Gastrointestinal manifestations in adult IgA vasculitis over 8.5 years: severity assessment and therapeutic outcomes

¹Department of Internal Medicine, Farhat Hached University Hospital, Sousse, Tunisia, ²Intensive Care Unit, Farhat Hached University Hospital, Sousse, Tunisia, ³Department of Dermatology, Farhat Hached University Hospital, Sousse, Tunisia, ⁴Department of Forensic Pathology, Sidi Bouzid Hospital, Sidi Bouzid, Tunisia, ⁵Department of Digestive Surgery, Badreddine Elaloui University Hospital, Kasserine, Tunisia

^&Corresponding author
Marwa Zghidi, Intensive Care Unit, Farhat Hached University Hospital, Sousse, Tunisia

Introduction    

IgA vasculitis (IgAV), previously known as Henoch-Schonlein purpura, is a small-vessel systemic vasculitis characterized by immune complex tissue deposits containing immunoglobulin A (IgA) [1,2]. This condition predominantly affects children and adolescents, with an estimated annual incidence of 10-20 cases per 100,000 children, compared to only 0.1-1.8 cases per 100,000 adults [3]. This 10- to 100-fold difference in incidence renders adult IgAV a genuinely rare disease, which has direct implications for study feasibility and sample size in single-center research.

The disease course in adults differs significantly from that in children [4]. Adult patients experience a higher incidence and greater severity of clinical manifestations, particularly gastrointestinal (GI) involvement. Short-term prognosis is largely determined by the severity of GI complications, while long-term outcomes depend on renal involvement [5,6]. Despite the clinical significance of GI manifestations in adult IgAV, management of digestive complications remains poorly codified. The existing literature on this subject is scarce, and evidence-based guidelines are not currently available [7]. This gap underscores the need for comprehensive studies examining the clinical spectrum, therapeutic approaches, and outcomes of GI involvement in adult IgAV. This study aimed to describe the clinical, therapeutic, and prognostic aspects of GI involvement in adult IgAV in a single-center cohort, with particular attention to severity assessment and treatment outcomes.

Methods     

Study design and population: this retrospective observational study included patients diagnosed with IgAV who were admitted to the Internal Medicine Department of Farhat Hached University Hospital, Sousse, Tunisia, between January 2014 and June 2022 (8.5 years). Patients aged 16 years or older at the time of diagnosis were included. The diagnosis of IgAV was established according to either the 1990 American College of Rheumatology (ACR) criteria or the 2012 Chapel Hill Consensus Conference (CHCC) nomenclature [1,2].

Inclusion criteria: age ≥16 years, confirmed IgAV diagnosis per ACR 1990 or CHCC 2012 criteria, complete medical records available, minimum follow-up of 6 months after treatment initiation.

Exclusion criteria: incomplete clinical records, pre-existing inflammatory bowel disease or other GI pathology that could confound assessment of GI involvement, loss to follow-up before completion of initial treatment.

Definition of gastrointestinal involvement: gastrointestinal involvement was defined by the presence of at least one clinical manifestation and at least one objective criterion (imaging or endoscopic/histological finding). Patients with only clinical symptoms, without objective confirmation, were not classified as having definite GI involvement.

Clinical manifestations: abdominal pain, vomiting, altered bowel movements, upper and/or lower GI bleeding.

Objective confirmation (at least one required): (1) imaging: abdominal ultrasound or CT scan evidence of GI wall thickening, intestinal ischemia, hematoma, perforation, or intussusception; (2) endoscopy/histology: leukocytoclastic vasculitis on digestive biopsy with or without IgA deposits on direct immunofluorescence.

Severity assessment: clinical severity was assessed using the Trouillier scoring system [7]: score ≥3 = severe; score = 2 = moderately severe; score = 0 or 1 = mild. Radiological severity was assessed by CT: severe if parietal thickening was present on multiple intestinal segments, or if ischemia, hematoma, perforation, or intussusception was identified.

Outcome definition

Prolonged remission: complete absence of GI symptoms for at least six consecutive months following completion of corticosteroid tapering, without re-introduction of corticosteroids or additional immunosuppressive agents during this period.

Special population: MALT lymphoma case: one patient was identified as having concurrent gastric MALT lymphoma. Given the distinct clinical trajectory and combined therapeutic regimen (corticosteroids + CHOP chemotherapy), this patient was excluded from the primary efficacy analysis and is described separately as a case note.

Statistical analysis: data were analyzed using SPSS software (version 25.0). The Pearson chi-square test or Fisher's exact test was used for categorical variables. Student's t-test was used for continuous variables. A p-value <0.05 was considered statistically significant. Given the descriptive and exploratory nature of this study and the limited sample size inherent to a rare adult disease, all p-values should be interpreted with caution.

Ethics approval: this retrospective chart review was conducted in accordance with the Declaration of Helsinki. Given the retrospective nature of the study and the complete anonymization of all data before analysis, the Institutional Ethics Committee of Farhat Hached University Hospital granted an exemption from full ethical review and waived the requirement for individual informed consent. The formal exemption letter issued by the Ethics Committee (reference: 30052026) is available upon request and has been submitted to the journal as a supplementary document. All data were anonymized before analysis.

