Pancreatitis: The great masquerader?

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Pancreatitis: The great masquerader?
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Nicholas S. Duca, MD
Kristian Feterik, MD, MBA
Jonhan Ho, MD, MS

A 55-year-old man presented to the emergency department with 1 week of bilateral lower-extremity joint pain associated with painful skin nodules. He had a history of chronic recurrent alcoholic pancreatitis. He denied abdominal pain, nausea, or vomiting.

Figure 1. The patient had multiple raised erythematous nodules on the lower extremities consistent with panniculitis.
Figure 1. The patient had multiple raised erythematous nodules on the lower extremities consistent with panniculitis.
Physical examination revealed synovitis of the ankles and knees bilaterally and circumferential erythematous nodules 0.5 to 1.5 cm in diameter on the lower extremities (Figure 1).

Results of initial laboratory testing:

  • Alkaline phosphatase 300 IU/L (reference range 36–108)
  • Erythrocyte sedimentation rate 81 mm/h (0–15)
  • Lipase 20,000 U/L (16–61).

Figure 2. Biopsy study revealed pancreatic panniculitis. The subcutis showed mixed inflammation with characteristic “ghost adipocytes” of adipocyte necrosis (red box) (hematoxylin and eosin, × 10).
Figure 2. Biopsy study revealed pancreatic panniculitis. The subcutis showed mixed inflammation with characteristic “ghost adipocytes” of adipocyte necrosis (red box) (hematoxylin and eosin, × 10).
Skin biopsy of lower-extremity lesions showed lobular necrosis of the subcutaneous fat, consistent with pancreatic panniculitis (Figure 2). Computed tomography revealed an acute exacerbation of chronic (“acute-on-chronic”) pancreatitis, with pseudocyst formation and pancreatic duct dilation.

Figure 3. Endoscopic retrograde cholangiopancreatography confirmed pancreatic stricture (arrow) and dilation of the pancreatic duct (box).
Figure 3. Endoscopic retrograde cholangiopancreatography confirmed pancreatic stricture (arrow) and dilation of the pancreatic duct (box).
Because of the persistent elevation in the serum lipase level and the dilation of the pancreatic duct shown on imaging, endoscopic retro­grade cholangiopancreatography was done to evaluate for malignant obstruction; it confirmed pancreatic duct stricture and dilation (Figure 3). Brush cytology study was negative for pancreatic or biliary malignancy. The pancreatic duct was dilated and stented, and the panniculitis and polyarthritis rapidly improved, with normalization of serum lipase levels. At a 3-month follow-up visit, the patient was asymptomatic with no recurrence of pancreatitis, panniculitis, or polyarthritis. He was subsequently lost to follow-up.

AN ATYPICAL PRESENTATION OF A COMMON DISEASE

Epidemiology and pathophysiology

Pancreatitis, panniculitis, and polyarthritis syndrome is a rare systemic complication of pancreatic disease occurring most often in middle-aged men with an acute exacerbation of chronic pancreatitis and a history of alcohol use disorder.1,2 It is also associated with pancreatic pseudocyst, pancreas divisum, and pancreatic adenocarcinoma.3–6 It is characterized by systemic fat necrosis secondary to severe and persistent elevation of pancreatic enzymes. The mortality rate is high; in a case series of 25 patients, 24% died within days to weeks after admission.1

Clinical presentation and treatment

The diagnosis of pancreatitis, panniculitis, and polyarthritis syndrome is often missed. Abdominal pain is mild or absent in over 60% of patients.1 Therefore, a high index of suspicion is required for early diagnosis.

The differential diagnosis includes sarcoidosis (including Löfgren syndrome), subcutaneous infection, and vasculitis. “Ghost adipocytes” on skin biopsy are pathognomonic for pancreatic panniculitis and are the result of saponification; they appear to be anuclear, with basophilic material throughout the cytoplasm.7 Arthrocentesis of affected joints may reveal thick, creamy material, rich in triglycerides, which is diagnostic of pancreatic arthritis.1,8

Treatment relies on correction of the underlying pancreatic pathology. Pancreatitis, panniculitis, and polyarthritis syndrome has been successfully treated by cyst gastrostomy, pancreatic duct stenting, and pancreaticoduodenectomy.7,9–11

