Introduction
Pancreatic panniculitis is a rare skin manifestation of pancreatic disease. It is
believed to result from seepage of pancreatic enzymes into the systemic circulation,
which leads to skin and occasionally joint manifestations. It is reported to occur
in up to 3% of patients with pancreatic disease.
1
Pancreatic panniculitis can develop before, concomitantly with, or after the diagnosis
of clinically detectable pancreatic conditions. The condition is most frequently associated
with acute pancreatitis, chronic pancreatitis, and pancreatic carcinoma. The most
common carcinoma is acinar cell type.
Here we report an unusual association of pancreatic panniculitis preceding a single
episode of acute pancreatitis and subsequent development of an intraductal papillary
mucinous neoplasm (IPMN).
Case report
A 61-year-old female nondrinker and nonsmoker was first seen by the dermatology service
for a putative diagnosis of recurrent bilateral lower limb cellulitis. She was previously
admitted on 3 occasions over 2 months with presumed lower limb cellulitis treated
with oral and intravenous antibiotics. She had a medical history of schizophrenia
for which she was taking risperidone. Examination found multiple tender erythematous
nodules on both lower limbs extending to the thighs. The nodules were nonsuppurative
throughout (Fig 1). Skin biopsies results showed striking fat necrosis in the dermis
and subcutis with focal neutrophilic infiltrate. Ghost outlines of fat cells were
seen with focal basophilia, raising the possibility of pancreatic fat necrosis (Fig
2). Her amylase was 148 IU/L (reference range, 0–100 IU/L).
The patient attended the gastroenterology outpatient clinic 4 weeks later, and on
the day of consultation presented with her first attack of acute pancreatitis (sudden-onset
epigastric pain with serum amylase 5,500 IU/L). Liver function tests, serum calcium,
and triglycerides were normal. A computed tomography (CT) scan of the pancreas and
magnetic resonance cholangiopancreatography (MRCP) confirmed grade 2 nonnecrotizing
pancreatitis. This condition was treated successfully with intravenous fluids and
analgesia. There was a small thrombus in the proximal splenic vein, close to the portal-splenic
confluence. No direct communication with the pancreatic ductal system was visualized.
The main pancreatic duct (MPD) was normal, and there were no dilated branch ducts.
Endoscopic ultrasound scan (EUS) at that time found the main pancreatic duct to be
in contact with the portal/splenic confluence, but no direct communication was seen.
In addition, there was a small cystic 6-mm lesion in the upper isthmus/body junction
but at a distance from the MPD and vessels. The pancreatic parenchyma was normal without
stigmata of chronic pancreatitis. The biliary system was normal and without biliary
lithiasis. The thrombus was treated successfully with anticoagulants. Her pain rapidly
settled, and pancreatic enzymes returned to normal within a few days. Follow-up EUS
1 year later found 2 small elongated cysts in contact with the MPD at the level of
isthmus (11 × 4 mm) and midbody (6 mm). This finding was consistent with small dilated
accessory ducts (ie, branch duct IPMNs), which revealed minimal enlargement on yearly
MRCP (Fig 3). The panniculitis resolved spontaneously within 2 to 3 months.
She was subsequently lost to follow-up but had been well up to July 2015 when she
presented with a 1-week history of painless obstructive jaundice. She had no associated
weight loss. Serum amylase was normal. A CT scan of the abdomen and EUS identified
a 4.7-cm ill-defined solid and cystic mass in the pancreatic head emanating from the
dilated MPD (maximum diameter, 13 mm). This mass was felt to be consistent with mixed
main duct and branch duct IPMN with malignant transformation close to upper head and
isthmus. Involvement of the mesenteric fat and the superior mesenteric vein was also
noted. EUS-guided fine-needle aspiration biopsy confirmed a pancreatic adenocarcinoma.
She was referred for a surgical opinion, but her tumor was deemed unsuitable for resection.
She is currently undergoing systemic chemotherapy.
Discussion
Pancreatic panniculitis generally affects the lower limbs and buttocks but has been
reported to occur on the trunk and upper extremities.
2
The differential diagnosis includes erythema nodosum, erythema induratum, alpha-1
antitrypsin deficiency–associated panniculitis, trauma-induced panniculitis, and cutaneous
metastases. Histology from a skin biopsy of pancreatic panniculitis typically shows
lobular panniculitis with fat necrosis, basophilic debris, and anucleated adipocytes
with a partially digested shadowy cell membrane, also known as ghostlike cells.
Lipase and amylase have been detected in areas of subcutaneous fat necrosis associated
with pancreatic disease, suggesting that these enzymes have a role in the development
of pancreatic panniculitis.3, 4 Notably, pancreatic panniculitis has been reported
to occur in patients with low or normal serum pancreatic enzymes, suggesting a multifactorial
process.
5
Zellman
6
suggested that additional factors are required for the development of pancreatic panniculitis,
such as increased vessel permeability, allowing the pancreatic enzymes to leak out
of the circulation and into subcutaneous fat. Other case reports in the literature
support this theory of vascular permeability, for example, pancreatic panniculitis
occurring after femoral vein catheterization
7
and paracentesis.
8
There are 2 reports in the literature of patients with IPMN having pancreatic panniculitis.
One patient presented with weight loss and was subsequently found to have a pancreatic
mass on abdominal CT scan. The cutaneous lesions occurred 2 days after pancreaticoduodenectomy.
9
The second patient presented with a 10-week history of multiple tender subcutaneous
nodules; IPMN was detected following diagnosis of pancreatic panniculitis.
10
We highlight this case of pancreatic panniculitis given the unusual sequence of events:
the initial dermatologic condition possibly resulted from a small dilated branch duct
communicating with the portal venous system. As a consequence, there was seepage of
pancreatic enzymes into the systemic circulation, leading to the development of pancreatic
panniculitis. IPMN was the cause of pancreatic panniculitis in this case, and malignant
transformation was discovered 3 years later. It is intriguing that the patient's skin
lesions resolved despite progression of the pancreatic disease.