Intraluminal dissection of the esophagus in an adolescent male: an unusual presentation of eosinophilic esophagitis successfully treated with dupilumab

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disorder defined by symptoms of esophageal dysfunction and histological evidence of eosinophilic infiltration (≥15 eosinophils/high-power field (HPF)) [1]. The incidence of EoE has markedly increased over recent decades, particularly among children and adolescents. Common clinical presentations include dysphagia, food impaction, and feeding difficulties. Typical endoscopic findings include esophageal rings, linear furrows, and strictures [2]. Rarely, EoE may present with structural complications such as intraluminal dissection esophagus, which may mimic congenital anomalies or sequelae of esophageal trauma [3, 4]. Such presentations are seldom reported and may delay diagnosis, especially in the absence of typical atopic features. Pathophysiologically, chronic eosinophilic inflammation induces epithelial damage, basal cell hyperplasia, sub-epithelial fibrosis, and tissue remodeling. In severe or prolonged cases, these processes may extend transmurally, compromising esophageal wall integrity and leading to submucosal dissection or false lumen formation [5–7]. Here, we report ahe case of complicated EoE onset, misinterpreted initially as pericarditis and as an esophageal intraluminal dissection. After the correct diagnosis of EoE, the patient was successfully treated with dupilumab. A 17-year-old male with a 1-year history of idiopathic pericarditis (diagnosed based on retrosternal and left-sided chest pain, fever, and a minimal pericardial effusion) presented to the Emergency Department with acute-onset retrosternal chest pain that worsened in the supine position and was associated with sudden-onset dysphagia to both solids and liquids. The patient denied any symptoms suggestive of gastroesophageal reflux disease, including acid reflux, heartburn, vomiting, or epigastric pain. No allergic comorbidities, prior endoscopic procedures, or trauma were reported. His previous episode of pericarditis was successfully treated with ibuprofen and colchicine, resulting in complete symptom resolution. Upon presentation, the patient was hemodynamically stable and well nourished. Clinical examination revealed no pericardial friction rub, and cardiovascular and pulmonary auscultations were unremarkable. Laboratory evaluation showed normal complete blood count (190 peripheral eosinophils per microliter), electrolytes, troponin, amylase, liver function, and renal function tests. C-reactive protein was elevated at 12.52 mg/dL. Chest radiography was unremarkable. A cardiologic evaluation ruled out recurrent pericarditis. Nevertheless, the patient was empirically started on 600 mg of ibuprofen twice daily and a proton-pump inhibitor. Despite adherence to treatment, symptoms persisted and the dysphagia worsened. A repeat cardiologic assessment, including electrocardiography and echocardiography, revealed no abnormalities. Given the ongoing symptoms, the patient was admitted for further evaluation. A contrast esophagogram demonstrated abnormal contrast flow into a longitudinal, pouch-like structure in the distal esophagus, with delayed contrast clearance and persistent paraesophageal opacification. These findings raised suspicion of an esophageal duplication (cystic or tubular) or, less likely, an acquired diverticulum (Fig. 1). (A) Pretreatment endoscopic image at diagnosis showing markedly inflamed erythematous and edematous mucosa of the distal esophagus with diffuse trachealization and a few whitish spots. (B) Follow-up endoscopic image after initiation of dupilumab therapy showing a pink, healthy-appearing mucosa without whitish spots, although an orifice at 40 cm from the dental arcade remains visible within the esophageal lumen. (C) Esophagogram showing the esophagus on the left side with a small ‘ring-sign’ indentation along the distal third. Closely adjacent to it, also on the left, a tubular structure filled with contrast agent is seen extending from the distal to the proximal third of the esophagus. (D) Coronal-plane CT scan showing findings similar to those on the esophagogram: on the right, the esophagus filled with water-soluble contrast agent; on the left, a linear cavity filled with contrast in the distal third and with air in the proximal third. (E) Sagittal-plane CT scan showing the esophageal lumen posteriorly, filled with contrast medium, and an anterior lumen that is not yet opacified. (F) Axial CT scan with the arrow indicating the orifice of communication between the contrast-filled esophagus and the adjacent lumen with a lamellar appearance. A contrast-enhanced thoracic CT scan with oral Gastrografin revealed a tubular, well-defined structure in the right paramedian mediastinum, extending ∼15 cm craniocaudally from the carina to the distal esophagus, just proximal to the diaphragmatic hiatus. The structure was partially filled with contrast and communicated with the distal third of the esophagus (Fig. 1). Subsequent esophagogastroduodenoscopy revealed diffusely edematous esophageal mucosa, longitudinal trachealization, and multiple ulcerations with hyperemic bases and some white mucosal exudates. At 25 cm from the upper incisors (UI), a 3- to 4-mm orifice