Resolution Of Gastrointestinal Symptoms Research Articles

Probiotics, prebiotics and food allergy.

Background. The prevalence of food allergy (FA) has increased, a possible consequence of intestinal dysbiosis, environmental or genetic factors. Currently, no formal indications exist for probiotic or prebiotic supplementation in FA. This review aims to analyse the role of probiotics and prebiotics in the prevention and treatment of FA. Methods. A PubMed/Medline search was carried out on articles published between 2011 and 2021 with the following query: ("Food Hypersensitivity"[Mesh]) AND (("Probiotics"[Mesh]) OR ("Prebiotics"[Mesh])). Subsequently, the titles and abstracts were analysed and selected according to established criteria. After full reading of these articles, 54 were included and a narrative review was performed. Results. The review was structured in the following sections: i) Cow's Milk Proteins Allergy (CMA), ii) Food Allergy to Peanuts and iii) Prevention of Food Allergy. In CMA, several studies have supported the benefits of extensively hydrolysed casein formula supplemented with Lactobacillus Rhamnosus GG in the earlier acquisition of tolerance to cow's milk proteins, resolution of gastrointestinal symptoms and prevention of other allergic manifestations. In peanut oral immunotherapy (OI), supplementation with Lactobacillus Rhamnosus CGMCC 1.3724 seems to have a favourable impact in inducing a sustained desensitization response. Regarding the use of probiotics in the prevention of FA, this assumption lacks robust scientific evidence in order to confirm the effectiveness. Current evidence supports the use of oligosaccharides from breast milk in the first months of life for preventing atopic dermatitis, FA and asthma. Conclusions. The potential of probiotics to be used as therapeutic adjuvants in CMA and peanut OI is promising. However, there is inconsistency regarding the type of probiotic, the dose and duration of supplementation. Further studies are needed to clarify the role of probiotics and prebiotics in FA.

Long Term Outcomes in Patients with Anti-DPPX Autoimmunity (S22.009)

<h3>Objective:</h3> To describe long term outcomes in anti-DPPX encephalitis. <h3>Background:</h3> Dipeptidyl-peptidase-like protein 6 (DDPX) antibody-associated encephalitis is a rare type of immune-mediated encephalitis characterized by cognitive disorder, neuropsychiatric symptoms, and CNS hyperexcitability, preceded by prodromal weight loss and diarrhea. Although anti-DPPX encephalitis has been described to be immunotherapy responsive, data regarding long-term outcomes is lacking. <h3>Design/Methods:</h3> We retrospectively identified anti-DPPX encephalitis patients across all three Mayo Clinic sites using the neuroimmunology lab database with the following inclusion criteria: 1) DPPX cell-based assay positive samples in serum and CSF; 2) duration of follow up of at least 36 months from symptom onset to last follow up. <h3>Results:</h3> Six anti-DDPX patients were included (median age, 56.5 years; range, 28–70 years) with a median follow up of 70.5 months (range 42–144 months). Of these 67% (4/6) were males. Median time from symptom onset to initiation of treatment was 15.5 months (range 4–48 months). Only 16% (1/6) had a malignancy identified (CLL). All patients had prodromal weight loss and gastrointestinal (GI) symptoms. All patients had cognitive impairment ranging from mild symptoms to dementia. One had neuropsychiatric symptoms including agitation, paranoia, and delusions. Seizures were documented in 33% (2/6), none were drug resistant. All patients had resolution of GI symptoms at last follow up, but all had persistence of sleep disturbances. 100% (6/6) had relapses. One patient died who had severe dysautonomia, but cause of death is unknown. The rest had stability or improvement in symptoms determined objectively with Kokmen mental status exam, ambulatory status (5/6) and ability to return to work (1/6). 33% (2/6) were able to discontinue immunotherapy and remained stable. <h3>Conclusions:</h3> Overall long-term outcomes are good in anti-DPPX encephalitis. Relapses are common, particularly in the setting of weaning off immunotherapy. Patients can improve symptoms on treatment, but full resolution and return to premorbid baseline is unlikely. <b>Disclosure:</b> Dr. Dominguez has nothing to disclose. The institution of Dr. McKeon has received research support from Euroimmun AG. The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care. Dr. Lopez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Lopez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech .

Comparison of Hospitalized COVID-19 Patients in Terms of Disease Course According to the Presence of Gastrointestinal Symptoms Before and After Admission.

