Introduction

Celiac disease (CD) is a chronic disorder that requires regular medical follow-up [1]. Poor adherence to a gluten-free diet (GFD) is common in clinical practice and frequently associated with poor outcomes [2, 3]. CD patients further experience significant symptom burden when not fully adherent to a GFD resulting in a negative impact on quality of life [4]. Despite the risks of increased morbidity and mortality when not adequately managed, patients with CD are not adequately followed up in the outpatient setting [5]. Currently, the only effective treatment for CD is strict adherence to a GFD. Given the ubiquitous presence of gluten in Western diets, adherence is a difficult prospect for many patients. However, dietary adherence confers clinical, serologic, and histologic normalization over time [6]. Barriers to adherence are manifold including educational, financial, behavioral, and health care delivery factors [7].

The best way to deliver high quality medical care for CD patients is unknown. Patient preference in the United Kingdom is to follow with a dietitian with a physician available if needed [8]. Follow-up with a primary care physician was effective in Finland [9] . In the United States, dedicated multidisciplinary CD programs are emerging with the goal to improve the care of patients with CD by helping with GFD adherence and monitoring. However, there is no information about the effectiveness of a dedicated CD program on celiac quality care metrics and outcomes. Our hypothesis is that a dedicated CD program may improve care quality and outcomes. The main aim of the study was to estimate the frequency of clinically relevant CD quality care metrics as surrogate markers of adherence to current CD guidelines [10]. A secondary aim was to determine the potential benefits of short-term outcomes such as symptom resolution and serological response conferred by diagnosis and management at a dedicated CD program during regular clinical follow-up.

Methods

Study Design

This study was a retrospective cohort study and was approved by the Cleveland Clinic Foundation Institutional Review Board.

Participants

Patients in this study were identified through chart retrieval via electronic medical record at our tertiary care center. CD patients were identified by ICD code for CD (K90.0) or dermatitis herpetiformis (L13.0), and further filtered for patients seen by a gastroenterologist. Additional inclusion criteria were adult (≥ 18 years of age at diagnosis) patients. Included patients were then divided into two groups – those seen by a gastroenterologist associated with our dedicated CD program and those seen by a gastroenterologist outside of the CD program (standard of care). The CD program at Cleveland Clinic was established in 9/1/2019. Once identified and sorted into their cohort, patients were then assessed for presence of a biopsy-proven diagnosis in the chart; those without a biopsy-proven CD diagnosis were excluded. For each patient diagnosed and seen in the CD program, a patient was randomly selected from the pool of patients diagnosed and seen by a gastroenterologist outside of the CD program (standard of care).

Data Abstraction

Two single physician reviewers (A.M.F., K.P.) not involved in the care of the patients performed chart review in a uniform manner for all patients. “Zero time” was defined as the date of CD diagnosis by intestinal biopsy. Follow-up time was defined as last documented clinical follow-up or up to 2 years, whichever was first. Celiac quality care metric data based on recommendations by national and/or international CD guidelines were collected for both groups and included: referral to a dietitian (strong recommendation), medical and dietitian follow-up (strong recommendation), bone densitometry scan (DXA) (strong recommendation), hepatitis B immunity testing (assessed as testing for hepatitis B surface antibody) (suggested), documented discussion about vaccinations (strong recommendation), testing first-degree relatives (strong recommendation), and follow-up serology (strong recommendation) [10,11,12,13,14]. We additionally assessed for presence of iron deficiency anemia, which was defined as ferritin less than 30 ng/mL accompanied by hemoglobin less than 12 g/dL. Resolution of the iron deficiency anemia was defined as improvement of hemoglobin above 12 g/dL and ferritin above 100 ng/mL. We assessed symptom resolution as well as serological response (defined as partial response or seroconversion) based on anti-tissue transglutaminase IgA levels before and after starting a gluten-free diet. Partial response was arbitrarily defined as > 50% decrease from serologic values at diagnosis, while seroconversion required a normal value as defined by the range of the test kit [15]. All patients’ serologic testing was done with a testing kit proprietary to Cleveland Clinic Foundation; the range of normal values for this testing kit were 0–20 U/mL.

Statistical Analysis

Descriptive statistics were used to demonstrate demographics and quality care measures among patients. Continuous variables were expressed as medians while categorical variables were expressed as percentages.

Univariate analysis was performed to compare celiac center and standard of care patients. We used Pearson’s chi square for all quality metrics as they were categorical variables. Patients with missing data for any given outcome were excluded from analysis for the respective outcome.

