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Gastrointestinal involvement occurs in most patients with systemic sclerosis and is subclinical in about one third. Early pathology is characterized by vasculopathy, resulting in tissue ischemia and progressive dysfunction. Noninvasive esophageal studies using semisolid bolus scintigraphy are sensitive but lack specificity. Long-term treatment of reflux with high-dose proton pump inhibitors appears safe and effective for symptom relief and may prevent recurrence of esophagitis and stricture. Dyspepsia may result from gastroparesis and antral distension. Gastric antral vascular ectasia is a vascular manifestation, and bleeding may be controlled endoscopically. Prokinetic agents effective in pseudoobstruction include metoclopramide, domperidone, cisapride, octreotide, and erythromycin. Patients with intestinal neuropathy or response to bolus octreotide are more probable long-term responders. The combination of octreotide and erythromycin may be particularly effective in systemic sclerosis. The combination of cisapride and erythromycin may cause serious cardiac arrhythmia and is contraindicated. Omeprazole may predispose to small intestinal bacterial overgrowth. Malabsorption not responding to antibiotic therapy should be investigated with small-bowel biopsy to rule out more unusual causes. Pneumatosis cystoides intestinalis may be due to excessive hydrogen production by intestinal bacteria altering the partial pressure of nitrogen in the intestinal wall. In selected cases, surgery for intestinal failure is an option with resection or bypass of affected segments or placement of enterostomy tubes for feeding or decompression. Careful preoperative characterization of intestinal segments is required.
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PMID:Gastrointestinal features of scleroderma. 901 61

Management of patients with progressive systemic sclerosis requires a thorough gastroenterological examination and a profound knowledge of possible gastrointestinal manifestations of the disease. The esophagus is the gastrointestinal segment most often involved. Smooth muscle atrophy leads to a loss of esophageal peristalsis, a defect of the lower esophageal sphincter, and gastric hypomotility, thus predisposing to severe reflux esophagitis. A rational diagnostic approach includes standard manometry and endoscopy. The prevention of strictures is the main aim of therapeutic efforts that may consist of lifestyle changes, prokinetic drugs, long-term application of proton pump inhibitors, and, if inevitable, surgical intervention. Involvement of the small intestine and colon is less common but may lead to life-threatening complications like chronic pseudoobstruction or pneumatosis cystoides intestinalis. The main therapeutic options consist of antibiotics for bacterial overgrowth and nutritional supplementation. Recently, a preliminary study with octreotide yielded promising results. Anorectal dysfunction can lead to fecal incontinence or rectal prolapse.
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PMID:Gastrointestinal manifestations of progressive systemic sclerosis. 914 82

Systemic sclerosis (SS) is characterized by sclerosis of the dermis and internal organs and by vascular abnormalities. Although the pathophysiology of the disease has been partly elucidated, the efficacy of long-term treatments remains limited, with no significant increase in survival in prospective studies. Conventional drug treatments are disappointing in clinical practice, and in a recent prospective randomized study standard-dose D-penicillamine was not more effective than mini-dose D-penicillamine. New long-term treatments are emerging for diffuse SS, including cyclophosphamide for patients with progressive interstitial lung disease or stem cell transplantation for those with early organ involvement. The most effective treatments remain symptomatic, such as angiotensin-converting enzyme inhibitors for acute renal crisis, calcium channel antagonists for Raynaud's phenomenon, and proton pump inhibitors for the complications of gastroesophageal reflux. This review article focuses on long-term treatments that are most likely to be effective and suggests symptomatic treatment strategies tailored to specific organ involvements.
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PMID:Treating systemic sclerosis in 2001. 1170 5

Systemic sclerosis is an extremely variable disease in its manifestations and consequently, treatment needs to be individualized depending on the specific problems that each patient has. Limited scleroderma patients have a prolonged duration of Raynaud's phenomenon and puffy fingers before they develop any skin thickening, digital ulcers or gastrointestinal symptoms. They are likely to present with all the classic manifestations of scleroderma. Diffuse scleroderma patients have a much more acute systemic onset with marked whole hand swelling and may initially have only subtle skin thickening. A good understanding of the differences between the natural history of limited and diffuse scleroderma will enable the physician to treat present problems and anticipate future ones more effectively. One should determine which major subset and organ systems are involved before deciding on the appropriate therapy. Advances in organ-specific therapy, particularly calcium channel antagonists in Raynaud's phenomenon, proton pump inhibitors in esophageal reflux, intravenous iloprost and endothelin receptor antagonists in pulmonary hypertension, and ACE inhibitors in renal crisis, have decreased morbidity and mortality in patients with scleroderma. Studies of aggressive therapies to prevent or improve pulmonary fibrosis are in progress. Further clinical experience in wound healing, gastrointestinal malabsorption and physical therapy for loss of motion has helped patients to have a more comfortable life. In recent years, a significant number of controlled clinical trials have been performed and there has been improved understanding of the best way to perform studies and of which patients are most likely to respond to therapy. Penicillamine, methotrexate, photopheresis, relaxin, interferons, and cyclosporine have all been studied in controlled trials with variable outcomes. Although an overall remittive therapy has not yet been determined, new, potentially useful agents are being investigated.
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PMID:Treatment of systemic sclerosis. 1172 50

