European Journal of Pediatrics

, Volume 165, Issue 8, pp 560–565

Successful conservative management of idiopathic fibrosing pancreatitis in children

Authors

  • Wael El-Matary
    • Royal Victoria Infirmary
    • Royal Liverpool Children’s NHS Trust
  • Stephen Hodges
    • Royal Victoria Infirmary
  • Suzanne Davison
    • Children’s Liver UnitSt James’s University Hospital
  • Patricia McClean
    • Children’s Liver UnitSt James’s University Hospital
  • Abubaker Elbadri
    • Whiston Hospital
  • Mark D. Stringer
    • Children’s Liver UnitSt James’s University Hospital
Original Paper

DOI: 10.1007/s00431-006-0115-2

Cite this article as:
El-Matary, W., Casson, D., Hodges, S. et al. Eur J Pediatr (2006) 165: 560. doi:10.1007/s00431-006-0115-2

Abstract

Idiopathic fibrosing pancreatitis, a rare cause of obstructive jaundice and abdominal pain in children, which has certain features in common with the emerging entity of autoimmune pancreatitis as described in adults, has frequently been managed surgically. We present our experience of successful conservative management of this condition in children. Three children (6–12 years; two girls, one boy) presented with a short history of abdominal pain followed by obstructive jaundice. Abdominal ultrasonographic examination in each case showed dilated intrahepatic and common bile ducts with a bulky pancreas, predominantly the head. These findings were confirmed by magnetic resonance imaging. In two cases, the diagnosis of fibrosing pancreatitis was made by exclusion after extensive investigation. The third case had a percutaneous ultrasound-guided pancreatic needle biopsy. Two patients were managed by supportive medical therapy alone, whilst the third, with symptomatic obstructive jaundice, underwent temporary endoscopic stenting of the common bile duct. Cases have been followed-up for 12–49 months. There was complete clinical and biochemical resolution of obstructive jaundice in all three cases. Plasma bilirubin concentrations decreased to normal within 3–8 weeks. Serial abdominal imaging showed a gradual resolution of biliary dilatation and abnormal pancreatic morphology with subsequent pancreatic atrophy. Two children developed steatorrhoea that responded to pancreatic enzyme supplements, and one patient developed diabetes mellitus. None of the cases needed invasive surgery for diagnosis or management. Conclusion: With careful radiological and biochemical assessment and monitoring, invasive surgery can be avoided in the management of fibrosing pancreatitis. The eventual outcome is no different from reported surgically treated cases.

Keywords

PancreatitisChildrenJaundice

Abbreviations

CBD

Common bile duct

MRCP

Magnetic resonance cholangiopancreatography

ERCP

Endoscopic retrograde cholangiopancreatography

Introduction

Fibrosing pancreatitis, a rare condition of unknown pathogenesis and natural history, has been described in children and young adults. It is often associated with obstructive jaundice due to compression of the common bile duct (CBD) as it passes through the swollen head of the pancreas [1]. This association of the common bile duct obstruction and fibrosing pancreatitis has been reported in fewer than 40 patients; a surgical approach to diagnosis and treatment has been advocated in most cases [4, 5]. We present three cases of chronic fibrosing pancreatitis; two of them were successfully managed without surgical intervention, whilst the third was treated by endoscopic therapy alone.

Case one

A 12-year-old boy presented with a 1-month history of mild right upper quadrant pain and intermittent fever, followed by jaundice with dark urine and pale stools. On examination, he had mild jaundice, scratch marks on his limbs, and a tender enlarged liver. Weight and height were just above the 75th percentile.

Laboratory investigations on admission are summarised in Table 1. Radiology work-up included an abdominal ultrasound examination, which showed a normal liver with dilated intrahepatic bile ducts, common bile ducts and pancreatic ducts. The gall bladder was distended with no calculi. Magnetic resonance cholangiopancreatography (MRCP) showed an enlarged pancreatic head with obstruction of the common bile and pancreatic ducts; there was no evidence of local metastasis or lymph-node enlargement (Fig. 1). The neck and body of the pancreas appeared atrophic. A percutaneous ultrasound-guided needle biopsy of the pancreatic head confirmed the diagnosis of fibrosing pancreatitis (Fig. 2a,b).
Table 1

Initial laboratory investigations and results of the three patients presented

Results at presentation (reference range)

Case 1

Case 2

Case 3

Plasma amylase (20–110 IU/l)

34

44

36

Serum albumin (32–56 g/l)

41

40

38

Clotting profile

N

N

N

Conjugated bilirubin (0–2 μmol/l)

84

93

106

C-reactive protein (<10 mg/l)

<10

3

77

ALT (0–40 IU/l)

