My patient's sibling or parent has celiac disease

**Is the relative a parent, child, or infant?**
Parent/child
Has this relative reduced or eliminated gluten intake for any reason?
No, gluten intake has not been reduced
Is the patient symptomatic?
### No For *asymptomatic* children or adults, screen for celiac disease immediately for adults or beginning at age 3 years for children^[1](#fhir-question-154e033da684832eef8780b02200886f)^, using TTG-IgA antibody and total serum IgA (a value above 20 mg/dl would make this test reliable). Add IgG based testing such as deamidated gliadin IgG for IgA deficient individuals.
**Results of Celiac Disease Screening**
### Positive Celiac Disease Assay A diagnosis of celiac disease must be confirmed by biopsy for asymptomatic first degree relatives of a patient with celiac disease. In the event that biopsy does not confirm celiac disease, while there may be “false positives” due to alternative conditions such as other autoimmunity or infections, the relative is possibly on the cusp of developing celiac disease. In this situation repeat TTG-IgA screening in 6 months and continue to follow until increase prompts reassessment for celiac disease, or until resolution occurs.
### Negative Celiac Disease Assay Perform HLA typing for celiac disease risk genes (HLA DQ2(DQA1\*05:01/05:05 and DQB1\*02:01/02:02), DQ8 (DQA1\*03:01 and DQB1\*03:02), and/or ½ DQ2 (DQA1\*05:01/05:05 or DQB1\*02:01/02:02) at a lab which reports the ½ DQ2 heterodimer. Alternatively this can be performed alongside initial serologic screening to avoid an additional blood draw. Individuals who do not carry a risk gene do not require further celiac disease serological screening. Repeated screening for genetically at-risk children may be conducted approximately every 2-3 years.^[2](#fhir-question-9a07d0cc3fa9e5ae3d6b34e018d666a1),[3](#fhir-question-9231a113a2544f625c3e0970bc3af532)^ Less frequent intervals (approximately every 5 years) may be appropriate for adults.
### YES Children or adults with concerning symptoms (such as gastrointestinal, growth, or nutritional concerns) warrant serologic screening with TTG-IgA antibody and total serum IgA (a value above 20 mg/dl would make this test reliable) at any time alongside assessment for other conditions. For children under age 2 add deamidated gliadin IgG, though a greater likelihood of false negative serologies has been reported in very young children^[1](#fhir-question-154e033da684832eef8780b02200886f),[4](#fhir-question-2bbe3f3e2bd385e5b274173883f2d6fb),[5](#fhir-question-2462a97b2734ca7331ad392530655051)^. If clinical suspicion for celiac disease is high, EGD may be considered despite negative serologies, and especially if IgA deficient. Adults with concerning symptoms should be referred to their provider for comprehensive evaluation.
Yes, gluten intake has been reduced or eliminated
Is the patient symptomatic?
### NO For *asymptomatic* adults or children over age 2-3 years, resume an unrestricted diet containing gluten (roughly 2 servings of gluten - e.g., 2 slices of wheat-based bread - daily for 6-8 weeks)^[6](#fhir-question-d21c275f96d617ea3cc35e85c22405f6),[7](#fhir-question-adfb960c4dcb1fbf6bd7cf3e6e5947e1)^ in advance of serologic screening. Following gluten reintroduction, screen for celiac disease in adults immediately, and in children beginning at age 3 years with TTG-IgA antibody and total serum IgA (a value above 20 mg/dl would make this test reliable). Add IgG based testing such as deamidated gliadin IgG for IgA deficient individuals. Repeated screening for genetically at-risk children may be conducted approximately every 2-3 years.^[2](#fhir-question-9a07d0cc3fa9e5ae3d6b34e018d666a1),[3](#fhir-question-9231a113a2544f625c3e0970bc3af532)^ Less frequent intervals (approximately every 5 years) may be appropriate for adults.
Results of Celiac Disease Screening
### Positive Celiac Disease Assay A diagnosis of celiac disease must be confirmed by biopsy for asymptomatic first degree relatives of a patient with celiac disease.
### Negative Celiac Disease Assay Perform HLA typing for celiac disease risk genes (HLA DQ2(DQA1\*05:01/05:05 and DQB1\*02:01/02:02), DQ8 (DQA1\*03:01 and DQB1\*03:02), and/or ½ DQ2 (DQA1\*05:01/05:05 or DQB1\*02:01/02:02) at a lab which reports the ½ DQ2 heterodimer. Alternatively this can be performed alongside initial serologic screening to avoid an additional blood draw. Individuals who do not carry a risk gene do not require further celiac disease serological screening. Repeated screening for genetically at-risk children may be conducted approximately every 2-3 years.^[2](#fhir-question-9a07d0cc3fa9e5ae3d6b34e018d666a1),[3](#fhir-question-9231a113a2544f625c3e0970bc3af532)^ Less frequent intervals (approximately every 5 years) may be appropriate for adults.
