Quality standards for celiac disease comprehensive care units: A Spanish multidisciplinary consensus integrating professional expertise and patient perspectives

Table 1 Patient-identified concerns in celiac disease care and their clinical justification for quality standards

	Patient concern	Clinical justification for quality standards
1	Insufficient knowledge, low clinical suspicion, and poor awareness of diagnostic guidelines among physicians	CD has very heterogeneous presentation patterns, leading to delayed or missed diagnoses and long-term complications. Specialized units can standardize diagnostic pathways and improve early detection
2	Difficulties in ensuring timely referral to specialized settings	Excessive delays between symptom onset and diagnosis are common, resulting in prolonged patient morbidity and dissatisfaction
3	Lack of clearly defined criteria for recommending duodenal biopsy in patients with strong clinical suspicion but negative anti-tissue transglutaminase type 2 antibodies	Clinical practice regarding seronegative CD shows wide variability, which can lead to both underdiagnosis and overdiagnosis
4	Lack of clinical indicators for non-celiac gluten/wheat sensitivity	Structured protocols are needed to distinguish non-celiac gluten/wheat sensitivity from CD and other conditions that may mimic gluten-related disorders
5	Doubts regarding the appropriateness of advanced diagnostic procedures in uncertain cases	Novel and clear evidence-based algorithms are necessary to avoid unnecessary or insufficient advanced testing
6	Limited knowledge and training among clinicians who recommend a GFD	Insufficient clinician training often results in suboptimal dietary advice and poor adherence. There is a clear need for accurate and evidence-based dietary education as part of multidisciplinary support
7	Lack of policies for the general inclusion of dietitians in healthcare systems and, more specifically, in CD care	Delayed or absent patient access to dietitians in both primary and secondary care reduces the effectiveness of nutritional interventions and worsens patient outcomes
8	Limited resources for adequate psychological support, especially for children and adolescents recently diagnosed with CD	Unaddressed psychological needs may lead to maladaptive coping strategies, reduced dietary adherence, and persistent negative emotions, especially in the first year following diagnosis
9	Uncertainty about adherence to international guidelines for investigating non-responsive CD	Overall, non-adherence to evidence-based recommendations results in reduced rates of mucosal healing, impaired quality of life, and increased healthcare utilization due to unresolved or worsening disease. Regular, guideline-driven follow-up and multidisciplinary care are essential to optimize outcomes in this complex patient population
10	Lack of consensus regarding which patients can be monitored in primary care, which require specialist follow-up, and when shared management is appropriate	Specialist-led care (gastroenterology or pediatrics) is associated with higher rates of dietitian involvement and better dietary adherence compared with primary care alone. However, primary care follow-up can be suitable if there is access to structured dietary counselling and clear protocols for monitoring complications and adherence

CD: Celiac disease; GFD: Gluten-free diet.

Table 2 Structural quality standards for establishing a Comprehensive Care Unit for patients with Celiac Disease