This study aimed to find the prevalence of gastrointestinal symptoms in hospitalized COVID-19 patients and to investigate the effects of gastrointestinal symptoms on the course of the disease during hospitalization. Patients who were hospitalized due to COVID-19 were included in this retrospective study. The diagnostic method of COVID-19 was either a positive reverse transcription polymerase chain reaction test or a typical finding in chest computed tomography. This study was conducted by contacting patients by phone 1 month after they were discharged from hospital to investigate gastrointestinal symptoms. Patients' laboratory findings at the time of admission, medications they used, and clinical findings were obtained from hospital records retrospectively. Patients with gastrointestinal symptoms were divided into 2 groups according to the start of treatment: pre-treatment and post-treatment groups. At least 1 gastrointestinal symptom (anorexia, weight loss, diarrhea, nausea, vomiting, and abdominal pain) was present in 67.5% of 435 patients (55.6% male, mean age 52.8). If anorexia and weight loss are excluded, the rate of the presence of at least 1 gastrointestinal symptom is 54%. Gastrointestinal symptoms were present in 48.9% before the initiation of COVID-19 treatment. The most prevalent 3 symptoms were anorexia, weight loss, and diarrhea (56%, 52%, and 35.6%, respectively). Presence of pre-treatment gastrointestinal symptoms was associated with elevated C-reactive protein levels. Pre-treatment gastrointestinal symptoms were more common in those who received oxygen supply and who were intubated. Resolution of gastrointestinal symptoms takes longer time in those who were admitted to intensive care unit. Weight loss and diarrhea were more common in COVID-19 patients with gastrointestinal symptoms who were intubated than who were not intubated. Abdominal pain was not found to be a significant predictor of disease severity. The prevalence of at least 1 gastrointestinal symptom in hospitalized COVID-19 patients was 67%. The most prevalent symptoms were anorexia, weight loss, and diarrhea. Presence of pre-treatment gastrointestinal symptoms was associated with elevated C-reactive protein levels, use of oxygen supply, and intubation. Gastrointestinal symptoms persist longer in those admitted to intensive care unit.

Narsoplimab for severe transplant-associated thrombotic microangiopathy

BackgroundTransplantation-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome linked to the overactivation of complement pathways. It manifests with microangiopathic hemolytic anemia, consumptive thrombocytopenia, and microvascular thrombosis leading to ischemic tissue injury. Mannose residues on fungi and viruses activate the mannose-binding lectin complement pathway, and hence activation of the lectin pathway could be one of the reasons for triggering TA-TMA. Narsoplimab, a human monoclonal antibody targeting MASP-2 is a potent inhibitor of the lectin pathway. We describe the transplant course of a pediatric patient who developed TA-TMA following Candida-triggered macrophage activation syndrome and was treated with Narsoplimab. The data collection was performed prospectively.Case presentationThe six-year-old girl underwent a human leucocyte antigen (HLA) haploidentical hematopoietic stem cell transplant using post-transplant Cyclophosphamide for severe aplastic anemia. In the second week of the transplant, the patient developed macrophage activation syndrome necessitating treatment with steroids and intravenous immunoglobulin. Subsequently, USG abdomen and blood fungal PCR revealed the diagnosis of hepatosplenic candidiasis. Candida-triggered macrophage activation syndrome responded to antifungals, steroids, intravenous immunoglobulin, and alemtuzumab. However, the subsequent clinical course was complicated by thrombotic microangiopathy. The patient developed hypertension in the 2nd week, followed by high lactate dehydrogenase (1010 U/L), schistocytes (5 per hpf), low haptoglobin (< 5 mg/dl), thrombocytopenia, and anemia in the 3rd week. Ciclosporin was stopped, and the patient was treated with 10 days of defibrotide without response. The course was further complicated by the involvement of the gastrointestinal tract and kidneys. She had per rectal bleeding with frequent but low-volume stools, severe abdominal pain, and hypoalbuminemia with a rising urine protein:creatinine ratio. Narsoplimab was started in the 5th week of the transplant. A fall in lactate dehydrogenase was observed after starting Narsoplimab. This was followed by the resolution of gastrointestinal symptoms, proteinuria, and recovery of cytopenia. The second episode of TA-TMA occurred with parvoviraemia and was also successfully treated with Narsoplimab.ConclusionLectin pathway inhibition could be useful in treating the fatal complication of transplant-associated thrombotic microangiopathy.

