Performance of the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 Instrument as a Clinical Decision Aid in the Routine Clinical Care of Patients With Systemic Sclerosis

Norina Zampatti; Alexandru Garaiman; Suzana Jordan; Rucsandra Dobrota; Mike Oliver Becker; Britta Maurer; Oliver Distler; Carina Mihai

Disclosures

Arthritis Res Ther. 2021;23(125) 

In This Article

Discussion

To our best knowledge, this is the first study to analyze the performance of the UCLA GIT 2.0 in a large real-life cohort of unselected patients with SSc. Our results show that the UCLA GIT 2.0 score and its reflux subscale identified patients with SSc, in whom EGD was recommended by experts, with a sensitivity of over 70% and a specificity of about 50%.

The recommendation for EGD was made in all patients by a rheumatologist with experience in SSc, at the annual visit of the patient and following a comprehensive investigation, as defined by the EUSTAR guidelines.[1] There was no regular use of the UCLA GIT 2.0 questionnaire to decide further GI tract investigation. We excluded patients with concomitant acute GI bleeding or a history of cancer in the upper GI tract, as in these cases, the indication for EGD would be driven by other criteria than the symptoms captured by the UCLA GIT 2.0.

Considering that several clinical or laboratory data might influence the indication of EGD, or might predict EGD findings, we adjusted the analyses for all these parameters, which were included as covariates for the GLMM models after a careful selection based on clinical judgment and evidence from published literature. For example, we expected the recommendation for EGD to be favored by anemia, possibly caused by gastrointestinal bleeding, which is frequent in SSc, especially in the presence of GAVE;[5] however, our data did not show any association between Hb and the referral to EGD. On the other hand, mRSS was significantly associated with the recommendation for EGD, but the very small OR suggests that this association is of little clinical significance. As expected, patients with a history of Barrett's esophagus were more frequently referred to EGD. We did not have enough data on significant weight loss or decrease in Hb, and no data on other objective markers of GI involvement, such as F-calprotectin, to include these among the selected covariates.

The recommendation to perform EGD was significantly associated with higher UCLA GIT 2.0 reflux, distention/bloating, and social functioning subscale scores, as well as with higher total scores. As expected, we found similar significant associations for individual symptoms like heartburn, dysphagia, and regurgitation, as well as for these symptoms clustered together as esophageal symptoms and stomach symptoms. These results support the use of the UCLA GIT 2.0 questionnaire in practice, as it provides the attending rheumatologist with detailed information on gastrointestinal symptoms and helps orientating the further investigation of the GI tract.

In the second part of the study, we analyzed the hypothesis that the reflux subscale or the total score of the UCLA GIT 2.0 would be associated with endoscopic esophagitis or with a pathologic EGD in general. Data on the associations of the UCLA GIT 2.0 with objective upper GI tract findings in patients with SSc are scarce. Previous studies analyzed smaller groups of selected patients, in whom GI tract investigation and completion of the UCLA GIT 2.0 were performed systematically and within a narrow time interval.[18–20] A prospective study on 55 patients with SSc and clinically significant upper GI tract symptoms found a moderate correlation between the reflux scale of the UCLA GIT 2.0 with endoscopic esophagitis; the reflux subscale was also discriminative between patients with and without pathologic findings on esophageal manometry.[18] Another study on 40 patients with SSc, of whom 85% reported upper GI tract symptoms, found an association of higher reflux and total UCLA GIT 2.0 scores with decreased amplitude of distal esophageal contractions.[19] A very recent study on 31 patients with SSc, assessing esophageal motility dysfunction by scintigraphy, found a significant association of esophageal emptying activity with the GIT 2.0 reflux score, but not with the other subscales and the total UCLA GIT 2.0 score.[20]

In our study on a large cohort of real-life patients, neither the total UCLA GIT 2.0 score nor the reflux subscale correlated with endoscopic esophagitis. The only parameters showing associations with this outcome were the EUSTAR-recorded "esophageal symptoms" (defined as the presence of reflux and/or dysphagia), and the mRSS. For the latter, the very low OR suggests the association is of little clinical importance. Not surprisingly, the symptom interpretation by the physician (as presence or absence of "esophageal symptoms") performed better than single symptoms such as "heartburn", as recorded in the patient EMR, in detecting patients with esophagitis.

The lack of correlation between esophagitis and single symptoms or the UCLA GIT 2.0 reflux scale may be explained by several factors, among which the non-systematic use of EGD, the variable time between EGD and the UCLA GIT 2.0 completion, and the use of PPI in about 60% of patients. Moreover, large studies performed by gastroenterologists in patients with gastro-esophageal reflux disease (GERD) have shown that an expert history, as well as GERD questionnaires, such as the reflux disease questionnaire and gastroesophageal reflux disease questionnaire, have important limitations when compared with objective testing for GERD by EGD or functional testing.[21–23] Studies with systematic EGD in unselected patients with SSc are scarce.[24,25] In a single-center SSc cohort study, Petcu et al. found endoscopic esophagitis in 8/22 patients without any GI symptoms and in 39/57 patients with GI symptoms. Only 12/26 patients with gastroesophageal reflux symptoms had esophagitis on endoscopy.[24] The authors advocate for the routine use of EGD during the early stage of SSc, even in the absence of typical symptoms.

The strengths of our study rely in the large, real-life cohort of unselected patients from a tertiary SSc center with long-standing experience, and in the statistical methods applied, which allow adjusting for a large number of independent parameters potentially associated with the study outcomes. The study also has several limitations, which include the partially retrospective data collection. However, the large majority of the data were collected prospectively following the EUSTAR recommendations.[1] There was considerable variability in performing EGD, as in some patients this was not done despite being recommended, and in others it may have been done in another center, with the results not recorded in the EMR of our hospital. However, over 70% of EGD recommended by our center were performed and the respective results were available in the hospital EMR. It is possible that some reports of EGD performed outside our hospital may have not reached us, but we assume that in many of these cases EGD was probably not done, as our center strives to obtain all medical information of the patients and communication between local medical facilities is generally good. Another limitation is the time of ± 3 months allowed between questionnaire completion and EGD, which is quite long and may have contributed to the lack of correlation between UCLA GIT 2.0 scores and the results of the EGD. Finally, yet importantly, treatment with PPI was not recorded into detail and we were not able to analyze the indication for PPI, doses, or compliance.

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