An 18-year old female was diagnosed in 2003 with lupus enteritis on basis of acute abdominal complaints and a typical target image (small bowel wall edema with abnormal bowel-wall enhancement) on abdominal CT-scan. At that time she received prednisolone 5 mg and HCQ 400 mg on a daily basis as she had been diagnosed with lupus 2 years earlier based on cutaneous involvement, cytopenia, and presence of antinuclear antibodies with positive search for anti-dsDNA antibodies. She was administered IV methylprednisolone with rapid improvement. She was recently reevaluated for recurrent abdominal pain and nausea. Physical examination on admission was unremarkable. Biology showed a lupus anticoagulant (without history of thrombosis or abortion), positive ANA and ds-DNA without other signs of active SLE (SLEDAI 1). A CT scan was normal. Treatment was unchanged. No recurrence could be objectified until present.

A 31 year-old female had been diagnosed with lupus in 2000 when she presented with arthritis, malar rash, pericarditis, positive ANA and ds-DNA antibodies. In 2006, she developed acute abdominal pain with nausea and vomiting. At that time, her daily treatment consisted of prednisone 10 mg per day and HCQ 400 mg per day. She presented no clinical signs of lupus activity (SLEDAI 3). An abdominal CT-scan revealed small bowel edema with target sign. She received IV methylprednisolone (1 g per day for 2 days) and tapered oral prednisone, with prompt clinical and radiological recovery (the follow-up CT-scan at 10 days was normal). However, she presented a similar episode 8 months later while on prednisone 5 mg per day and HCQ. She was again administered IV methylprednisolone (1g per day for 3 days), and a long-term treatment with MMF 2 g per day was initiated. MMF was halted in 2008 because of a pregnancy wish, with no recurrence of lupus enteritis until present.

A 47 year-old female, diagnosed with SLE at the age of 43, was admitted in 2007 with anorexia, weight loss and a 1-month history of asthenia, intermittent fever, nausea, vomiting and arthralgia. In this patient, SLE was diagnosed based on a history of arthritis, oral ulcers, lupus nephritis, and presence of antinuclear antibodies with positive search for anti-dsDNA antibodies. At admission, her abdomen was mildly tender. Relevant biology results included lymphocytopenia (1472/mm³), positive antinuclear antibody (ANA) at 1:1600, highly elevated anti ds-DNA (> 300 U/mL, normal range 0–27 U/mL), low serum albumin (28 g/L), normal C3 complement fraction (0.78 g/L, normal range: 0.72-1.39 g/L), low C4 (0.09 g/L, normal range; 0.15-0.32 g/L) and CH50 (63%, normal range: 70-130%), increased proteinuria (2.25 g/L) with normal creatinine value, and suppressed TSH; C-reactive protein (CRP) were normal, antiphospholipid (aPL) antibodies were negative. She was diagnosed with SLE flare with class III + V lupus nephritis and associated Graves hyperthyroidism. The Systemic lupus erythematosus disease activity (SLEDAI) score was 19. She was started on IV methylprednisolone (1g per day for 3 days) and a concomitant first dose of IV cyclophosphamide (CYC) was administered, followed by oral prednisone (1 mg/kg/day). Four days later, she developed acute abdominal pain and vomiting. Abdominal CT-scan revealed thickened wall with target sign of the terminal ileum, ascites and peritoneal enhancement after intravenous (IV) contrast (Figure 1). Concomitant lupus enteritis was diagnosed and IV methylprednisolone was resumed (40 mg per day). Abdominal pain disappeared over the next three days and oral prednisone could be reinstated six days later. She further received 11 monthly cycles of CYC (IV 750 mg/m²) for lupus nephritis. Finally, she regained weight and on maintenance therapy with hydroxychloroquine (HCQ) 400 mg per day, mycophenolate mofetil (MMF) 2 g per day and oral prednisone slowly tapered to 5 mg per day no recurrence of abdominal pain was observed until present (December 2011).

