Gluten-related Disorders From Bench to Bedside

CD, NCGS, and wheat allergy share some similarities, but exhibit important clinical differences (Table 3). Their multiple possible presentations make diagnosis difficult, and therapy being dietary, without a pharmacologic option, leads to challenges in treatment. When approaching a patient in clinic with gluten-related symptoms, consider the differential diagnosis including CD, NCGS, and wheat allergy. Recall the definitions covered in this narrative review, consider the likelihood of diagnosis given epidemiology, and characterize their clinical phenotype. Perform a proper and guideline-directed evaluation for CD (Figure 2); only after this status is known, implement dietary measures accordingly. Finally, follow these patients clinically for symptomatic improvement, development of complications, concomitant-related conditions, and routine high-quality care.Table 3Comparison of CD and NCGSCDNCGSWheat allergyDescriptionImmune-mediated enteropathyNon-allergic, immune reaction to glutenAllergic, immune-mediatedEpidemiology1%?0.2%PathophysiologyInnate and adaptive immune response to glutenUnclear, innate immune response, increased toll-like receptor expressionIgE-mediated responseSymptom onsetDays to weeksHours to daysMinutes to hoursConsequencesVillous atrophy (decrease in the villous height to crypt depth ratio below the normal range of 3-5:1), increased IELs (>25 IELs per 100 epithelial cells), damage to the small intestine, long-term complicationsNo villous atrophy, may have increased IELs or normal histology in small intestineNo villous atrophy, some cases result in anaphylaxisGluten ingestionRequired to trigger responseLikely required to trigger responseWheat required to trigger allergic responseGeneticsHLA DQ2/DQ8 requiredVariable, no requirementNo requirementDiagnosisSerology and duodenal biopsyEvaluation of response to 6 weeks of GFD and 2 weeks of placebo/gluten challengeaSalerno criteria for research and clinical trials (less helpful in clinical practice).Serum wheat IgE, skin prick testing, evaluation by allergistTreatmentStrict GFDLimiting gluten in diet to tolerated amountEpinephrine pen, avoidanceCD, Celiac disease; GFD, gluten-free diet; HLA, human leukocyte antigen; IELs, intraepithelial lymphocytes; IgE, immunoglobulin E; NCGS, non-celiac gluten sensitivity.a Salerno criteria for research and clinical trials (less helpful in clinical practice). Open table in a new tab