Abstract
Hemorrhagic cystitis is generally a benign self-limited disorder, however there are some severe cases which are associated to a significant blood loss. The etiology may be either bacterial, viral or chemical in origin; though the cause is not identified in most of the cases. Immunocompromised patients or patients who have undergone chemotherapy or radiation constitute the highest risk group. There are only a few articles about hemorrhagic cystitis in pregnancy, frequently associated with preterm labor. We describe, for the first time in literature, one patient with a clinical status of hematuria in two consequent pregnancies, without any identified cause and a medical history negative for recurrent or hemorrhagic cystitis and we report an overview of literature concerning this topic.
Introduction
Hemorrhagic cystitis is generally a benign self-limited disorder, however there are some severe cases which are associated to a significant blood loss. The etiology may be either bacterial, viral or chemical in origin; though the cause is not identified in most of the cases. Immunocompromised patients or patients who have undergone chemotherapy or radiation constitute the highest risk group. There are only a few articles about hemorrhagic cystitis in pregnancy, frequently associated with preterm labor [1, 2]. We describe, for the first time in Literature, one patient with a clinical status of hematuria in two consequent pregnancies, without any identified cause and a medical history negative for recurrent or hemorrhagic cystitis and we report an overview of literature concerning this topic.
Case report and a review of literature
We report a case of a Caucasian 42-year-old woman, para 0000. Her medical history was negative for allergy and noteworthy comorbidities. On 2001, she underwent laparoscopy for endometriosis. On 2013, during 1st trimester of her first spontaneous pregnancy, evolving physiologically, she complained 3 episodes of hematuria without any associated lower urinary tract symptoms such as dysuria. Patient was taking only prenatal vitamins. Each episode lasted for approximately 1 week.
Her laboratory values were significant for mild anemia with hematocrit of 33% (normal 34–44%). The platelet count was 313×109/l (normal 165–415×109/l) and white blood cell count was 6.5×109/l (normal 3.5–9.0×109/l). Her coagulation parameters were normal. The serum electrolytes were also within normal range. Her renal function was preserved with a creatinine of 0.9 mg/dl (normal 0.5–0.9 mg/dl). Urine analysis revealed 3+ hemoglobin and no protein. Urine microscopy showed 182 red blood cells per high power field. Urine cultures were negative for any bacterial infections. No evidence of intercurrent viral infection was present. Therefore, a cystoscopy was performed, resulting negative for any lesions or erythema.
Urinalyses, done in the 2nd-3rd trimester, resulted normal and negative for hematuria.
Pregnancy hesitated in a spontaneous delivery at term on July 2013 of a baby girl of normal weight (3.200 gr). No placental abnormalities resulted at histological examination.
On October 2015, during 1st trimester of her 2nd spontaneous pregnancy, evolving physiologically, she complained again 2 episodes of hematuria. Also in this case, urine analysis and culture were negative and the episodes self-limited without any medical intervention.
For the first and the second pregnancy, the only laboratory abnormalities consisted of the presence of hemoglobin in urine analysis. Urinalyses, done in the 2nd-3rd trimester, resulted normal and negative for hematuria. Pregnancy, also this time, has hesitated in a spontaneous delivery at term on May 2016 of a baby boy of normal weight (3.450 gr).
Between the two pregnancies, no noteworthy comorbidities or miscarriages were detected.
In both cases, the episodes of hematuria self-limited without any specific treatment. Patient was encouraged to increase the daily water amount (up to 3.5 Liter) and a prophylactic antibiotic (single-dose fosfomycin) was prescribed.
Very little has been written in the obstetric literature about hemorrhagic cystitis in pregnancy and its management.
In fact, Figueroa-Damián et al. [1] presented one patient with a clinical status of hematuria, dysuria, frequency, urgency and premature labor, due to urine bacterial infection; Fakhoury et al., [2] reported 2 cases: a 16 years-old Hispanic woman at 30 weeks and a 29 years-old African American at 33 weeks with a gross hematuria and a previous E.coli urine infection treated with antibiotics. In the first case woman had a preterm delivery at 34 weeks while the second one delivered at 39 weeks.
Discussion
Hemorrhagic cystitis is gross hematuria and symptoms of cystitis. Usually a self-limiting entity, it is found mainly in children and cancer patients receiving chemotherapy or radiation. In a small number of patients, hemorrhagic cystitis can be severe and require aggressive management. In literature, there are only a few articles about hemorrhagic cystitis in pregnancy, frequently associated with preterm labor [1, 2].
We describe, for the first time in Literature, one patient with a clinical status of hematuria in two consequent pregnancies, without any identified cause and a medical history negative for recurrent or hemorrhagic cystitis prior pregnancies.
In literature, only 3 cases have been reported [1, 2] and in all cases due to infective urine episodes. Therefore, the unique aspect of our case report is that no infective or iatrogenic causes have been identified but for two consequent pregnancies these episodes have been experienced, suggesting that they may be connected by each other’s links. In fact, we hypothesized that these episodes of hematuria may be due to pregnancy-related immunological changes. To support this hypothesis, in both cases, hematuria interested 1st trimester, the period that create a pro-inflammatory environment [3, 4]. In fact, no episodes of hematuria occurred during 2nd and 3rd trimester.
During normal pregnancy, the human decidua contains a high number of immune cells, such as macrophages, natural killer (NK] cells and regulatory T cells (Treg) [5–8].
From the adaptive immune system, B cells are absent, but T lymphocytes constitute about 3–10% of the decidual immune cells. During the first trimester, NK cells, dendritic cells and macrophages infiltrate the decidua and accumulate around the invading trophoblast cells [9, 10].
NK cells, overexpressed in pregnancy, in particular during 1st trimester, causes the maturation of proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 to engage the innate immune system at basis of hemorrhagic cystitis [11]. However, long-term follow-up, larger series of patients and specific immunogenetic factors are necessary to confirm these hypotheses.