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      Pancreatitis aguda en paciente pediátrico afecto de síndrome inflamatorio multisistémico atribuido a COVID-19 Translated title: Acute pancreatitis in children with COVID-19-associated multisystem inflammatory syndrome

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          Abstract

          Sr. Editor: En mayo de 2020 se describe por primera vez el síndrome inflamatorio multisistémico (SIM) caracterizado por una inflamación significativa con rasgos similares a la enfermedad de Kawasaki (EK). Aunque la relación etiológica no está aún definida, este síndrome resulta coincidente en el tiempo con la pandemia del SARS-CoV-2 y en la mayoría de las ocasiones se asocia con infección pasada o reciente por este virus 1 . Existen pocos datos sobre pacientes con esta enfermedad. Aunque la clínica abdominal es frecuente en pediatría, existen pocos datos y la bibliografía al respecto es escasa, sobre pancreatitis aguda en el niño afecto de este síndrome2, 3, 4, 5. Presentamos el caso de un niño de 10 años que acude a urgencias de un hospital terciario por dolor abdominal de localización en hemiabdomen derecho con vómitos y fiebre asociada de nueve días de evolución. Se trata de un paciente sin antecedentes personales de interés que en el mes previo a esta consulta presentó infección aguda por COVID-19 diagnosticado por PCR realizada en contexto de síndrome febril autolimitado. En la exploración, se objetiva un exantema eritematoso macular generalizado, labios rojos agrietados, eritema conjuntival bilateral no supurativo y dolor con defensa abdominal a nivel de fosa iliaca derecha. Se realizó una ecografía y un TC abdominal donde no se objetivan hallazgos compatibles con abdomen agudo ni otras alteraciones intraabdominales incluyendo área pancreática. De igual manera, se realizó analítica sanguínea objetivándose leucocitosis con neutrofilia y una llamativa elevación de enzimas cardíacas (valores en tabla 1 ). Esto motivó la realización de una ecografía cardíaca donde se pudo apreciar dilatación coronaria izquierda y derrame pericárdico leve. Los hallazgos clínicos y analíticos orientaron el caso a un síndrome inflamatorio multisistémico tipo Kawasaki atribuido a infección por COVID-19 (el paciente tenía IgG positivas a SARS-CoV-2), por lo que se inició tratamiento con inmunoglobulina y ácido acetilsalicílico a dosis antiinflamatoria. Tabla 1 Pruebas complementarias realizadas durante el ingreso de paciente afecto de SIM vinculado a infección pasada por SARS-CoV-2 Tabla 1 Día 1 Día 3 Día 8 Día 14 Leucocitos totales (/mcl) 18.430 13.900 9.860 6.640 Neutrófilos (/mcl) 13.560 7.740 6.210 3.470 Linfocitos (/mcl) 1.950 2.700 1.960 2.420 Monocitos (/mcl) 810 400 860 830 Eosinófilos (/mcl) 1.050 710 740 550 PCT (ng/mL) 2,30 1,10 0,19 < 0,5 PCR (mg/L) 103.90 63,30 4,40 2,19 Troponina T (ng/L) 376 14 8 7 NT-ProBNP (pg/mL) 4.636 902 54 26 Amilasa (U/L) * 189 226 153 Lipasa (U/L) * 122 114 55 Ecografía abdominal Vesícula biliar con contenido en su interior. Ectasia pielocalicial grado I derecha. Adenopatías mesentéricas en FID aumentadas de tamaño, hipoecoicas y con pérdida del hilio graso, asociando cambios inflamatorios de la grasa periadenopática. Sin alteraciones a nivel de apéndice cecal ni otras alteraciones a nivel intraabdominal. Engrosamiento de cabeza y parte del cuerpo pancreático. Disminución de tamaño de adenopatías en FID, persistiendo cambios inflamatorios en la grasa periadenopatía. Persiste el engrosamiento de cabeza pancreática sin apreciarse cambios inflamatorios en la grasa de celda pancreática. Mejoría de las adenopatías y de la afectación de la grasa locoregional de FID. TC abdominal Adenopatías de tamaño patológico en FID y de menor tamaño en la raíz del mesenterio. Sin otras alteraciones intraabdominales. * No disponemos de los valores de amilasa y lipasa al ingreso. Durante el ingreso presentó importante mejoría tanto clínica como analítica tras la administración de tratamiento farmacológico (evolución analítica en tabla 1). Sin embargo, al octavo día de ingreso, comenzó con dolor abdominal de localización en epigastrio irradiado en banda. Esto motivó la solicitud de una ecografía abdominal objetivándose engrosamiento de cabeza y cuello de páncreas, también se le practicó una analítica sanguínea donde se encontró aumento de enzimas pancreáticas (valores en tabla 1). Dichos hallazgos, además de la clínica sugestiva, según los