Panniculitis associated with pancreatic disease

Author: Dr Lucy Webber, Clinical Fellow in Dermatology, Department of Dermatology, University Hospital Bristol, UK. DermNet NZ Editor-in-Chief, A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. September 2017. Copy editor: Gus Mitchell. September 2017.

What is panniculitis?

Panniculitis is a group of conditions that involve inflammation of subcutaneous fat. Despite having diverse causes, most forms of panniculitis have the same clinical appearance.

What is panniculitis associated with pancreatic disease?

Pancreatic panniculitis is inflammation of subcutaneous fat associated with pancreatic disease, most commonly:

  • Pancreatic cancer
  • Acute pancreatitis
  • Chronic pancreatitis.

Rarely, panninculitis can be associated with other pancreatic disorders including pancreatic pseudocysts, pancreas divisum and vascular pancreatic fistulas. It has also been reported in patients with human immunodeficiency virus infection (HIV).

Pancreatic panniculitis associated with pancreatic cancer

Who gets pancreatic panniculitis?

Pancreatic panniculitis is rare and is estimated to occur in 2–3% of all patients with pancreatic disease. Its incidence is higher amongst alcoholic males. 

What causes pancreatic panniculitis?

The exact cause of pancreatic panniculitis remains unclear and several mechanisms have been implicated in its pathogenesis. The release of pancreatic enzymes, including lipase, amylase and trypsin, is believed to be the most significant factor.

  • Trypsin is thought to increase the permeability of the microcirculation and lymphatic channels, allowing lipase and amylase to enter the peripheral circulation.
  • Within fat lobules, these enzymes promote lipolysis, adipocyte necrosis and panniculitis.
  • This theory is supported by the presence of elevated pancreatic enzyme levels in the skin lesions, blood and urine of most patients with pancreatic panniculitis, even in the absence of detectable pancreatic disease.
  • However, some patients have normal serum pancreatic enzyme levels.

Other pathogenic factors may include:

  • Vascular damage
  • Deposition of immune complexes
  • Release of adipokines (adipocyte–generated cytokines).

What are the clinical features of pancreatic panniculitis

Pancreatic panniculitis typically presents with:

  • Thickened, firm nodules and/or plaques on the lower limbs (usually on the shins or around the ankles)
  • Erythematous, suppurative lesions producing brown, sterile, viscous liquid caused by fat liquefaction
  • Pain or tenderness
  • Ulceration and fistulation of necrotic fat to skin
  • Fever, polyarthritis and abdominal pain.

Fat necrosis induced by pancreatic enzymes is not always confined to subcutaneous fat and may appear elsewhere, particularly in fat around the joints, which can cause arthritis. The arthritis can affect single or multiple small and large joints and may be migratory, intermittent or persistent, and can progress to chondronecrosis or osteonecrosis.

Panniculitis associated with pancreatic cancer is more likely to ulcerate, persist and recur in comparison to lesions associated with inflammatory pancreatic disease. Cutaneous lesions associated with pancreatic cancer have also been reported to occur in areas other than the lower limbs including the thighs, abdomen, buttocks, arms, scalp and chest.

How is pancreatic panniculitis diagnosed?

Panniculitis is diagnosed and classified by a combination of clinical features and skin biopsy findings. In up to 40% of cases of pancreatic panniculitis, skin lesions are the presenting feature of pancreatic disease.  

The association of panniculitis with a pancreatic tumour may be recognised by the Schmid triad:

  1. Eosinophilia
  2. Panniculitis
  3. Arthritis.

Histopathological diagnosis

Panniculitis is classified histologically as mostly septal panniculitis (inflammation in the fibrous septa which surround subcutaneous fat lobules) or lobular panniculitis (inflammation of the fat).

Most types of panniculitis have both lobular and septal inflammation. Further classification is based on whether there is subcutaneous vasculitis, and the type of inflammation noted (neutrophils, lymphocytes, histiocytes, granulomas).

In the very early stages of pancreatic panniculitis, a septal pattern of lymphoplasmacytic inflammation is seen. As the condition progresses, a predominantly lobular panniculitis is seen without associated vasculitis.

The histological hallmark of pancreatic panniculitis is the presence of ‘ghost cells’. These are necrotic adipocytes that turn into an amorphous or granular blue–grey substance. The infiltrate surrounding ghost cells is predominantly neutrophilic, hence pancreatic panniculitis is also termed a neutrophilic panniculitis.

Diagnosis of pancreatic disease

Diagnosis of underlying pancreatic disease can be made by imaging and blood tests.


  • Computed tomography (CT)
  • Magnetic retrograde cholangiopancreatography (MRCP)
  • Endoscopic retrograde cholangiopancreatography (ERCP)

Blood tests

  • Elevated serum levels of pancreatic enzymes — these do not correlate with the severity of pancreatic panniculitis.
  • Eosinophilia and leukaemoid reaction in peripheral blood may indicate pancreatic malignancy.
  • Tumour markers such as Ca19–9 and carcinoembryonic antigen (CEA) may also be raised in pancreatic cancer.

What is the differential diagnosis for pancreatic panniculitis?

The most common form of panniculitis is erythema nodosum. See panniculitis for the full list of causes and classifications of the disease.

The main clinical differential diagnoses for pancreatic panniculitis are:

What is the treatment for pancreatic panniculitis?

Treatment of pancreatic panniculitis should address the underlying pancreatic pathology and may include surgical or endoscopic management. The cutaneous lesions usually heal once this has occurred. In some patients with pancreatic cancer, administration of octreotide (a somatostatin analogue which inhibits pancreatic pancreatic enzyme production) has resulted in significant improvement of pancreatic panniculitis.

Topical corticosteroids, non–steroidal anti–inflammatory drugs and immunosuppressive drugs are not usually effective treatments for pancreatic panniculitis.

If ulceration occurs, compression hosiery may be required to aid healing.

What is the outcome for pancreatic panniculitis?

The outcome for pancreatic panniculitis depends on the underlying disease process. It has a high mortality rate unless the underlying pancreatic abnormality is reversed. The prognosis is particularly poor in cases of pancreatic panniculitis related to pancreatic malignancy.

Several studies have shown resolution of pancreatic panniculitis after surgical or medical management of the pancreatic disease.

Once the underlying condition is treated, cutaneous lesions will slowly resolve, leaving post–inflammatory change. 

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