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An unremitting, deranged inflammatory response characterizes chronic pancreatitis (CP) in children and is modulated by environmental and genetic factors.
Unlike adults, the etiology of pediatric CP involves congenital or anatomic variants, genetic mutations, or autoimmune disease.
The diagnostic work-up of children suspected to have CP should include sweat chloride assessment, genetic assay for CFTR, SPINK1, and PRSS mutations, endoscopic and/or radiographic imaging, and autoimmune testing.
Initial therapy for CP includes treatment for symptoms including pain and endocrine and/or exocrine insufficiency. However, more invasive endoscopic or surgical therapy may be necessary and is often predicated on degrees of ductal obstruction and parenchymal disease.
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Chronic pancreatitis (CP) in the pediatric population is uncommon; as a result, its incidence and prevalence are not well established. Studies estimate the disease's prevalence as 3 to 10 cases per 100,000 inhabitants per year. While 70% of adults with CP report a history of alcohol abuse, the etiology in children varies significantly, and the time between onset of symptoms and diagnosis can be months if not years. The clinical consequences include an abdominal pain syndrome, diet intolerance, and the need for repeated hospitalization.
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Pancreatitis results from significant parenchymal and acinar destruction due to inappropriate activation of digestive enzymes accompanied by varying degrees of inflammation, fibrosis, and loss of function. Duration of symptoms and detectable pathologic gland change determine whether the disease is acute, recurrent, or chronic. In acute pancreatitis (AP), severe, systemic inflammation leads to microvascular ischemia and obstruction of the pancreatic acini, but the process is self-limited. Recurrent pancreatitis is an episode after a period of remission and may represent an inherent problem or susceptibility. In contrast, ongoing pancreatic inflammation and destruction that never fully abates as demonstrated by specific clinical, biochemical, or radiographic abnormalities indicates CP.
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The pathogenesis of CP is unknown; however, it has been postulated that repeat episodes of acute pancreatitis led to chronic disease. Recently, Whitcomb and colleagues have proposed that CP arises from an interplay of environmental triggers of pancreatic injury, genetic susceptibilities, and factors leading to a deranged inflammatory response. This process is initiated by a sentinel acute pancreatic event (SAPE). The SAPE activates normally quiescent pancreatic stellate cells into myofibroblast-like cells that express the cytoskeletal protein α-smooth muscle actin and produce extracellular matrix. This activation is further potentiated by platelets recruited to the pancreas that release platelet-derived growth factor (PDGF) and transforming growth factor (TGF) β as well as damaged ductal and acinar cells release of basic fibroblast growth factor (bFGF). Recent research has demonstrated the increased expression of certain cytokines and activation of the mitogen-activated pathway (MAP) kinase system, both of which are pro-inflammatory, with subsequent down regulation of the anti-inflammatory proliferator-activated receptor pathway (PPAR) γ system. Abnormal host genotypes regulating these systems may increase susceptibility to chronic inflammation.
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