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Gastrointestinal lesions of eosinophilic granulomatosis with polyangiitis: a prediction model and clinical patterns

Arthritis Research & Therapy volume 27, Article number: 3 (2025) Cite this article

Abstract

Objective

Severe gastrointestinal lesions are associated with a poor prognosis in eosinophilic granulomatosis with polyangiitis (EGPA). The goal of this study was to develop an effective predictive model for gastrointestinal lesions and to examine clinical patterns, associated factors, treatment, and outcomes of gastrointestinal lesions in EGPA.

Methods

We retrospectively enrolled 165 EGPA patients. The independent associated factors were analyzed using multivariate logistic regression. A nomogram was conducted to quantify the predictive factors. The correlation between different organ lesions was calculated to explore the clinical patterns.

Results

A total of 52 patients had gastrointestinal lesions, and 22 developed severe disorders. Common manifestations included abdominal pain (78%), diarrhea (40.4%), and nausea and/or vomiting (32.7%). Severe gastrointestinal lesions included hemorrhage (26.9%), ulcers (17.3%), obstruction (9.6%), and pancreatitis (5.8%). Eosinophilic tissue infiltration, weight loss, and myalgia were independently associated with gastrointestinal involvement. Patients with severe gastrointestinal lesions had a shorter duration from initial symptoms to EGPA diagnosis, less frequent asthma, and ear-nose-throat involvement, and were more likely to receive methylprednisolone pulse. Weight loss, central nervous system involvement, myalgia, and eosinophilic tissue infiltration were retained in the nomogram. An eosinophil ratio of over 19.2% identified gastrointestinal lesions. Significantly more patients with gastrointestinal involvement had a Five Factor Score ≥ 2. Five well-defined clinical models were identified, including the brain-gut pattern.

Conclusions

Severe gastrointestinal lesions are common in EGPA and early detection is critical. Eosinophils are an important factor associated with gastrointestinal involvement of EGPA. We developed a model to predict the risk of gastrointestinal lesions. The brain-gut pattern might deserve further investigation in EGPA.

Introduction

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, multi-system, inflammatory autoimmune disease, classified as a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis of the small-to-medium-sized vessels. EGPA is characterized by asthma, eosinophilia, and necrotizing vasculitis [1]. The median age at EGPA onset is 50 years [2]. EGPA shows no significant sex predominance; however, our previous study indicated that male and female patients show distinct disease phenotypes [3].

EGPA frequently presents with eosinophilic (respiratory system involvement, cardiomyopathy, gastroenteritis) and vasculitis phenotypes (neuropathy, glomerulonephritis) based on the ANCA status [2, 4]. Gastrointestinal (GI) lesions are common in the evolving process of EGPA, ranging from 8 to 78% in previous reports [5,6,7,8]. Severe GI manifestations are associated with a poor prognosis in EGPA according to Five Factor Score (FFS), contributing to a significantly higher mortality rate in ANCA-associated vasculitis [9, 10]. Therefore, recognizing GI lesions earlier is of great clinical significance. However, owing to the rarity of EGPA, a comprehensive investigation into GI lesions of EGPA has been lacking in a relatively large cohort, especially in recent years.

In this study, we retrospectively analyzed detailed clinical characteristics and established a prediction model for the development of GI involvement based on a longitudinal Chinese EGPA cohort, aiming to provide more evidence-based recommendations.

Methods

Patients

This is a comprehensive retrospective cohort study. A total of 165 hospitalized patients were recruited from Peking Union Medical College Hospital (PUMCH) between January 2007 and December 2020. Every patient met the 1990 American College of Rheumatology classification criteria for EGPA [11]. The diagnosis was confirmed by two rheumatologists certified by PUMCH. Since this is a retrospective study, patient consent was not required, but their privacy was well protected. This study was approved by the Ethics Committee of PUMCH (number S-K1385, Beijing, China).

Clinical assessment

When patients showed clinical symptoms or signs of GI involvement, such as abdominal pain, diarrhea, nausea, vomiting, acid regurgitation, abdominal distension, melena, hematemesis, and jaundice, or when routine laboratory tests suggested GI bleeding, including repeated positive fecal occult blood test and anemia, imaging (abdominal computed tomography or magnetic resonance imaging), endoscopic examination, and/or tissue biopsy were conducted (at least one instrumental examination). Other causes of GI lesions were excluded from the study. Severe GI involvement includes GI bleeding, perforation, ulcers, obstruction, and pancreatitis, associated with EGPA. Other system involvement was defined based on clinical presentation, laboratory testing, imaging, histopathology, and the detailed definitions can be found in our previous studies [12, 13]. In particular, severe asthma refers to asthma that required ongoing glucocorticoid (GC) medication, such as a high-dose of an inhaled, oral, or intravenous GCs or asthma with persistent dyspnea. In this study, eosinophil ratio is defined as the proportion of eosinophils to white blood cells in peripheral blood. Eosinophilic tissue infiltration is defined as eosinophils infiltrating any organs, including GI tract or other organs, such as the skin, lung, kidney, cardiac, and nerves considering that EGPA is a multi-organs disease with same pathological basis. At diagnosis, EGPA disease activity was calculated using the 1994 Birmingham Vasculitis Activity Score (BVAS) [14], and the prognoses were analyzed using the 2011 FFS [10].

The initial treatment primarily consisted of GCs and immunosuppressants for remission induction. Methylprednisolone (MP) pulse therapy was defined as 0.5–1.0 grams per day for 3–5 days, and high- and medium-dose prednisone was administered at 1–2 mg/kg/d and 0.5–0.8 mg/kg/d, respectively. Complete remission meant BVAS decreasing to zero, and partial relief meant BVAS reducing by more than half for at least six months. All-cause mortality was analyzed in this cohort.

Statistical analysis

Statistical analyses were conducted using IBM SPSS (version 25.0, Armonk, NY, USA), Prism (version 9, GraphPad, San Diego, CA, USA), and R 4.3.1 (https://www.r-project.org/). Statistical differences were determined at a two-sided P < 0.05. Categorical variables were presented as numbers and percentages and were compared using the χ2 test or Fisher’s test. Continuous variables were described as mean ± standard deviation for normally distributed data or median (interquartile range) for skewed data. Continuous data were evaluated using either t tests or nonparametric tests, as needed. Correlations were calculated using Pearson for quantitative data or Spearman analysis for nonparametric variables. A receiver operating characteristic (ROC) curve was plotted to identify the predictive ability of the eosinophil ratio for GI lesions and determined the cut-off values. Survival analysis was conducted using Kaplan–Meier curves and compared using log-rank tests. Multivariate logistic regression analysis was performed to assess independent factors for GI involvement. A nomogram was created with the aim of facilitating the calculation of the prediction score for GI lesions in EGPA. The model performance was evaluated using the concordance index (C-index), calibration curve, and ROC curve. The internal validation of the model was performed using Bootstrap with 1000 resamplings.

Results

Demographic features of patients with EGPA in this cohort

In this EGPA cohort, GI lesions were observed in 52 (31.5%) patients. Among the patients with GI manifestations, 22 developed severe GI disorder and the remaining 30 presented with relatively mild symptoms. The average age of EGPA patients was 45.3 ± 14.7 years and the ratio of male to female was 1.5:1 (98 males: 67 females). The median duration from the initial symptoms to EGPA diagnosis was 12 (IQR, 1–47) months, and the median duration from allergy to EGPA diagnosis was 25 (IQR, 2–74) months.

Clinical characteristics of GI involvement in patients with EGPA

The clinical characteristics of 22 patients with EGPA-related GI involvement in this cohort are summarized in Table 1. Furthermore, we reviewed the clinical features, treatment, and outcomes of patients with severe GI involvement in Table 2 to provide more details. The most common manifestations were abdominal pain (78%), diarrhea (40.4%), and nausea and/or vomiting (32.7%). Severe GI involvement mainly presented as upper and/or lower GI hemorrhages (14/52, 26.9%), ulcers (9/52, 17.3%), and obstructions (5/52, 9.6%). All five patients with obstruction had incomplete bowel obstruction, characterized by abdominal pain, reduced defecation and exhaust, and abdominal distension. Pancreatitis occurred in three patients with EGPA (5.8%), characterized by young age (26, 27, and 38 years old), and imaging showing that the pancreas was plump or diffusely enlarged. One patient experienced a recurrent attack of pancreatitis, which was considered chronic inflammation. Another patient was complicated with pancreatic pseudocyst, causing worsening abdominal pain. Through CT-guided percutaneous drainage of pseudocysts, his abdominal pain was alleviated and the amylase decreased to the normal range. GI perforation was observed in two patients with upper and lower GI involvement. Both patients were under 40 years of age, developed severe infections, and died within two months. The most common site of lesions was the upper GI tract including the stomach and duodenum, followed by the lower GI tract, which mainly included the small intestine and colorectum. Occasionally, the pancreas and gallbladder were affected.

Table 1 Characteristics of gastrointestinal involvement in EGPA
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Table 2 Clinical features, treatment, and outcomes of EGPA patients with severe GI lesions
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Twenty-eight patients with EGPA and GI lesions had post-operative pathology. Of these, twenty-three patients presented with chronic or acute inflammation of GI mucosa with eosinophilic infiltration, indicating eosinophilic gastroenteritis. A few patients showed lymphoid follicle formation or lymphocyte aggregation (six patients), inflammatory exudation (three patients), granulation tissue formation (one patient), or necrosis (one patient).

Comparison of clinical features between EGPA patients with and without GI lesions

GI-affected group had a significantly higher eosinophil ratio [32.0 (IQR 20.5–46.4) % vs. 23.5 (IQR 12.6–37.5) %, P = 0.016] than GI-unaffected group (Table 3). Compared to GI-unaffected group, GI-affected group had higher percentages of eosinophilic tissue infiltration (detected in any organs) (82.9% vs. 55.3%, P = 0.006), weight loss (55.8% vs. 32.7%, P = 0.005), and central nervous system (CNS) involvement (26.9% vs. 10.6%, P = 0.008). Fever, myalgia, and skin involvement were more common in GI-affected group than in GI-unaffected group; however, the differences were not significant (P > 0.05). Other clinical manifestations, demographics, and laboratory test results present no statistical differences between patients with and without GI lesions.

Table 3 Comparison of clinical features between EGPA patients with and without GI lesions
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Disease activity and prognosis assessment at baseline

As shown in Table 3, the baseline disease activity in GI-affected group was higher than that in GI-unaffected group, as evaluated by median BVAS (18 vs. 14, P = 0.001). When we removed GI domain from the BVAS system, the two groups were comparable (16 vs. 14, P = 0.116). Regarding the prognosis assessment at baseline, the percentage of FFS ≥ 2 was higher in GI-affected group than in GI-unaffected group (32.7% vs. 9.7%, P < 0.001).

Stratified analysis of EGPA patients with GI lesions

Patients with GI lesions were stratified into two subgroups: patients with and without severe GI lesions (Table 4). The group with severe GI lesions had a shorter duration from the initial symptoms to EGPA diagnosis compared with the group without severe GI lesions [4 (IQR 1–18) versus 18 (IQR 7–60) months, P = 0.028]. Concerning laboratory examinations, higher trends were observed in erythrocyte sedimentation rate [44 (IQR 29–66) vs. 29 (IQR 6–45) mm/1h, P = 0.056] and C-reactive protein [39.5 (IQR 10.6–87.2) vs. 6.8 (IQR 2.0–40.7) mg/L, P = 0.053]. Notably, positive proteinase 3-ANCA results were only observed in severe GI-affected group (13.6% vs. 0%, P = 0.070). Regarding clinical manifestations, the group with severe GI lesions had less frequent severe asthma (45.5% vs. 76.7%, P = 0.021) and ear-nose-throat (ENT) involvement (45.5% vs. 80.0%, P = 0.010) than the group without severe GI lesions. The proportion of patients with CNS involvement was relatively higher in the severe GI-affected group (40.9% vs. 16.7%, P = 0.052), but the difference between the two groups did not reach statistical significance.

Table 4 Clinical features of EGPA patients with severe gastrointestinal lesions
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Independent factors associated with the development of GI lesions in patients with EGPA

We further analyzed independent factors associated with GI involvement in patients with EGPA using a multivariable logistic regression model (Fig. 1). Eosinophilic tissue infiltration (detected in any organs) (odds ratio [OR] 5.814, 95% confidence interval [CI] 1.747–19.344, P = 0.004), weight loss (OR 3.334, 95% CI 1.188–9.355, P = 0.022), and myalgia (OR 3.902, 95% CI 1.059–14.373, P = 0.041) were the significant factors associated with GI lesions in EGPA.

Fig. 1
figure 1

Independent factors associated with gastrointestinal involvement in patients with EGPA. Multivariate logistic regression analysis was conducted for patients with gastrointestinal lesions in EGPA and the result is presented with the forest plot. CNS, central nervous system; EGPA, eosinophilic granulomatosis with polyangiitis; OR, odds ratio. Eosinophilic tissue infiltration refers to eosinophils infiltrating in any organs

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Prediction model and internal validation

Next, we established a risk prediction model via a nomogram (Fig. 2A). The final model retained weight loss, CNS involvement, myalgia, and eosinophilic tissue infiltration (detected in any organs). Each item was assigned points according to its value, and the sum of all points was associated with the predicted probability of GI lesions. The C-index for this model was 0.772 (95% CI: 0.698–0.846), and the corrected C-index was 0.755. Internal validation of the model was performed using bootstrap. The calibration curve for 1000 bootstrap replications presents a comparison of the actual and predicted probabilities in Fig. 2B. To analyze the risk stratification produced by the final equation, we outlined the ROC curve to evaluate our model in Fig. 2C (AUC = 0.772).

