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Revista Española de Enfermedades Digestivas

versión impresa ISSN 1130-0108

Rev. esp. enferm. dig. vol.101 no.8 Madrid ago. 2009




Pancreatitis and systemic lupus erythematosus

Pancreatitis y lupus eritematoso sistémico



J. Lariño Noia, F. Macías García, S. Seijo Ríos, J. Iglesias García and J. E. Domínguez Muñoz

Gastroenterology Department. University Hospital of Santiago. Santiago de Compostela. A Coruña, Spain





Gastrointestinal symptoms in patients with SLE are common, specifically abdominal pain. However, the rate of pancreatic diseases is much lower and does not reach 5% according to published series in Europe and the USA. This association between SLE and pancreatic disease is basically at the expense of episodes of acute pancreatitis. An association with chronic pancreatitis is much more uncommon, and only four articles have been published showing this relationship.
Three cases of SLE-associated pancreatitis are described, and disease onset, etiological factors, and clinical progression are analyzed. A review of the literature and a brief discussion about pathophysiological mechanisms and the role of corticosteroids are also included.

Key words: Systemic lupus erythematosus. Acute pancreatitis. Chronic pancreatitis.


Los síntomas gastrointestinales en los pacientes con lupus eritematoso sistémico (LES) son comunes, específicamente el dolor abdominal. Sin embargo la tasa de enfermedades pancreáticas es mucho menor, una tasa que no alcanza ni al 5% según las series publicadas en Europa y EE. UU. Esta asociación entre enfermedades pancreáticas y LES es fundamentalmente a expensas de episodios de pancreatitis aguda. La asociación con pancreatitis crónica es muchísimo más infrecuente, teniendo en cuenta que tan sólo cuatro artículos han sido publicados reflejando esta asociación.
Describimos tres casos de asociación entre pancreatitis y LES, analizando el debut de la enfermedad, los factores etiológicos y también la evolución clínica. Hemos realizado, además, una breve discusión de la fisiopatología y del papel de corticosteroides, así como una revisión de la literatura.

Palabras clave: Pancreatitis aguda. Pancreatitis crónica. Lupus eritematoso sistémico.



Since the first association between systemic lupus erythematosus (SLE) and pancreatitis was documented by Reifenstein et al. in 1939 (1), very few reports about the prevalence of pancreatic diseases in this rheumatologic disorder have been reported.

Gastrointestinal symptoms in patients with SLE are common, specifically abdominal pain; as described in some series, it has been shown to have a prevalence of 19.2% (2). The rate of pancreatitis in patients with SLE varies depending on individual series from Europe and the United States between 0.7 and 4% (3,4). This association is mainly at the expense of acute episodes of pancreatitis; however only four reports have been published regarding this relationship with chronic pancreatitis (5-7).

Three cases of SLE-associated pancreatitis are described, and disease onset, etiological factors and clinical progression are analyzed. A review of the literature and a brief discussion about the pathophysiological mechanisms and the role of corticosteroids are also included.



A retrospective review of hospital admissions at Gastroenterology Department, University Hospital, Santiago de Compostela during 2001-2005 with the dual diagnosis of systemic lupus erythematosus and pancreatitis was made. Demographic data, clinical intervention, and progression parameters of pancreatic disease were identified.

These patients were collected by searching our institution's computer database using the key words "pancreatitis" and "SLE". Demographic information registered from the medical charts included subject age, gender, time (years) from the initial diagnosis of SLE, alcohol abuse, medications, specially corticosteroids, and criteria used for SLE diagnosis.

Clinical data collected included symptoms, SLE activity with a list of organs or systems involved, initial pancreatic enzymes, number of admissions for pancreatitis, and serologies for antinuclear antibodies (ANA) and C-reactive protein levels. All radiological results were documented, including abdominal ultrasounds, helical CT, cholangiopancreatic resonance (MRPC), endoscopic retrograde cholangiopancreatography (ERPC), and endoscopic ultrasounds (EUS). Complications related to acute pancreatitis, mode of therapy and progression of disease were also noted.


