Systemic mastocytosis is a subset of mastocytosis, which also includes cutaneous mastocytosis and mast cell sarcoma. Mastocytosis has been linked to somatic gain-of-function mutations of the c-KIT gene. KIT is a tyrosine kinase receptor that plays an important role in regulating the normal proliferation, maturation, adhesion, and chemotaxis of mast cells. 

Mast cell density has been discovered to be significantly higher in the myometrium of pregnant women than in women who are not pregnant. In addition, systemic mast cell activation from exposure to allergens in sensitized patients can bring about an immediate and substantial rise in myometrial contractions.

Scientists have proposed that mast cells play a role in mediating uterine contractility in pregnancy. There have also been reports of recurrent breastfeeding anaphylaxis in otherwise healthy women, suggesting that hormonal changes affect mast cell activation and degranulation. 

“Collectively, all these data support the hypothesis that [mast cells] are strongly involved in the human reproductive function, and that the physiological changes that occur during pregnancy could significantly affect [mast cell] activity,” Ferrari and colleagues wrote in Frontiers in Oncology. “Conversely, there is little data about the behaviour and the functional modifications of neoplastic [mast cells] during pregnancy in women with [systemic mastocytosis].” 

Case Study: Systemic Mastocytosis Diagnosed in Early Pregnancy

In Obstetrics & Gynecology, Watson and colleagues presented a rare case of a pregnancy complicated by systemic mastocytosis. A 32-year-old woman (gravida 7, para 2) presented with early pregnancy. Just 6 weeks prior, she had had a successful vacuum-assisted vaginal delivery. 

Four years earlier, at 31 weeks of gestation, she presented with regular contractions and abdominal pain. Due to fetal bradycardia, she underwent an emergency Cesarean section, which was unsuccessful. Postoperatively, her tryptase level was highly elevated (231 ng/mL); a follow-up test 3 weeks later revealed that it was still high (49.7 ng/mL). Additional tests revealed an elevated 24-hour urine 11-beta prostaglandin F2 alpha (6837 ng/24hr) and elevated N-methylhistamine (628 mcg/g creatinine). Systemic mastocytosis was suspected but the patient refused bone marrow biopsy. 

Read more about systemic mastocytosis etiology 

During her present visit, her laboratory results revealed elevated tryptase (50.7 ng/mL), elevated 24-hour urine 11-beta prostaglandin F2 alpha (8373 ng/24hr), and elevated N-methylhistamine (473 mcg/g creatinine). She tested positive for the serum c-Kit Asp-816-Val gene mutation. The patient was diagnosed with systemic mastocytosis but again refused bone marrow biopsy. 

As a precaution against a flare of mastocytosis, the patient was prescribed cetirizine 10 mg once daily during her pregnancy. The anesthetic plan formulated a month prior to her expected delivery date was for a repeat Cesarean delivery to be performed under spinal anesthesia. 

A Cesarean section was initiated upon continuing contractions at 36 weeks of gestation. The patient was administered IV dexamethasone 4 mg and IV diphenhydramine 12.5 mg as prophylaxis for mast cell release. She had a successful delivery. 

Ten minutes later, the patient experienced difficulty breathing, throat tightness, and a drop in oxygen saturation to 92%. She was treated with oxygen, IV epinephrine 0.05 mcg (administered 3 times over 5 minutes), IV diphenhydramine 12.5 mg, and IV dexamethasone 4 mg. She was then transferred to the intensive care unit for further observation. 

Implications for Both Mother and Child 

In the case of this patient, an elevated tryptase level helped raise the suspicion of systemic mastocytosis. This is because tryptase is a preformed component in mast cells (along with histamine). “An elevated tryptase level helps confirm a mast cell-mediated reaction and is therefore high in anaphylactoid reactions,” Watson and colleagues wrote. 

Stress, including labor, can trigger the release of mast cells in a pregnant woman with systemic mastocytosis. Anesthetic management is focused on preventing an anaphylactoid reaction from occurring and preparing to treat mast cell degranulation if it occurs before, during, or after delivery. In the case of this patient, she experienced an anaphylactic reaction almost immediately after delivery. 

Pregnancy in a patient with systemic mastocytosis is complicated by the need to balance the interests of the mother and the embryo. In the case of the mother, pregnancy can potentially worsen mastocytosis, putting her at risk of clinical deterioration. In the case of the embryo, drug toxicity and obstetric complications may hinder successful growth and delivery. 

Read more about systemic mastocytosis treatment 

To add to the challenges faced by physicians, the clinical manifestations of mastocytosis can be unpredictable. “Patients can experience a significant improvement of their health’s status with reduction in frequency and intensity of [mast cell] mediator-release symptoms, or can suffer by a worsening of symptoms,” Ferrari and colleagues wrote. “Moreover, the severity of symptoms can be different in the same patient in consecutive pregnancies.”

Because of the cross-disciplinary implications of systemic mastocytosis in a pregnant woman, “the patient should be referred to a reference center, and managed by a mastocytosis-dedicated multidisciplinary team, including a high-risk obstetrician, an hematologist, an allergist and an anesthesiologist,” Ferrari and colleagues wrote. 

This case study highlights the need for vigilance during prenatal assessments. It also demonstrates how systemic mastocytosis can affect pregnancy, and vice versa. It is vital for the health and well-being of both mother and baby that cases such as these are managed effectively. 

References

Ferrari J, Benvenuti P, Bono E, Fiorelli N, Elena C. Mastocytosis: fertility and pregnancy management in a rare diseaseFront Oncol. 2022;12:874178. doi:10.3389/fonc.2022.874178

Watson KD, Arendt KW, Watson WJ, Volcheck GW. Systemic mastocytosis complicating pregnancyObstet Gynecol. 2012;119(2 Pt 2):486-489. doi:10.1097/AOG.0b013e318242d3c5