We also performed a sensitivity analysis to assess for statistically significant differences in frequency of quality care metrics between contemporary standard of care patients (2019 and after) and those diagnosed prior to CD program establishment (pre-2019). This analysis consisted of dividing the standard of care patients into pre- and post-2019 subgroups; we then conducted Pearson’s chi square analyses to look for differences in frequency of quality care metric variables.

Results

A total of 340 patients were included: 120 patients (median age 37.4 years, 89 (74%) women) in the CD program and 220 patients (median age 43.6 years, 166 (76%) women in the standard of care group Table 1. The diagnosis dates for patients in the CD program spanned from 2019 to 2021 while standard of care patients were diagnosed between 2013 and 2021 (159 (72.3%) diagnosed between 2013 and 2019; 61 (27.73%) after 2019). Sensitivity analysis of standard of care patients according to diagnosis date (pre- and post-2019) showed no statistically significant difference with respect to frequency of celiac quality care metrics. Table 2.

Table 1 Participant demographics and baseline characteristics
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Table 2 Comparison of the frequency of celiac quality care metrics among patients in the standard of care group diagnosed pre- and post- 2019
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We observed a significantly greater implementation of celiac care quality metrics in CD program patients compared to the standard of care. Figure 1. Specifically, frequencies of referral to a dietitian (95.0% vs 69.1%, p < 0.00001), medical (100% vs 71.4%, p < 0.00001) and dietitian follow-up (66.7% vs 44.1%, p = 0.0001) follow-up, bone densitometry scan (DXA) (76.7% vs 29.5%, p < 0.00001), hepatitis B testing (71.6% vs 21.8%, p < 0.00001), documented vaccine discussion (75% vs 9.1%, p < 0.00001), documented discussion of first-degree family member testing (92.5% vs 14.1%, p < 0.00001), and follow-up serology (94.2% vs 63.6%, p < 0.0001) were all significantly higher in the CD program.

Fig. 1
figure 1

Comparison of the Frequency of Celiac Quality Care Metrics among Patients in the Celiac Disease Program and Patients in the Standard of Care. *p =  < .00001; **p < 0.0001

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With respect to symptom changes between cohorts, diarrhea was present in 144 (43.6%) of the CD patients and it was the most common symptom at diagnosis for each group. (Diarrhea resolved in 38 (82.6%) in 157 the CD program as opposed to 63 (64.2%) in the standard of care after starting a GFD (p = 0.025). Abdominal pain was present in 15 CD program patients and 107 standard of care patients; it resolved in 8 program patients and 64 standard of care patients (p = 0.63). Atrophic glossitis was present in 4 CD program patients and 0 standard of care patients initially; it resolved in all 4 program patients (p ≤ 0.0001). All other symptoms intestinal (steatorrhea and bloating), all other extra intestinal symptoms (dermatitis herpetiformis and peripheral neuropathy), and iron deficiency anemia did not differ between the groups with respect to the number of patients in which they resolved (Table 1).

Among 113 patients with follow-up serology in the CD program, 71 (62.8%) achieved serological response (34 partial, 37 seroconversion). Among 140 patients with follow-up serology in the standard of care, 88 (62.8%) achieved serological response (30 partial, 58 seroconversion). As such, there was no significant difference between the two cohorts with respect to serological response (p > 0.99).

Discussion

The primary finding in this study is that a dedicated Celiac Disease Program improves celiac quality care metrics in real life and may further improve outcomes such as diarrhea resolution compared to standard of care. Figure 2. This study demonstrates the benefits of a multidisciplinary team specifically assembled to deliver high quality care in patients with CD.

Fig. 2
figure 2

A proposed follow-up algorithm for adults with newly-diagnosed celiac disease. DXA, dual energy absorptometry [1] at diagnosis or within 1 year; [2] Covid-19, Hepatitis B immunity, influenza, herpes zoster, and pneumococcal; consider vaccine administration during office visit to improve compliance [3] Discussion of recommendations for testing 1st degree family members and revisit on the recommendation during follow-up; [4] No consensus. At our CD program we check CBC, ferritin, ALT, albumin, vitamin D, vitamin B12, folate, TSH, zinc; [5] after confirmation of mucosal healing follow-up every year may be reasonable

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A dedicated Celiac Disease Program is a multidisciplinary team assembled with the objective of delivering high quality care for CD patients. It is comprised of members from various disciplines and typically includes gastroenterologists (with one acting as a program director), expert celiac dietitians (skilled and experienced in the GFD), gastrointestinal pathologists, bone and calcium specialists from endocrinology, nurse coordinators, gastrointestinal psychologist, and a diverse group of consultative specialists to help with specific symptoms or clinical situations like neurology, dermatology, hematology, allergy and immunology, among others.

