Early Onset of Pediatric Autoimmune Pancreatitis at the US-Mexican Border

Introduction

Pancreatic disease in children is uncommon but comprises of diverse etiologies and carries significant morbidity and mortality [1]. Although it is rare, acute pancreatitis is the most common pediatric pancreatic disease and recent literatures have shown an increasing incidence in children [1, 2, 3, 4, 5]. Autoimmune pancreatitis (AIP) in the pediatric population is thought to be an uncommon cause of acute and chronic pancreatitis but the true epidemiology remains unclear and more cases have been recently recognized [6, 7, 8, 9]. AIP can be classified into 2 types: Type 1 or AIP without granulocyte epithelial lesions (GELs), and type 2 or AIP with GEL. Type 1 is more commonly seen in elderly males with clinical presentation of obstructive jaundice, extra pancreatic involvement, and elevated serum immunoglobulin (Ig)G4. Pancreatic histopathology typically shows periductal dense infiltration of plasma cells and lymphocytes; storiform fibrosis; venulitis with lymphocytes and plasma cells frequently causing destruction of the affected vein; and profound IgG4 positive plasma cells (> 10 cells per high- power field [HPF]) [10]. Type 2 is more common in younger patients with equal sex distribution [10, 11]. Unlike type 1, patients do not have elevated serum IgG4 or other organ involvement (OOI), and they are more prone to present with abdominal pain, and have lower tendency to present with obstructive jaundice [10, 12]. Type 1 and 2 can often be distinguished by serum IgG4 level, OOI, and histology. Both types have similar radiologic pancreatic imaging findings. Computed tomography (CT) or magnetic resonance imaging (MRI) is a commonly used method for pancreatic imaging. Diffusely enlarged pancreas (especially with a capsule- like rim) without pancreatic ductal dilatation or pancreatic low density mass is highly suggestive of AIP [10]. In comparison to adults, there have been no reported cases of AIP definitive type 1 in children and radiological findings seem to be less intense [6]. Early recognition of the disease is important since the few reports in the literature available for pediatric AIP shows a drastic response to steroid therapy, which leads to avoiding unnecessary invasive procedures in children [6, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25]. Although there is a favorable response to steroids, some reported cases describe other autoimmune diseases later in life, particularly inflammatory bowel disease in AIP type 2 [6, 17, 25]. Up to our best knowledge, there are no defined guidelines for diagnosis and treatment of AIP in children. We will describe a small case series of early onset pediatric AIP and its comparison to the other reported cases in the literature.

Case 1

A previously healthy 4 year-old Hispanic male, presented with a four-day history of worsening severe epigastric pain and persistent emesis after being hit in the stomach by his friend. Past medical history and family histories were insignificant. Blood tests showed amylase 102 IU/L (normal range 25 – 115 IU/L), lipase 1208 IU/L (normal range 36 – 285 IU/L), and total bilirubin 0.5 mg/dL. Abdominal ultrasound (US) revealed a normal gallbladder, biliary tree, and pancreas. Magnetic resonance cholangiopancreatography (MRCP) showed peripancreatic, perihepatic and pericolic fluid, normal bile duct, and partially visualized pancreatic duct; the pancreatic duct in the region of the head was not visualized. The patient was treated with conservative management and was started on a low-fat diet after resolution of the abdominal pain, which the patient tolerated well. Since the pancreatic duct was not fully visualized, a repeat MRCP was scheduled 1 month later but the patient was lost to follow up. Two years later, at the age of six, the patient re- presented with a four-day history of epigastric pain. He denied recent trauma and had been doing well during the interim. Blood tests showed amylase 88 IU/L, lipase 525 IU/L (normal range 36 – 285 IU/L), total bilirubin 0.4 mg/dL, HDL 37 mg/dL, triglyceride 89 mg/dL, cholesterol 148 mg/dL, normal liver function tests, ANA positive with titer of 1:160, and normal IgG4 level. Abdominal US revealed focal swelling of the head of the pancreas. MRCP showed mildly enlarged pancreas with mass-like effect at the pancreatic head causing partial obstruction of the distal common bile duct and pancreatic duct (Figure 1). An ultrasound guided percutaneous pancreatic core- biopsy showed benign inflammatory fibrosis with lymphoplasmacytic infiltration, frequent eosinophils, and parenchymal acinar destruction without any neoplastic process. Granulocytic epithelial lesions (GEL) causing duct disruption was not found and IgG4 stain was negative. The patient was started on daily oral Prednisone 20 mg. Resolution of the patient’s symptoms was noted in less than 48 hours and a diagnosis of AIP probable type 2 was confirmed. At 1 month follow up, the patient’s symptoms resolved and serum lipase normalized. A repeat abdominal ultrasound at that time showed resolution of the pancreatic inflammation and normalization of the pancreatic anatomy. Oral prednisone was continued for 6 months and then slowly tapered without reoccurrence of symptoms.

Click to enlarge

Figure 1: MRI results for case 1 and 2. 1-1 and 2-1 show a low T2 intensity mass-like effect at the pancreatic head (arrow). 1-2 shows partially obstructed pancreatic duct and distal common bile duct at the pancreatic head (arrows). 2-2 shows narrowing of the distal common bile duct at the level of the pancreatic head due to the mass- like effect (arrow).

