Intrauterine device reaction

Mirena IUD© is a levonorgesterol hormone eluting IUD. Anaphylaxis from hormones, particularly progesterone, are well described, and levonorgesterol is a progestin. Acute urticaria following placement of IUD releasing levonorgesterol has been described (1,2,3). In these cases the patients experienced urticaria, dizziness, abdominal pain and/or light headedness within 2 hours, and signs and symptoms worsened over the next several hours. The IUDs were removed within 12 hours of placement with resolution of signs and symptoms. No testing was performed.

Pereira et al described a case of a pruritic eruption developing within 24 hours of placement of a Mirena© IUD (4). The rash was diagnosed as “autoimmune progesterone dermatitis” and treated with topical corticosteroids and oral antihistamine. The IUD was removed after 45 days.

According to the Mirena© manufacturer, skin rash and urticaria occur in 1:1000-1:10,000 (4). Another paper in the literature describes an ‘allergic reaction” requiring removal of the IUD in a series of 678 women (5)

Progesterone hypersensitivity has been reported with exposure to both endogenous and exogenous progesterone. The manifestations are heterogeneous and include rash, urticaria, angioedema, asthma and anaphylaxis (6). Proposed immune responses include both IgE dependent and cell mediated immunity. Allergy testing has been utilized with progesterone in assessment of this condition and cases have been treated with omalizumab (7,8). There are also reports of desensitization to progesterone to permit pregnancy (9). Hormonal skin testing for IgE mediated reactions is not standardized but has been utilized (10).

I would doubt other materials used had any role to play. There is a report of polyethylene glycol in the lubricant used for vaginal ultrasound causing a systemic reaction (11). The manifestations in this case were within minutes of the procedure. Nevertheless, you may wish to ask the gynecologist if any products used contained polyethylene glycol.

In summary, I suspect the signs and symptoms were the result of hypersensitivity to levonorgesterol. The reaction was not as rapid as many of the cases in the literature but remains the most likely culprit. I would avoid IUDs containing progestin. There also may be problems in the future with progesterone containing oral contraceptives or menstrual related symptoms, including catamenial anaphylaxis (12). Skin testing could be used to assess this problem if it occurs. I would not recommend epinephrine autoinjector at this point, but this is a consideration.

1. Emeryk-Maksymiuk, Justyna, et al. "Acute urticaria: an extremely rare adverse effect of levonorgestrel-releasing intrauterine system as a possible manifestation of progestogen hypersensitivity syndrome." Advances in Dermatology and Allergology/Postȩpy Dermatologii i Alergologii 35.5 (2018): 530.
2. Chen X, Wu X, Zhu H. Acute urticaria as a side effect of the Mirena® levonorgestrel-releasing intrauterine system): a case report. BMC Res Notes. 2014;7:209.
3. Pereira A, Coker A. Hypersensitivity to Mirena – a rare complication. J Obstet Gynaecol. 2003;23:81.
4. Mirena – product information. Available at: http://www.bayerresources.com.au/resources/uploads/PI/file9399.pdf.
5. Clinical performance of the levonorgestrel intrauterine system in routine use by the UK Family Planning and Reproductive Health Research Network: 5-year report. Cox M, Tripp J, Blacksell S. J Fam Plann Reprod Health Care. 2002 Apr; 28(2):73-7.
6. Foer D, Buchkeit KM, Gargiulo AR, et al. Progesteron hypersensitivity in 24 cases: diagnosis, management and proposed renaming and classification. J Allergy Clin Immunol Pract. 2016;4:723–9.
7. Foer D, Buchheit KM. Progestogen hypersensitivity: presentation and natural history. Ann Allergy Asthma Immunol 2019;122:156-59.
8. Heffler E, Fichera S, Nicolosi G, Crimi N. Anaphylaxis due to progesterone hypersensitivity successfully treated with omalizumab. The journal of allergy and clinical immunology In practice 2017.
9. Prieto-Garcia A, Sloane DE, Gargiulo AR, Feldweg AM, Castells M. Autoimmune progesterone dermatitis: clinical presentation and management with progesterone desensitization for successful in vitro fertilization. Fertility and sterility 2011;95(3):1121 e1129–1113.
10. Itsekson AM, Yonit B, Ze'ev IH, Matitiyahu Z, Shmuel K. Safety and value of skin test to sex hormones and sex hormone sensitivity desensitization in women with premenstrual syndrome. World Allergy Organ J. 2019;12(6):100041. Published 2019 Jun 8. doi:10.1016/j.waojou.2019.100041
11. Jakubovic BD, Saperia C, Sussman GL. Anaphylaxis following a transvaginal ultrasound. Allergy Asthma Clin Immunol 2016; 12: 3.
12. Lin K, Rasheed A, Lin S, Gerolemou L. Catamenial anaphylaxis: a woman under monthly progesterone curse. BMJ Case Rep. 2018;2018:bcr2017222047. Published 2018 Jan 4. doi:10.1136/bcr-2017-222047

All my best.
Dennis K. Ledford, MD, FAAAAI