TAKE-HOME POINTS

  • Pancreatitis, panniculitis, and polyarthritis syndrome mimics rheumatologic disease and often presents without abdominal pain.
  • The diagnosis is confirmed by the presence of elevated serum lipase or amylase, pancreatic imaging showing pancreatitis, and ghost adipocytes on skin biopsy.
  • Treatment is aimed at correcting the underlying pancreatic abnormality.
References
  1. Narváez J, Bianchi MM, Santo P, et al. Pancreatitis, panniculitis, and polyarthritis. Semin Arthritis Rheum 2010; 39(5):417–423. doi:10.1016/j.semarthrit.2008.10.001
  2. Mourad FH, Hannoush HM, Bahlawan M, Uthman I, Uthman S. Panniculitis and arthritis as the presenting manifestation of chronic pancreatitis. J Clin Gastroenterol 2001; 32(3):259–261. pmid:11246359
  3. Borowicz J, Morrison M, Hogan D, Miller R. Subcutaneous fat necrosis/panniculitis and polyarthritis associated with acinar cell carcinoma of the pancreas: a rare presentation of pancreatitis, panniculitis and polyarthritis syndrome. J Drugs Dermatol 2010; 9(9):1145–1150. pmid:20865849
  4. Hudson-Peacock MJ, Regnard CF, Farr PM. Liquefying panniculitis associated with acinous carcinoma of the pancreas responding to octreotide. J R Soc Med 1994; 87(6):361–362. pmid:8046712
  5. Vasdev V, Bhakuni D, Narayanan K, Jain R. Intramedullary fat necrosis, polyarthritis and panniculitis with pancreatic tumor: a case report. Int J Rheum Dis 2010; 13(4):e74–e78. doi:10.1111/j.1756-185X.2010.01548.x
  6. Haber RM, Assaad DM. Panniculitis associated with a pancreas divisum. J Am Acad Dermatol 1986; 14(2 pt 2):331–334. pmid:3950133
  7. Francombe J, Kingsnorth AN, Tunn E. Panniculitis, arthritis and pancreatitis. Br J Rheumatol 1995; 34(7):680–683. pmid:7670790
  8. Price-Forbes AN, Filer A, Udeshi UL, Rai A. Progression of imaging in pancreatitis panniculitis polyarthritis (PPP) syndrome. Scand J Rheumatol 2006; 35(1):72–74. doi:10.1080/03009740500228073
  9. Harris MD, Bucobo JC, Buscaglia JM. Pancreatitis, panniculitis, polyarthritis syndrome successfully treated with EUS-guided cyst-gastrostomy. Gastrointest Endosc 2010; 72(2):456–458. doi:10.1016/j.gie.2009.11.040
  10. Lambiase P, Seery JP, Taylor-Robinson SD, Thompson JN, Hughes JM, Walters JR. Resolution of panniculitis after placement of pancreatic duct stent in chronic pancreatitis. Am J Gastroenterol 1996; 91(9):1835–1837. pmid:8792709
  11. Potts JR. Pancreatic-portal vein fistula with disseminated fat necrosis treated by pancreaticoduodenectomy. South Med J 1991; 84(5):632–635. pmid:2035087
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Nicholas S. Duca, MD
Assistant Professor of Medicine, Division of General Internal Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA

Kristian Feterik, MD, MBA
Division of General Internal Medicine, University of Pittsburgh, PA

Jonhan Ho, MD, MS
Department of Dermatology and Pathology, University of Pittsburgh, PA

Address: Nicholas S. Duca, MD, Division of General Internal Medicine, Penn State Health Milton S. Hershey Medical Center, 500 University Drive H034, Hershey, PA 17036; nduca@pennstatehealth.psu.edu

Issue
Cleveland Clinic Journal of Medicine - 85(10)
Publications
Cleveland Clinic Journal of Medicine
Topics
Gastroenterology
Dermatology
Rheumatology
Page Number
752-753
Legacy Keywords
pancreas, pancreatitis, panniculitis, polyarthritis, PPP syndrome, bile duct stricture, masquerader, ghost adipocytes adipocyte necrosis, skin nodules, alkaline phosphatase, skin biopsy, erythrocyte sedimentation rate, lipase, Nicholas Duca, Kristian Feterik, Jonhan Ho
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The Clinical Picture
Author(s)
Nicholas S. Duca, MD
Kristian Feterik, MD, MBA
Jonhan Ho, MD, MS
Author(s)
Nicholas S. Duca, MD
Kristian Feterik, MD, MBA
Jonhan Ho, MD, MS
Author and Disclosure Information

