoD

  • Abbreviations: CT, computed tomography; hpf, high-power field; OTC, over-the-counter; PPI, proton pump inhibitor.
  • cHypothetical cases based in part on an actual patient journey from claims analysis as described in Chehade M et al. J Allergy Clin Immunol Pract. 2021.8
  • Cases include use of medications not approved by the US Food and Drug Administration for the treatment of EG/EoD, but reflect treatments commonly used in practice to manage symptoms.
  • Source: Data on File. Hypothetical Patient Claims Analysis. Allakos. April 2020.

A SYSTEMATIC BIOPSY PROTOCOL CAN HELP DETECT EG/EoD11

References:  1. Talley NJ, Kamboj AP, Chey WD, et al. Endoscopy and systematic biopsy of patients with chronic gastrointestinal symptoms leads to high discovery rate of patients who meet histologic criteria for eosinophilic gastritis and/or eosinophilic duodenitis. Presented at: Digestive Disease Week Virtual; May 22, 2021.  2. Alhmoud T, Hanson JA, Parasher G. Eosinophilic gastroenteritis: an underdiagnosed condition. Dig Dis Sci. 2016;61(9):2585-2592. doi:10.1007/s10620-016-4203-5.  3. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systemic review of population-based studies. Lancet. 2017;390:2769-2778. doi:10.1016/S0140-6736(17)32448-0.  4. Licari A, Votto M, Scudeller L, et al. Epidemiology of nonesophageal eosinophilic gastrointestinal diseases in symptomatic patients: a systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2020;8(6):1994-2003.e2. doi:10.1016/j.jaip.2020.01.060.  5. Moayyedi PM, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil N. ACG and CAG clinical guildeline: management of dyspepsia. Am J Gastroenterol. 2017;112(7):988-1013. doi:10.1038/ajg.2017.154.  6. Smalley W, Falck-Ytter C, Carrasco-Labra A, Wani S, Lytvyn L, Falck-Ytter Y. AGA clinical practice guidelines on the laboratory evaluation of functional diarrhea and diarrhea-predominant irritable bowel syndrome in adults (IBS-D). Gastroenterology. 2019;157(3):851-854. doi:10.1053/j.gastro.2019.07.004.  7. Reed C, Woosley JT, Dellon ES. Clinical characteristics, treatment outcomes, and resource utilization in children and adults with eosinophilic gastroenteritis. Dig Liver Dis. 2015;47(3):197-201. doi:10.1016/j.dld.2014.11.009.  8. Chehade M, Kamboj AP, Atkins D, Gehman LT. Diagnostic delay in patients with eosinophilic gastritis and/or duodenitis: a population-based study. J Allergy Clin Immunol Pract. 2021;9(5):2050-2059.e20. doi:10.1016/j.jaip.2020.12.054.  9. Pesek RD, Rothenberg ME. Eosinophilic gastrointestinal disease below the belt. J Allergy Clin Immunol. 2020;145(1):87-89.e1. doi:10.1016/j.jaci.2019.10.013.  10. Egan M, Furuta GT. Eosinophilic gastrointestinal diseases beyond eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2018;121(2):162-167. doi:10.1016/j.anai.2018.06.013.  11. Dellon ES, Gonsalves N, Rothenberg ME, et al. Optimization of eosinophilic gastritis/duodenitis detection requires evaluation of multiple high-powered fields in each of 8 gastric and 4 duodenal biopsies: analysis from a randomized trial. Poster presented at: Digestive Disease Week Virtual; May 21, 2021.