Christopher Mill

Development of anaphylactic cow's milk allergy following cow's milk elimination for eosinophilic esophagitis in a teenager

IgE-mediated cow’s milk allergy (CMA) is one of the most common food allergies in childhood. It presents in infancy and is outgrown by about 50% at age 5 years, and 75% by teenage years. Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease that affects the esophagus. The disease can cause significant morbidity due to symptoms and long-term complications. Management of EoE involves either medical (swallowed topical corticosteroids) or dietary interventions. Swallowed corticosteroids have been shown to reduce symptoms and eosinophilic inflammation in patients, but there is cause for concern because the effect ceases with discontinuation of the medication and there are concerns such as adrenal suppression with their long-term use. Cow’s milk is the most commonly implicated food trigger in EoE. Elimination of milk has been shown to have a positive response in about 65% of patients with EoE. It is common practice to recommend milk elimination in patients with EoE, particularly when the family prefers a dietary intervention. Single food elimination may require only 1 additional endoscopy after diagnosis for evaluation, and allows for more dietary freedom when compared with multiple food elimination. Although many children with EoE have experienced benefits after eliminating cow’s milk, one of the hypothesized but not yet well-characterized consequences is the development of IgEmediated milk allergy brought upon by milk avoidance. Only 2 such cases have been reported in the literature: 1 in Toronto and 1 in Philadelphia. Both cases were of young children with previously negative skin prick test (SPT) results who consumed milk regularly before its elimination for EoE. Upon accidental reexposure to milk after 1 and 2.5 years of strict milk elimination, respectively, these 2 cases experienced convincing symptoms of IgE-mediated allergic reaction, and subsequently demonstrated positive SPT result to milk. Other circumstances in which dietary interventions have led to unintended consequences include the development of IgE-mediated food allergy subsequent to foods withheld for food proteineinduced enterocolitis syndrome, recurrence of IgE-mediated food allergy after passing oral food challenges but subsequent food avoidance, and development of EoE with oral immunotherapy for IgE-mediated food allergy. We describe a young lady with a history of atopic dermatitis (outgrown at age 3 years), moderate persistent asthma, and seasonal allergic rhinitis who was diagnosed with EoE at the age of 15 years. Her symptoms leading up to diagnosis were vomiting, food regurgitation, and weight loss. Her upper endoscopy demonstrated increased counts of 24 eosinophils/hpf proximally, 2 mid and 100 distally (Note: diagnosis of EoE if >15 eosinophils/hpf in 1 or more biopsy specimens) while on a trial of proton pump inhibitor. Postdiagnosis in discussion with the family and the patient, they opted for the strict elimination of cow’s milk as a treatment for her EoE. She had presumed IgE-mediated CMA at age 9 months (history of immediate flushing and sneezing), which was outgrown at age 3 years. SPT results were unavailable. She had been consuming and tolerating milk products without any reactions since age 3 years and otherwise did not have any food allergies. Before elimination for EoE, the patient had a positive SPT result to milk (wheal 9 mm), but it was interpreted as a clinically irrelevant result given that she had been tolerating milk in full servings regularly without immediate reactions since age 3 years. However, after strictly avoiding cow’s milk/dairy for 4 months, she experienced 4 IgE-mediated allergic reactions in the same month—1 reaction with impressive lip swelling and 3 reactions with severe vomiting/shortness of breath/lightheadedness—with symptoms beginning 20 to 30 minutes after accidental consumption of milk products. The first reaction occurred after eating a piece of pizza, the second after eating Thanksgiving dinner with several foods containing butter, and the third and fourth occurred after eating meatballs with ricotta cheese. No treatment was given for any of these reactions, and the symptoms resolved within 3 hours. At the follow-up visit, SPT to milk was repeated and the wheal was shown to be 10 mm 6 mm (clinical cutoff, wheal <3 mm). Cow’s milk specific IgE returned at 8.99 kU/L (clinical cutoff, <0.35 kU/L). The patient was told to strictly avoid milk and prescribed an epinephrine autoinjector to treat future accidental exposure to milk products. This case of development of anaphylactic CMA following its elimination for EoE is unique for several reasons:

Impact of supervised epinephrine autoinjector administration during food challenges on parent confidence

the background of numerous plasma cells and foamy histiocytes. Lipid laden vacuoles were also seen (Fig 1F). Thus, a diagnosis of xanthogranulomatous lesion was made. Immunohistochemistry revealed positivity for CD3, CD20, CD68 (histiocyte specific), CD138, and CD134 (blood vessel specific). CD1a, CD30, CD15, and Latent Membrane Protein were negative. Liver and renal function tests results were within normal limits. Enzyme-linked immunosorbent assay results for human immunodeficiency virus, hepatitis B surface antigen, hepatitis C antigen were negative. A diagnostic endoscopy of the nasal cavity was normal. Positron emission tomography confirmed the absence of any systemic involvement. The patient was diagnosed as having adult-onset asthma and periocular xanthogranuloma (AAPOX). He was prescribed oral prednisolone, 1 mg/kg per day, and advised slow taper for a 3month period. He was also prescribed prism glasses to alleviate his double vision. A telephone conversation 45 months later revealed that he is continuing to take low-dose oral steroids (10 mg/d) under the care of a local physician and is symptom free (Fig 1G). The patient has been advised to undergo regular systemic evaluation. Xanthogranulomatous diseases are a group of noneLangerhans cell histiocytosis characterized histopathologically by the presence of Touton giant cells, lymphocytes, plasma cells, and histiocytes. Areas of fibrosis or necrosis may also be seen.1 It may involve the orbit and the adnexa in the following forms: (1) adult-onset xanthogranuloma, (2) AAPOX, (3) necrobiotic xanthogranuloma, or (4) Erdheim-Chester disease. Diseases with predominantly xanthomatized histiocytes form a major part of the non-Langerhan histiocytosis and are of unknown origina.2 Histopathologic and immunohistochemical analysis along with systemic investigations are imperative for accurate diagnosis.1 AAPOX is associated with late-onset asthma with bilateral anterior orbital or preseptal lesions (the overlying skin typically displaying a yellowish tint). Simultaneous involvement of conjunctiva along with the skin and orbit has also been reported.3 Associated lymphadenopathy and paraproteinemia indicate an underlying disorder of B-cell proliferation. Our patient did not have any systemic involvement. Because of the rarity of this disease, the management guidelines are not yet well defined. It is mandatory to perform a thorough search for systemic involvement and to rule out Erdheim-Chester disease, which involves multiple organs and has a devastating course and response to treatment. Fluorodeoxyglucose positron emission tomography and computed tomography are useful as an initial investigation and as a follow-up tool.4 Treatment options for AAPOX comprise systemic steroids, immunosuppressants, and surgery. When the lesions are confined to the anterior orbit, surgery or debulking alone has been successful in a few cases.1,2,5e8 Intralesional steroid injections may be useful in isolated preseptal or anterior orbital involvement but come with the inherent risk of central retinal artery occlusion, ophthalmic artery occlusion, glaucoma, eyelid necrosis, and subcutaneous fat atrophy.9 Systemic steroids are