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Scleroderma and Collagen Vascular Disorders
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Scleroderma and other connective tissue diseases such as systemic lupus erythematosis, dermatomyositis, Behçet’s disease and polyarteritis nodosa are uncommon but can result in multisystem disease including abnormalities in the GI tract. Gastrointestinal motility disorders have been most clearly associated with scleroderma (systemic sclerosis) and are the focus of this chapter.
Scleroderma (systemic sclerosis [SSc]) is a rare, complex fibrosing disease with an insidious onset and unknown etiology. Systemic sclerosis results from several pathologic processes: cellular; humoral autoimmunity; and specific vascular changes. The pathophysiology of GI dysmotility appears to result from vascular ischemia followed by neural dysfunction, and then smooth muscle dysfunction with fibrosis of the lamina propria. In addition, antibody inhibition of muscarinic enteric cholinergic neurotransmission may be induced. Sclerodermatous gastrointestinal (GI) involvement is a major source of morbidity and is the direct cause of death in 11% of cases. Scleroderma is generally described in two forms: limited cutaneous systemic sclerosis; and diffuse systemic sclerosis (dSSc), with a common feature being ultimate fibrosing disease. The GI tract may be involved in both subsets of SSc, although more commonly in dSSc. Characteristic antibodies found in the limited cutaneous form include antinuclear antibodies (ANA) and anticentromere antibodies; in dSSc, a positive ANA (found in <90% SSc patients) and anti-Scl-70 can be found.
Epidemiology
Scleroderma has variable presentation and geographical variation, making it difficult to study its epidemiology. Prevalence is strongly influenced by early diagnosis and prolonged survival, which have improved in SSc in the last decades. The reported prevalence ranges widely from 7 to 489 per million. It is higher in the United States (240 per million) and Australia than in many other countries. systemic sclerosis occurs more frequently in women (3:1 to 4:1) and particularly in black women, with initial symptoms presenting in the third decade.
About 10% of adults with SSc note the onset of symptoms during childhood. From a GI perspective, gastroesophageal reflux and/or dysmotility was less frequent in children, occurring in 8% of juvenile SSc compared with 79% of adult patients.
The overall mortality in SSc is higher than in the general population. Patients who do not develop severe organ involvement in the first 5 years of disease have a better survival rate.
Pathogenesis of Scleroderma
Although the definitive pathogenic course of SSc remains unknown, the disorder appears to start with microvascular changes and endothelial activation followed by immune cell activation (B cells, T cells and macrophages) with the development of autoantibodies, and release of cytokines and growth factors. Subsequently, through presumed mediator interaction, profibrotic fibroblastic cell proliferation occurs with ensuing fibrosis. Genetic factors are probably important in the pathogenesis of SSc and there is increasing evidence to support this, although no gene has yet been identified. Environmental etiologies have been proposed and include exposure to chemicals (including silica, solvents, silicone, epoxy resins) and viruses (high prevalence of cytomegalovirus antibodies have been found).
Clinical Features and Pathophysiology
The GI tract is one of the most commonly involved organs in SSc with progressive changes throughout the GI tract — collagen replaces vascular and enteric smooth muscle and results in autonomic dysfunction with consequent smooth muscle changes resulting in reduction or loss of motility, luminal dilation and eventual organ failure.These changes also occur in other connective tissue disorders.
Esophagus
More than 50% of SSc patients have esophageal disease, specifically in the distal two-thirds of the esophagus where the pathologic lesion is atrophy of the smooth muscle (muscularis propria). Later, collagen deposition results in fibrosis and thickening. The function of the upper esophageal sphincter (UES), pharynx and proximal skeletal muscle is spared. Although definite changes occur in the vasculature and the nerves, there is controversy about the order of involvement. Autonomic dysfunction also impacts on esophageal and lower esophageal sphincter function. Esophageal motility disorders also occur in patients with sytemic lupus erythematosis and rheumatoid arthritis (RA) with 7% complaining of dysphagia and 20% nausea. Amyloid deposits in the esophagus also may affect swallowing in patients with long-standing RA. Dysphagia from esophageal hypomotility has been reported in up to 35% of patients with dermatomyositis/polymyositis.
Patients’ symptoms closely mirror these esophageal changes and include dysphagia for liquids and solids, heartburn, and regurgitation in as many as 82% of SSc patients. The findings with esophageal motility studies are summarized in the Table (page 28). The lower esophageal sphincter pressure is often low (Figure). Low amplitude but peristaltic contractions in the distal two-thirds of the esophagus are present initially, with loss of peristalsis as the disease progresses.
Dysphagia is usually related to esophageal dysmotility with abnormal bolus transit as well as to esophageal reflux, but this result from secondary esophagitis and strictures. Heartburn is normally worse at night or postprandially. The lack of buffering capacity of saliva resulting from Sjogren’s syndrome in scleroderma increases the potential for mucosal damage from acid reflux. As the disease worsens, patients can experience early satiety, regurgitation of food, malnutrition and even food bolus impaction, requiring intervention. Impaired esophageal clearance may result in drug-induced esophagitis with drugs such as quinidine, potassium chloride, bisphosphonates and NSAIDs. The cutaneous manifestations of Raynaud’s phenomenona are associated with esophageal motility dysfunction in scleroderma.
As a result of these esophageal dysfunctions, SSc patients are at risk for associated complications that include gastroesophageal reflux disease (GERD) with secondary esophagitis, Barrett’s esophagus and strictures (seen in approximately 40%). Dysfunction of the LES and delayed gastric emptying contribute to GERD, and loss of esophageal clearance increases the risk of subsequent complications.
Excerpted from
Parkman HP, McCallum RW, Rao SSC, eds. GI Motility Testing: A Laboratory and Office Handbook (pp 429-442) © 2011 SLACK Incorporated.
- References:
- Chifflot H, et al. Semin Arthritis Rheum. 2008;37:223-235.
- Denton CP. Arth Res Ther. 2007;9(Suppl 2):S6.2007;229:139-144.
- Ebert EC. J Clin Gastrol. 2008;42 (1):5-12.
- Eckes B, et al. Arch Dermatol Res. 2007;229:139-144.
- Goldblatt F, et al. Gastroenterology. 2002;123:1144-1150.
- Jaovisidha K, et al. Semin Arthritis Rheum. 2004;34:689-702.
- Martini G, et al. Arthritis Rheum. 2006;54(12):3971-3978.
- Mayes MD. Rheum Dis N Am. 2003;29:239-254.
- Moore SC, et al. Am J Health Syst Pharm. 2008;65:315-322.
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