A 7-year-old male child with a normal birth history presented with chronic regurgitation and non-bloody, non-bilious emesis on breastmilk since birth. Symptoms were unrelieved by the Proton Pump Inhibitor (PPI) Lansoprazole, the trial of different formulae as well as maternal dietary restrictions. Differentials like pyloric stenosis and malrotation were ruled out by ultrasonography and upper GI series. He had no weight loss, diarrhoea, oliguria or respiratory distress. Family history was significant for mild intermittent asthma in his mother and seasonal allergies in both parents. His 4-year-old sister had allergic colitis since the first year of her life and suffered from poor weight gain until 3 years of age. At 7 months of age, the patient developed poor weight, requiring nutritional supplementation and occupational therapy for feeding. Over time, he developed atopy with multiple food allergies, a chronic maculopapular rash, and congestion, for which multiple dietary changes were advised with no clinical improvement. He required two hospitalisations due to Failure to Thrive (FTT) and dehydration. His Gastroesophageal Reflux Disease (GERD) with emesis had progressively worsened with age, and he developed a chronic nocturnal dry cough, which was not relieved with PPIs; hence, he was referred to our centre at 12 months of age for further evaluation. A Modified Barium Swallow study was normal, determining normal swallowing. Skin prick testing was performed using a standardised paediatric food and aeroallergen panel including milk, egg, wheat, soy, peanut, tree nuts, dust mite, pollens and moulds. Serum-specific IgE testing was conducted for corresponding food allergens. Patch testing was performed using a standardised food allergen series. These revealed allergies to eggs, milk and penicillin. Molecular allergen diagnostics were not utilised. He was diagnosed as well with Allergic Rhinitis and Atopic dermatitis, partially responsive to topical steroids and oral antihistamines. Initially, we started him on a diet restricting milk and eggs and counselled parents about food avoidances, label reading, cross-contamination, food allergy resources and anaphylactic symptoms. Considering his family history of asthma, atopy and his cough, he started Albuterol as needed, which was found to be effective. Given his GERD symptoms, the PPI was continued, and he was also given antihistamines. At 13 months of age, he presented to the Emergency department (ED) with an acute febrile illness and a maculopapular rash with hypoglycemia to 30 mg/dL and dehydration, where he was managed symptomatically. At 14 months, while admitted to our hospital due to a 2-day febrile illness and Upper respiratory tract infection (URI) symptoms he again had hypoglycemia to 66 mg/dL. He had an extensive workup over the course of two hospital admissions for his severe and prolonged hypoglycemia episodes and noted delayed linear growth velocity. Evaluation revealed Growth Hormone (GH) deficiency with a low Insulin like Growth Factor-1 (IGF-1) and a normal cortisol response. He was started on GH infusions after a normal Brain Magnetic Resonance Imaging (MRI). Genetic work-up showed long-chain fatty acid deficiency, and was managed with cornstarch supplementation. At 16 months, his cough became productive with nighttime awakenings and unresponsive to inhaled corticosteroids. A sweat chloride test ordered was normal, ruling out Cystic Fibrosis. Bronchoscopy with bronchoalveolar lavage and an upper endoscopy were performed. Results revealed Tracheomalacia and Oesophageal Eosinophilia (30 eos/hpf mid, 20 eos/hpf distal oesophagus) consistent with possible Eosinophilic oesophagitis (EoE) but since the patient had stopped PPIs at the time of his scopes, GERD as the cause of his findings could not be ruled out. Celiac and infectious workup was negative. A pH probe showed normal results, making reflux a less likely cause of his symptoms. Given that asthma is a common cause of chronic cough and considering the patient's history of atopy, Fluticasone and Salmeterol inhaled combination therapy were started and he was continued on antihistamines. PPIs were also restarted due to the presence of vomiting, with strict dietary restrictions, and he was closely followed. At 22 months, he presented with chest congestion and exercise intolerance and was treated with oral steroids. A follow-up endoscopy confirmed eosinophilic oesophagitis, with 14 eosinophils/hpf in the mid and 30 eosinophils/hpf in the distal oesophagus, accompanied by reactive changes (Figures 1 and 2). Dietary elimination initially targeted foods with documented sensitisation (milk and egg), with empirical addition of peanuts and tree nuts due to persistent symptoms and high allergenic potential. A stepwise approach was chosen over a Four-food elimination diet given the patient's young age, nutritional vulnerability and prior restrictive diets, and he was also started on oral viscous budesonide 1 mg swallowed daily with continued PPIs. After 3 months of Budesonide, dietary restrictions, PPI and antihistamine therapy in addition to his fluticasone/salmeterol inhaled therapy, he attained histological remission of his EoE in a repeat upper gastroendoscopy. After this, Budesonide was decreased to 0.5 mg daily along with