Nicholas S. Duca, MD
Assistant Professor of Medicine, Division of General Internal Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA

Kristian Feterik, MD, MBA
Division of General Internal Medicine, University of Pittsburgh, PA

Jonhan Ho, MD, MS
Department of Dermatology and Pathology, University of Pittsburgh, PA

Address: Nicholas S. Duca, MD, Division of General Internal Medicine, Penn State Health Milton S. Hershey Medical Center, 500 University Drive H034, Hershey, PA 17036; nduca@pennstatehealth.psu.edu

Author and Disclosure Information

Nicholas S. Duca, MD
Assistant Professor of Medicine, Division of General Internal Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA

Kristian Feterik, MD, MBA
Division of General Internal Medicine, University of Pittsburgh, PA

Jonhan Ho, MD, MS
Department of Dermatology and Pathology, University of Pittsburgh, PA

Address: Nicholas S. Duca, MD, Division of General Internal Medicine, Penn State Health Milton S. Hershey Medical Center, 500 University Drive H034, Hershey, PA 17036; nduca@pennstatehealth.psu.edu

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A 55-year-old man presented to the emergency department with 1 week of bilateral lower-extremity joint pain associated with painful skin nodules. He had a history of chronic recurrent alcoholic pancreatitis. He denied abdominal pain, nausea, or vomiting.

Figure 1. The patient had multiple raised erythematous nodules on the lower extremities consistent with panniculitis.
Figure 1. The patient had multiple raised erythematous nodules on the lower extremities consistent with panniculitis.
Physical examination revealed synovitis of the ankles and knees bilaterally and circumferential erythematous nodules 0.5 to 1.5 cm in diameter on the lower extremities (Figure 1).

Results of initial laboratory testing:

  • Alkaline phosphatase 300 IU/L (reference range 36–108)
  • Erythrocyte sedimentation rate 81 mm/h (0–15)
  • Lipase 20,000 U/L (16–61).

Figure 2. Biopsy study revealed pancreatic panniculitis. The subcutis showed mixed inflammation with characteristic “ghost adipocytes” of adipocyte necrosis (red box) (hematoxylin and eosin, × 10).
Figure 2. Biopsy study revealed pancreatic panniculitis. The subcutis showed mixed inflammation with characteristic “ghost adipocytes” of adipocyte necrosis (red box) (hematoxylin and eosin, × 10).
Skin biopsy of lower-extremity lesions showed lobular necrosis of the subcutaneous fat, consistent with pancreatic panniculitis (Figure 2). Computed tomography revealed an acute exacerbation of chronic (“acute-on-chronic”) pancreatitis, with pseudocyst formation and pancreatic duct dilation.

Figure 3. Endoscopic retrograde cholangiopancreatography confirmed pancreatic stricture (arrow) and dilation of the pancreatic duct (box).
Figure 3. Endoscopic retrograde cholangiopancreatography confirmed pancreatic stricture (arrow) and dilation of the pancreatic duct (box).
Because of the persistent elevation in the serum lipase level and the dilation of the pancreatic duct shown on imaging, endoscopic retro­grade cholangiopancreatography was done to evaluate for malignant obstruction; it confirmed pancreatic duct stricture and dilation (Figure 3). Brush cytology study was negative for pancreatic or biliary malignancy. The pancreatic duct was dilated and stented, and the panniculitis and polyarthritis rapidly improved, with normalization of serum lipase levels. At a 3-month follow-up visit, the patient was asymptomatic with no recurrence of pancreatitis, panniculitis, or polyarthritis. He was subsequently lost to follow-up.

