Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2024;14(2):e2024130 1 Hereditary Angioedema Exacerbated by Estrogen Supplementation Treatment for Uterine Fibroid: A Therapeutic Challenge Alicja Mesjasz1, Kinga Bojahr1, Jan Romantowski1, Marek Niedoszytko1 1 Department of Allergology, Faculty of Medicine, Medical University of Gdansk, Poland Key words: hereditary angioedema, HAE, HAE type II Citation: Mesjasz A, Bojahr K, Romantowski J, Niedoszytko M. Hereditary Angioedema Exacerbated by Estrogen Supplementation Treatment for Uterine Fibroid: A Therapeutic Challenge. Dermatol Pract Concept. 2024;14(2):e2024130. DOI: https://doi.org/10.5826/dpc.1402a130 Accepted: December 14, 2023; Published: April 2024 Copyright: ©2024 Mesjasz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Alicja Mesjasz and Kinga Bojahr contributed equally to this work. Corresponding Author: Kinga Bojahr, Department of Allergology, Faculty of Medicine, Medical University of Gdansk, Poland. Telephone: +48-798-732-181 Email: kingabojahr@gumed.edu.pl Introduction Hereditary angioedema (HAE) type 2 is a rare genetic disease caused by the decreased activity of C1-inhibitor (C1-INH), resulting in an increased bradykinin level in the blood [1]. There are several known triggers for exacerbations, includ- ing physical trauma, stress, or drugs, including angiotensin converting enzyme (ACE) inhibitors [1]. The clinical mani- festations of HAE comprise recurrent episodes of subcutane- ous and submucosal edema in any part of the body, although the face, neck, limbs, gastrointestinal tract, and genitalia are most commonly affected [2]. Case Presentation A 30-year-old female in good general condition was ad- mitted to the hospital with swollen joints and erythema marginatum on her wrists, palms, and around mammary papillae. The patient had neither a family history of similar symptoms nor had she previously experienced them. Initially, rheumatoid arthritis was suggested, though the diagnosis was not confirmed (European Alliance of Associations for Rheumatology guidelines; EULAR), and with symptoms re- ceding, the patient was discharged from the hospital. Just be- fore hospitalization, she had started taking ethinylestradiol and levonorgestrel combination contraceptive pills to reduce bleeding associated with uterine fibroid. In the following months, the patient experienced re- current abdominal pain and limb angioedema episodes. However, five months later, symptoms became more se- vere, and face angioedema was also accompanied by prob- lems with swallowing (Figures 1 and 2). The patient had taken a high dose of antihistamines and systemic steroids at home, followed by epinephrine administration later in 2 Research Letter | Dermatol Pract Concept. 2024;14(2):e2024130 the Emergency Department. She did not respond to the therapy but demonstrated gradual improvement over the course of time. With normal C1-INH serum concentration (0.17 G/L) and its low activity (28%), the final diagnosis was HAE type 2 [2]. The patient was instructed to avoid taking any medications containing estrogen and was given a plasma-derived C1-INH as a severe attack treatment and short-term prophylaxis. Nonetheless, due to the vaginal in- fection, the patient has used vaginal globules with estriol and Lactobacillus acidophilus, which triggered the symp- toms of HAE type 2 again. Overall, the withdrawal of estrogen hormone supple- mentation improved the symptoms significantly. However, management of uterine fibroid treatment was also required. As the uterine fibroid was difficult to operate, and a hys- terectomy was not a reasonable option for such a young patient, progesterone-only contraceptive pills were adminis- tered, with positive outcomes. Figure 1. Skin lesions accompanying angioedema; erythema marginatum. Figure 2. Angioedema on the patient’s hands. Conclusions The attacks of HAE type 2 may be fatal, especially be- cause the treatment used in allergic histamine-dependent angioedema is not effective in bradykinin-dependent HAE type 2 [3]. Therefore, it is necessary to raise awareness of this rare disease. References 1. Kargarsharif F, Mehranmehr N, Zahedi Fard S, Fazlollahi MR. Type I and Type II Hereditary Angioedema: Clinical and Labora- tory Findings in Iranian Patients . Arch Iran Med 2015;18:425–9. 2. Bernstein JA. Severity of hereditary angioedema, prevalence, and diagnostic considerations. Am J Manag Care 2018;24:S292–8. 3. Fijen LM, Bork K, Cohn DM. Current and Prospective Targets of Pharmacologic Treatment of Hereditary Angioedema Types 1 and 2. Clin Rev Allergy Immunol 2021;61:66–76. https://doi .org/10.1007/S12016-021-08832-X.