成人亨诺-舍恩莱因紫癜的临床回顾及与胃肠道受累相关的预测因素分析

《Frontiers in Immunology》：Clinical review of adult Henoch–Sch?nlein purpura and analysis of predictors related to gastrointestinal involvement

成人HSP胃肠受累预测因子及临床特征研究。通过回顾性分析206例成人HSP患者，发现胃肠受累组（22.82%）较非胃肠组（77.18%）更易出现广泛性紫癜、水疱样/坏死性皮疹及关节受累，D-二聚体>1040μg/L为独立预测因子（OR=1.460）。胃肠受累患者误诊率高达23.40%，治疗需加强早期识别。

　　
Henoch–Sch?nlein purpura (HSP) represents a small-vessel vasculitis primarily affecting children but with distinct clinical patterns and worse outcomes in adults. This study systematically investigated predictors of gastrointestinal (GI) involvement in adult HSP patients through a retrospective analysis of 206 cases, providing critical insights into disease progression and diagnostic challenges.

The study categorized patients into two groups based on GI involvement: 47 (22.82%) with GI+ involvement and 159 (77.18%) without (GI?). Key differences emerged between groups. GI+ patients demonstrated more extensive skin lesions extending beyond lower limbs, higher prevalence of atypical rashes such as bullae and necrosis, and significantly increased joint involvement compared to GI? counterparts. This aligns with prior observations in pediatric populations where severe skin manifestations correlate with gastrointestinal complications, though the adult-specific association with joint involvement represents a novel finding.

Laboratory analysis revealed profound systemic inflammation in GI+ patients. Elevated D-dimer (>1,040 μg/L) emerged as the sole independent predictor of GI involvement through multivariate logistic regression (OR=1.460, 95% CI 1.151-1.852, P<0.05). This finding reflects the pathophysiological mechanism of HSP, where endothelial damage triggers coagulation cascade activation and microthrombi formation, leading to compensatory fibrinolysis and elevated D-dimer. Notably, while CRP showed significant group differences, its clinical utility as a predictive biomarker remained uncertain due to conflicting evidence in previous studies.

The study documented a 9.71% overall misdiagnosis rate, escalating to 23.40% in GI+ patients. Particular vulnerability existed in cases presenting solely with abdominal pain (50% misdiagnosis rate), often leading to inappropriate gastric protection therapy and subsequent complications like intestinal necrosis. This underscores the critical need for integrating systemic inflammatory markers with clinical presentation patterns in HSP diagnosis.

Regarding treatment, patients with GI+ involvement received higher methylprednisolone dosages (0.73±0.22 mg/kg/day vs 0.59±0.18 mg/kg/day) and more aggressive immunosuppressive regimens, including cyclophosphamide and immunoglobulin therapy. However, no significant difference in disease duration was observed between groups, suggesting that treatment intensity rather than disease course correlates with GI involvement severity.

Prognostic analysis highlighted prolonged hospitalization (mean 21.3 vs 9.8 days) and higher recurrence risk (16.99% vs 9.87%) in GI+ patients, though no significant difference in overall mortality was noted. The median recurrence interval of 13.5 months extended the clinical follow-up window, revealing long-term complications even after initial treatment. Notably, all recurrent cases presented solely with skin rashes initially, highlighting the potential for silent gastrointestinal involvement.

The study identified three critical predictors for GI involvement: 1) atypical rashes (blisters/necrosis) showing 34.04% prevalence in GI+ vs 3.03% in GI?; 2) elevated D-dimer levels (≥1,040 μg/L) present in 68.09% of GI+ patients versus 34.57% in GI?; and 3) joint involvement occurring in 53.19% of GI+ vs 21.38% of GI?. These findings were validated through ROC curve analysis with D-dimer demonstrating 95.7% sensitivity and 76.1% specificity.

Pathophysiological implications suggest dual mechanisms for GI involvement. First, the IgA1 glycosylation defect leads to immune complex deposition in mesenteric microvasculature, causing mucosal edema and hemorrhage. Second, systemic inflammation drives endothelial dysfunction, promoting platelet activation and fibrinolysis. The elevated D-dimer serves as both a diagnostic marker and a therapeutic indicator, correlating with disease severity and treatment response.

Clinical implications are substantial. For diagnosis, the combination of atypical rashes (especially necrotic lesions) with D-dimer >1,040 μg/L should trigger algorithmic consideration of GI involvement. For treatment, the observed dose difference (0.14 mg/kg/day) in methylprednisolone administration between groups suggests potential therapeutic targets. However, the lack of significant renal involvement correlation requires further validation.

Limitations include single-center retrospective design and potential recall bias affecting recurrence data. The small sample size (47 GI+ cases) limits generalizability, particularly regarding rare complications like intestinal perforation. Despite these constraints, the study advances predictive models by establishing D-dimer as a validated biomarker for GI involvement, a finding with potential impact on early intervention and outcome prediction.

The discovery of elevated D-dimer as an independent predictor provides a novel diagnostic tool. Clinicians can now prioritize patients with D-dimer >1,040 μg/L for endoscopic evaluation or fecal occult blood testing, particularly when accompanied by atypical rashes or joint symptoms. This approach may reduce misdiagnosis rates and enable timely initiation of immunosuppressive therapies to prevent progression to severe complications.

The study also reveals important phenotypic differences between pediatric and adult HSP. While pediatric cases more frequently show renal involvement, adult patients exhibit stronger GI-joint axis correlations. This divergence may stem from differing pathogenic pathways in adults, where systemic inflammation and coagulopathy play more dominant roles in multi-organ involvement.

In summary, this investigation establishes a comprehensive predictive framework for GI involvement in adult HSP through clinical presentation patterns (extensive skin lesions, joint involvement) and specific biomarkers (D-dimer >1,040 μg/L). The findings not only improve diagnostic accuracy but also inform therapeutic strategies by identifying high-risk subgroups requiring more aggressive intervention. Future research should focus on longitudinal tracking of D-dimer levels to assess their utility in monitoring disease activity and recurrence risk.