Frontiers in Medical Case Reports (FMCR)
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Pages: 01-08

Date of Publication: 30-Nov--0001

Acute Pancreatitis in Systemic Lupus Erythematosus: A Series of 27 Cases

Author: BELLAMINE Hind, BARAKAT Leila, BENZAKOUR Meryem, MOUDATIR Mina, ECHCHILALI Khadija, ELKABLI Hassan

Category: Medical Case Reports

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Abstract:

Acute pancreatitis is a rare and potentially fatal complication of systemic lupus erythematosus (SLE). This study aimed to describe the epidemiological, clinical, radiological, and evolutionary characteristics of acute pancreatitis (AP) in patients with systemic lupus erythematosus. Data from patients who met the revised ACR EULAR criteria for the diagnosis of LES were analyzed retrospectively. SLE activity was assessed according to the SLEDAI activity index, with a mean estimate of 14.

This study included 400 patients with LES admitted between January 2010 and December 2022, of whom 27 patients were diagnosed with pancreatitis. The prevalence of pancreatitis in patients with SLE was 6.75% (27/400). Acute pancreatitis occurred mainly during active SLE, and involved more organs. The outcome was good in 60% of cases, with a 40% mortality rate in lupus-associated AP.

After ruling out other causes, acute pancreatitis can be associated with SLE, if it occurs concomitantly with other signs of lupus flare-up. The diagnosis is made when the symptoms improve with specific treatment. The aim of our work is to describe the epidemiological profile, modes of presentation of lupus pancreatitis, therapeutic features and evolutionary profile of patients.

Keywords: Pancreatitis, Lupus Pancreatitis, Systemic Lupus Erythematosus

Full Text:

Introduction

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory disease characterized by the presence of autoantibodies and immune complex formation. The occurrence of acute pancreatitis (AP) during systemic lupus erythematosus (SLE) is known but rare, and exceptionally revelatory. The objective of our work is to describe epidemiological, clinical, radiological and evolutive characteristics of lupus pancreatitis in a Moroccan series.

Materials and Methods

Twenty-seven observations of lupus pancreatitis were retrospectively collated in the Casablanca internal medicine department, from 400 exploited cases of systemic lupus erythematosus meeting ACR criteria, over a 12-year period from January 2010 to December 2022. The diagnosis of lupus pancreatitis was retained in the absence of other causes of pancreatitis: biliary lithiasis, toxic (drugs or ethyl intoxication), traumatic and neoplastic, as evaluated by the Balthazar score.

Results

Of the 400 SLE cases analyzed, 27 patients had lupus PA, a frequency of 6.75%. These included 25 women and 2 men, with a mean age of 31 years (15 to 52 years). Pancreatic involvement was revelatory of lupus in 8 cases, and observed during a relapse of the disease in 19 patients, with a diagnostic delay of 26 months. The revealing clinical symptoms were abdominal pain, epigastralgia and vomiting in 22 patients (81.4%), diarrhoea in 2 cases (7.4%), fever in 7 patients (26%), and two patients were asymptomatic (7.4%). Biologically, lipaemia was greater than 3 times normal in all patients, 62.9% of cases presented an inflammatory syndrome at the time of pancreatitis, hepatic function tests were perturbed in 8 patients, and lipid profiles were abnormal in 6 patients. Abdominal CT scans showed Balthazar grade A pancreatitis in 6 cases (22%), grade B in 11 cases (40.7%), grade C in two cases (7.4%), grade D in three cases (11%), and grade E in five cases (18.5%). Systemic manifestations associated with AP included hematological involvement in 25 cases, renal involvement in 10 cases, neurological involvement in 10 cases, cardiac involvement in 2 cases, and ocular involvement in only 1 case. SAPL associated with LES was found in 2 patients. The mean calculated SLEDAI was 14. All our patients were receiving hydroxychloroquine 400mg/d, and most of them were already being treated for other systemic disorders, notably corticosteroids in 18 patients, immunosuppressants such as mycophenolate 2g/d in 3 patients, azathioprine 150mg/d in 9 patients and cyclophosphamide in 6 patients. Treatment of AP was based on digestive rest, bolus corticosteroid therapy of 500mg-1g/day for 3 days in 12 patients, immunosuppressive cyclophosphamide 1g in 8 patients, and azathioprine in 3 patients. Evolution was good in 59.2% of cases, with improvement of the digestive tract and normalization of lipemia at D15 of treatment. Two patients were complicated by macrophagic activation syndrome. Both had renal involvement, and one had additional cardiopulmonary involvement. We noted one case of gayet wernick complicating acute pancreatitis (AP). Eleven deaths were unfortunately reported, of which four were directly related to pancreatitis, and the rest to renal damage and infections.

