Systemic Lupus Erythematosus (SLE) is a multi-systemic autoimmune disease characterized by deposition of auto-antibodies and immune complexes in tissues and cells. Onset of the disease in childhood can be insidious with nonspecific symptoms such as fever, malaise, and weight loss or it can be acute with involvement of one or more organs or systems (e.g., kidney, skin, central nervous system, joints, or blood). Gastrointestinal symptoms appear in one third of patients with known SLE during their lifetime but very rarely does the condition present with acute abdomen as the only sign. Differentiating a patient with an acute abdomen secondary to SLE is therefore a real challenge and may be associated with a delay in the correct diagnosis. We describe two pediatric cases of SLE with acute abdomen as the sole presenting sign of the disease.
A 10 year-old-girl was admitted to a district general hospital with severe abdominal pain and fever. Acute appendicitis was suspected, and she had her appendix removed. During the following days abdominal pain and fever persisted. Eight days after surgery she became hypertensive (180/145 mmHg) and oliguric. She was then transferred to our hospital. On admission she was febrile, and the abdomen was tense and tender. Urine output was reduced and the arterial pressure was high (160/100 mmHg). Laboratory tests showed moderate anemia (Hemoglobin 9.7 g/dl) and renal failure (creatinine 1.4 mg/dl) secondary to glomerulonephritis (urine microscopy positive for glomerular erythrocytes and casts). A plain abdominal radiograph revealed air-fluid levels in the bowels. She underwent an emergency laparotomy which revealed purulent peritonitis with necrosis and multiple perforations of the distal ileum and of the cecum. The terminal 40 cm of the ileum together with the cecum were resected. Histological analysis of the surgical specimen showed an inflammatory edema of the intestinal wall with necrotic areas and extensive ulceration, hemorrhage, and arterial thrombosis suggestive of an SLE-like necrotic-hemorrhagic ulcerous vasculitis. Autoantibody screen by immunofluorescence (ANA 1:640 with homogeneous pattern, antiDNA 1:320, C3 70 mg/dl, C4 10 mg/dl) confirmed the diagnosis of SLE. Treatment with prednisone (intravenous 2 mg/Kg/day for 10 days then orally) and cyclophosphamide (intravenous 1.8 mg per Kg for 10 days then orally) was associated with complete remission of the symptoms within three weeks. Since then, the girl has remained asymptomatic albeit with constant positive ANA (from 1:80 to 1: 320) and low C4 (<8 mg/dl). Steroid therapy and immuno-suppressant treatment (initially cyclophosphamide at the same dosage, substituted by azathioprine 1.5 mg per Kg after 10 months) were progressively reduced. Azathioprine was suspended after 4 years and steroid therapy was suspended after 12 years. At 17 years from the onset of SLE the patient is completely well without any treatment.
At the age of 16 years the patient was admitted to our hospital with a 48-hour history of abdominal pain in his right lower abdominal quadrant. He was febrile (40°C), and the abdomen was soft but tender to deep palpation. Blood tests showed positive inflammatory indices (C Reactive Protein 24.4 mg/dl, Erythrocyte Sedimentation Rate 113 mm/hr, White Cell Count 13,700/mm3, Platelets 117,000/mm3). The patient underwent emergency abdominal surgery that revealed an abundant hemorrhagic fluid in the abdominal cavity with a necrotic and perforated appendix, which was removed. The terminal ileum was edematous and inflamed. Over the following two days there were several episodes of gastrointestinal bleeding leading to anemia (hemoglobin decreased from 12.3 g/dl to 8.1 g/dl). Coagulation values were abnormal (International Normalized Ratio 5) with normal liver function tests. There was no significant response to repeated infusion of plasma and blood products. We performed the Lupus-like Anticoagulant test, on the suspicion of a vasculitic process, which proved positive. Further tests confirmed the presence of an ongoing autoimmune process: low complement levels (C3 9 mg/dl, C4 8 mg/dl), positive ANA (immunofluorescence 1:160), positive ANCA (ELISA test: p-ANCA 14.59 IU/ml, c-ANCA 19.14 IU/ml), positive anti-DNA antibodies (ELISA test 130.79 IU/ml), and positive anticardiolipin antibodies (ELISA test:10.87 U/ml). High-dose corticosteroid therapy was started (prednisone 2 mg/Kg/day). Neither a scintigraphy with colloids nor an abdominal computed tomography scan could identify the site of intestinal bleeding. Four days after appendix removal gastrointestinal bleeding was still present. A repeat laparotomy showed edema and dilatation of the terminal ileum and cecum with bleeding from both the mucosal and serosal surfaces. An ileo-cecal resection (40 cm) with direct ileo-colic anastomosis was performed. Histological examination of the resected intestinal specimen showed edema and hemorrhagic infarction of submucosa and mesentery with diffuse vasculitis involving mainly the venules. Small and medium vessels showed mixed inflammatory cell infiltration with polymorphonuclear leukocyte prevalence. A careful history taking revealed that the patient had had a recent transient episode of malar rash, which reappeared following the second surgical intervention. Diagnosis of SLE was made based upon the presence of three diagnostic criteria of the American College of Rheumatology (ANA positive, anti-DNA antibody positive, and malar rash) associated with histologic evidence of SLE vasculitis (1). He was promptly treated with an infusion of cyclophosphamide (1g) and high-dose steroid (prednisone 2 mg/Kg) with rapid and sustained disappearance of intestinal bleeding and fever. Three months later he has received two further intravenous infusions of cyclophosphamide (1 per month) and remission was maintained on a reduced prednisone dosage of 0.8 mg/Kg. His clinical condition is now excellent. Laboratory tests normalized (C3 60 mg/dl, C4 12 mg/dl) and auto-antibodies vanished (ANA, ANCA, anti-DNA, and anticardiolipin antibodies).