Fig. 2
figure 2

Prediction model performance and internal validation for GI lesions in patients with EGPA. (A) Nomogram predicting the probability of GI lesions in patients with EGPA. Points for weight loss, CNS lesions, myalgia, and Eos infiltration can be acquired using a point caliper and then summed to obtain a total score. (B) Calibration curve of GI lesions prediction model was obtained by comparing the observed and predicted risk of GI lesions in patients with EGPA. (C) Receiver operating characteristic curve of the GI lesions prediction model. AUC: area under the curve; CNS, central nervous system; EGPA, eosinophilic granulomatosis with polyangiitis; Eos_infiltration, eosinophilic tissue infiltration (detected in any organs); GI, gastrointestinal

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Eosinophils were an important parameter in assessing disease activity and predicting GI lesions

Based on the above analysis in Table 3, we found that the eosinophil ratio was significantly higher in the GI-affected group, and the eosinophilic tissue infiltration (detected in any organs) was the most significant independent factor associated with GI lesions in patients with EGPA. We further performed the correlation analysis between the circulating eosinophils and BVAS at baseline (Fig. 3A and B) and found that both the eosinophil ratio (r = 0.160, P = 0.045) and eosinophil count (r = 0.233, P = 0.004) in blood were positively correlated with BVAS at baseline. In addition, the cutoff value of the circulating eosinophil ratio was calculated to identify the GI lesions in patients with EGPA (Fig. 3C). The optimum cutoff value of the eosinophil ratio was 19.2% with a sensitivity of 82.0% and a specificity of 41.7% (area under the curve = 0.62, P = 0.0098).

Fig. 3
figure 3

Eosinophils were an important parameter to assess disease activity and predict GI lesions in EGPA. Correlation of BVAS with eosinophil ratio (A) and count (B). Pearson correlation was calibrated for the analysis. (C) Receiver operating characteristic curve of eosinophil ratio for identifying patients with GI lesions in EGPA. AUC: area under the curve; BVAS, Birmingham Vasculitis Activity Score; EGPA, eosinophilic granulomatosis with polyangiitis; EOS, eosinophil; GI, gastrointestinal

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Identification of clinical patterns of EGPA based on phenotype clusters

Five clinical patterns were identified using correlation matrix analysis (Fig. 4). “Brain-gut pattern” was well-defined based on an association between CNS lesions and GI involvement. “Joint-muscle-skin pattern” can be found in the figure, where arthritis, myalgia, and skin involvement show a close link. Cardiac manifestations were separately identified as a unique pattern on the cluster panel of EGPA (Cardiac pattern). “Respiratory pattern” was constructed based on the association between asthma and ear-nose-throat involvement. “Renal-peripheral nervous system pattern” was observed as the fifth pattern, characterized with an association between renal and peripheral nervous system involvement.

Fig. 4
figure 4

Correlation analysis of different organ involvement. Spearman’s correlation coefficient is utilized to assess the correlation between two variables. A coefficient value approaching 1 signifies a stronger positive correlation, a value approaching − 1 indicates a stronger negative correlation and a value approaching 0 indicates a weak correlation. CNS, central nervous system; ENT, ear-nose-throat; PNS, peripheral nervous system

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Treatment and outcomes

The induction therapies used in this cohort were GCs and immunosuppressants, with CYC as the primary immunosuppressive agent. MP pulse was administered more frequently in patients with severe GI involvement than in patients without severe GI involvement (50.0% vs. 16.7%, P = 0.010; Table 4). The median follow-up duration was 23 months (range 1–120 months). Overall, there was no significant difference in the outcomes between GI-affected and GI-unaffected groups (P = 0.414; Fig. 5A). The all-cause mortality rate was 8% (4/52) in GI-affected group and 4% (5/112) in GI-unaffected group. Of the four deaths in GI-affected group, two patients had severe GI lesions including perforation and bleeding, one with cerebral hemorrhage, and the other patient died from septic shock and multiple organs failure. Moreover, the cumulative survival was comparable between the two groups, although it tended to be lower in GI-affected group (log-rank test, P = 0.429; Fig. 5B).