Discussion

The occurrence of acute pancreatitis during systemic lupus erythematosus (SLE) is known but rare, its prevalence varying from 0.6 to 0.9% to 3.5% (Wang et al., 2016), its incidence is estimated between 0.4 and 1, 1 case per 1000 lupus per year, different rates of LES-related pancreatitis have been reported in different cohorts, 25 patients out of 2974 cases of LES (0.85%) (Derk and DeHoratius, 2004; Saab et al., 1998) and 63 patients out of 1811 with LES (3.5%) (Makol and Petri, 2010).

The median age of onset of AP in our study was 31 years, similar to most other studies (Yang et al., 2012; Wang et al., 2011), although in the largest Indian series of lupus pancreatitis, the median age of onset was 24 years (Muhammed et al., 2022).

A recent study of 264 cases from 11 articles observed a trend towards the onset of AP within the first 3 years of diagnosis of SLE (Alina et al., 2021); in our study, more than half the patients developed pancreatitis within the first year of the disease.

Pancreatic involvement is more often acute than chronic. According to various series, pancreatitis is revelatory of SLE in 22% of cases (Makol and Petri, 2010; Larino Noia et al., 2009; Wang et al., 2005; Dhir et al., 2011), and correlates with lupus activity; in our experience, AP was revelatory in 29% of cases, which occurred in the context of active lupus in most of our patients with SLEDAI above 4. This suggests that lupus-related autoimmunity may be the cause of AP.

Acute pancreatitis is often associated with severe visceral damage such as renal and neurological involvement (Yu et al., 2016), in our work, 25 patients presented with other systemic manifestations of systemic lupus erythematosus (Table 1).

Table1: Association of pancreatitis and other visceral disorders in lupus in literature series.

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The etiology of AP in a lupus patient is often difficult to determine. Its pathogenesis is multifactorial, and several etiologies are often incriminated, such as an ischemic mechanism due to vasculitis or thrombosis due to an associated antiphospholipid antibody syndrome, an autoimmune mechanism, or a drug-induced lesion related to lupus treatments such as corticoids and mycophenolate mofetil, or an intercurrent infectious disease (Ben Dhaou et al., 2013).

That said, the diagnosis of AP should only be made after evaluating other etiologies, such as obstructive (gallstones, pancreas divisum), toxic-metabolic (alcohol, hypercalcemia, hypertriglyceridemia) or iatrogenic, given that some of the drugs associated with lupus, such as azathioprine, mycophenolate, cyclosporine or corticosteroids, may be incriminated as a cause of acute pancreatitis (Wang et al., 2016).

Histologically, the specimen shows inflammatory infiltrates and necrosis. Vascular lesions, including thrombosis and vasculitis, are rare (Breuer et al., 2006). These histopathological features are indistinguishable from pancreatitis due to other causes, but this is rarely available, and no histology was performed in our patients.

Clinically, overall, around 20-50% of Lupus patients may develop gastrointestinal symptoms (Dima et al., 2017). The clinical manifestations of our patients are very similar to the literature, based on abdominal pain as the first complaint, reported in most patients (Arbaoui et al., 2020) (Table 2). Acute pancreatitis should be suspected in any lupus patient with acute abdominal pain; however, lupus pancreatitis may be clinically silent and of incidental discovery (Wang et al., 2016), although there are rare cases of silent pancreatitis in which imaging may reveal the diagnosis (Alibegovic et al., 2017).

Table 2: Comparison of clinical features of patients with lupus-associated pancreatitis with other series in the literature.

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As in their study, Medeiros, et al. (2011) reported an incidence of 5.1% of subclinical pancreatitis. In our series, two patients were asymptomatic (stage A).

The diagnosis of pancreatitis can be confirmed by measuring enzyme levels and imaging; in fact, 97% of cases are diagnosed on the basis of increased blood lipase or amylase levels (Yang et al., 2012). Serum lipase has good sensitivity and specificity in the diagnosis of acute pancreatitis (Cappell, 2008), and its measurement is recommended by the French National Authority for Health (HAS) as it attains its peak more rapidly, within 24 hours of the onset of clinical signs. A level greater than three times normal within 48 hours of the onset of clinical signs confirms the presence of pancreatitis. Lipasemia was consistently elevated in our patients. However, its elevation does not correlate with the severity of acute pancreatitis (Malka and Rosa-Hezode, 2001), and it is not a screening, monitoring or severity assessment test.

