1954
Letters to the Editor
patients and accessibility of direct-acting anti-HCV agents (DAA). Dr Muir has presented a timely and balanced review of the prevalence and treatment strategies for chronic HCV, but we have a long way to go in terms of treating a sizeable proportion of those afflicted (1). While HCV is highly prevalent, affecting more than four million patients (2), only 25% of these cases are known (3). Active efforts to detect cases using the new Centers for Disease Control and Prevention screening guidelines are needed. As we cannot wait to treat a certain group of patients with risk factors for rapid progress of fibrosis or with advanced fibrosis, DAA definitely have great value and excellent cost-saving potential in these cases in the short and long run. However, for asymptomatic 0–2 fibrosis cases the value of this treatment may be relatively lower, as two-thirds may have slow progression and one-third may not develop cirrhosis (4) (http://www.cdc.gov/hepatitis/HCV/ HCVfaq.htm#section1). For asymptomatic patients with the early disease without risk factors, can we wait for short periods for the more cost-effective regimens to appear? In addition, as rightly stated by Dr Muir, there are concerns about the accessibility of DAA. Dr Muir’s article implies ~60% of HCV patients are likely uninsured or under Medicaid and/or Medicare. A sizeable number may not have any insurance due to some states’ rejection of federal money for Medicaid expansion (1). Only one-third of the HCV patients have private insurance (1). This could have chilling effects on both public (Medicaid/Medicare/health exchanges) and private healthcare funding agencies. Many payers do not have the money to fund these expensive treatments. For example, Oregon’s Medicaid needed $360 million to cover DAA alone, whereas its total annual prescription drug budget is only $370 million (http://www.washingtonpost.com/blogs/ wonkblog/wp/2014/07/24/the-drugthats-forcing-americas-most-importantand-uncomfortable-health-care-debate/). Owing to high costs, many state Medicaid agencies have already restricted the use of DAA to solely stage 3–4 fibrosis cases.
The American Journal of GASTROENTEROLOGY
nature publishing group
The inaccessibility of DAA cases also raises the following issue: what treatment options are available for Medicaid patients with stage 0–2 chronic HCV, or for patients supported by lower-budget county health plans that support older regimens through non-profit foundations, since American Association for the Study of Liver Diseases/Infectious Diseases Society of America (AASLD/ IDSA) guidelines do not recommend older regimens like ribavirin/pegylated interferon/ 1st gen protease inhibitor treatment (even though they are 65–80% effective) (http://www.hcvguidelines.org/full-report/ initial-treatment-hcv-infection-patientsstarting-treatment)? Hopefully, we will formulate a more pragmatic regimen within the next 18–24 months. By this time multiple new products will hopefully be approved, and free market competition will bring prices down to an affordable level. However, there is concern that a “shadow pricing” strategy may limit the decline in price (http://www.washingtonpost.com/blogs/wonkblog/wp/2014/07/24/ the-drug-thats-forcing-americas-mostimportant-and-uncomfortable-health-caredebate/). As providers, we should continue to seek better coverage for our vulnerable patients and work to improve detection of this disease. CONFLICT OF INTEREST The author declares no conflict of interest. REFERENCES 1. Muir AI. The rapid evolution of treatment strategies for hepatitis C. Am J Gastroenterol 2014;109:628–35. 2. Denniston MM, Jiles RB, Klkevens RM et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med 2014;160:293–300. 3. IOM (Institute of Medicine). Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C The National Academies Press: Washington, DC, 2010. 4. Seeff LB. The history of the “natural history” of hepatitis C (1968–2009). Liver Int 2009;29: (Suppl 1)89–99.