AN ATYPICAL PRESENTATION OF A COMMON DISEASE

Epidemiology and pathophysiology

Pancreatitis, panniculitis, and polyarthritis syndrome is a rare systemic complication of pancreatic disease occurring most often in middle-aged men with an acute exacerbation of chronic pancreatitis and a history of alcohol use disorder.1,2 It is also associated with pancreatic pseudocyst, pancreas divisum, and pancreatic adenocarcinoma.3–6 It is characterized by systemic fat necrosis secondary to severe and persistent elevation of pancreatic enzymes. The mortality rate is high; in a case series of 25 patients, 24% died within days to weeks after admission.1

Clinical presentation and treatment

The diagnosis of pancreatitis, panniculitis, and polyarthritis syndrome is often missed. Abdominal pain is mild or absent in over 60% of patients.1 Therefore, a high index of suspicion is required for early diagnosis.

The differential diagnosis includes sarcoidosis (including Löfgren syndrome), subcutaneous infection, and vasculitis. “Ghost adipocytes” on skin biopsy are pathognomonic for pancreatic panniculitis and are the result of saponification; they appear to be anuclear, with basophilic material throughout the cytoplasm.7 Arthrocentesis of affected joints may reveal thick, creamy material, rich in triglycerides, which is diagnostic of pancreatic arthritis.1,8

Treatment relies on correction of the underlying pancreatic pathology. Pancreatitis, panniculitis, and polyarthritis syndrome has been successfully treated by cyst gastrostomy, pancreatic duct stenting, and pancreaticoduodenectomy.7,9–11

TAKE-HOME POINTS

  • Pancreatitis, panniculitis, and polyarthritis syndrome mimics rheumatologic disease and often presents without abdominal pain.
  • The diagnosis is confirmed by the presence of elevated serum lipase or amylase, pancreatic imaging showing pancreatitis, and ghost adipocytes on skin biopsy.
  • Treatment is aimed at correcting the underlying pancreatic abnormality.

A 55-year-old man presented to the emergency department with 1 week of bilateral lower-extremity joint pain associated with painful skin nodules. He had a history of chronic recurrent alcoholic pancreatitis. He denied abdominal pain, nausea, or vomiting.

Figure 1. The patient had multiple raised erythematous nodules on the lower extremities consistent with panniculitis.
Figure 1. The patient had multiple raised erythematous nodules on the lower extremities consistent with panniculitis.
Physical examination revealed synovitis of the ankles and knees bilaterally and circumferential erythematous nodules 0.5 to 1.5 cm in diameter on the lower extremities (Figure 1).

Results of initial laboratory testing:

  • Alkaline phosphatase 300 IU/L (reference range 36–108)
  • Erythrocyte sedimentation rate 81 mm/h (0–15)
  • Lipase 20,000 U/L (16–61).

Figure 2. Biopsy study revealed pancreatic panniculitis. The subcutis showed mixed inflammation with characteristic “ghost adipocytes” of adipocyte necrosis (red box) (hematoxylin and eosin, × 10).
Figure 2. Biopsy study revealed pancreatic panniculitis. The subcutis showed mixed inflammation with characteristic “ghost adipocytes” of adipocyte necrosis (red box) (hematoxylin and eosin, × 10).
Skin biopsy of lower-extremity lesions showed lobular necrosis of the subcutaneous fat, consistent with pancreatic panniculitis (Figure 2). Computed tomography revealed an acute exacerbation of chronic (“acute-on-chronic”) pancreatitis, with pseudocyst formation and pancreatic duct dilation.

Figure 3. Endoscopic retrograde cholangiopancreatography confirmed pancreatic stricture (arrow) and dilation of the pancreatic duct (box).
Figure 3. Endoscopic retrograde cholangiopancreatography confirmed pancreatic stricture (arrow) and dilation of the pancreatic duct (box).
Because of the persistent elevation in the serum lipase level and the dilation of the pancreatic duct shown on imaging, endoscopic retro­grade cholangiopancreatography was done to evaluate for malignant obstruction; it confirmed pancreatic duct stricture and dilation (Figure 3). Brush cytology study was negative for pancreatic or biliary malignancy. The pancreatic duct was dilated and stented, and the panniculitis and polyarthritis rapidly improved, with normalization of serum lipase levels. At a 3-month follow-up visit, the patient was asymptomatic with no recurrence of pancreatitis, panniculitis, or polyarthritis. He was subsequently lost to follow-up.