Fig. 5
figure 5

Outcomes and survival of patients with EGPA with GI involvement. (A) Comparison of outcomes between patients with and without GI involvement in this EGPA cohort. (B) Comparison of cumulative survival rates between patients with and without GI involvement. CR, complete remission; EGPA, eosinophilic granulomatosis with polyangiitis; GI, gastrointestinal; PR, partial relief

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Discussion

Severe GI lesions are not rare in EGPA and are often linked to life-threatening manifestations. In this study, three patients with GI lesions suffered from perforation, hemorrhage, or obstruction, and finally died, indicating that severe GI lesions could contribute to an unfavorable prognosis in patients with EGPA. Similarly, a cohort study from France that included various types of systemic vasculitis showed that vasculitis accompanied by GI lesions had a terrible outcome in more than one-third of cases [15]. On the other hand, asthma and ENT lesions were significantly less common in the group with severe GI lesions, suggesting that the presence of asthma and ENT lesions may predict a more favorable prognosis. Consistently, the 2011 FFS system for systemic necrotizing vasculitis also indicated that ENT symptoms were associated with a reduced risk of mortality [10]. In this study, patients with severe GI manifestations exhibited a shorter duration from the initial symptoms to EGPA diagnosis. However, the development of asthma and ENT involvement is typically chronic and latent, which may take decades to manifest. In addition, Barcik et al. highlighted that the development of asthma is tightly linked to gut microbiota [16]. It is possible that patients with severe GI lesions have changes in gut microbiota, which can further influence the onset of asthma. This is an interesting and emerging field that requires further exploration and demonstration.

Conversely, GI lesions are a rare complication of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), which occurs in 6.5% of these patients [17]. Abdominal pain and GI bleeding are the most frequent symptoms in these patients, and GI bleeding was common cause of mortality [18, 19]. The difference in GI lesions’ incidence between EGPA and other forms of ANCA-associated vasculitis underlines the distinctiveness of EGPA from GPA and MPA [1, 20], which may be attributed to eosinophil infiltration in the GI walls in EGPA. GI histology of EGPA in our cohort is characterized by eosinophilic gastroenteritis. The eosinophils infiltrated in different layers of the GI tract correspond to various manifestations. Specifically, mucosal eosinophil infiltration gives rise to diarrhea, vomiting, bleeding, or malabsorption, while muscular involvement is frequently associated with obstructive symptoms [21].

The potential risk factors associated with GI lesions in EGPA were explored in this cohort. Eosinophilic tissue infiltration (detected in any organs), weight loss, and myalgia were independently associated with GI lesions. Circulating eosinophil count and eosinophil ratio were positively correlated with disease activity and the eosinophil ratio aids in predicting the onset of GI lesions. Studies also indicate that eosinophilia in EGPA is not only an important biomarker but also plays an essential role in the pathogenesis of GI lesions by the release of various lipid mediators, cytokines, and cytotoxic secondary granule constituents [22,23,24]. In EGPA, weight loss was a prominent predictor for GI involvement, which could be related to malabsorption of patients affected by GI lesions. The higher frequency of myalgia in patients with GI lesions might signify a potent role of eosinophilia in muscle involvement, potentially associated with the release of eosinophil cationic protein [25]. Our nomogram provided a more precise prediction model for GI lesions in patients with EGPA, suggesting that GI lesions should be screened carefully when weight loss, myalgia, CNS manifestations, and/or eosinophilic tissue infiltration (detected in any organs) are present.

The underlying association between diverse clinical phenotypes is a research focus. Our previous study revealed that ANCA status is closely related to clinical phenotypes in EGPA [12]. Sang‑Won Lee et al. divided 210 patients with AAV into five clusters based on clinical and laboratory features, highlighting the phenotypic heterogeneity [26]. In this study, five well-defined clinical patterns were identified. First, the brain-gut pattern is prominent. Notably, three out of the four patients in GI-affected group died from severe GI or CNS lesions, hinting that the patients within the phenotype had an unfavorable prognosis. The GI tract is not only the largest immune organ, but also the largest nervous organ [27]. Close interactions are revealed between the CNS, immune system, and gut microbiome [28, 29]. Neurons modulate immune response both in the GI tract and internal organs [30]. Conversely, microbes resided in the GI tract affect neuro-immune functions through diverse pathways [31]. Brain-gut-microbiome has been implicated in the pathogenesis of autoimmune diseases such as inflammatory bowel disease [32]. The joint-muscle-skin pattern involves the superficial organs, and patients with this pattern might have a better condition and usually do not require intensive treatment. Cardiac involvement is a unique pattern, and its independent associated factor was baseline eosinophil count [13]. Asthma and ENT manifestations were clustered as the respiratory pattern, which might be associated with allergy. Renal and peripheral nervous system involvement form a pattern and their common ground lies in a higher MPO-ANCA positivity [12, 33]. Clinical pattern identification helps find the commonalities and correlations, analyze the prognoses, and develop precision treatment strategies for varied phenotypes. As Augusto Vaglio has envisioned, future studies focusing on genotype-phenotype, genotype-prognosis, and pharmacogenomics are likely to improve our understanding of AAV and refine our approaches to disease management [20].