S1851 Chilaiditi Syndrome: A Case Report

Introduction: Chilaiditi’s sign was first defined over one hundred years ago by Demetrius Chilaiditi. Chilaiditi sign has a 0.025% to 0.28% incidence worldwide with a male to female ratio of 4:1. The bowel segments most commonly found interposed between the liver and diaphragm are the colonic hepatic flexure and transverse colon, however interposition of the small bowel can also occur. The following criteria must be met to diagnose Chilaiditi sign based on radiological findings: the right hemidiaphragm must be elevated above the liver by the intestine, the bowel must be distended by air to illustrate pseudo-pneumoperitoneum, and the superior margin of the liver must be depressed below the level of the left hemidiaphragm. Case description/methods: A 75 year-old-male presented with right sided flank pain for the past 9 months. He denied symptoms of nausea, vomiting, fever, chills, change in appetite, unexplained weight change, night sweats, melena or hematochezia. He reported chronic intermittent constipation, but he typically stooled daily or every other day. He had normal colonoscopy one year prior. Due to chronic nature of his pain, CT abdomen and pelvis was obtained. It showed anterior interposition of the hepatic flexure of the colon along the liver and right hemidiaphragm; this may be seen with Chilaiditi syndrome (Figure 1). Surgical correction was discussed, but conservative measures including diet, stool softeners, and exercise to promote weight loss and bowel regularity was instituted with resolution of gastrointestinal symptoms. Discussion: Patients with anatomical variants including absence, laxity, or elongation of the suspensory ligament are at increased risk for developing pathologic interposition. In patients with Chilaiditi syndrome, most common presenting symptoms abdominal pain, abdominal distention, nausea, emesis, constipation, and obstipation. The differential of Chilaiditi syndrome includes bowel obstruction, volvulus, intussusception, ischemic bowel, diverticulitis, appendicitis, subphrenic abscess, and pneumoperitoneum. In asymptomatic patients with Chilaiditi sign, treatment is usually conservative with stool softeners/laxatives and no interventions needed. Surgical intervention is indicated when the obstruction does not resolve with conservative management or there is evidence of bowel ischemia. The appropriate surgical approach depends on which segment of colon is interposed.Figure 1.: CT shows anterior interposition of the hepatic flexure of the colon along the liver and right hemidiaphragm.

An Herbal Formulation of Jiawei Xiaoyao for the Treatment of Functional Dyspepsia: A Multicenter, Randomized, Placebo-Controlled, Clinical Trial.

INTRODUCTION:To investigate the efficacy and safety of an herbal formulation of Jiawei Xiaoyao (JX) on gastrointestinal symptoms in patients with functional dyspepsia (FD) who had previously rejected standard therapies of proton pump inhibitors, H2 blockers, or Helicobacter pylori eradication.METHODS:A total of 144 adult men and women with FD according to the Rome III criteria were recruited at 9 sites in China from August 2017 to April 2019. Participants were randomized to receive either a JX pill or placebo (12 g/d, 6 g twice a day) for 4 weeks. The primary end point was the change in the total Gastrointestinal Symptom Score (GIS) from baseline to week 4. The secondary end points included the scores on the Hamilton Depression Scale and the Hamilton Anxiety Scale. The safety outcomes included the results of the complete blood count, the liver function test, the renal function test, urinalysis, the fecal occult blood test, and an electrocardiogram.RESULTS:Data from 141 patients (JX pill, n = 70; placebo, n = 71) were statistically analyzed. The mean ± SD of the GIS for the JX pill group at baseline and 4 weeks was 9.3 ± 3.1 and 3.8 ± 3.0, respectively; the mean ± SD of the GIS for the placebo group at baseline and 4 weeks was 9.5 ± 3.4 and 5.3 ± 4.4, respectively (change from baseline to 4 weeks in the JX pill group vs change from baseline in the control group, −1.3 points; P = 0.013). The JX pill group showed greater improvement in both the Hamilton Depression Scale and Hamilton Anxiety Scale scores from baseline to 4 weeks than the placebo group, but the difference was not significant. The total number of adverse events was 30 in the JX pill group vs 20 in the placebo group (P = 0.240).DISCUSSION:The JX pill was superior to the placebo in terms of improving the GIS in patients with FD but did not significantly improve depression or anxiety symptoms. These findings suggest that the JX pill may have a positive effect on the resolution of gastrointestinal symptoms in patients with FD who are seeking alternative therapies.

