Catherine Bartholomew

CASE REPORT: Systemic Sarcoidosis Presenting as a Granulomatous Tattoo Reaction Secondary to Interferon-α Treatment for Chronic Hepatitis C and Review of the Literature

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Immune alterations involving heightened T-helper-1 responses have been proposed to play a major role in the pathogenesis of sarcoidosis. Interferon-alpha therapy and hepatitis C infection have been implicated in the development of a variety of autoimmune diseases. However, despite the wide use of IFN-alpha therapy for hepatitis C, only a few cases of sarcoidosis have been reported in this context. We report the case of a 42-year-old white female with hepatitis C, who developed systemic sarcoidosis shortly after therapy with IFN-alpha2b. The disease was heralded by the appearance of a cutaneous sarcoid/ foreign body granulomatous reaction at the site of an old tattoo. The sarcoidosis responded to a short course of oral prednisone therapy. We also reviewed the other reported cases and discussed the possible immunological mechanisms involved.

Rapamycin Inhibition of mTOR Reduces Levels of the Na+/H+ Exchanger 3 in Intestines of Mice and Humans, Leading to Diarrhea

BACKGROUND & AIMS The immunosuppressant rapamycin frequently causes noninfectious diarrhea in organ transplant recipients. We investigated the mechanisms of this process. METHODS We performed a retrospective analysis of renal transplant recipients treated with rapamycin from 2003 through 2010 at Albany Medical College, collecting data on serum levels of rapamycin. Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsy specimens from patients who did and did not receive rapamycin (controls), in ileum tissues from rats or mice given rapamycin, and in mice with intestine-specific disruption of mammalian target of rapamycin (Mtor) (mTOR(f/f):Villin-cre mice) or Atg7 (Atg7(flox/flox); Villin-Cre). Exchange activity and intestinal water absorption were measured using a pH-sensitive dye and small intestine perfusion, respectively. RESULTS Episodes of noninfectious diarrhea occurred in organ recipients after increases in serum levels of rapamycin. The expression of NHE3 was reduced in the ileal brush border of patients with diarrhea. In rats and mice, continuous administration of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed in mice with intestinal deletion of ATG7, indicating that autophagy is required for the reduction. Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). The intestines of mice with intestine-specific deletion of mTOR were dilated and contained large amounts of liquid stools; they also had reduced levels of total NHE3 and NHERF1 compared with control mice. We observed a significant reduction in Na(+)/H(+) exchange activity in ileum tissues from these mice. CONCLUSIONS Rapamycin inhibition of mTOR reduces levels of NHE3 and Na(+)/H(+) exchange activity in intestinal tissues of patients and rodents. This process appears to require the autophagic activity mediated by ATG7. Loss of mTOR regulation of NHE3 could mediate the development of diarrhea in patients undergoing rapamycin therapy.

A new lysozyme tyr54asn mutation causing amyloidosis in a family of Swedish ancestry with gastrointestinal symptoms

Familial amyloidoses are a group of inherited disorders that cause deposition of misfolded amyloidogenic proteins in various tissues, resulting in organ dysfunction. Point mutations in the coding region of seven different genes are known to cause clinically significant systemic amyloid disease. We describe a new mutation in exon 2 of the lysozyme gene associated with amyloidosis (ALys) in a 61-year-old woman with a 7-year history of non-bloody, watery diarrhea, and weight loss. Biopsies of the duodenum and stomach were positive for amyloid deposits in the lamina propria and blood vessels. Direct DNA sequencing of the lysozyme gene revealed a single base nucleotide transversion from T to A at the first position of codon 54, resulting in replacement of Tyr by Asn in the mature lysozyme protein (pTyr54Asn). Immunoblot analysis of amyloid fibrils extracted from a fat tissue sample confirmed lysozyme as the amyloid protein. Clinically, the phenotype associated with this lysozyme mutation featured chronic abdominal pain, diarrhea, weight loss, malabsorption, and sicca syndrome. There was no associated nephropathy as has been reported for other ALys mutations. We describe a new mutant lysozyme that presents with abdominal discomfort, diarrhea, weight loss, and sicca syndrome.

CASE REPORT: Hepatic Pseudocyst as the First Presentation of Squamous Cell Carcinoma of Uterine Cervix

We describe a patient with diffuse polycystic disease of the liver. The patients polycystic liver disease was found to be due to liver metastases from squamous cell carcinoma of the uterine cervix. No evidence of discrete masses was found in the liver using abdominal CT scan. Pseudocystic formation in the liver secondary to squamous cell carcinoma is very rare and has not previously been reported as a first presentation of a cervical cancer. Metastatic neoplasms need to be considered in the differential diagnosis of hepatic cysts.

Duodenal perforation by an inferior vena cava filter with staphylococcal bacteremia: a case report

BackgroundInferior vena cava filter complications can range from dislodgement to perforation. Patients who present with concomitant bacteremia have rarely been reported. Persistent bacteremia usually results from direct bacterial seeding from a source other than perforation of surrounding viscus. It is unclear if the risk of perforation is higher in patients who are bacteremic due to other causes.Case presentationWe report an interesting case of a 67-year-old white woman who presented with fever, chills, and right upper quadrant abdominal pain. Her blood cultures were positive for methicillin-sensitive Staphylococcus aureus with no obvious source. Upon further investigation, she was found to have an inferior vena cava filter perforating her duodenum. The cause of her abdominal pain was explained by the inferior vena cava filter penetrating the duodenum; however, the source of bacteremia could not be ascertained. The inferior vena cava filter was removed successfully, and she was discharged on an intravenous antibiotic. Her symptoms resolved soon after the filter was removed.ConclusionsThe use of inferior vena cava filters has increased significantly in recent years. This is likely due to their wider availability and safer placement techniques. With increasing use, the complications arising from these filters have been on the rise as well. It is very important for clinicians to be aware of these complications to avoid delays in diagnosis and patient care.

