|Ahead of print publication
Pancreatitis in systemic lupus erythematosus: Clinical characterization and outcome analysis in concurrent pancreatitis and lupus
Sheba Charles, Benzeeta Pinto, Vineeta Shobha
Department of Clinical Immunology and Rheumatology, St. John's Medical College, Bengaluru, Karnataka, India
|Date of Submission||14-Oct-2020|
|Date of Acceptance||14-Nov-2020|
Department of Clinical Immunology and Rheumatology, St. John's Medical College, Sarjapur Road, Bengaluru - 560 034, Karnataka
Source of Support: None, Conflict of Interest: None
Objective: Pancreatitis in systemic lupus erythematosus (SLE) continues is an often under-diagnosed entity with high morbidity and mortality. The objective of this case series is to study the demographics and outcomes of lupus pancreatitis and to compare with available medical literature.
Materials and Methods: Records of SLE patients admitted in our hospital between January 2012 and May 2018, were examined retrospectively. Clinical and laboratory parameters of the patients who were diagnosed with SLE and pancreatitis were obtained and analyzed.
Results: The prevalence of pancreatitis in our cohort was 1.33% with 77% female preponderance. All the patients presented within 3 years of lupus onset. Pancreatitis was often associated with other disease manifestations of SLE and the mean Systemic Lupus Erythematosus Disease Activity Index 2K score at presentation was 17.4 ± 7.82. None of the patients were positive for APLA antibodies. All our patients were treated with high-dose steroids and other immunosuppression as indicated for concomitant disease activity. Complications were seen in only one patient who eventually succumbed to the disease.
Conclusions: Pancreatitis in SLE is associated with disease activity. High index of suspicion, early diagnosis, and institution of steroids and immunosuppressive therapy lead to a good outcome.
Keywords: Disease activity, pancreatitis, systemic lupus erythematosus
|How to cite this URL:|
Charles S, Pinto B, Shobha V. Pancreatitis in systemic lupus erythematosus: Clinical characterization and outcome analysis in concurrent pancreatitis and lupus. Indian J Rheumatol [Epub ahead of print] [cited 2021 Jun 18]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=313580
| Introduction|| |
Pancreatitis associated with systemic lupus erythematosus (SLE) is rare, the reported frequency being 0.2%–8.2%, with an annual incidence at 0.4–1.1/1000 patients.,, More than half of SLE-related acute pancreatitis (AP) develop complications if not treated promptly. Nesher et al. reviewed 77 cases and reported a mortality of 3% in patients without complications as compared to 45% in patients with complications. About 22% of patients may experience recurrent acute episodes, whereas 5%–14% develop chronic pancreatitis., The incidence of SLE-related pancreatitis may be underestimated because the isolated elevation of pancreatic enzymes without symptoms, is usually not diagnosed or reported. It is estimated that 30.5% of SLE patients have asymptomatic hyperamylasemia. The significance of asymptomatic hyperamylasemia in lupus is unclear. The pathogenic mechanism of SLE-related pancreatitis is not well explained, although vascular damage has often been postulated as an important factor. Necrotizing vasculitis, occlusion of arteries, and arterioles by thrombi resulting from severe hypertension or antiphospholipid syndrome, intimal thickening and proliferation, and immune complex deposition with complement activation in the wall of pancreatic arteries have been postulated. In this case series, we reviewed the clinical manifestations and treatment of nine patients of SLE-associated pancreatitis and their outcome.
| Materials and Methods|| |
Retrospective record review was performed for SLE patients who were admitted with pancreatitis to St. John's Medical College and Hospital, during the period of 2012–2018. SLE was diagnosed as per the systemic lupus international collaborating clinics 2012 revised criteria. A diagnosis of AP was established in accordance with the American gastroenterological association (AGA) 2018 guidelines; by the presence of typical clinical symptoms and >3-fold elevation of serum amylase or lipase or evidence of computer tomography (CT) scan or ultrasonography imaging findings. The severity of pancreatitis was assessed using the Bedside Index of severity in Acute Pancreatitis (BISAP) score and Revised Atlanta 2012 score. CT severity index (CTSI) score was documented in patients for whom CT scan of the abdomen was done. Other causes of AP such as mechanical obstruction (choledocholithiasis), toxic-metabolic etiologies (alcohol intake, drugs, hypercalcemia, or hypertriglyceridemia), infection, or trauma were excluded in each case.
