High Prevalence of Pseudo-Pelger–Huët Anomaly and Neutrophil Dysplasia in Children with Celiac Disease: A Retrospective Case–Control Study

Background/Objectives: Celiac disease (CD) is a chronic immune-mediated disorder associated with a broad spectrum of extraintestinal manifestations, including hematological abnormalities. Although anemia and micronutrient deficiencies are well recognized, neutrophil morphological abnormalities have not been systematically investigated in pediatric CD; this study aimed to evaluate peripheral blood smear findings in children with CD compared with healthy controls. Methods: This retrospective case–control study included 70 children with CD and 74 healthy controls; demographic characteristics, anthropometric measurements, hematological and biochemical parameters, and peripheral blood smear findings were analyzed and compared between groups. Results: Children with CD had significantly higher frequencies of underweight status (15.7% vs. 2.7%) and short stature (21.4% vs. 1.4%) than controls. Most hematological and biochemical parameters were comparable between groups, except for platelet counts and ferritin levels, which differed significantly. Pseudo-Pelger–Huët anomaly (PPHA) was identified in 87.1% of children with CD versus 8.1% of controls (p < 0.001), and neutrophil dysplasia was observed in 52.9% versus 1.4%, respectively (p < 0.001). After adjustment for age and sex, CD remained strongly associated with PPHA (adjusted OR 81.19, 95% CI 28.65–278.45), neutrophil dysplasia (adjusted OR 93.85, 95% CI 18.46–1724.96), and the combined presence of both abnormalities (adjusted OR 79.89, 95% CI 15.86–1461.89) (all p < 0.001). ROC analysis demonstrated excellent discrimination between CD and controls (AUC = 0.924; sensitivity = 90.0%; specificity = 91.9%). Within the CD cohort, PPHA and dysplasia were not associated with celiac antibody positivity, gluten-free diet adherence, vitamin D deficiency, or comorbid conditions. Conclusions: To our knowledge, this is the first study to systematically evaluate peripheral blood smear morphology in pediatric CD, demonstrating a remarkably high prevalence of PPHA and neutrophil dysplasia. These findings suggest that neutrophil morphological abnormalities may represent an underrecognized hematological manifestation of pediatric CD, potentially reflecting chronic immune-mediated alterations in granulopoiesis. Further prospective studies are needed to clarify their pathogenesis, clinical significance, and reversibility following long-term gluten-free diet treatment.