D1.503 - Immunoglobulin Abnormalities in Cronkhite-Canada Syndrome: A Focus on IgE and IgG4

Cronkhite–Canada syndrome (CCS) is a rare, nonhereditary disease characterized by diffuse gastrointestinal polyposis and ectodermal abnormalities. Although traditionally classified as a gastrointestinal disorder, its frequent association with autoimmune diseases, favorable responsiveness to immunosuppressive therapy suggest a broader immune-mediated pathogenesis. Notably, sporadic reports of elevated total IgE (T-IgE) and IgG4 raise the possibility that CCS may share immunological features relevant to allergy and type 2 immune responses. However, the prevalence and clinical implications of these abnormalities remain unclear.

We retrospectively analyzed clinical and laboratory data from CCS patients admitted to Peking Union Medical College Hospital between December 2009 and September 2025, who underwent serum immunoglobulin testing.

Seventy-seven patients were included (median age at onset: 58 years; 76.6% male). In addition to prominent gastrointestinal symptoms (diarrhea, 88.3%), ectodermal manifestations were highly prevalent, including onychodystrophy (97.4%), hyperpigmentation (89.6%), alopecia (75.3%), and hypogeusia (75.3%). A history of allergy was present in 23.4% of patients, mainly drug allergy.Median serum T-IgE was 161.0 KuA/L (IQR 27.2–398.9 KuA/L). Elevated T-IgE (>60 KuA/L) was observed in 67.4% of patients, with 62.8% exceeding 100 KuA/L. Importantly, patients with markedly elevated T-IgE (>100 KuA/L) exhibited a significantly higher prevalence of alopecia compared with those with lower levels (P = 0.039), whereas T-IgE levels were not associated with allergy history or systemic inflammatory markers (Erythrocyte Sedimentation Rate [ESR], high-sensitivity C-reactive Protein [hsCRP]). Reduced total IgG (ref: 7-17 g/L) was observed in 40.0% of patients, and elevated IgG4(ref: <1400 mg/L) in 20.6%, although IgG4 elevation was not linked to distinct clinical phenotypes.

In this large single-center cohort, abnormalities in serum immunoglobulin levels, particularly elevated T-IgE and IgG4, were frequently observed in patients with CCS. Elevated T-IgE was associated with alopecia but not with a history of allergic disease or systemic inflammatory markers. These findings suggest that immunoglobulin dysregulation is a common laboratory feature of CCS and may be relevant to its clinical phenotype. Further studies are warranted to clarify the underlying mechanisms and the clinical significance of these immunological abnormalities.