THU0632 Identification of aberrant t-cell phenotype in episodic angioedema with hypereosinophilia (GLEICH SYNDROME) in 30 patients: frequency, cliniclal implication and prognosis
Authors: N. Abisror, A. Mekinian, A. Dechartres, O. Fain, J.E. Kahn
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Gleich's syndrome or "Episodic Angioedema with eosinophilia"(EAE) is a rare disorder characterised by recurrent episodes of angioedema, concomitant hypereosinophilia and frequent elevated serum Immunoglobin M (IgM) levels. So far, no series were reported in literature. <h3>Objectives</h3> In this retrospective French study we report the clinical spectrum and therapeutic management of patients with EAE in a large French nationwide retrospective multicenter cohort study, with a particular focus on lymphoid variant of hypereosinophilic syndromes-related EAE. <h3>Results</h3> Thirty patients were included with a median age at diagnosis of 41 years<sup>5–84</sup> and a median follow up duration of 53 months.<sup>31–99</sup> The median time between two angioedema crises was 30 days<sup>7–192</sup> and the median duration of each crisis was 5.5 days<sup>1–90</sup> with swelling affected the face, the neck, the upper limbs, and the lower limbs. Twelve patients (40%) had an abdominal. The median blood eosinophil count at diagnosis was 6.9 G/L [1.44–53.5] and total serum IgM levels were increased in 20 patients (67%). Abnormal T-cell immunophenotypes were detected in 12 patients (40%):CD3-CD4+in 8 patients, CD3 +CD4+CD7 in 2, CD3-CD3ic+CD4 CD8-CD5+CD7 in 1 patient and CD3 +4–8–2+5+7+TCR γδ in 1 patients with presence of clonal TCR γ gene rearrangement in 5 cases (17%). Fourteen patients (47%) had bone marrow cytology and/or histology revealing high eosinophil counts and/or infiltration by non-dystrophic eosinophils in all cases. Eosinophilic perivascular infiltration (without vasculitis) was reported in 2 patients (7%) in which a skin biopsy was performed. An eosinophilic infiltrate was also found in various organs (stomach, gallbladder, liver, ileon, and colon) that were biopsied and/or surgically removed. All 30 patients were initially treated with glucocorticoid with a median initial dose of 40 mg of daily prednisone.<sup>5–80</sup> After first line treatment and a median time of 15.2 months (95% CI: 9.4–50.1), disease was considered as uncontrolled in 24 patients (80%) with relapses in 15 patients (50%) or glucocorticoid's dependence in 9 (30%). Glucocorticoid-sparing agents were used in 14 cases (47%) for relapses (n=8) or glucocorticoid- dependence (n=6). Associated treatments consisted of interferon-α (n=8, 27%), mepolizumab (n=2, 7%), ciclosporin A (n=5, 17%), methotrexate (n=4, 13%), hydroxycarbamide (n=2, 7%). The presence of an abnormal T-cell population was the sole factor associated with a shorter time to relapse (hazard ratio 4.15 [CI 95% 1.18–14.66; p=0.02). Two deaths occurred during follow-up (7%) due to lymphoma evolution for one and unexplained sudden death for the other. <h3>Conclusions</h3> EAE could be classified as a lymphoid variant of hypereosinophilic syndrome but that it is an heterogeneous condition. Although patients usually respond well to glucocorticoids, those with a circulating T-cell clonal population are at higher risk of both relapse and lymphoma suggesting necessity to long-term treatment and close monitoring. <h3>Disclosure of Interest</h3> None declared