Severe eczema and Hyper-IgE in Loeys–Dietz-syndrome — Contribution to new findings of immune dysregulation in connective tissue disorders

• LDS patients can present with severe immune dysregulation resembling HIES.
• Skeletal and connective tissue manifestations in LDS and HIES have similarities.
• In contrast to HIES, Th17 and memory B-cell differentiation appear to be normal in LDS patients.

Loeys–Dietz syndrome (LDS) is a connective tissue disorder caused by monoallelic mutations in TGFBR1 and TGFBR2, which encode for subunits of the transforming growth factor beta (TGFβ) receptor. Affected patients are identified by vascular aneurysms with tortuosity and distinct morphological presentations similar to Marfan syndrome; however, an additional predisposition towards asthma and allergy has recently been found. We describe two patients with a novel missense mutation in TGFBR1 presenting with highly elevated levels of IgE and severe eczema similar to autosomal-dominant Hyper-IgE syndrome (HIES). Mild allergic manifestations with normal up to moderately increased IgE were observed in 3 out of 6 additional LDS patients. A comparison of this cohort with 4 HIES patients illustrates the significant overlap of both syndromes including eczema and elevated IgE as well as skeletal and connective tissue manifestations.