Outcomes and factors associated with tolerance in infants with non-IgE-mediated cow's milk allergy with gastrointestinal manifestations

Abstract Objectives To evaluate outcomes of oral food challenge (OFC) test to assess tolerance in infants with non-IgE-mediated cow's milk allergy (CMA) with gastrointestinal manifestations and explore clinical data predictive of these outcomes. Methods Single-center retrospective study including infants (age < 12 months) who were referred for CMA between 2000 and 2018 and underwent OFC on follow-up. A univariate logistic regression test was performed to evaluate variables associated with the outcomes of the follow-up OFC test. Results Eighty-two patients were included, 50% were male. Eighteen patients had a positive OFC test (22%). Most patients had presented with hematochezia (77%). The median age of symptom onset was 30 days. Two-thirds of the patients were on appropriate infant formula (extensively hydrolyzed or amino acid-based formula), exclusively or in association with breastfeeding. The median time on an elimination diet before the OFC test was 8 months (Q1 6 - Q3 11 months). All cases with positive follow-up OFC tests (n= 18) had been exposed to cow's milk-based formula before the first clinical manifestation of CMA. Five out of eight cases with Food Protein-Induced Enterocolitis Syndrome (FPIES) had positive OFC tests. Exposure to cow's milk-based formula before diagnosis, a history of other food allergies, hematochezia and diarrhea were predictors of a positive OFC test. Conclusions In infants with non-IgE-mediated CMPA with gastrointestinal manifestations, the use of cow's milk-based formula, a history of other food allergies, and hematochezia and diarrhea upon initial presentation were associated factors for the later achievement of tolerance.

Colelitíase sintomática como apresentação de colangite esclerosante primária na infância - série de casos e revisão de literatura / Symptomatic cholelithiasis as the presentation of pediatric primary sclerosing cholangitis - case series and literature review

ABSTRACT BACKGROUND: Primary sclerosing cholangitis (PSC) is a rare hepatobiliary disorder, whose etiology remains not fully elucidated. Given how rare PSC is in childhood, until the recent publication of a multicenter international collaboration, even data on its characteristics and natural history were scarce. Symptomatic cholelithiasis has not been previously reported as the presentation of PSC. OBJECTIVE: The aim of this study was the diagnosis of PSC following the initial unusual presentation with symptomatic cholelithiasis, that followed an atypical clinical course that could not be explained by cholelithiasis alone. A literature review was also conducted. METHODS: We conducted a retrospective chart review of three patients, who were diagnosed and/or followed at the Clinics Hospital, University of Campinas - Sao Paulo/ Brazil, between 2014 and 2020. Data analyzed included gender, age of presentation, past medical history, imaging findings, laboratory results, endoscopic evaluation, response to medical therapy and follow-up. RESULTS: Age at time of presentation with cholelithiasis varied from 10 to 12 years. In two of the cases reported, a more subacute onset of symptoms preceded the episode of cholelithiasis. Two patients were managed with cholecystectomy, not followed by any surgical complications, one patient was managed conservatively. Percutaneous liver biopsy was performed in all three cases, showing histological findings compatible with PSC. Associated inflammatory bowel disease (IBD) was not seen in any of the patients. The patients have been followed for a mean time of 3.4 years. CONCLUSION: PSC and cholelithiasis are both rare in the pediatric population. This study reports on symptomatic cholelithiasis as a presentation of PSC and raises the importance of suspecting an underlying hepatobiliary disorder in children with cholelithiasis without any known predisposing factors and/or that follow an atypical clinical course for cholelithiasis alone.

RESUMO CONTEXTO: A colangite esclerosante primária (CEP) é uma doença hepatobiliar rara, cuja etiologia ainda não está totalmente elucidada. Dada a raridade do CEP na infância, até a recente publicação de uma colaboração multicêntrica internacional, mesmo dados sobre suas características e história natural eram escassos. A colelitíase sintomática não foi relatada anteriormente como a apresentação inicial de CEP na infância. OBJETIVO: O objetivo deste estudo foi o diagnóstico de CEP após a apresentação inicial incomum com colelitíase sintomática, que seguiu um curso clínico atípico que não poderia ser explicado apenas pela colelitíase. Também foi realizada uma revisão da literatura. MÉTODOS: Foi realizada uma revisão retrospectiva dos prontuários de três pacientes, que foram diagnosticados e/ou acompanhados no Hospital das Clínicas da Universidade Estadual de Campinas - São Paulo / Brasil, entre 2014 e 2020. Os dados analisados incluíram sexo, idade de apresentação, história médica pregressa, achados de imagem, resultados laboratoriais, avaliação endoscópica, resposta à terapia médica e acompanhamento. RESULTADOS: A idade no momento da apresentação da colelitíase variou de 10 a 12 anos. Em dois dos casos relatados, um início mais subagudo dos sintomas precedeu o episódio de colelitíase. Dois pacientes foram tratados com colecistectomia, não seguida de qualquer complicação cirúrgica, e um paciente foi tratado de forma conservadora. Biópsia hepática percutânea foi realizada em todos os três casos, mostrando achados histológicos compatíveis com CEP. Doença inflamatória intestinal associada não foi observada em nenhum dos pacientes. Os pacientes foram acompanhados por um tempo médio de 3,4 anos. CONCLUSÃO: CEP e colelitíase são raras na população pediátrica. Este estudo relata a colelitíase sintomática como uma apresentação de CEP e levanta a importância da suspeita de doença hepatobiliar subjacente em crianças com colelitíase sem quaisquer fatores predisponentes conhecidos e/ou que seguem um curso clínico atípico.