Concurrence of Eosinophilic Esophagitis and Dyshidrotic Eczema

To the Editor:

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease marked by esophageal dysfunction and eosinophilic inflammation triggered by food or inhaled allergens.¹ EoE is strongly associated with atopic comorbidities such as asthma, allergic rhinitis, food allergy, and atopic Dermatitis. However, its association with dyshidrotic eczema (DE)—a form of eczema that is related to, but distinct from, atopic Dermatitis with different dermatologic distribution, inciting factors, and treatment options—has not been described. DE is marked by intensely pruritic “tapioca pudding-like” vesicles localized to the hands and feet. It is most common in young adults and can be triggered by stress and exposure to contact allergens such as nickel, including in food.² One hypothesis regarding its pathogenesis describes an increase in type 2 (T2) cytokines and immune cells such as lymphocytes, histiocytes, and eosinophils in the epidermis. Abundance of these cells causes eosinophilic spongiosis, a histological feature of DE inflammation that results in loose packing of epidermal cells and impaired epithelial integrity.³

Here, we present 4 patients with EoE and DE that worsened or resolved concurrently (Table 1). EoE was diagnosed according to consensus guidelines¹ by a gastroenterologist. DE was diagnosed either by a dermatologist or an allergist. While EoE is known to be strongly associated with atopic Dermatitis, to our knowledge, this is the first report of EoE and concurrent DE. None of these patients had a history of atopic Dermatitis, but all had other allergic conditions, such as allergic rhinitis, asthma, and food allergy. All 4 patients described DE lesions on their hands, and 2 patients also noted them on their feet. All patients also noted that their DE flares coincided with worsening dysphagia symptoms. In case 2, exacerbations of both EoE and DE were associated with corn consumption. Corn has been shown to be a trigger in some patients with EoE, and it is not considered to be a high nickel-containing food that could worsen DE.

TABLE 1.

Four Cases Revealing Concurrent Eosinophilic Esophagitis and Dyshidrotic Eczema

Case	Age	Sex	Atopic History	EoE History*	DE Presentation†	Course of Disease
1	34	M	allergic rhinitis	Presenting symptoms: Food impaction requiring esophageal dilation Endoscopies: Initial: >50 eos/hpf After SS ± PPI: >15 eos/hpf After Dupilumab: 0 eos/hpf	Pruritic, firm bumps on the hands and feet, which worsen when his esophageal symptoms are severe.	After 6 months of Dupilumab therapy, the patient achieved deep remission of his EoE and control of his DE. When the patient stopped Dupilumab, his EoE symptoms returned, and he reported associated flares of DE localized to his feet.
2	13	F	allergic rhinitis food allergy	Presenting symptoms: Abdominal pain, chest pain, and coughing with food ingestion. Endoscopies: Initial: >100 eos/hpf After elemental diet: 0 eos/hpf After adding corn: >40 eos/hpf After corn elimination: 5–12 eos/hpf	Pruritic, firm bumps on her fingers and the soles of her feet, which developed 4 years after her EoE diagnosis. Treated with clobetasol.	The patient was found to have multiple food triggers, including milk, wheat, soy, corn, egg, fish, nuts, and melon. Initiation of an elemental formula diet in 2018 led to histologic remission of EoE and remission of the patient's reported eczema. A corn reintroduction trial led to increased disease activity with endoscopy indicating high levels of esophageal eosinophils (>40 eos/hpf). At the same time, the patient also developed a pruritic rash on her fingers and the soles of her feet consistent with that of DE. Steroid ointment and re-elimination of corn from her diet improved dermatological symptoms and endoscopy indicated significantly reduced eosinophil levels (5–12 eos/hpf).
3	41	M	asthma allergic rhinitis food allergy	Presenting symptoms: Dysphagia Endoscopies: Initial: >15 eos/hpf After SS: 0 eos/hpf After stopping SS: >50 eos/hpf, esophageal tear	Blisters and cracking of the skin around his cuticles, which occurred around the time that he was initially diagnosed with EoE. Treated with clobetasol.	The patient initially presented with concomitant DE and EoE. He experienced clinical improvement in his EoE and DE when avoiding barley and rye. The patient reported DE flares on the intertriginous areas of his fingers, specifically on the right hand and nail beds, which he reports coincided with his most severe EoE symptoms.
4	14	F	asthma allergic rhinitis	Presenting symptoms: Recurrent dysphagia Endoscopies: Initial: >90 eos/hpf After high-dose PPI: >50 eos/hpf	Eczema characterized as dry bumps between the fingers bilaterally	Patient attempted high-dose PPI and although it improved her symptoms, she did not achieve histologic remission. Throughout the COVID-19 pandemic, the patient discontinued treatment and reported moderate episodes of dysphagia with concurrent eczema exacerbations.

^* All patients diagnosed with EoE by a gastroenterologist according to consensus guidelines.

^† Patients 2 and 3 were diagnosed with DE by a dermatologist, patients 1 and 4 by an allergist.

DE, dyshidrotic eczema; EoE, eosinophilic esophagitis; PPI, proton pump inhibitor; SS, swallowed steroids.

It is interesting to note that Dupilumab, an anti-IL4/IL13 monoclonal antibody, resolved disease activity of both EoE and DE in case 1. A previously reported case series described significant reduction of DE symptoms upon treatment with Dupilumab.⁴ It is thought that this could be due to blocking IL-13, which is known to downregulate tight junctions, leading to reduced epithelial integrity.⁵ These findings suggest that the pathophysiology of DE may involve a similar T2 inflammatory response as EoE.

This letter suggests that DE may be a skin manifestation of systemic EoE inflammation, and/or that both conditions are driven by a similar underlying pathophysiology of T2 inflammation and epithelial barrier dysfunction. This letter is limited in that it describes a small number of patients seen at a tertiary medical center, temporality of EoE and DE was not established in all patients, and not all patients were followed by Dermatology. Regardless, these findings suggest a novel association between EoE and DE, and further prospective investigation confirming this observation is warranted.