In 2008, a 27-year old female was transferred because of severe generalized edema that developed 1 month after delivery at 35 weeks of a healthy girl. In this patient, diagnosis of SLE was based on arthritis, cytopenia, and presence of antinuclear antibodies with positive search for anti-dsDNA antibodies. She had been also diagnosed with class V lupus nephritis in 2007 and treated with MMF and cyclosporine that were interrupted 3 months later because of pregnancy. On admission, she was on prednisone 10 mg per day. She presented predominant abdominal complaints with pain and diarrhea. Physical examination revealed bilateral leg edema and tender abdomen. Biology showed leukopenia with neutropenia (560/mm³) and heavy proteinuria (30 g/L). She had active lupus (SLEDAI 10). Her abdominal CT-scan showed edema of the proximal jejunum with target sign and moderate ascites. Treatment consisted of IV methylprednisolone 1 g per day for 3 days, tapered oral prednisone 0.5 mg/kg and long-term HCQ 400 mg per day and MMF 2 g per day with no relapse until present.

A 28 year-old woman presented in 2008 with a 2-day history of abdominal pain, diarrhea and vomiting. At that time she received low dose corticosteroids (5 mg/day of prednisone), HCQ and Coumadin on a daily basis. She was diagnosed with SLE based on arthritis, serositis, cutaneous involvement, and presence of antinuclear antibodies with positive search for anti-dsDNA antibodies and aPL syndrome at the age of 18 when she presented pulmonary embolism and lupus anticoagulant was detected. Biology was notable for low CH50 and C3 complement levels and INR 4.2. An abdominal CT revealed intestinal edema with target sign and moderate ascites without mesenteric thrombosis. She received 1000 mg IV methylprednisolone for 3 days, with rapid improvement. Because she presented 2 similar episodes over the next 6 months a treatment with MMF and later AZA was installed, however she continued to present chronic intermittent abdominal pain and diarrhea. Multiple repeat imaging and extensive abdominal workup were normal. She is currently treated with HCQ, low dose steroids (5 mg/day of prednisone) and Coumadin and continues to present sporadic abdominal discomfort.

A 28-year-old woman presented in 2008 with abdominal pain and vomiting. She was diagnosed with SLE 10 years before because of arthritis, lupus nephritis, and presence of antinuclear antibodies with positive search for anti-dsDNA antibodies. She had trouble with compliance and she was not regularly taking medication for the last two years. In retrospect, she mentioned a similar episode 1 year before which had been successfully treated with oral steroids. Biology was remarkable for low complement, lymphocytopenia and significant proteinuria. Abdominal CT revealed small bowel edema with target sign. She was treated with IV methylprednisolone 1 g/day for 3 days with rapid improvement. Oral prednisolone was rapidly tapered and daily HCQ was added. She was subsequently lost for follow up.

A 48-year-old woman presented in 2010 with a two-day history of abdominal pain and vomiting. She was on daily low dose corticosteroids and HCQ. She had been diagnosed with SLE 2 years before, when she presented with arthritis, cutaneous involvement, cytopenia, and presence of antinuclear antibodies with positive search for anti-dsDNA antibodies. Physical examination was remarkable for abdominal guarding and extensive livedo reticularis. Biology revealed low complement but no argument for hemolysis. Abdominal CT showed edema with target sign of the proximal ileum. She received prednisone 2 mg/kg/day with rapid improvement. Daily MMF was added a few months later, when she presented a severe cutaneous flare because it was felt at that time that she would benefit from additional immunosuppressive therapy as a manner to better control disease activity. She had no recurrence of abdominal pain until present.

Including the 7 new cases, 150 patients (111 women; 8 men, 31 not mentioned) fulfilling our inclusion criteria for lupus enteritis have been reported in the literature 1 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 . Mean age at diagnosis of lupus enteritis was 32.5 years, the youngest patient was 13 and the oldest was 72 years old. Male–female ratio was 1/14. In 19 of the 146 (13%) patients in whom this information was available, SLE was diagnosed simultaneously with the first episode of enteritis. Two patients presented enteritis before diagnosis of SLE 14 20 ; one presented a necrotizing vasculitis of the ileum 1 month before diagnosis of SLE, another had lesions in the small intestine on capsule endoscopy 4 months before diagnosis of SLE. When patients were already diagnosed with SLE (n = 126), median time from SLE diagnosis to first episode of enteritis was 60 months (range: 5 months to 20 years).