1
Digestive Diseases Care for ALL LLC, Lakeland, Florida, USA. Correspondence: Mahumudul Haque, MD, PhD, Digestive Diseases Care for ALL LLC, 3126 Highlands Lakeview Circle, Lakeland, Florida 33812, USA. E-mail: [email protected]
Somatic Mosaicism in Esophageal Atresia Damian Bednarczyk, MSc1, Izabela Makowska, MSc1, Maria Malgorzata Sasiadek, MD1 and Robert Smigiel, MD2 doi:10.1038/ajg.2014.346
To the Editor: Congenital esophageal atresia (EA; OMIM 189960) is a developmental defect characterized by loss of continuity of the esophagus often with an abnormal connection between the trachea and the esophagus—tracheoesophageal fistula (TEF). The incidence of EA/TEF is approx. 1 per 4,100 births (1). Forty-five percent of patients with EA present an isolated form without any additional associated anomalies. In the remaining patients, EA coexists with other defects (syndromic form) (1). In the group of syndromic patients VACTERL (vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects) association, CHARGE (congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina) syndrome, another non-chromosomal syndrome, Down’s syndrome, Edward’s syndrome, or another chromosomal syndrome can be diagnosed (1). The pathogenesis of EA is poorly understood and therefore etiology seems to be enigmatic, but it is thought that this defect arises due to errors in early embryonic development. In recent years, a number of genetic alterations have been identified in patients with syndromic EA (2,3), but there is no literature that reports diseasecausing mutations in patients with isolated EA. Therefore, the specific risk factors for congenital EA still remain unknown (4). The female patient was born at 38 weeks of gestation by cesarean delivery because of fetal multiple congenital defects diagnosed by ultrasonography. At birth her weight was 2600 g (3–10 centile), and length was 50 cm (10 centile). Physical and diagnostic examinations after birth revealed EA/TEF
VOLUME 109 | DECEMBER 2014 www.amjgastro.com
Letters to the Editor
nature publishing group
1 (9)
2 (12)
6 (13)
7 (10)
13 (9)
14 (10)
19 (13)
20 (14)
3 (11)
8 (10)
4 (11)
9 (12)
15 (11)
10 (11)
11 (13)
16 (14)
21 (12)
5 (9)
22 (14)
12 (8)
17 (11)
18 (10)
X (8)
Y (7)
Figure 1. Result of comparative genomic hybridization analysis performed on DNA isolated from the esophagus.
1 (6)
2 (10)
3 (10)
6 (11)
7 (10)
8 (9)
13 (14)
14 (8)
15 (11)
19 (16)
20 (14)
9 (12)
21 (16)
5 (10)
4 (5)
10 (13)
16 (15)
22 (16)
11 (13)
12 (11)
17 (15)
18 (15)
X (6)
Y (8)
Figure 2. Result of comparative genomic hybridization analysis performed on DNA isolated from the blood.
(type IIIB), ventricular septal defect, and defect in the kidneys. The clinical symptoms resembled partial VATER (vertebral defects, © 2014 by the American College of Gastroenterology
anal atresia, tracheoesophageal fistula with esophageal atresia, and radial or renal dysplasia) association. She was operated on the
first day of life by thoracoscopic approach and the lower pouch of her esophagus (entire wall) was collected for DNA isolation The American Journal of GASTROENTEROLOGY
1955
1956
Letters to the Editor
and further molecular analysis. Follow-up at 4 years showed a normal psychomotor, social and intellectual development, scoliosis of the thoracic part of the backbone, and no facial or hand and feet dysmorphism. Using the comparative genomic hybridization technique we revealed deletions of 7q11.1–7q11.2, 16p11.2–16p13.2, 16p13.3, 16q11.2–16q12.2 and 19p13.1–19p13.3 chromosomal regions in the esophagus (Figure 1) and no chromosomal aberrations in blood (Figure 2) in the same patient resulting in somatic mosaicism. No other tissues were analyzed. We validated 19p13 deletion using quantitative real-time PCR and MLPA. Recent scientific reports suggest that in the process of cell differentiation genome rearrangements may occur (5–7). This somatic cell mosaicism can be formed after fertilization in the early stages of embryonic development, being one of the mechanisms for the differentiation of various tissues (8). More and more reports in the literature describe somatic mosaicism as well as the cause of various diseases (9). The chromosome deletions described by us in this paper are large DNA losses and may be pathogenic alterations with significance in the etiology of this developmental defect. We suspect that 7q11.1–7q11.2, 16p11.2– 16p13.2, 16p13.3, 16q11.2–16q12.2 and 19p13.1–19p13.3 chromosomal regions may contain key genes, regulatory sequences, or other genetic elements playing an important role in esophagus development. For