The Pathogenesis of Esophageal Dysfunction in Scleroderma and Raynaud's Disease

Cohen, Sidney; Fisher, Robert S.; Lipshutz, William; Turner, Robert; Myers, Allen R.; Schumacher, Ralph

doi:10.1172/jci107084

Cited by 179 publications

(50 citation statements)

References 18 publications

(18 reference statements)

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“…Cohen et al [10] postulated a concept of the underlying pathomechanisms with regard to these symptoms: neural lesions may occur early and can cause an irreversible disruption of the esophageal motor function followed by development of significant smooth muscle atrophy. The associated reduced esophageal motility thereafter contributes to gastroesophageal reflux [11], heartburn, esophageal strictures, sore throat and even continuous microaspiration followed by pneumonia.…”

Section: Discussionmentioning

confidence: 99%

Profile of gastrointestinal involvement in patients with systemic sclerosis

et al. 2011

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Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis. Methods: The multi-symptom questionnaire was used at baseline and after one year in registered patients of the DNSS. In addition the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. Results: The results of the study show that in reality a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/ sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Conclusions: Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after one year of follow up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis. Methods:The multi-symptom questionnaire was used at baseline and after one year in registered patients of the DNSS. In addition the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. Results:The results of the study show tha...

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Section: Discussionmentioning

confidence: 99%

Profile of gastrointestinal involvement in patients with systemic sclerosis

et al. 2011

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“…Studies examining the effect of methacholine (acetyl-␤-methylcholine) (4), another muscarinic agonist, in the human esophagus revealed the preservation of the effect of that agonist, whereas the effect of agents targeting the nerves was severely affected (10). There are different possibilities for these observations.…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells

Singh¹,

Mehendiratta²,

Galdo

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Recent findings of an ultrastructural study of the esophagus (46) also supported a primary vascular cause, rather than a neurogenic (47) or myopathic process, of esophageal dysfunction in progressive systemic sclerosis. Thus, a functional, with or without accompanying structural, vascular disease may be an important contributor to the pathogenesis of PSS.…”

Section: Discussionmentioning

confidence: 94%

Nifedipine and esophageal dysfunction in progressive systemic sclerosis. A controlled manometric study

Kahan¹,

Bour²,

Couturier³

et al. 1985

Arthritis & Rheumatism

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We evaluated the effect of the calcium channel blocking agent, nifedipine, on esophageal dysfunction in 15 patients with progressive systemic sclerosis, using a double-blind, randomized, crossover, placebo-controlled manometric study. Nifedipine significantly decreased lower esophageal sphincter pressure in these patients; this reduced lower esophageal sphincter pressure may cause gastroesophageal reflux. Thus, nifedipine may have detrimental effects on progressive systemic sclerosis patients.The pathogenesis of esophageal dysfunction in progressive systemic sclerosis (scleroderma; PSS) has not been well elucidated (1,2). PSS is characterized by vascular and microvascular abnormalities (1-4), excessive fibroblastic activity (5,6), and collagen deposition in numerous organs (1,2,7). The possibility that the lesions in target organs are a reflection of a primary fibrous tissue overgrowth leading to secondary vascular compromise has not been ruled out. Nevertheless, a growing body of evidence based on studies of several organs involved in PSS suggests that the vascular system per se may be the primary target organ and that the lesions are a manifestation of focal ischemic injury resulting from functional, with or without accompanying structural, vascular disease (~4 , 8 4 4 ) .Nifedipine, a calcium channel blocking agent, is effective in the treatment of coronary vasospasm ( I 5-18). We (19-21) and others (22)(23)(24)(25) have shown that nifedipine is effective in the treatment of idiopathic Raynaud's phenomenon and Raynaud's phenomenon occurring with progressive systemic sclerosis. Thus, if a microvascular abnormality is a contributor to the pathogenesis of scleroderma, nifedipine may be useful in the treatment of patients with early disease.However, nifedipine may have detrimental effects caused by its direct action on the lower esophageal sphincter. The actions of nifedipine on smooth muscle cells are well documented (15)(16)(17)(18). Several studies have shown that the drug decreases the lower esophageal sphincter pressure (LESP) in patients with achalasia (26,27). If nifedipine also decreases the LESP in patients with progressive systemic sclerosis, this could lead to gastroesophageal reflux.In the present investigation, we used a controlled, double-blind, randomized, crossover manometric study to evaluate the effect of nifedipine on I5 patients with progressive systemic sclerosis and esophageal dysfunction. Our trial demonstrates that nifedipine significantly decreases the lower esophageal sphincter pressure in patients with PSS. PATIENTS AND METHODSPatients. Fifteen patients with progressive systemic sclerosis and diffuse scleroderma were studied. All patients satisfied the American Rheumatism Association preliminary criteria for classification of definite systemic sclerosis (28). None of the patients had the CREST syndrome variant (calcinosis, Raynaud's phenomenon, esophageal dysmo-NIFEDIPINE IN PSS 49 1 tility, sclerodactyly, telangiectasias) of PSS (29). The presence of the esophageal symptoms of heartbur...

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The Pathogenesis of Esophageal Dysfunction in Scleroderma and Raynaud's Disease

Cited by 179 publications

References 18 publications

Profile of gastrointestinal involvement in patients with systemic sclerosis

Profile of gastrointestinal involvement in patients with systemic sclerosis

Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells

Nifedipine and esophageal dysfunction in progressive systemic sclerosis. A controlled manometric study

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