1 A rare complication of pancreatitis - PPP Syndrome (Pancreatitis, Panniculitis, Polyarthritis)

2 Abstract: PPP syndrome is the concomitant association of Pancreatitis, Polyarthritis and Panniculitis. Exact
3 pathogenesis of extra pancreatic manifestations are not well understood but is believed to be due to very high
4 levels of circulating pancreatic enzymes. A delay in diagnosis of the underlying pancreatitis has been associated
5 with higher mortality.

6 Key Words: PPP syndrome, Pancreatitis, Panniculitis, Poly arthritis, Ghost cells.

7 Case report

8 A 45-year-old gentleman, presented with a 4 day history of severe abdominal pain and vomiting following an
9 episode of alcohol binge. A diagnosis of Acute Pancreatitis was made based on past history of alcoholic
10 pancreatitis, clinical examination findings and lab results [elevated S.amylase (278IU/L) and S.lipase
11 (823IU/L)]. CECT abdomen showed features of acute on chronic pancreatitis with a necrotic collection of 2.8 x
12 2cm at head region with complete thrombosis of left branch of portal vein, partial thrombosis of right branch
13 and main port vein. There was no evidence of gall stone disease. (Fig. 1 )

14 He progressed well in the first 48 hours with standard medical management [ nil per oral regime,
15 meropenam, intravenous fluids and opioid analgesics]. On day 3, he developed multiple, tender, erythematous,
16 poorly defined, subcutaneous nodules over lower extremities and painful swelling over both knee joints( Fig 2).
17 Subcutaneous nodule was fluctuant and aspiration yielded necrotic material. Culture and sensitivity of the
18 aspirate was sterile. Biopsy from the skin nodule showed histological features of lobular panniculitis and ghost
19 cells. (Fig 3) MRI of the knee joint showed marrow edema.(Fig. 4 ). Symptoms pointed towards a possibility of
20 PPP syndrome.

21 Abdominal symptoms had resolved within 48 hours and he tolerated oral feeds well but Serum Amylase and
22 Lipase levels remained elevated over the course in the ward. Non steroidal anti-inflammatory therapy
23 [Etoricoxib] gave some improvement to the joint pain, hence was advised to continue for 3 weeks. Skin nodules
24 disappeared gradually over the next week. He was discharged at the end of second week. At 6 months follow up,
25 the patient remains asymptomatic and fully ambulant with some residual pain and wasting of left knee and leg,
26 which is being managed with physiotherapy and is showing marked improvement.

27 Discussion

28 PPP syndrome was described for the first time by Boswell et al. in 1973[1]. Till then approximately 60 cases
29 have been reported[2]. It typically affects middle aged men with chronic alcohol abuse. High levels of
30 circulating pancreatic enzymes have been implicated in the literature. Elevated levels of circulating pancreatic
31 enzymes are associated with more severe extra pancreatic manifestations in PPP syndrome. Fistulisation
32 between the pancreatic pseudocyst and superior mesenteric vein (SMV) have been reported in some cases. Such
33 fistulations leads to spillage of pancreatic juice into the portal circulation. This may be the cause of Superior
34 Mesenteric or Portal Vein thrombosis in such reported patients, including ours.

35 Pancreatic panniculitis was first described by Hans Chiari in 1883[3]. It affects 2-3% of patients with pancreatic
36 disorders. Clinically it appears as ill defined, tender, erythematous and oedematous nodules usually located over
37 legs. Sometimes these nodules may ulcerate and drain an oily viscous substance. These nodules tend to subside
38 when the circulating pancreatic enzymes come to normal levels leaving a hypo pigmented and atrophic scar.
39 Pathognomonic feature of pancreatic panniculitis is lobular panniculitis without vasculitis. There is coagulative
40 necrosis of adipocytes which leads to the formation of characteristic ghost cells[4].