Gastrointestinal symptoms in patients with proven SLE are well recognized, and occur in approximately 30% of patients. Among all patients with gastrointestinal symptoms, 75% show signs of vasculitis (2). The severity of clinical presentation of gastrointestinal SLE can vary from moderate gastroenteritis to severe abdominal pain, which can mimic an acute abdomen. Intestinal perforation due to mesenteric vasculitis is considered a severe life-threatening complication. The signs and symptoms of mesenteric vasculitis are not typical and pose a difficult differential diagnosis with several other diseases of the gastrointestinal tract (3). In one of the few studies that has analyzed abdominal complications of SLE, 15 of 140 patients had acute abdomen, 11 underwent an exploratory laparotomy, and, of these, 6 had an intestinal perforation (4). It is, however, much more rare to find SLE presenting with acute abdomen. In a review of SLE patients with vasculitic presentation, only 1 of 540 had acute abdomen as the initial presentation (5). The suspicion that a patient with acute abdominal symptoms might have SLE is rarely raised in patients previously asymptomatic. Standard investigations in this setting rarely investigate the possibility of mesenteric vasculitis. Plain abdominal films and barium contrasts have a low diagnostic yield. Abdominal Computed Tomography scans can only highlight generic signs such as dilated intestinal loops, thickening of the intestinal wall, and ascites. Scintigraphy with technetium-99m is suggestive of gastrointestinal vasculitis in 75% of patients with intestinal SLE but it is not clinically very helpful in that 13% of SLE patients without gastrointestinal symptoms will have the same findings (2). The two patients presented here have had an unremarkable medical history until the onset of acute abdominal symptoms. Both underwent emergency surgery for suspected appendicitis, which proved to be necrotic and perforated with the presence of hemorrhagic peritoneal fluid. Persistence of gastrointestinal symptoms following initial surgery caused both patients to undergo further surgery. The intestine, which was necrotic and perforated due to vasculitis of the mesenteric vessels, was then resected. The clinical picture together with laboratory data and histologic analysis of the resected specimen allowed the diagnosis of SLE in both patients. In the only other similar case report found in the literature, SLE-associated mesenteric vasculitis was taken into account because of thrombocytopenia (6). In the study by Zizic (4), 8 of 15 patients with SLE-associated intestinal vasculitis died and only 4 patients responded to corticosteroid therapy before surgery. In the second case presented here, steroid therapy was administered immediately but further surgery was still necessary because of ongoing intestinal bleeding. It is nonetheless believed that knowledge of the diagnosis and consequent prompt therapy was a sure advantage for this patient, as shown by the benign postoperative recovery. Both cases described show that, despite its rareness, severe intestinal vasculitis may be the only presenting symptom of SLE. The finding at laparotomy of bloody ascites and extensive bowel wall hemorrage or infarction should raise the suspicion of SLE and lead to appropriate specific diagnostic testing.
We treated our patients with the usual doses of steroids and cyclophosphamide. More aggressive treatment with steroid pulse therapy could also be considered. Two patients with SLE gastrointestinal vasculitis receiving such therapy (intravenous methylprednisolone 1 g. daily for three consecutive days) have been described (7,8). One of them recovered, whereas the other did not improve and ultimately died of septic shock. We must also consider that steroid pulse therapy carries a substantial risk of complications (infections and worsening of hypertension). Therefore, its use needs a careful evaluation and the decision to give it must be taken on a case-by-case basis.
1. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25:1271–77.
2. Wang SJ, Lan JL, Lin WY, et al. Three-phase abdominal scintigraphy in lupus vasculitis of the gastrointestinal tract. Clin Nuc Med 1995; 20:695–98.
3. Shapeero LG, Myers A, Oberkircher PE, Miller WT. Acute reversible lupus vasculitis of the gastrointestinal tract. Radiology 1974; 112:569–74.
4. Zizic TM, Classen JN, Stevens MB. Acute abdominal complications of systemic lupus erythematosus and polyarteritis nodosa. Am J Med 1982; 73:525–31.
5. Drenkard C, Villa AR, Reyes E, Abello M, Alarcon-Segovia D. Vasculitis in systemic lupus erythematosus. Lupus 1997; 6:235–42.
6. Rodriguez LR, Carpo G, Gertner M. Acute gastrointestinal vasculitis as the initial presentation of SLE. Am J Emerg Med 2001; 19: 90–91.
7. Tanaka H, Waga S, Tateyama T et al Interstitial cystitis and ileus in pediatric-onset systemic lupus erythematosus Pediatr Nephrol 2000; 14:859–61.
8. Ebberhard A, Shore A, Silverman E, Laxer R Bowel perforation and interstitial cystitis in childhood systemic lupus erythematosus. J Rheumatol 1991; 18:746–7.