Case report 1

A 39-year-old female previously diagnosed with Raynaud syndrome, Buerger's disease, femoral head avascular necrosis and SLE at the age of 27, with hematological (anemia, leukopenia, low complement levels), immunological (ANA, anti-DNA+, anticardiolipin+, anti-Ro+, anti-La+), articular, and cutaneous-mucosal (discoid lupus, Raynaud phenomenon, small-vessel vasculitis) activity.

The medication received until that moment was prednisone, amlodipine, cloroquine, omeprazole, calcium, aspirine, alprazolam, and transdermal fentanyl. She had no toxic habits. There was no cause-effect relationship, and there were no signs of lupus disease activity. Main symptoms included abdominal epigastric pain accompanied by nausea and vomiting. Lipase: 970 IU/L (normal through 295 IU/l), amylase: 168 IU/L, GOT: 10 IU/L, GPT: 9 IU/L, GGT: 26 IU/L, AP: 186 IU/L, bilirubin: 0.2 mg/dl, VSG: 79 mm, Hb: 12.5 g/dL, WBCs: 6230/mm3 (70% PMNs), TG: 115 mg/dL, ANA+: 1/80. There was no evidence of biliary disease on abdominal ultrasounds. On CT scans an acute fluid collection in the pancreas tail seems possible. She was finally diagnosed with a first episode of mild acute idiopathic pancreatitis with a good clinical outcome after with hydroelectrolytic replacement and analgesic administration.

A month after this event another episode of abdominal pain similar to the previous one but without hyperlipasemia (293 IU/l) took place; CT revealed the presence of several large pseudocysts on the pancreatic body and tail as a result of the previous event, which resulted in external compression of the stomach on upper endoscopy. Therefore, an endoscopic ultrasonogram was performed that identified large pseudocysts in the body of the pancreas; however, there was no distortion on parenchymal or ductal structures suggestive of chronic pancreatitis. ERCP confirmed that there was no communication of cysts with the main pancreatic duct; moreover, it also showed the normal appearance of the main and secondary pancreatic ducts. After conservative management the patient was discharged in a few days, with a normal clinical follow-up. A CT scan was performed six months after the first episode, which showed a decrease in cyst size.

After several months, an amputation of the left foot was performed because of necrotic lesions secondary to vasculitis. In the postoperative period she developed severe abdominal pain and distension, with gas-liquid levels on abdominal radiograms and important dilatation of the ascending colon. Because of her clinical worsening and after visualizing on CT scan signs of cecal perforation, the patient was operated upon (right hemicolectomy with ileostomy and mucosal fistula). However, the patient died a few days afterwards as a result of abdominal sepsis.


Case report 2

A 30-year-old female allergic to rifampicin. She had anorexia nervosa and an appendectomy during childhood. Diagnosed at the age of 23 with SLE, within the third term of pregnancy, with serological (ANA+, anti-DNA+, anti-SM+, anticardiolipin+), hematological (autoimmune thrombopenia, anemia, leukopenia, lymphopenia), articular, and cutaneous-mucosal (lupus pernio, malar rash, cutaneous acute lupus, Raynaud syndrome) activity. She also had a history of acute hepatitis (presumably by azathioprine), miliary tuberculosis, and upper gastrointestinal bleeding from a Mallory-Weiss syndrome.

Her first episode of acute pancreatitis was at the age of 24, in correlation with an admission for lupus activity (hematological manifestations) with high levels of transaminases (GOT/GPT 404/291 IU/L), GGT 424 IU/L, AP 421 IU/L, total bilirubin 0.5 mg/dl) ANA+ 1/100, and antiDNA+, considered by physicians within the context of a lupus flare-up (at that moment the patient was azathioprine-free, under treatment with prednisone and cloroquine, and later with cyclophosphamide bolus). She had withdrawn from alcohol but not from tobacco. After six days in hospital she developed severe abdominal pain and biochemical abnormalities consistent with acute pancreatitis: lipase 13706 IU/l, amylase 3124 IU/l, GOT 393 IU/L, GPT 185 IU/L, GGT 478 IU/L, AP 632 IU/L, total bilirubin 2.3 mg/dl, TG 237 mg/dL, Ca 7.8 mg/dL, albumin 3.9 mg/dl, leukocytes 3780 (86% PMNs, 10% lymphocytes), and CRP 0.45 mg/dl. There was no evidence of biliary disease on abdominal ultrasounds. On CT a pancreatic head enlargement with no necrosis was seen, as well as bilateral pleural effusion and massive ascites (ascitic fluid amylase was 6644 mg/dl, 3280 cells with PMN predominance, and 3.3 g of protein). After conservative treatment and empiric antibiotic therapy with imipenem the patient recovered with no complications. She was finally diagnosed with acute mild idiopathic pancreatitis according to the Atlanta classification.

