Type one autoimmune pancreatitis based on clinical diagnosis: A case report

Abstract

BACKGROUND

Autoimmune pancreatitis (AIP) is a rare form of autoimmune-mediated pancreatitis, which is easily misdiagnosed as pancreatic cancer and thus treated surgically. We studied the diagnosis and treatment of a patient with type 1 AIP recently admitted to our hospital, and reviewed the literature to provide a reference for clinical diagnosis of AIP.

CASE SUMMARY

The chief complaint was yellowing of the body, eyes and urine for 21 d. The patient's clinical presentation was obstructive jaundice and imaging suggested pancreatic swelling. It was difficult to distinguish between inflammation and tumor. Serum immunoglobulin G4 (IgG4) was markedly elevated. IgG4 is an important serological marker for type 1 AIP. The patient was diagnosed with AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment. After applying hormonal therapy, the patient's symptoms improved significantly. At the same time, imaging suggested that pancreatic swelling subsided, and liver function and other biochemical indicators decreased. The treatment was effective.

CONCLUSION

In patients with pancreatic swelling, the possibility of AIP should be considered.

Key Words: Autoimmune pancreatitis; Characteristics; Diagnosis; Immunoglobulin G4; Case report

Core Tip: Autoimmune pancreatitis (AIP) has a low global incidence. Patients with pancreatic swelling need to differentiate between general pancreatitis and AIP. We report a clinical case and review the diagnosis of AIP in terms of clinical symptoms, physical examinations, laboratory examinations, and imaging examinations. To improve clinicians' ability to diagnose AIP will reduce misdiagnosis and increase the effectiveness of treatment.

INTRODUCTION

Autoimmune pancreatitis (AIP) is a rare autoimmune-mediated pancreatitis with an incidence of about 10.1/100000[1], whose pathogenesis is still unclear and is effectively treated with corticosteroids. However, AIP is difficult to differentiate from general pancreatitis or pancreatic cancer. It is important to improve the diagnosis and differentiation ability of clinicians. In this article, we report the medical record data of a representative patient with type 1 AIP recently admitted, to provide a reference for clinicians to diagnose the disease and improve understanding and diagnosis of AIP.

CASE PRESENTATION

Chief complaints

A 43-year-old Chinese man suffered from yellowing of the skin and mucous membranes of the eyes for 21 d.

History of present illness

A 43-year-old male patient was admitted on July 3, 2023, without any obvious cause. He had yellow coloring of the body and eyes, yellow urine, yellow stool, no itching of the skin, no anorexia, no nausea and vomiting, no chills, no fever, and no abdominal pain. On July 22, 2023, the patient went to the outpatient clinic of the Shunde Hospital of the Guangzhou University of Traditional Chinese Medicine in Guangzhou for diagnosis and treatment. His liver function was checked at the emergency clinic: Alanine aminotransferase 324.0 U/L, alkaline phosphatase 660.39 U/L, γ-glutamyl transferase 1173.96 U/L, total bilirubin 129.60 μmol/L, conjugated bilirubin 50.0 μmol/L, unconjugated bilirubin 27.10 μmol/L, and δ-bilirubin 52.50 μmol/L. White blood cell count was 13.61 × 10⁹/L, absolute neutrophil count was 8.14 × 10⁹/L. Hepatitis A antibody IgM, and five hepatitis B indicators were normal. Ultrasound showed a suspected solid focal lesion in the head of the pancreas (the nature of which was to be determined), dilatation of the upper portion of the common bile duct and intraductal bile ducts, and enlargement of the pancreas. Polyene phosphatidylcholine was given to protect the liver after symptomatic treatment, but without symptom relief. On July 24, 2023, the patient was hospitalized for further diagnosis and treatment.

History of past illness

The patient denied past medical history.

Personal and family history

The patient reported no significant abnormalities in his personal or family history.

Physical examination

Vital signs were stable, the whole body of the skin and mucous membranes showed moderate yellow stain, and the sclera showed mild yellow stain. The whole abdomen was flat, no gastrointestinal type and peristaltic wave, no epigastric pulsation, no varicose veins in the abdominal wall, soft abdomen, no abdominal pressure, no rebound pain, and no palpable mass.

Laboratory examinations

There were no significant abnormalities in carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9), α-fetoprotein, hepatitis C immunoglobulin G (IgG) antibody, autoimmune liver disease quantitative test, autoimmune liver disease antibody spectrum, and hepatitis E test.

Imaging examinations

Computed tomography (CT) plain scan, CT enhanced scan and reconstruction of the whole abdomen showed: pancreatic swelling and peripancreatic oozing (inflammatory changes suggestive of AIP); and dilated intra- and extrahepatic bile ducts. Cholecystitis and prostate calcification were considered.

At the time of admission, CT plain scan and enhanced scan of the whole abdomen showed swollen pancreas, and pericardium-like low density shadow at the edge with sheath-like changes. CT enhanced scan showed that the pancreatic ducts were not dilated, and peripancreatic oozing. There was no dilatation of the pancreatic ducts and some peripancreatic exudation. The intra- and extrahepatic bile ducts were dilated and the gallbladder was slightly enlarged (Figure 1).

