Study Reveals Research Gaps on Acute Pancreatitis in Sickle Cell Disease

A systematic review evaluating the presence of acute pancreatitis in children and adults with sickle cell disease (SCD) revealed the available literature on its prevalence and severity is limited to case reports and few observational studies.¹

Although the investigative team from the University of Alabama at Birmingham had planned an additional meta-analysis, it could not be performed due to a shortage of studies with similar populations, exposures, and comparison groups.

“Prospectively designed studies aiming to proactively evaluate acute pancreatitis in individuals with SCD who present with abdominal pain are needed to improve timely diagnosis of acute pancreatitis in SCD and outcomes,” wrote the investigative team, led by Chinenye R. Dike, MD, department of pediatrics, division of gastroenterology, hepatology, and nutrition, University of Alabama at Birmingham.

Approximately 100,00 people in the US are affected by SCD, an inherited blood disorder linked to reduced life expectancy and pain in the form of vaso-occlusive crises (VOCs).² Pain location is often varied in individuals experiencing a VOC, including abdominal pain, a presenting symptom for disorders, including acute pancreatitis.³

Those with SCD are potentially at an increased risk of acute pancreatitis due to microvascular ischemic and an increased incidence of gallstone disease.⁴ Dike and colleagues noted that, despite this increased risk, children with SCD who presented to their institution’s emergency department (ED) over 2 years were rarely investigated for gastrointestinal disorders.¹

Citing the plausibility of an elevated risk of acute pancreatitis in SCD, the team conducted a systematic review to assess its presence among a population with SCD, compared with the general population. A systematic search was performed in PubMed, EMBASE, CINAHL, Scopus, Web of Science Core Collection, and WHO Global Index Medicus from inception to May 2023.

Studies matching inclusion criteria examined the prevalence of acute pancreatitis, defined using adult and pediatric guidelines, in both children and adults with SCD, compared with the general population. Two authors screened 280 titles and abstracts independently, of which 56 were screened for full-text review and 33 studies met inclusion criteria.

Of these studies, 17 were case reports, 1 was a case series of 4 studies, and 15 were retrospective cohort studies – 18 of the 33 studies in the review included children. A total of 8 of the 17 acute pancreatitis case reports were in patients with the HbSS genotype, while two were in individuals with sickle beta thalassemia and one with the HbSoArab genotype.

Notably, 3 of the 4 acute pancreatitis cases reported in the case series were identified in individuals with the HbSS genotype.

Upon further analysis, Dike and colleagues found only two retrospective cohort studies estimating the prevalence of AP in SCD, at 2% and 7%, respectively. These estimates were based on a diagnosis of acute pancreatitis in those who presented with abdominal pain and were tested, as no natural history studies were identified that systematically evaluated for acute pancreatitis.

The search identified 14 patients who experienced complications among the 21 cases of acute pancreatitis. Of the 17 patients from the case reports, 12 experienced an acute complication, including respiratory complications (n = ≥4), splenic complications (n = 3), and pancreatic pseudocyst (n = 2). One patient died due to acute pancreatitis complications.

Each case of acute pancreatitis was associated with two identified etiologies – 8 patients had acute pancreatitis caused by cholelithiasis or choledocholithiasis, including 7 (41%) from the case reports. Among the two retrospective studies assessing the etiology of acute pancreatitis in children, biliary disease caused by SCD was present in 12% and 34% of the cohorts, respectively.

Dike and colleagues noted the importance of establishing the etiology of pancreatitis in patients with SCD, to determine the risk of gallstone-related acute pancreatitis, compared with a general population.

“Future studies should also determine the risk factors for AP in patients with SCD because there might be unique risk factors such as increased incidence of gallstone disease and ischemic injury due to repeated sickle cell crises,” they wrote.

References

1. _{Dike CR, DadeMatthews A, DadeMatthews O, et al. Acute Pancreatitis in Individuals with Sickle Cell Disease: A Systematic Review. J Clin Med. 2024;13(16):4712. Published 2024 Aug 11. doi:10.3390/jcm13164712}
2. _{Mangla A, Ehsan M, Agarwal N, et al. Sickle Cell Anemia. [Updated 2023 Sep 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482164/}
3. _{McClish DK, Smith WR, Dahman BA, et al. Pain site frequency and location in sickle cell disease: the PiSCES project. Pain. 2009;145(1-2):246-251. doi:10.1016/j.pain.2009.06.029}
4. _{Roberts SE, Morrison-Rees S, John A, Williams JG, Brown TH, Samuel DG. The incidence and aetiology of acute pancreatitis across Europe. Pancreatology. 2017;17(2):155-165. doi:10.1016/j.pan.2017.01.005}