Differential diagnosis and management of enteropathies found in the context of seronegative villous atrophy (VA) are still a clinical challenge. Although seronegative coeliac disease may be the most frequent cause of serology-negative VA, other conditions must be taken into account in the differential diagnosis of seronegative VA. The rarity of these enteropathies with frequent overlapping of histological features may result in misclassification of such patients as affected by a seronegative or a refractory form of coeliac disease with consequent inappropriate treatments and long-term morbidity. The aim of this review is to summarize the current knowledge and to provide an evidence base and practical algorithmic approach for the investigation and management of seronegative VA.
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