GC therapy combined with CYC was the dominant treatment strategy in this study, and MP pulse was used more frequently in patients with severe GI involvement. This treatment strategy alone was effective in most patients. Surgery can be considered when life-threatening conditions occur such as GI perforation and continued severe GI bleeding. In a large cohort of patients with MPA and GPA, surgery was performed for those with GI perforation or severe bleeding, indicating close cooperation between surgeons and rheumatologists is required [17]. High doses of GCs may induce peritonitis without clinical signs and hamper the healing of GI walls. Therefore, more precise GC-sparing strategy should be explored in the prospective trials. Notably, novel therapies targeting interleukin-5 signaling have been shown to be efficacious and safe for some patients with EGPA, including Mepolizumab and Benralizumab, which can induce eosinophil depletion [34,35,36,37]. Given that eosinophils are crucial in the GI lesions of EGPA, Mepolizumab or Benralizumab may have remarkable effects, which need further investigation in real-world clinical trials.

Loïc Guillevin et al., in 2005, reported a low 5-year survival rate in patients with AAV, especially before 1990. Prognosis had dramatically improved after 1990, probably thanks to better management for severely ill patients, with prompt surgical intervention and the combined use of GCs and immunosuppressants [38]. In the past twenty years, the mortality of patients with EGPA has significantly decreased. In our study, the cumulative mortality for all patients with EGPA was around 5.5%. No significant outcome differences were found between patients with and without GI lesions. Possible reasons are as follows: first, the sample size and the follow-up duration may have been insufficient to reveal the statistical differences. Second, patients with severe GI lesions in our hospital received the positive and effective treatment due to early detection and diagnosis, which benefited from our increasing insight into EGPA.

This study had limitations. As a retrospective study, the analysis indicators may be incomplete, and the statistical efficiency may be reduced. Owing to the rarity of EGPA, the sample size remained relatively small, and the prediction model was not tested with an external cohort. As a result, collaboration across medical centers, as well as a prospective long-term follow-up study, is warranted to obtain more evidence-based medical data on patients with EGPA.

Conclusions

GI lesions are frequently seen in patients with EGPA and severe conditions can manifest as bleeding, obstruction, pancreatitis, and perforation. Eosinophilic tissue infiltration (detected in any organs), weight loss, and myalgia are independent factors associated with GI lesions in EGPA. Furthermore, we developed a scoring model that predicted the risk of GI lesions onset in patients with EGPA. Five unique phenotypic patterns were identified, underscoring the importance of recognizing the strong link between diverse clinical manifestations in EGPA.

Data availability

No datasets were generated or analysed during the current study.

References

  1. White JPE, Dubey S. Eosinophilic granulomatosis with polyangiitis: a review. Autoimmun rev. 2023;22(1).

  2. Emmi G, Bettiol A, Gelain E, Bajema IM, Berti A, Burns S, et al. Evidence-based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis. Nat Rev Rheumatol. 2023;19(6):378–93.

    Article  PubMed  Google Scholar 

  3. Liu S, Han L, Li M, Tian X, Zeng X, Lu Y, et al. Sex differences in clinical manifestations of hospitalized patients with Eosinophilic Granulomatosis with Polyangiitis: a retrospective cohort study. J Rheumatol. 2023;50(10):1318–25.

    Article  CAS  PubMed  Google Scholar 

  4. Lyons PA, Peters JE, Alberici F, Liley J, Coulson RMR, Astle W, et al. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat Commun. 2019;10(1):5120.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Mouthon L, Dunogue B, Guillevin L. Diagnosis and classification of eosinophilic granulomatosis with polyangiitis (formerly named Churg-Strauss syndrome). J Autoimmun. 2014;48–49:99–103.

    Article  PubMed  Google Scholar 

  6. Li R, Chen Y, Zhang S, Peng L, Zhou J, Fei Y, et al. Clinical characteristics and long-term outcome of patients with gastrointestinal involvement in eosinophilic granulomatosis with polyangiitis. Front Immunol. 2022;13:1099722.

    Article  CAS  PubMed  Google Scholar 

  7. Kawasaki K, Nakamura S, Esaki M, Kurahara K, Eizuka M, Okamoto Y, et al. Gastrointestinal involvement in patients with vasculitis: IgA vasculitis and eosinophilic granulomatosis with polyangiitis. Endosc Int Open. 2019;7(11):E1333–43.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fijolek J, Radzikowska E. Eosinophilic granulomatosis with polyangiitis – advances in pathogenesis, diagnosis, and treatment. Front Med. 2023;10.