Position	Definition	Mean	CV (%)	Agreement
11	The CCU-CD should be located in a center that has access to professionals from various disciplines with proven experience in the diagnostic process of CD, including pediatric and adult gastroenterologists, clinical laboratory specialists, immunologists, geneticists, pathologists, and dietitian-nutritionists. These professionals may belong to the same center or to an affiliated or reference center that ensures standardized reporting in accordance with national and international protocols and guidelines	9.86	3.64	Very high
2	The CCU-CD should have access to hematology, biochemistry, and/or immunology laboratories equipped with specific profiles for performing complete blood counts, macronutrient analyses (proteins, lipid profile, glucose), and micronutrient assessments (vitamins and minerals), as well as updated and validated CD-specific serological tests, including total IgA, anti-tTG2 IgA and IgG, and anti-EMA IgA and IgG. Testing should also include measurement of GIP in urine and/or stool, as well as any other assays that contribute to the differential diagnosis of CD or the identification of associated clinical conditions (e.g., fecal calprotectin, fecal occult blood, or fecal pancreatic elastase). These determinations may be carried out in the institution’s own laboratories or in collaborating or reference laboratories	9.64	6.83	Very high
3	The CCU-CD should have access to a microbiology laboratory capable of detecting microbial agents (viruses, bacteria, fungi, and parasites) that may cause villous atrophy, as well as for testing for infections caused by HIV, mycobacteria, and Cryptosporidium	9.55	8.99	Very high
4	The CCU-CD should have access to testing for serological markers characteristic of other immune-mediated diseases (e.g., autoimmune atrophic gastritis) and/or causes of non-celiac enteropathy (e.g., autoimmune enteropathy). These assessments may be performed within the center or through a collaborating or reference laboratory	9.64	6.03	Very high
5	The CCU-CD should have access to a laboratory capable of performing full HLA-DQ genotyping to determine genetic susceptibility to CD and to stratify risk according to the genetic profile (DQ2.5, DQ8, DQ2.2, and DQ7.5)	9.86	3.56	Very high
6	The CCU-CD should be located in a center with a digestive endoscopy unit equipped to obtain biopsy samples for histological examination, as well as to conduct follow-up evaluations and identify CD-related complications. These units should also offer capsule endoscopy and enteroscopy when clinically indicated	9.68	5.87	Very high
7	The CCU-CD should be located in a center with a pathology department staffed by technicians and pathologists experienced in processing, recognizing, and grading histological lesions consistent with CD, and in performing differential diagnoses with other forms of enteropathy. The team should also be skilled in identifying other morphological abnormalities that may explain persistent symptoms in cases of non-responsive CD, such as microscopic colitis	9.32	12.12	Very high
8	The CCU-CD should have the capacity to obtain the intraepithelial lymphogram by flow cytometry for its patients, either at its own center or by referring samples to an experienced center. These centers should have received expert guidance during the initial implementation of the technique to ensure accurate and reliable interpretation of results, thereby supporting appropriate diagnostic assessment and patient follow-up	9.50	7.79	Very high
9	The CCU-CD should have access to a radiology department equipped with appropriate imaging modalities for the detection of potential complications or diseases associated with CD: Ultrasound, computed tomography, and magnetic resonance imaging. In cases with suspected type II refractory CD, positron emission tomography scanning should also be available, either within the center or through an affiliated or reference institution	9.14	14.45	Very high
10	The CCU-CD should include at least one consultation room where a specialist, either a pediatric gastroenterologist or an adult gastroenterologist, can provide personalized, expert care for the diagnosis and follow-up of patients with CD	9.77	4.39	Very high
11	The CCU-CD should have qualified professionals (preferably dietitians or dietitian-nutritionists) experienced in providing dietary and nutritional counseling for patients with CD as well as GFD. These professionals should work in close collaboration with the physicians responsible for patient care and provide support both at the time of diagnosis and during follow-up. Dietary counseling should be individualized, taking into account patient age, family environment, and cultural preferences	8.86	22.37	Very high
12	The CCU-CD should have specific tools to evaluate adherence to the GFD, particularly in non-responsive patients. These tools should include validated dietary questionnaires (administered by qualified personnel, preferably dietitians or dietitian-nutritionists) and the measurement of GIP in urine and/or stool	9.59	8.30	Very high
131	The CCU-CD should have the support of an endocrinology and nutrition unit to assist in the specialized management of adult patients with complex nutritional deficiencies resulting from malabsorption, debilitating complications requiring enteral or parenteral nutritional support (e.g., jejunoileitis or lymphoma), and other forms of malnutrition (such as overweight or obesity) or associated endocrinopathies (e.g., type 1 diabetes, thyroid disease)	9.57	7.06	Very high
14	The CCU-CD should collaborate with psychiatrists and/or clinical psychologists to support the management of psychiatric comorbidities or any other condition affecting the psychological and emotional well-being of patients (both children and adults), within a holistic and comprehensive model of care	9.18	13.29	Very high
15	The CCU-CD should be led by a pediatric or adult gastroenterologist with specific dedication and experience in the different dimensions of CD (clinical care, teaching, and research). This leadership role may be shared by more than one professional	9.32	14.20	Very high
16	The CCU-CD should have validated tools to assess health-related quality of life in both pediatric and adult patients, using age-appropriate questionnaires. These assessments should be performed regularly by professionals trained in their interpretation to ensure continuous patient monitoring	8.95	13.99	Very high
17	The center hosting the CCU-CD should include a day hospital facility where intravenous treatments can be administered safely, such as parenteral iron or, in the future, biological therapies	9.14	14.45	Very high
181	The CCU-CD should have access to inpatient facilities to ensure continuity of care in cases requiring hospitalization due to CD-related complications	9.71	7.38	Very high

¹Not assessed in round 2 because they achieved a high degree of consensus (CV < 25%) and received no suggestions for modification during round 1.

CV: Coefficient of variation; CCU-CD: Comprehensive Care Unit for patients with Celiac Disease; CD: Celiac disease; HIV: Human immunodeficiency virus; tTG2: Tissue transglutaminase type 2; EMA: Endomysial antibodies; GIP: Gluten immunogenic peptides; GFD: Gluten-free diet.

Table 3 Process quality standards for establishing a Comprehensive Care Unit for patients with Celiac Disease

Position	Definition	Mean	CV (%)	Agreement
1	The diagnostic process for CD should ideally begin after confirming that the patient is consuming gluten. If the patient has previously followed a GFD, the exact dates should be documented in the clinical record whenever possible, and alternative diagnostic approaches should be considered if gluten exposure is deemed insufficient or interrupted	9.77	4.39	Very high
2	Following CD diagnosis, each patient should be assigned either a pediatric or adult gastroenterologist, as appropriate, for disease follow-up. Once clinical and serological response to the GFD has been confirmed, long-term follow-up may be conducted by a pediatrician or primary care physician under a consensus-based protocol	8.59	27.28	Very high
3	The medical record should include detailed documentation of the diagnostic criteria used to establish the CD diagnosis in both children and adults, as well as appropriate ICD coding for statistical and epidemiological purposes	10.00	0.00	Very high
4	The laboratory providing serological results to the CCU-CD must adhere to current diagnostic guideline recommendations for measuring anti-tTG2 and anti-EMA of IgA and IgG classes (the latter for IgA-deficient patients). A validated method must also be available to confirm IgA deficiency. Assay kits used should be clearly stated in reports, along with their sensitivity and specificity. Reports should also specify the diagnostic cut-offs required for positive results and for no-biopsy approach in children and adolescents, according to ESPGHAN recommendations. A note should clarify that quantitative results are method-dependent and may not be directly interchangeable with those obtained by other analytical systems. Internal quality control must be performed daily, and participation in external quality programs is mandatory	9.86	3.56	Very high
5	The CCU-CD should provide patients with a means of communication for reporting relevant clinical changes. Depending on available resources, this may include telephone contact, institutional email, or specific digital platforms	9.50	8.44	Very high
6	The CCU-CD must base its procedures on national and international guidelines and apply protocols supported by the best available scientific evidence to ensure excellence in diagnosis, treatment, and follow-up. These protocols should incorporate the elements described in Table 5 and undergo regular review and updating	9.36	12.99	Very high
7	Laboratories performing HLA genetic testing must provide standardized reports meeting the minimum requirements recommended by the SEEC to ensure accurate interpretation. To ensure compliance, it is advisable that the reports be endorsed by the SEEC	9.82	4.02	Very high
8	The CCU-CD should establish, in collaboration with the endoscopy and pathology departments, a Standard Operating Procedure defining the number and type of samples, as well as the collection and transport procedures for duodenal biopsies, both for histological study and intraepithelial lymphogram analysis by flow cytometry	9.73	5.66	Very high
9	Laboratories performing immunophenotyping of duodenal lymphocyte populations (intraepithelial lymphograms) should use standardized flow cytometry methods with regular quality control and, preferably, staff experienced in intestinal mucosa. Reports should meet the minimum requirements suggested by the SEEC to ensure accurate interpretation	9.82	5.10	Very high
10	The pathology department should provide standardized reports that supply pediatric and adult gastroenterologists with all necessary information for clinical interpretation. Reports should include a validated classification of histological lesions and a detailed description of findings to guide diagnosis and follow-up	9.86	3.56	Very high
11	Duodenal biopsy interpretation should be carried out by pathologists experienced in recognizing characteristic lesions. Double reading by two pathologists is recommended for all cases and mandatory in those with diagnostic uncertainty	9.77	4.39	Very high
12	The CCU-CD should offer newly diagnosed and follow-up CD patients access to dietary and nutritional counseling by qualified professionals (preferably dietitians or dietitian-nutritionists). Follow-up should be intensified in non-responsive cases or when symptoms persist	9.50	7.08	Very high
13	The CCU-CD should conduct regular nutritional follow-up to identify and correct nutritional deficiencies and monitor nutritional status over time. These data should be systematically recorded in the medical history	9.32	14.58	Very high
14	The CCU-CD should provide updated information on vaccination recommendations for CD patients, both at diagnosis and during follow-up, in accordance with regional public health guidelines	9.32	9.59	High
15	The CCU-CD should implement a clinical monitoring program focused on safety for patients receiving immunosuppressive or, in the future, biological therapies	9.45	11.18	Very high
16	The CCU-CD should inform patients about the existence of patient associations, which represent valuable complementary resources for psychosocial support and education on CD-related aspects	9.69	6.68	Very high