RIOCIGUAT AND GASTROPARESIS: A NOVEL ADVERSE EFFECT

SESSION TITLE: Fellows Pulmonary Vascular Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Riociguat is a novel agent for the treatment of pulmonary arterial hypertension (PAH) with known gastrointestinal side effects of nausea, vomiting, and diarrhea. We present a patient initiated on riociguat leading to severe gastroparesis, an adverse effect not previously described. CASE PRESENTATION: KB is a 53-year-old female with a history of rheumatoid arthritis (RA) and scleroderma who developed rapidly progressive dyspnea over 2 months. An echo demonstrated right heart strain, a comprehensive PH workup ensued and right heart catheterization (RHC) confirmed PAH.(Hemodynamics attached) She was initiated on combination therapy, riociguat and macitentan, with rapid clinical improvement. Three weeks later, she was admitted with nausea, vomiting, and newly elevated transaminases. Macitentan was held due to hepatotoxicity concerns without resolution of gastrointestinal symptoms. Esophagogastroduodenoscopy and abdominal CT scan were unrevealing. A gastric function study revealed pronounced dysmotility with 11% gastric emptying at 90 minutes. Promotility agents were added without benefit. We attributed her gastroparesis to scleroderma, continued riociguat and discharged her with modest improvement in GI symptoms. She was readmitted within a week with ongoing nausea and vomiting. We suspected drug involvement, stopped riociguat and observed marked improvement in 72 hours with complete resolution of GI symptoms at one month. DISCUSSION: KB is the first reported case of riociguat-induced gastroparesis. Onset of symptoms were approximately three weeks after starting riociguat. Initially assumed secondary to scleroderma, gastroparetic symptoms abated only after complete withdrawal of drug. Riociguat stimulates vascular smooth muscle via the nitric oxide-soluble guanyl cyclase-cyclic GMP (NO-sGC-cGMP) pathway. All three medications for pulmonary arterial hypertension targeting the NO pathway have been linked to gastrointestinal (GI) side effects, but a disproportionately high frequency of GI effects are associated with riociguat(1). The effect may be due to the high expression of sGC in the GI tract, including smooth muscle cells, interstitial cells of Cajal, and fibroblast-like cells(2). CONCLUSIONS: Nausea and vomiting are well-described side effects of riociguat that typically improve with anti-emetic therapy and time. We report a novel case of gastroparesis attributable to riociguat that failed to respond to usual therapies. Subjects predisposed to gastroparesis due to underlying connective tissue disease may be at additive risk. Reference #1: Khouri C, Lepelley M, Roustit M et al. Comparative safety of drugs targeting the nitric oxide pathway in pulmonary hypertension. Chest 2018; 154 (1):136-147. Reference #2: Lies B, Groneberg D, Friebe A. Toward a better understanding of gastrointestinal nitrergic neuromuscular transmission. Neurogastroenterol Motil 2014 Jul;26(7):901-12. DISCLOSURES: No relevant relationships by John Kingrey, source=Web Response No relevant relationships by Ami Perry, source=Web Response

Repeated Courses of Orally Administered Fecal Microbiota Transplantation for the Treatment of Steroid Resistant and Steroid Dependent Intestinal Acute Graft Vs. Host Disease: A Pilot Study (NCT 03214289)

Background: Steroid-resistant (SR) intestinal acute graft versus host disease (aGVHD) is a devastating complication of allogeneic hematopoietic stem cell transplantation. Preliminary reports suggest that fecal microbiota transplantation (FMT) administered through a nasogastric tube or colonoscopy may be an effective treatment. We report the results of a single-arm pilot study (NCT 03214289) using FMT in capsules to treat SR or steroid dependent (SD) intestinal aGVHD.Methods: The primary outcome was the occurrence of severe adverse events (SAEs) at 28 days post last FMT course. Secondary outcomes included GVHD response. Complete response (CR) was defined as resolution of gastrointestinal symptoms or reduction of steroid dose to 5 mg of prednisone. Partial response was defined as a decrease in severity of GVHD by at least one stage or a ≥40% reduction in steroid dose. Patients were eligible if they had SR or SD gut aGVHD without active infection or neutropenia. Per-protocol, participants received a course of 30 frozen capsules of fecal matter over two consecutive days. FMT courses could be repeated from the same or a different donor, at the treating physician's discretion. Capsules are produced from healthy unrelated donors who underwent vigorous screening. They are taken orally and are flavorless and odor-free. To characterize the impact of the FMT on the gut microbiota, stool samples of recipients were serially collected and underwent 16s rRNA sequencing.Results: To date, we have enrolled 7 patients with intestinal aGVHD (6 SR, 1 SD) (Table). The median dose of methylprednisolone (MP) was 1 mg/kg (interquartile range [IQR] 0.8-1.3 mg/kg). FMT was administered at a median of 39 days (IQR 21-58 days) from aGVHD diagnosis. A total of 15 courses of FMT were given. Patients received a range of 1-3 FMT courses (median 2). The capsules were well tolerated. Patient #1 developed Enterococcus Faecium bacteremia 2 days following the second FMT. To track the source of bacteremia, we performed targeted metagenomic sequencing. The enterococcus strain from the blood culture was identified in the recipient's pre-FMT stool sample but not in the FMT inoculum (i.e., capsule), confirming that the bacteremia was not an FMT complication. Similarly, patient #6 developed Pseudomonas aeruginosa bacteremia 3 days after the 2nd FMT. 16s rRNA sequencing of the donor capsule failed to demonstrate Pseudomonas taxa. No other SAEs suspected to be related to the FMT were observed. Two patients achieved a CR with complete resolution of GVHD symptoms. Patient #6 had a partial improvement following the 1st FMT, with a reduction of MP from 2 mg/kg to 1.3 mg/kg. Three days after the 2nd FMT, she developed fatal pseudomonas bacteremia, not related to the FMT as detailed above. At last follow-up (median 61 days, IQR 40-99), 3/7 patients were alive. Three patients died from consequences of active GVHD, while one patients who responded to FMT and was free of GVHD, succumbed to an invasive Aspergillus infection of the brain.16s rRNA sequencing of stool samples revealed bacterial domination (i.e., occupation of at least 40% of the microbiota by a single predominating taxon) of Escherichia(E) coli in four patients before FMT, with a major reduction following therapy. FMT was associated with the introduction of new bacteria and an increase in bacterial diversity in the recipient's stool (Figure).Conclusions: We demonstrate for the first time the utility of fecal microbiota transplantation in orally administered capsules for the treatment of severe intestinal acute GVHD. The capsules were well tolerated and safe. Metagenomic sequencing proved that a bacterial infection following FMT was not related to the procedure. Sequencing of the stool sample revealed bacterial domination with E.coli in 4/7 patients prior to the first FMT. Following FMT, bacterial diversity increased. Finally, 2/7 patients attained a complete response following therapy, suggesting a potential role of FMT in patient management.Figure. (A) Heatmap of operational taxonomics units (OTU). Each column marks a sequenced stool sample at a specific time point and rows individual taxas. The color code indicates relative abundance. Dotted lines represent an FMT course. Before FMT all patients, aside from patient #6, had markedly reduced diversity, with enrichment of OTUs following treatment. (B). Change of bacterial diversity, measured by the Shanon diversity index before and after FMTs. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

How genetic testing can lead to targeted management of XIAP deficiency-related inflammatory bowel disease.

X-linked lymphoproliferative disease type 2 (XLP-2, OMIM 300635) is a primary immunodeficiency caused by the loss of X chromosome-linked inhibitor of apoptosis (XIAP), the X-linked inhibitor of apoptosis gene at Xq25. XLP-2 individuals are susceptible to several specific and potentially fatal infections, such as Epstein-Barr virus (EBV). Children with XIAP-related XLP-2 may present with either familial hemophagocytic lymphohistiocytosis, often triggered in response to EBV infection, or with a treatment-refractory severe pediatric form of inflammatory bowel disease (IBD) that might be diagnosed as Crohn disease. However, this monogenic cause of IBD is distinct from adult Crohn disease (a polygenic and multifactorial disease) in its etiology and responsiveness to therapy. XLP-2 and the associated IBD symptoms are managed by a reduced-intensity conditioning regimen with an allogeneic hematopoietic stem cell transplantation that causes resolution of gastrointestinal symptoms. Exome sequencing has enabled identification of XIAP-deficient diseased individuals and has altered their morbidity by providing potentially lifesaving strategies in a timely and effective manner. Here, we summarize XLP-2 IBD treatment history and patient morbidity/mortality since its original identification in 2006. Since XLP-2 is rare, cases are probably undergiagnosed or misdiagnosed. Consideration of XLP-2 in children with severe symptoms of IBD can prevent serious morbidities and mortality, avoid unnecessary procedures, and expedite specific targeted therapy.Genet Med 19 2, 133-143.

