Eosinophilic esophagitis

Classification according to ICD-10
K20	Esophagitis
ICD-10 online (WHO version 2019)

The eosinophilic esophagitis (EE or EoE) is an immune-mediated, chronic inflammatory disease of the esophagus (esophagus) with the typical symptom of dysphagia varying degrees. It was described for the first time in 1977 and recognized as an independent disease in 1978. Formerly considered a rarity , eosinophilic esophagitis has been increasingly diagnosed in industrialized countries since the late 1990s and is now considered the second most common inflammatory disease of the esophagus after reflux esophagitis ( GERD ). This is due on the one hand to a better perception of the investigators, on the other hand to an increase in the incidence of the disease. European guidelines for therapy and treatment have existed since 2017, a German guideline is still pending.

Epidemiology

While individual cases were assumed after the initial description of the disease, the prevalence is now 13–49 cases per 100,000 inhabitants, the incidence is 1–20 new cases per 100,000 inhabitants per year, with the male sex with m: w = 7: 3 is preferentially affected. The disease occurs in children as well as in adolescents and adults. Eosinophilic esophagitis can occur at any age, but with an increasing incidence in children and with a peak in adults between 30 and 50 years of age. About 75% of the patients also have another atopic disease. A further increase in the number of cases is observed in all industrial nations, which is not only due to better detection, but actually also to increasing disease rates.

causes

While eosinophilic inflammation is the histological distinguishing feature of eosinophilic esophagitis, this eosinophilia is only the result of an inflammatory process that has not yet been fully understood. On the one hand, various food components play a role in the development of the inflammation. On the other hand, there are indications of a familial accumulation, which makes a (partly) genetic cause probable. For example, an increased association with variants on a region of chromosome 5q22 has been described. Overall, the EoE is considered a misdirected response of the immune system (“allergic asthma of the esophagus”), in which antigen-presenting T cells are initially activated by allergens. These trigger an inflammatory cascade through which eosinophilic granulocytes from the bone marrow migrate into the esophagus under the influence of interleukin -5 and eotaxin . These immigrated eosinophilic granulocytes, in turn, maintain the local inflammation and thus cause fibrosis and angiogenesis , which in turn favors the inflammation. The release of histamine and other mediators is considered to be the cause of the ring formation and dysmotility . The influence of acid reflux on reflux disease ( reflux oesophagitis ) remains unexplained . Since at least some of the patients respond to therapy with proton pump inhibitors in the long term, acid reflux is assumed to play a role in the development and / or persistence.

morphology

The endoscopically visible changes in the esophagus are varied and depend on the duration of the disease. In addition to the so-called tree ring aspect and the highly vulnerable crepe-paper mucosa, longitudinal furrows and other changes in the mucosa are seen. Bottlenecks (strictures or stenoses) occur with long-term illness. Since the first endoscopy is often performed as part of an emergency situation due to the bolus obstruction , the sometimes only discreet changes may be overlooked. Longitudinal furrows with thickening of the mucosa can occasionally be seen on endoscopic ultrasound.

diagnosis

Endoscopy with simultaneous sampling has the highest priority in diagnosing the disease. Other procedures, for example a barium swallow or endoscopic ultrasound, enable the presentation of complications in the case of long-term illness. The diagnosis is made based on three criteria:

1. at least 15 eosinophils per main field of view
2. clinical symptoms of dysphagia
3. Exclude other conditions that can lead to eosinophilia or dysphagia, such as reflux disease (GERD), eosinophilic gastroenteritis, and Schatzki's ring .

The definition of the main field of vision is not standardized internationally or nationally. The standard size is that a main field of view corresponds to about 0.3 mm ". In order to achieve a high diagnostic hit rate in the sampling, a sufficient number of tissue samples must be taken during the endoscopy . A scheme of two samples each from the upper, middle one applies and lower (3 cm above the Z-line) esophagus as sufficient. In addition, samples are taken from the stomach and the duodenum to rule out eosinophilic gastroenteritis , an important differential diagnosis of eosinophilic esophagitis. General testing of food allergies via laboratory tests ( RAST , IgE) or other tests (epicutaneous and intracutaneous skin tests) have no significance in EoE due to their low informative value according to European guidelines.

