Episodic angioedema with eosinophilia (Gleich's syndrome) associated with urticarial vasculitis: a coincidence or a novel clinical entity?

Abstract

Episodic angioedema with eosinophilia (EAE) is a rare condition characterized by recurrent attacks of angioedema and urticaria accompanied by a marked elevation of peripheral eosinophil count. We report the case of a young female patient diagnosed with EAE associated with urticarial vasculitis. A 40-year-old female patient was admitted to our institution due to recurrent episodes of cheek and eyelid angioedema in the previous year. Episodes of facial angioedema lasted for two months with spontaneous remission afterwards. In addition, she presented pruritic and painful skin eruptions of erythematous circles, which persisted for longer than 24 h, that were palpable, somewhat purplish, and more pronounced on the face, arms, and trunk. Laboratory investigation showed a sustained elevation of white cell counts with marked eosinophilia. Serum IgM, IgE, and IgA were normal; IgG was slightly elevated. C1-esterase inhibitor and tryptase test were normal. Reverse transcriptase-polymerase chain reaction was performed for detection of FIP1L1-PDGFRA and BCR-ABL rearrangements. None of these alterations were found. Skin biopsies were suggestive of urticarial vasculitis. The patient was submitted to esophagogastroduodenoscopy, which showed mild chronic gastritis, with no eosinophilic infiltration. Cardiac dimensions and function were normal. Abdominal ultrasound and total body CT-scan failed to show lymphadenopathy, organomegaly, and tumors. We report the first case of association between episodic angioedema with eosinophilia and urticarial vasculitis. It is possible that both conditions share a physiopathological mechanism, suggesting that it is not just a chance association.

Figure 1. A, Asymmetrical facial angioedema. Angioedema was more prominent on the cheek and eyelid. B, Presence of hives on the thorax. Pruritic and painful purplish papules were observed on the left anterior thorax (black arrow). C, Urticarial circles that emerged on the lateral neck. D, Painful purplish macules can be seen, suggesting vasculitis.

Figure 2. A, Bone marrow biopsy (HE 400×, scale bar 0.1 μm) with an enrichment of eosinophils. B, Bone marrow biopsy (200×, scale bar 0.2 μm) with CD117 immunostaining, suggesting an increase of mast cells. The immunostaining for myeloperoxidase (C, 100×, scale bar 0.4 μm) shows an elevated myeloid to erythroid proportion. Bone marrow presented grade 1 fibrosis, as evidenced by reticulin staining (D, 200×, scale bar 0.2 μm). Panels E (40×, scale bar 1 μm) and F (400×, scale bar 0.1 μm), Skin biopsy showing dermal small capillary vessels with inflammatory infiltrate in the walls, suggesting urticarial vasculitis.

Figure 3. Serial blood cell counts after the patient began treatment. Dashed lines represent the simple moving average trend. Leukocyte counts, especially neutrophils and eosinophils, present a sinusoidal-like trend, suggesting a cyclic pattern. One could think that the cyclic shape could be due to irregular adherence of the patient to corticoid-based treatment. Another explanation could be that the multilineage cell cycling observed in patients with episodic angioedema with eosinophilia occurs despite corticoid treatment.