  9. Guillevin L, Lhote F, Gayraud M, Cohen P, Jarrousse B, Lortholary O, et al. Prognostic factors in polyarteritis nodosa and churg-Strauss syndrome. A prospective study in 342 patients. Medicine. 1996;75(1):17–28.

    Article  CAS  PubMed  Google Scholar 

  10. Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, Toumelin PL. The five-factor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine. 2011;90(1):19–27.

    Article  PubMed  Google Scholar 

  11. Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990;33(8):1094–100.

    Article  CAS  PubMed  Google Scholar 

  12. Liu S, Han L, Liu Y, Yang J, Zhang Y, Li M, et al. Clinical significance of MPO-ANCA in Eosinophilic Granulomatosis with Polyangiitis: experience from a longitudinal Chinese cohort. Front Immunol. 2022;13:885198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu S, Guo L, Zhang Z, Li M, Zeng X, Wang L, et al. Cardiac manifestations of eosinophilic granulomatosis with polyangiitis from a single-center cohort in China: clinical features and associated factors. Ther Adv Chronic Dis. 2021;12:2040622320987051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Luqmani RA, Bacon PA, Moots RJ, Janssen BA, Pall A, Emery P, et al. Birmingham Vasculitis Activity score (BVAS) in systemic necrotizing vasculitis. QJM: Monthly J Association Physicians. 1994;87(11):671–8.

    CAS  Google Scholar 

  15. Gendreau S, Porcher R, Thoreau B, Paule R, Maurier F, Goulenok T, et al. Characteristics and risk factors for poor outcome in patients with systemic vasculitis involving the gastrointestinal tract. Semin Arthritis Rheum. 2021;51(2):436–41.

    Article  CAS  PubMed  Google Scholar 

  16. Barcik W, Boutin RCT, Sokolowska M, Finlay BB. The role of lung and gut microbiota in the Pathology of Asthma. Immunity. 2020;52(2):241–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Eriksson P, Segelmark M, Hallböök O, Frequency. Diagnosis, treatment, and Outcome of Gastrointestinal Disease in granulomatosis with polyangiitis and microscopic polyangiitis. J Rheumatol. 2018;45(4):529–37.

    Article  PubMed  Google Scholar 

  18. Masiak A, Zdrojewski Ł, Zdrojewski Z, Bułło-Piontecka B, Rutkowski B. Gastrointestinal tract involvement in granulomatosis with polyangiitis. Prz Gastroenterol. 2016;11(4):270–5.

    PubMed  PubMed Central  Google Scholar 

  19. Latus J, Koetter I, Fritz P, Kimmel M, Biegger D, Ott G, et al. Gastrointestinal involvement in granulomatosis with polyangiitis and microscopic polyangiitis: histological features and outcome. Int J Rheum Dis. 2014;17(4):412–9.

    Article  PubMed  Google Scholar 

  20. Trivioli G, Marquez A, Martorana D, Tesi M, Kronbichler A, Lyons PA, et al. Genetics of ANCA-associated vasculitis: role in pathogenesis, classification and management. Nat Rev Rheumatol. 2022;18(10):559–74.

    Article  CAS  PubMed  Google Scholar 

  21. Hogan SP, Rothenberg ME. Eosinophil function in Eosinophil-associated gastrointestinal disorders. Curr Allergy Asthma Rep. 2006;6(1):65–71.

    Article  CAS  PubMed  Google Scholar 

  22. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol. 2004;113(1):11–28. quiz 9.

    Article  CAS  PubMed  Google Scholar 

  23. Khoury P, Grayson PC, Klion AD. Eosinophils in vasculitis: characteristics and roles in pathogenesis. Nat Rev Rheumatol. 2014;10(8):474–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Diny NL, Rose NR, Cihakova D. Eosinophils in Autoimmune diseases. Front Immunol. 2017;8:484.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Sugihara R, Kumamoto T, Ito T, Ueyama H, Toyoshima I, Tsuda T. Human muscle protein degradation in vitro by eosinophil cationic protein (ECP). Muscle Nerve. 2001;24(12):1627–34.

    Article  CAS  PubMed  Google Scholar 

  26. Lee LE, Pyo JY, Ahn SS, Song JJ, Park Y-B, Lee S-W. Antineutrophil cytoplasmic antibody-associated vasculitis classification by cluster analysis based on clinical phenotypes: a single-center retrospective cohort study. Clin Rheumatol. 2023;43(1):367–76.

