A case of advanced systemic sclerosis with severe GERD successfully treated with acotiamide
© Kato et al. 2016
Received: 14 January 2016
Accepted: 6 April 2016
Published: 13 April 2016
The majority of systemic sclerosis (SSc) patients have gastrointestinal tract involvement, but therapies of prokinetic agents are usually unsatisfactory. Patients are often compromised by the use of steroid; therefore, a surgical indication including fundoplication has been controversial. There is no report that advanced SSc with severe gastroesophageal reflux disease (GERD) is successfully treated with acotiamide, which is the acetylcholinesterase (AChE) inhibitor designed for functional dyspepsia (FD). We report a 44-year-old woman of SSc with severe GERD successfully treated with acotiamide. She had received medical treatment in our hospital since 2003. She had been aware of the significant gastroesophageal reflux symptoms (e.g., heartburn, chest pain, and dysphagia) due to the development of esophageal hardening associated with SSc since 2014. As a result of upper gastrointestinal series, upper gastrointestinal endoscopy, and 24-h pH monitoring and frequency scale for the symptoms of the GERD (FSSG) scoring, she has been diagnosed with GERD associated with SSc. First of all, she started to take prokinetic agents Rikkunshito and mosapride and proton pump inhibitor; there was no change in reflux symptoms. So, we started to prescribe her the acotiamide.
After oral administration started, reflux symptoms have been improved. Five months after oral administration, FSSG score, a questionnaire for evaluation of the symptoms of GERD, was improved. Since its introduction of acotiamide, the patient has kept free from symptoms for 6 months.
Keywordsacotiamide systemic sclerosis gastroesophageal reflux disease (GERD) functional dyspepsia (FD) frequency scale for the symptoms of the GERD (FSSG)
Systemic sclerosis (SSc) is a multisystem and chronic disease characterized by abnormalities of small blood vessels and fibrosis of the skin and internal organs. SSc, when advanced, is often compromised with severe gastroesophageal reflux disease (GERD), which may be lethal in a worst-case scenario. A wide variety of medication has been used [1–5]; however, none of them are promising for patients with SSc. In addition, patients with SSc are often compromised by the use of steroid; therefore, a surgical indication including fundoplication has been controversial.
In this short communication, we describe our recent case of advanced SSc patients with severe GERD, who was successfully treated with a new drug originally designed for functional dyspepsia (FD).
Since the introduction of acotiamide, the patient has been free from symptoms to date.
In 1994, Sjogren proposed a progression of SSc with gastrointestinal involvement, vascular damage, neurogenic impairment, and myogenic dysfunction with the replacement of normal smooth muscle by collagens fibrosis and atrophy . It is distinguished in diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc) whether skin hardening exceeds an elbow or a knee . Next to the skin, the gastrointestinal tract is the second most common site of SSc organ damage that can affect patients with lcSSc and dcSSc . It affects the gastrointestinal tract in more than 80 % of patients. Reflux esophagitis is found in 50–90 % of SSc patients [7, 10].
The common characteristics of GERD seen in SSc patients are as follows. The upper GI series often shows peristaltic decrease and expansion of the lower esophagus. The upper gastrointestinal endoscopy shows linear redness and erosion of the lower esophagus caused by the reflux, which often merges with the Barett esophagus. In addition, the merger frequency of esophageal cancer is often in SSc. Esophageal dysmotility leads to impaired acid clearance, and 24-h monitoring shows prolongation of esophageal exposure time to gastric acid .
Its treatment, either medical or surgical, has been still challenging. The major medical treatment option includes use of histamine-2 receptor antagonist (H2RA) and/or proton pomp inhibitor (PPI) for the purpose of controlling stimulation and inflammation of the esophageal mucosa by the gastric acid reflux [12–14]. Surgery, e.g., Nissen fundoplication, can be considered for drug-resistant reflux disease . These medical/surgical treatments have been shown not as promising as those for reflux patients without SSc .
The last option for SSc patients with severe GERD is a group of prokinetic drugs. A wide variety of prokinetic agents have been used, such as mosapride citrate, metoclopramide, domperidone, erythromycin, octreotide, and dinoprost [1–5]. However, therapies of traditional prokinetic agents are usually unsatisfactory for severe GERD patients.
Acotiamide is the novel prokinetic agent basically designed for FD; it is the acetylcholinesterase (AChE) inhibitor. FD is a chronic disorder of sensation and movement (peristalsis) in the upper gastrointestinal tract. The acetylcholine (Ach) is released from cholinergic nerve terminals and lets the gastrointestinal tract shrink by binding to the muscarinic receptor of the gastrointestinal smooth muscle. It is thought that the Ach is broken down immediately by AChE and enterokinesis is regulated by this reaction. Acotiamide inhibits AChE and regulates the resolution of Ach. As a result, it increases the quantity of ACh available in the synaptic cleft and therefore improves enterokinesis .
We have prescribed a variety of traditional prokinetic agents, without obtaining even temporary relief of her symptoms. Therefore, we prescribed acotiamide. We performed upper gastrointestinal series, gastrointestinal endoscopy, 24-h pH monitoring, and the quality of life (QOL) scores for the assessment of gastroesophageal reflux before and after oral administration of acotiamide on this patient. No changes were observed before and after treatment in the upper GI series and upper gastrointestinal endoscopy. Acotiamide does not show the emission promoting effect on the normal gastric emptying in rats. However, prior research reports that acotiamide does improve the gastric emptying during restraint stress. Acotiamide might have led to symptom improvement due to the suppressed response to stress by decreasing the expression of NmU, a stress-related gene in the hypothalamus, via the vagus nerve .We think this may be a partial reason why our patient showed improvement of her GI symptoms.
In the 24-h pH monitoring, DeMeester score even showed a worsening from 117 to 211. However, FSSG, which is one of the established QOL scoring system, showed improvement from total 34 to 21 points. FSSG is a questionnaire composed of 12 questions and classified into two groups, which are five items related to “dysmotility” symptoms and seven items to “acid reflux” symptoms. In our case, the score related to both symptoms were improved from 17 to 10 points and 17 points to 11 points, respectively. As we describe later, these improvements can be explained by the pharmacological effects of acotiamide on both the gastric and the esophageal functions.
In fact, this patient was clearly aware of the improvement of clinical symptoms, and QOL has been improved.
In our case, traditional prokinetic agents attempted prior to acotiamide were not effective. Only acotiamide showed substantial relief of the patient’s symptom. We speculated this might be because of these two factors: (1) pharmacologically, acotiamide may not only affect the gastric emptying but also improve fundic accommodation of adaptive relaxation, and (2) acotiamide may directly act on the esophageal body and improve esophageal peristalsis. The authors have reached the above speculation based on the results of FSSG score: improvements of early satiety and chest discomfort. The question score “Do you feel full while eating meals?” was improved from 4 points to 2 points and “Do some things get stuck when you swallow?” was improved from 3 points to 2 points, respectively.
We have experienced a case of advanced SSc with severe GERD successfully treated with acotiamide. Acotiamide might become a help of advanced SSc with severe GERD patient whose surgical indication has been controversial.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
frequency scale for the symptoms of the GERD
gastroesophageal reflux disease
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