63

40

220

Alk. phos (160–500 IU/l)

1000

405

N/A

GGT (0– 90 U/l)

60

69

421

Cholesterol (3.1–5.4 mmol/l)

N/A

N/A

14.2

Immunoglobulin profile

N

N

N

Autoantibody screena

N

N

N

Sweat test

N

N

N

CA 19-9 tumour marker (<33 kU/l)

N/A

266

239

CF gene testing

Neg

Neg

Neg

Viral hepatitis screen

Neg

Neg

Neg

Alpha-fetoprotein

Neg

Neg

Neg

Carcinoembryonic antigen

N

N

N

Fecal elastase (>200 μg/g stool)

<60

61

Undetectable

ALT Alanine aminotransferase, Alk phos. alkaline phosphatase, GGT gammaglutamyl transpeptidase, CF cystic fibrosis, N normal, N/A not available, Neg negative

aAutoantibody screen included antismooth muscle antibodies, anitinuclear antibodies, antiliver kidney microsomal antibodies, antisoluble liver antigen antibodies, antimitochondrial antibodies and perinuclear antineutrophil cytoplasmic antibodies

https://static-content.springer.com/image/art%3A10.1007%2Fs00431-006-0115-2/MediaObjects/431_2006_115_Fig1_HTML.gif
Fig. 1

A magnetic resonance cholangiopancreatography (MRCP) showing a diffuse enlargement of the pancreatic head with dilated common bile duct and gall bladder

https://static-content.springer.com/image/art%3A10.1007%2Fs00431-006-0115-2/MediaObjects/431_2006_115_Fig2_HTML.gif
Fig. 2a, b

Histopathology of the pancreatic needle biopsy from case 1. a Replacement of acini by fibroblasts/fibrous tissue and some destruction of islets resulting in cellular cords or ribbons. b Islet (arrow) disrupted into ribbons or cords of cells by fibrous tissue which completely replaces surrounding acini. Some lymphocytic and plasma cell infiltration

In order to relieve his symptomatic biliary obstruction the patient underwent endoscopic retrograde cholangiopancreatography (ERCP), which showed a normal gall bladder, a short smooth stricture in the lower third of the common bile duct and a slightly dilated pancreatic duct in the body of the pancreas. After insertion of a biliary stent, he made a good recovery with complete resolution of jaundice. However, a month later he developed steatorrhea. Stool chymotrypsin levels were consistently low, and fat globules were present in his stools. He was started on pancreatic enzyme supplements with good effect. Serum levels of fat-soluble vitamins were normal.

The biliary stent was electively removed by endoscopy 8 weeks later. He continued on pancreatic supplements and remained well with good weight gain >75th percentile. On a follow-up ultrasound abdominal examination 2 months after presentation, the abnormal hypoechoic area in the head of the pancreas was smaller, biliary duct dilatation had resolved and no other abnormalities were noted. Three years later, a follow-up MRCP scan showed complete atrophy of the body and tail of the pancreas but a pancreatic head of reasonably normal volume and signal characteristics. Liver function tests, fat-soluble vitamin levels, glycosylated haemoglobin (haemoglobin A1c), full blood count and clotting profile were all normal; and the patient remains well with good growth.

Case two

An 11-year-old girl developed jaundice following a 2–3 month period of tiredness, occasional headaches and back pains. There was no relevant past medical history. On examination, she appeared well, though jaundiced. Her weight was 55.8 Kg (98th percentile) and height 155.6 cms (91st–98th percentiles). She had no stigmata of chronic liver disease. Abdominal examination was unremarkable apart from mild epigastric fullness. There was no palpable lymphadenopathy.

Her investigations are summarised in Table 1. She had glycosuria with a fasting blood glucose level of 13 mmol/l and a 2-h post-prandial glucose of 14.4 mmol/l. Her haemoglobin A1c was slightly elevated at 6.7% (normal<6.1%). She also had a low serum level of vitamin D (9 μg/l). An abdominal ultrasound scan showed dilated intrahepatic bile ducts and common bile duct. The pancreas appeared generally hypoechoic, but no obvious masses were seen. MR imaging showed proximal bile duct dilatation with a stricture of the common bile duct within the pancreas. There was no pancreatic duct dilatation. The pancreas had an abnormal signal throughout the entire gland with reduced signal intensity on the T1-weighted sequences and reduced enhancement post-gadolinium; these appearances suggested a diffuse inflammatory process. There was no evidence of a focal abnormality, in particular, no evidence of a tumour in the head of the pancreas.

