Modeling Symptom Severity and Estimated Gluten Ingestion in Celiac Disease Patients on a Gluten-Free Diet

Jack A. Syage^1, and Philip T. Lavin²

¹ImmunogenX, Newport Beach, CA, United States

²Boston Biostatistics Research Foundation, Framingham, MA, United States

Cite this paper:
Jack A. Syage and Philip T. Lavin. Modeling Symptom Severity and Estimated Gluten Ingestion in Celiac Disease Patients on a Gluten-Free Diet. International Journal of Celiac Disease. 2020; 8(3):85-89. doi: 10.12691/ijcd-8-3-3

Abstract

Introduction: It is common for celiac disease (CD) patients on a gluten-free diet to accidentally consume gluten that can cause symptomatic distress and histologic damage. We present an algorithm to relate the quantity of gluten intake to the severity of episodic symptoms for abdominal pain, bloating and tiredness in CD patients. Methods: This analysis employs a model based on data from the CeliAction study for latiglutenase (ALV003-1221; NCT01917630). A previously estimated average daily quantity of gluten consumed by these trial patients along with the data for frequency and severity of the symptoms for abdominal pain, bloating, and tiredness allowed us to estimate the relationship between episodic inadvertent gluten ingestion and symptom severity. Results: The CD trial patients were previously estimated to consume a mean of 354 mg/day. From the study data, these patients experienced at least one symptom (of six possible) almost every day (6.13/week) and on average experienced 2-3 different symptoms per symptom event. The most common severity (on a 1-5 scale) was 2 for abdominal pain and 3 for bloating and tiredness corresponding to 1.1, 0.9, and 0.7 g gluten consumed per event. The frequency that a severe symptom (4 or 5) occurs during a symptomatic event equates to about 10%, 27%, and 33% for abdominal pain, bloating, and tiredness and correlates to 2.1, 1.2, and 1.0 g gluten consumed per event, respectively. Conclusions: This model suggests that the quantity of ingested gluten varies per event type and likely includes periodic gluten exposures of substantial quantity.

Keywords:
celiac disease gluten gastrointestinal symptoms

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References:

[1]	Catassi C, Fabiani E, Iacono G et al. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am Soc Clin Nutr. 2007; 85: 160-166.
[2]	Syage JA, Kelly CP, Dickason MA, Cebolla Ramirez A, Leon F, Dominguez R, Sealey-Voyksner JA. Determination of gluten consumption in celiac disease patients on a gluten-free diet. Am J Clin Nutr.2018; 107: 201-207.
[3]	Hoppe C, Gøbel R, Kristensen M, Lind MV, Matthiessen J, Christensen T, Trolle E, Fagt S, Madsen ML, Husby S. Intake and sources of gluten in 20- to 75-year-old Danish adults: a national dietary survey. Eur J Nutr.2017; 56: 107-117.
[4]	Murray JA, Kelly CP, Green P HR et al. No Difference Between Latiglutenase and Placebo in Reducing Villous Atrophy or Improving Symptoms in Patients with Symptomatic Celiac Disease, Gastroenterology.2017; 152: 787-798.
[5]	Syage JA, Murray JA, Green PHR, Khosla C. Latiglutenase improves symptoms in seropositive celiac disease patients while on a gluten-free diet. Dig Dis Sci.2017;62:2428-2432.
[6]	Syage JA, Green PHR, Khosla C, Adelman DC, Sealey-Voyksner JA, Murray JA. Latiglutenase Treatment for Celiac Disease: Symptom and Quality of Life Improvement for Seropositive Patients on a Gluten-Free Diet. GastroHep. 2019; 1: 293-301.
[7]	Leffler DA, Acaster S, Gallop K, Adelman DC. A Novel Patient-Derived Conceptual Model of the Impact of Celiac Disease in Adults: Implications for Patient-Reported Outcome and Health-Related Quality-of-Life Instrument Development. Value in Health. 2017; 20: 637-643.
[8]	Hindryckx P, Leveseque BG, Holvoet T et al.Disease activity indices in celiac disease: systematic review and recommendations for clinical trials, Gut. 2018; 67: 61-69.
[9]	Comino I, Real A, Vivas S, Síglez MÁ, Caminero A, Nistal E, Casqueiro J, Rodríguez-Herrera A, Cebolla A, Sousa C. Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in stool. Am J Clin Nutr. 2012; 95: 670-7.
[10]	Comino I, Fernandez-Banares F, Esteve M, Ortigosa L,Castillejo G, Fambuena B, Ribes-Koninckx C, Sierra C, Rodriguez-Herrara A, Salazar JC, et al. Fecal gluten peptides reveal limitations of serological tests and food questionnaires for monitoring gluten-free diet in celiac disease patients. Am J Gastroenterol. 2016; 111: 1456-1465.
[11]	Moreno ML, Cebolla A, Munoz-Suano A, Carrillo-Carrion C, Comino I, Pizarro A, Leon F, Rodriguez-Herrera A, Sousa C.Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing. Gut. 2017; 66: 250-257.
[12]	Lähdeaho ML, Kaukinen K, Laurila K, Vuotikka P, Koivurova OP, Kärjä-Lahdensuu T, Marcantonio A, Adelman DC, Mäki M. Glutenase ALV003 Attenuates Gluten-Induced Mucosal Injury in Patients With Celiac Disease. Gastroenterology. 2014; 146: 1649-1658.
[13]	Kelly CP, Green PHR, Murray JA, DiMarino A, Colatrella A, Leffler DA, et al. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther. 2013; 37: 252-262.
[14]	Brar P, Kwon GY, Egbuna II, Holleran S, Ramakrishnan R, Bhagat G, Green PHR. Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease. Dig Liver Dis. 2006; 39: 26-29.
[15]	Mahadev S, Murray J.A. Wu T-T, Chandan VS, Torbenson MS, et. al. Factors associated with villus atrophy in symptomatic coeliac disease patients on a gluten-free diet. Aliment Pharmacol Ther. 2017; 45: 1084-1093.
[16]	Sainsbury A, Sanders DS, Ford AC. Prevalence of irritable bowel syndrome-type symptoms in patients with celiac disease: a meta-analysis. Clinical Gastroenterology and Hepatology. 2013; 11: 359-365.