Critical aneurysmal dilatation of the thoracic aorta in young adolescents with variant hyperimmunoglobulin E syndrome

Abstract

The autosomal-dominant (AD) form of the hyperimmunoglobulin E syndrome (HIES) has been described as a multisystem disorder including immune, skeletal and dental abnormalities. Recently, the evaluation of patients from families in which HIES was inherited in a manner more consistent with autosomal-recessive (AR) inheritance, showed that AR-HIES is a clinically distinct disease entity. In addition to classical immunologic findings of AD-HIES, the AR form presents with severe recurrent fungal and viral infections with herpes zoster, herpes simplex and characteristic mollusca contagiosa. Furthermore, cerebral vascular sequelae, including vasculitis, infarction and haemorrhage were noted. In this report, we describe the clinical picture of two patients who showed remarkable resemblance to the description of AR-HIES, but also developed fatal aneurysmal dilatation of the thoracic aorta in adolescence. This finding may further consummate the clinical picture of AR-HIES and emphasize the possibility to develop early aortitis, most likely preceding the critical aneurysm formation at older age. This process should be anticipated during childhood in cases with AR-HIES.

A review on the vascular features of the hyperimmunoglobulin E syndrome

“…Autopsies of two further patients with AR‐HIES who died from pneumonia were reported by Van der Meer et al. [7]. Post mortem examination of the aorta of the first patient showed media necrosis, sclerosis and severe infiltration of the adventitial layer with plasmocytes, indicating the presence of aortitis.…”

“…Target organ damage is unusual with mild eosinophilia, but its occurrence in association with moderate to severe eosinophilia (absolute eosinophil count > 1500/µl) does not appear to depend upon the specific cause of eosinophilia [26]. The limited pathological studies [7,11,18] did not show eosinophilic infiltration in the tissue of HIES patients except in Shamberger's [13] case. Does the absence of eosinophilic infiltration exclude the role for eosinophilia?…”

“…The patient reported by Van der Meer et al. [7] refused surgical replacement for thoracic aorta aneurysm and was treated palliatively with metoprolol. Young et al.…”

“…There is now a growing body of evidence to support the vascular anomalies seen in HIES as a characteristic feature of the disease. Vascular anomalies have been noted in HIES from some of the descriptions made of the syndrome [5][6][7][8][9]. The spectrum of vascular features of HIES have not been recognized previously.…”

Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis

“…We confirmed In conclusion, we show that endogenous expression of SOCS3 in T cells interrupts a major regulatory pathway in atherosclerosis through inhibition of IL17 production. Inter estingly, patients have been identified with defective STAT3 signaling (Minegishi et al, 2007) and IL17 production (Ma et al, 2008;Milner et al, 2008), and recent observational studies have reported the abnormal occurrence of vascular in flammation (van der Meer et al, 2006;Ling et al, 2007) in this setting despite the absence of classical cardiovascular risk factors. Although the reported vascular abnormalities con sisted mainly of inflammatory vascular aneurysms, some cases decrease in its expression by medial SMCs underlying ad vanced lesions (Fig.…”