Demographic information including the age at onset of SLE, gender, duration between onset of SLE and AP, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score at diagnosis of pancreatitis, presence or absence of confounding factors, clinical symptoms, laboratory findings, medications (especially corticosteroid, and immunosuppressive agents), and outcome were documented. The clinical correlates have been documented as frequencies and percentages and as a geographic mean wherever feasible.
| Results|| |
Nine patients of SLE with pancreatitis were identified from our database of 673 case records of SLE over the study period, accounting for an approximate prevalence of 1.33%. The average age of presentation was 28.78 years (range 19–40), 77% (7/9) being women. Baseline characteristics and lupus manifestations are summarized in [Table 1].
All the episodes of pancreatitis were documented within the first 3 years of diagnosis of SLE, 7/10 at the time of initial diagnosis. The most common presenting symptom was atypical epigastric or nonspecific abdominal pain (100%). Only one patient reported nausea and vomiting. Diarrhea was documented in two and paralytic ileus in one. The mean SLEDAI 2K score was 17.4 ± 7.82 at the time of onset of pancreatitis.
Two patients were on treatment for SLE, before the onset of pancreatitis, which included methotrexate (current use) in one and azathioprine (past use) in another. None had received azathioprine or cyclosporine within the preceding 3 months. Six patients had received steroids during the concurrent episode of pancreatic illness. These are summarized in [Table 2].
During three episodes of pancreatitis, abdominal pain was one of the presenting complaints. The others developed 3–4 days after initiation of high-dose steroid for the other concurrent manifestations of SLE. All our patients received high-dose steroid therapy. However, the short duration of steroid therapy features suggestive of ongoing activity, and exclusion of other etiologies supported the diagnosis of pancreatitis secondary to SLE.
Nine out of the ten pancreatitis episodes were associated with other features of SLE flare, as evidenced by the SLEDAI 2K score. Concomitant lupus features seen, are documented in [Table 1].
The severity of pancreatitis was based on BISAP and modified Atlanta 2012 score. Three patients (cases one, eight, and nine) had a BISAP score >2. Three patients (cases one, four, and six) scored moderate severity on the Revised Atlanta score due to the presence of peripancreatic fluid collection, another (case eight) was scored very severe due to the presence of local complication (pancreatic necrosis) along with persistent (>48 h) organ failure. CT scan of the abdomen could be obtained during eight episodes only. Based on the CTSI score, two patients were graded as moderate severity (score of 4–6) and one patient had severe pancreatitis with a score of 8 [Figure 1]. The one patient who had severe pancreatitis developed refractory hypocalcemia, diarrhea, hemorrhagic pancreatitis, acute respiratory distress syndrome, sepsis (ventilator-associated pneumonia), and succumbed to her illness.
|Figure 1: Contrastenhanced computed tomography of the abdomen showing hypodense, nonenhancing body and tail of the pancreas|
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| Discussion and Literature Review|| |
Pancreatitis in SLE is an extremely rare occurrence with the reported prevalence among the cohort studies, ranging from 0.85% to 3.5%., Female preponderance of SLE pancreatitis parallels to lupus sex preponderance. Majority of the cases manifest pancreatitis within the first few years of diagnosis with SLE. In the retrospective cohort study by Wang et al. all 52 cases of SLE pancreatitis had presented within 1 year of diagnosis with SLE and all of them had concurrent manifestations of active disease. The most common clinical manifestation of pancreatitis reported is abdominal pain (88%), followed by nausea or vomiting (46%). Other less frequent manifestations include diarrhea (9%), loss of appetite and weight loss, and panniculitis (only few case reports). Our patients presented with abdominal pain and either nausea, vomiting, or diarrhea and had a similar frequency of clinical features at presentation. High index of suspicion, early testing of pancreatic enzymes despite atypical clinical manifestations permitted quick diagnosis and institution of appropriate therapy.