Figure 1 Computed tomography before treatment. A: Computed tomography (CT)-plain scan; B: CT-enhanced; C: CT-coronal plane.

Further diagnostic work-up

The patient was positive for hepatic schistosomiasis IgG antibody. Magnetic resonance cholangiopancreatography (MRCP) showed widespread dilatation of intrahepatic bile ducts, and proximal middle dilatation of the common bile duct. IG4 level was elevated to 14.7 g/L (normal range: 0.03–2.01 g/L). After admission, he received hepatoprotective, choleretic, anti-inflammatory, anti-infective and supportive symptomatic treatment. Antibodies to hepatitis A, hepatitis B, hepatitis C and hepatitis E viruses and autoimmune liver disease were normal.

FINAL DIAGNOSIS

Combining the patient's history, signs, laboratory examinations, and imaging examinations, the final diagnosis was: AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment.

TREATMENT

On July 29, 2023, the patient initiated hormonal shock therapy (prednisone acetate tablets, 45 mg/d), and was discharged from the hospital on August 2, 2023. He also received hepatoprotective therapy (diammonium glycyrrhizinate enteric-coated capsules 150 mg tid, bicyclol tablets 50 mg tid). The bicyclol tablets were changed to glucuronolactone tablets (0.2 g tid) on August 10. Ursodeoxycholic acid capsules were added on August 24 (250 mg qd), and the dose of prednisone acetate tablets was adjusted to 35 mg/d. The dose of prednisone acetate tablets was adjusted further to 25 mg/d, 15 mg/d and 10 mg/d on September 9, September 23 and October 7, respectively. The treatment was maintained until now. The results of laboratory tests during treatment were significantly improved (Table 1). Ultrasound comparison before and after treatment is shown in Figures 2 and 3.

Figure 2 Pancreatic swelling before autoimmune pancreatitis treatment. A: Head of the pancreas; B: Body and tail of the pancreas.

Figure 3 Pancreatic swelling after autoimmune pancreatitis treatment. A: Head of the pancreas; B: Body of the pancreas; C: Toil of the pancreas.

Table 1 Laboratory results during treatments.

Item/time	July 24, 2023	July 26, 2023	July 29, 2023	August 1, 2023	August 20, 2023	October 7, 2023	Reference point
WBC (× 109/L)	10.98	12.04	12.71	14.50	14.70	12.01	3.50-9.50
ALT (U/L)	231.80		210.80	172.10	27.50	24.70	9.00-50.00
AST (U/L)	138.20		117.90	66.80	19.90	23.00	15.00-40.00
TBIL (μmol/L)	69.40		31.60	24.10	16.70	10.70	0.00-26.00
DBIL (μmol/L)	59.50		29.40	23.80	10.10	4.10	0.00-8.00
IgG4 (g/L)		14.70			10.80		0.03-2.01

WBC: White blood cell count; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; DBIL: Direct bilirubin; IgG4: Immunoglobulin G4.

OUTCOME AND FOLLOW-UP

The patient's skin mucosa and eye color returned to normal. Liver function and bilirubin returned to normal. IgG4 gradually approached the normal range. The size of the pancreas was close to normal in imaging examination. The patient was recommended to undergo repeat pancreatic ultrasound elastometry.

DISCUSSION

AIP is a rare form of autoimmune-mediated pancreatitis, which is distributed worldwide, with a predominance of type 1. The clinical presentation is mainly obstructive jaundice and epigastric pain. The pathogenesis of the disease is still unclear, and it often involves extrapancreatic organs, such as the biliary tract, salivary glands and gastrointestinal tract, and hormonal therapy is effective. The imaging manifestations of AIP are diffuse and limited. It is difficult to distinguish from general pancreatitis when it is diffuse, and when it is a mass, it is easy to misdiagnose as pancreatic cancer. It is important to strengthen clinicians' ability to diagnose AIP to avoid delaying treatment or increasing patients' physical, economic and psychological burdens. In this paper, we discuss the diagnosis of AIP in a case admitted to our hospital and retrospectively analyze the relevant data.

We searched for cases in the past 5 years in PubMed with "(autoimmune pancreatitis) and (case report)". In accordance with the 2010 International Association of Pancreatic Diseases (IAPD) diagnostic criteria for AIP, 50 relevant case reports were selected, totaling 51 cases of AIP (Table 2).

Table 2 Summary of case data, n (%).

	Autoimmune pancreatitis (n = 51)
Sex
Male	39 (76)
Women	12 (24)
Age (yr)
< 50	15 (30)
50-60	19 (37)
> 60	17 (33)
Clinical symptom
Jaundice	33 (65)
Abdominal pain	22 (43)
Wasting away, fever etc.	10 (20)
Not have	4 (8)
Laboratory tests
CA19-9
Ascend	14 (27)
Normalcy	12 (24)
Not mentioned	25 (49)
IgG4
Ascend	45 (88)
Normalcy	4 (8)
Not mentioned	2 (4)
Swollen parts of the pancreas
Head of pancreas	30 (59)
Tail of pancreas	7 (14)
The whole pancreas	14 (27)
Diagnostic methods
Surgical resection	14 (27)
Puncture biopsy	27 (53)
Clinical diagnosis	10 (20)

CA19-9: Carbohydrate antigen 19-9; IgG4: Immunoglobulin G4.

