Recurrent Postpartum Anaphylaxis With Breast-Feeding
Shank, Jessica J. MD; Olney, Stacey C. MD; Lin, Fang L. MD; McNamara, Michael F. DO
From the Departments of Obstetrics & Gynecology and Allergy & Immunology, Naval Medical Center San Diego, San Diego, California.
Corresponding author: Jessica J. Shank, MD, Naval Medical Center San Diego, Department of Obstetrics & Gynecology, 34800 Bob Wilson Drive, San Diego, CA 92134; e-mail: Jessica.firstname.lastname@example.org.
Financial Disclosure The authors did not report any potential conflicts of interest.
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BACKGROUND: Anaphylaxis associated with breast-feeding is a rare but potentially life-threatening event.
CASE: This woman reported anaphylaxis with three previous pregnancies while breast-feeding. With her fourth pregnancy she was treated with corticosteroids and antihistamines after delivery. Despite treatment, she developed urticaria, facial edema, and throat tightening, less severe than prior episodes. Her symptoms resolved with epinephrine and antihistamine but recurred with subsequent breast-feeding. On postpartum day 4 she had no symptoms while breast-feeding.
CONCLUSION: Three cases of postpartum breast-feeding anaphylaxis have been reported. Although the pathophysiology is unclear, it may involve the decrease in progesterone and rise of prolactin causing mast cell degranulation. Avoidance of nonsteroidal antiinflammatories and prophylaxis with corticosteroids and antihistamines may offer the best protection.
Lactation anaphylaxis is an extremely rare condition, with only three previously reported cases. Nevertheless, it is a serous and potentially life-threatening condition, where early recognition and treatment are important.
We report a patient who had anaphylactic reactions on postpartum day 3 while breast-feeding after delivery of each of her four children. She was able to breast-feed on the days both before and after the events without such reactions.
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A 35-year-old gravida 4 para 3 had a history of anaphylaxis on postpartum day 3 with all three previous pregnancies. Three days after delivery of her first neonate, she developed hives, swollen eyelids, choking, coughing, and wheezing, which lasted overnight. The second pregnancy was significant for hives, shortness of breath, and cyanosis on postpartum day 3, which required epinephrine injection and intensive care unit admission. Codeine was used before this reaction. She had a similar reaction again 3 days after delivery of her third neonate, which required repeated epinephrine injections over 24 hours. All three episodes were associated with breast-feeding. Other medical history was notable for mild asthma and gestational diabetes. Because of her previous postpartum anaphylaxis history, she was referred to the Allergy Division for an evaluation. Workup at that time included negative skin tests to common aeroallergens and latex. Her lung function was normal on spirometry. A recommendation was made that she receive prednisone 30 mg twice daily and cetirizine 10 mg once daily beginning immediately after delivery in an attempt to prevent postpartum anaphylaxis. This recommendation was directly passed on to her obstetrician before delivery.
The prenatal course of her current pregnancy was significant for gestational diabetes controlled with glyburide and a history of genital herpes on acyclovir suppression beginning at 35 weeks. She presented in labor at term and was started on penicillin for group B streptococci prophylaxis. She received an epidural anesthesia and had an uncomplicated spontaneous vaginal delivery of a healthy male neonate. As per the above recommendation, she began prednisone and cetirizine prophylaxis. Postpartum days 1 and 2 were unremarkable, and breast-feeding occurred without difficulty. Ibuprofen and acetaminophen were provided for pain control. Three days after delivery, while breast-feeding, she developed raised, erythematous, pruritic patches on her arms, chest, and back, with periorbital and oral swelling. The rash worsened after each episode of breast-feeding. She had received a total of six doses of 800 mg ibuprofen before the first onset of hives, and was subsequently discontinued. Her symptoms began to diminish after intravenous diphenhydramine, but with each attempt to breast-feed, the facial edema and rash returned. She was subsequently also given an epinephrine injection and ranitidine for control of her symptoms, which subsided overnight. Her symptoms did not return despite continuing to breast-feed throughout the rest of her hospital stay. Upon discharge, the patient was given strict instructions that if her symptoms returned to use the epinephrine auto-injector and to go immediately to the emergency department. The patient was discharged home and continued breast-feeding with no further symptoms.
