Dr. Venumadhav, Dr.Bhanu vikraman, Dr. C. Jayakumar
Department of Pediatrics, Amrita Institute of Medical Sciences
Introduction
Nine year-old male child presented with difficulty swallowing food and intermittent episodes of abdominal pain and vomiting of 2 months duration. Parents noticed that child eats in small quantities and lubricates with water after each bite. He had a significant weight loss of 3 kgs over the same period
He is developmentally normal and immunised for age.He has a history of Atopy and Allergic rhinitis.
Examination and Investigations:
On examination child was thin built. Blood investigations showed normal counts with peripheral eosinophilia. (TC-9100, N52,L-37,E-11, Hb-13.2, Plt-372) and normal inflammatory markers (CRP-2)
USG Abdomen done was normal. Endoscopy done showed concentric rings, erosions, furrows, edema and superficial white exudates.
Above pictures showing superficial white exudates and concentric rings, erosions.
Differential Diagnosis
GERD,
Pill Oesophagitis(Medication induced mucosal injury) ,
Infection,
Hypereosinophillic syndrome,
Eoisinophillic esophagitis,
Crohns.
Treatment and outcome
Histopathology done showed thickened mucosa with basal cell hyperplasia, Papillary elongation, dilated intercellular spaces, eosinophillic surface layering and eosinophillic microabscesses (>15 intraepithelialEosinophills/hpf)
USG Abdomen done was normal, Colonoscopy done was normal.
Fecal calprotectin was within normal limits.
Based on clinical , Endoscopic and histopathological findings, a diagnosis of eosiophillic esophagitis was made.
He was started on proton pump inhibitors (Tab Pantoprozole 1mg/kg) ,Topical steroids (oral budesonide respules(1mg/day), Fluticasone MDI(440mcg/day). He was started on two food elimination diet(Milk +Wheat).
Repeat endoscopy performed after 6 weeks demonstrated improvement in the mucosal lesions, indicating a positive response to treatment. Treatment was continued for a period of 8 weeks.
Treatment strategy followed is as per above protocol.
DISCUSSION:
Eosinophillic esophagitis is a chronic immune or Antigen-mediated process.
Clinically, it presents with various esophageal dysfunction
Pathologically, there is mucosal inflammation predominantly with eosinophils, which is confined to the esophagus only.
Gene responsible for EoE was TSLP (thymic stromal lymphopoietin) which is located in the 5q22 region of male X chromosome. TSLP stimulates Th2 cells and induces eotaxin-3. The stimulated Th2 cells activate various proinflammatory cytokines such as IL5, IL13, and IL15, which recruit eosinophils. Eotaxin-3 is overexpressed in the esophageal mucosa in EoE patients. Overall, this immunogenic process starts as an allergic response to various environmental antigens, food, or aeroallergens and leads to the inflammation of esophageal mucosa. TGF-B is responsible for remodeling of esophageal mucosa and smooth muscle dysfunction.
Pediatric patients can present with dysphagia, nausea, vomiting, food intolerance, abdominal pain, and weight loss. A history of various atopic conditions such as asthma, atopic dermatitis, seasonal allergy, food allergy, allergic rhinitis, and eczema may be present as well.
Histopathology reveals extensive eosinophils infiltrated esophageal mucosa, in addition to mast cells, basophils, basal cell hyperplasia, elongated papillae, superficial layering of eosinophils, extracellular eosinophilic granules, and fibrosis of sub-epithelium.
Patients with a history of atopy to food generally respond well to dietary therapy. The approach to dietary therapy is to avoid the specific food if present. If no specific allergenic food or agent is present, a trial of the six food elimination diet (SFED) can be pursued. The six most common allergenic food that should be avoided in EoE patients are cow’s milk, wheat, peanut/tree nut, egg, soy, and seafood/shellfish.
In patients diagnosed with EoE, trial of PPI 20 mg to 40 mg oral daily or twice daily as a first line therapy for 8weeks . Those who respond to PPI therapy with symptomatic improvement, endoscopy with esophageal biopsy should be repeated. If no eosinophils present in repeat biopsy, the diagnosis is either acid mediated GERD with eosinophilia or non GERD PPI responsive EoE with unknown mechanism. If both symptoms and eosinophils persists after treatment with PPI, the diagnosis is immune mediated EoE. In case of immune mediated EoE, the American College of Gastroenterology (ACG) highly recommend to use topical (swallowed not inhaled) steroids for total 8 weeks.
Newer methods of diagnosis:
Esophageal String Test- capsule technology-Gets esophageal secretions & Eosinophilic granule proteins & Cytokines
Trans-nasal Endoscopy: Can get biopsy
FLIP {Functional Luminal Imaging Probe} : Measure Esophageal Distensibility and Compliance
Newer methods of treatment:
1)Dopilumab:Recombinant Monoclonal IgG4 antibody targeting the a chain of the IL-4 receptor( IL-4Ra), Blocks IL4 and IL13.
2) Anti-IgE = Omalizumab (Subcutaneous injection)
3)Anti CRTH2- {Chemoattractant receptor-homologous molecule on Th2 cells) (CRTH2)}= OC000459 (Oral tablets)
4)Anti-Transforming growth factor b1 (TGF-b1)
Take home messageIn children with solid food dysphagia and a background of atopy, maintaining a high index of suspicion for Eosinophilic esophagitis is crucial for prompt diagnosis and effective management