AN ATYPICAL PRESENTATION OF A COMMON DISEASE

Epidemiology and pathophysiology

Pancreatitis, panniculitis, and polyarthritis syndrome is a rare systemic complication of pancreatic disease occurring most often in middle-aged men with an acute exacerbation of chronic pancreatitis and a history of alcohol use disorder.1,2 It is also associated with pancreatic pseudocyst, pancreas divisum, and pancreatic adenocarcinoma.3–6 It is characterized by systemic fat necrosis secondary to severe and persistent elevation of pancreatic enzymes. The mortality rate is high; in a case series of 25 patients, 24% died within days to weeks after admission.1

Clinical presentation and treatment

The diagnosis of pancreatitis, panniculitis, and polyarthritis syndrome is often missed. Abdominal pain is mild or absent in over 60% of patients.1 Therefore, a high index of suspicion is required for early diagnosis.

The differential diagnosis includes sarcoidosis (including Löfgren syndrome), subcutaneous infection, and vasculitis. “Ghost adipocytes” on skin biopsy are pathognomonic for pancreatic panniculitis and are the result of saponification; they appear to be anuclear, with basophilic material throughout the cytoplasm.7 Arthrocentesis of affected joints may reveal thick, creamy material, rich in triglycerides, which is diagnostic of pancreatic arthritis.1,8

Treatment relies on correction of the underlying pancreatic pathology. Pancreatitis, panniculitis, and polyarthritis syndrome has been successfully treated by cyst gastrostomy, pancreatic duct stenting, and pancreaticoduodenectomy.7,9–11