Gastrointestinal involvement occurs in most patients with systemic sclerosis. Pathology is characterized by vasculopathy, resulting in tissue ischemia, progressive dysfunction and fibrosis. In its diffuse and visceral pattern, digestive manifestations may involve most of the intestinal tract and are the most frequent before renal, cardiac and pulmonary involvement. Whatever the visceral extension, about 80% of patients have digestive manifestations including gastroesophageal reflux, abnormalities of intestinal motility leading to chronic intestinal pseudo-obstruction and small bowel bacterial overgrowth and malnutrition. Long-term treatment of reflux with high-dose proton pump inhibitors appears safe and effective for symptom relief and may prevent recurrence of esophagitis and stricture. Prokinetic agents effective in pseudoobstruction include metoclopramide, domperidone, octreotide, and erythromycin.
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PMID:[Digestive manifestations in systemic sclerosis]. 1221 92

The spectrum of scleroderma spans Raynaud's phenomenon, localized forms of skin fibrosis and the clinically most important forms of systemic sclerosis that involve inflammatory, vascular and fibrotic pathology. A closer relationship between these disparate conditions is now appreciated, and skin sclerosis is no longer regarded as mandatory for the diagnosis of systemic sclerosis. There have been recent and substantial changes in disease classification, the appreciation of its natural history and the investigation and treatment of organ-based complications. Although scleroderma still has a high case-specific mortality, there have been major improvements in the management of renal and pulmonary disease, and areas such as gastrointestinal tract involvement can also often be improved. Each of these areas is reviewed, and progress in understanding pathogenesis also described. The management of organ-based complications has benefited from advances in other branches of medicine. Angiotensin-converting enzyme inhibitors for scleroderma renal crisis, proton pump inhibitors for reflux oesophagitis and advanced therapies for classes III and IV pulmonary arterial hypertension exemplify progress in the treatment of systemic sclerosis. There is also the prospect of targeted, cytokine-directed treatments that may for the first time offer the prospect of genuine disease-modifying intervention in early-stage disease. In parallel with these developments, there has been substantial progress in disease assessment with the construction and initial validation of tools to assess skin biomechanics, functional impairment and the severity and activity of systemic sclerosis. It is likely that clinical trials performed over the next few years will transform the management of systemic sclerosis and help to dispel its reputation as one of the least treatable of the autoimmune rheumatic diseases.
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PMID:Scleroderma--clinical and pathological advances. 1515 41

Systemic sclerosis (SSc) is a severe fibrotic multiorgan connective tissue disease. Vascular abnormalities such as fingertip ulcers and Raynaud's syndrome as well as involvement of organs including the lungs, heart, kidney and the gastrointestinal tract are prominent features of the disease. There are currently no disease modifying drugs available that can modify the course of the disease. In this review we will discuss medications that have been found to be effective in improving specific organ involvement due to SSc. For the treatment of gastroesophageal reflux disease (GERD), proton pump inhibitors are effective agents. In the setting of clinically significant gastrointestinal dysmotility, metoclopramide, erythromycin and octreotide may be beneficial. Small bowel bacterial overgrowth should be treated with oral antibiotics. Angiotensin converting enzyme inhibitors are the first-line agents for acute renal crisis. A variety of treatment options are available for Raynaud's phenomenon and include calcium channel blockers, iloprost (i. v.), losartan, fluoxetine and sildenafil. Fingertip ulcers can be prevented by using the endothelin receptor antagonist bosentan. The therapeutic options for treatment of pulmonary hypertension associated with SSc include bosentan, sildenafil and various prostacyclin analogs (eg, epoprostenol, treprostinil, iloprost). Sitaxentan, ambrisentan and new phosphodiesterase-5 inhibitors could be new options for therapy as well. Therapeutic options for interstitial lung fibrosis include cyclophosphamide, however, clinical effects are mild to moderate. Methotrexate has been used to treat skin fibrosis and can be beneficial when arthritis is present.
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PMID:[Systemic sclerosis]. 1855 72

