Assessment of GIT Vasculopathy in SSc and Its Multisystem Correlations

Systemic sclerosis (SSc) is a rare, chronic autoimmune disease characterized by a complex pathophysiology involving humoral and cellular immunity, endothelial cells, and fibroblasts, leading to widespread vascular injury and excessive deposition of collagen fibers in the skin and major internal organs.

Vasculopathy is one of the main hallmarks of SSc; an early and accelerated atherosclerosis has been described in SSc; the underlying vasculopathy leads to significant impairment of blood flow due to the combined macro- and microvascular involvement. This vascular pathology may involve major organs such as the lungs, heart, GIT, and kidneys. While clinical observations and basic studies suggest that microvascular vasculopathy is of paramount importance throughout all the phases of SSc, increasing evidence suggests that macrovascular involvement also plays a critical role in the disease. Gastrointestinal (GI) involvement is highly prevalent, affecting up to 90% of SSc patients. It often remains subclinical until significant tissue damage has occurred, due to the progression of vasculopathy and fibrosis. Once symptoms develop, SSc-related GI involvement significantly worsens morbidity and mortality, patients frequently suffer marked emotional and social burdens, and advanced GI disease correlates with a more than twofold increased risk of death. The GI manifestations of SSc are heterogeneous, with possible involvement at any level, from the oral cavity down to the esophagus, stomach, small and large intestines, as well as the liver and pancreas, causing several clinical manifestations.

Upper GI involvement may result in esophageal dysmotility, gastroesophageal reflux disease (GERD), gastroparesis, GI bleeding due to esophagitis, esophageal or gastric ulcers, or gastric antral vascular ectasia (GAVE). Moreover, esophageal dysfunction has been closely linked to interstitial lung disease, indicating a possible pathogenic relationship. Lower GI-tract involvement (i.e., small intestine, large intestine, and anorectal) can also be severe, with complications including small intestinal bacterial overgrowth (SIBO), intestinal pseudo-obstruction, intestinal pneumatosis, and fecal incontinence. Impaired GI perfusion may be linked to motility disorders, which are key contributors to stasis, bowel dilation, bacterial overgrowth, malabsorption, weight loss, and ultimately reduced survival rate.

Early recognition of GI involvement is essential for symptom control and the prevention of complications. However, the diagnosis of GI involvement is challenging because it is often delayed by the lack of signs and symptoms early in the disease. Moreover, several diagnostic investigations that are useful in defining GI involvement are either invasive, expensive, or not very informative.

The involvement of the splanchnic circulation has only recently gained attention, despite vasculopathy being a systemic feature of SSc.

The vasculature of the GI tract can be evaluated noninvasively using abdominal Doppler ultrasound (DUS), a valuable tool that enables assessment of the GI vasculature and associated structures, including extra-intestinal features and splanchnic vessels. DUS measures signals from visceral vessels supplying the GI tract and evaluates the celiac trunk (CT), superior mesenteric artery (SMA), and inferior mesenteric artery (IMA) using pulsed Doppler scanning. It provides several quantifiable hemodynamic parameters, such as peak systolic, mean, and end-diastolic velocities, resistive index (RI), pulsatility index (PI), and blood flow volume.

Few studies have specifically investigated vascular abnormalities in the small and large intestines, particularly those affecting the superior and inferior mesenteric arteries. Among them, only one study has examined the correlation between DUS parameters of these mesenteric arteries and the involvement of other organs.