She was reevaluated by the Allergy Division because she suffered these reactions despite the recommended pretreatment. Skin tests to the patient’s breast milk and oxytocin were negative. Prolactin was not available for skin testing. In addition to prophylactic treatment with steroids and antihistamines, she was advised to avoid all nonsteroidal antiinflammarory medicines if she is to have another pregnancy.
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The first report of a case of anaphylaxis associated with breast-feeding was in Lancet in 1991 1 and describes a 29-year-old woman with generalized urticaria and upper airway angioedema with each breast-feeding over 3 days after the birth of her first child. She was taking aspirin at the time, and the episodes resolved even with continuation of breast-feeding once the aspirin was discontinued. One month later she had another anaphylactic episode within a few minutes of breast-feeding while taking paracetamol (acetaminophen). After the birth of her second child 5 years later, she suffered similar episodes after breast-feeding despite not taking any aspirin or acetaminophen. Suppression of lactation was ultimately required for both postpartum periods. The authors suggested that the anaphylactic episodes were triggered by breast-feeding, milk let-down, and aspirin use and that progesterone may be a factor.
In the Journal of Human Lactation in 1998,2 a second case describes a 30-year-old woman with hives, throat edema, and wheezing after breast-feeding on postpartum day 3. She had breast-fed uneventfully for the first 48 hours after birth and was able to continue to breast-feed without subsequent reactions beginning on postpartum day 4. She was taking ibuprofen for pain control. The authors suggest that breast-feeding triggered the anaphylactic reactions in this woman and that nonsteroidal antiinflammarory medicines were probably a contributing factor.
The most recent report (European Annals of Allergy and Clinical Immunology 2007)3 describes a 31-year-old woman with a generalized rash, airway angioedema, wheezing, hypotension, and loss of consciousness 72 hours after the delivery of her first child. These symptoms occurred again with her second child in a similar manner. The episodes were temporally associated with breast-feeding and subsided when breast-feeding was discontinued or lactation suppressed. The authors suggest that the symptoms could be due to the actions of oxytocin and corticotropin-releasing hormone on mast cells, facilitated by the absence of the stabilizing role of progesterone, resulting in degranulation release of histamine and other mediators.
Lactation anaphylaxis remains a rare occurrence, and the actual pathogenesis of the reaction remains unclear. Prior case reports suggest a relationship to the hormone shifts related to the end of gestation and the beginning of lactation. The rapid decrease in progesterone after the delivery of the placenta in the presence of a high level of prolactin allows for the process of lactogenesis.4 This process typically occurs around postpartum days 2 to 3, which relates well to the appearance of symptoms in this patient as well as two of the three patients in the previous case reports. The use of nonsteroidal antiinflammatory medications is also cited as a contributing factor. These agents are known to exacerbate urticaria and anaphylaxis.5
Recent studies have shown that during pregnancy, increased numbers of mast cells are found in the mammary gland and uterus.6 It has also been shown that progesterone has a stabilizing effect on the mast cell membrane, whereas estrogen increases mast cell degranulation and histamine release. The abrupt withdrawal of progesterone after delivery may facilitate the release of histamine. Steroid levels also peak with labor and delivery and then quickly decline. The removal of corticosteroid suppression of mast cells may also predispose these women to anaphylactic reactions. There may be many other mechanisms related to breast-feeding in these particular patients that have not yet been discovered because of the rarity of such events. For those patients with a previous history of anaphylaxis while breast-feeding, a prophylactic regimen with corticosteroids and antihistamines begun immediately after delivery and avoidance of all nonsteroidal antiinflammatory medications may offer the best protection.
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