As for amylasemia, even in the presence of acute pancreatitis, values may be at the limit of normal (Derk and DeHoratius, 2004).

A variety of biological manifestations may accompany this complication, such as cytolysis and moderate cholestasis. Hematological involvement is present in 100% of cases, compared with 61% of uncomplicated lupus (Yang et al., 2012), often in the form of anemia and cytopenia, and thrombocytopenia, which has been reported in 48% of cases of lupus pancreatitis (Breuer et al., 2006); renal involvement, frequent in SLE, is another risk factor for increased pancreatic enzymes (Medeiros et al., 2011), but pancreatitis does not appear to have a direct effect on renal function.

It is sometimes difficult to distinguish between what is due to pancreatitis and what is due to SLE itself, especially when it comes to hematological and renal damage (Breuer et al., 2006).

However, it would appear that thrombocytopenia, along with hypertriglyceridemia and increased sedimentation rate, are the only parameters statistically associated with pancreatitis (Medeiros et al., 2011).

As for imaging, echo-endoscopy makes an important contribution to the diagnosis of pancreatitis, enabling not only visualization of the pancreatic parenchyma and the bile and pancreatic ducts, but also the performance of pancreatic biopsies. Abdominal ultrasound will show signs of enlarged pancreas, peripancreatic inflammation and increased vascularity (Johnson et al., 2014). It also helps identify other causes of AP such as gallstones, structural anomalies and local complications such as pseudocysts, ascites and abdominal collections.

CT is generally reserved for patients with diagnostic confusion, and better characterizes complications such as pancreatic oedema, necrosis and peripancreatic fluid collections (Johnson et al., 2014). The severity of necrosis on CT can predict the outcome of AP (Sahu et al., 2017). All our patients underwent CT scans, eight of whom were already at the stage of necrosis.

MRI is more efficient, and will better define the nature of the necrotic flows. The PAL is hyposignal T1 and hypersignal T2; after injection of gadolinium, with late enhancement of the gland. Therapeutically, there is no well-established consensus on the management of acute lupus pancreatitis. The treatment of lupus AP is similar to that of the general population: absolute diet initially, followed by early nutrition within 48 to 72 h, or enteral nutrition for severe AP to reduce the risk of infection and mortality, IV hydration and analgesia (Guyot et al., 2021).

Although corticosteroids and immunosuppressants have been implicated in the occurrence of fatal haemorrhagic pancreatitis in SLE (Reynolds et al., 1982), although this condition is generally corticosteroid-sensitive, they usually allow the vasculitis to heal (Eaker and Toskes, 2018). The occurrence of pancreatitis in the course of SLE should not, therefore, lead to the discontinuation or reduction of corticosteroid therapy, unless its responsibility in the occurrence of pancreatitis is formally established. In our 27 observations, the introduction of high-dose corticosteroids improved the clinical and laboratory symptoms of 16 patients.

In a review of the literature by Breuer, et al. (2006), based on a series of 77 lupus patients, treatment of acute lupus pancreatitis included corticosteroid therapy in 83% of cases, combined with immunosuppressive therapy with azathioprine in 10% and cyclophosphamide in 7%. Six patients (7%) were treated with plasmapheresis and two with intravenous gamma globulin. The course of lupus pancreatitis is generally good, but the severity of the initial presentation and/or delay in diagnosis could lead to early mortality. Although pancreatic involvement is only rarely observed in SLE, it is one of the most severe clinical situations (Wang et al., 2016). The mortality rate appears to be higher than in lupus without pancreatic involvement (Alina et al., 2021), which is also attributable to other associated systemic disorders, as in our study, where we observed eleven deaths, two of which were complicated by MAS, and one by Gayet Wernick syndrome. In order to avoid such major complications, some authors insist on the importance of systematic screening for acute pancreatitis (AP), for early diagnosis and treatment (Makol and Petri, 2010; Breuer et al., 2006).

Conclusion

Acute pancreatitis is a relatively rare complication of SLE, usually occurring in the course of severe, relapsing lupus disease and associated with severe visceral damage such as renal and neurological involvement. Lupus etiology is difficult to prove. Improvement under specific treatment is the key to incriminating lupus. The disease is generally corticosteroid-sensitive, but the severity of the initial symptoms can lead to early death.

Conflicts of Interest: The authors declare that they have no ties of interest.

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