Results     

Patient selection: as shown in the patient flow diagram for this study (Figure 1). Of 34 patients initially identified with a diagnosis of IgA vasculitis over the 8.5-year study period, 4 were excluded: 1 due to incomplete medical records, 2 due to pre-existing gastrointestinal disease that could confound GI involvement assessment, and 1 due to loss to follow-up before treatment completion. The remaining 30 patients were included in the present study.

General population characteristics: over the 8.5-year study period, 30 patients were diagnosed with IgAV and included in this study, corresponding to a mean accrual rate of 3.5 cases per year. The mean age at diagnosis was 45.6±18.1 years (range: 16-83 years). The cohort consisted of 14 men (46.7%) and 16 women (53.3%), with a male-to-female ratio of 0.87. A family history of autoimmune disease was identified in two patients (6.7%). Organ involvement is presented in Table 1.

Gastrointestinal manifestations: gastrointestinal involvement was present in 20 patients (66.7%). All 20 patients had objective confirmation of GI involvement: 18 by CT imaging, 12 by upper GI endoscopy, and 4 by colonoscopy; 8 patients had both imaging and endoscopic confirmation. Clinical manifestations are detailed in Table 2. Abdominal pain was reported by all patients (100%), vomiting in 14 (70%), GI bleeding in 8 (40%), and altered bowel movements in 6 (30%). Hematemesis and melena each occurred in 4 cases (20%).

Clinical and radiological severity: using the Trouillier clinical severity score, severe digestive involvement (score ≥3) was found in 9 patients (45%), moderately severe disease (score = 2) in 6 patients (30%), and mild disease in 5 patients (25%). Severe radiological involvement was identified in 7 of 18 patients who underwent CT imaging (39%). Distribution is presented in Table 3.

Endoscopic and histological findings: upper GI endoscopy was performed in 12 of 20 patients (60%). The most common findings were mucosal erythema (75% of those scoped), petechial purpura (60%), and mucosal erosions (50%). Colonoscopy was performed in 8 patients, revealing abnormal findings in 4 (50%), predominantly circumscribed erythematous lesions of 3-10 mm. Direct immunofluorescence demonstrated IgA deposits in 2 patients (10% of all GI patients; 17% of those biopsied). These findings are summarized in Table 4.

Associated conditions: helicobacter pylori infection was identified in 4 patients (20%). All received eradication therapy. Complete resolution of cutaneous and gastric manifestations occurred in 1 patient following eradication alone. The remaining 3 patients required additional corticosteroid therapy; 2 achieved prolonged remission, and 1 had a partial response.

Case note: gastric MALT lymphoma: one 43-year-old female patient with IgAV and GI involvement was found to have concurrent gastric MALT lymphoma on endoscopic biopsy. H. pylori infection was confirmed. She received combined prednisone (0.5 mg/kg for 6 months) and CHOP chemotherapy, achieving complete histological and clinical remission at 12-month follow-up. This patient was excluded from the primary treatment outcome analysis.

Treatment and outcomes: corticosteroid therapy was administered to all 19 patients in the primary efficacy analysis. The typical regimen was prednisone 0.5-1 mg/kg/day with gradual tapering over 8-12 weeks. Prolonged remission (absence of GI symptoms for ≥6 months after treatment completion) was achieved in 12 patients (63%). Seven patients (37%) experienced persistent symptoms or relapse requiring treatment adjustment.

Predictive factors: gastrointestinal involvement was numerically more frequent in male patients (p=0.058), but this difference did not reach statistical significance. No significant association was identified between GI involvement and cutaneous purpura distribution, renal involvement, or age at diagnosis.

Discussion     

This single-center descriptive study provides data on GI involvement in adult IgAV over the years. The low accrual rate of 3.5 cases/year, yielding only 30 patients over 8.5 years, itself constitutes an important finding, directly reflecting the rarity of IgAV in the adult population. The GI involvement occurred in 20 patients (66.7%). The most common symptom was abdominal pain (100%), followed by vomiting (70%) and GI bleeding (40%). In addition, the current study finds that male gender showed a non-significant trend toward increased GI involvement (p=0.058).

Clinical manifestations and severity: the predominance of abdominal pain (100%), high frequency of vomiting (70%), and GI bleeding (40%) confirms the significant morbidity of GI involvement in adult IgAV. Systematic application of the Trouillier score allowed objective disease stratification. Our severity distribution is broadly consistent with the original Trouillier cohort [7], which reported severe disease in 66.7%. The more severe GI phenotype in adults compared to children is well recognized and may relate to higher comorbidity burden, delayed diagnosis, or age-related differences in immune regulation [4,8].

