|Year : 2023 | Volume
| Issue : 1 | Page : 35-40
Clinical profile of acute pancreatitis in children and adolescents from a single center in Northern India
Nida Mirza1, Sagar Mehta2, Karunesh Kumar2, Smita Malhotra2, Anupam Sibal2
1 Department of Pediatrics, SAIMS, Indore, Madhya Pradesh, India
2 Department of Pediatric Gastroenterology, Indraprastha Apollo Hospital, New Delhi, India
|Date of Submission||25-Feb-2022|
|Date of Decision||01-Sep-2022|
|Date of Acceptance||30-Sep-2022|
|Date of Web Publication||12-Dec-2022|
504, Pearl Palms, Indore, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: There has been an increase in incidence of pancreatitis in children all over the world; studies in developed countries shown multiple etiological factors such as drugs, infections, trauma, anatomic abnormalities, and/or genetic pancreatitis in children; however, there are sparse data from the developing countries. This study was undertaken to determine the characteristics of Indian children with acute pancreatitis (AP), mainly the clinical features, etiology, complication, association, genetic factors, and outcome and recurrence.
Methods: We performed a retrospective study of all patients under the age of 18 years, who had a final diagnosis of pancreatitis admitted at our center between 2017 and 2019.
Results: During the 3-year period from 2017 to 2019, 40 patients were admitted at our center with AP. We found a definite etiology in 62.5% cases of patients, which were broadly grouped into seven etiologies: structural, genetic, drug induced, concurrent illness, cholelithiasis related, metabolic, and autoimmune. Recurrence of acute episodes was noted in 13 patients (32.5%). Of these, 11 were found to have a genetic mutation, underlying structural abnormality, or concurrent illness. In our study, we found that 23 patients (57.5%) had mild AP, while 14 patients (35%) had moderately severe pancreatitis; however, 3 patients (7.5%) had severe AP.
Discussion: We found that most cases of pancreatitis in children were of mild severity, and the etiology was quite different than adults, and most cases of acute recurrent pancreatitis have a definite etiology of either genetic mutation or structural anomaly.
Keywords: Acute pancreatitis, pancreatitis, recurrent pancreatitis
|How to cite this article:|
Mirza N, Mehta S, Kumar K, Malhotra S, Sibal A. Clinical profile of acute pancreatitis in children and adolescents from a single center in Northern India. J Indian Assoc Pediatr Surg 2023;28:35-40
|How to cite this URL:|
Mirza N, Mehta S, Kumar K, Malhotra S, Sibal A. Clinical profile of acute pancreatitis in children and adolescents from a single center in Northern India. J Indian Assoc Pediatr Surg [serial online] 2023 [cited 2023 Feb 8];28:35-40. Available from: https://www.jiaps.com/text.asp?2023/28/1/35/363423
| Introduction|| |
Acute pancreatitis (AP) is an acute inflammatory process of the pancreas, diagnosed by abdominal pain, elevations of serum pancreatic enzymes, and radiological changes in pancreas. Pancreatitis may cause mild-to-severe degrees of injury to the pancreas, peripancreatic area, and other organs of human body. AP, which is reversible, is characterized by edema of the interstitium, inflammatory cell infiltration with varying degrees of necrosis, apoptosis, and hemorrhage; previously, pancreatitis was considered rare among children; however, over the past two decades, there has been an increased incidence of pancreatitis in children over the world., The cause of increased incidence is considered more awareness of pancreatitis among pediatricians and easy access of lipase testing in developed countries;,,,,,, however, there are sparse data regarding the etiology, natural history, and complication of pancreatitis in children, especially from the developing countries. In India, only few studies on childhood AP were done., This study was undertaken to determine the characteristics of Indian children with AP, mainly the clinical features, etiology, complication, association, genetic factors, and outcome
| Methods|| |
We performed a retrospective study of all patients under the age of 18 years, who had a final diagnosis of pancreatitis (first episode) admitted at our center between 2017 and 2019. Ethical clearance to conduct the study was obtained from the Institutional Ethics Committee. Inclusion criteria included the patients below 18 years of age and with a diagnosis of AP according to the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure), that is least 2 of the following: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase ≥3 times upper limits of normal (reference ranges: amylase 20-90 U/L, lipase 10-45 U/L), and (3) imaging findings consistent with AP. ARP was considered two or more episodes of AP with intervening return to baseline: complete resolution of pain (=1 month pain-free interval) or complete normalization of pancreatic enzymes levels with resolution of pain (can be shorter interval than 1 month). Using a standardized data collection form history, points were collected, which include gender, height, weight, body mass index (BMI), medical history, medications, and family history, and clinical examination findings, biochemical laboratory, exome sequencing (for genetic causes), and radiological investigations were collected, which include serum transaminase, lipase level, amylase level, total bilirubin level, triglyceride level, serum cholesterol, ultrasound results, computed tomography (CT) results, and magnetic resonance cholangiopancreatography results. Severity, etiology, and complication of pancreatitis were stated based on clinical and investigation findings; recurrent episodes were noted, and patients were characterized as acute and acute recurrent pancreatitis. Severity of pancreatitis is defined by revised Atlanta classification as mild, moderately severe, and severely acute. Mild AP is defined by no organ failure, no local or systemic complications, and usually resolves in the 1st week. Moderately severe AP is defined by the presence of transient organ failure (<48 h), local complications, or exacerbation of comorbid disease. Severe AP is defined by persistent organ failure (>48 h). Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst, and walled-off necrosis (sterile or infected). We did genetic sequencing (next generation sequencing) in all cases of ARP, except in those who had pancreaticobiliary structural anomaly leading to recurrent pancreatitis. Statistics were calculated using SPSS 25 IBM SPSS 25 Software, Chicago, U.S.A.
| Results|| |
During the 3-year period, 40 patients (males – 62.5%) were admitted at our center with AP. The mean age of patients was 9.3 years (range: 1–17 years). The median number of patients diagnosed in this study was 13/year. The association between gender and severity of AP was not significant (P = 0.116). Positive family history of pancreatitis was found in only one child out of 40 patients. The most common presenting symptom was abdominal pain (90%), followed by vomiting and fever. Jaundice was present in three children (7.5%), and all of these were diagnosed with choledochal cyst (CDC). The mean duration of symptoms before admission to hospital was 3.23 days. On abdominal examination, epigastric tenderness was present in 55% of patients, while others had diffuse tenderness. Twenty percent of patients had mild abdominal distension on clinical examination. The radiological features of pancreatitis were detected in 28 patients (70%) by transabdominal ultrasonography. The most common finding was bulky and edematous pancreas. The mean duration of hospital stay was 8.3 days. The mean duration of stay in hospital was higher in moderately severe and severe group compared to those with mild AP, but it was not statistically significant (P = 0.08). In our study, we found that 23 patients (57.5%) had mild AP, while 14 (35%) had moderately severe pancreatitis; however, 3 (7.5%) had severe AP. We found a definite etiology in 25 patients (62.5%), which were broadly grouped into seven etiologies: structural, genetic, drug induced, concurrent illness, cholelithiasis related, metabolic, and autoimmune. However, in 15 patients (37.5%), we did not find any cause and labeled them as idiopathic [Table 1].
There were six patients with a structural abnormality, which included five with CDC and a child with pancreatic duct anomaly. All the cases were mild in severity. All the patients of CDC underwent surgical correction. Two children from this group had recurrence; one child with corrected CDC had abnormal pancreaticobiliary union (APBU), while the other child with pancreatic duct anomaly was found to have PRSS1 mutation on genetic testing. Four patients (10%) of AP were drug induced in our study. We found chemotherapy agent L-asparaginase in three and valproate in one as causative agents.