Scleroderma or systemic sclerosis (SSc) is a connective tissue disease (CTD) associated with fibrosing and vascular complications involving multiple organs. The care of these patients in the critical care setting is frequently challenging due to multiple complications and refractory organ involvement. However, awareness of specific organ involvement associated with scleroderma can allow many complications to be anticipated and effectively treated. Cardiac involvement can lead to arrhythmias and heart failure, whereas pulmonary involvement can be associated with pulmonary arterial hypertension, fibrosis, or both. Renal vascular disease and scleroderma renal crisis (SRC), once a uniformly fatal complication, is particularly important to recognize early, as it can be treated successfully. Gastrointestinal involvement can lead to bleeding, aspiration, obstruction, and malabsorption. Severe Raynaud may lead to digital ischemia and gangrene. Therapies must target involved organ system or organ systems. Corticosteroids, a mainstay for related CTDs, do not typically provide any benefit and may cause harm. Vasodilators can effectively treat vascular complications but must target the appropriate vascular bed. Proactive utilization of proton pump inhibitors, recognition of bleeding from gastrointestinal vascular ectasia, and nutritional support can considerably ameliorate gastrointestinal morbidities. Effective treatment of fibrotic complications remains elusive and is the current frontier for scleroderma therapeutics.
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PMID:Care of patients with scleroderma in the intensive care setting. 2054 65

Investigation into the upper GI-tract of patients suffering from systemic sclerosis [SSc] and mixed connective tissue disease [MCTD] without symptoms of GI-tract involvement early in the course of the disease to diagnose inflammatory and motility disorders. We retrospectively analysed patients with SSc and MCTD who underwent oesophago-gastro-duodenoscopy [OGD] within a year of the first diagnosis. Patients with a Rodnan skin score above 5, proton pump inhibitors and treatment regimes potentially harmful to the mucosa of the upper GI-tract were excluded. Mucosal damage of the oesophagus was classified according to the Los Angeles Classification. Oesophageal dysmotility was assessed during OGD and confirmed by video cineradiography. A total of thirteen patients with SSc and six with MCTD fulfilled the inclusion criteria. OGD revealed reflux-oesophagitis in 77%, dysmotility of the distal oesophagus in 85%, gastritis in 92% [31% erosive gastritis] and Helicobacter pylori positivity in 38% of our patients suffering from SSc. Patients with MCTD showed features of reflux-oesophagitis, dysmotility of the distal oesophagus, gastritis and dysmotility of the stomach in 0.6%. In all thirteen patients with SSc, significant pathology of the upper GI-tract was found. The results of this study might indicate that OGD should be performed early in patients diagnosed with SSc, even if they do not report typical symptoms. An early diagnose of GI involvement might be followed by an effective therapy and therefore subsequently may improve the prognosis.
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PMID:Early endoscopy in systemic sclerosis without gastrointestinal symptoms. 2071 92

Platelet activation and aggregation are key elements of the pathogenesis of acute coronary syndromes, of endothelial damage in chronic inflammatory and connective tissue disease (i.e. systemic sclerosis-SSc). Patients affected by chronic inflammatory diseases as well as by connective tissue diseases such as systemic sclerosis, often have the need to take anti-platelet therapy (e.g. ASA or clopidogrel). Current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a proton pump inhibitor (PPI) to reduce gastrointestinal bleeding. Although each single PPI has similar efficacy in many cases, differences between them should be considered when choosing a treatment regimen. Many studies show PPI and clopidogrel drug interaction, with clopidogrel non-responsiveness in about 25% of the population. Only pantoprazole, which does not inhibit CYP P450 2C19, doesn't seem to have interaction with clopidogrel or other drugs. Patients affected by systemic sclerosis have high frequency of oesophageal mucosal abnormalities and should take long-term PPI therapy. When addressing long-term therapy safety data are clearly needed. Two recent studies have reported increased hip fracture rates with long-term PPI use, raising concerns about adverse effects of this class of drugs on mineral metabolism. The use of PPIs is also associated with an increase in the risk of development of Clostridium difficile infection (CDI) and the use of PPIs during CDI treatment is associated with an increased risk of recurrence. In order to achieve the desired results and, as with all medications, PPIs should always be used appropriately taking care never to exceed correct dosage and duration. When necessary use of pantoprazole arises as one of the best possible choices.
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PMID:Proton pump inhibitors in rheumatic diseases: clinical practice, drug interactions, bone fractures and risk of infections. 2150 44


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