Gluten-related disorders: From celiac disease diagnosis to other gluten sensitivity

Abstract Celiac disease is a prevalent immune-mediated enteropathy that leads to significant morbidity due to malabsorption, micronutrient deficiencies, and heightened malignancy risk. The objective of this study is to synthesise current diagnostic practices and emerging approaches, encompassing clinical, serological, histological, and genetic tools for detecting and managing gluten-related disorders. This literature review is based on peer-reviewed publications and clinical guidelines from the past two decades, highlighting foundational practices and novel insights into serological testing, biopsy protocols, and HLA-DQ genotyping. The results demonstrate that immunoglobulin (Ig) A anti-tissue transglutaminase remains the primary screening modality for individuals over 2 years of age, due to its high sensitivity and specificity, while IgG-based assays are essential for those with IgA deficiency or equivocal presentations. Endoscopic duodenal biopsy confirms villous atrophy, crypt hyperplasia, and lymphocytic infiltration, although patchy lesions necessitate multiple sampling sites. Advances in HLA-DQ2/DQ8 testing further refine diagnostic certainty, particularly in atypical or equivocal cases, with strong negative predictive value helping rule out celiac disease. Both non-celiac gluten sensitivity and wheat allergy frequently exhibit a similar spectrum of symptoms; however, the methods employed to diagnose these conditions diverge considerably. For instance, in the case of wheat allergy, clinicians often rely on procedures such as quantifying IgE concentrations, skin-prick assessments, or analysing other specific immunological markers. Conversely, non-celiac gluten sensitivity is identified using a completely different diagnostic framework. Neurological and dermatological manifestations, such as gluten ataxia or dermatitis herpetiformis, also warrant consideration, underscoring the multifaceted nature of gluten-associated disorders.