Oral Cavity

Oral ulceration is a common feature of SLE, occurring in 6 to 52% of patients.¹ Oral ulcers is one of the 11 American College of Rheumatology (ACR) revised criteria for the classification of SLE, and is a marker for disease activity. Typically, these ulcers are superficial, painless, and mostly found on the hard palate, buccal cavity, and vermiform border. Less commonly, ulcers may also develop in the nasal cavity and the pharyngeal wall. Histology is usually nonspecific.

Chronic discoid lupus erythematosus (DLE) may develop in the oral mucosa. Up to 24% of patients with chronic cutaneous LE had concomitant mucous membrane lesions.² Mucosal DLE usually starts as a painless erythematosus patch that slowly matures into a chronic plaque-like lesion. It is frequently found in the buccal mucosa, but the palate and tongue may also be involved. DLE lesions can be severely painful, and their morphology may be confused with lichen planus or leukoplakia. Tissue biopsy may show lupus-specific histopathology similar to that of the skin.

Oral ulceration may also be caused by infection and therapy of SLE. Viral infection such as herpes simplex and fungal infections such as candidiasis may lead to painful oral ulcers and plaque-like lesions. Immunosuppressive agents such as cyclophosphamide and methotrexate may induce mucositis and mucosal ulceration.

Sicca symptoms such as dry mouth and dry eyes are fairly common in SLE patients. Manoussakis and colleagues³ reported a 9.2% prevalence of secondary Sjögren’s syndrome in 283 unselected SLE patients using the American-European classification criteria. The clinical presentation of Sjögren’s syndrome in SLE was no different from that of primary Sjögren’s syndrome, but older age, Raynaud’s phenomenon, anti-Ro, anti-La, and rheumatoid factor were more frequent in SLE patients, whereas renal disease, lymphadenopathy, and thrombocytopenia were less common.

SLE patients are prone to poor dental health. This is a result of multiple factors, including disease activity, reduced salivary flow, bleeding diathesis, and the use of medications such as corticosteroids (risk of gingival infection), aspirin, and nonsteroidal anti-inflammatory drugs (NSAIDs) (platelet dysfunction), cyclosporin A (gingivitis, gingival hypertrophy), methotrexate (stomatitis and mucositis), antiepileptic agents (gum hypertrophy), and tricyclic antidepressants (which worsen sicca).

Meyer and colleagues⁴ studied the frequency of oral, dental, and periodontal findings in 46 patients with SLE. Compared with healthy matched controls, oral mucosal lesions such as aphthous ulcers, erythema, gingival overgrowth, and hemorrhage were more frequently found in SLE patients (48% vs. 25%). The extent of periodontal disease was related to the severity and duration of SLE. In addition to disease and treatment-related factors, chronic periodontitis in SLE has also been linked to genetic factors such as the FcgammaRIIa polymorphisms⁵ and the antineutrophil cytoplasmic antibodies.⁶ Periodontal disease may pose a potentially serious health risk in SLE patients because a recent systematic review suggested a modest association between periodontitis and cardiovascular diseases.⁷

Esophagus

Dysphagia occurs in 1 to 13% and heartburn in 11 to 50% of patients with SLE.¹ These may be attributed to dry mouth, esophageal hypomotility, esophagitis, or esophageal ulceration because of acid reflux and infection. Manometry studies reveal functional abnormalities of the esophagus in 10 to 32% of SLE patients.^8,9 Aperistalsis or hypoperistalsis is most frequently found in the upper one-third of the esophagus,⁹ and is associated with Raynaud’s phenomenon in some studies.⁸ The reasons for esophageal hypomotility in SLE remain elusive. Skeletal muscle fiber atrophy, inflammatory reaction in the esophageal muscles, and ischemic or vasculitic damage of the Auerbach plexus have been postulated.

Esophagitis with ulceration was reported in 3 to 5% of patients with SLE.¹ This may be caused by gastroesophageal reflux or infections such as Candida, herpes simplex, and cytomegalovirus (CMV). Endoscopic examination with biopsy is necessary to establish the diagnosis. A true vasculitis leading to esophageal ulceration is probably rare.¹⁰ In addition, medications such as NSAIDs and the bisphosphonates are occasionally associated with esophagitis and bleeding esophageal ulcers.

Stomach

Gastritis, gastric erosion, and ulceration in SLE patients may result from treatment with high-dose corticosteroids and NSAIDs. In two studies of acute abdomen in SLE patients, perforated peptic ulcer was diagnosed in 6 to 8% of cases.^11,12 While the exact incidence of peptic ulcer disease in SLE patients is unknown, adverse effects of medications are the most common causes. Vasculitis of the gastric mucosa related to active SLE causing ulceration and bleeding is exceedingly rare.

Although pernicious anemia has been reported in patients with SLE, its prevalence is low. A study of 30 SLE patients reported that only one patient (3%) suffered from pernicious anemia characterized by low serum cobalamin level, macrocytic anemia, and the presence of antibody against intrinsic factor.¹³ Another study indicated that 19% of female SLE patients had low serum cobalamin levels, but none developed overt anemia.¹⁴

Gastric antral vascular ectasia (GAVE) is a rare vascular malformation in the GI tract that may cause acute or chronic bleeding. The characteristic endoscopic appearance is a collection of red spots of ectatic vessels arranged in stripes along the antral rugal folds. GAVE is mostly found in patients with systemic sclerosis, but has been reported in SLE.¹⁵

Although the stomach is relatively resistant to infection, CMV gastritis has been reported in heavily immunocompromised patients. Renal transplant recipients who receive mycophenolate mofetil (MMF)-based immunosuppressive protocols are prone to disseminated CMV infections. As MMF is increasingly used in patients with SLE, CMV infection of the GI tract should not be overlooked.