continued PPI, and he maintained his histological remission. Peripheral blood eosinophil counts were monitored serially, with an initial elevation of 768 cells/UI. decreasing to 450–400 cells/UI in correlation with treatment response, and subsequently remaining within the normal range. Overall, his asthma symptoms improved in parallel with EoE control. At 6 years, due to persistent allergic rhinitis and eczema requiring intermittent steroids, therapy was transitioned to Dupilumab (200 mg biweekly) with continued PPI use. Follow up endoscopy 4 months later showed EoE in continued remission. Now aged 7 years old, the child remains asymptomatic, with well-controlled asthma, atopy and EoE on Dupilumab, inhaled budesonide/formoterol and antihistamines, with normal growth and nutrition. He has also been gaining weight without GI symptoms despite stopping use of PPI. He has been evaluated for nutritional deficiencies, renal function, osteopenia and Clostridium difficile, and results were normal. To aid interpretation of the complex clinical data, Table 1 summarises the treatment interventions and corresponding responses. 20 eos/hpf in the distal oesophagus with reactive changes Start of oral viscous budesonide 1 mg daily, continued omeprazole 20 mg once daily, and removed milk, eggs, peanuts and tree nuts from diet 30 eos/hpf in the distal oesophagus with reactive changes Oral viscous budesonide 1 mg once daily 0 eos/hpf in the distal oesophagus with reactive changes 12 eos/hpf in the distal oesophagus with reactive changes 2 eos/hpf in the mid oesophagus Oral viscous budesonide 0.5 mg once daily Asthma control test score 27 (consistent with well-controlled asthma per parent/patient assessment) 9 eos/hpf in the distal oesophagus IN HISTOLOGICAL REMISSION 0 eos/hpf in the mid oesophagus 15 eosinophils per high-power field) and located in the middle or proximal oesophagus as well 8. Most importantly, many patients with EoE have a history of atopy or peripheral eosinophilia and are more likely to fail to respond to antireflux treatment 8. Given the child was already on other treatment modalities, Dupilumab was initiated at a biweekly dose with a plan for escalation to weekly dosing if the response was inadequate. Given the patient's favourable and sustained clinical and histological response, dose escalation was not required. The clinical trajectory of our patient improved substantially after a targeted approach for EoE was initiated with dietary elimination, PPIs, topical steroids, and later Dupilumab injections. Currently, the patient continues limited avoidance of previously identified trigger foods while tolerating a broader diet without gastrointestinal symptoms. This case highlights the importance of considering EoE in children with atypical or treatment-refractory asthma, and the response in our patient is most likely due to a combined therapeutic effect rather than attributing to a single intervention. These interventions not only stabilised his pulmonary status but also are hopefully preventing complications such as oesophageal remodelling or strictures, feeding aversions and long-term growth delays, in turn improving his quality of life. Our case findings support the growing literature of co-occurrence of EoE and Asthma, by documenting clinical and histological improvements in both EoE and Asthma symptoms following specific EoE targeted therapy 9-11. The delay in diagnosis complements similar challenges seen in other reports, where EoE remained undiagnosed until endoscopic evaluation was performed. It also supports the theory that EoE is not merely a gastrointestinal disease but a systemic allergic disorder with long term complications, emphasising that asthma is controlled not just with inhalations but also with treatment of underlying oesophageal inflammation. We advocate for early gastroendoscopic in addition to a bronchoscopic evaluation in children with difficult to control asthma, particularly when accompanied by GI symptoms or atopy, and for a multidisciplinary approach involving gastroenterology, pulmonology, allergy-immunology and nutrition. Sameena Tabassum: conceptualisation of research idea, data collection, review of literature, writing – original draft, supervision, synthesis of inferences and recommendations. Keslar Just: review of literature, data collection, writing – original draft, synthesis of inferences and recommendations. Mili Jyotsna: review of literature, writing – original draft, synthesis of inferences and recommendations. Anayansi Lasso-Pirot: conceptualisation of research idea, review of literature, led and supervised the study, writing – review and editing. The authors have nothing to report. The authors have nothing to report. The authors declare that the research presented in this manuscript adheres to the ethical principles outlined by the Institutional Review Board of the University of Maryland School of Medicine. All procedures involving human participants were conducted in accordance with the ethical standards of the University of Maryland of School of Medicine, United States and the Declaration of Helsinki (1964), as revised in 2013. Informed consent was taken from the patient's guardians. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Tabassum et al. (Fri,) studied this question.