There is a definite association between pancreatitis and lupus activity as evidenced by the mean SLEDAI scores documented in all the cohort studies and most of the case reports. Multiorgan involvement is remarkable during the eventual course of illness. Increased frequency of neurological and psychiatry manifestations was documented by Goel et al. and Makol and Petri respectively. This was not replicated in our series of patients. Otherwise, the other organ involvement in our case series (renal involvement 55.56%, serositis 55.56%, arthritis–77.78%, and neuropsychiatric 22.2%), seems to be comparable to that noted in literature.
Nesher et al. reported ANA positivity in 98% and ds DNA in 73%, in their review. Only 33.34% of our patients were positive for dsDNA. All our patients had low complement levels, which helped in diagnosing pancreatitis secondary to SLE. Some of the earlier cohort studies reported low complements too, the range being 55%–100%.,,, Few retrospective series have found association with Antiphospholipid antibodies (APLA). In another study done from South India by Goel et al., 40% association with APLA antibodies was reported.,, However, none of our patients was APLA positive.
The rate of complications in “untreated” pancreatitis is as high as 57%, with mortality of up to 45%, which is higher than those observed in non-SLE populations.,, Local complications include necrotizing pancreatitis, hemorrhagic pancreatitis, and pseudocysts (12%).,, Around 14%–22% showed a chronic course (chronic pancreatitis or recurrences)., Makol and Petri have reported recurrence in 43% of patients with SLE pancreatitis (27/63). Other complications as reported by Nesher et al., include respiratory failure (22%), recurrent pancreatitis (22%), ascites (19%), pleural effusion (18%), acute renal failure (14%), and circulatory shock (12%). In our series, we noted a very low complication rate. The outcome was good in the majority of our patients, probably because of the milder severity of pancreatitis as well as early diagnosis and institution of high dose steroid in addition to conventional supportive treatment. In our cohort, the choice of additional immunosuppressant primarily depended on nonpancreatitis manifestations of lupus and patient preferences.
Medical literature review reveals that nearly 83% of lupus pancreatitis were treated with high dose steroid. The morbidity and mortality seem to be high in cases where the steroid dose was rapidly decreased. Patients on glucocorticoids before the onset of pancreatitis also had a better prognosis in comparison to those who were not.,, In our cohort also, pancreatitis responded well to high dose steroids with a resolution of symptoms as early as 1 day. Evidence does not support the earlier claims that azathioprine and steroid may predispose to or exacerbate pancreatitis in lupus. In a retrospective study by Yang et al., where 40% (11/27) did not receive increased dosage of the steroid, the mortality was 37.04%.
Intravenous immunoglobulins (IVIG) and plasmapheresis were used in some cases associated with severe pancreatitis. Yu et al., in their study, compared the use of plasmapheresis along with steroids versus steroids alone. They concluded that the remission rate was higher (70% vs. 25%; P = 0.024), whereas the total dose of steroid (31 mg/day vs. 47.9 mg/day; P = 0.002) and the need for concomitant antibiotic use (30% vs. 56.3%) were less in the group which received plasmapheresis additionally. This needs to be confirmed in larger studies with a bigger sample size. None of our patients had received IVIG or plasmapheresis.
| Conclusions|| |
Pancreatitis may present as the initial manifestation in a previously undiagnosed case of lupus. It is associated with high disease activity in most patients. Our series of patients predominantly had mild-to-moderate pancreatitis with good outcome, largely attributable to early diagnosis and prompt treatment. There are no guidelines so far on the type, dosage, and duration of steroid to be used in SLE pancreatitis; this needs further study.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]