### Yes For *symptomatic* adults or children, consider screening with TTG-IgA and total serum IgA (a value above 20 mg/dl would make this test reliable) alongside assessment for other conditions, though negative results should be interpreted with caution. Symptomatic adults should also be referred to their provider for further evaluation. If clinical suspicion for celiac disease is high, consider a period of liberalized gluten intake (roughly 2 servings of gluten - e.g., 2 slices of wheat-based bread - daily for 6-8 weeks)^[6](#fhir-question-d21c275f96d617ea3cc35e85c22405f6),[7](#fhir-question-adfb960c4dcb1fbf6bd7cf3e6e5947e1)^ before performing EGD with biopsy to diminish the likelihood of an equivocal biopsy result.
Infant
Has gluten been introduced in the diet?
### No Do not screen for celiac disease until after gluten introduction into the diet. Introduce gluten gradually as per American Academy of Pediatrics recommendations^[8](#fhir-question-cc6c1990892516843f18671f7ec0288f)^. There may be benefit to overlapping gluten introduction with ongoing breastfeeding for children at risk^[9](#fhir-question-b46f48b15432c0b1a05cfe2d6d41d1c2)^, although most recent evidence shows no effect of breastfeeding upon celiac disease risk^[10](#fhir-question-fbf64740e8a4374404e2fb19480feefa),[11](#fhir-question-e792dee7141e2f621e270ffbdabc9344)^. For *asymptomatic* children, screen for celiac disease beginning at age 3 years with TTG-IgA antibody and total serum IgA (a value above 20 mg/dl would make this test reliable). Add IgG based testing such as deamidated gliadin IgG for IgA deficient individuals. Repeated screening for genetically at-risk children may be conducted approximately every 2-3 years.^[2](#fhir-question-9a07d0cc3fa9e5ae3d6b34e018d666a1),[3](#fhir-question-9231a113a2544f625c3e0970bc3af532)^
Yes
Has the patient had reduced gluten intake following the diagnosis of a relative with celiac disease?
No, gluten intake has not been reduced
Is the patient symptomatic?
### No For *asymptomatic* children or adults, screen for celiac disease beginning at age 3 years for children, using TTG-IgA antibody and total serum IgA (a value above 20 mg/dl would make this test reliable). Add IgG based testing such as deamidated gliadin IgG for IgA deficient individuals.
Results of Celiac Disease Screening
### Positive Celiac Disease Assay A diagnosis of celiac disease must be confirmed by biopsy for asymptomatic first degree relatives of a patient with celiac disease.
### Negative Celiac Disease Assay Perform HLA typing for celiac disease risk genes (HLA DQ2(DQA1\*05:01/05:05 and DQB1\*02:01/02:02), DQ8 (DQA1\*03:01 and DQB1\*03:02), and/or ½ DQ2 (DQA1\*05:01/05:05 or DQB1\*02:01/02:02) at a lab which reports the ½ DQ2 heterodimer. Alternatively this can be performed alongside initial serologic screening to avoid an additional blood draw. Individuals who do not carry a risk gene do not require further celiac disease serological screening. Repeated screening for genetically at-risk children may be conducted approximately every 2-3 years.^[2](#fhir-question-9a07d0cc3fa9e5ae3d6b34e018d666a1),[3](#fhir-question-9231a113a2544f625c3e0970bc3af532)^
### Yes Infants with a family history of celiac disease who demonstrate concerning symptoms (such as gastrointestinal, growth, or nutritional concerns) warrant serologic assessment for celiac disease as a part of a comprehensive evaluation. This should be performed with TTG-IgA antibody and total serum IgA (a value above 20 mg/dl would make this test reliable) along with deamidated gliadin IgG, though a greater likelihood of false negative serologies has been reported in very young children (REF).. If clinical suspicion for celiac disease is high, EGD may be considered despite negative serologies, and especially if IgA deficient.
Yes, gluten intake has been reduced or eliminated
Is the patient symptomatic?
### No For *asymptomatic* infants, resume an unrestricted diet containing gluten with gradual reintroduction in an age-appropriate manner. Screen for celiac disease beginning at age 3 years with TTG-IgA antibody and total serum IgA (a value above 20 mg/dl would make this test reliable). Add IgG based testing such as deamidated gliadin IgG for IgA deficient individuals.
### Yes For *symptomatic* infants in whom gluten has been reduced or eliminated, alongside a comprehensive evaluation for other conditions screen for celiac disease with TTG-IgA antibody and total serum IgA (a value above 20 mg/dl would make this test reliable) as well as deamidated gliadin IgG. In the setting of restricted gluten intake, negative results should be interpreted with caution. If clinically feasible, reintroduce gluten gradually and in an age-appropriate manner prior to endoscopy (although endoscopy may be necessary even if this is not possible). If the infant cannot tolerate gluten introduction or if the family declines this, consider HLA typing for celiac disease risk genes (HLA DQ2 (DQA1\*05:01/05:05 and DQB1\*02:01/02:02), DQ8 (DQA1\*03:01 and DQB1\*03:02), and/or ½ DQ2 (DQA1\*05:01/05:05 or DQB1\*02:01/02:02) at a lab which reports the ½ DQ2 heterodimer. A negative result would preclude a celiac disease diagnosis and other causes of the patient’s symptoms should continue to be pursued. Parents should be cautioned that despite a family history of celiac disease, presence of a celiac disease risk gene does not confirm a diagnosis of celiac disease. In such cases, even clinical response to a gluten-free diet cannot confirm a celiac disease diagnosis in an infant who is seronegative with normal biopsies though on a gluten-free diet.
Footnotes
Hill ID, Fasano A, Guandalini S, Hoffenberg E, Levy J, Reilly N, et al. NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders. J Pediatr Gastroenterol Nutr. 2016;63(1):156-65. Epub 2016/05/18 2016/04/02. doi: 10.1016/j.jpeds.2016.04.014 10.1097/mpg.0000000000001216. PubMed PMID: 27035374.
Goldberg D, Kryszak D, Fasano A, Green PH. Screening for celiac disease in family members: is follow-up testing necessary? Digestive diseases and sciences. 2007;52(4):1082-6. doi: 10.1007/s10620-006-9518-1. PubMed PMID: 17380406.
Hogberg L, Falth-Magnusson K, Grodzinsky E, Stenhammar L. Familial prevalence of coeliac disease: a twenty-year follow-up study. Scandinavian journal of gastroenterology. 2003;38(1):61-5. PubMed PMID: 12608466.
Brusca I, Carroccio A, Tonutti E, Villalta D, Tozzoli R, Barrale M, et al. The old and new tests for celiac disease: which is the best test combination to diagnose celiac disease in pediatric patients? Clinical chemistry and laboratory medicine. 2011;50(1):111-7. doi: 10.1515/CCLM.2011.714. PubMed PMID: 21942854.
Lammi A, Arikoski P, Hakulinen A, Schwab U, Uusitupa M, Heinonen S, et al. Development of gliadin-specific immune responses in children with HLA-associated genetic risk for celiac disease. Scandinavian journal of gastroenterology. 2016;51(2):168-77. doi: 10.3109/00365521.2015.1067328. PubMed PMID: 26161465.
Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. 2006;131(6):1981-2002. doi: 10.1053/j.gastro.2006.10.004. PubMed PMID: 17087937.
Leffler D, Schuppan D, Pallav K, Najarian R, Goldsmith JD, Hansen J, et al. Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease. Gut. 2013;62(7):996-1004. doi: http://dx.doi.org/10.1136/gutjnl-2012-302196. PubMed PMID: 22619366; PubMed Central PMCID: PMCNIHMS380622 PMC3525791
Section on B. Breastfeeding and the use of human milk. Pediatrics. 2012;129(3):e827-41. doi: 10.1542/peds.2011-3552. PubMed PMID: 22371471
Ivarsson A, Hernell O, Stenlund H, Persson LA. Breast-feeding protects against celiac disease. The American journal of clinical nutrition. 2002;75(5):914-21. PubMed PMID: 11976167.
Vriezinga SL, Auricchio R, Bravi E, Castillejo G, Chmielewska A, Crespo Escobar P, et al. Randomized feeding intervention in infants at high risk for celiac disease. The New England journal of medicine. 2014;371(14):1304-15. doi: 10.1056/NEJMoa1404172. PubMed PMID: 25271603.
Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S, et al. Introduction of gluten, HLA status, and the risk of celiac disease in children. The New England journal of medicine. 2014;371(14):1295-303. doi: 10.1056/NEJMoa1400697. PubMed PMID: 25271602.