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Pathophysiology of systemic sclerosis
Source publication
The gastrointestinal tract (GI) is the second most affected organ system in individuals suffering from systemic/localized scleroderma (SSc) or localized scleroderma. SSc can affect any part of the GI, between the oral cavity and anorectum. The annual incidence of SSc in the United States is estimated to be 19.3 cases per million adults, with the hi...
Citations
... Involvement of the upper and lower gastrointestinal tract (GIT) can occur in SSc [58]. The esophagus is the most commonly affected part of the GI tract, occurring in > 80% of SSc patients [59], although any part can be involved. ...
Purpose of Review
Systemic sclerosis (SSc) is a chronic, multisystem, autoimmune disease characterized by fibrosis, vasculopathy and immune system dysregulation. We provide a comprehensive review of features of systemic sclerosis that can potentially present to the allergist.
Recent Findings
A thorough understanding of the management options is crucial for clinicians involved in the care of patients with SSc to optimize clinical outcomes. Management of systemic sclerosis has drastically changed in the last decade and continues to evolve.
Summary
This review provides an overview of management strategies for the various symptoms including skin, upper and lower airway, gastrointestinal and vascular manifestations. Institution of treatment early in the disease, including referral to rheumatology or specialized scleroderma centers, can help to both prevent and manage disease complications, and improve patient quality-of-life. While the landscape of systemic sclerosis management has evolved, we continue to recognize that there is still a need for better biomarkers and targeted therapies.
... We also found that fewer years of education, self-reported race or ethnicity other than White, living in Canada or the UK, having a higher BMI, pruritus, pain intensity and mRSS were associated with greater impairment in satisfaction with one's social functioning. Among those with large associations, gastrointestinal involvement may reduce one's ability to carry out social roles due to symptoms such as nausea, abdominal pain or faecal incontinence 36 ; pulmonary arterial hypertension can cause breathlessness, fatigue and dizziness, which can impact the ability to perform everyday tasks such as travelling to work or taking care of household chores 37 38 ; hand and joint involvement can decrease one's the ability to carry out many tasks necessary for work or household roles 8 ; overlap syndromes, including rheumatoid arthritis or Sjogren's syndrome, present their own challenges and can exacerbate other symptom-related barriers from SSc. ...
Objective
The objectives were to (1) compare satisfaction with social roles and activities in a large multinational systemic sclerosis (SSc) cohort to general population normative data and (2) identify sociodemographic, lifestyle and SSc disease factors associated with satisfaction with social roles and activities.
Methods
Participants in the Scleroderma Patient-centered Intervention Network Cohort completed the Patient Reported Outcomes Information System Version 2 satisfaction with social roles and activities domain questionnaire. Multivariable regression was used to assess associations with sociodemographic, lifestyle and disease factors.
Results
Among 2385 participants, mean satisfaction with social roles and activities T-score (48.1, SD=9.9) was slightly lower than the US general population (mean=50, SD=10). Factors independently associated with satisfaction were years of education (0.54 per SD, 95% CI 0.14 to 0.93); non-White race or ethnicity (−1.13, 95% CI −2.18 to –0.08); living in Canada (−1.33, 95% CI −2.40 to –0.26 (reference USA)) or the UK (−2.49, 95% CI −3.92 to –1.06); body mass index (−1.08 per SD, 95% CI −1.47 to –0.69); gastrointestinal involvement (−3.16, 95% CI −4.27 to –2.05); digital ulcers (−1.90, 95% CI −3.05 to –0.76); moderate (−1.62, 95% CI −2.78 to –0.45) or severe (−2.26, 95% CI −3.99 to –0.52) small joint contractures; interstitial lung disease (−1.11, 95% CI −1.97 to –0.25); pulmonary arterial hypertension (−2.69, 95% CI −4.08 to –1.30); rheumatoid arthritis (−2.51, 95% CI −4.28 to –0.73); and Sjogren’s syndrome (−2.42, 95% CI −3.96 to –0.88).
Conclusion
Mean satisfaction with social roles and activities is slightly lower in SSc than the general population and associated with multiple sociodemographic and disease factors.
... An increased deposition of collagen and other components of the extracellular matrix leads to fibrotic changes in the upper and lower GI tract, resulting in dysmotility, malabsorption, malnutrition, and dilation of the intestine [46,47]. The commonly reported symptoms of SSc include meteorism (87%), fecal incontinence (23%), and features related to reduced esophageal motility or gastroparesis like dysphagia, heartburn, and gastrointestinal reflux symptoms [6,46]. ...