The most frequent symptoms were focal or diffuse abdominal pain (146/150; 97%), ascites (71/91: 78%, clinical or radiological), nausea (36/74; 49%), vomiting (31/74; 42%), diarrhea (24/74; 32%) and fever (15/74; 20%) (Table 2). A surgical abdomen with guarding and rebound was found in 33/105 cases (31%). Four patients had clinically evident digestive bleeding. Fifty-three patients (35%) had other clinical features of active SLE, including lupus nephritis (n = 37), serositis (n = 15), neuropsychiatric manifestations (n = 11), rash (n = 8), arthritis (n = 6), oral ulceration (n = 4) and recent alopecia (n = 1). One patient had concomitant HSV esophagitis that was treated with Acyclovir 46 . The mean SLEDAI score was 14.6 (range: 3–19) for the 64 patients in whom this data was reported. When a long-term treatment for SLE was reported (89 cases), patients were on low dose corticosteroids (median dose of equivalent prednisone: 10 mg per day, range 5–15 mg); five patients were on HCQ while they presented the first episode of enteritis. Two patients (with known lupus) developed enteritis shortly after delivery 26 . No patients presented concomitant pancreatitis and enteritis. None of the patients exhibited signs of concurrent cutaneous vasculitis.

None of these features are specific. ANA: antinuclear antibodies; Ds-DNA: Double stranded DNA; CRP: C-reactive protein; Target sign: Abnormal bowel wall enhancement; Comb sign: Increased number of visible mesenteric vessels.

When relevant laboratory data were available (n = 48), patients presented hematological anomalies including anemia (52%) (3 had a positive Coombs test), leukocytopenia and/or lymphocytopenia (40%) and thrombocytopenia (21%). Median C-Reactive Protein (CRP) value (reported in 16 cases) was 2.0 mg/dL (range 0–8.2 mg/dL). Hypocomplementemia was reported in 30 of 34 cases (88%). When autoimmune profile was discussed (n = 94), ANA were positive in 92% and ds-DNA in 74%. Anti-RNP was positive in 28%, anti-SSA in 26% and anti-Sm antibodies in 24%. When urinary analysis was mentioned (n = 43), significant proteinuria (>0.5 g/24 h or ++ on dipstick) was present in 47%. Mean serum protein was 5.7 g/dL (17 patients). One patient had renal failure 43 ; another had elevated transaminases and amylase 29 . Positive aPL antibodies were detected in 25/84 patients (30%). Seven patients fulfilled diagnostic criteria for the aPL syndrome. One patient had cryoglobulin 31 (type not mentioned); no patient had positive ANCA reported. When analyzed (n = 9), ascites was a sterile exudate, unless perforation had occurred (1 case) 14 .

Abdominal CT scanning was performed in 132 of 150 patients (88%). Other imaging modalities included plain or contrast enhanced abdominal X-ray (22/150 patients, 15%), abdominal echography (10/150, 7%) and mesenteric angiography (5/150, 3%). One patient was diagnosed with lupus enteritis on capsule endoscopy. All patients underwent small bowel imaging using at least one imaging modality. Therefore, in all patients lupus enteritis was diagnosed on the basis of a confirmed diagnosis of SLE, and on both clinical and radiological signs of lupus enteritis, by one or more of the available imaging modalities. The most frequent radiographic anomalies (repeat imaging on recurrence included) were bowel wall edema (161/176, 91% of all episodes; 151/159, 95% of CT images), abnormal bowel-wall enhancement (double halo or target sign) in 68/96 (71%) and dilatation of bowel lumen in 43/176 (24%). Ascites was observed in (71/91, 78%). Mesenteric abnormalities such as engorgement of mesenteric vessels, increased number of visible vessels (comb sign), and increased attenuation of mesenteric fat were present in 68/96 (71%). No patient had evidence for mesenteric thrombosis on CT. One patient presented diminished mesenteric blood flow on angiography, linked by the authors to histologically confirmed small vessel vasculitis 15 . Seventeen percent had digestive endoscopy (25/150), with normal macroscopic findings in 60%. One patient underwent capsule endoscopy, revealing multiple small ulcers and scars 20 . When the distribution of intestinal involvement was detailed, jejunum and ileum were the most frequent implicated segments (83 and 84% respectively), followed by colon (19%), duodenum (17%) and rectum (4%). Four percent (6/150) of patients developed pneumatosis intestinalis. Eight patients presented urinary bladder wall edema (lupus cystitis) concomitant with enteritis, which was linked to an associated hydronephrosis in five.

