06 January 2023: Articles
Challenging differential diagnosis, Rare diseaseChristina H.J. Yang 12ABCDEF*, Elizabeth N. Eykman3BCDE, Christopher J. Smith4BCD, James Bacon4BCD, Jonathan M. Morris24BCD, Rodney J. Baber 4EF, Sean K.M. Seeho 24ADE
Am J Case Rep 2023; 24:e938276
BACKGROUND: Vernix caseosa peritonitis (VCP) is a rare complication that typically presents following an otherwise uneventful cesarean section. Leakage of vernix caseosa into the peritoneum is thought to elicit a granulomatous foreign body reaction. Symptoms can be similar to other acute abdominal conditions, and diagnosis is confirmed by intraoperative findings and histological examination. Peritoneal lavage with supportive measures is the mainstay of treatment and recovery.
CASE REPORT: Case 1 was a 30-year-old woman who developed right iliac fossa pain, fever, tachycardia, and tachypnea less than a week after her lower segment cesarean section (LSCS). She underwent a laparoscopy for a peritonitic abdomen and concern for intra-abdominal sepsis. A peritoneal biopsy demonstrated histological changes consistent with VCP. Case 2 was a 39-year-old woman who underwent a LSCS. After discharge, she re-presented with generalized abdominal pain. With computed tomography (CT) scan findings suggestive of appendicitis, an appendectomy was performed, and vernix caseosa was detected in all quadrants. Case 3 was a 33-year-old woman who presented with fever, vomiting, diarrhea, and iliac fossa pain 9 days following an LSCS. She was given analgesia and antibiotics for a pelvic fluid collection noted on CT scan. She re-presented with tense swelling and pain above her cesarean section incision. Laparoscopy revealed adhesions over the lower abdomen and pelvis and white plaques suggestive of vernix caseosa along the peritoneal side walls.
CONCLUSIONS: The rising incidence of cesarean births worldwide creates the potential for increased numbers of VCP cases. Greater recognition of VCP is warranted to prevent unnecessary procedures.
Keywords: Abdomen, Acute, Cesarean Section, Laparoscopy, Laparotomy, peritonitis, Vernix Caseosa
Vernix caseosa is present on the skin of newborns and serves a protective function, including being antimicrobial and moisturizing . Macroscopically, vernix caseosa, “cheesy varnish” in Latin, appears as white cheese-like material covering the skin of newborns. Microscopically, vernix caseosa consists of sebum, fetal epithelial cells, and lanugo hair [2–4].
Information regarding vernix caseosa peritonitis (VCP) has been limited to case reports and series, with a total of 34 cases published since the original article in 1976 [2,4–27]. VCP is more commonly reported after cesarean section. However, as the understanding of VCP has expanded, it has been described following vaginal delivery [21,25] as well as during pregnancy [7,10]. In addition, 2 cases of VCP were found in appendectomy specimens from neonates who underwent the procedure for gastroschisis .
The limited number of reported cases of VCP suggests that it may be underdiagnosed and/or misdiagnosed. The clinical presentation of VCP can often mimic more common acute abdominal conditions and result in unnecessary procedures, such as appendectomy, colon resection, hysterectomy, cholecystectomy, and salpingo-oophorectomy to excise healthy organs [4–6,14]. Furthermore, the need for histological examination and nonspecific findings with imaging impede the diagnosis of VCP.
This paper includes 3 cases presenting to a hospital in Sydney, Australia, in which VCP was diagnosed following birth and describes their clinical presentation, test results, management, and outcomes.
A 30-year-old nulliparous woman delivered a baby girl weighing 3.668 kg at 40 weeks of gestation via a lower segment cesarean section (LSCS) after failure to progress in labor. Four days later, she noted worsening right iliac fossa pain radiating to the right hypochondrium and left iliac fossa. The following day, the woman was diaphoretic and had generalized abdominal pain, which was treated with opioid analgesia. During this time, she was noted to have leukocytosis (14×109/L), elevated lactate (2.3 mmol/L), and elevated C-reactive protein (CRP) level of 111 mg/L. A CT scan revealed inflammatory change involving the anterior wall of the cecum without appendiceal involvement. She was subsequently started on ceftriaxone and metronidazole. On day 6, she became febrile, tachycardic, and tachypneic, with a firm and distended abdomen, suspicious for intra-abdominal sepsis. A laparoscopy exposed widespread inflammatory changes and adhesions, for which adhesiolysis and peritoneal washout were performed. A peritoneal biopsy obtained from the procedure demonstrated keratin fragments, mainly neutrophilic inflammatory exudate, and multi-nucleated foreign body – type giant cells, a finding consistent with VCP (Figure 1).