... An increased deposition of collagen and other components of the extracellular matrix leads to fibrotic changes in the upper and lower GI tract, resulting in dysmotility, malabsorption, malnutrition, and dilation of the intestine [46,47]. The commonly reported symptoms of SSc include meteorism (87%), fecal incontinence (23%), and features related to reduced esophageal motility or gastroparesis like dysphagia, heartburn, and gastrointestinal reflux symptoms [6,46]. In addition to the pulmonary clinical manifestations, coughing and a sore voice can occur [47,48]. ...
... The EULAR Scleroderma Trial and Research cohort revealed 6.6% of deaths from SSc that resulted from gastrointestinal complications among elderly patients and patients with diffuse skin involvement [46,67]. The fibrosis of oral and perioral tissues, chronic inflammation, deformity of the oral cavity, and misalignment of osseous structures that result in microstomia and malocclusion of the teeth are the causes of oropharyngeal problems [46]. ...
Systemic sclerosis (also known as scleroderma) is a chronic fibrosing autoimmune disease with both skin and multisystem organ involvement. Scleroderma has the highest mortality among all rheumatic diseases. The pathophysiology mechanism of systemic sclerosis is a progressive self-amplifying process, which involves widespread microvascular damage, followed by a dysregulation of innate and adaptive immunity and inflammation and diffuse fibrosis of the skin and visceral organs. Fibrosis of internal organs is a hint for systemic sclerosis, moreover associated with interstitial lung disease (SSc-ILD) is a complex process. In order to correlate scientific data from the literature with clinical experience, we present the case of a 56-year-old woman who was diagnosed with systemic sclerosis 16 years ago. The association of numerous comorbidities characterized by a considerable level of seriousness characterizes this case: the highly extensive systemic damage, the cardiovascular impact of the illness, and the existence of severe pulmonary arterial hypertension. The systemic and clinical manifestations, respiratory functional tests, radiological features, and specific therapy are discussed.
... 40-70% of systemic sclerosis patients experience small bowel movement which is associated with bacterial growth leading to malabsorption showing that GI complications are more common in systemic sclerosis. 5 Studies have shown that 50% of systemic sclerosis patients experience clinically significant and symptomatic GI involvement. Magnesium plays a crucial role as a cation being implicated in many biochemical and physiological processes in our bodies. ...
Proton pump inhibitors (PPI) are the class of drugs used to treat a wide variety of disorders related to the stomach's acid production. Although it is considered safe for short term use, reports revealed that many serious life-threatening adverse reactions occurred from long term use. Here we report a case of hypomagnesemia and hypocalcemia induced by long-term use of PPIs in a patient with crest syndrome. From his past history, it was revealed that he was on pantoprazole 40 mg for more than 3 months. While he was admitted here for other complaints, we were able to discover that he had hypomagnesemia defined by low magnesium level of 1.3 mg/dL. As a consequence, he also showed signs of hypocalcemia with a low calcium level of 7 mg/dL. A peculiar complaint seen in this patient was three episodes of supraventricular tachycardia which is the most common cardiac manifestations of hypomagnesemia. As a conclusion, hypomagnesemia can sometimes be asymptomatic and cause unspecific and serious manifestations such as asthenia, paresthesia’s, seizures, arrhythmias, and cardiac arrest. Hence routine monitoring of serum magnesium and calcium levels should be made mandatory in practice for patients on long term use of PPI. Besides, it should be kept in mind that interchanging PPI class with histamine 2 receptor antagonist or fitful use of PPI may not cause hypomagnesemia.
... Gastrointestinal symptoms or respiratory symptoms are occasionally the first manifestations [1]. Esophageal dysmotility is one of the most frequent complications, present in approximately 90% of patients with SSc, and patients with primarily gastrointestinal symptoms are associated with increased mortality [7][8][9]. Esophageal smooth muscle damage (atrophy and fibrosis), caused by ischemia, nerve damage, and inflammatory factors, can lead to esophageal dysmotility, particularly in the lower esophageal smooth muscle in decreased esophageal clearance [8][9][10]. In addition, dysphagia is the other important comorbidity affecting the quality of life of patients with SSc. ...
... Esophageal dysmotility is one of the most frequent complications, present in approximately 90% of patients with SSc, and patients with primarily gastrointestinal symptoms are associated with increased mortality [7][8][9]. Esophageal smooth muscle damage (atrophy and fibrosis), caused by ischemia, nerve damage, and inflammatory factors, can lead to esophageal dysmotility, particularly in the lower esophageal smooth muscle in decreased esophageal clearance [8][9][10]. In addition, dysphagia is the other important comorbidity affecting the quality of life of patients with SSc. ...