A Case of Lialda®-Induced Pancreatitis

Introduction: A 63-year-old woman with a 5-year history of ulcerative colitis controlled with Lialda® for 2 years, psoriasis, and atrial fibrillation presented with acute pancreatitis. For the past several months, the patient experienced intermittent severe epigastric pain that radiated to her right upper quadrant and shoulder associated with nausea and vomiting. Her symptoms persisted despite a cholecystectomy for cholelithiasis in January 2014. In March, she had severe pancreatitis with a lipase level of 3000 U/L and a CT abdomen/pelvis showing inflammation surrounding the pancreas. She did not drink alcohol and a subsequent MRCP did not observe any evidence of common bile duct dilation or filling defect and showed resolving pancreatitis without obvious complications. The patient was kept NPO and her Lialda was stopped. However, the patient could not tolerate a diet and started to have watery, bloody, non-mucoid, explosive diarrhea 5 times per day associated with crampy, abdominal pain similar to her ulcerative colitis flares. She was started on mesalamine rectal enemas and Asacol®. Her diet was advanced and she was initially doing well, until she had abdominal pain after taking mesalamine. Due to concern over recurrent mild pancreatitis, the mesalamines were stopped and budesonide was started. The patient tolerated the medication well and was discharged with resolution of gastrointestinal symptoms. While azathioprine and mercaptopurine have been widely associated with acute pancreatitis (between 1-6% of exposed individuals develop acute pancreatitis), mesalamine-induced pancreatitis is rare. A population-based case-control study by Munk et al did not discern a significant association between the use of 5-ASA agents and increased risk of acute pancreatitis. In fact, Munk et al observed that patients with ulcerative colitis had a 1.5-fold greater risk of developing pancreatitis than patients without ulcerative colitis. Lialda-induced pancreatitis was only observed in 2 cases in clinical trials, both of which were attributed to hypersensitivity reactions. In this case, the patient likely first developed a Lialda-induced pancreatitis and then an ulcerative colitis flare once the Lialda was held. She was tried on an alternative 5-ASA agent but again developed abdominal pain possibly secondary to a mild pancreatitis. These episodes of drug-induced pancreatitis may have been due to the pH-dependent coating Lialda and Asacol share or to a general class effect of 5-ASA agents. This case describes a rare side effect of a common ulcerative colitis medication. In the future, physicians should consider pancreatitis on their differential for chronic abdominal pain in patients taking Lialda or other 5-ASA agents.

Intra‐arterial methylprednisolone for the management of steroid‐refractory acute gastrointestinal and hepatic graft versus host disease

Intra‐arterial methylprednisolone for the management of steroid‐refractory acute gastrointestinal and hepatic graft versus host disease

Repeated Dientamoeba fragilis Infections: A Case Report of Two Families from Sydney, Australia

We report cases of two unrelated families who both presented with recurrent Dienta-moeba fragilis infections. Subsequent antimicrobial therapy resulted in the clearance of D. fragilis and total resolution of gastrointestinal symptoms in both families. This report highlights the potentially recurrent nature of D. fragilis infections and the need for laboratories to routinely test for this organism.