Thirty-four patients underwent biopsy, either endoscopic or surgically. Macroscopic findings were described as segmental areas of edematous (n = 8), hyperemic (n = 2) or ischemic (n = 1) bowel with or without ulceration (n = 5), necrosis (n = 3), wall thinning (n = 2) or perforation (n = 1). Two patients had white nodules or plaques on the peritoneal surface 31 47 . Microscopic findings included cellular infiltration of the submucosal (n = 2) and muscular (n = 2) layers with or without edema (n = 3) or vasculitis. Hemorrhage was present in the muscular and subserosal layers in 2 cases. Nine patients 1 11 12 15 16 18 29 37 , 48 who underwent biopsy had straightforward histologic vasculitis (26% of biopsies, 9/150, 6% of population), confirmed exclusively on laparotomy. Vasculitis has been characterized as necrotizing vasculitis with fibrinoid necrosis (n = 5), with panmural (n = 1) predominant eosinophilic (n = 2), neutrophilic (n = 1) or mixed (n = 1) infiltrate. Vessels in submucosal (n = 6), muscular (n = 4) and serosal (n = 3) layers as well as mesenteric vessels (n = 2) were affected. Both arterioles and venules (n = 1) could be affected or in contrast a pattern of involvement of veins and venules with sparing of arteries (n = 1) was reported. One patient had vasculitis of the polyarteritis nodosa type (medium size vessels). Microvascular thrombus formation was reported in 3 cases 14 16 47 . One of these patients had aPL antibodies (low positive anticardiolipin); none had diagnostic criteria for the aPL syndrome 49 . Other findings included complement deposition on immunofluorescence in intestinal veins and basement membrane (n = 1) 48 .

Detailed treatment is shown in Additional file 1: Table S1. All patients received corticosteroids as initial treatment, either intravenous (IV) or oral (PO). IV corticosteroids (122/141, 87 %) in form of methylprednisolone were administered in doses ranging from 40 mg per day over 1 mg/kg per day to 30 mg/kg per day in a fatal pediatric case 19 . Average duration of IV treatment was 4 days, ranging from 1 to 34 days, commonly until clinical improvement was obtained. When oral steroids were chosen as initial treatment (19/141 13%), prednisolone was delivered in doses ranging from 20 mg per day to 2 mg/kg per day, tapered over several weeks to months to a median daily maintenance dose of 5 mg (range 5–20 mg). Ninety-four (141/150) percent of patients received corticosteroids alone. Additional immunosuppression on initial treatment (n = 11) consisted of PO (n = 1) or IV cyclophosphamide (CYC) at 500 mg/m² to 750mg/m². This was justified by concomitant severe organ involvement in 5 (central nervous system involvement in 2 32 43 , lupus nephritis in 3 18 47 ), associated intestinal necrosis in 4 12 19 29 35 37 and persistent abdominal pain despite of IV steroids in one patient 12 . Seventeen patients underwent laparotomy, of which 10 (7%) had resection for necrosis or perforation.

Relief of symptoms took typically less than a week (range: 2 days to 8 weeks), with parallel biological and radiological normalization. Long-term maintenance therapy after a first episode (other than prednisolone) consisted of HCQ (n = 7), MMF (n = 3), azathioprine (AZA) (n = 2) and oral chlorambucil (n = 1).

Recurrence, i.e. more than one episode of enteritis, was reported in 34 patients (23%) with a median number of 3 episodes (range: 2–9). When we considered patients with reported observance of at least 1 year (n = 30), recurrences occurred in 25%. On recurrent episodes, corticosteroids were used similar to first episodes. Additional immunosuppression consisted of IV CYC (n = 4) 1 25 43 44 , MMF (n = 4) 25 34 44 , AZA (n = 4) 25 34 43 , Rituximab (n = 2) 34 44 and PO CYC (n = 1) 34 . Declared morbidity included short bowel syndrome with home total parenteral nutrition (n = 1) 37 , recurrent abdominal bloating and dyspepsia (n = 1) 25 and recurrent abdominal pain without imaging abnormalities (n = 2). Four patients died after a median follow-up of 18 months, yielding a mortality rate of 2.7%. Reported causes of death included diffuse necrosis of intestinal tract (n = 1) 14 , associated neurologic complications (n = 1) 11 and sepsis (n = 1) 19 .