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Persistent abdominal distension, bilious emesis, and feeding intolerance in an infant without anatomical bowel obstruction

Year: 2024

Type: article

Abstract: A baby girl born at 38 weeks of gestation, with an uneventful antenatal history, develops bilious emesis and abdominal distension on the second day of life. She is admitted to the neonatal intensive care unit (NICU). Initial comprehensive workup, including complete blood count, C-reactive protein, erythrocyte sedimentation rate, complete metabolic panel, ammonia, lactic acid, blood culture, urine culture, and cerebral spinal fluid culture, are normal. An upper gastrointestinal (GI) barium series shows dilated bowel loops without evidence of any anatomical abnormality. A barium enema shows adynamic ileus with a small caliber of the distal colon. Subsequently, suction rectal biopsies are performed to show the presence of ganglion cells. She is managed conservatively with supportive care, including nasogastric decompression and parenteral nutrition. She continues to have symptoms of abdominal distension, intermittent bilious vomiting, and persistent air-fluid levels on serial abdominal imaging. The presentation of abdominal distension, feeding intolerance, and bilious emesis in early neonatal life is highly suggestive of anatomical obstruction (e.g., intestinal atresia, malrotation, or volvulus) and requires immediate evaluation. As was done in our case, systemic infection and metabolic diseases also need to be excluded. A diagnostic exploratory laparotomy was performed during her second week of life, but no specific cause of her symptoms could be identified. Notably, her distal ileum had a “corkscrew” appearance and was resected (Figure 1). Histological evaluation was interpreted as normal without any evidence of inflammation or significant neuromuscular pathology. We still do not have a diagnosis as this baby enters her third week of life in the NICU. We are looking at maintaining her on parenteral nutrition without a clear plan to feed her. Her symptoms of abdominal distension, feeding intolerance, and intermittent emesis remain unexplained. Whole-genome sequencing was performed to rule out any underlying genetic causes. It showed a variant of uncertain significance in the HFN1B gene but was otherwise unremarkable. At 12 weeks of age, she undergoes a second laparotomy with gastrostomy tube placement and creation of a decompressing ileostomy. While she remains hemodynamically stable, she is unable to tolerate feeding and is totally dependent on TPN. Based on a nonrevealing evaluation and persistent obstructive symptoms with abdominal distension, feeding intolerance, intermittent bilious emesis, and dependency on parenteral nutrition for several months, our patient fulfilled the diagnostic criteria for chronic intestinal pseudo-obstruction (CIPO). In children, this is now referred to as pediatric intestinal pseudo-obstruction or “PIPO.” Ultimately, an enteric neuromuscular pathology expert was asked to review full-thickness sections from the resection specimen. That review revealed a diagnosis of congenital myenteric hypoganglionosis. Our patient had a prolonged NICU stay for several months. She was managed with supportive care requiring parenteral nutrition. She was able to tolerate minimal amounts of enteral feeds. She was eventually discharged on “home parenteral nutrition” with trophic gastrostomy tube feeds and close follow-up. The field of study of intestinal pseudo-obstruction does not identify specific diagnostic criteria for the entities described. In general, chronic intestinal pseudo-obstruction (CIPO) is used to describe the entity of intestinal pseudo-obstruction, which when it occurs in children is referred to as PIPO.1 Chronic myenteric hypogangliosis (CMH) is a more specific term that has been used to describe the findings in the patient in this case report. CMH is a congenital disorder that typically presents with signs of severe pseudo-obstruction, generally in the neonatal period.2 The pathological findings of relatively small myenteric ganglia composed of small (immature) myenteric ganglion cells with reduced surrounding neuropil and disproportionately few neuronal nuclei (NeuN) and calretinin-immunoreactive ganglion cells (as compared to controls) suggested the underlying diagnosis of CMH in our patient (Figures 2 and 3). PIPO is considered among the most severe gut motility disorders and is associated with a high mortality rate of about 30% in children.3, 4 Manometry studies are difficult to perform and interpret in very young infants and the diagnostic yield of full-thickness bowel biopsies is low. Reasons for low diagnostic yield of histopathological specimens are in part due to the lack of a standardized approach to process and interpret biopsy specimens and paucity of pathologists with sufficient experience to confidently interpret these specimens. CMH is also referred to as “pseudo-Hirschsprung's disease” (pseudo-HD) due to overlap in clinical presentation with HD.5, 6 CMH may involve large segments of small intestine and/or colon and is not amenable to surgical correction. Thus, patients with CMH require long-term parenteral nutrition and ultimately intestinal transplantation for survival.5, 6 The histopathological diagnosis of CMH is challenging and requires a pathologist with expertise in interpreting enteric neuromuscular pathology. Despite some overlap, the histopathological findings in CMH are distinct from HD. In contrast to HD in which histological findings include complete absence of ganglion on rectal biopsies, patients with CMH have quantitative