Cyproheptadine Treatment of COVID-19-Induced Enteritis: Implications for Hyperinflammatory Phase Management

A patient presented with COVID-19-induced enteritis and colitis associated with a high D-dimer. Serotonin released by activated platelets can lead to inflammation and multiorgan failure in COVID-19 infection. Cyproheptadine blocks serotonin receptors. In light of a prior report that showed that cyproheptadine successfully treated neurologic sequelae in COVID-19, we applied this treatment to this patient. Rapid clinical improvement and reduction of D-dimer occurred after 3 doses of cyproheptadine. This inexpensive, well-Tolerated, oral medication may be applicable to treat hyperinflammatory sequelae of COVID-19 infection.Copyright © 2023 American College of Gastroent. All rights reserved.

Case Presentation Competition, 5 Back to Basics

Serotonin syndrome associated with clozapine withdrawal and concurrent selective serotonin reuptake inhibitor (SSRI) use has previously been reported. A 56-year-old female with schizophrenia was admitted for pyrexia, rigidity, and altered mental state after her second dose of clozapine restart. She had discontinued her long-term clozapine 2 weeks prior. She developed ventilatory failure, reduced consciousness, eye deviation, and worsening rigidity, requiring ICU support. Examination showed a right upper motor neurone syndrome with absent ankle reflexes. She had raised inflammatory markers and creatine kinase. Serum neuropathy, encephalitis screen, and COVID PCR were negative. Respiratory investigations were unfruitful. MRI head and spine did not show brain or cord signal change to correlate to signs. Lumbar puncture showed a quiet CSF, negative culture, viral PCR, and encephalitis antibodies. EEG showed bihemispheric background slowing. Despite clinical improvement, repeat examination showed persistent signs. She was diagnosed with serotonin syndrome after developing a bilateral tremor. Treatment with cyproheptadine correlated with an improvement in her signs, cognitive state, and EEG. Serotonin syndrome can present with reversible neuromuscular signs. With clozapine withdrawal, it can require a prolonged time course of recovery in contrast with classical serotonin syndrome. Cyprohepta- dine can cause agranulocytosis and this delays clozapine restart.

A Case of Beriberi After MIS-C

Introduction: As of June 2021, 4 million children have tested positive for COVID-19 in the US. In contrast to adults, children are often hospitalized with gastrointestinal symptoms including persistent vomiting. Pancreatitis has also been seen in MISC, which can lead to malnutrition. Most physician learn about thiamine deficiency and Wernicke Encephalopathy in patients with severe alcoholism or in low-income settings. We cared for a child with Wernicke Encephalopathy due to subacute malnutrition and weight loss after pancreatitis secondary to MISC in the US. Case Description: A 13-year-old female presented to Levine Children's Hospital with weight loss. She was diagnosed with COVID on 1/23/21 with 1 week of URI symptoms, with baseline weight 165 pounds (BMI 31.1). She was seen in an Emergency Department (ED) on 3/1/21 for vomiting with lipase 350u/L;she received fluids and was discharged. She represented on 3/7/21 with persistent symptoms weighing 135.5 pounds (BMI 25.6) with lipase 790u/L. She was discharged after three days with a diagnosis of post-COVID pancreatitis and lipase 600u/L. After discharge, she continued losing weight despite ondansetron. She followed up with GI on 3/15, weighing 130 pounds (BMI 24.5). An abdominal MRI and endoscopy were normal. She was started on omeprazole and cyproheptadine. She presented to Levine Children's Hospital on 3/24/21 for a second opinion. Upon admission, her serum lipase was 895u/L and she weighed 115 pounds (BMI 21.7). She was started on dextrose-containing fluids and developed seizures on 3/27/21. MRI brain was normal. Ophthalmology noted bilateral abducens nerve palsy. She developed worsening mental status and respiratory failure, so was intubated. A repeat MRI brain revealed posterior reversible encephalopathy syndrome and findings specific for Wernicke Encephalopathy. Thiamine level was low, and empiric thiamine was initiated. She was started on feeds and clinically improved. She was then extubated and showed improvements in her motor function and ability to follow commands. She transferred to inpatient rehab and continues to make progress. Discussion: Identification of the degree of malnutrition for this patient was difficult to obtain due to non-communicating EMRs. This limited the providers' ability to accurately quantify the degree of weight loss and the potential for Thiamine deficiency. The combination of limited body storage and short half-life can result in total depletion of thiamine stores within 2 weeks leading to altered mental status. Unfortunately, stigmatization of obesity in children has been well documented and malnutrition may be overlooked due to a normal BMI. Conclusion: Obtaining growth charts for patients presenting with weight loss is important as they provide objective data and help prevent obesity bias. If a child has a history of weight loss and develops altered mental status, vitamin B deficiencies should be considered in the differential. Pancreatitis associated with MIS-C can cause significant malnutrition leading to Wernicke Encephalopathy.

Unprovoked serotonin syndrome-like presentation of SARS-CoV-2 infection: A small case series.

Clinicians and researchers have reported an array of neurological abnormalities in coronavirus disease 2019 (COVID-19), and while serotonin excess has been observed we are unaware of reports of central nervous system serotonin toxicity in COVID-19. We present two cases that resemble serotonin syndrome in COVID-19, but without identifiable inciting medications. A 54-year-old with multiple sclerosis and diabetes mellitus presented with altered mental status. His altered sensorium was attributed to diabetic ketoacidosis, but his condition quickly deteriorated with fever to 105 degrees Fahrenheit, rigidity in all extremities, inducible clonus, and hyperreflexia. He was intubated and was treated for possible meningitis and seizure. Neurologic workup was negative for acute pathology. Despite acetaminophen, his core temperature remained elevated to 105 degrees Fahrenheit. He was treated with external cooling and cyproheptadine and within 48 h, his fever, rigidity, hyperreflexia, and clonus resolved. He was extubated and discharged home on day 14. A 72-year-old with hyperlipidemia was admitted with tremors, 4 days after testing positive for COVID-19. His symptoms rapidly worsened, and he was transferred to the Intensive Care Unit on day 3 in extremis, febrile to 104.4 degrees Fahrenheit, heart rate of 180 beats per minute, and apparent whole body myoclonus. He was intubated and developed fever refractory to acetaminophen requiring external cooling. Extensive neurologic workup was negative. He received cyproheptadine and slowly improved. He was extubated and discharged to rehab on day 11. These cases represent a unique presentation in COVID-19 that must be considered and requires a high index of suspicion.