    Article  PubMed  Google Scholar 

  27. Niesler B, Kuerten S, Demir IE, Schäfer KH. Disorders of the enteric nervous system - a holistic view. Nat Reviews Gastroenterol Hepatol. 2021;18(6):393–410.

    Article  Google Scholar 

  28. Sharon G, Sampson TR, Geschwind DH, Mazmanian SK. The Central Nervous System and the gut Microbiome. Cell. 2016;167(4):915–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Godinho-Silva C, Cardoso F, Veiga-Fernandes H. Neuro-Immune cell units: a New Paradigm in Physiology. Annu Rev Immunol. 2019;37:19–46.

    Article  CAS  PubMed  Google Scholar 

  30. Pavlov VA, Tracey KJ. Neural regulation of immunity: molecular mechanisms and clinical translation. Nat Neurosci. 2017;20(2):156–66.

    Article  CAS  PubMed  Google Scholar 

  31. Chiu I, Rolls A. Editorial overview: brain, gut and immune system interactions. Curr Opin Neurobiol. 2020;62:iii–v.

    Article  CAS  PubMed  Google Scholar 

  32. Bonaz BL, Bernstein CN. Brain-gut interactions in inflammatory bowel disease. Gastroenterology. 2013;144(1):36–49.

    Article  PubMed  Google Scholar 

  33. Zhang Z, Liu S, Guo L, Wang L, Wu Q, Zheng W, et al. Clinical characteristics of Peripheral Neuropathy in Eosinophilic Granulomatosis with polyangiitis: a retrospective single-center study in China. J Immunol Res. 2020;2020:1–10.

    CAS  Google Scholar 

  34. Bettiol A, Urban ML, Dagna L, Cottin V, Franceschini F, Del Giacco S, et al. Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis: a European Multicenter Observational Study. Arthritis Rheumatol. 2022;74(2):295–306.

    Article  CAS  PubMed  Google Scholar 

  35. Nanzer AM, Maynard-Paquette AC, Alam V, Green L, Thomson L, Lam J, et al. Long-term effectiveness of Benralizumab in Eosinophilic Granulomatosis with Polyangiitis. J Allergy Clin Immunol Pract. 2024;12(3):724–32.

    Article  CAS  PubMed  Google Scholar 

  36. Bettiol A, Urban ML, Padoan R, Groh M, Lopalco G, Egan A, et al. Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study. Lancet Rheumatol. 2023;5(12):e707–15.

    Article  CAS  PubMed  Google Scholar 

  37. Wechsler ME, Nair P, Terrier B, Walz B, Bourdin A, Jayne DRW, et al. Benralizumab versus Mepolizumab for Eosinophilic granulomatosis with Polyangiitis. N Engl J Med. 2024;390(10):911–21.

    Article  CAS  PubMed  Google Scholar 

  38. Pagnoux C, Mahr A, Cohen P, Guillevin L. Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine. 2005;84(2):115–28.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank all the patients who participated in our study and all the professional staff at our hospital.

Funding

This work was supported by the Chinese National Key Technology R&D Program, Ministry of Science and Technology (2022YFC2504600), Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2023-RW320-01), Bethune Charitable Foundation (PAYJ-057), Beijing Chao-Yang Hospital Golden Seeds Foundation (CYJZ202216), Fundamental Research Funds for the Central Universities (3332022107).

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Author notes

  1. Suying Liu and Yunjiao Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, the Ministry of Education Key Laboratory, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China

    Suying Liu, Yunjiao Yang, Chengmei He, Mengtao Li, Xinping Tian, Li Wang & Fengchun Zhang

  2. Department of Rheumatology and Clinical Immunology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

    Suying Liu & Juan Meng

  3. Department of Rheumatology and Clinical Immunology, the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Linna Han

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Contributions

LW and FZ designed the study. SL wrote the manuscript. LW revised the manuscript. LH, SL, YY, and CH collected the data. SL and YY analyzed the data. ML, XT, LW, and FZ enrolled and managed the patients. JM provided technical advice. All authors critically reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Li Wang or Fengchun Zhang.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of PUMCH (number S-K1385, Beijing, China). As a retrospective study, the patient consent was not required but their privacy was protected well.

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Not applicable.

Competing interests

The authors declare no competing interests.

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Liu, S., Yang, Y., Han, L. et al. Gastrointestinal lesions of eosinophilic granulomatosis with polyangiitis: a prediction model and clinical patterns. Arthritis Res Ther 27, 3 (2025). https://doi.org/10.1186/s13075-024-03467-7

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Keywords

Arthritis Research & Therapy

ISSN: 1478-6362

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