example, the 19p13 chromosomal region contains the LDLR gene, which is involved in cholesterol metabolism. Cholesterol acts in the proper functioning of the Sonic Hedgehog signaling pathway, which is instrumental in patterning of the early embryo and is essential to foregut development (10). We hypothesize that genetic mosaicism may be the cause of the EA and this readily explains the difficulty in identifying pathogenic mutations in patients with isolated EA. ACKNOWLEDGMENTS This study was accepted by the Bioethical Committee of Wroclaw Medical University and was supported by the National Science Center, Poland (grant number 5349/B/ P01/2011/40). The American Journal of GASTROENTEROLOGY
nature publishing group
CONFLICT OF INTEREST The authors declare no conflict of interest. REFERENCES 1. Pedersen RN, Calzolari E, Husby S et al. Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regions. Arch Dis Child 2012;97: 227–32. 2. Bednarczyk D, Sasiadek MM, Smigiel R. Chromosome aberrations and gene mutations in patients with esophageal atresia. J Pediatr Gastroenterol Nutr 2013;57:688–93. 3. Smigiel R, Lebioda A, Blaszczynski M et al. Alternations in genes expression of pathway signaling in esophageal tissue with atresia: results of expression microarray profiling. Dis Esophagus, advance online publication, 27 January 2014; doi: 10.1111/dote.12173 (e-pub ahead of print). 4. Bednarczyk D, Smigiel R, Sasiadek MM. The role of genetic and environmental factors in the etiology of esophageal atresia and tracheoesophageal fistula. Postepy Hig Med Dosw (Online) 2014;68:238–46. 5. Rodríguez-Santiago B, Malats N, Rothman N et al. Mosaic uniparental disomies and aneuploidies as large structural variants of the human genome. Am J Hum Genet 2010;87:129–38. 6. Astolfi PA, Salamini F, Sgaramella V. Are we genomic mosaics? Variations of the genome of somatic cells can contribute to diversify our phenotypes. Curr Genomics 2010;11:379–86. 7. Mkrtchyan H, Gross M, Hinreiner S et al. The human genome puzzle - the role of copy number variation in somatic mosaicism. Curr Genomics 2010;11:426–31. 8. Mkrtchyan H, Gross M, Hinreiner S et al. Early embryonic chromosome instability results in stable mosaic pattern in human tissues. PLoS One 2010;5:e9591. 9. Poduri A, Evrony GD, Cai X et al. Somatic mutation, genomic variation, and neurological disease. Science 2013;341:1237758. 10. Litingtung Y, Lei L, Westphal H et al. Sonic hedgehog is essential to foregut development. Nat Genet 1998;20:58–61. 1
Department of Genetics, Wroclaw Medical University, Wroclaw, Poland; 2Department of Social Paediatrics, Wroclaw Medical University, Wroclaw, Poland. Correspondence: Damian Bednarczyk, MSc, Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wroclaw, Poland. E-mail: [email protected]
Diverticulitis after Fecal Microbiota Transplant for C. difficile Infection Amar Mandalia, MD1, Colleen S. Kraft, MD2 and Tanvi Dhere, MD3 doi:10.1038/ajg.2014.350
To the Editor: Fecal microbiota transplantation (FMT) has become a cornerstone of the management of recurrent and refractory Clostridium difficile infection (CDI) (1). Although it is safe and tolerable, adverse events have been reported with FMT via colonoscopy (1–5). Here we report the first case of diverticulitis occurring after an FMT for the treatment of recurrent CDI. The patient was a 78-year-old Caucasian woman with a history of recurrent diverticulitis who had at least four episodes of recurrent CDI and had been treated with metronidazole and vancomcyin. She also had a history of coronary atherosclerotic heart disease, insulin-dependent diabetes, and hypertension. She had a partial colectomy over 10 years ago for self-reported Crohn’s disease that had since been in remission. Because of the history of recurrent CDI, an FMT via colonoscopy was performed. One hundred grams of donor stool diluted in 250 ml of sterile saline, as previously described, was infused into the most proximal colon (6). The colonoscopy revealed moderate diverticular disease in the left colon, and no macroscopic evidence of Crohn’s disease. The FMT procedure was performed without difficulty, and the patient was discharged from the endoscopy suite with no complaints. On her ride home 2 to 3 hours after the procedure, the patient developed severe diffuse abdominal pain. She went to a local emergency department (ED) and was found to be febrile to 40°C. A CT scan performed at that ED visit confirmed uncomplicated left-sided diverticulitis (Figure 1). She was admitted to the hospital and placed on antibiotics, to which she responded well and was discharged home uneventfully. In the past 3 months post FMT, the patient has not had a recurrence of CDI despite being treated with antibiotics after the FMT. Diverticulitis as a complication of FMT has never been reported in the literature. The pathogenesis of diverticulitis is not fully understood; however, the literature does highlight the role of dysbiosis as a plausible mechanism (7). Fecal material may collect in a diverticulum, leading to obstruction followed by distention and flora overgrowth. Aerobic and anaeroVOLUME 109 | DECEMBER 2014 www.amjgastro.com
