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.