The patient was started on prednisone after surgery but received only 2 days of therapy due to worsening hypertension and associated headaches on a background of pre-eclampsia. The patient’s medication was later stepped down to amoxicillin and clavulanate, and she continued antibiotic therapy for a total 18-day course. She was discharged from hospital on day 10. At 6 weeks postpartum, she had ongoing right-sided abdominal discomfort, but achieved pain resolution by post-partum week 10.
A 39-year-old nulliparous woman with a background of syndrome of inappropriate anti-diuretic hormone (SIADH) underwent an uncomplicated emergency LSCS at 39 weeks of gestation for failure to progress in labor and delivered a baby girl weighing 4.255 kg. She was discharged 3 days later but presented to the Emergency Department 8 days postoperatively with sharp, constant generalized abdominal pain that was most tender in the right iliac fossa. She had not had a bowel movement during the previous 4 days and had not passed flatus for 2 days. A leukocytosis (17.4×109/L) with neutrophilia (14.9×109/L) and elevated CRP level (367 mg/L) were noted. An ultrasound scan demonstrated free fluid in the abdomen and pelvis, and a CT scan revealed a tubular structure arising from the posterior cecum, suspicious for appendicitis and coexisting bowel ileus. Laparoscopic examination exposed vernix caseosa in all 4 quadrants of the abdomen, most notably in the right lower quadrant. The patient’s appendix was removed, and a peritoneal washout was performed. Histopathological analysis of the appendix was normal. However, near its serosa was keratinous material accompanied by multinucleated giant cells (Figure 2). The patient required a 3-week admission in hospital for treatment of pain. Intravenous antibiotics were given for 2 weeks for empiric treatment of possible group B streptococcus infection, but blood cultures failed to reveal any causative organisms.
The patient had ongoing abdominal pain for 9 months and twice presented to the Emergency Department with severe pain. Both times she was treated with analgesia and intravenous fluids and discharged. Nearly 2 years after her initial LSCS, she had an elective LSCS and gave birth to twins; both the operation and recovery were without complications.
A 33-year-old nulliparous woman with obstetric cholestasis was induced at 38 weeks of gestation. After failure to progress in labor, she underwent an emergency LSCS to deliver a baby boy weighing 3.45 kg and was discharged home without issues on day 3. Nine days after surgery, the woman had low-grade fever and experienced vomiting, diarrhea, and left lower quadrant abdominal pain. An abdominal ultrasound revealed a heterogeneous hematoma within the endometrial cavity as well as a small volume of free fluid within the pelvis. She was also noted to have hypokalemia (2.8 mmol/L), with raised CRP level (221 mg/L), leukocytosis (14×109/L), and thrombocytosis (>1000×109/L). The patient’s urine specimen exhibited a strong presence of leukocytes. A contrast CT scan of her abdomen and pelvis displayed an irregular, lobulated fluid collection between the uterus and bladder, suggestive of infected material. She was treated with antibiotics and discharged home on day 13.
The patient re-presented 4 weeks following birth with severe abdominal pain and tense swelling above the cesarean incision. She was found to have a raised white cell count (16.4×109/L), thrombocytosis (999×109/L), and elevated CRP (100 mg/L). A diagnostic laparoscopy was performed, which demonstrated significant adhesions over the lower abdomen and pouch of Douglas. Along the peritoneal side walls were white plaques, suggestive of vernix caseosa. A peritoneal biopsy showed fibrotic tissue containing mononuclear and foreign body–type multinucleated giant cells, but no diagnostic squamous cells. A thorough peritoneal washout was performed.
The patient required multiple pain consultations during her hospital admission, and was discharged home on day 3 with prednisone, analgesia, and antibiotics. She had no residual abdominal pain at postpartum week 6. Two years later, she had an uncomplicated pregnancy and a spontaneous vaginal delivery of her second child.