Imaging and endoscopic evaluation: computed tomography imaging identified severe radiological involvement in 39% of patients who underwent imaging. The characteristic features of intestinal wall thickening and mesenteric edema facilitated early diagnosis [5,9]. Upper GI endoscopy and colonoscopy findings in our cohort, including mucosal erythema, petechial purpura, and erosions, are consistent with those reported in previous series [10,11]. The limited histological yield from endoscopic biopsies, IgA deposits confirmed in only 17% of biopsied patients, reflects the superficial nature of most endoscopic biopsies and the patchy distribution of vasculitic lesions [12,13].

Therapeutic considerations: prolonged remission was achieved in 63% of patients, consistent with the efficacy of corticosteroids in GI IgAV reported in both pediatric and adult studies [14,15]. However, the absence of a control group and retrospective design limit causal inference. The 37% rate of partial response or relapse highlights the need for steroid-sparing alternatives in refractory disease.

Helicobacter pylori and associated malignancy: H. pylori was identified in 20% of patients. The association between H. pylori infection and IgAV has been previously described, with several reports suggesting that eradication may contribute to disease resolution in a subset of patients [16,17]. In our cohort, eradication alone was sufficient in only one case, suggesting a limited independent role in disease maintenance in most patients. The MALT lymphoma case illustrates the importance of systematic malignancy screening in adult IgAV, particularly in patients over 40 years of age [18-20].

Predictive factors: the non-significant trend toward increased GI involvement in male patients (p=0.058) is consistent with observations by Hočevar et al. [21] but remains hypothesis-generating in our cohort. Several biomarkers, including D-dimer [22], neutrophil-to-lymphocyte ratio [23], and fecal calprotectin [24] have been proposed as predictive markers and warrant prospective evaluation.

Study limitations: this study has several limitations that must be acknowledged. Most fundamentally, the sample size of 30 patients, despite an 8.5-year collection period, is small for a single-center study. This low accrual rate is not a methodological limitation but rather an inherent epidemiological constraint: IgAV is predominantly a disease of childhood, with an estimated annual incidence of 10-20 per 100,000 in children and only 0.1-1.8 per 100,000 in adults [3]. This condition makes it nearly impossible to achieve large sample sizes in a single-institution study without multi-year follow-up. Our accrual rate of 3.5 cases/year is consistent with the published epidemiology of adult IgAV and reflects the true rarity of this condition rather than a recruitment failure.

As a direct consequence of this small sample size, the multivariable analysis is underpowered. The absence of statistically significant predictors, including the male gender trend (p=0.058) should be interpreted as reflecting insufficient power rather than a true absence of association. A formal post-hoc power calculation confirms that a sample of 20 patients with GI involvement provides less than 40% power to detect a moderate effect size at alpha=0.05. Additional limitations include the retrospective single-center design, which introduces selection bias and limits generalizability. These limitations underscore the critical need for multicenter and international collaborative registries to study adult IgAV. Pooling data across multiple centers, ideally within a prospective registry framework, is the only feasible approach to achieving the sample sizes required for robust prognostic and therapeutic studies in this rare adult disease.

Conclusion     

In this single-center descriptive series spanning 8.5 years, the accrual of only 30 adult patients with IgAV confirms that IgAV is a rare disease in adults despite its relative frequency in children. GI manifestations occurred in approximately two-thirds of patients and were frequently severe by standardized scoring. Systematic use of clinical and radiological severity scores facilitated therapeutic decision-making. Corticosteroid therapy achieved prolonged remission in 63% of patients. The male gender showed a non-significant trend toward increased GI involvement requiring validation in larger cohorts.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Amira Atig, Marwa Zghidi, Yosr Bousokkaya: conceptualization, data collection, statistical analysis, writing original draft. Amira Atig, Marwa Zghidi, Nadia Ghariani, Wathek Thaljaoui: Methodology, writing review and editing. Amira Atig, Marwa Zghidi, Nadia Ghariani, Abdelnacer Nefis: supervision, validation, final approval. All authors have read and approved the final version of this manuscript.

Acknowledgments     

The authors wish to thank the medical and nursing staff of the Internal Medicine departments for their valuable contribution to patient care and data collection.

Tables and figure     

Table 1: frequency and distribution of organ system involvement among adult IgA vasculitis patients at Farhat Hached University Hospital, Sousse, Tunisia, January 2014-June 2022 (N=30)

Table 2: frequency of clinical gastrointestinal manifestations among adult IgA vasculitis patients with confirmed gastrointestinal involvement at Farhat Hached University Hospital, Sousse, Tunisia, January 2014-June 2022 (N=20)

Table 3: clinical and radiological severity of gastrointestinal involvement assessed by the Trouillier scoring system and CT imaging among adult IgA vasculitis at Farhat Hached University Hospital, Sousse, Tunisia, January 2014-June 2022 (N=20)

Table 4: endoscopic and histological findings in adult IgA vasculitis patients with gastrointestinal involvement undergoing upper gastrointestinal endoscopy, colonoscopy, and mucosal biopsy at Farhat Hached University Hospital, Sousse, Tunisia, January 2014-June 2022

Figure 1: STROBE flow diagram of patient selection and outcomes; IgAV: IgA vasculitis; GI: gastrointestinal; MALT: mucosa-associated lymphoid tissue

References