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Summary Background Growth retardation is well described in childhood‐onset inflammatory bowel disease (IBD). Aims To study if childhood‐onset IBD is associated with reduced final adult height. Methods We identified 4201 individuals diagnosed with childhood‐onset IBD 1990‐2014 (Crohn's disease: n = 1640; ulcerative colitis: n = 2201 and IBD‐unclassified = 360) in the Swedish National Patient Register. Results Patients with IBD attained a lower adult height compared to reference individuals (adjusted mean height difference [AMHD] −0.9 cm [95% CI −1.1 to −0.7]) and to their healthy siblings (AMHD −0.8 cm [−1.0 to −0.6]). Patients with Crohn’s disease (CD) were slightly shorter than patients with ulcerative colitis (UC; −1.3 cm vs −0.6 cm). Lower adult height was more often seen in patients with pre‐pubertal disease onset (AMHD −1.6 cm [−2.0 to −1.2]), and in patients with a more severe disease course (AMHD −1.9 cm, [−2.4 to −1.4]). Some 5.0% of CD and 4.3% of UC patients were classified as growth retarded vs 2.5% of matched reference individuals (OR 2.42 [95% CI 1.85‐3.17] and 1.74 [1.36‐2.22] respectively). Conclusion Patients with childhood‐onset IBD on average attain a slightly lower adult height than their healthy peers. Adult height was more reduced in patients with pre‐pubertal onset of disease and in those with a more severe disease course.

Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.