Seven children (17.5%) had concurrent illness [Table 2] that included hematological malignancy (lymphoma and leukemia) (n = 3), steroid-dependent nephrotic syndrome (nephrotic syndrome) (n = 3), and one patient with Laurence-Moon-Biedl (LMB) syndrome. Most patients had mild AP (n = 5) in this group, while a child with SDNS had severe AP and later succumbed during the hospital stay of 5 days. On the other hand, the mean duration of stay in children who survived was 7.8 days. Multiple recurrences were observed in two children with SDNS and also in a case of LMB syndrome during the study. Interestingly, on evaluation of recurrent AP, we found PRSS1 mutation in one child with SDNS. With respect to three children with nephrotic syndrome, the median age was 15 years, and all of them were obese (BMI >2 z-score).
Cholelithiasis was a causative factor of AP in one patient, who presented with mild AP. This child was obese (BMI >2 z-score) without any history of gall stones. We found metabolic cause in a young girl child having recurrent pancreatitis. On NGS, a heterozygous mutation in MUT gene (methylmalonic acidemia) was detected.
One girl was diagnosed with IgG4-related autoimmune pancreatitis. She presented with mild abdominal pain and jaundice; on investigation, she was found to have elevated serum IgG4 and responded very well to corticosteroid treatment, thus confirmed the diagnosis of autoimmune pancreatitis type 1.
Fifteen children with AP were classified in idiopathic group. The median lipase level was 2470, and the median age was 14 years. Severity of AP was mild in six, moderately severe in seven, and severe AP in two patients. Identifiable recurrence of AP was documented in two patients. We did not find any genetic etiology on NGS in these patients. Hypertriglyceridemia, hypercalcemia, and hyperparathyroidism were not found associated with AP in our study.
Recurrence of acute episodes was noted in 13 patients (32.5%). Of these, 11 were found to have a genetic mutation, underlying structural abnormality, or concurrent illness. In this group, definite genetic mutation was found in six (46.2%) patients, while two had nephrotic syndrome, one had LMB syndrome, one had choledochal cyst with pancreaticobiliary junction anomaly, one had suspected methylmalonic acidemia (heterozygous mutation in MUT gene), and two were idiopathic.
On CT scan examination, necrotizing pancreatitis was seen in nine patients (22.5%), and vessel thrombosis (in splenic and/or portal vein) was noted in five (12.5%) patients. Local complications were acute pancreatic fluid collection in eight (20%) and acute necrotic collection in three (7.5%) patients initially, and later, pseudocyst developed in two patients (5%) and walled-off pancreatic necrosis in three patients (7.5%) on follow-up. The complications were self-limiting in most of the patients. A 12-year girl with idiopathic AP developed a large walled-off necrosis (WON) that formed pseudoaneurysm of a pancreaticoduodenal artery. She needed angiographic embolization which was uneventful. Mortality was observed in one patient (2.5%) of acute case with concurrent SDNS, who presented with SAP and multiple organ dysfunctions.
We found genetic mutations in six patients with ARP-PRSS1 (n = 2), SPINK1 (n = 2), CFTR (n = 1), and SPINK with PRSS1 (n = 1) mutation. Among the identifiable mutations in our study, PRSS1 and SPINK1 mutations were already reported, while CFTR was the novel variant mutations [Table 3]. Interestingly, PRSS1 mutation was detected in two patients with other suspected etiological factors (n = 2); of these, one had pancreatic duct anomaly and another had steroid-dependent nephrotic syndrome.
|Table 3: Mild acute pancreatitis versus moderately severe and severely acute pancreatitis: First acute pancreatitis episode characteristics (data presented as mean values)|
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| Discussion|| |
In this study, we have described etiology, clinical feature, and recurrence in children diagnosed as AP at our center. Various studies from all over the world have identified increasing incidence of AP in children. An Indian study has shown an increasing trend in number of AP cases in children in India. We diagnosed 13 patients of AP per year (median), which is comparable to a recent retrospective study. Increasing awareness among pediatrician and improved diagnostic availability may be the reason for this. AP is seen across all age groups. The mean age of patients in our study was comparable to a recent Turkish study. We had most cases presenting in the older age group (>11 years) that also saw higher number of SAP and idiopathic cases, which is similar to other studies [Table 4].