Gastrointestinal Symptoms Associated with Orthostatic Intolerance

The term orthostatic intolerance is used to describe symptoms of hemodynamic instability such as lightheadedness, fatigue, impaired cognition and syncope that develop on assuming an upright posture. Common forms of orthostatic intolerance in childhood include postural tachycardia syndrome and neurally mediated hypotension. A descriptive report of the clinical characteristics of patients presenting with gastrointestinal symptoms who are ultimately found to have orthostatic intolerance. A medical record review of all patients referred to the pediatric gastroenterology service at the Johns Hopkins Children's Center who had an abnormal tilt table test between June 1996 and December 2000. Of 24 eligible subjects aged 9-17 years (mean, 14.3 years), four had postural tachycardia syndrome, eight had both postural tachycardia and neurally mediated hypotension, and 12 had neurally mediated hypotension alone. The most common presenting gastrointestinal symptoms were abdominal pain, nausea and vomiting. Median number of gastrointestinal symptoms per patient was 3 (range, 1-7), and 87% of the patients experienced gastrointestinal symptoms for more than 1 year and 48% experienced gastrointestinal symptoms for more than 3 years. Follow-up information was available on 18 patients. Seventy-eight percent of patients (14 of 18) had complete resolution of symptoms with treatment of orthostatic intolerance. Pediatric patients with chronic upper gastrointestinal symptoms may have underlying orthostatic intolerance. In patients with upper gastrointestinal symptoms and orthostatic intolerance, treatment of orthostatic intolerance may result in resolution of gastrointestinal symptoms.

Hypercalcemia due to excess 1,25-dihydroxyvitamin D in Crohn’s disease

Hypercalcemia has been described in patients with a number of granulomatous diseases, including sarcoidosis and mycobacterial infection. Disordered vitamin D metabolism is the root cause for the elevated serum calcium levels. A similar mechanism of abnormal vitamin D metabolism explained the hypercalcemia occurring in patients with lymphoma. Crohn's disease is a granulomatous disorder that is more commonly associated with hypocalcemia caused by poor calcium intake and decreased intestinal calcium absorption related to vitamin D deficiency as a consequence of malabsorption. A man with Crohn's disease who presented with hypercalcemia and acute renal failure is described. Biochemical parameters showed an elevated 1,25-dihydroxyvitamin D level, with a low-normal 25-hydroxyvitamin D level and decreased parathyroid hormone level. Inflammatory bowel disease had been clinically active during the preceding 2 months. With resolution of gastrointestinal symptoms, serum calcium, vitamin D, and parathyroid hormone levels returned to normal. Serum creatinine levels decreased toward normal. Angiotensin-converting enzyme (ACE) levels have been reported to be elevated in patients with sarcoidosis, particularly in the setting of active disease with hypercalcemia. Controversy exists about ACE levels in the face of active Crohn's disease: 1 report noted elevated levels, whereas other publications reported depressed levels. Our patient had an elevated ACE level in the setting of active bowel disease and hypercalcemia, and ACE levels returned to normal with resolution of gastrointestinal symptoms.

Arsenic intoxication presenting as a myelodysplastic syndrome: A case report

A case of arsenic intoxication presenting as a myelodysplastic syndrome is reported. A 41-year-old woman with a 6-month history of gastrointestinal and neurological symptoms was noted to be pancytopenic at presentation. A bone marrow aspirate revealed dysmyelopoietic changes involving all three marrow cell lines. Subsequent analysis of urine for heavy metals demonstrated very high levels of arsenic. Treatment with British anti-Lewisite (BAL) resulted in the resolution of gastrointestinal symptoms and hematological abnormalities although the neurological complications progressed. This case emphasizes that heavy metal intoxication should be considered in the differential diagnosis of any individual presenting with the hematological features of myelodysplasia especially when accompanied by clinical features considered atypical for primary or secondary myelodysplasia.

Endoscopic, radiographic, and clinical response to prolonged bowel rest and home parenteral nutrition in Crohn's disease.

Total parenteral nutrition is widely used as a therapeutic measure in patients with severe, active Crohn's disease unresponsive to conventional medical management. We have reviewed our experience with 10 patients with nonfistulous Crohn's disease treated by home parenteral nutrition (HPN) and bowel rest (nothing-by-mouth) assessing the nutritional, radiologic, endoscopic, and clinical responses. After a mean of 4.1 months of treatment, all patients had a marked improvement in nutritional status and resolution of gastrointestinal symptoms; 90% reduced their corticosteroid dose. Eight of nine patients had endoscopic and/or radiographic evidence of mucosal healing. Although 60% of patients were able to avoid surgery and tolerate refeeding, all six patients continue to require steroids to control symptoms. Our study suggests that HPN and bowel rest is a useful therapeutic approach to selected patients with active Crohn's disease, which permits a reduction in corticosteroid dosage and partial healing of mucosal lesions in most. Further studies are required to determine which patients should receive HPN and its optimal duration.