Case 2

A previously healthy 3 year-old Hispanic female presented with a seven-day history of worsening epigastric pain, non-bloody non-bilious emesis, and mild scleralicterus. The family denied abdominal trauma, past medical history, and family history of gastrointestinal pathology. Blood tests showed lipase 30IU/L (normal range 36 – 285 IU/L), total bilirubin 7.0 mg/dL, direct bilirubin 4.9 mg/dL, AST 122IU/L, ALT 232IU/L, ALP 1118IU/L, GGT 978IU/L, ANA positive with a titer of 1:160, and IgG4 level was normal. Studies for CMV, EBV, and hepatitis A, B, and C were negative. Liver-kidney microsomal antibody and smooth muscle antibody were negative. Abdominal ultrasound showed diffuse swelling of the pancreas with markedly dilated common bile duct; mild central intrahepatic biliary ductal dilatation; no pancreatic ductal dilatation; and no evidence of stones and cholecystitis. MRCP showed enlarged pancreas with mass-like effect at the pancreatic head causing partial obstruction of the common bile duct and pancreatic duct (Figure 1). AIP type 2 was highly suspected but the family refused pancreatic biopsy. The patient was started on Methylprednisolone 20 mg IV, which was eventually changed to daily oral Prednisone 20 mg. After 48 hours of steroid therapy, there was remarkable improvement in the patient’s symptoms and laboratory markers and a diagnosis of AIP - not otherwise specified (NOS) was made. At 1 month follow up, the patient’s symptoms had completely resolved and laboratory markers normalized. Abdominal ultrasound repeated at that time showed normal pancreatic anatomy without inflammation. Prednisone was gradually tapered after 6 months of therapy without reoccurrence of abdominal pain or symptoms at 12 months follow up.

Discussion

Autoimmune pancreatitis (AIP) is a rare entity among children and there are no well-established guidelines for its diagnosis and length of therapy. There are two types of histological patterns to AIP defined by the International Consensus Diagnostic Criteria (ICDC): lymphoplasmacytic sclerosing pancreatitis (LPSP) or AIP without granulocyte epithelial lesions (GELs) and idiopathic duct-centric pancreatitis (IDCP) or AIP with GEL. The term AIP type 1 and type 2 are used for clinical profiles of LPSP and IDCP, respectively, because pancreatic histology often is not obtained. AIP type 1 is an IgG4-related disease characterized by elevated serum IgG4 levels, involves other organs with infiltration of IgG4-positive plasma cells, and is more common in elderly Asian males [10, 17, 19]. Type 2 is more common in the younger population with no gender preference, has a normal serum IgG4 level, and is commonly associated with inflammatory bowel disease, especially ulcerative colitis [10, 12, 15, 17, 19]. Because type 2 does not have serological markers, in order to make a definite diagnosis, histological confirmation of IDCP is necessary [10]. Clinically, patients with type 2 are more likely to present with abdominal pain and are less likely to present with obstructive jaundice [17]. Of all the cases that have been reported for children, none have had “AIP definitive type 1” (Table 1) [6]. The treatment for AIP is steroid administration and generally patients show good response to treatment.

presentation Serum Amylas

Symptoms at initial

Age (years

Serum

Patient numbe

Seru

m ANA

IgG4 (mg/dL)

Treatment

Patholog

y ICDC classificatio

Comorbid conditions Abdomin

CT/ERCP:

Diffusely

enlarged pancreas with

1 11 M ＋ ＋ ＋ WNL /

ND ー WNL

stricture of lower bile duct and pancreatic duct.

# 6 CT: Mass-like enlargement of the pancreatic head with lower

2 14 F ND ＋ ND WNL /

ND ー 190

bile duct stricture and caliber irregularity of the pancreatic duct.

CT: Pancreatic head mass and dilated common

3 10 M ＋ ＋ ＋ WNL /

WNL ー WNL

bile duct CT: Pancreatic head mass with dilated common bile # 7

4 15 M ND ＋ ＋ WNL /

WNL ー WNL

duct and pancreatic duct CT - guided / Lymphoplasmacytic

Scarce ＋ Definitive

AIP-2 Steroid therapy ＋ ー None

infiltration with neutrophils infiltrating the lining epithelium of pancreatic ducts Endoscopic papillotomy and CT - guided / Lymphoplasmacytic infiltration, periductal and lobular ー ＋ AIP therapy UC 1 year later No steroid neutrophilic infiltation biliary stent insertion.

PD / Ductocentriclymphoplasmacytic

31 cells/HP ＋ AIP PD No steroid therapy None

inflammation and fibrosis F

Transduodenal laparoscopic TCB /

10 cells/HP ND Probable

AIP-1 Steroid therapy ＋ ー Developed Celiac disease 1 year later Ductocentriclymphoplasmacytic inflammation and venulitis F

association with other autoimmune diseases (i.e. inflammatory bowel disease) to decrease the morbidity when followed as an outpatient. Also, approximately 70% of the cases reported could not be clearly classified as either type 1 or type 2, and treatment methods differed depending on the reported cases, raising the question that there may be a need to create a pediatric-specific diagnostic criteria and treatment guideline for AIP.

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