41 Joint involvement is usually symmetric polyarthritis involving small and large joints[5]. Lower limb joints
42 are more commonly affected, and it follows the distribution of panniculitis. The arthritis, a rare complication of
43 pancreatitis is usually transient but it may occasionally follow a more chronic course in some patients. Earliest
44 radiological abnormality is marrow oedema which is best demonstrated in an MRI. Other features like marrow
45 fat necrosis, bone sclerosis and bone necrosis develop over weeks to months. MRI is more sensitive in detecting
46 bone marrow abnormalities and may add to early diagnostic information[6].

47 The treatment of PPP syndrome is mainly focused on underlying pancreatic disease[7]. Early recognition is
48 key in success of treatment. Panniculitis and Arthritis may precede abdominal symptoms which may leads to

1
1 delay in the diagnosis[8]. Management of panniculitis and arthritis with steroid is ineffective. NSAIDs will give
2 symptomatic relief but does not alter the progression of disease.

3 A high mortality is seen when there is a delay in detecting underlying pancreatic disease in PPP syndrome.
4 Clinicians should be aware of this syndrome and be able to include PPP syndrome as a differential diagnosis
5 when a patient presents with panniculitis and osteoarticular manifestation. Most patients can be managed
6 conservatively but surgical intervention may be helpful in a patient with pseudo cyst-SMV/portal vein fistula.

7 References

8 [1] V. Ferri et al., “Pancreatic disease, panniculitis, polyarthrtitis syndrome successfully treated with total
9 pancreatectomy: Case report and literature review,” Int. J. Surg. Case Rep., vol. 28, no. 2016, pp. 223–
10 226, 2016, doi: 10.1016/j.ijscr.2016.09.019.
11 [2] M. Plier, P. Durez, M. Komuta, and A. Raptis, “Severe panniculitis and polyarthritis caused by acinar
12 cell carcinoma arising from an ectopic pancreas,” BMJ Case Rep., vol. 2017, no. C, pp. 1–3, 2017, doi:
13 10.1136/bcr-2017-222241.
14 [3] W. Dieker et al., “Pancreatitis, panniculitis and polyarthritis (PPP-) syndrome caused by post-
15 pancreatitis pseudocyst with mesenteric fistula. Diagnosis and successful surgical treatment. Case report
16 and review of literature,” Int. J. Surg. Case Rep., vol. 31, no. 2017, pp. 170–175, 2017, doi:
17 10.1016/j.ijscr.2017.01.037.
18 [4] D. García-Romero and F. Vanaclocha, “Pancreatic Panniculitis,” Dermatol. Clin., vol. 26, no. 4, pp.
19 465–470, 2008, doi: 10.1016/j.det.2008.05.009.
20 [5] J. Narváez et al., “Pancreatitis, panniculitis, and polyarthritis,” Semin. Arthritis Rheum., vol. 39, no. 5,
21 pp. 417–423, 2010, doi: 10.1016/j.semarthrit.2008.10.001.
22 [6] S. Agarwal, A. Sasi, A. Ray, R. S. Jadon, and N. Vikram, “Pancreatitis panniculitis polyarthritis
23 syndrome with multiple bone infarcts,” Qjm, vol. 112, no. 1, pp. 43–44, 2019, doi:
24 10.1093/qjmed/hcy244.
25 [7] I. Loverdos et al., “A case of pancreatitis, panniculitis and polyarthritis syndrome: Elucidating the
26 pathophysiologic mechanisms of a rare condition,” J. Pediatr. Surg. Case Reports, vol. 3, no. 5, pp.
27 223–226, 2015, doi: 10.1016/j.epsc.2015.03.014.
28 [8] E. J. Kim et al., “Pancreatitis, Panniculitis, and Polyarthritis Syndrome Simulating Cellulitis and Gouty
29 Arthritis,” Korean J. Gastroenterol., vol. 74, no. 3, pp. 175–182, 2019, doi: 10.4166/kjg.2019.74.3.175.
30
31 Legends

32 Fig 1 - CECT Portal phase showing partial thrombosis of main portal vein.

33 Fig 2 - subcutaneous nodule

34 Fig 3 - Lobular Panniculitis ( H & E 40X )

35 Fig 4 - Proton density fat saturated coronal image showing patchy hyper intensities in upper tibia suggestive of
36 marrow edema