Clinical Features of Hereditary and Mast Cell-mediated Angioedema Focusing on the Differential Diagnosis in Japanese Patients

Abstract

Objective The present study was designed to identify the clinical characteristics that permit the differential diagnosis of hereditary angioedema (HAE) and mast cell-mediated angioedema (Mast-AE) during the first consultation. Methods The medical histories and laboratory data of 46 patients with HAE and 41 patients with Mast-AE were compared. Results The average age of onset in the HAE group (19.8±9.0 years) was significantly lower than that in the Mast-AE group (35.2±12.0 years). The incidence of familial angioedema (AE) in the HAE group (73.9%) was significantly higher than that in the Mast-AE group (9.7%). The frequency of history of AE in the extremities, larynx, or gastrointestinal tract was significantly higher in the HAE group. The frequency of AE episodes of the lips and eyelids was significantly lower in the HAE group. The serum C4 concentration and CH50 titer were lower than the normal limit in 91.3% and 45.6% of the patients in the HAE group, respectively; in Mast-AE group the serum C4 concentration and CH50 titer were significantly lower than the normal limit in 4.8% and 0% of the patients, the difference between the two groups was statistically significant. A C1-inhibitor (C1-INH) activity level of <50% was observed in all of the HAE patients, but none of the Mast-AE patients. The mean serum IgE titer in the HAE group (120.8±130.5 IU/mL) was significantly lower than that in the Mast-AE group (262.2±314.9 IU/mL). Conclusion The parameters within the patients' medical histories, such as the age at the onset of AE, a family history of AE, and the locations of past AE episodes are critical for the successful diagnosis of the disease. Measurements of the C4 and C1-INH activity are very useful for differential diagnosis of HAE from Mast-AE.

Keywords: C1-inhibitor; C4; IgE; hereditary angioedema; mast cell.

Figure 1.

Pictures of angioedema from patients with hereditary angioedema. a: A 38-year-old female patient. Marked swelling of the left lower limb was observed. b: A 19-year-old female patient. Enhanced computed tomography of the abdomen demonstrated an expanded edematous small intestine (arrow head) and the accumulation of intestinal fluid.

Figure 2.

Dot plots of the complement system parameters. a: The serum levels of C3. b: The serum levels of C4. c: The serum titers of CH50. d: The serum activities of C1-inhibitor. The gray zone represents the normal range. The horizontal broken line represents the limit of quantitation. The horizontal line of Fig. 2d indicates a C1-inhibitor activity level of 50%, which is stated in the diagnostic criteria (12). HAE: hereditary angioedema, Mast-AE: mast cell-mediated angioedema, C1-INH: C1-inhibitor