CV: Coefficient of variation; CCU-CD: Comprehensive Care Unit for patients with Celiac Disease; CD: Celiac disease; tTG2: Tissue transglutaminase type 2; EMA: Endomysial antibodies; ICD: International Classification of Disease; GFD: Gluten-free diet; SEEC: Spanish Society for Celiac Disease.

Table 4 Scientific and educational activity quality standards for establishing a Comprehensive Care Unit for patients with Celiac Disease

Position	Definition	Mean	CV (%)	Agreement
1	The CCU-CD should, ideally, establish a registry of all actively followed patients within the specialized consultation setting, in full compliance with current data protection legislation. The registry should clearly identify cases of seronegative CD, CD with low-risk or non-compatible HLA genetics, non-responsive CD, and potential CD. Preferably, cases should be entered into a unified national registry provided by the SEEC. This registry may be used for both clinical and research purposes and, when possible, should be complemented by the collection of biological samples according to predefined Standard Operating Procedures	9.05	17.22	Very high
2	The CCU-CD should, ideally, have access to a biobank experienced in sample handling or, alternatively, establish its own sample collection to support research activities. The unit should also have the necessary infrastructure to ensure proper long-term storage of samples	9.27	14.19	Very high
3	Members of the CCU-CD should actively participate in or promote research studies related to CD	9.86	3.56	Very high
4	At least one member of the CCU-CD should participate annually in a training or continuing education activity on CD, such as congresses, courses, workshops, or specialized seminars. Continuing education should cover both clinical and research aspects	9.64	8.19	Very high
5	All professionals involved in the diagnostic process of CD, including clinical and laboratory staff, should promote joint meetings (e.g., clinical case sessions) to share and reinforce up-to-date knowledge on CD within the multidisciplinary team	9.77	4.39	Very high

CV: Coefficient of variation; CCU-CD: Comprehensive Care Unit for patients with Celiac Disease; CD: Celiac disease; ; SEEC: Spanish Society for Celiac Disease.

Table 5 Essential elements to be included in clinical protocols supporting Comprehensive Care Unit for patients with Celiac Disease procedures

Phase	Essential elements
Diagnosis	Coordinated and consensual approach with primary care and other specialized units, clearly defining referral criteria as well as symptoms and signs that should raise clinical suspicion of CD
	Management of biopsies deemed inadequate for histopathological assessment. Measures to be taken should be included (e.g., preparing additional tissue sections, repeating the biopsy, or applying supplementary histopathological techniques)
	Procedures for accurate differential diagnosis of seronegative enteropathies, applicable to both lymphocytic duodenosis (Marsh 1) and villous atrophy (Marsh 3a)
	Diagnosis in individuals already on a GFD. The protocol should address cases in which the patient cannot tolerate or declines the gluten challenge, acknowledging that this may preclude a definitive diagnosis of CD
Treatment and follow-up	Follow-up protocol, defining the responsibilities of different levels of care: Specify which patients should continue follow-up in the hospital setting, which in primary care, and when shared care is appropriate
	Assessment of TSH levels for early detection of autoimmune thyroid disease
	Early detection of metabolic bone disease, including evaluation of calcium-phosphate metabolism and bone densitometry
	Indications and conditions for intravenous iron replacement in patients with CD and iron deficiency
	Transition from pediatric to adult care, specifying timing, process, and participants. A standardized transfer report should be completed by pediatric gastroenterologists, including all relevant clinical information for the adult gastroenterologist (diagnostic details, nutritional deficiencies at diagnosis, response to the GFD, adherence, and unresolved issues)
	Differential diagnosis of non-responsive CD in accordance with current clinical practice guideline recommendations

CD: Celiac disease; GFD: Gluten-free diet; TSH: Thyroid-stimulating hormone.