TAKE-HOME POINTS

  • Pancreatitis, panniculitis, and polyarthritis syndrome mimics rheumatologic disease and often presents without abdominal pain.
  • The diagnosis is confirmed by the presence of elevated serum lipase or amylase, pancreatic imaging showing pancreatitis, and ghost adipocytes on skin biopsy.
  • Treatment is aimed at correcting the underlying pancreatic abnormality.
References
  1. Narváez J, Bianchi MM, Santo P, et al. Pancreatitis, panniculitis, and polyarthritis. Semin Arthritis Rheum 2010; 39(5):417–423. doi:10.1016/j.semarthrit.2008.10.001
  2. Mourad FH, Hannoush HM, Bahlawan M, Uthman I, Uthman S. Panniculitis and arthritis as the presenting manifestation of chronic pancreatitis. J Clin Gastroenterol 2001; 32(3):259–261. pmid:11246359
  3. Borowicz J, Morrison M, Hogan D, Miller R. Subcutaneous fat necrosis/panniculitis and polyarthritis associated with acinar cell carcinoma of the pancreas: a rare presentation of pancreatitis, panniculitis and polyarthritis syndrome. J Drugs Dermatol 2010; 9(9):1145–1150. pmid:20865849
  4. Hudson-Peacock MJ, Regnard CF, Farr PM. Liquefying panniculitis associated with acinous carcinoma of the pancreas responding to octreotide. J R Soc Med 1994; 87(6):361–362. pmid:8046712
  5. Vasdev V, Bhakuni D, Narayanan K, Jain R. Intramedullary fat necrosis, polyarthritis and panniculitis with pancreatic tumor: a case report. Int J Rheum Dis 2010; 13(4):e74–e78. doi:10.1111/j.1756-185X.2010.01548.x
  6. Haber RM, Assaad DM. Panniculitis associated with a pancreas divisum. J Am Acad Dermatol 1986; 14(2 pt 2):331–334. pmid:3950133
  7. Francombe J, Kingsnorth AN, Tunn E. Panniculitis, arthritis and pancreatitis. Br J Rheumatol 1995; 34(7):680–683. pmid:7670790
  8. Price-Forbes AN, Filer A, Udeshi UL, Rai A. Progression of imaging in pancreatitis panniculitis polyarthritis (PPP) syndrome. Scand J Rheumatol 2006; 35(1):72–74. doi:10.1080/03009740500228073
  9. Harris MD, Bucobo JC, Buscaglia JM. Pancreatitis, panniculitis, polyarthritis syndrome successfully treated with EUS-guided cyst-gastrostomy. Gastrointest Endosc 2010; 72(2):456–458. doi:10.1016/j.gie.2009.11.040
  10. Lambiase P, Seery JP, Taylor-Robinson SD, Thompson JN, Hughes JM, Walters JR. Resolution of panniculitis after placement of pancreatic duct stent in chronic pancreatitis. Am J Gastroenterol 1996; 91(9):1835–1837. pmid:8792709
  11. Potts JR. Pancreatic-portal vein fistula with disseminated fat necrosis treated by pancreaticoduodenectomy. South Med J 1991; 84(5):632–635. pmid:2035087
References
  1. Narváez J, Bianchi MM, Santo P, et al. Pancreatitis, panniculitis, and polyarthritis. Semin Arthritis Rheum 2010; 39(5):417–423. doi:10.1016/j.semarthrit.2008.10.001
  2. Mourad FH, Hannoush HM, Bahlawan M, Uthman I, Uthman S. Panniculitis and arthritis as the presenting manifestation of chronic pancreatitis. J Clin Gastroenterol 2001; 32(3):259–261. pmid:11246359
  3. Borowicz J, Morrison M, Hogan D, Miller R. Subcutaneous fat necrosis/panniculitis and polyarthritis associated with acinar cell carcinoma of the pancreas: a rare presentation of pancreatitis, panniculitis and polyarthritis syndrome. J Drugs Dermatol 2010; 9(9):1145–1150. pmid:20865849
  4. Hudson-Peacock MJ, Regnard CF, Farr PM. Liquefying panniculitis associated with acinous carcinoma of the pancreas responding to octreotide. J R Soc Med 1994; 87(6):361–362. pmid:8046712
  5. Vasdev V, Bhakuni D, Narayanan K, Jain R. Intramedullary fat necrosis, polyarthritis and panniculitis with pancreatic tumor: a case report. Int J Rheum Dis 2010; 13(4):e74–e78. doi:10.1111/j.1756-185X.2010.01548.x
  6. Haber RM, Assaad DM. Panniculitis associated with a pancreas divisum. J Am Acad Dermatol 1986; 14(2 pt 2):331–334. pmid:3950133
  7. Francombe J, Kingsnorth AN, Tunn E. Panniculitis, arthritis and pancreatitis. Br J Rheumatol 1995; 34(7):680–683. pmid:7670790
  8. Price-Forbes AN, Filer A, Udeshi UL, Rai A. Progression of imaging in pancreatitis panniculitis polyarthritis (PPP) syndrome. Scand J Rheumatol 2006; 35(1):72–74. doi:10.1080/03009740500228073
  9. Harris MD, Bucobo JC, Buscaglia JM. Pancreatitis, panniculitis, polyarthritis syndrome successfully treated with EUS-guided cyst-gastrostomy. Gastrointest Endosc 2010; 72(2):456–458. doi:10.1016/j.gie.2009.11.040
  10. Lambiase P, Seery JP, Taylor-Robinson SD, Thompson JN, Hughes JM, Walters JR. Resolution of panniculitis after placement of pancreatic duct stent in chronic pancreatitis. Am J Gastroenterol 1996; 91(9):1835–1837. pmid:8792709
  11. Potts JR. Pancreatic-portal vein fistula with disseminated fat necrosis treated by pancreaticoduodenectomy. South Med J 1991; 84(5):632–635. pmid:2035087
Issue
Cleveland Clinic Journal of Medicine - 85(10)
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Cleveland Clinic Journal of Medicine - 85(10)
Page Number
752-753
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752-753
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Cleveland Clinic Journal of Medicine
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Pancreatitis: The great masquerader?
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Pancreatitis: The great masquerader?
Legacy Keywords
pancreas, pancreatitis, panniculitis, polyarthritis, PPP syndrome, bile duct stricture, masquerader, ghost adipocytes adipocyte necrosis, skin nodules, alkaline phosphatase, skin biopsy, erythrocyte sedimentation rate, lipase, Nicholas Duca, Kristian Feterik, Jonhan Ho
Legacy Keywords
pancreas, pancreatitis, panniculitis, polyarthritis, PPP syndrome, bile duct stricture, masquerader, ghost adipocytes adipocyte necrosis, skin nodules, alkaline phosphatase, skin biopsy, erythrocyte sedimentation rate, lipase, Nicholas Duca, Kristian Feterik, Jonhan Ho
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