criterios de Arkansas (prueba de imagen con afectación de área pancreática, elevación de enzimas pancreáticas y dolor abdominal de localización en epigastrio/hipocondrio izquierdo), eran compatibles con pancreatitis aguda. El paciente presentó evolución clínica, analítica y ecográfica favorable en controles sucesivos habiendo sido tratado exclusivamente con dieta blanda y reposo relativo sin precisar tratamiento dirigido hacia dicha pancreatitis. El paciente permaneció durante 15 días en la unidad de hospitalización. En la actualidad se dispone de escasa bibliografía que reporte casos de pancreatitis aguda en población pediátrica en pacientes afectos de SIM3, 4, 5. El mecanismo fisiopatológico y la relación entre pancreatitis aguda y SARS-CoV-2 es aún desconocido. Varios estudios apoyan la teoría de la afectación directa del tejido pancreático por el virus tras entrar en contacto a través del receptor de la enzima convertidora de la angiotensina (ECA2) aunque se necesitan más investigaciones para conocer la relación entre la pancreatitis aguda en niños y la infección por COVID-19 6 . Son necesarios más datos en población pediátrica a fin de estudiar este nuevo síndrome y sus posibles complicaciones.

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          ACE2 Expression in Pancreas May Cause Pancreatic Damage After SARS-CoV-2 Infection

          Furong Liu, Xin Long, Bixiang Zhang … (2020)
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            COVID-19-associated Multisystem Inflammatory Syndrome in Children Presenting as Acute Pancreatitis

            James Stevens, Jefferson Brownell, A. Jay Freeman … (2020)
            In April 2020, a newly recognized pediatric disorder associated with COVID-19 characterized by significant inflammation with symptoms resembling Kawasaki disease was described by medical teams in the United States, the United Kingdom, and Italy. Before these reports, data from the initial COVID-19 outbreaks in China had not found the virus to cause significant morbidity or mortality in children. To date, pancreatitis has not yet been reported in either acute SARS-CoV-2 infection in children or the subsequent inflammatory syndrome. We describe a patient who presented with acute pancreatitis before rapidly progressing to multisystem organ dysfunction consistent with multisystem inflammatory syndrome in children due to COVID-19. Clinicians should be aware that in the context of the COVID-19 pandemic, pancreatitis can be an early presentation of multisystem inflammatory syndrome in children.
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              Pancreatitis in Pediatric Patients With COVID-19

              Nicole L Samies, April Yarbrough, Suresh Boppana (2020)
              INTRODUCTION Over the past several months, understanding of the novel coronavirus disease 2019 (COVID-19) has grown extensively with new findings of organ system involvement reported on a regular basis. Pulmonary manifestations of the disease appear to be the most common presentation of COVID-19, but extrapulmonary disease including gastrointestinal symptomatology are becoming more apparent. To date, the association between COVID-19 and pancreatitis has been limited to a few case reports, mostly in adult patients. This case series illustrates the clinical presentation of 3 pediatric patients who were diagnosed with pancreatitis about a week after the onset of COVID-19 symptoms. Diagnosis of pancreatitis was based on 2 of 3 following criteria: (1) abdominal pain, (2) amylase and lipase elevated over 3 times the upper limit of normal, and/or (3) abdominal imaging consistent with pancreatitis [1]. Although the direct causation is hard to prove, the temporal association does suggest the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pancreatitis in children. CASE 1 A previously healthy, obese, 15-year-old male presented to the emergency department with non-bloody, non-bilious vomiting, worsening epigastric abdominal pain, and fever that began on the day of presentation. He reported a week of nasal congestion, anosmia, and ageusia. On examination, he was hemodynamically stable with mild tenderness to palpation of the epigastric region and no signs of respiratory distress. Initial laboratory studies demonstrated a normal white blood cell count of 4.5 × 103/uL with 18.6% lymphocytes, c-reactive protein (CRP) of 1.47 mg/dL, and sedimentation rate (ESR) of 4 mm/h. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were slightly elevated to 53 and 86 U/L, respectively, and his lipase was elevated to 233 U/L. His glycated hemoglobin test (hemoglobin A1C) and triglycerides were within the normal range. An abdominal computed tomography (CT) demonstrated mild stranding around the head of the pancreas and proximal duodenum with scattered ground-glass opacities in bilateral lower lung fields (See Table 1). Based on the laboratory results and abdominal imaging, he was diagnosed with acute pancreatitis. Due to symptoms of anosmia and ageusia and lower lung field findings on imaging, a SARS-CoV-2 real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed, which was positive confirming the diagnosis of COVID-19. He was admitted and placed on intravenous fluids and a liquid diet and prescribed pain medications to ease his abdominal pain. He was discharged on day 3 of admission with resolution of abdominal pain, improving lipase level, and tolerating a normal diet. There were no signs of respiratory distress throughout his entire hospitalization. Table 1. Summary of the Clinical and Laboratory Findings for the 3 SARS-CoV-2-Infected Children Presenting With Pancreatitis Case 1 Case 2 Case 3 Race Caucasian Hispanic Asian BMI 34.4 29.5 18.7 Pulmonary symptoms Nasal congestion None reported Cough Extrapulmonary symptoms Anosmia, ageusia, vomiting, and abdominal pain Headache, chills, tactile fever, abdominal pain, hematochezia, and epistaxis Subjective fever, nausea, and abdominal pain Physical exam findings Epigastric tenderness Epigastric tenderness Epigastric tenderness WBC (4.19–9.43 × 103/uL)a 4.5 8.4 3.4 Percent lymphocytes(15.5%–56.6%)a 18.6 17.3 51.5 Absolute lymphocyte count (0.97–3.96 × 103/uL)a 0.85 1.46 1.74 CRP (0–0.5 mg/dL)a 1.47 24.11 Not performed ESR (0–15 mm/h)a 4 99 Not performed Serum Glucose (60–100 mg/dL)a 126 90 82 AST (14–35 U/L)a /ALT (9–24 U/L)a 53/86 47/54 15/9.6 Lipase (4–39 U/L)a 233 582 1909 Gastrointestinal findings on imaging Mild stranding around the head of the pancreas Fatty infiltration of the liver, enlarged appendix, and normal pancreas Hepatomegaly, single gallstone, and prominence of the pancreas Pulmonary findings on imaging Scattered ground-glass opacities in bilateral lung fields Interstitial opacities with peribronchial thickening Not evaluated SARS-CoV-2 RT-PCR Positive Positive Positive Abbreviations: BMI, body mass index; WBC, white blood cell; CRP, c-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase, ESR, sedimentation rate; RT-PCR, real-time reverse transcription-polymerase chain reaction. aNumerical values within parentheses indicate the normal range for each laboratory test. CASE 2 A previously healthy, overweight, 11-year-old male presented to the emergency department with periumbilical abdominal pain and poor oral intake for 2 days. He also reported headache, chills, tactile fever, and intermittent hematochezia and epistaxis of 8 days duration prior to presentation. He was tested for SARS-CoV-2 antibodies by his pediatrician 6 days into his illness (2 days prior to admission) and was found to be positive. On physical exam, he was noted to be hemodynamically stable with epigastric tenderness but no signs of respiratory distress. Initial laboratory studies demonstrated mild leukocytosis of 8.4 × 103/uL with 17.3% lymphocytes, mild thrombocytopenia to 140 × 103/uL, CRP of 24.11 mg/dL, and ESR of 99 mm/h. AST and ALT were slightly elevated (47 and 54 U/L, respectively), and amylase and lipase were elevated to 156 and 582 U/L, respectively. His triglycerides were elevated to 251 mg/dL, but his cholesterol was within a normal range. Abdominal CT demonstrated diffuse fatty infiltration of the liver, enlarged appendix suggestive of uncomplicated appendicitis, and a normal pancreas. Chest radiography noted central interstitial opacities with peribronchial thickening (See Table 1). He was diagnosed with appendicitis and pancreatitis and admitted to the hospital where he was made NPO (nothing by mouth) and started on intravenous fluids and piperacillin-tazobactam. Repeat laboratory studies demonstrated an increase of his amylase and lipase to 215 and 953 U/L, respectively. The diagnosis of COVID-19 was confirmed with a positive RT-PCR for SARS-CoV-2. With continued epigastric pain more concerning for pancreatitis rather than appendicitis, antibiotics were discontinued. His abdominal pain improved with the advancement of his diet, and he