Gastrointestinal, hepatic, and pancreatic disorders in systemic lupus erythematosus

Mesenteric/Intestinal vasculitis/lupus enteritis

The prevalence of intestinal vasculitis in SLE patients ranges from 0.2% to 9.7% and among those who present with acute abdominal pain, intestinal vasculitis is diagnosed in 29%–65% of patients. This manifestation is more commonly observed in Asian patients.

Symptoms of mesenteric vasculitis range from mild abdominal bloating with a variable degree of nausea, vomiting, fever, and loose stool to intestinal perforation which manifests as severe diffuse abdominal pain, abdominal distension, rebound tenderness, and paralytic ileus. In serious cases, mucosal ulceration leading to extensive GI bleeding, intussusception, and bowel gangrene may develop. Serological and clinical disease activity in other organs is usually present.

An accurate and timely diagnosis of mesenteric vasculitis is essential. Other SLE and nonSLE-related causes of abdominal pain must be excluded. Plain radiograph of the abdomen is insensitive for diagnosing lupus mesenteric vasculitis at its early stage. In established disease, X-rays may demonstrate pseudo-obstruction, ileus, or dilatation of the bowel loops, effacement of the mucosal folds, submucosal edema as a result of bowel ischemia (thumbprinting appearance), and uncommonly pneumatosis cystoids intestinalis (gas cysts within the submucosa or subserosa of the intestine). Intraabdominal free gas may be seen after intestinal perforation.

Computer tomography (CT) scan of the abdomen is the most useful diagnostic tool for mesenteric vasculitis. Apart from excluding other intraabdominal pathologies such as abscesses and collections, cholecystitis, and pancreatitis with or without pseudocyst formation, a contrast CT scan may demonstrate focal or diffuse bowel wall thickening with double halo or target sign (enhancing outer and inner rim with hypoattenuation in the center), prominent mesenteric vessels with palisade pattern or comb-like appearance supplying focally or diffusely dilated bowel loops, and ascites. Segmental or multifocal involvement of the small and large bowel loops is highly suggestive of ischemic changes due to vasculitis. Early CT findings of lupus enteritis are reversible on immunosuppressive treatment. Besides, CT angiography may help in differentiating lupus enteritis with thrombosis of the major mesenteric vessels.

Upper and lower endoscopies in lupus enteritis may show signs of ischemia and mucosal ulceration. The typical histopathological findings are usually observed in the arterioles and venules of the submucosa of the bowel wall rather than the medium-sized mesenteric arteries. Vasculitic lesions tend to be segmental and focal. Immunohistochemical staining of the tunica adventitia and media may reveal immune complex, C3 complement, and fibrinogen deposition. Fibrinoid necrosis, intraluminal thrombosis of affected vessels, acute, or chronic inflammatory infiltrates consisting of lymphocytes, plasma cells, histiocytes, and neutrophils may also be demonstrated.

Although any vessels can be involved, the territory of the superior mesenteric artery (jejunum and ileum) is most frequently affected by lupus enteritis. The pathogenesis of lupus enteritis remains elusive. Immune complex-mediated vasculitis with complement activation that induces inflammation, microvascular injury, ischemia, and edema of the bowel wall, leading to increase in vascular permeability, is thought to be the mechanism.

The mortality of lupus enteritis is high, depending on the extent of vascular involvement and the rapidity of diagnosis and treatment. Aggressive immunosuppressive therapy with high-dose intravenous pulse methylprednisolone should be given early. Patients should be monitored closely and surgical intervention is indicated when a rapid clinical response is not achieved or there is clinical and radiological suspicion of bowel perforation. Lupus enteritis may recur in more than half of patients, especially in those with a bowel wall thickness of >9 mm at presentation. Intravenous pulse cyclophosphamide has been used with success in refractory lupus enteritis and reducing recurrence.