Four years later she developed a second episode of acute pancreatitis (in this case and in the following one with no correlation with a lupus flare-up). At this moment the patient was on prednisone, methotrexate, cloroquine, NSAIDs and lansoprazole. Lipase levels were of 2,532 IU/l, amylase 715, GOT 8 IU/L, GPT 13 IU/L, GGT 55 IU/L, AP 167 IU/L, total bilirubin 0.5 mg/dL, TG 192 mg/dL, VSG 24 mm, CRP 1.44. Once again abdominal ultrasounds did not reveal any biliary abnormality. This event was considered mild AP with idiopathic etiology despite the fact that two weeks before two medications had been introduced: methotrexate and an NSAID. With the recommendation of avoiding any potential pancreatotoxic medication the patient was discharged and followed up in our outpatient unit.

Three months later she was readmitted with a third episode of AP. An endoscopic ultranosonogram was then obtained. A small pseudocyst in the pancreas tail and echoendoscopic criteria for chronic pancreatitis (hyperechoic foci and strands with lobularity of the parenchyma with an irregular hyperechogenic wall in the main pancreatic duct) could also be observed (Fig. 1). These results were confirmed with a cholangiopancreatic MRI scan using secretine and gadolinium (Fig. 2).


On the subsequent six months the patient developed another three events of acute pancreatitis, all of them mild and idiopathic, with a normal reduction in pseudocyst size.

The patient is now asymptomatic and on outpatient follow-up, with no signs of exocrine (triglycerides-mixed 13C test) or endocrine (HbA1c in normal levels) insufficiency.


Case report 3

A 34-year-old female diagnosed with SLE at the age of 16, with mainly cutaneous (malar rash, lupus pernio, calcinosis cutis), hematological (anemia, thrombopenia, leucopenia), immunological (ANA+, anti-DNA+, anticardiolipin+), serosal (pleuropericarditis), articular, and renal (proliferative glomerulonephritis type III of WHO) involvement.

At the age of 32 she was admitted for a lupus flare-up (leukopenia and lymphopenia, ANA+ 1/640, anti-DNA+, anti-SM+, anticardiolipin+). She was under treatment with prednisone, cloroquine, pentoxiphiline, and omeprazole. She had never drunk or smoked. During admission she developed fever and oropharyngeal candidiasis, with leukopenia and lymphocyte levels below 200/mm3, reason why fluconazole (good response) and P. carinii prophylaxis with trimethoprim-sulfamethoxazole (TMP-STX) were introduced. After 72 hours from treatment onset she complained of abdominal pain and developed biochemical alterations compatible with AP: lipase 2139 IU/l, amylase 534, GOT 67 IU/L, GPT 195 IU/L, GGT 661 IU/L, PA 169 IU/L, total bilirubin 0.39 mg/dL, Ca 8.7 mg/dL, CRP < 0.4, VSG 45 mm, TG 474 mg/dL, 11.7 g/dL hemoglobin, 4740 leukocytes (90% PMNs, 8% lymphocytes). Abdominal ultrasounds did not show any biliary abnormalities. CT showed small areas of focal edema, and acute fluid collections next to the pancreas tail, in the paracolic space and in the pararenal left anterior space. TMP-STX was discontinued and the patient recovered in a few days with conservative treatment and empiric antibiotherapy based on imipenem. She finally was diagnosed with acute mild idiopathic pancreatitis, according to the Atlanta classification and APACHE-II score, and possible etiological factors considered included treatment with sulfamides and high-level triglycerides (never previously documented and probably related to parenteral nutrition).

Discharged from hospital and classified as idiopathic pancreatitis, an echoendoscopy was made. In this exploration signs of chronic pancreatitis were observed (lobular pattern with hyperechoic foci and strands, and an irregular pancreatic duct with hyperechogenic wall). However no signs of exocrine (triglyceride-mixed 13C test normal) or endocrine (HbA1c normal) insufficiency were present. Moreover, nutritional parameters such as retinol-binding protein (RBP) and prealbumin were within normal ranges.