A conservative approach was adopted, particularly since the patient’s jaundice was improving. Her diabetes mellitus was managed by diet, and she was given pancreatic enzyme supplements and fat-soluble vitamins in view of her exocrine insufficiency. She made a good recovery with complete resolution of jaundice and pain. One year later, she was well. Her diabetes was well-controlled by diet alone, and her abdominal ultrasound scan showed no evidence of biliary duct dilatation or pancreatic head enlargement.

At the age of 14 years, she presented with a 2-month history of pallor, headache and easy fatigability followed by 2 weeks of bloody diarrhoea and abdominal pain. Her Hb was 7.4 g/dl with normal inflammatory markers. Apart from a low albumin of 28 g/l, her liver function tests and serum amylase were normal. Her autoantibody screen, including antineutrophil cytoplasmic antibodies, and immunoglobulin profile remained normal. Hb A1c was 3.4%.

She underwent upper and lower gastrointestinal endoscopies and biopsies, which showed a picture consistent with ulcerative colitis. She responded well to steroids.

Case three

A 6-year-old girl presented with an acute onset of jaundice preceded by a few weeks of progressive abdominal pain. Her stools were reported to be pale and difficult to flush. She had no relevant past medical history. On examination, she was jaundiced and had a tender right hypochondrium. Her investigations are summarised in Table 1. An ultrasound scan demonstrated a dilated biliary system and gall bladder with a bulky pancreas. She had a normal sweat test, random and fasting blood glucose levels, and fat-soluble vitamin levels. An MRCP showed a diffusely enlarged pancreas, particularly the head. The gall bladder was markedly distended. There was no lymphadenopathy or evidence of a malignancy.

A diagnosis of idiopathic fibrosing pancreatitis was made. She commenced on pancreatic enzyme supplements, and her stools became normal. During the next 2 weeks, her jaundice resolved, the bilirubin level fell to 39 μmol/l and ALT to 213 U/l. Serum cholesterol and CRP normalised. A follow-up ultrasound examination showed a less-dilated biliary system. The pancreatic head remained enlarged with a lobular outline but slightly smaller than previously. Five weeks after the diagnosis, there was no common bile duct dilatation and the pancreatic head, although still bulkier than normal, was notably smaller on ultrasound scan. Her jaundice resolved completely, and liver function tests returned to normal. The patient remains well but still requires pancreatic supplementation. Her HbA1c is normal.

Discussion

Idiopathic fibrosing pancreatitis in childhood is rare and typically presents with obstructive jaundice. Most case reports describe biliary diversion procedures in the management of this condition (Table 2) [1, 3, 4, 16, 17]. Sylvester et al. described the management of four cases: two were treated by temporary endoscopic stenting of CBD, one underwent cholecystostomy tube drainage and one child had a choledochojejunostomy [16]. Since the eventual outcome was not significantly different, they recommended that CBD stenting, as opposed to major surgical intervention, was sufficient to treat this condition. Another recent report reached a similar conclusion [7].
Table 2

Examples of reported cases of fibrosing pancreatitis in children

Authors

Number of cases

Age (years)

Sex

Symptoms

Pathology

Alvear and Petro [1]

1

11

F

Abdominal pain, weight loss, nausea and vomiting

Not reported

Amerson and Ricketts [2]

4

10–12

3M

Abdominal pain and jaundice in all of them

Chronic fibrosing pancreatitis

Buchta and Bell [3]

1

12

F

Abdominal pain, jaundice and vomiting

Severe fibrosis

Harb and Naon [4]

1

3

F

Abdominal pain and jaundice

Fibrosing pancreatitis

Lewin-Smith et al. [9]

1

13

M

Abdominal pain, jaundice, weight loss and vomiting

Chronic sclerosing pancreatitis with active destruction of glands

Sieno et al. [12]

1

13

M

Abdominal pain, vomiting and fever

Not reported

Sylvester et al. [16]

4

1.5–13

3F

3 abdominal pain and jaundice, 1 only jaundice

3 extensive fibrosis

M Male, F female

We report three children, two of whom were managed without any intervention and the third case underwent temporary endoscopic biliary stenting to relieve symptomatic jaundice. The outcome of these three cases was not different from those children reported in the literature treated surgically [1, 3, 9, 17].

It appears that the natural history of fibrosing pancreatitis is to progress from pancreatic enlargement (which may be more focal in the head of the gland) to atrophy. As this process occurs over several weeks, the common bile duct obstruction in the head of the pancreas gradually resolves spontaneously. There is no evidence that surgical biliary diversion influences the natural history of the pancreatic disease.