Letters to the Editor
patients and accessibility of direct-acting anti-HCV agents (DAA). Dr Muir has presented a timely and balanced review of the prevalence and treatment strategies for chronic HCV, but we have a long way to go in terms of treating a sizeable proportion of those afflicted (1). While HCV is highly prevalent, affecting more than four million patients (2), only 25% of these cases are known (3). Active efforts to detect cases using the new Centers for Disease Control and Prevention screening guidelines are needed. As we cannot wait to treat a certain group of patients with risk factors for rapid progress of fibrosis or with advanced fibrosis, DAA definitely have great value and excellent cost-saving potential in these cases in the short and long run. However, for asymptomatic 0–2 fibrosis cases the value of this treatment may be relatively lower, as two-thirds may have slow progression and one-third may not develop cirrhosis (4) (http://www.cdc.gov/hepatitis/HCV/ HCVfaq.htm#section1). For asymptomatic patients with the early disease without risk factors, can we wait for short periods for the more cost-effective regimens to appear? In addition, as rightly stated by Dr Muir, there are concerns about the accessibility of DAA. Dr Muir’s article implies ~60% of HCV patients are likely uninsured or under Medicaid and/or Medicare. A sizeable number may not have any insurance due to some states’ rejection of federal money for Medicaid expansion (1). Only one-third of the HCV patients have private insurance (1). This could have chilling effects on both public (Medicaid/Medicare/health exchanges) and private healthcare funding agencies. Many payers do not have the money to fund these expensive treatments. For example, Oregon’s Medicaid needed $360 million to cover DAA alone, whereas its total annual prescription drug budget is only $370 million (http://www.washingtonpost.com/blogs/ wonkblog/wp/2014/07/24/the-drugthats-forcing-americas-most-importantand-uncomfortable-health-care-debate/). Owing to high costs, many state Medicaid agencies have already restricted the use of DAA to solely stage 3–4 fibrosis cases.
The American Journal of GASTROENTEROLOGY
nature publishing group
The inaccessibility of DAA cases also raises the following issue: what treatment options are available for Medicaid patients with stage 0–2 chronic HCV, or for patients supported by lower-budget county health plans that support older regimens through non-profit foundations, since American Association for the Study of Liver Diseases/Infectious Diseases Society of America (AASLD/ IDSA) guidelines do not recommend older regimens like ribavirin/pegylated interferon/ 1st gen protease inhibitor treatment (even though they are 65–80% effective) (http://www.hcvguidelines.org/full-report/ initial-treatment-hcv-infection-patientsstarting-treatment)? Hopefully, we will formulate a more pragmatic regimen within the next 18–24 months. By this time multiple new products will hopefully be approved, and free market competition will bring prices down to an affordable level. However, there is concern that a “shadow pricing” strategy may limit the decline in price (http://www.washingtonpost.com/blogs/wonkblog/wp/2014/07/24/ the-drug-thats-forcing-americas-mostimportant-and-uncomfortable-health-caredebate/). As providers, we should continue to seek better coverage for our vulnerable patients and work to improve detection of this disease. CONFLICT OF INTEREST The author declares no conflict of interest. REFERENCES 1. Muir AI. The rapid evolution of treatment strategies for hepatitis C. Am J Gastroenterol 2014;109:628–35. 2. Denniston MM, Jiles RB, Klkevens RM et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med 2014;160:293–300. 3. IOM (Institute of Medicine). Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C The National Academies Press: Washington, DC, 2010. 4. Seeff LB. The history of the “natural history” of hepatitis C (1968–2009). Liver Int 2009;29: (Suppl 1)89–99.