was identified; a radiographic contrast medium was injected into the tract, revealing an intraluminal dissection of the esophagus with re-entry into the main lumen 40 cm from the UI (Fig. 1). Additional findings included gastroesophageal junction incompetence (observed in retroversion, not in direct view), diffuse gastric erythema, and congested duodenal mucosa. Histopathological examination of esophageal biopsies demonstrated characteristic features of EoE, including basal zone hyperplasia, intercellular space dilation, and significant eosinophilic infiltration: 19 eosinophils per HPF in the proximal esophagus (25 cm), 39/HPF in the mid-esophagus (30 cm), and 17/HPF in the distal esophagus (35 cm). Based on clinical, endoscopic, and histological findings, a diagnosis of EoE complicated by submucosal inflammation and intraluminal dissection was established. Due to the disease severity and structural complications, treatment with the monoclonal antibody dupilumab targeting interleukin-4 and interleukin-13 pathways was initiated at 300 mg subcutaneously once weekly. This was initially combined with oral viscous budesonide (1 mg twice daily) and pantoprazole (20 mg twice daily). The patient reported rapid symptomatic improvement. Budesonide and the proton-pump inhibitor were gradually tapered and discontinued, and the patient continued with dupilumab monotherapy. After ∼6 months, follow-up CT demonstrated complete resolution of the previously described esophageal dissection. Follow-up esophagogastroduodenoscopy demonstrated marked mucosal healing with a normal esophageal mucosa appearance, with residual semi-annular scarring in the upper esophagus and a mild trachealization pattern. No exudates or longitudinal furrows were observed, except for a single short furrow in the distal esophagus. The cranial orifice at 25 cm was no longer visualized, while the caudal orifice at 40 cm remained detectable (Fig. 1). The mucosa beyond the esophagus appeared regular. Repeat biopsies showed eosinophil counts that were reduced but still above the normal threshold (35 eosinophils/HPF in the mid-esophagus and 30/HPF in the upper esophagus). At subsequent clinical follow-up, the patient remained asymptomatic with stable remission. After the diagnosis of EoE, the previous history of idiopathic pericarditis was questioned. The initially reported echocardiographic signs of pericarditis resulted as being minimal and they suddenly disappeared after the ibuprofen therapy. Indeed, the boy, when properly asked for symptoms besides chest pain, revealed sudden dysphagia and odynophagia that were interpreted at that time as post-infective. This case represents an unusual manifestation of pediatric-onset EoE with intraluminal esophageal dissection, likely resulting from submucosal tunneling caused by chronic eosinophil-mediated inflammation. Chronic inflammation may induce submucosal fibrosis (due to TGF-β, Tumor Necrosis Factor-Beta) and tissue remodeling, leading to weakening and separation of the submucosal layers. Inflammatory changes and increased mucosal fragility, together with esophageal remodeling, further increase the risk of intraluminal dissection [3–8]. Differential diagnoses such as esophageal duplication cyst or acquired diverticulum were initially considered. However, these conditions are typically associated with congenital anomalies or with mechanisms of pulsion or traction [4–9]. In the present clinical context, the absence of congenital abnormalities and the histopathological findings supported an inflammatory etiology (Table 1). Key differentiating features of esophageal wall anomalies. Furthermore, these findings challenge the previous diagnosis of pericarditis, established mainly on clinical and echocardiographic grounds. The symptoms, such as chest pain, might have arisen directly from the EoE or an eosinophilic inflammatory involvement of the pericardium potentially related to the EoE itself by contiguity cannot be excluded [10, 11]. The use of dupilumab was associated with substantial clinical, endoscopic, and radiologic improvement [12], including near resolution of the pseudodiverticular tract. These findings support its potential role in managing EoE with deeper or transmural involvement. While topical corticosteroids remain the first-line treatment in most cases, their effect is largely limited to the superficial mucosa. In contrast, systemic biologics may provide broader anti-inflammatory action in cases involving extensive tissue remodeling [6]. In conclusion, this case highlights the need to consider EoE in young patients presenting with acute-onset retrosternal chest pain associated with dysphagia and atypical esophageal morphology, including intraluminal dissection of the esophagus, particularly in the absence of prior instrumentation or trauma. Early recognition and histologic confirmation are crucial for prompt and effective management. Furthermore, the case supports the therapeutic utility of dupilumab in complex EoE phenotypes, including those with structural complications not typically amenable to mucosa-targeted therapies. Writing original draft: S.R. Draft revision and clinical management: S.R., P.L., L.S. Clinical management: N.d.B., S.S., F.F. Radiologic imaging: F.F. No funding. Conflict of Interest Conference fees (Sanofi): S.R., P.L., and N.d.B.