In two of our cases, it was considered that there was sufficient clinical, laboratory, and radiological evidence to diagnose fibrosing pancreatitis without the need for a confirmatory pancreatic biopsy. Idiopathic fibrosing pancreatitis is typically a diffuse inflammatory condition of the pancreas associated with a smooth benign-looking stricture in the distal common bile duct and evidence of exocrine, or less commonly endocrine, pancreatic insufficiency [9, 17]. Occasionally, the radiological appearances are more focal in the head of the pancreas, and if a pancreatic tumour cannot be excluded, a percutaneous ultrasound-guided needle biopsy of the pancreas should be performed. Fibrosing pancreatitis runs a variable course but typically progresses toward pancreatic atrophy with exocrine insufficiency. Diabetes mellitus is unusual, and any impairment of glycemic control tends to be mild. There are no reports of long-term follow up in this condition [9, 16], but one of our patients (case 1) has now been under review for 3 years and remains well despite the continued need for pancreatic enzyme supplements. We are also aware (authors’ experience) of a case that presented 14 years ago at the age of 6 years with a similar picture and was managed with a surgical drainage procedure (cholecystostomy). The diagnosis of fibrosing pancreatitis was confirmed by pancreatic biopsy taken at laparotomy. Interestingly this patient has no long-term pancreatic insufficiency. Therefore in view of the apparently benign outcome it would seem even more prudent to advocate a minimally invasive management plan for this condition.

There is a broad differential diagnosis for a common bile duct stricture in a child, which may be congenital or acquired. The former includes choledochal cyst pathology, which may also be associated with pancreatitis [5, 18]. Acquired causes include inflammatory, immunologic, traumatic and neoplastic disorders [5]. Pancreatic tumours may occur but are relatively rare in children [14]. Nevertheless, in patients with suspected fibrosing pancreatitis, a pancreatic tumour should be excluded by detailed imaging with or without biopsy. Cystic fibrosis can also lead to a similar picture of a common bile duct stricture [8]. There was no evidence of any of these conditions in our patients. Patients with hereditary pancreatitis usually experience recurrent attacks of severe epigastric pain associated with destruction of pancreatic parenchyma and distortion of pancreatic ducts. By definition, the diagnosis is confirmed by a family history of recurrent pancreatitis and/or genetic studies [10]. None of our patients had a family history of pancreatic disease. The radiological findings, outcome and progress of the patients are against PSC. The clinical and radiological features were entirely in keeping with fibrosing pancreatitis.

Many pancreatic disorders have a poorly defined pathogenesis. However, progress is being made such that genetic causes of hereditary pancreatitis have been identified, and clinical and diagnostic criteria for autoimmune pancreatitis are evolving [11, 15]. Several descriptive terms, such as sclerosing pancreatitis, primary inflammatory pancreatitis and lymphoplasmacytic pancreatitis have been used to describe pancreatic disorders similar to fibrosing pancreatitis and may all be part of the spectrum of autoimmune pancreatitis. It is interesting to note that our second patient presented with ulcerative colitis 3 years after her initial presentation, but the other two patients have not suffered any autoimmune problem. An association between fibrosing pancreatitis and inflammatory bowel diseases has been previously described [12]. Long-term follow-up of children with fibrosing pancreatitis may reveal the subsequent development of autoimmune pathology.

Despite the uncertainty about the aetiopathogenesis of fibrosing pancreatitis, we have demonstrated that biliary diversion procedures are unnecessary in these children. With careful monitoring, spontaneous resolution of obstructive jaundice may be observed.

Plasma amylase measurements were consistently normal in all three of our cases. This has also been the case in other examples of fibrosing pancreatitis [3, 4, 16]. Interestingly, plasma CA 19-9 was elevated significantly in both patients in whom this marker was measured, but this may simply be a non-specific marker of biliary obstruction in these patients. A follow-up CA 19-9 level in two cases was normal. CA 19-9 is a useful tumour marker in adults with pancreatic cancer, but it can also be elevated in patients with pancreatitis, chronic liver disease, and chronic biliary obstruction [6].

In summary, three previously healthy children with no relevant family history of pancreatic disease presented with symptoms of biliary obstruction secondary to idiopathic fibrosing pancreatitis. Obstructive jaundice resolved spontaneously in two, whilst the third child was successfully treated by temporary endoscopic biliary stenting. All three developed pancreatic exocrine insufficiency, and one developed mild diabetes mellitus. The natural history and long-term follow-up of this rare condition requires further study. We have demonstrated that these children can be successfully managed without surgical biliary diversion and invasive procedures provided they are not markedly symptomatic (e.g., severe itching) and that they are carefully assessed and monitored clinically, biochemically and sonographically, especially in the first month or two after presentation. Worsening of clinical symptoms, absence of biochemical improvement and/or diagnostic doubt are indications for more invasive diagnostic and therapeutic procedures.

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© Springer-Verlag 2006