CORRECT DIAGNOSIS:
Pancreatic panniculitis
DISCUSSION:
A triad of pancreatic panniculitis, pancreatitis, and polyarthritis describes an extremely rare entity known as PPP syndrome. Currently, only 25 well-documented cases exist in the literature. Pancreatic panniculitis is a rare form of subcutaneous fat necrosis associated with underlying pancreatic disease. Pancreatic panniculitis has been found in roughly 2-3% of patients with acute or chronic pancreatitis, and pancreatic carcinoma (acinar cell type). Joint disease has been reported in 54-80% of cases, most commonly involving the ankles, knees, wrists, and MCP joints of the hands.
Pancreatic panniculitis in the setting of PPP syndrome commonly presents with ill-defined, red-brown, exquisitely tender, edematous subcutaneous nodules on the lower legs. Less common locations include the thighs, buttocks, arms, abdomen, and chest. The subcutaneous nodules may spontaneously ulcerate and exude oily, viscous material as a result of the liquefactive necrosis of adipocytes. Patients with PPP syndrome typically present with mild to absent abdominal symptoms and coexisting joint pain, pitting edema, and subcutaneous nodules.
The exact pathogenesis of PPP syndrome remains unclear. It has been hypothesized that serum trypsin released from the damaged pancreas is responsible for increased vascular permeability, thus allowing the release of lipase and amylase from the blood vessels into the surrounding subcutis and bone marrow. These enzymes bind adipocytes and hydrolyze triglycerides into free fatty acids, initiating inflammation and necrosis. Intraosseous fat necrosis is responsible for the development of multiple osteolytic bone lesions and endosteal erosions seen on plain radiographs and CT scans. Needle aspiration of the arthritic joints often yields yellow, viscous, purulent fluid with lipid crystals and elevated lipase levels.
Histopathologic findings of pancreatic panniculitis demonstrate lobular subcutaneous inflammation with liquefactive necrosis of adipocytes in the subcutis, leading to the characteristic appearance of “ghost adipocytes”. Ghost adipocytes are cells with absent nuclei containing fine basophilic homogenous material in the presence of fat saponification. Fat saponification is a result of free fatty acids combining with calcium in the setting of elevated pancreatic enzymes within the subcutis.
The differential diagnosis of pancreatic panniculitis should include erythema nodosum, erythema induratum, α1-antitrypsin deficiency, lupus profundus, and cutaneous polyarteritis nodosa.
Treatment of PPP syndrome is largely supportive, with a focus on correcting the underlying pancreatic disease. NSAIDs, corticosteroids, and octreotide have been utilized with minimal effectiveness. Plasmapheresis is an effective treatment option in patients with persistent hyperamylasemia and hyperlipasemia. Often reserved for severe refractory disease, a cholecystectomy and/or a pancreatic duct removal have demonstrated success in the management of chronic pancreatitis and panniculitis. More importantly, the diagnosis of pancreatic panniculitis could be an early indicator of an occult pancreatic malignancy and should prompt early evaluation with a multidisciplinary approach.
TREATMENT:
The patient underwent a pancreaticoduodenectomy (Whipple procedure) with significant improvement in his pancreatic enzymes, lower extremity subcutaneous nodules, and arthritis. He is currently being followed by rheumatology and internal medicine.
REFERENCES:
Arbeláez-Cortés Á, Vanegas-García A, Restrepo-Escobar M, et al. Polyarthritis and pancreatic panniculitis associated with pancreatic carcinoma. J Clin Rheumatol. 2014;20(8):433-436.
Borowicz J, Morrison M, Hogan D, et al. 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):1145-1149.
Francombe J, Kingsnorth A, Tunn E. Panniculitis, arthritis and pancreatitis. Brit J Rheum. 1995;34:680-683.
Narvaez J, Bianchi M, Santo P, et al. Pancreatitis, panniculitis, and polyarthritis. Semin Arthritis Rheum. 2010;39(5):417-423.
Additional Comment: A rare triad composed of lobular panniculitis in the setting of pancreatitis and polyarthritis is termed in the literature as PPP syndrome. Pancreatic panniculitis is a rare form of subcutaneous fat necrosis associated with underlying pancreatic disease. We describe a case of pancreatic panniculitis, pancreatitis, and polyarthritis (PPP syndrome) and review the relevant literature associated with this rare clinical syndrome. We report a patient diagnosed with PPP syndrome with well-documented evidence of joint involvement, subcutaneous fat necrosis, and chronic pancreatitis. In addition to our case, there are currently only 26 reported cases of PPP syndrome. After extensive literature review, we report a case of PPP syndrome in a 69-year-old man who presented with numerous lower extremity subcutaneous nodules on the bilateral lower legs with coexisting joint swelling and pancreatitis. We confirmed the diagnosis of pancreatic panniculitis histopathologically. Laboratory and imaging data confirmed joint and pancreatic involvement. Based on the triad of findings, in this case, we made a diagnosis of PPP syndrome. PPP syndrome is a diagnosis composed of a triad of pancreatic panniculitis, pancreatitis, and polyarthritis. Despite numerous adjuvant therapies, definitive treatment requires correction of the underlying pancreatic disease.
