The pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease

To determine the pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease, the lower esophageal sphincter (LES) was tested with: (a) methacholine acting directly at the cholinergic receptor on the muscle; (b) edrophonium, a cholinesterase inhibitor, enhancing the effect of released acetylcholine; and (c) gastrin I, acting through the release of acetylcholine. 10 patients with Raynaud's disease and 22 patients with scleroderma were compared with 20 normals and 20 patients with isolated LES incompetence. The mean basal LES pressure in normals was significantly greater than that recorded in both patients with scleroderma and Raynaud's disease. Six patients having scleroderma with normal peristalsis had an LES pressure significantly greater than that noted in 16 patients having scleroderma with abnormal peristalsis. In all groups, the per cent increase in LES pressure was similar when tested by direct muscle stimulation by methacholine. The response to agents that acted indirectly through intact cholinergic nerves differed in these groups. The LES response to gastrin I distinguished patients with normal peristalsis from those with abnormal peristalsis. The patients with normal peristalsis, either with scleroderma or with Raynaud's disease showed only a partial reduction in their response to gastrin I. The response to gastrin I was markedly reduced only in patients with abnormal peristalsis. These data indicate that in patients with scleroderma and Raynaud's disease, the LES response to direct muscle stimulation by methacholine was intact while the response to gastrin I and edrophonium was diminished.