Mesenteric insufficiency

Atherosclerosis of the mesenteric arteries should be considered in SLE patients who present with chronic intermittent abdominal pain (“intestinal angina”). Symptoms usually start in the postprandial state and persist for several hours. Symptoms may worsen over time and weight loss may develop for fear of eating. Concomitant atherosclerotic disease in the coronary and carotid vessels supports the diagnosis. SLE patients with long-standing disease, traditional vascular risk factors, renal insufficiency, persistent proteinuria, antiphospholipid antibodies, and chronic corticosteroid therapy are at risk.

The diagnosis of chronic mesenteric insufficiency relies on a high index of suspicion. Conventional angiography is the gold standard imaging procedure. Digital subtraction angiography and magnetic resonance angiography are adjunctive diagnostic modalities.

Acute mesenteric ischemia can result from thrombosis of the mesenteric arterial or venous systems. Classically, abdominal pain is persistent and disproportionately severe relative to physical signs. Bowel infarction and perforation may manifest as acute surgical abdomen, fever, bloody diarrhea, melena, and hypotension. SLE patients with underlying chronic mesenteric insufficiency or the antiphospholipid antibodies are prone to acute intestinal ischemia, which may be precipitated by hypoperfusion states.

Surgical revascularization and percutaneous transluminal mesenteric angioplasty with or without a stent are treatment options for patients with chronic mesenteric ischemia. Acute mesenteric thrombosis causing bowel gangrene should be treated by surgical exploration and embolectomy. Long-term anticoagulation should be given to patients who qualify with the antiphospholipid syndrome.

Intestinal pseudo-obstruction

Intestinal pseudo-obstruction (IPO) is a syndrome characterized by impaired intestinal motility leading to features of a mechanical bowel obstruction. This condition is rare but more commonly reported in Asian patients with SLE. IPO may be the initial presentation of SLE and usually occurs in the setting of an active lupus. The small bowel is more commonly affected than the large bowel.

Common presenting symptoms of IPO are subacute onset of abdominal pain, nausea, vomiting, abdominal distension, and constipation. The abdomen is diffusely tender with sluggish or absent bowel sounds. Rebound tenderness is usually absent unless there is bowel perforation. X-ray and CT examination may demonstrate multiple dilated bowel loops with fluid level and thickened bowel wall ( Fig. 46.1 ). Mechanical causes for intestinal obstruction should be excluded, preferably by nonsurgical means but laparotomy may be necessary in some patients.

Manometry motility studies in patients with IPO may demonstrate esophageal aperistalsis and intestinal hypomotility. Interestingly, more than two-thirds of the reported cases of SLE-related IPO had concomitant ureterohydronephrosis and contracted/thickened urinary bladder, with the majority demonstrating histological features of chronic interstitial cystitis.

The coexistence of ureterohydronephrosis in many patients with SLE-related IPO and dilatation of the biliary tract (megacholedochus) in occasional patients indicates that the basic pathophysiology is dysmotility of the intestinal musculature. The association with autoimmune cystitis and the demonstration of antibodies against proliferating cell nuclear antigen in some patients suggest that immune complex-mediated vasculitis may be a mechanism for inflammation and subsequent damage of the visceral smooth muscles, leading to atrophy, fibrosis, and loss of function of the bowel wall. Other postulated mechanisms for visceral smooth muscle dysfunction include a primary myopathy of the bowel musculature, neuropathy of the enteric nerves or the visceral autonomic nervous system, and direct cytotoxicity of antibodies directed against the smooth muscle of the gut wall.

SLE-related IPO often responds to high-dose corticosteroids. Additional immunosuppressive agents such as azathioprine, cyclosporin A, and cyclophosphamide have been used with success in some reports. Other adjunctive therapies for IPO are nasogastric tube insertion, intravenous fluid, parental nutrition, broad spectrum antibiotics, and prokinetic agents such as erythromycin, metoclopramide, and octreotide (a long-acting somatostatin analog). Early recognition of IPO in SLE patients and timely initiation of immunosuppressive therapy are important because the condition is potentially reversible with nonsurgical measures. However, some patients may have a relapsing course despite maintenance immunosuppressive treatment.