**6. Clinical associations**

Some retrospective studies and case reports have tried to identify an association between lymphocytic esophagitis and other clinical conditions. Whether it was inflammatory bowel disease, gastroesophageal reflux disease, celiac disease, asthma, allergies, irritants, or connective tissue diseases (lupus, Behçet's disease), no relationship could be identified [2, 11–13, 16].

Lymphocytic esophagitis is isolated to the esophagus. It does not coexist with other digestive lymphocytosis such as lymphocytic colitis or lymphocytic gastritis. There is no correlation between these distinct entities. In a case series from Purdy *et al*., some patients had concomitant biopsies from the rest of the digestive tract (stomach, small intestine, or colon). The histologic findings in these biopsies were various and secondary to preexisting conditions. No lymphocytic entity was observed in the rest of the gastrointestinal tract [8].

#### **6.1. Gastroesophageal reflux disease**

One of the main research efforts was to identify a relationship between lymphocytic esophagitis and reflux. Unfortunately, no association has been established between these two conditions [2, 12]. Indeed, only 22 out of 119 patients in the cohort from Haque *et al*. had gastroesophageal reflux disease [2].

#### **6.2. Crohn's disease**

In the cohort from Rubio *et al*., 8 of 20 patients had Crohn's disease [1]. However, subsequent studies failed to replicate this association with inflammatory bowel disease [2, 11, 17]. Nevertheless, while it appears that it is not associated with inflammatory bowel disease in adults, lymphocytic esophagitis may be a manifestation of upper gastrointestinal Crohn's disease in the pediatric population [1, 12, 10]. Indeed, seven out of eight Crohn's disease patients from Rubio *et al*. were pediatric cases. Purdy *et al*. confirmed this association with the pediatric Crohn's disease [1].

#### **6.3. Eosinophilic esophagitis**

Eosinophilic esophagitis has also been a subject of study and comparison with lymphocytic esophagitis. The clinical and endoscopic manifestations of lymphocytic esophagitis can be confused with those of eosinophilic esophagitis. It is only histology that allows us to differentiate these two entities. Felinization is not pathognomonic of eosinophilic esophagitis, hence the importance of biopsy [2].

In a recent cohort from Rubio *et al*., out of 311 biopsies with an increased number of intraepithelial lymphocytes, 33 cases were a compound of lymphocytic esophagitis and eosinophilic esophagitis [9]. We can thus ask whether these are two distinct conditions or whether one is the continuum of the other. However, this assumption remains a hypothesis and requires to be studied.

#### **6.4. Motility disorders**

Since 2014, an interest for esophageal motility disorders in lymphocytic esophagitis has arisen. Recent studies have demonstrated an association with achalasia and primary esophageal motility disorder (nutcracker esophagus, ineffective esophageal motility, and diffuse spasm) [18].

In 2015, Xue *et al*. noticed that esophageal biopsies in patients with primary esophageal motility abnormalities had CD4 + intraepithelial lymphocytosis. Moreover, Xue evoked the possibility of a new clinical entity that they called "dysmotility-associated LE." We still need further studies to better understand and characterize this association [11].
