Clinical Practice Guideline
Developed for the
Aerospace Medical Association
by their constituent organization
Overview: Eosinophils are not distributed homogeneously throughout the gastrointestinal tract. Typically, the highest numbers are found in the cecum and appendix, while esophageal epithelium is unique in being devoid of eosinophils under normal conditions. Eosinophilic inflammation of the GI tract may be secondary to other diseases, or may represent a primary process. Primary eosinophilic diseases are divided into eosinophilic esophagitis (EE) and eosinophilic gastroenteritis (EG), which may be seen in adults or children, and food protein-induced enterocolitis (FPEIC) and eosinophilic proctitis (EP), which are pediatric diseases.
EE may be associated with allergy (atopic) or may occur in isolated fashion (idiopathic). EE appears to be a new disease, first recognized in 1973, but it was rarely diagnosed before the past decade and may be accelerating in incidence. The majority of cases have been in men in their 20s to 30s, although later presentations have been described. Individual and/or family histories of allergic diseases (food allergies, atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis) have been noted in 62 to 85% of individuals with EE. EE mimics gastroesophageal reflux disease (GERD) and may result in narrowing and stricture of the esophagus, although strictures are more commonly proximal in EE. EE is differentiated from GERD on the basis of the magnitude of mucosal eosinophilia and the lack of response to acid suppression. In some cases, the diagnosis was prompted by a poor response to surgical treatment such as fundoplication. Adults usually present with dysphagia, and in particular a history of food impaction is common. Symptoms have usually been present for 4.5 years prior to diagnosis. The diagnostic criteria for EE have not been firmly established; >15-20 eosinophils per high-power field (HPF) on mucosal biopsy appears to be the most common cut-off. Endoscopic findings seen with EE include strictures (frequently proximal), linear furrow, small-caliber esophagus and multiple white papules (eosinophilic microabscesses).
Long-term prognosis is unknown. One study followed 30 (22 men and 8 women) adult patients for up to 11.5 years with EE; dysphagia persisted in 29 individuals (major negative effect on one individual and minor on 15). Attacks of dysphagia were more frequent in patients with blood eosinophilia or pronounced endoscopic alterations. The esophageal eosinophilic infiltration persisted but did spontaneously decrease over time (from an average of 78.7 to 40.3 cells/HPF). Fibrosis of the esophageal lamina propria occurred, but did not progress to involve the stomach or duodenum.
Treatment of EE is based on limited clinical experience, case series and small controlled trials. Even the optimal goal of treatment is unknown (control of symptoms versus resolution of eosinophilic inflammation). Regardless of the endpoint, acid suppression is usually not successful or at best achieves a partial response; however it may be helpful in a subset of patients with coexisting reflux, since acid exposure can cause eosinophilic inflammation. Dilation of strictures may be initial therapy for individuals with dysphagia and food impaction. Systemic or topical corticosteroids have been shown to improve symptoms. Topical corticosteroids have been administered by metered-dose inhaler (MDI), using preparations marketed for asthma control, e.g. fluticasone (220mcg/puff, twice daily). Patients are instructed to actuate the inhaler into the mouth without inhaling, swallow the deposited aerosol, and rinse and gargle afterwards. The high relapse rate (~65%) noted in one study in children suggests that chronic or repeated therapy may be needed. Elimination and in particular elemental diets have shown improvement in children and adolescents. Antihistamines, cromolyn and montelukast (at doses of about 100 mg/day), and mepolizumab have been used; their efficacy has not been established.