was discharged home on hospital day of 4 once tolerating a normal diet. CASE 3 A 16-year-old female with a history of pancreatitis over a year ago presented to the emergency department with nausea and epigastric abdominal pain radiating to her back for 3 days duration. She was unable to tolerate any food or liquids. She did report having subjective fever and a slight cough about a week prior to presentation and was found to be positive for SARS-CoV-2. On physical exam, she was hemodynamically stable with mild epigastric pain but without signs of respiratory distress. Pertinent laboratory findings include slight leukopenia to 3.4 × 103/uL with 51.5% lymphocytes, mild neutropenia to 1.3 × 103/uL, normal liver enzymes, an elevated lipase to 1909 U/L, and normal triglycerides and cholesterol. Repeat COVID testing was also positive. Her abdominal ultrasound demonstrated mild hepatomegaly, a single gallstone, and prominence of the pancreatic head, tail, and duct (See Table 1). She was admitted and started on intravenous fluids, pain medications, and a clear liquid diet. Because of her previous history of pancreatitis, an evaluation for a possible genetic etiology was performed and was negative. As her symptoms improved, her diet was slowly advanced, and she was discharged on day 3 of hospitalization. She did not develop any respiratory symptoms during her hospitalization. DISCUSSION The association of pancreatitis and COVID-19 infection has been suggested over the past several months with a few case reports, but there has only been 1 report of pancreatitis in a child to our knowledge. Unlike our patients, the 7-year old in the previous case report presented with necrotizing pancreatitis 2 weeks prior to her COVID-19 diagnosis [2]. Pancreatitis has been reported in several viral diseases, including mumps, measles, Epstein-Barr virus, hepatitis A and E, and Coxsackievirus [1, 3], thus making the association between SARS-CoV-2 and pancreatitis plausible. All 3 of our patients who were under the age of 16 developed symptoms about a week into their COVID-19 illness. Although the patient in case 1 did not have a SARS-CoV-2 test at the onset of his symptoms, the presence of anosmia and ageusia is highly suggestive of COVID-19. The proposed pathophysiology of the involvement of the pancreas by SARS-CoV-2 is because of the expression of angiotensin-converting enzyme 2 in both the islet cells and the exocrine portions of the pancreas [4]. Pancreatic injury during an acute SARS-CoV-2 infection could also be secondary to an immune-mediated injury [3, 5]. Although it is difficult to rule out other possible etiologies for pancreatitis in the 3 patients presented in this report, especially since a complete medication history was not obtained, the timeline of diagnosis with COVID-19 and pancreatitis appears to have a temporal association. Thus, providers should consider SARS-CoV-2 in their differential diagnoses when managing patients with extrapulmonary symptoms including gastrointestinal symptoms.
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                Journal
                Journal ID (nlm-ta): An Pediatr (Barc)
                Journal ID (iso-abbrev): An Pediatr (Barc)
                Title: Anales De Pediatria (Barcelona, Spain : 2003)
                Publisher: Published by Elsevier España, S.L.U. on behalf of Asociación Española de Pediatría.
                ISSN (Print): 1695-4033
                ISSN (Electronic): 1695-9531
                Publication date PMC-release: 27 February 2021
                Publication date (Electronic): 27 February 2021
                Affiliations
                [a ]Servicio de Pediatría. Hospital Universitario Donostia (San Sebastián), Gipuzkoa, España
                [b ]Servicio de Gastroenterología Pediátrica. Hospital Universitario Donostia (San Sebastián), Gipuzkoa, España
                Author notes
                [* ]Autor para correspondencia.
                Article
                Publisher Item ID: S1695-4033(21)00115-6
                DOI: 10.1016/j.anpedi.2021.01.013
                PMC ID: 7910146
                SO-VID: 1bdc395f-90a1-4c7f-8e71-352759aafb96
                Copyright © © 2021 Published by Elsevier España, S.L.U. on behalf of Asociación Española de Pediatría.
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                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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