Tu1642 Inhibition of mTOR Mediates Alleviation of Intestinal Fibrosis via Suppression of Myofibroblast Proliferation

a porcine model of stress-induced gut injury. Nine-week-old pigs that were previously subjected to early weaning stress, co-mingled with unfamiliar (non-littermate) pigs to induce social stress. Six-hours following social stress, animals were treated daily with either lubiprostone (μ0.3μg/ kg) or placebo once daily gavage PO for 3-days. Following the treatment period, colonic tissues were harvested and mounted in Ussing chambers. The transepithelial electrical resistance (TER) in the colon of stressed pigs was found to be reduced by 30% compared to control non-stressed pig colon (p,0.01). Stressed pigs treated with lubiprostone showed significantly increased TER compared to placebo treated stressed pigs. Consistent with the changes in TER, stressed placebo-treated pigs had increased paracellular flux of 3H-mannitol, and treatment with lubiprostone prevented the increase in paracellular flux of mannitol caused by stress. Initial histopathological evaluation of tissues revealed no differences between groups in epithelial appearance, which appeared normal and continuous. However, further evaluation of the mucosa and sub mucosa is required. Thus, data demonstrate a beneficial influence of lubiprostone on intestinal barrier properties in a porcine model of psychosocial stress. * (Amitiza) -R-Tech-Ueno, Tokyo, Japan

Erratum to: Duodenal perforation by an inferior vena cava filter with staphylococcal bacteremia: a case report

Background: Inferior vena cava filter complications can range from dislodgement to perforation. Patients who present with concomitant bacteremia have rarely been reported. Persistent bacteremia usually results from direct bacterial seeding from a source other than perforation of surrounding viscus. It is unclear if the risk of perforation is higher in patients who are bacteremic due to other causes. Case presentation: We report an interesting case of a 67-year-old white woman who presented with fever, chills, and right upper quadrant abdominal pain. Her blood cultures were positive for methicillin-sensitive Staphylococcus aureus with no obvious source. Upon further investigation, she was found to have an inferior vena cava filter perforating her duodenum. The cause of her abdominal pain was explained by the inferior vena cava filter penetrating the duodenum; however, the source of bacteremia could not be ascertained. The inferior vena cava filter was removed successfully, and she was discharged on an intravenous antibiotic. Her symptoms resolved soon after the filter was removed. Conclusions: The use of inferior vena cava filters has increased significantly in recent years. This is likely due to their wider availability and safer placement techniques. With increasing use, the complications arising from these filters have been on the rise as well. It is very important for clinicians to be aware of these complications to avoid delays in diagnosis and patient care.

Autoimmune Enteropathy, A Rare Cause of Intractable Diarrhea Presenting in an 80-Year-Old Man: P-6 YI

The patient commenced with systemic steroid and immunomodulator therapy. His symptoms improved to one bowel movement a day with an increase in his weight. However, as the steroids were tapered, the diarrhea returned. Thereafter, therapy with intravenous infusion of infliximab was initiated. The patient is currently receiving azathioprine and infliximab while re-attempting to taper steroid therapy in an effort to control symptoms.

Sa1102 Refractory Anemia Due to Pyridoxine Deficiency in Patients With Crohn's Disease or Cirrhosis

Background/Aims: Pyridoxine or vitamin B6 deficiency is an established cause of sideroblastic anemia through the inhibition of heme synthesis. Reduced levels of this micronutrient has also been implicated in sickle cell anemia and anemia of pregnancy. In 1984, Diehl et al demonstrated an association between low serum alanine transaminase (ALT) and pyridoxine deficiency. The correlation between decreased pyridoxine and serum ALT level can therefore serve as a tool to identify patients with microcytic anemia associated with pyridoxine deficiency. Malabsorption is a prominent cause of pyridoxine deficiency, which is frequent in patients with IBD. Similarly, patients with cirrhosis suffer from defects in vitamin metabolism and thus are also susceptible to pyridoxine deficiency. We conducted a prospective study to identify pyridoxine deficiency in these patients using low ALT values as a marker of B6 deficiency. We theorize that supplementation with pyridoxine will correct the anemia. Methods: Patients with anemia who had either cirrhosis or Crohns disease at Albany Medical Center and some from Johns Hopkins Hospital were identified. Of the 203 patients with Crohns disease and 202 patients with cirrhosis, 29 and 33 patients, respectively, met the inclusion criteria and were incorporated into this study. Inclusion criteria were hematocrit < 36 g/dL, mean corpuscular volume (MCV) < 80, total iron < 30 ug/dL, and ALT < 25 IU/ L. Patients with folate deficiency or vitamin B12 deficiency were excluded from the study. Results: All eligible patients were contacted by letters or telephone calls. Preliminary results from the first 8 patients with microcytic anemia refractory to iron supplementation revealed low serum ALT and lower than normal plasma pyridoxine levels. These patients were prescribed 50 mg of oral pyridoxine to be taken daily. A repeat pyridoxine level, complete blood count, and iron studies were redrawn at the end of 2 months of treatment to evaluate for improvement in anemia. Of those 8 patients, six patients have completed treatment with improvement in hematocrit, ALT and pyridoxine levels. The remainig patients from both groups continue to be investigated. Conclusions: Persistent anemia unresponsive to iron supplementation associated with low ALT level may be due to pyridoxine deficiency in malnourished patients with chronic gastrointestinal or liver disease.