Young Man with Chronic Pancreatitis in 15 of His Relatives - Hereditary Pancreatitis?

39 yo AAM with a PMH of chronic pancreatitis, DM, HTN is admitted to the hospitals with CC: abdominal pain x 1 month. He also c/o fever and chills, and 20-pound weight loss over 2 months.

PMH:
Chronic pancreatitis since he was 19 yo.
He was admitted to another hospital 2 weeks ago with the same abdominal pain, treated for pancreatitis and a PICC line was placed for PPN.

FMH:
15 male members on his father's side of the family that had DM and pancreatitis

SH:
Never a heavy drinker, quit drinking 2 years ago

Medications:
Lisinopril, Pancrease, Metoprolol, Elavil, Neurontin, Demerol, Remeron, Duragesic

Physical examination:
VS 39.1-70-20-138/90
Asking for pain meds for abdominal pain, in NAD
PICC line - left upper arm
Chest: CTA (B)
Abdomen: Soft, diffuse tenderness, no rebound, decreased BS

What do you think is going on?
Pancreatitis - acute, chronic or acute on chronic?
Why is he febrile?
Infected pseudocyst?

What labs would you order?
CBCD, CMP, Amylase, Lipase, Blood Cx x 2
CT of the abdomen and pelvis

Labs


CBC, BMP, ESR, CRP

CT of the abdomen showed calcifications in the pancreatic head and mildly dilated pancreatic duct.

What happened?


Temperature curve during the hospital stay, cultures

Blood Cx were taken. One of the 2 blood cx grew Candida.

ID consult was called, Diflucan started and PICC line was removed, the tip of the line was cultured. The tip of the PICC line grew Candida.

What is the one very important thing that you have to do when a patient is having fungemia?
Ophthalmoscopy because Candida can cause retinitis and blindness.
Luckily, this patient had no retinitis.

What happened?
Diflucan brought down the fever and he started eating although the abdominal pain persisted. He was sent for ERCP with a question regarding performing pancreatic stenting vs. pancreaticojejunostomy.

What else? Why does he have so many relatives with pancreatitis?
There is a rare condition called hereditary pancreatitis which affects multiple members of one family. Read more below.

What did we learn form this case?
Blood cultures are very important in the evaluation of any febrile illness.
Treat fungemia immediately and perform an ophthalmoscopy.
Remember that pancreatitis can be due to a rare genetic disorder called hereditary pancreatitis


Q & A about hereditary pancreatitis

What is hereditary pancreatitis?
This is an unusual form of pancreatitis with a familial predisposition. The gene mutations causing most cases of hereditary pancreatitis have been identified in the cationic trypsinogen gene. The known mutations are trypsinogen R117H and N211. These may predispose to acute pancreatitis by eliminating one of the fail-safe mechanisms used by the pancreas to eliminate prematurely activated trypsin. The first attack typically occurs within the first two decades of life.
Source: Pubmed

What is the cause?
Currently, there are two common, and more than 6 uncommon cationic trypsinogen gene mutations that are associated with hereditary pancreatitis. The major mutations are known as cationic trypsinogen R122H and N29I. These are the two mutations (R122H or N29I) in the cationic trypsinogen gene (PRSS1 gene).
Source: Univ of Cincinnati, Pubmed

How common is hereditary pancreatitis?
In the U.S., it is estimated that at least 1,000 individuals are affected with hereditary pancreatitis. Hereditary pancreatitis should always be considered in patients who present with recurrent pancreatitis with a family history of pancreatic disease.
Source: Univ of Cincinnati

When to test a patient for hereditary pancreatitis?
Cationic trypsinogen (PRSS1) gene mutation analysis in a symptomatic patient:
Recurrent (>2) attacks of acute pancreatitis for which there is no explanation
OR
Unexplained (idiopathic) chronic pancreatitis
OR
A family history of pancreatitis in a first-degree, or second-degree relative
OR
An unexplained episode of documented pancreatitis occurring in a child
Source: NGC

How many genes are involved?
Two. It has been found that mutations of cationic trypsinogen gene (PRSS1) and serine protease inhibitor, Kazal type 1 gene (SPINK1) increase the susceptibility of chronic pancreatitis.
Source: Pubmed

More resources:
Hereditary Pancreatitis Research - David C. Whitcomb, MD, PhD - 1, 2
Hereditary Pancreatitis Registery


Q & A - Pain of chronic pancreatitis

What is the reason for the pain of chronic pancreatitis?
The pathogenesis of pain in chronic pancreatitis remains an enigma. The cause of pain is almost certainly multifactorial and may vary at different stages of the disease process. These factors may include inflammatory infiltration with influx of pain transmittent substances into damaged nerve ends, and the development of pancreatic ductal and tissue fluid hypertension due to morphological changes of the pancreas.
Source: Pubmed: 1, 2, Thomson Best Practice of Medicine

How to treat the pain of chronic pancreatitis?
A trial of high-dose Pancrease and Pepcid should precede the use of narcotics or any invasive treatment.

The evidence supporting the use of endoscopic therapy for pain in chronic pancreatitis is preliminary and largely confined to short-term observations. Although sphincterotomy, lithotripsy, and pancreatic duct stenting may hold promise, these procedures need further evaluation.

Although there have been no controlled trials comparing surgery with other treatments, experience indicates benefit in at least some patients. However, the failure rate of 20%-40% in even the most enthusiastic reports, as well as the potential for surgical morbidity and mortality, warrant reserving surgery for patients with severe pain not responsive to lesser tactics.

Source: NGC
Guideline for treatment of pain in chronic pancreatitis - Gastroenterology 1998, UpToDate

Is surgery helpful?
This is not clear. There is no "gold standard" in the surgical management of pancreatic pain. This is mainly due to the paucity of RCTs in the field of pancreatic surgery. With only 4 RCTs reported in the world literature it is difficult to state categorically what is the optimal treatment for this difficult group of patients.
Source: Pubmed, UpToDate