Q:

11/8/2011 
I have recently seen a 47 year old female with recurrent episodes of unilateral eyelid swelling. She does not have any triggers for the eyelid swelling including foods, medications, or insect stings. She does not have associated urticaria or respiratory distress. The episodes generally resolve within 24-48 hours after the onset of symptoms with antihistamines. She does not have fever with the episodes of angioedema. Her past medical history is positive for both allergic rhinitis and food allergy to fish and shellfish. She does not have asthma and her family history is negative for autoimmune disease.

 

Laboratory testing for angioedema demonstrated normal C1 esterase levels and function and a normal C1q, normal C4, ANA, and comprehensive metabolic panel. Lab testing did demonstrate mild normocytic anemia (Hgb 11.2), eosinophilia (AEC 1200), elevated ESR (31 mm/hr), and an elevated C4. I am still awaiting a total trytpase level. I have also recently ordered stool for O and P, toxocara serolgies, and immunoglboulin levels.

 

If evaluation for parasitic infection and other causes of eosinophilia are negative, do you think the eosinophilia is due to her underlying atopy or a form of episodic angioedema and eosinophilia? Are there any other conditions that could manifest as angioedema associated with eosinophilia that you are aware of?

 

Thanks in advance for you help.

A:

Thank you for your recent inquiry.

There is a very rich body of literature regarding the syndrome of "angioedema and eosinophilia". Unfortunately the syndrome, although reported repeatedly, does not have a known etiology, and therefore it is unlikely that you will find the cause of these manifestations in your patient. However, I think that you have done due diligence in the evaluation. The only further suggestion would be to perform, in addition to stools for ova and parasites, a serological workup (ELISA) for parasites. In the absence of any known etiology then I believe your patient would probably fit into the classic "angioedema and eosinophilia" described in the references that I have copied for you below. This syndrome itself has been subdivided into several categories. I believe you might find the Banerji and Weller reference from Immunology and Allergy Clinics of North America helpful in orienting you in this regard and perhaps placing your patient into one of these subcategories of this syndrome.

Thank you again for your inquiry and we hope this response is helpful to you.

http://bloodjournal.hematologylibrary.org/content/79/3/688.full.pdf

Ann Allergy. 1993 Mar;70(3):243-8.
Episodic angioedema with eosinophilia: a case associated with T cell activation and cytokine production.
Putterman C, Barak V, Caraco Y, Neuman T, Shalit M.
Source
Department of Oncology, Hadassah University Medical Center, Jerusalem, Israel.
Abstract
Episodic angioedema with eosinophilia is a rare syndrome, characterized by periodic attacks of fever, myalgia, angioedema, and oliguria, associated with an increased eosinophil count. The pathogenesis of this disorder is incompletely understood. We describe an additional patient with episodic angioedema and eosinophilia, and review the literature regarding the clinical features and treatment of this disease. Previous hypotheses regarding disease mechanisms are discussed. In our patient, we found high basal levels of interleukin-1 (IL-1) and soluble interleukin-2 receptor (sIL-2R), with further increases in levels of both mediators during attacks. We suggest that IL-1 and T cell activation may play a role in the pathophysiology of episodic angioedema with eosinophilia.

Nonepisodic Angioedema Associated with Eosinophilia: Report of 4 Cases and Review of 33 Young Female Patients Reported in Japan
R. Chikamaa, M. Hosokawab, T. Miyazawab, R. Miurac, T. Suzukic, H. Tagamia
Department of Dermatology, Tohoku University School of Medicine, and Departments of
Dermatology and Internal Medicine, Sendai Teishin Hospital, Sendai, Japan
Address of Corresponding Author
Dermatology 1998;197:321-325 (DOI: 10.1159/000018025
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.

Ann Allergy Asthma Immunol. 2008 Feb;100(2):172-4.
Episodic angioedema with eosinophilia: successful treatment with imatinib.
Scranton SE, Wild CA, England RW
Immunol Allergy Clin North Am. 2006 Nov;26(4):769-81.
Cytokine-associated angioedema syndromes including episodic angioedema with eosinophilia (Gleich's Syndrome).
Banerji A, Weller PF, Sheikh J.
Source
Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Abstract
Angioedema can be associated with many disorders and the presentation can be variable. Subsets of the angioedema syndromes are thought to be cytokine mediated (Table 1). Of these, the best described are the episodic angioedema with eosinophilia syndrome (Gleich's syndrome) and non-episodicangioedema with eosinophilia, which share some common features, but appear to have differences in pathophysiology. NERDS (nodules, eosinophilia, rheumatism, dermatitis and swelling), Clarkson syndrome (idiopathic capillary leak syndrome), and angioedema associated with aldesleukin (human recombinant IL-2) and IFN-alpha have also been reported in the literature, and have been discussed in this review. There is still much to be learned about the pathophysiology, diagnosis, and treatment of patients with these disorders. Our hope is that this review will be of help to those readers who care for patients with these disorders, and will stimulate interest in further research into the pathophysiology of these conditions.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology