Chronic Gastrointestinal Dysmotility Research Articles

Safety of prolonged use of metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis

BackgroundMetoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc). MethodsA quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25–80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks. ResultsEighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used. ConclusionsUse of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.

Paraneoplastic neurological syndrome: an evolving story.

Paraneoplastic neurological syndrome (PNS) comprises a group of neurological disorders that result from a misguided immune response to the nervous system triggered by a distant tumor. These disorders frequently manifest before the diagnosis of the underlying neoplasm. Since the first reported case in 1888 by Oppenheim, the knowledge in this area has evolved rapidly. Several classic PNS have been described, such as limbic encephalitis, paraneoplastic cerebellar degeneration, encephalomyelitis, opsoclonus-myoclonus, sensory neuronopathy, Lambert-Eaton Myasthenic syndrome, and chronic gastrointestinal dysmotility. It is now recognized that PNS can have varied nonclassical manifestations that extend beyond the traditional syndromic descriptions. Multiple onconeural antibodies with high specificity for certain tumor types and neurological phenotypes have been discovered over the past 3 decades. Increasing use of immune checkpoint inhibitors (ICIs) has led to increased recognition of neurologic ICI-related adverse events. Some of these resemble PNS. In this article, we review the clinical, oncologic, and immunopathogenic associations of PNS.

S2795 Not Your Common Diarrhea

INTRODUCTION: Chronic diarrhea is a common encountered problem in the outpatient setting. Differential includes infectious, inflammatory, and malignant etiologies. We present a rare cause of chronic diarrhea, emphasizing need for physician awareness. CASE DESCRIPTION/METHODS: A 68-year-old male presented with chronic diarrhea, up to 12 bowel movements/day with nocturnal stools for the past 12 months. He described diffuse abdominal discomfort, dysgeusia, dysphagia, loss of appetite, & unintentional weight loss of 15 pounds over 1 year. Physical exam was benign. Initial labs including CBC, CMP, ESR, TSH, lipase, and infectious stool studies were unremarkable. An upper endoscopy showed mild antral erythema. Colonoscopy revealed multiple polyps less than 1 cm in size which were removed. Random biopsies were taken from the colon. Biopsies from the stomach, duodenum, and colon demonstrated amyloid deposits with apple-green birefringence on Congo red stain. Patient was referred to a tertiary care center for further evaluation, where a bone marrow biopsy revealed plasma cells expressing monotypic lambda cytoplasmic immunoglobuin light chains with CD38 & CD138, and no CD19 or CD45. This profile was consistent with AL (lambda) type amyloid deposition. He was further found to have amyloid deposits in the kidney, autonomic nerves, and heart. He received treatment with CyBordD (cyclophosphamide, bortezomib, dexamethasone) and an autologous stem cell transplantation. He is now in deep remission of AL amyloidosis. DISCUSSION: Chronic diarrhea is a common symptom, but can have a rare underlying etiology, such as amyloidosis. Prompt workup with endoscopy & biopsy with Congo red stain are diagnostically essential. Additionally, as different types of amyloidosis require different therapies, the diagnosis must be confirmed by biopsy with immunostaining. Gastrointestinal (GI) amyloidosis is a rare disease, clinically apparent in one percent of patients with AL (primary) amyloidosis. It can present as any of 4 syndromes: GI bleeding, malabsorption, protein-losing gastroenteropathy, or chronic GI dysmotility. The pathogenesis involves amyloid deposition in the muscularis mucosae, submucosa, and muscularis propria, which leads to protrusions & thickening of the intestinal wall. The prognosis of AL amyloidosis patients with GI involvement is worse than those without, as it may involve other organs and present with advanced disease. Therefore, early recognition, diagnosis, and management are crucial.

1975 Not Your Typical GI Bleeding: Gastrointestinal Involvement in Systemic Amyloidosis

INTRODUCTION: Systemic amyloidosis is a rare disease that occurs preeminently in the elderly and can affect different kind of organ systems depending on the locality of amyloid build-up. Most typically fibril formation causes damage to the kidney and heart. Here, we report the case of a man with systemic amyloidosis and sudden onset of Hematochezia. CASE DESCRIPTION/METHODS: A 90 y/o male with a history of chronic heart failure due to amyloidosis of unknown origin, CAD, AFib, HTN, HLD, OSAS, peripheral vascular disease, CKD and diverticulosis presented to the ED with one episode of bright red blood per rectum and microcytic anemia. On arrival patient did not have any abdominal pain, nausea, vomiting, or diarrhea. He continued to have several bloody episodes. Rectal exam showed bright red blood with clot and hard brown Bristol 1 stool balls without blood. Initial work up including CBC, CMP, and coags was notable for Hb 9.7 g/dl, Plts 137 × 10(3)/uL, Troponin 0.19 ng/mL, PT 36.6s, and INR 2.8. The patient received IV fluids and 3 units of RBCs, blood thinners and anti-platelet medication were held, and patient was prepped for colonoscopy. Endoscopy showed diffuse, friable, patchy, hemorrhagic mucosa in the transverse colon, hepatic flexure, ascending colon, and cecum, consistent with amyloid. Diverticulosis was confirmed with no evidence of active bleeding. No endoscopic interventions were performed given minimal benefit and risk of high rebleeding. DISCUSSION: There are about 30 different types of amyloidosis with a varying spectrum of clinical presentation.[i] In a retrospective study 3% of patients with amyloidosis had biopsy proven involvement in the GI tract.[ii] Intestinal involvement usually presents clinically with either GI bleeding, malabsorption, protein-losing gastro-enteropathy, or chronic gastrointestinal dysmotility. Given his cardiac and abdominal history and presentation with lower GI bleeding differential diagnosis were initially drawn to diverticular bleeding versus ischemic colitis. In this case, the colonoscopy results and pre-condition of amyloidosis were attributed to be the cause of hematochezia. Biopsies were not collected given bleeding risk and low impact on further management.

Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses

Although chronic gastrointestinal dysmotility syndromes are a common worldwide health problem, underlying causes for these disorders are poorly understood. We show that flavivirus infection of enteric neurons leads to acute neuronal injury and cell death, inflammation, bowel dilation, and slowing of intestinal transit in mice. Flavivirus-primed CD8+ Tcells promote these phenotypes, as their absence diminished enteric neuron injury and intestinal transit delays, and their adoptive transfer reestablished dysmotility after flavivirus infection. Remarkably, mice surviving acute flavivirus infection developed chronic gastrointestinal dysmotility that was exacerbated by immunization with an unrelated alphavirus vaccine or exposure to a non-infectious inflammatory stimulus. This model of chronic post-infectious gastrointestinal dysmotility in mice suggests that viral infections with tropism for enteric neurons and the ensuing immune response might contribute to the development of bowel motility disorders in humans. These results suggest an opportunity for unique approaches to diagnosis and therapy of gastrointestinal dysmotility syndromes.

A Case of a Non-Cancerous, Ulcerated Gastric Mass: Gastric Amyloidosis Causing Coffee Ground Emesis

Primary amyloidosis, or light chain (AL) amyloidosis is a rare finding in the gastrointestinal (GI) tract with 1% of patients with symptomatic gastric amyloidosis. Of these, 25-45% present with bleeding. We report a case of a patient with gastric AL amyloidosis presenting with upper GI bleeding, who was also found to have amyloidosis in a transplanted kidney he received about 20 years ago. A 71 year old man with end stage renal disease from hypertension, status post deceased donor kidney transplant in 1999, and heart failure with reduced ejection fraction presented with acute decompensated heart failure. His course was complicated by new deep venous thrombosis and non-ST elevation myocardial ischemia with a peak troponin of 20. He was subsequently started on a heparin drip but developed coffee ground emesis with a nadir hemoglobin of 6.3 gm/dL (baseline of 10) requiring blood transfusions. Initial endoscopy revealed class D esophagitis, a large, friable 7 cm ulceration with heaped margins in the pyloric channel extending into the antrum with adherent clot that was successfully removed, and no stigmata of active bleeding. Biopsy of the ulcer margin demonstrated reactive inflammation with negative H. pylori. Repeat biopsy from an endoscopy performed three days later for recurrent bleeding revealed findings of amyloidosis. This sample was analyzed by mass spectrometry, confirming AL (kappa) type amyloid deposition. His echo findings revealed worsening heart failure with severe diastolic dysfunction in a restrictive pattern concerning for amyloidosis but his cardiac MRI was negative for classical cardiac amyloid. A subsequent biopsy of his transplanted kidney revealed amyloidosis by Congo red stain and sclerosing glomerulopathy, but bone marrow biopsy was normal. He was started on chemotherapy with cyclophosphamide and bortezomib, but ultimately expired four months after his diagnosis. While gastric amyloidosis is an infrequent phenomenon, its visual characteristics with mucosal friability and erythema may mimic gastric cancer and should be considered in the differential when evaluating such masses. These patients may present with GI bleeding, malabsorption, protein-losing enteropathy, or chronic GI dysmotility, and correctly diagnosing amyloidosis may alter their management and prognosis.2616_A Figure 1. Ulceration after clot removed on initial EGD2616_B Figure 2. Fungating ulceration seen on second EGD2616_C Figure 3. Amyloidosis on Congo Red Stain

An Atypical Place for Amyloidosis

Amyloidosis is the abnormal extracellular tissue deposition of insoluble, pathologic fibrils composed of antiparallel beta-pleated sheets. Deposition can be systemic or organ-specific. Symptomatic gastric amyloidosis is rare given that only 0.08% of those afflicted with the disease demonstrate gastrointestinal bleeding, malabsorption, protein-losing gastroenteropathy, and chronic gastrointestinal dysmotility. A known correlation exists between multiple myeloma and amyloidosis. This is a case of a 75 year old male with multiple myeloma who was found to have gastric and duodenal amyloidosis on evaluation of nausea, abdominal pain and dysphagia with EGD. For his multiple myeloma the patient underwent treatment for several months with dexamethasone, cyclophosphamide, and bortezomide. On a follow up visit, he endorsed several weeks of nausea, epigastric abdominal pain and dysphagia (mainly to solids) and thus EGD was performed. He was found to have a mild, non-obstructing Schatzki ring at the gastroesophageal junction. It was dilated to a maximum TTS balloon size of 20mm with complete resolution of luminal narrowing. He was also found to have localized moderately erythematous mucosa without bleeding in the gastric antrum as well as two 5mm non-bleeding cratered duodenal bulb ulcers with no stigmata of bleeding. These sites were biopsied and confirmed to have abundant amyloid deposition in the lamina propria via the Congo red special stain. Amyloid deposition can occur in the lower esophageal sphincter thereby decreasing lower esophageal sphincter pressure and cause symptoms of dysphagia and acid reflux, however typical symptoms of gastrointestinal amyloidosis include hematochezia, melena, malabsorption and dysmotility. Gastric amyloidosis, though rare, should be considered on differential diagnosis in individuals with known multiple myeloma who present with nausea, abdominal pain and dysphagia.

Chronic Gastrointestinal Dysmotility and Pain Following Total Pancreatectomy with Islet Autotransplantation for Chronic Pancreatitis

BackgroundThe prevalence and impact of chronic gastrointestinal dysmotility following total pancreactectomy with islet autotransplantation (TP-IAT) for chronic pancreatitis is not known. MethodsA cross-sectional study of all patients who underwent TP-IAT at our institution from August 2011 to November 2015 was undertaken. The GCSI (Gastroparesis Cardinal Symptom Index), PAGI-SYM (Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index), PAC-SYM (Patient Assessment of Constipation Symptoms), Bristol stool chart, 12-item Short Form Health Survey (SF-12), and visual analog scale for pain were administered ≥4 weeks following TP-IAT. Key ResultsThe prevalence of any dysmotility symptoms in patients who completed the survey (33/45, 73%) post-TP-IAT was 45%. Post-TP-IAT, the mean reduction in opioid dosing was 77.6 oral morphine equivalents (OMEs) (95% CI 32.1–123.0, p = 0.002) with 42% of patients requiring no opioids. There was significant negative correlation between dysmotility scores and SF-12 physical scores (r = −0.46, p = 0.008, 95% CI −0.70 to −0.13). Self-reported abdominal pain had significant negative correlation with both physical and mental SF-12 scores (r = −0.67, p < 0.001, 95% CI −0.83 to −0.41 and r = −0.39, p = 0.03, 95% CI −0.65 to −0.04). There was no correlation between gastrointestinal dysmotility and self-reported pain. Conclusions and InferencesSymptoms of chronic gastrointestinal dysmotility and chronic abdominal pain are common post-TP-IAT and will need to be better recognized and differentiated to improve the management of these patients.

Gastrointestinal Amyloidosis: A Rare Cause of Chronic Diarrhea

Introduction: GI manifestations of amyloidosis include GI bleeding, malabsorption, protein losing enteropathy and rarely chronic gastrointestinal dysmotility. We present a case of amyloidosis-related chronic gastrointestinal dysmotility that presented as chronic diarrhea. Case: A 65 year old male was transferred from an outside hospital for a 6 month history of diarrhea and orthostatic hypotension. He had a history of diabetes and hypertension and had been hospitalized for a month prior to transfer. Orthostasis workup included CT head, carotid US, random cortisol and cosyntropin stimulation test which were all normal. Echocardiogram was done to rule out cardiac causes of orthostasis and showed an EF of 55%, mild LV hypertrophy and diastolic dysfunction. Chronic diarrhea workup included fecal leukocytes, Giardia stool antigen, C. difficile toxin PCR, stool microscopy and culture, US abdomen, CT abdomen, EGD, colonoscopy and celiac panel which were all normal. Orthostasis was felt to be due to volume depletion from diarrhea and autonomic dysfunction.On arrival he was notably orthostatic with BP dropping from 156/90mmHg to 74/44mmHg and was treated aggressively with IV fluids, increasing doses of fludrocortisone and midodrine. He continued to have 5-6 loose bowel movements daily despite loperamide. EMG showed advanced sensory and motor polyneuropathy thought to be due to DM. A repeat echo showed an EF of 60% and severe concentric LV hypertrophy with increased echogenicity. Cardiac MRI showed severe left ventricular hypertrophy with evidence of delayed hyper enhancement in the mesocardial anterior septum and anterolateral walls on delayed images consistent with cardiac amyloidosis. A fat pad biopsy followed by a repeat EGD and colonoscopy with duodenal and colonic biopsies were all positive for AL amyloid. Diarrhea improved with Lomotil and he was discharged with a follow up with Hematology. Discussion: Chronic diarrhea is a rare presentation of gastrointestinal amyloidosis. Only 3% of the cases of amyloidosis have biopsy proven amyloid involvement of the GI tract. Of these, approximately 80% have systemic amyloidosis at the time of diagnosis. Considering the non-specific appearance of GI amyloidosis on endoscopy/colonoscopy, the diagnosis requires a tissue biopsy with confirmatory staining or amyloid fibrils seen on electron microscopy. It is important to consider the diagnosis of amyloidosis while evaluating chronic diarrhea with other systemic manifestations.Figure 1Figure 2Figure 3

920 Chronic Gastrointestinal Dysmotility and Its Effect on Quality of Life in Chronic Pancreatitis Patients Following Total Pancreatectomy With Islet Autotransplantation (TP-IAT)

920 Chronic Gastrointestinal Dysmotility and Its Effect on Quality of Life in Chronic Pancreatitis Patients Following Total Pancreatectomy With Islet Autotransplantation (TP-IAT)

Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility.

Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under-recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility (AGID). Twenty-three subjects evaluated at the Mayo Clinic for suspected AGID (August 2006-February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy-manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6-12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra-intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re-evaluated had scintigraphic evidence of improvement. The majority of responders who were re-evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy.

A Novel 3670-Base Pair Mitochondrial DNA Deletion Resulting in Multi-systemic Manifestations in a Child

Mitochondrial DNA (mtDNA) deletion is a rare occurrence that results in defects to oxidative phosphorylation. The common clinical presentations of mtDNA deletion vary but include mitochondrial myopathy, Pearson syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. Here, we report the case of a 10-year-old boy who presented with progressive deterioration of his clinical status (which included hypoglycemia, short stature, sensorineural hearing loss, retinitis pigmentosa, and chronic gastrointestinal dysmotility) that progressed to acute deterioration with pancreatitis, Fanconi syndrome, lactic acidosis, and acute encephalopathy. Following treatment, the patient was stabilized and his neurological condition improved. Through a combination of histological examinations and biochemical and molecular analyses, mitochondrial disease was confirmed. A novel 3670-base pair deletion (deletion of mtDNA nt 7,628-11,297) was identified in the muscle tissue. A direct repeat of CTACT at the breakpoints was also detected.

Evolution of acute cytomegalovirus gastritis to chronic gastrointestinal dysmotility in a nonimmunocompromised adult

A 30-year-old nonimmunocompromised woman developed chronic gastrointestinal dysmotility as a consequence of acute cytomegalovirus infection. The acute nature of the infection was documented by high immunoglobulin M antibody titer to cytomegalovirus (CMV); the chronicity of the infection was shown by persistence of CMV in biopsy specimens of her gastrointestinal tract over a 2½-year period. Gastrointestinal dysmotility was confirmed by delayed emptying on gastric nuclear scintigraphy, by retrograde propagation of migrating myoelectric complexes on small intestinal manometry, and by presence of tachygastria on cutaneous electrogastrography. The patient's nausea, vomiting, abdominal pain, and early satiety resolved after a short course of treatment with leuprolide acetate but returned after medication was discontinued. Her symptoms persisted despite clearance of CMV from the gastrointestinal tract after a course of treatment with ganciclovir. These observations show that acute CMV infection can cause gastrointestinal dysmotility in nonimmunocompromised individuals and that the disturbance in gastrointestinal motor function may persist for years after viral infection of the gastrointestinal tract has been eradicated. GASTROENTEROLOGY 1999;116:953-958