and qualitative abnormalities of ganglion cells including a markedly decreased number of ganglion cells with small sized ganglia and nerves in the myenteric plexus.7 The diagnosis may be associated with depletion of surrounding neuropil and cytological immaturity of ganglion cells. The histological details might be missed if the biopsy sample is small and/or does not involve muscularis propria to allow detailed evaluation of the myenteric plexus. In addition, immunohistochemical features may be helpful in the diagnosis of CMH. Selective deficiency of non-nitrergic neurons resulting from failure of survival or proliferation of their progenitors has been proposed to be the basis of CMH, although the exact etiology is not known yet. Absence of NeuN and calretinin-immunoreactive antigens is highly suggestive of CMH.2, 8 This case sheds light on PIPO, a rare and one of the most severe and debilitating pediatric GI motility disorders. PIPO is usually suspected in patients with feeding intolerance, bilious emesis, abdominal distention, and dilated loops of small bowel with air-fluid levels on imaging in the absence of mechanical obstruction, including Hirschsprung disease, metabolic, endocrine, and electrolyte abnormalities. A large proportion of patients with PIPO have clinical symptoms that start in the first month of life and often require prolonged parenteral nutrition, and surgical interventions for feedings, decompression, diversion, and so on. The diagnosis of PIPO can be difficult to make due to its variable clinical presentation, presence of other comorbidities, organ involvement, and a lack of a single definitive diagnostic test or biomarker. It is important to note that an immature intestinal motility pattern found in preterm infants may mimic the neonatal onset of PIPO, and thus, this diagnosis should be made with caution in this group, given the migrating motor complex does not appear in its mature form until a gestational age of 34–35 weeks. There are three district etiologies of PIPO (primary, secondary, and idiopathic) that are further classified into myopathic, neuropathic, and mesenchymopathic types that can be associated with other genetic syndromes and diseases. Though most cases of PIPO are sporadic, genetic testing in syndromic phenotypes can be helpful given recent advances in the discovery of a genetic mutation associated with PIPO.9 Although not done in this infant and despite its limitations, antroduodenal manometry performed and interpreted by a neurogastroenterology and motility expert can be a valuable test to help confirm the diagnosis, clarify the type of PIPO and assess clinical response to prokinetics. Analysis of a full-thickness intestinal biopsy by a center with the necessary expertise in neuromuscular specimen evaluation can be paramount in unraveling structural changes in the neuromuscular layer that can provide further insight into the diagnosis. For example, CMH diagnosed in this newborn is extremely rare. Currently, there is no clear consensus regarding diagnostic criteria that require significant deviations in ganglion size and morphology on evaluation of a full-thickness intestinal biopsy. There is still much to uncover about PIPO and its subtypes. Whether this entity is part of a spectrum of PIPO or a stand-alone diagnosis is yet to be determined. Management of PIPO is challenging. Children with PIPO secondary to CMH are managed conservatively with supportive care. Surgical interventions like ileostomy or colostomy may confer some symptomatic improvement and help preserve some bowel motility and function.10, 11 The ultimate goal is to preserve bowel function and prevent the patient from going into intestinal failure. Effective management of small bowel bacterial overgrowth with judicious use of antibiotics, enteral feeding support, managing parenteral nutrition to minimize hepatic complications, and decompressing the bowel to minimize pain and abdominal distention requires close coordination within the multidisciplinary team. In severe cases of CMH, the patients may need long-term parenteral nutrition, eventually requiring intestinal transplantation for survival. Given the significant comorbidities and multiple complexities, nutritional concerns, chronic GI symptoms, and long-term psychological challenges, an interdisciplinary team approach is necessary in the care of these patients. A collaborative research network is needed to help clarify genotype-phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies for patients with PIPO. Persistent symptoms of intestinal obstruction (feeding intolerance, emesis, abdominal distension, and distended bowel loops on imaging) in the absence of a fixed obstructive lesion should raise suspicion for PIPO. In a patient such as the newborn presented here, the presence of ganglion cells on rectal biopsies does not rule out the possibility of intestinal enteropathies like CMH. A high index of suspicion is needed for diagnosis of CMH and expert pathology consultation may be required. A patient with CMH may need prolonged supportive care with parenteral nutrition. The overall prognosis is guarded in case of severe CMH with high morbidity and mortality. A multidisciplinary team approach (including gastroenterologists, surgeons, social workers, psychologists, and pathologists) is crucial to improve patient prognosis and outcome. The authors have nothing to report. The authors declare no conflicts of interest. Informed consent was obtained from the patient's family.

Source: JPGN Reports

DOI: 10.1002/jpr3.12151

Authors: Muhammad Rehan Khan, Anshu Maheshwari, Daniel J. Robertson, Julie Khlevner, Raj P. Kapur, Manu R. Sood