Isao Ohsawa1,2, Atsushi Fukunaga3, Shinya Imamura3, Kazumasa Iwamoto4, Akio Tanaka4, Michihiro Hide4, Daisuke Honda2, Kouhei Yamashita5, Chisako Fujiwara6, Osamu Ishikawa6, Takeo Yamaguchi7, Junichi Maehara8, Tomoya Hirose9,10, Masahiro Ieko11, Kunihiko Umekita12, Yuya Nakamura1, Hiromichi Gotoh1. 1. Department of Nephrology, Internal Medicine, Saiyu Soka Hospital, Soka City, Saitama, Japan. 2. Department of Nephrology, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan. 3. Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. 4. Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima City, Hiroshima, Japan. 5. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan. 6. Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi City, Gunma, Japan. 7. Department of Gastroenterology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya City, Nagoya, Japan. 8. Department of Acute Care and General Medicine, Saiseikai Kumamoto Hospital, Kumamoto City, Kumamoto Japan. 9. Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka Japan. 10. Emergency and Critical Care Medical Center, Osaka Police Hospital, Osaka City, Osaka, Japan. 11. Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan. 12. Department of Rheumatology, Infectious Diseases and Laboratory Medicine, University of Miyazaki, Miyazaki City, Miyazaki, Japan.
Abstract
BACKGROUND: Hereditary angioedema (HAE) is a rare but life-threatening condition. HAE types I and II (HAE-1/2) result from C1-inhibitor (C1-INH) deficiency. However, recent genetic analysis has established a new type of HAE with normal C1-INH (HAEnC1-INH). The mutations of factor XII, plasminogen, angiopoietin 1, and kininogen 1 genes may be the cause of HAEnC1-INH. Nevertheless, other causative molecules (HAE-unknown) may be involved. The Japanese therapeutic environment for HAE has been improving owing to the self-subcutaneous injection of icatibant, which was approved for the treatment of acute attack and enables early therapy. Erythema marginatum (EM) is a visible prodromal symptom which occasionally occurs prior to an angioedema attack; hence, recognizing the risk of an acute attack is important for early treatment. However, the detailed characteristics of EM remain unclear. In this study, we first investigated the clinical manifestations of EM in Japanese patients with HAE. METHODS: A 20-point survey was developed and distributed to 40 physicians to gather clinical data on EM from patients with HAE. RESULTS: Data on 68 patients with HAE (58 patients with HAE-1/2 and 10 patients with HAE-unknown) were collected. Of the patients with HAE-1/2, 53.4% experienced EM, whereas 43.1% did not. The forearm was the most frequent area of EM (64.5%), followed by the abdomen (29.0%) and upper arm and precordium (19.3%). Of the HAE-1/2 patients with EM, 41.9% always had angioedema following EM, while 29.0% always had colocalization of EM with angioedema. Moreover, 3.2% showed a correlation between the awareness of EM and severity of an angioedema attack. In 60.9% of HAE-1/2 patients with EM, the interval between the awareness of EM and appearance of angioedema was <3 h. Of the patients with HAE-unknown, 30.0% also experienced EM. CONCLUSION: We confirmed that more than one-half of Japanese patients with HAE-1/2 and one-third of those with HAE-unknown develop EM as the prodromal symptom of an angioedema attack. Physicians should communicate the significance of EM to patients with HAE to prepare them for possible imminent attacks.
BACKGROUND: Hereditary angioedema (HAE) is a rare but life-threatening condition. HAE types I and II (HAE-1/2) result from C1-inhibitor (C1-INH) deficiency. However, recent genetic analysis has established a new type of HAE with normal C1-INH (HAEnC1-INH). The mutations of factor XII, plasminogen, angiopoietin 1, and kininogen 1 genes may be the cause of HAEnC1-INH. Nevertheless, other causative molecules (HAE-unknown) may be involved. The Japanese therapeutic environment for HAE has been improving owing to the self-subcutaneous injection of icatibant, which was approved for the treatment of acute attack and enables early therapy. Erythema marginatum (EM) is a visible prodromal symptom which occasionally occurs prior to an angioedema attack; hence, recognizing the risk of an acute attack is important for early treatment. However, the detailed characteristics of EM remain unclear. In this study, we first investigated the clinical manifestations of EM in Japanese patients with HAE. METHODS: A 20-point survey was developed and distributed to 40 physicians to gather clinical data on EM from patients with HAE. RESULTS: Data on 68 patients with HAE (58 patients with HAE-1/2 and 10 patients with HAE-unknown) were collected. Of the patients with HAE-1/2, 53.4% experienced EM, whereas 43.1% did not. The forearm was the most frequent area of EM (64.5%), followed by the abdomen (29.0%) and upper arm and precordium (19.3%). Of the HAE-1/2 patients with EM, 41.9% always had angioedema following EM, while 29.0% always had colocalization of EM with angioedema. Moreover, 3.2% showed a correlation between the awareness of EM and severity of an angioedema attack. In 60.9% of HAE-1/2 patients with EM, the interval between the awareness of EM and appearance of angioedema was <3 h. Of the patients with HAE-unknown, 30.0% also experienced EM. CONCLUSION: We confirmed that more than one-half of Japanese patients with HAE-1/2 and one-third of those with HAE-unknown develop EM as the prodromal symptom of an angioedema attack. Physicians should communicate the significance of EM to patients with HAE to prepare them for possible imminent attacks.
Authors: Michael J Prematta; Againdra K Bewtra; Robyn J Levy; Richard L Wasserman; Kraig W Jacobson; Thomas Machnig; Timothy J Craig Journal: Adv Ther Date: 2012-09-27 Impact factor: 3.845