Nonepisodic Angioedema Associated with Eosinophilia: Report of 4 Cases and Review of 33 Young Female Patients Reported in Japan

Abstract

Background: In 1984, Gleich et al. described 4 patients with episodic angioedema associated with eosinophilia (EAE), which was characterized by recurrent episodes of angioedema and urticaria, eosinophilia, elevated serum IgM, fever, increased body weight and a benign course without involvement of the internal organs demonstrating that it was a clinical entity distinct from the hypereosinophilic syndrome. Thereafter, 37 cases of EAE have been reported in Japan, 33 cases of which, although similar, had a different evolution from classical EAE. Objective: To describe 4 cases and review the cases of angioedema associated with eosinophilia reported in Japan. Results: Four Japanese female patients had persistent angioedema mainly involving the hands and lower legs, and eosinophilia which resolved within a few months. The review of the 37 cases of EAE in the Japanese literature demonstrated that in 33 cases, there were common characteristics which differed from EAE. These included: (1) the absence of recurrent attacks; (2) the predominance of young females (20–37 years, with a mean of 26 years); (3) the localization of the angioedema to the extremities; (4) the absence of increase in the serum IgM level, and (5) the effectiveness of low-dose prednisone or even the occurrence of spontaneous remission. Conclusion: We propose that persistent angioedema with eosinophilia can be classified into 2 types, i.e. one being an episodic (recurrent) type as reported by Gleich and a nonepisodic type as our 4 cases and others found in the Japanese literature.

Histological Classification and Differential Diagnosis of Nonepisodic Angioedema With Eosinophilia

“…Most cases of EAE have been reported in young or middle-aged adult men in the Western countries who required steroid therapy. 2 The histology of EAE usually reveals diffuse dermatitis with marked eosinophilic infiltration and dermal edema. 1,3 To the best of our knowledge, no previous cases of EAE in association with granulomatous lesions have been reported.…”

“…Most of the existing literature indicates that the histology of NEAE presents in a nonspecific pattern of superficial and deep dermatitis with eosinophilic and lymphocytic infiltration in addition to variable dermal edema, 2,6,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] although only 10 cases of NEAE have been presented with granulomatous reaction histologically as indicated in a few previous reports. 2,[28][29][30][31][32][33][34][35] This study sought to clarify the histological variation of NEAE and identify the characteristic histological features of NEAE, particularly the granulomatous lesions.…”

“…2,[28][29][30][31][32][33][34][35] This study sought to clarify the histological variation of NEAE and identify the characteristic histological features of NEAE, particularly the granulomatous lesions.…”

Seronegative Sjögren syndrome with asymptomatic autoimmune sclerosing pancreatitis

“…The clinical findings in our two patients and 33 previously described cases of NEAE are summarized in Table 1 [2,3,[7][8][9][10][11][12][13][14][15][16][17][18][19]. EAE has been reported mainly from Europe and the United States, while all the patients with NEAE were Japanese.…”

“…Immunological abnormalities are considered to play an important role in the pathogenesis of ASP based on the presence of autoantibodies and hypergammaglobulinemia, particularly IgG4 in the active phase [2,3]. ASP is often associated with other disorders, including retroperitoneal fibrosis and sclerosing cholangitis [4,5].…”