While the details of its pathophysiology are not well understood, VCP is generally considered to be a granulomatous foreign body reaction to vernix caseosa within the amniotic fluid . Traditionally, the explanation of this has been vernix caseosa-containing amniotic fluid spilling or leaking into the peritoneal cavity during a caesarean section. Higher concentration of vernix caseosa in amniotic fluid during difficult labor and excessive manipulation of the fetus have been considered as contributing factors to the development of VCP . Interestingly, each patient in this case series had a medical comorbidity (case 1: pre-eclampsia; case 2: SIADH; case 3: obstetric cholestasis); however, there are no previous reports of these comorbidities being present in women with VCP.
The most common presentation of VCP includes abdominal pain and fever following a cesarean section [4,7,9,16]. The mean time from LSCS to VCP presentation is 10 days and ranges from 0 to 35 days. Leukocytosis is often present, accompanied by raised inflammatory markers. This pattern of presentation often results in a provisional diagnosis of common abdominal conditions, including appendicitis and cholecystitis [2,4–27]. Imaging generally yields inconclusive results, including normal tissues, fluid accumulation in the peritoneal cavity, or possible abscesses or nodules [3,7–9,11–13,15,16,24]. Failure of pain resolution commonly leads to a laparotomy or laparos-copy to further investigate the source of ailment [17,20–25].
The typical macroscopic appearance of VCP is of widespread white cheesy exudates on the serosal surfaces of multiple viscera. Adhesions in the peritoneal cavity are commonly reported, and a non-purulent peritoneal collection can also be present [2,10,15,16]. Abdominal organs are generally not inflamed; however, because an acute abdominal condition is often the provisional diagnosis, the appendix and other parts of the bowel are often removed.
Common microscopic histopathological findings include anucleate squamous cells, hair shafts, and giant cell foreign body reactions. A mixed inflammatory response is associated with anucleate squamous cells, which can appear individually or in clumps [16,29]. The histological appearance varies depending on the time since the trigger event . Features of acute inflammation with predominantly neutrophils is typical of short time intervals and a transition to a granulomatous foreign body reaction occurs with time [10,22,30].
The mainstay of treatment for VCP – peritoneal lavage alone and without organ removal – is generally sufficient to resolve most cases . Intravenous antibiotics and fluids are almost always given as supportive measures at initial presentation. Steroid therapy has been used in some cases to reduce symptoms, especially when microbiological cultures are negative [11,24,26].
Identification of predisposing factors for VCP is difficult due to a lack of data. Possible factors include oligohydramnios and excessive manipulation of the fetus during difficult labor, both of which would increase concentration of vernix caseosa in amniotic fluid . Other considerations include maternal and fetal factors affecting the prevalence of vernix caseosa itself, such as multiparous mothers who ingest medications and dietary supplements during pregnancy, female infant, full-term gestation, and high birth weight .
The rising rates of cesarean births globally may cause an increased incidence of VCP . The incidence of VCP can be lowered if thorough peritoneal lavage during surgery was common practice, thereby reducing the concentration of or eliminating vernix caseosa contamination in the peritoneal cavity . However, this may not be effective in some women in whom immunological hypersensitivity is hypothesized to play a key role in the development of VCP . Interestingly, in 1 case of a surrogate mother with VCP, a possible heightened immune response was suggested . There are too few cases at present to determine whether parity may be a predis-posing factor to the development of VCP.
Inadequate recognition of VCP and inconsistent and limited available data hinder the formation of high-quality clinical recommendations or protocols for the identification and management of VCP. However, it is important to consider VCP as a potential diagnosis in women presenting with acute abdomen postpartum and consider peritoneal lavage as a therapeutic intervention prior to consideration of organ excision, especially in the setting of investigations with undifferentiated findings. Future case reports would benefit from a structured format of reporting to improve data collection and analysis, so that factors associated with VCP are identified and its treatment optimized.
FiguresFigure 1.. Microscopic view of peritoneal biopsy sample obtained from patient with vernix caseosa peritonitis showing dense neutrophilic inflammation (yellow arrow) surrounding keratin fragments with some fibrin. Figure 2.. Inflammatory response near appendiceal serosa with features of vernix caseosa peritonitis. Keratinous material (yellow arrow) surrounded by granulomatous inflammation including foreign body – type giant cells (black arrows). Neutrophils, lymphocytes, and histiocytes are also seen.
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