Postpartum fibroid degeneration associated with elevated procalcitonin levels

Introduction

The timely diagnosis of infection during pregnancy is paramount for the health of the mother and her fetus. Normal inflammatory responses, such as fever and tachycardia, have not been accurate predictors of infection during pregnancy and postpartum as they can be unreliable [1]. Procalcitonin (PCT) can be used during this period to more accurately assess for an infectious state. PCT can be detected as early as 2 h post-exposure, increases seen in 3–4 h, peak at 6 h, and persist for 20–72 h [1]. It was initially thought that elevations in PCT only occurred in bacterial sepsis; however, elevations can occur secondary to pro-inflammatory stimuli and have been documented in autoimmune disease, severe trauma, surgery, heat stroke, cardiogenic shock, and fungal and parasitic infections [2].

Studies have shown elevated PCT levels in relation to inflammatory conditions, such as asymptomatic bacteriuria, preterm premature rupture of membranes, or hypertensive pathologies [1], but not documented solely in relation to degeneration of uterine leiomyomas. Uterine leiomyomas, also known as fibroids, are common tumors of the female reproductive tract, estimated to occur in 20–40% of women by 35 years of age [3]. During pregnancy, progesterone provides a stimulatory effect and the resultant growth of fibroids can be significant [4]. Most myomas are asymptomatic, however, the rapid rate of growth in pregnancy can cause the fibroid to outgrow its blood supply. This causes hemorrhagic infarction, also known as red or carneous degeneration [4, 5], and most commonly presents with abdominal pain and tenderness [5]. Our case describes a patient whose pregnancy was complicated by degenerating fibroids during her pregnancy. Subsequently, her postpartum course was complicated by suspected infection with a significant elevation in procalcitonin, likely secondary to the fibroid degeneration. While fibroid degeneration can be common during the prenatal course, this degree of inflammatory response in relation to PCT levels has not been published in literature. Here, we report a case of severely elevated PCT, diagnosis, and management in a postpartum patient.

Case presentation

A 34-year-old nulliparous female was admitted at in the 39th week of pregnancy for labor induction secondary to pre-eclampsia without severe features, as she met criteria due to elevated blood pressures and a protein/creatinine ratio of 0.39. Her pregnancy had been complicated by degenerating fibroids and recurrent urinary tract infections. Ultrasounds throughout the pregnancy showed large fibroids, measuring 6.9 × 7.41 × 5.46 cm (anterior subserosal), 10.27 × 8.72 × 6.28 cm (right lateral subserosal), and 10.38 × 8.68 × 6.39 cm (anterior subserosal) as per her most recent ultrasound. During her prenatal course, her pregnancy was complicated by fibroid degeneration with hospital admission at 16 weeks and 20 weeks for which she was treated successfully with short courses of indomethacin. After she presented for induction of labor, her intrapartum course was uncomplicated and she had a normal spontaneous vaginal delivery of a healthy female infant.

The patient had routine obstetric care until her second postpartum day when she developed severe chills. She was noted to be tachycardic up to 160 beats per minute (bpm) and febrile with an oral temperature of 39.1 °C/102.5 °F. The remainder of her vital signs were unremarkable (Table 1). The patient denied any other symptoms, sick contacts or recent travel outside the United States. Physical examination revealed tachycardia and abdominal tenderness upon palpation of the fibroids.

Intravenous fluids and acetaminophen were administered, yet the patient remained febrile with repeat temperature at 39.2 °C/102.7 °F. Differential diagnosis included degenerating fibroids, endometritis, pneumonia, and venous thromboembolism. Given possible infectious etiology, the patient had cultures drawn and was started on IV ampicillin and gentamicin. Chest X-ray revealed no consolidations and lower extremity Doppler studies showed no venous thromboembolism. Blood and urine cultures were negative, and EKG showed sinus tachycardia. CBC was significant for decreased white blood cell count to 2.95/mm³, a hemoglobin of 8.6 g/dL, hematocrit of 30.2%, and platelet count of 150,000 mm³. Patient also had bandemia of 7.2%, neutrophilia of 85.2%, and elevated lactate of 2.2 mmol/L (Table 2).

Blood work was repeated 6 h after initiation of antibiotic therapy. Leukopenia had resolved, but neutrophilia continued to be predominant at 96.5% with a bandemia of 7.0% and increasing lactate of 3.5 mmol/L. Due to persistent tachycardia, a CT PA was conducted which showed no filling defects. Despite 24 h of antibiotic therapy the patient remained febrile. A pelvic MRI was obtained as no source of infection had been identified. The MRI showed a uterus measuring 25.3 × 14.2 × 23.4 cm in size. The endometrium contained blood products and irregularity with mild hyperenhancement was noted on the right aspect of the uterine body (Figure 1). Six dominant intramural and broad-based subserosal fibroids were seen, measuring up to 10.2 cm in diameter. The lesions demonstrated T1 hyperintensity with low T2 signal remains and lack of enhancement, consistent with hemorrhagic degeneration (Figure 2).