Symptoms

The leading symptom of eosinophilic esophagitis is dysphagia in varying degrees. In the case of children, avoidance behavior is in the foreground, which is learned unconsciously. Families often report of "slow eaters" or "late drinkers". The delayed and reduced food intake often leads to failure to thrive . If left untreated, eosinophilic esophagitis leads to the development of fibrosis with loss of elasticity of the esophagus due to the persistent inflammatory activity. This leads to the formation of strictures, which in turn leads to so-called bolus obstruction, in which solid food “gets stuck”. In this way, a patient is often presented to a healthcare facility for the first time as an emergency after a bolus event has occurred. If left untreated, the progression of inflammation ultimately leads to loss of function of the esophagus and scarred stenoses. It is not uncommon for these to be expanded endoscopically to enable food to be consumed at all.

therapy

According to the current understanding of the disease, a cure for eosinophilic esophagitis is not possible. After drug or diet therapy has ended, the disease often recurs, so it is currently assumed that long-term treatment is required. The disease can be treated well, so that long-term freedom from symptoms can often be achieved. Treatment includes drug, diet and endoscopic therapy.

Medical therapy

Drug therapy primarily includes proton pump inhibitors (PPIs) and topical corticosteroids . Some of the patients are known as PPI responders , whose disease responds well to treatment with proton pump inhibitors. The dose used corresponds to 2 × 20–40 mg omeprazole (or the equivalent dose of another PPI). Response rates of around 50% can be achieved with this therapy. With long-term use, about 70% of PPI responders remain in healing. The response rate is higher when using topical corticosteroids, which has been considerably simplified since 2018 with the introduction of a budesonide orodispersible tablet. With a dose of 2 × 1 mg, response rates of about 2/3 of the patients are achieved, in some cases higher with longer lasting therapy. A maintenance treatment with half the dose (2 x 0.5 mg or 1 mg to night) leads Nachbeobachtungszeiträumen over two years to a continuing cure at about 3/4 of the initial responding patients. The most frequent side effect is a thrush of the esophagus ( around 20% ) , which usually fails easily and can be treated with antimycotics if necessary . Other anti-allergic drugs currently have no place in the treatment of the disease.

Diet therapy

Since EoE is a special form of food allergy , an elimination diet can be used to try to find the triggering allergen. The so-called 6-Foods Elimination Diet has proven itself . First a strict diet without milk, chicken eggs, wheat, nuts, soy and seafood is started. After six weeks, the effect is checked using endoscopy with samples taken from the esophagus. If the disease is found to be cured in the tissue sample, the first of the six omitted allergens can be reintroduced into the menu. After a further six weeks, another check is carried out by means of endoscopy and sampling. If the tissue sample continues to heal, the next allergen can be added to the menu, etc. If a renewed eosinophilic inflammation is found in the tissue sample after one of the six allergens has been added, this allergen is considered to be the trigger and must be avoided permanently. In the elimination diet, it is important that all six main allergens are tested in the manner described, as the esophagus can react to several allergens. This means that in addition to the first endoscopy, six more endoscopies are necessary. This high effort, combined with the complex diet, leads to poor acceptance of this form of therapy despite the relatively high success rate of 75% .

Endoscopic Therapy

Treatment of complications of eosinophilic esophagitis is the field of endoscopic therapy. Due to the permanent inflammation, strictures and stenoses occur, which can be expanded either with bougies or balloon dilation. However, endoscopic therapy does not replace the permanent continuation of the treatment of the underlying inflammation with medication or diet.

Complications and course

The persistent inflammation leads to fibrosis and increasing loss of peristalsis of the esophagus. This promotes bolus events (“sticking” of solid foods). In the long term, there is a risk of developing strictures and stenoses, which then make the above-mentioned endoscopic therapy necessary. So far there is no evidence that eosinophilic esophagitis favors cancer development.

