A 35-year-old Caucasian female presents with anemia, malaise, bloating, and diarrhea. Past genetic testing revealed that this patient carries the HLA-DQ2 allele. The physician suspects that the patient's presentation is dietary in cause. Which of the following findings would definitively confirm this diagnosis?

Biopsy of the duodenum showing atrophy and blunting of villi

CT scan showing inflammation of the small bowel wall

Biopsy of the colon showing epithelial cell apoptosis

Esophageal endoscopy showing lower esophageal metaplasia

Liver biopsy showing apoptosis of hepatocytes

A 36-year-old man is brought to the emergency department 3 hours after the onset of progressively worsening upper abdominal pain and 4 episodes of vomiting. His father had a myocardial infarction at the age of 40 years. Physical examination shows tenderness and guarding in the epigastrium. Bowel sounds are decreased. His serum amylase is 400 U/L. Symptomatic treatment and therapy with fenofibrate are initiated. Further evaluation of this patient is most likely to show which of the following findings?

Separate dorsal and ventral pancreatic ducts

A 21-year-old female presents to her obstetrician because she has stopped getting her period, after being irregular for the last 3 months. Upon further questioning, the patient reveals that she has had a 17 lb. unintended weight loss, endorses chronic diarrhea, abdominal pain, and constipation that waxes and wanes. Family history is notable only for an older brother with Type 1 Diabetes. She is healthy, and is eager to gain back some weight. Her OBGYN refers her to a gastroenterologist, but first sends serology laboratory studies for IgA anti-tissue transglutaminase antibodies (IgA-tTG). These results come back positive at > 10x the upper limit of normal. Which of the following is the gastroenterologist likely to find on endoscopy and duodenal biopsy?

Villous atrophy with crypt lengthening and intraepithelial lymphocytes

Friable mucosal pseudopolyps with biopsy notable for crypt abscesses

Cobblestoning with biopsy showing transmural inflammation and noncaseating granulomas

Foamy macrophages, which stain PAS positive

Normal appearing villi and biopsy

A 15-year-old girl is brought to the physician because of an 8-month history of fatigue, intermittent postprandial abdominal bloating and discomfort, foul-smelling, watery diarrhea, and a 7-kg (15-lb) weight loss. She developed a pruritic rash on her knees 3 days ago. Physical examination shows several tense, excoriated vesicles on the knees bilaterally. The abdomen is soft and nontender. Her hemoglobin concentration is 8.2 g/dL and mean corpuscular volume is 76 μm3. Further evaluation of this patient is most likely to show which of the following findings?

IgA tissue transglutaminase antibodies

Elevated serum amylase concentration

Intraluminal esophageal membrane

Periodic acid-Schiff-positive macrophages

A 22-year-old woman presents to the emergency department with a 3-day history of fever and abdominal pain. She says that the pain is located in the left lower quadrant of the abdomen and feels crampy in nature. The pain has been associated with bloody diarrhea and joint tenderness. She has no past medical history but says that she returned 2 weeks ago from vacation in Asia where she tried many new foods. Her family history is significant for multiple cancers in close relatives. Physical exam reveals swollen ulcers on her legs, and colonoscopy reveals contiguous ulcerations from the rectum through the descending colon. Which of the following is associated with the most likely cause of this patient's symptoms?

Perinuclear anti-neutrophil cytoplasmic antibodies

A 46-year-old man is brought to the emergency department because of severe epigastric pain and vomiting for the past 4 hours. The pain is constant, radiates to his back, and is worse on lying down. He has had 3–4 episodes of greenish-colored vomit. He was treated for H. pylori infection around 2 months ago with triple-regimen therapy. He has atrial fibrillation and hypertension. He owns a distillery on the outskirts of a town. The patient drinks 4–5 alcoholic beverages daily. Current medications include dabigatran and metoprolol. He appears uncomfortable. His temperature is 37.8°C (100°F), pulse is 102/min, and blood pressure is 138/86 mm Hg. Examination shows severe epigastric tenderness to palpation with guarding but no rebound. Bowel sounds are hypoactive. Rectal examination shows no abnormalities. Laboratory studies show: Hematocrit 53% Leukocyte count 11,300/mm3 Serum Na+ 133 mEq/L Cl- 98 mEq/L K+ 3.1 mEq/L Calcium 7.8 mg/dL Urea nitrogen 43 mg/dL Glucose 271 mg/dL Creatinine 2.0 mg/dL Total bilirubin 0.7 mg/dL Alkaline phosphatase 61 U/L AST 19 U/L ALT 17 U/L γ-glutamyl transferase (GGT) 88 u/L (N=5–50 U/L) Lipase 900 U/L (N=14–280 U/L) Which of the following is the most appropriate next step in management?