Systemic sclerosis (SSc) is often associated with dysphagia and esophageal dysmotility; however, only a few clinical studies on this topic have been conducted. Patients with SSc who underwent swallowing examinations and esophagography at our institution between 2010 and 2022 were included. A retrospective evaluation of the patients’ backgrounds, autoantibody positivity, swallowing function, and esophageal motility was performed using medical charts. The association between dysphagia and esophageal dysmotility in patients with SSc and respective risk factors was investigated. Data were collected from 50 patients. Anti-topoisomerase I antibodies (ATA) and anti-centromere antibodies (ACA) were detected in 21 (42%) and 11 (22%) patients, respectively. Dysphagia was present in 13 patients (26%), and esophageal dysmotility in 34 patients (68%). ATA-positive patients had a higher risk for dysphagia (p = 0.027); ACA-positive patients had a significantly lower risk (p = 0.046). Older age and laryngeal sensory deficits were identified as risk factors for dysphagia; however, no risk factors for esophageal dysmotility were identified. No correlation was found between dysphagia and esophageal dysmotility. Esophageal dysmotility is more common in patients with SSc than in those with dysphagia. Autoantibodies can be predictors of dysphagia, and dysphagia must be carefully considered in ATA-positive and elderly patients with SSc.
Objectives
Gastric involvement in patients with early systemic sclerosis (SSc) has not been previously investigated. We aim to evaluate the association of gastric dysrhythmias with gastrointestinal (GI) symptoms and nailfold video capillaroscopy (NVC).
Methods
Cross-sectional study. Patients with early SSc, completed the UCLA GIT 2.0 questionnaire, performed an NVC, and a surface Electrogastrography (EGG). Descriptive statistics was used for demographic and clinical characteristics and Fisher and Kendall Tau tests were used for association analysis.
Results
75 patients were screened, 30 patients were consecutively enrolled, 29 performed the EGG and 1 patient had a non-interpretable NVC. 29/30 were female with a mean age of 48.7 years (25–72). The mean disease duration from the first non-RP symptom was 22.6 +/-10.8 months and most of the patients had limited disease (76.6%). Total GIT 2.0 score symptoms were moderate-severe in 63% of the participants and 28/29 had an abnormal EGG. Bradygastria was the most common pattern present in 70% of the participants. NVC patterns: 17% early, 34% active, 28% scleroderma-like, 14% non-specific, and 2 patients had a normal NVC. There was no association between severe GI symptoms or NVC patterns and severely abnormal EGG, but the presence of bradygastria was associated with severe impairment in the social functioning area (p 0.018).
Conclusions
Gastric dysmotility is common in early SSc and there is a lack of correlation between GI symptoms and NVC scleroderma patterns. EGG is a sensitive, cheap, and non-invasive exam, that may be an alternative to early diagnosis of GI involvement.
Aims: Gastrointestinal (GI) involvement is frequently observed in Systemic sclerosis (SSc). Considering the effect of GI involvement on SSc patients, the risk of malnutrition might be increased. The study aimed to evaluate GI involvement and the risk for malnutrition and to demonstrate the relationship between disease-related features and risk factors for malnutrition in SSc patients. Methods: SSc-related clinical features and disease severity evaluated with Physician Global Assessment (PGA) were recorded. Detailed GI symptoms and the impact of GI involvement on patients were assessed with the UCLA SCTC GIT 2.0 questionnaire. Nutritional status was evaluated with Body Mass Index (BMI) and the Malnutritional Universal Screening Tool (MUST). Results: 104 SSc patients were involved in the study. Mean age of patients with SSc was 52.24±12.82 years. GI involvement was found in 85.7% of patients. 76% of patients had GI symptoms. The median BMI of patients was 25.3 (9) kg/m² with 4.8% of patients categorized as underweight. The assessment of risk for malnutrition using MUST showed 74% of patients at low risk, 16% at moderate risk, and 9.6% at high risk. No important association was detected between risk groups for malnutrition and UCLA GIT 2.0 score. A significant association was found between moderate to high risk for malnutrition and dcSSc (OR 3.12, %95 CI:1.26-7.73; P=0.01), the presence of GI symptoms (OR 5.32, %95 CI:1.16-24.36; P=0.03), the decrease in oral aperture (OR 0.35, %95 CI:0.15-0.79; p:0.02), and severity of the disease investigated by PGA score (OR 1.52, %95 CI:1.09-2.13; p=0.01). Conclusion: GI involvement is a common manifestation in SSc patients. Approximately 26% of patients were at moderate to high risk for malnutrition. Several SSc-specific clinical features, including disease severity, the presence of GI symptoms, dcSSc, and a decrease in oral aperture were related to a higher risk for malnutrition.