EG is eosinophilic infiltration of one or more segments of the GI tract with signs and symptoms related to the layer(s) [mucosa, muscle, and/or subserosa] and extent of bowel involved. In published reports, the stomach (26 to 81%) and small intestine (28 to 100%) are the predominant areas affected. EG is a rare disease, affecting males and females equally. In mucosal disease, typical symptoms are abdominal pain, nausea, vomiting, and diarrhea with endoscopic biopsy frequently confirming eosinophilic infiltration. In muscle disease symptoms of gastric outlet and intestinal obstruction are common due to a thickened, rigid gut from the eosinophilic infiltration. In subserosal disease individuals usually present with ascites which is markedly eosinophilic. Elevated peripheral eosinophil counts are seen frequently in mucosal and subserosal disease. EG is associated with atopy such as asthma and allergies in 40 to 50 % of the cases. Treatment is primarily oral steroids; cromolyn, montuklast and elimination diets have shown mixed efficacy. The natural history of EG is not well known; some individuals have no recurrence, while a few will flare concurrently with or immediately after prednisone taper, and still others may experience periodic flares months to years after the initial episode.
Aeromedical Concerns: Symptoms relevant to aviation include dysphagia, food impaction, nausea, vomiting, chest and/or abdominal pain. The symptoms are of concern primarily due to the potential impact while performing aircrew duties and the effects on mission safety and completion. Topical corticosteroid therapy, administered via MDI as described earlier, is acceptable for military waiver. Montelukast therapy is also waiverable in the military, although of uncertain benefit; while doses in excess of 10 mg have not shown additional benefit in asthma, doses as high as 800 mg have not shown appreciable toxicity either. Approved antihistamines, loratadine (Claritin®) or fexofenadine (Allegra®) and cromolyn are acceptable for waiver. Waiver is not recommended while on oral steroids. If the individual is asymptomatic after oral steroids, waiver could be considered after the pituitary axis has returned to normal function (based on Cortrosyn® stimulation testing).
Medical Work-up: The aviator needs to submit a history with special attention to symptoms, frequency, duration, treatment, precipitating factors, action taken to mitigate recurrence, as well as documentation from the gastroenterologist outlining the evaluation (to include the endoscopy report), pathology report, and treatment recommendations. It may be useful to include an allergy consultation addressing possible food allergies.
Air Force: In the US Air Force, a history of EE and EG is disqualifying for all flying classes. It is not waiverable in untrained aircrew. It is potentially waiverable in trained aircrew if individual has no aeromedically significant complications and remains asymptomatic on or off waiverable medications.
Army: Eosinophilic inflammation of the GI tract, eosinophilic esophagitis (EE) and eosinophilic gastroenteritis (EG), are not discussed in the Army physical standards regulation or Aeromedical Policy Letters. Non-eosinophilic esophagitis is discussed in the Army Aeromedical Policy Letter for reflux disease.
Navy: Waiver will be considered only in asymptomatic, stable cases.
Applicants: Considered Disqualifying / Waiver considered on case by case basis.
Designated: Considered Disqualifying / Waiver recommended if asymptomatic while on
or off medications.
FOLLOW-UP: Annual submission with consult from FP, IM or GI unless otherwise specified
Civilian: This condition could potentially be waiverable in the civilian population depending on the aeromedically significant findings. The same circumstances as mentioned in the section on aeromedical concerns apply in the civilian sector. Oral corticosteroids in doses above 20 mg equivalent of prednisone are not acceptable. Topical corticosteroids would be acceptable as would montelukast, loratadine and Fexofenadine.
Air Force: A review of the AIMWTS database showed two cases of EE and no cases of EG. Of the two cases, one was disqualified (symptomatic) and the other was granted a waiver (asymptomatic).
Army The Aeromedical Epidemiological Data Repository (AEDR) catalogs all Army flight physicals since 1960. There have been approximately 160,000 individual aircrew entered in this database. During this period of time, there were 26 aeromedical summaries, which include 3 applicants. Of those, there were only 2 medical suspensions and those were among rated pilots. During the same period, there were 10 requests for waiver in non-rated aircrew and all were granted.
Navy: Precise statistics are not available at this time.
Civilian: There is no specific pathology code for this condition in the FAA’s system.
ICD-9-CM for eosinophilic esophagitis, complications, and eosinophilic gastroenteritis
Stricture and stenosis of esophagus
Other, other specified disorders of esophagus
Other and unspecified noninfectious gastroenteritis and colitis
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Prepared by Dr. Karen Fox
Date: September 26, 2010