Endoscopic retrograde cholangio-pancreatography

A previously healthy 48-year-old man comes to the physician because of a 3-week history of progressively worsening jaundice, generalized itching, and epigastric discomfort. He also complains of nausea and loss of appetite. His stools have looked like clay for the past week. He has returned from a vacation in Thailand one week ago, where he got a new tattoo. He is sexually active with multiple partners and does not use protection. His vital signs are within normal limits. Examination shows jaundice and scleral icterus. Superficial excoriations are seen on all limbs. Abdominal examination shows no abnormalities. Serum studies show a fasting glucose level of 198 mg/dL, total bilirubin concentration of 10.6 mg/dL, direct bilirubin concentration of 9.8 mg/dl, and alkaline phosphatase activity of 450 U/L. Abdominal ultrasonography shows dilation of the biliary and pancreatic ducts and a 3-cm hypoechoic solid mass with irregular margins in the head of the pancreas. An elevation of which of the following serum findings is most specific for this patient's condition?

Elevated anti-neutrophil cytoplasmic antibodies

A 15-year-old African-American male with a BMI of 22 is brought to his physician by his mother to address concerns about a change in his dietary habits. The patient's mother notes that he is constantly hungry and thirsty, despite his eating and drinking water in excess. She also reports an increase in his use of the bathroom. The physician begins explaining that her son's symptoms are likely due to which of the following?

Pancreatic islet hyperplasia and hypertrophy

Amyloid deposition in pancreatic islets

Autoimmune pancreatitis for USMLE Step 3: High-Yield Internal Medicine Lessons

Overview & Pathophysiology - Pancreas Under Fire

A chronic fibro-inflammatory process driven by immune dysregulation, often mimicking pancreatic cancer.
Two distinct subtypes:
- Type 1 (Lymphoplasmacytic Sclerosing Pancreatitis): A manifestation of systemic IgG4-related disease (IgG4-RD). Typically affects males >60 years. Histology shows dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis.
- Type 2 (Idiopathic Duct-Centric Pancreatitis): A pancreas-specific disorder strongly associated with IBD (UC > Crohn's). Not related to IgG4. Histology shows neutrophilic infiltration of the ductal epithelium (granulocytic epithelial lesions or GELs).

CT: Diffusely enlarged, hypoattenuating pancreas

⭐ Type 1 AIP characteristically presents with a diffusely enlarged, featureless, "sausage-shaped" pancreas on imaging and is highly responsive to steroid therapy.

Clinical Presentation & Diagnosis - The Great Pretender

Presents insidiously, often mimicking pancreatic cancer.
- Painless obstructive jaundice (most common presentation).
- Mild, recurrent abdominal pain or back pain; weight loss.
Two distinct types:
- Type 1 (IgG4-related): Affects older males (>60), involves other organs (bile ducts, retroperitoneum, salivary glands), and shows ↑ serum IgG4.
- Type 2 (Idiopathic Duct-Centric): Affects younger patients, is strongly associated with IBD (especially Ulcerative Colitis), and has normal IgG4 levels.
Key Investigations:
- Imaging: Diffusely enlarged, "sausage-shaped" pancreas with a featureless border and a surrounding capsule-like rim on CT/MRI.
- Serology: ↑ Serum IgG4 (>135 mg/dL) is highly suggestive of Type 1.

⭐ Often presents as painless obstructive jaundice, making it a key mimic of pancreatic adenocarcinoma. Biopsy is often required for differentiation.

Diagnosis: Based on 📌 HISORt criteria (Histology, Imaging, Serology, Other organ involvement, Response to therapy).

Histology & Types - Two Faces of Inflammation

Histology of Autoimmune Pancreatitis

Feature	Type 1 AIP (LGPS)	Type 2 AIP (IDCP)
Histology	Lymphoplasmacytic Sclerosing Pancreatitis (LGPS); dense periductal lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis.	Idiopathic Duct-Centric Pancreatitis (IDCP); ductal neutrophilic infiltration (Granulocytic Epithelial Lesion - GEL), minimal fibrosis.
Serum IgG4	↑↑ Elevated in >80%	Normal
Systemic	IgG4-Related Disease (IgG4-RD); affects bile ducts, salivary glands, kidneys.	Pancreas-specific; rarely other organs.
Association	IgG4-RD	Inflammatory Bowel Disease (IBD), esp. Ulcerative Colitis (~30%).
Relapse	Common post-steroids	Rare

Treatment & Management - Cooling the Flames

Primary Goal: Induce remission, prevent relapse, and manage complications (e.g., biliary strictures).

⭐ Rituximab is increasingly used as a first-line agent for induction or for steroid-refractory/dependent disease, especially in Type 1 AIP, due to its high efficacy and steroid-sparing effects.

Often mimics pancreatic cancer but features a "sausage-shaped" pancreas on imaging and elevated serum IgG4 levels (in Type 1).

Type 1 is part of a systemic IgG4-related disease, affecting other organs like bile ducts and retroperitoneum.

Type 2 is pancreas-specific and strongly associated with inflammatory bowel disease (IBD), particularly ulcerative colitis.

Histology shows lymphoplasmacytic sclerosing pancreatitis (Type 1) or duct-centric inflammation (Type 2).

Hallmark feature is a dramatic response to corticosteroids.

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