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Ongoing symptoms in treated celiac disease (CD) are frequent and are commonly thought of as being due to infractions to a gluten-free diet (GFD) or complications.To study the etiology and natural history of clinically relevant events (CREs) throughout follow-up and identify predictors thereof to guide follow-up.CREs (symptoms/signs requiring diagnostic/therapeutic interventions) occurring in celiac patients between January-2000 and May-2021 were retrospectively collected between June and September 2021 and analysed.One-hundred-and-eighty-nine adult patients (133 F, age at diagnosis 36 ± 13 years, median follow-up 103 months, IQR 54-156) were enrolled. CREs were very common (88/189, 47%), but hardly due to poor GFD adherence (4%) or complications (2%). Interestingly, leading etiologies were functional gastrointestinal disorders (30%), reflux disease (18%) and micronutrient deficiencies (10%). Age at diagnosis ≥ 45 years (HR 1.68, 95%CI 1.05-2.69, p = 0.03) and classical pattern of CD (HR 1.63, 95%CI 1.04-2.54, p = 0.03) were predictors of CREs on a multivariable Cox model. At 5 years, 46% of classical patients ≥ 45 years old at diagnosis were event-free, while this was 62% for non-classical/silent ≥ 45 years, 60% for classical 45 years, and 80% for non-classical/silent 45 years.CREs occurred in almost half of CD patients during follow-up, with functional disorders being very common. New follow-up strategies for adult CD may be developed based on age and clinical pattern at diagnosis.

ObjectiveThe differential diagnosis and management of seronegative enteropathies is challenging due to the rarity of these conditions, the overlap of clinical and histopathological features and the current lack of an international consensus on their nomenclature.DesignThis is a narrative review providing pragmatic guide on the investigation and clinical management of seronegative enteropathies in adults based on the available literature and our clinical experience.ConclusionsSeronegative coeliac disease is the most frequent cause among the heterogeneous group of seronegative enteropathies and its diagnosis is confirmed by the clinical and histological response to a gluten-free diet after the exclusion of other causes of villous atrophy. Correct identification and targeted management of seronegative enteropathies is mandatory because of the variation in terms of clinical outcomes and prognosis.