Small Intestine

Intestinal Pseudo-Obstruction

Intestinal pseudo-obstruction (IPO) is a clinical syndrome characterized by impaired intestinal motility as a result of dysfunction of the visceral smooth muscle or the enteric nervous system. IPO may be the initial presentation of SLE and usually occurs in the setting of active lupus.²⁵ The small bowel is more commonly involved than the large bowel.

Common presenting symptoms of IPO are a subacute onset of abdominal pain, nausea, vomiting, abdominal distention, and constipation. Physical examination often reveals a diffusely tender abdomen with sluggish or absent bowel sound. Rebound tenderness is usually absent. Radiologic examinations may demonstrate dilated, fluid-filled bowel loops, with thickened bowel wall and multiple fluid levels (Fig. 34.1). Organic causes for intestinal obstruction should be sought, preferably by nonsurgical assessment but laparotomy may be necessary in some patients.

Fig. 34.1 An SLE patient with intestinal pseudo-obstruction. Plain abdominal radiograph shows multiple dilated small bowel loops with fluid levels.

Manometry motility studies in patients with IPO may demonstrate esophageal aperistalsis and intestinal hypomotility.²⁶ Interestingly, 63% of the reported cases of SLE-related IPO had concomitant ureterohydronephrosis and contracted urinary bladder, and around one-third of these patients had documented histologic features of interstitial cystitis.²⁵ Lupus interstitial cystitis may lead to bladder wall thickening and reduced bladder capacity. This may in turn induce ureterohydronephrosis because of detrusor muscle spasm and secondary vesiculo-ureteric reflux.

The pathogenesis of IPO in SLE is unclear. The association with autoimmune cystitis and the demonstration of antibodies against proliferating cell–nuclear antigen in some patients²⁷ suggests that vasculitis of the visceral smooth muscles is a mechanism which may lead to muscular damage and hypomotility. The simultaneous presence of ureterohydronephrosis in many patients with SLE-related IPO and the association of hypomotility of other parts of the GI tract indicate that the basic pathology may be dysmotility of the intestinal musculature. Whether this is caused by a primary myopathy, neuropathy, vasculitis, or antibodies directed against the smooth muscle of the gut wall requires further study.

Malabsorption

Intestinal malabsorption in SLE may result in protein losing enteropathy, hypoalbuminemia, and ascites. Mader and colleagues²⁸ screened 21 SLE patients for malabsorption by the D-xylose absorption test (DXT), microscopic examination of the stool for fat droplets, and biopsy from the second part of the duodenum. Two patients (10%) were found to have an abnormal DXT and excessive fecal fat excretion. In one of these patients, histologic examination revealed flattened and deformed villi with an inflammatory infiltrate. Immunoperoxidase staining did not reveal excessive deposition of immunoglobulins and light chains within the intestinal mucosa in these patients.

Up to 23% of patients with SLE may be tested positive for either the IgA or IgM antigliadin antibodies,²⁹ but biopsy-proven celiac disease (gluten-sensitive enteropathy) is exceedingly uncommon.

Protein-Losing Gastroenteropathy

Protein-losing gastroenteropathy (PLGE) is characterized by hypoalbuminemia secondary to loss of protein from the GI tract. It is usually identified by an elevated clearance of stool α1-antitrypsin or the technetium99m-labeled human serum albumin scan (Fig. 34.2). Significant loss of protein from the kidneys should be ruled out. A variety of pathologies from the stomach down to the colon may be responsible for protein loss. Investigations into the causes of PLGE such as gastrointestinal lymphoma, malabsorption state, bacterial overgrowth, chronic infection, polyposis, and lymphatic obstruction are essential. Endoscopic examination with mucosal biopsies, barium studies, radiologic examinations, and absorption tests may be required.

Fig. 34.2 99mTc-labelled human serum albumin (HSA) scan in a patient with SLE showing leakage of protein from the small bowel. A, An area of diffuse activity in upper and central lower abdomen at 2 hours (left). B, Intense activity at the ileocecal valve region at 7 hours (middle). C, Intense activity in cecum, ascending colon, and transverse colon at 24 hours (right).

PLGE is a rare manifestation of SLE, and fewer than 50 cases have been described. We recently reported 16 cases of SLE-related PLGE and reviewed 32 other patients in the literature.³⁰ PLGE was the presenting feature in three-quarters of our patients and most patients had active SLE in other organs. The most common presentation was generalized or dependent edema, and abdominal symptoms, such as pain, nonbloody diarrhea, nausea, vomiting, and anorexia. Protein leakage occurred more frequently from the small bowel (69%) than the large bowel (31%). Specific endoscopic, imaging, and histologic findings were often absent. The most common endoscopic appearance was mucosal edema.³¹ The biopsy was either normal or revealed nonspecific findings such as villous atrophy, submucosal edema, dilated lacteals, and inflammatory infiltrates. Definite lymphangiectasia, vasculitis, or C3 deposition in the capillary walls of the lamina propriae of villi was uncommon.

The exact pathogenesis of PLGE remains elusive. Mucosal disruption and increase in mucosal capillary permeability as a result of complement- or cytokine-mediated damage, mesenteric venulitis, and dilated/ruptured mucosal lacteals have been postulated.³⁰

Related posts:

Fertility in Systemic Lupus Erythematosus Antibodies to SSA/Ro and SSB/La: Potential Mechanisms of Tissue Injury in Neonatal Lupus-Congenital Heart Block Pregnancy The Nervous System in Systemic Lupus Erythematosus Cytotoxic Drug Treatment Systemic Lupus Erythematosus and Infections

Stay updated, free articles. Join our Telegram channel

Join