Figure 1:

MRI showing irregularity and mild hyperenhancement on the right aspect of the uterine body.

Multiple fibroids in the uterine body are visualized (marked with white stars).

Figure 2:

MRI with T1 hyperintensity and low T2 signal, consistent with hemorrhagic degeneration (marked with white stars).

As the patient continued to be febrile on broad spectrum antibiotics, she was started on scheduled 800 mg IV ibuprofen every 8 h with the presumed diagnosis of degenerating fibroids. Her lactic acidosis had resolved at this time but procalcitonin was significantly elevated at 34.03 ng/mL (normal at our institution is considered less than 0.05 ng/mL with >2.0 ng/mL being high risk for sepsis). Due to possibility of anaerobic infection, antibiotics were changed to IV meropenem by the infectious disease service. Blood cultures continued to be negative.

The patient was afebrile in the 24 h after starting IV ibuprofen, and the remainder of her vital signs were unremarkable. The PCT level decreased to 30.01 ng/mL with a final level of 12.11 ng/mL upon discharge. The patient was discharged with 3 days of IV ertapenem and had no further complications or complaints at her follow-up visit later that week.

Discussion

The management of fibroid degeneration during pregnancy mainly includes hydration and analgesia. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used agents in the management of pain related to uterine fibroids, both in pregnant and non-pregnant individuals. The pain from fibroids results from the release of prostaglandins from the damaged tissue, and improvement can usually be seen with the use of NSAIDs that function as prostaglandin synthetase inhibitors [5]. Indomethacin is used before 32 weeks gestation and for no longer than 48 h, with improvement in symptoms [6]. The patient above had cessation of fevers and improvement in her symptoms when scheduled IV Ibuprofen was started. Nevertheless, meropenem was also started shortly afterwards by the infectious disease specialists, so it is unclear whether the clinical improvement was due to a singular cause or a combination of both antibiotics and NSAIDs.

It is important to note that the severely elevated procalcitonin was likely due to her degenerating fibroids, given that no source of infection was identified. PCT elevation during pregnancy has been studied in relation to several conditions, but rarely in the context of degenerating fibroids. One case report demonstrates severe elevation in PCT to 59.71 ng/mL seen in the postpartum development of a leiomyoma to a pyomyoma [7]. Velasquez et al. [8] found that PCT levels on average were high in pregnancy for patients with bacterial infection (0.09 ng/mL) compared to non-infected patients (0.05). Agarwal et al. [1] analyzed patients with pregnancy-associated sepsis (PAS) and found that severe PAS had an average PCT of 3.12 ng/mL vs. an average of 0.49 ng/mL for non-severe PAS. Overall, higher PCT levels are associated with a higher risk of progression to severe sepsis and septic shock [9]. In the general population, PCT is an accurate measurement of infection as it rises and falls faster than other typical markers, yet reference intervals for use in pregnancy have not been established [9].

It is plausible to assume that our patient’s PCT elevation was due to her degenerating leiomyomas but may have also been influenced by her pre-eclampsia. Both pre-eclampsia and degenerating fibroids cause inflammatory states [9]. Gulec et al. [10] found that PCT levels in pre-eclamptic patients were significantly higher than in the control population. One limitation in this study is that no baseline level of PCT was known in this case. Therefore, it is unsure whether the elevation in PCT was due solely to degenerating fibroids, as it could have been affected by other variables such as pre-eclampsia. Further studies are also warranted to determine whether degenerating fibroids both inside and outside of pregnancy can cause an increase in PCT. If this is the case, the PCT elevation can be anticipated and unnecessary antibiotic therapy can be avoided.

In conclusion, this case describes a unique scenario in which multiple degenerating fibroids caused a severe increase in serum procalcitonin. Noninfectious causes are important to consider in the management of an acutely ill postpartum patient. Use of medications such as NSAIDs are essential when practicing conservative management of degenerating fibroids. In the future, the authors would consider obtaining inflammatory markers in similar patients during the third trimester. This would allow the provider to assess trends more accurately, and determine whether an inflammatory state is present prior to symptom manifestation. Further studies may include a cohort of patients with degenerating fibroids, in order to establish reference intervals of inflammatory markers in similar settings.