According to the INSPPIRE criteria, pediatric AP is diagnosed on the basis of abdominal pain, elevated serum pancreatic enzymes (>3 × ULN), and radiological evidence. As expected, acute abdominal pain was the most common presenting symptom in our series. Other reported symptoms include nausea and vomiting (40%–80%), abdominal distension, and fever (20%–30%), while jaundice, ascites, abdominal mass, and pleural effusion are infrequent, which is comparable to other studies done in children and adolescents. In our study, jaundice was seen as presenting feature in three children with AP who had underlying CDC. The most common examination finding was epigastric tenderness (55%).
The length of stay, when compared to mild cases, was higher in children with moderate and severe AP, which is similar to a study conducted in Bangladesh. However, unlike this study, we did not find any statistical significance between severities of AP with LOS.
The utility of ultrasonography in detecting AP is well documented in the literature. Antunes et al. reported nearly 80% sensitivity of USG; in our series, we found features indicating AP in 70% of patients.
The etiologies of childhood AP are diverse in nature.,, Idiopathic or undiagnosed patients constitute a major burden in the management of childhood AP. The list of genetic causes AP is ever growing; there still remains a larger section of idiopathic cases. In our series, we found a cause of AP in 65% of patients. The proportion of undiagnosed cases in this series (35%) is comparable to recent studies,, but lower than other Indian studies., This proportion was higher in children >11 years of age. We found structural anomalies (CDC and PD anomaly) in 17.5% of our patients; and most of these presented in early childhood. This number is significantly higher than previous studies.,, Chemotherapeutic agent PEG-asparaginase and valproic acid were identifiable causative agents as reported in the literature., Cholelithiasis-related AP was not a frequent finding in this study that is in contrast to previous reports.,, Certain known etiologies such as infections, trauma, and hypertriglyceridemia were not found in our series. Trauma is a common cause of pediatric AP; however, there was no history of trauma and suggestive clinical signs in our patients, may be due to as our hospital is not having a trauma center. Infective causes of AP in children are many; the presentation includes fever, rash, and lymphadenopathy in addition to other clinical features of AP. Since these were not present, we did not investigate for additional infectious agent. A recent study highlighted hypertriglyceridemia as infrequent cause of childhood AP. The mortality of our study (2.5%) was comparable to previous reports in children. There is a scarcity of Indian data on recurrence after initial episode of AP in children. In a previous Indian study, it stressed on the importance of follow-up of AP and ARP cases to look for progression to chronic pancreatitis (CP). Various studies have documented varying proportion of ARP cases. An Indian study reported 44% recurrence of AP, but most cases remained undiagnosed. Similarly, underlying genetic predisposition was identified in about 1/3rd of cases in an Italian study. In our study, 32.5% (13 cases) had a recurrence after an acute episode, of which 46.2% had genetic predisposition, one had metabolic disease (suspected methylmalonic acidemia), one had LMB syndrome, one had structural abnormality (CDC with APBU), two had SDNS, and two were undiagnosed. A case was previously reported described a case of MMA with recurrent episodes of AP which transitioned into CP. Interestingly, one undiagnosed case had positive family history of pancreatitis in father. Two cases had co-existing genetic predisposition in addition to earlier mentioned etiologies; one child had SDNS with PRSS1 mutation, while another case had pancreatic duct anomaly with PRSS1 mutation. Our study describes that the most children with recurrences of AP have an identifiable underlying predisposition, which is in contrast to a recent Indian study.
We tried to determine the underlying predisposing factors of AP and ARP in our cases. In the present study, structural, drug induced, hematological malignancies, and concurrent illness were the causative factors of AP, while known genetic mutation was a predisposing factor for ARP.
Unlike adults, pediatric AP is a complex disorder with multiple etiologies. Genetic predisposition and structural anomalies should be actively sought after in cases with positive family history, recurrences, and idiopathic cases.
The limitation of this study is its retrospective nature and small number of patients. Follow-up of many patients was incomplete to document episodes of recurrences and future course.
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Conflicts of interest
There are no conflicts of interest.
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