The patient is now asymptomatic with normal oral intake and on follow-up in our outpatient pancreas unit. A pancreatic cholangioresonance supported echoendoscopic results.



Despite the fact that the association between SLE and acute pancreatitis is well known (8), just four cases in the literature report chronic pancreatic disease in association with SLE. In our small series two patients were diagnosed with this disorder - one diagnosis was made MRCP and EUS, and both cases were suspected using the latter exploration, which highlights the importance of this procedure in the context of pancreatic diseases of unknown etiology (9). Case 2 is recurrent acute pancreatitis that finally led to the development of chronic pancreatitis, supporting Whitcomb's SAPE hypothesis (10). These two cases could be considered as early chronic pancreatitis, since none of them had calcifications or developed exo-endocrine pancreatic insufficiency, and were free of pain during outpatient follow-up.

Another point of discussion is related to the fact that the disease could appear in the context of a generalized flare-up or during a quiescence period. Indeed, some reports consider it an initial presentation of SLE (11). In our experience all forms of presentation are possible, but just one woman had the disease during an SLE flare-up. None of them were first presentations.

The pathogenic mechanism responsible for pancreatic damage in SLE awaits definition, but vascular damage as a cause has been stressed. This includes necrotizing vasculitis syndrome (12), occlusion of arteries and arterioles by thrombi resulting from severe hypotension or antiphospholipid syndrome (13,14), intimal thickening/proliferation (15), and immune complex deposition with complement activation in the wall of pancreatic arteries (16). None of our cases had antiphospholipid syndrome but perhaps case 1 is the clearest evidence of vascular involvement, considering the amount of vascular complications she had, one of them leading to her death. Moreover, despite the contribution of the immune system to pancreatic disease, these cases cannot be considered autoimmune pancreatitis per se, as they do not fulfill many international criteria for this well-documented disease (17).

Although common causes of pancreatitis such as biliary disease, alcohol abuse, or hypertriglyceridemia can occur in SLE patients, they have not appeared in our series. Other reports notice the possibility of drug toxicity (as we discuss below) or viral infection in an immunodepressed context (18).

Many SLE patients are on steroids, diuretics or immunosuppressive therapy, all of which have been implicated in the etiology (19). The role of corticosteroids is difficult to ascertain due to the natural coexistence of disease activity with high doses of prednisone (20). Initial studies support the negative effect of this drug on pancreatic disease, leading to considering corticoids as possibly related to acute pancreatitis (21,22). However, Saab et al. (23) published a series of 8 SLE patients with inactive disease whose AP episodes improved biochemically and clinically with an increase in corticosteroid doses. From this idea, and concerning our case series, in which the patients were on steroids in most cases, we support the therapeutical effect of this drug in the global context of the disease.

In our first case the AP episode started three days after an epoprostenol bolus injection, a prostaglandin analogue used as vasodilator in other diseases such as arterial pulmonary hypertension; by this fact, and the absence of previously documented cases, the potential association of the drug with pancreatic involvement is not considered.

In opposition to previous reports concerning the severity of SLE-AP episodes (24,25), and excluding pseudocysts as Atlanta criteria of severity, all cases reported were mild as noted from hospital stays and short recovery periods without intensive treatment measures. It is also important to take into account the recurrence of admissions of case 1 without fitting acute pancreatitis diagnosing criteria, with a clinical presentation of abdominal severe pain with normal values of pancreatic enzymes, pointing to the high incidence of gastrointestinal symptoms in SLE patients.

In summary, SLE is a known and infrequent cause of pancreatic disease in which a vascular mechanism is supposed to be involved in the pathogenesis. Corticosteroids do not seem to be involved in the development of the disease. Although the most common presentation is acute pancreatitis, the possibility of chronic disease is also important, pointing to the importance of high suspicion and the usefulness of imaging procedures such as EUS to achieve an early diagnosis.



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José Lariño Noia.
Servicio de Aparato Digestivo. Hospital Clínico Universitario de Santiago.
C/ Choupana, s/n. 15706 Santiago de Compostela. A Coruña, Spain.

Received: 19-01-09
Accepted: 22-01-09.


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