1
Digestive Diseases Care for ALL LLC, Lakeland, Florida, USA. Correspondence: Mahumudul Haque, MD, PhD, Digestive Diseases Care for ALL LLC, 3126 Highlands Lakeview Circle, Lakeland, Florida 33812, USA. E-mail: [email protected]
Somatic Mosaicism in Esophageal Atresia Damian Bednarczyk, MSc1, Izabela Makowska, MSc1, Maria Malgorzata Sasiadek, MD1 and Robert Smigiel, MD2 doi:10.1038/ajg.2014.346
To the Editor: Congenital esophageal atresia (EA; OMIM 189960) is a developmental defect characterized by loss of continuity of the esophagus often with an abnormal connection between the trachea and the esophagus—tracheoesophageal fistula (TEF). The incidence of EA/TEF is approx. 1 per 4,100 births (1). Forty-five percent of patients with EA present an isolated form without any additional associated anomalies. In the remaining patients, EA coexists with other defects (syndromic form) (1). In the group of syndromic patients VACTERL (vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects) association, CHARGE (congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina) syndrome, another non-chromosomal syndrome, Down’s syndrome, Edward’s syndrome, or another chromosomal syndrome can be diagnosed (1). The pathogenesis of EA is poorly understood and therefore etiology seems to be enigmatic, but it is thought that this defect arises due to errors in early embryonic development. In recent years, a number of genetic alterations have been identified in patients with syndromic EA (2,3), but there is no literature that reports diseasecausing mutations in patients with isolated EA. Therefore, the specific risk factors for congenital EA still remain unknown (4). The female patient was born at 38 weeks of gestation by cesarean delivery because of fetal multiple congenital defects diagnosed by ultrasonography. At birth her weight was 2600 g (3–10 centile), and length was 50 cm (10 centile). Physical and diagnostic examinations after birth revealed EA/TEF
VOLUME 109 | DECEMBER 2014 www.amjgastro.com
Letters to the Editor
nature publishing group
1 (9)
2 (12)
6 (13)
7 (10)
13 (9)
14 (10)
19 (13)
20 (14)
3 (11)
8 (10)
4 (11)
9 (12)
15 (11)
10 (11)
11 (13)
16 (14)
21 (12)
5 (9)
22 (14)
12 (8)
17 (11)
18 (10)
X (8)
Y (7)
Figure 1. Result of comparative genomic hybridization analysis performed on DNA isolated from the esophagus.
1 (6)
2 (10)
3 (10)
6 (11)
7 (10)
8 (9)
13 (14)
14 (8)
15 (11)
19 (16)
20 (14)
9 (12)
21 (16)
5 (10)
4 (5)
10 (13)
16 (15)
22 (16)
11 (13)
12 (11)
17 (15)
18 (15)
X (6)
Y (8)
Figure 2. Result of comparative genomic hybridization analysis performed on DNA isolated from the blood.
(type IIIB), ventricular septal defect, and defect in the kidneys. The clinical symptoms resembled partial VATER (vertebral defects, © 2014 by the American College of Gastroenterology
anal atresia, tracheoesophageal fistula with esophageal atresia, and radial or renal dysplasia) association. She was operated on the
first day of life by thoracoscopic approach and the lower pouch of her esophagus (entire wall) was collected for DNA isolation The American Journal of GASTROENTEROLOGY
1955
1956
Letters to the Editor
and further molecular analysis. Follow-up at 4 years showed a normal psychomotor, social and intellectual development, scoliosis of the thoracic part of the backbone, and no facial or hand and feet dysmorphism. Using the comparative genomic hybridization technique we revealed deletions of 7q11.1–7q11.2, 16p11.2–16p13.2, 16p13.3, 16q11.2–16q12.2 and 19p13.1–19p13.3 chromosomal regions in the esophagus (Figure 1) and no chromosomal aberrations in blood (Figure 2) in the same patient resulting in somatic mosaicism. No other tissues were analyzed. We validated 19p13 deletion using quantitative real-time PCR and MLPA. Recent scientific reports suggest that in the process of cell differentiation genome rearrangements may occur (5–7). This somatic cell mosaicism can be formed after fertilization in the early stages of embryonic development, being one of the mechanisms for the differentiation of various tissues (8). More and more reports in the literature describe somatic mosaicism as well as the cause of various diseases (9). The chromosome deletions described by us in this paper are large DNA losses and may be pathogenic alterations with significance in the etiology of this developmental defect. We suspect that 7q11.1–7q11.2, 16p11.2– 16p13.2, 16p13.3, 16q11.2–16q12.2 and 19p13.1–19p13.3 chromosomal regions may contain key genes, regulatory sequences, or other genetic elements playing an important role in esophagus development. For example, the 19p13 chromosomal region contains the LDLR gene, which is involved in cholesterol metabolism. Cholesterol acts in the proper functioning of the Sonic Hedgehog signaling pathway, which is instrumental in patterning of the early embryo and is essential to foregut development (10). We hypothesize that genetic mosaicism may be the cause of the EA and this readily explains the difficulty in identifying pathogenic mutations in patients with isolated EA. ACKNOWLEDGMENTS This study was accepted by the Bioethical Committee of Wroclaw Medical University and was supported by the National Science Center, Poland (grant number 5349/B/ P01/2011/40). The American Journal of GASTROENTEROLOGY
