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In systemic sclerosis (SSc), which affects the microcirculation and leads to fibrosis of skin and internal organs,1 the oesophagus and the colon are the gastrointestinal (GI) segments most commonly affected, even though other tracts can be impaired.2,3
In SSc, a few ultrastructural examinations of the oesophageal and rectal wall have been made,4,5 but no study has been carried out on the stomach. This prompted us to examine the gastric wall of a patient with SSc by transmission electron microscopy (TEM) in order to investigate the components of the muscle coat.
In 1997 a 52 year old woman, with limited SSc (lSSc) since 1979, came to our attention. She had Raynaud's phenomenon, sclerodactyly, anticentromere antibodies, and Sjöf-gren's syndrome, but no lung, heart, and kidney disease. From the onset of her SSc, the patient had severe involvement of the distal oesophagus, which was confirmed by oesophagogastroscopy.
In May 1998 the gastro-oesophageal symptoms worsened despite treatment (ranitidine and, later, omeprazole and cisapride) and the patient underwent a Nissen-Rossetti laparoscopic fundoplication. Eight months later, as she became progressively unable to eat, she underwent a total gastrectomy with a Roux-en-Y oesophagojejunal anastomosis operation.
Samples of gastric anterior wall near the greater curvature, from the fundus, corpus, and antrum, were obtained, processed routinely for electron microscopy and, then, ultrathin sections were observed by TEM Jeol 1010.
At TEM, in the muscle coat of the fundus, corpus, and antrum, wide areas of marked focal fibrosis, characterised by collagen and elastic fibre depositions, were seen surrounding smooth muscle cells (smcs) and widening intercellular spaces (figs 1A and B). This finding was in agreement both with the ultrastructural features of SSc of the skin6 and internal organs,7 and with the structural changes seen in the GI tract.3 The small number of fibroblasts found in the gastric muscle layers suggests that elastin and collagen fibres may be produced by smcs themselves, and not by fibroblasts, as shown in SSc skin.6 Indeed, considerable amounts of elastin were often found in invaginations of smc cell membrane. The fibrosis enveloping smcs might account for impaired cellular contraction and its propagation from cell to cell.
Several smcs were either contracted, with thickened dense bands (fig 1B), or stretched, with long and thin dense bands along the cell membrane (fig 1A), indicating a different stage of smc contraction in the SSc stomach. These observations disagreed with the ultrastructural findings in SSc oesophagus, where only thickened dense bands were seen, while long and thin dense bands were noticed in patients with diffuse oesophageal spasm.4
In smcs, cytoplasmic vacuolisation and swollen mitochondria (fig 1A) were often found. Moreover, myofilaments and thickened dense bodies were severely disarrayed (fig 1B), indicating an ineffective filament contraction.
In myenteric plexus, large sized neurones showed well preserved Golgi apparatus, rough endoplasmic reticulum, some lipofuscin bodies, and diffuse slight cytoplasmic vacuolisation. Nerve bundles containing many axons were close to vessels and smcs.
The axoplasm of nerve fibres was pale, oedematous, and scarce in neurotubules and neurofilaments, with occasional swollen mitochondria and lipofuscin bodies (figs 1C and E) as reported in nerve amyelinic bundles of SSc rectum wall.5
In SSc stomach, as seen in SSc oesophageal muscle coat, nerve endings close to smcs and vessels showed conserved morphology with intact synaptic vesicles containing electron dense granules (fig 1D).4 Often, abundant elastic and collagen fibres enveloped nerve endings, separating them from smcs (fig 1D). This finding, together with the alterations in the axoplasm cytoskeletal elements, may account for the impairment in axonal transport and in electric transmembrane transmission, respectively. These observations substantiate the alterations in nervous transmission that might be responsible for GI dismotility in advanced SSc.
Small vessels of the gastric muscle wall were lined by preserved endothelial cells, and the basement membrane was sometimes thickened or laminated, or both (fig 1E). In SSc skin and rectum wall microvessels, on the contrary, swollen endothelial cells occluding the lumen, and thickened and laminated perivascular basal lamina, were seen.5,8
In the stomach wall, the microvascular lumen was partially or completely occluded by erythrocytes and neutrophils (fig 1E), which contributed to tissue hypoperfusion and ischaemic damage. Neutrophils were also seen passing through the vascular wall into the interstitial space. Mast cells, rich in granules or partially degranulated, were present between vessels and smcs (fig 1F).
As far as we know this is the first study reporting ultrastructural modifications in the gastric wall of a patient with lSSc. Severe alterations of smcs and nerve components, and prominent fibrosis are the main hallmarks in the stomach of a patient with longstanding lSSc, while the microvasculature is quite preserved.
Ultrastructural studies performed up to now did not clarify whether smc alterations are primary or secondary to neural and/or vascular involvement, in the genesis of GI changes in SSc.9,10 Therefore, further studies on the GI tract of patients in the early phase of SSc are warranted in order to understand and clarify the primary target of the disease and its progression.
We are grateful to APAI (Associazione Patologie AutoImmuni) for continuous support.
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