Monitoring and long-term follow-up for patients with CD have been recommended in clinical practice [10,11,12,13,14]. Unfortunately, there is no consensus on how often, which specific tests, and who should perform the follow-up [15, 16]. Therefore, it is not surprising that medical follow-up is inadequate and at times non-existent [4]. A number of our patients are self-referred sharing with us that they were told to simply read about a GFD upon diagnosis with no set follow up plan in place for their care. In this study, patients seen in the CD program demonstrate a higher frequency of achieving clinically relevant celiac quality care metrics. Regular follow-up with a gastroenterologist, dietitian referral, and discussion of testing first-degree family members were observed in more than 92% of the CD program patients. This is in contrast with prior reports of suboptimal follow-up in patients with CD [4, 7]. Other celiac quality care metrics were also very frequent in the CD program such as follow-up serology, DXA scan referral, dietitian follow-up, and vaccine discussion including hepatitis B immunity check. Although less than in CD program patients (86.7%), follow-up serology was also frequent in the standard of care group (60.4%) suggesting better follow-up in these patients than previously reported with frequency of follow-up serology as low as 22% within 1 year [6]. Most celiac quality care metrics reported are strongly recommended by current CD guidelines [16]. However, there are controversial recommendations as exemplified by hepatitis B immunity check. As CD patients often lack immunity to initial hepatitis B vaccination, a booster dose is often recommended [17]. The improved hepatitis B serologic follow-up suggests that a CD program may be beneficial in identifying patients who could benefit from a booster dose. However, a recent study suggests the risk of hepatitis B infection in the United States is very low and not increased among CD patients as compared to general population [18].

A dedicated CD program improved short-term outcomes such as higher frequency of diarrhea resolution (82%) likely due to the improved follow-up in CD program patients with both physicians and dietitians as poor follow-up practices have been demonstrated to be associated with a negative impact on symptom resolution and serology [6, 19,20,21]. Seroconversion was not different among groups likely affected by the length of follow-up or surveillance bias meaning that patients with a repeat serology test in the standard of care group are perhaps a subgroup with more adequate follow-up and better adherence to the management plan. Therefore, a prospective design is needed to further explore any potential benefit on rate of seroconversion in patients followed in a CD program, the current rate of 63% is higher than historical reports [6]. Longer follow-up of this cohort may result in a higher rate of seroconversion, as previously demonstrated in a large Italian CD population under the “CD-Watch” program with seroconversion of 95% at 5 years [20].

One significant limitation in this study is the relative youth of our CD program; many patients seen in the program have not yet undergone repeat biopsy to assess histologic response. Although mucosal healing is achievable and desirable as goal of gluten-free diet, repeat biopsy after following a GFD to check for mucosal healing remains a controversial topic [19]. Another potential limitation is that celiac care guidelines underwent a significant shift with the American College of Gastroenterology update in 2013 and other published guidelines within the timeframe of diagnosis for our standard of care cohort [14]. While this change may potentially have affected celiac quality care metric adherence in the standard of care group, most patients in the standard of care cohort were diagnosed after the publication of these national guidelines. In addition, there was not a difference in the frequency of quality care metrics among patients diagnosed before or after 2019 in the standard of care cohort with a similar low frequency of quality care metrics regardless of the time of diagnosis. Ultimately a prospective study is warranted to explore the potential benefit of a CD program on not only celiac quality care metrics but also patient satisfaction, rate of seroconversion, quality of life, GFD adherence, cost, and rate of mucosal healing. It will be important to see if high quality metrics and improved outcomes reported in this single center study are reproducible in CD programs elsewhere; a multicenter study would further inform this topic. It will be also relevant to see the effect on celiac quality care metrics and outcomes for patients followed up by non-gastroenterologists like primary care physicians and nurse practitioners [22, 23].

In conclusion, a dedicated Celiac Disease Program improves celiac quality care metrics and may improve short-term outcomes such as diarrhea resolution as compared to standard care. This study that demonstrated the benefits of a multidisciplinary team specifically assembled to deliver high quality care in patients with CD.