nature publishing group
CONFLICT OF INTEREST The authors declare no conflict of interest. REFERENCES 1. Pedersen RN, Calzolari E, Husby S et al. Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regions. Arch Dis Child 2012;97: 227–32. 2. Bednarczyk D, Sasiadek MM, Smigiel R. Chromosome aberrations and gene mutations in patients with esophageal atresia. J Pediatr Gastroenterol Nutr 2013;57:688–93. 3. Smigiel R, Lebioda A, Blaszczynski M et al. Alternations in genes expression of pathway signaling in esophageal tissue with atresia: results of expression microarray profiling. Dis Esophagus, advance online publication, 27 January 2014; doi: 10.1111/dote.12173 (e-pub ahead of print). 4. Bednarczyk D, Smigiel R, Sasiadek MM. The role of genetic and environmental factors in the etiology of esophageal atresia and tracheoesophageal fistula. Postepy Hig Med Dosw (Online) 2014;68:238–46. 5. Rodríguez-Santiago B, Malats N, Rothman N et al. Mosaic uniparental disomies and aneuploidies as large structural variants of the human genome. Am J Hum Genet 2010;87:129–38. 6. Astolfi PA, Salamini F, Sgaramella V. Are we genomic mosaics? Variations of the genome of somatic cells can contribute to diversify our phenotypes. Curr Genomics 2010;11:379–86. 7. Mkrtchyan H, Gross M, Hinreiner S et al. The human genome puzzle - the role of copy number variation in somatic mosaicism. Curr Genomics 2010;11:426–31. 8. Mkrtchyan H, Gross M, Hinreiner S et al. Early embryonic chromosome instability results in stable mosaic pattern in human tissues. PLoS One 2010;5:e9591. 9. Poduri A, Evrony GD, Cai X et al. Somatic mutation, genomic variation, and neurological disease. Science 2013;341:1237758. 10. Litingtung Y, Lei L, Westphal H et al. Sonic hedgehog is essential to foregut development. Nat Genet 1998;20:58–61. 1
Department of Genetics, Wroclaw Medical University, Wroclaw, Poland; 2Department of Social Paediatrics, Wroclaw Medical University, Wroclaw, Poland. Correspondence: Damian Bednarczyk, MSc, Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wroclaw, Poland. E-mail: [email protected]
Diverticulitis after Fecal Microbiota Transplant for C. difficile Infection Amar Mandalia, MD1, Colleen S. Kraft, MD2 and Tanvi Dhere, MD3 doi:10.1038/ajg.2014.350
To the Editor: Fecal microbiota transplantation (FMT) has become a cornerstone of the management of recurrent and refractory Clostridium difficile infection (CDI) (1). Although it is safe and tolerable, adverse events have been reported with FMT via colonoscopy (1–5). Here we report the first case of diverticulitis occurring after an FMT for the treatment of recurrent CDI. The patient was a 78-year-old Caucasian woman with a history of recurrent diverticulitis who had at least four episodes of recurrent CDI and had been treated with metronidazole and vancomcyin. She also had a history of coronary atherosclerotic heart disease, insulin-dependent diabetes, and hypertension. She had a partial colectomy over 10 years ago for self-reported Crohn’s disease that had since been in remission. Because of the history of recurrent CDI, an FMT via colonoscopy was performed. One hundred grams of donor stool diluted in 250 ml of sterile saline, as previously described, was infused into the most proximal colon (6). The colonoscopy revealed moderate diverticular disease in the left colon, and no macroscopic evidence of Crohn’s disease. The FMT procedure was performed without difficulty, and the patient was discharged from the endoscopy suite with no complaints. On her ride home 2 to 3 hours after the procedure, the patient developed severe diffuse abdominal pain. She went to a local emergency department (ED) and was found to be febrile to 40°C. A CT scan performed at that ED visit confirmed uncomplicated left-sided diverticulitis (Figure 1). She was admitted to the hospital and placed on antibiotics, to which she responded well and was discharged home uneventfully. In the past 3 months post FMT, the patient has not had a recurrence of CDI despite being treated with antibiotics after the FMT. Diverticulitis as a complication of FMT has never been reported in the literature. The pathogenesis of diverticulitis is not fully understood; however, the literature does highlight the role of dysbiosis as a plausible mechanism (7). Fecal material may collect in a diverticulum, leading to obstruction followed by distention and flora overgrowth. Aerobic and anaeroVOLUME 109 | DECEMBER 2014 www.amjgastro.com