Individual evidence

1. ↑ JW Dobbins, D Sheahan, J Behar: Eosinophilic gastroenteritis with esophageal involvement . In: AGA (Ed.): Gastroenterology . No. 72 . Elsevier Verlag, 1977, p. 1312-1316 , PMID 870380 .
2. ↑ RT Landres, GR Kuster, W Strum: Eosinophilic esophagitis in a patient with vigorous achalasia . In: AGA (Ed.): Gastroenterology . tape 74 . Elsevier Verlag, 1978, p. 1298-1301 , PMID 648822 .
3. ↑ AJ Lucendo: Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults . In: United European Gastroenterology Journal . Vol 5, No. (3) . SAGE, 2017, p. 335-358 , doi : 10.1177 / 2050640616689525 , PMID 28507746 .
4. ↑ JW Potter, K Saeian, D Staff et al .: Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features . In: Gastrointestinal Endoscopy . No. 59 . Elsevier Verlag, 2004, p. 355-361 , doi : 10.1016 / s0016-5107 (03) 02713-5 , PMID 14997131 .
5. ^ ME Rothenberg et al .: Common variants at 5q22 associate with pediatric eosinophilic esophagitis . In: Nature genetics . No. 42 . Nature Publishing Group, 2010, p. 289-291 , doi : 10.1038 / ng.547 , PMID 20208534 .
6. ^ A Mishra, S Hogan, E Brandt, M Rothenberg: An etiological role for aeroallergens and eosinophilia in experimental esophagitis . In: Journal of Clinical Investigation . No. 107 . American Society for Clinical Investigation, 2001, pp. 83-90 , doi : 10.1172 / JCI10224 .
7. ^ A Mishra, SP Hogan, EB Brandt, ME Rothenberg: IL-5 promotes eosinophil trafficking to the esophagus . In: Journal of Immunology . tape 168 , no. (5) . American Association of Immunologists, 2002, pp. 2464-2469 , doi : 10.4049 / jimmunol.168.5.2464 , PMID 11859139 .
8. ↑ JW Leung, NS Mann: Pathogenesis of esophageal rings in eosinophilic esophagitis. In: Medical Hypotheses . No. 640 . Elsevier Verlag, 2005, p. 520-523 , doi : 10.1016 / j.mehy.2004.08.021 , PMID 15617859 .
9. ↑ VL Fox, S Nurko, GT Furuta: Eosinophilic esophagitis: it's not just kid's stuff. In: Gastrointestinal Endoscopy . No. 56 . Elsevier, 2002, p. 260-270 , doi : 10.1016 / s0016-5107 (02) 70188-0 , PMID 12145607 .
10. ^ AR Gupte, PV Draganov: Eosinophilic esophagitis. In: World Journal of Gastroenterology . No. 15 . Baishideng Publishing Group, 2009, p. 17-24 , doi : 10.3748 / wjg.15.17 , PMID 19115464 .
11. ↑ AS Arora, J Perrault, TC Smyrk .: Topical corticosteroid treatment of dysphagia due to eosinophilic esophagitis in adults. In: Mayo Clinic Proceedings . tape 78 , no. (7) . Elsevier Verlag, 2003, p. 830-835 , doi : 10.4065 / 78.7.830 .
12. ↑ DE Langdon: "Congenital" esophageal stenosis, corrugated ringed esophagus, and eosinophilic esophagitis. In: American Journal of Gastroenterology . tape 95 , no. (8) . Nature, 2000, pp. 2123-2124 , doi : 10.1111 / j.1572-0241.2000.02200.x , PMID 10950073 .
13. ^ KL Denning, A Al-Subu, Y Elitsur: Immunoreactivity of p53 and Ki-67 for dysplastic changes in children with eosinophilic esophagitis. In: Pediatric and Developmental Pathology . No. 16 . Springer Verlag, 2013, p. 331-336 , doi : 10.2350 / 13-03-1306-OA.1 , PMID 23718721 .

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