Soliris may raise worse outcomes risk for PNH patients with NEC
Case illustrates need to be mindful of 'gastrointestinal complications'
A young woman with paroxysmal nocturnal hemoglobinuria (PNH) developed neutropenic enterocolitis (NEC), a severe and life-threatening complication, after receiving treatment with Soliris (eculizumab), a case report indicates.
NEC is marked by severe inflammation of the large intestine, which may be associated with infection, due to a markedly low number of neutrophils, the “first responders” of the immune system.
While a number of factors can contribute to NEC, administering Soliris may have enhanced the immune imbalance that resulted in the patient’s death in a case researchers wrote “underscores the challenges in managing NEC and highlights the importance of early recognition and intervention in high-risk patients. The report, “Fatal Neutropenic Enterocolitis in a Young Female After the First Round of Eculizumab for Paroxysmal Nocturnal Hemoglobinuria,” was published in Cureus.
PNH is a rare disease marked by the destruction of blood cells, which is caused by an abnormal activation of the complement cascade, a part of the immune system. The most common symptoms include low red blood cell levels, or anemia, fatigue, shortness of breath, and abdominal pain.
In fewer than 4% of cases, patients develop severe neutropenia, or a marked reduction of neutrophils, which increases the risk for life-threatening conditions such as NEC. Also known as typhlitis, NEC is marked by inflammation, swelling and death of different parts of the large intestine. It mainly occurs in immunocompromised people.
The mainstay treatment for PNH are medications that block the complement system’s activation, such as Soliris. Its impact on the immune system “remains a subject of debate,” particularly in the gastrointestinal (GI) tract, however. The GI contains multiple immune cells and a unique microbiome, that is, a community of microbes living in the gut, with a well-balanced interaction between both.
Developing NEC after PNH treatment with Soliris
Here, clinicians at the Broward Health North in Florida and the University of Miami at Holy Cross describe the case of a 31-year-old woman with PNH who was treated with Soliris and later succumbed to NEC.
The woman had aplastic anemia, a deficiency in being able to produce sufficient red blood cells, due to PNH. She went to the emergency room after three days of severe abdominal pain, nausea, vomiting, diarrhea, fever, and chills. She had received the first round of Soliris treatment for PNH in the previous two days. She was in severe pain, with dry mouth and had a general tenderness in her abdomen.
Lab tests showed a severely low number of white blood cells, a depletion of neutrophils, below normal levels of the protein hemoglobin, which carries oxygen in red blood cells, and platelets, which are tiny blood cells involved in blood clotting. The woman’s symptoms led to a diagnosis of neutropenic sepsis, a life-threatening condition where very low numbers of neutrophils result in a severe infection developing.
Further blood tests revealed high levels of liver enzymes indicating liver damage and too much acid in the blood, called metabolic acidosis. A CT scan of the woman’s abdomen and pelvis confirmed thickening of the large intestinal wall, suggesting inflammation or enterocolitis.
She was immediately given fluids into a vein and was transferred to the intensive care unit where she received anti-fever medications along with a combination of large-spectrum antibiotics and an antifungal. She also started treatment with filgrastim (sold as Neupogen, among others) to boost her neutrophil production.
‘Gastrointestinal complications’
After a consultation with the general surgery department about her acute abdominal tenderness and the lack of bowel sounds, a nasogastric tube decompression was attempted. This procedure is intended to alleviate the pressure on the abdomen in patients with bowel obstruction or a distended abdomen, and involves inserting a thin, flexible tube through the nose, down the esophagus, and into the stomach.
The woman also received medications to increase her heart rate, but was intubated due to respiratory failure. Blood work confirmed a decrease in the levels of her blood cells, so surgery wasn’t considered as a viable option.
The woman suffered a cardiac arrest, but was reanimated. Blood cultures confirmed an infection with the multidrug-resistant bacteria strains Klebsiella pneumoniae and Enterococcus cloacae. Her antibiotic therapy was adjusted to include more appropriate antibiotics, but the woman developed multiorgan failure.
She received continuous dialysis, which filters the blood when the kidneys aren’t able to do it, along with blood transfusions.
The patient had another cardiac arrest and her condition continued to deteriorate, despite being resuscitated twice. A neurological exam revealed no standard, automatic brain responses such as blinking and swallowing. Brain MRI scans showed low blood flow to the brain and severe swelling, resulting in brain death.
The report highlights how “clinicians should remain vigilant for gastrointestinal complications and implement a multidisciplinary approach,” in PNH patients. This may involve “management of PNH and [Soliris] therapy, infectious disease for managing potential infections, nutrition for addressing dietary requirements, and surgical consultation when necessary,” the researchers wrote. “Such a comprehensive strategy is essential for optimizing management and improving patient outcomes.”
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