The male-to-female ratio was 3.25:1 (39:12) in all age groups. Jaundice and epigastric pain predominated in 33 (65%) and 22 (43%) of the patients, and the tumor index CA19-9 was elevated or normal in a similar proportion of the laboratory tests, while the serological IgG4 test was elevated in 45 (88%) patients. Imaging showed swelling of the head of the pancreas in 30 cases, the tail of the pancreatic body in seven, and the entire pancreas in 14. About 53% of AIP cases were diagnosed primarily by puncture biopsy, but 14 (27%) patients were eventually diagnosed surgically with AIP.

Type 1 AIP is common in middle-aged and older men, and the 50–60 years' age group is common, with no specific clinical manifestations, but mostly obstructive jaundice, epigastric pain and other symptoms. The fifty-one cases of AIP in the literature review were diagnosed with a single symptom of obstructive jaundice, which may be related to the fact that the biliary tract has the highest rate of involvement in AIP.

Serum IgG4 is an important and specific serological marker for type 1 AIP[2], and the IgG4 in the patient diagnosed in our hospital was 14.7 g/L, which was > 7 times the upper limit of normal value. In the literature, 88% of the patients had elevated IgG4, which means that it is an important diagnostic indicator for AIP. In addition, CA19-9 may be elevated in patients with AIP, and should be further considered for malignant pancreatic cancer. Some studies have shown that diagnosis of AIP can be improved by combining serum IgG4 (> 280 mg/dL) and CA19-9 (< 85.0 U/mL)[3], and the simultaneous detection of IgG4 and CA19-9 is of practical value in identifying pancreatic cancer.

The typical imaging manifestation of AIP on CT and MRI is diffuse enlargement of the pancreas, which resembles a sausage, commonly known as the sausage sign. Not all cases of AIP have this manifestation. In the present case, ultrasound showed that the head of the pancreas was enlarged and appeared to be a hypoechoic mass. CT of the whole abdomen showed that the pancreas was swollen, with pericardium-like hypodense shadows on the edges, which was a sheath-like change, and enhanced CT scan was uniformly strengthened, and the pancreatic ducts were not dilated, and there was a small amount of peripancreatic oozing, which was not the typical diffuse enlargement of AIP. In the literature, 59% of the patients had a mass in the head of the pancreas, which was easily misdiagnosed as pancreatic cancer, and it was difficult to diagnose AIP on the basis of imaging. Another noninvasive imaging technique, MRCP, can show the penetrating duct or icicle sign, which is beneficial to the diagnosis of AIP. However, MRCP failed to provide the basis for diagnosis in the present case, which was probably related to the experience level of the imaging physician. AIP cannot be diagnosed solely based on the imaging manifestations alone,

Histopathological examination is important in the diagnosis of AIP. Type 1 AIP is characterized by a large number of lymphoplasmacytic cells infiltrating around the pancreatic ducts, accompanied by tissue-matted fibrosis, and immunohistochemical staining reveals > 10 IgG4-positive cells per high-power field. Pancreatic tissue can be obtained by minimally invasive and surgical methods, and minimally invasive puncture biopsy, which accounted for about half of the 51 cases reported in the literature. The latest Japanese guideline[4] recommends the collection of histopathological specimens by endoscopic-ultrasound-guided, fine-needle aspiration. Surgical removal of pancreatic tissue is invasive, and AIP was diagnosed in this way in 27% of patients reported in the literature, which often occurs when puncture biopsy is negative and pancreatic cancer is highly suspected, making the accuracy of puncture biopsy important.

CONCLUSION

Type 1 AIP has no characteristic clinical manifestations, and the imaging manifestations are atypical or similar to those of pancreatic cancer. Therefore, it is easy to misdiagnose, and its diagnosis mainly relies on detection of serological IgG4 levels. Short-term diagnostic treatment with small doses of hormones has a role in identification of AIP, but diagnostic confirmation mainly relies on pathology. However, there are many clinical situations in which pathology is unavailable; for example, if the patient refuses to have a biopsy, as in our case. The cases reported in the literature included some pregnant women with AIP. Pregnant women are a special population that is unsuitable for surgery and biopsy, and these patients require physicians to have sufficient familiarity with AIP and vigilance, and accurate and rapid diagnosis can avoid aggravating the patient's burden and lead to early recovery. At present, the most widely recognized diagnostic standard is that issued by IAPD in 2011[5], which classifies the diagnosis into confirmed and suspected after comprehensive assessment of the diagnostic basis from five aspects, and can provide clinical diagnostic guidance for physicians.