- Email: [email protected]
Dysphagia: More Than Meets the Eye?
Accepted Manuscript Title: ‘Dysphagia: more than meets the eye?’ M.J. Armstrong, R. Ahmed, R. Boulton
PII: DOI: Reference:
S0016-5085(17)36171-1 10.1053/j.gastro.2017.09.012 YGAST 61434
To appear in: Gastroenterology Accepted Date: 15 September 2017 Please cite this article as: Armstrong M, Ahmed R, Boulton R, Title: ‘Dysphagia: more than meets the eye?’, Gastroenterology (2017), doi: 10.1053/j.gastro.2017.09.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: ‘Dysphagia: more than meets the eye?’ Armstrong MJ1*, Ahmed R2*, Boulton R2 Liver Unit, University Hospital Birmingham NHS foundation Trust, Birmingham, United Kingdom
2
Department of gastroenterology, University Hospital Birmingham NHS foundation Trust, Birmingham,
RI PT
1
United Kingdom
Corresponding Author: Dr Matthew James Armstrong PhD MRCP
Mindelsohn Way Edgbaston, Birmingham B15 2GW Tel: 0044 7968470622
Author contributions:
TE D
Email: [email protected]
M AN U
Liver Unit, Queen Elizabeth University Hospital Birmingham
SC
*authors contributed equally
EP
MJA, RA and RB collected the data, drafted and finalised the manuscript.
AC C
Conflict of interests:
All authors have no conflict of interests to declare.
Acknowledgements:
The authors would like to thank Dr’s M Elshafie and A Pallan for providing the histopathological and radiological opinions and images, respectively.
ACCEPTED MANUSCRIPT QUESTION A 70 year old female presented with significant weight loss, odynophagia and dysphagia. She was a smoker, with no relevant family history. There was no evidence of lymphadenopathy on examination and her The initial upper GI endoscopy showed inflammation and
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routine blood tests were unremarkable.
ulceration in the distal oesophagus (Figure A), but this did not resolve with standard acid suppression with proton pump inhibitor therapy.
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TE D
M AN U
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What is the most likely diagnosis?
ACCEPTED MANUSCRIPT DISCUSSION Endoscopy revealed a 3cm distal oesophageal ulcer (Figure A) and the biopsy was reported as benign oesophagitis. A computer tomography (CT) thorax showed a circumferential thickening in the distal 6.5 cm,
RI PT
suggesting possible malignancy (Figure B). Endoscopic ultrasound (EUS) confirmed thickening of the oesophageal wall supporting the CT thorax findings (Figure C). However, both EUS guided fine needle aspiration and endoscopic mucosal resection revealed no evidence of malignancy, despite suggestive imaging and weight loss. The initial endoscopic oesophageal biopsy from the ulcer edge was therefore re-
SC
examined. Despite the absence of hyphae on haemotoxylin and eosin (H&E), periodic acid schiff diastase (PAS-D) staining was undertaken, as the presence of numerous polymorph infiltrates in the squamous cell
M AN U
layer remained unexplained and unresolved despite proton pump inhibitor treatment. Subsequently, PAS-D confirmed the presence of candida hyphae (arrows, Figure D). The patient was treated with 100 mg fluconazole once daily for 3 weeks and symptoms completely resolved, with 5 kg weight gain (12%). Repeat upper GI endoscopy revealed complete resolution of the oesophageal ulceration (Figure E). Candida is the most common cause of infectious oesophagitis, occurring in 11 and 3% of patients with HIV and non-HIV,
TE D
respectively (1). The main predisposing factors include antibiotic use, inhaled steroids, radiation- or chemotherapy, haematologic malignancies, and compromised immune systems. Other risk factors include
EP
oesophageal dysmotility (i.e. achalasia), diabetes, malnutrition, advanced age and smoking (2). Most cases of oesophageal candidiasis present with odynophagia and if longstanding can result in weight
AC C
loss, however, in the absence of predisposing factors is more likely to be asymptomatic. There is often concomittant oropharyngeal involvement and classical diffuse, raised, linear plaques that can be removed from the oesophageal mucosa on endoscopy. Rarely, as in the current case, candidiasis can cause deep oesophageal ulceration (<3%) in the absence of plaques (3). The differential diagnosis in such cases includes gastrointestinal reflux disease, drug induced, caustic/foreign body injury, herpes simplex virus and malignancy. In the absence of pseudohyphae on high resolution H&E stains, studies have recommended proceeding to PAS-D staining with unexplained ulceration and/or suspicious morphology (prominent
ACCEPTED MANUSCRIPT desquamated or hyper-pink parakeratosis, acute inflammation, and/or intraepithelial lymphocytosis) (1). First-line treatment is fluconazole and the patient’s symptoms should fully resolve.
RI PT
References: 1. Takahashi Y, Nagata N, Shimbo T, Nishijima T, Watanabe K, Aoki T, et al. Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients: An Endoscopy-Based Cross-Sectional Study of 6011 Patients. Medicine (Baltimore) 2015;94:e2138.
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2. Alsomali MI, Arnold MA, Frankel WL, Graham RP, Hart PA, et al. Challenges to “Classic” Esophageal Candidiasis. Am J Clin Pathol 2017;147:33-42.
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3. Rajablou M, Batts KP. Candida infection presenting as multiple ulcerated masses. Gastrointestinal
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Endoscopy 2017;65:164-165
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PII: DOI: Reference:
S0016-5085(17)36171-1 10.1053/j.gastro.2017.09.012 YGAST 61434
To appear in: Gastroenterology Accepted Date: 15 September 2017 Please cite this article as: Armstrong M, Ahmed R, Boulton R, Title: ‘Dysphagia: more than meets the eye?’, Gastroenterology (2017), doi: 10.1053/j.gastro.2017.09.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: ‘Dysphagia: more than meets the eye?’ Armstrong MJ1*, Ahmed R2*, Boulton R2 Liver Unit, University Hospital Birmingham NHS foundation Trust, Birmingham, United Kingdom
2
Department of gastroenterology, University Hospital Birmingham NHS foundation Trust, Birmingham,
RI PT
1
United Kingdom
Corresponding Author: Dr Matthew James Armstrong PhD MRCP
Mindelsohn Way Edgbaston, Birmingham B15 2GW Tel: 0044 7968470622
Author contributions:
TE D
Email: [email protected]
M AN U
Liver Unit, Queen Elizabeth University Hospital Birmingham
SC
*authors contributed equally
EP
MJA, RA and RB collected the data, drafted and finalised the manuscript.
AC C
Conflict of interests:
All authors have no conflict of interests to declare.
Acknowledgements:
The authors would like to thank Dr’s M Elshafie and A Pallan for providing the histopathological and radiological opinions and images, respectively.
ACCEPTED MANUSCRIPT QUESTION A 70 year old female presented with significant weight loss, odynophagia and dysphagia. She was a smoker, with no relevant family history. There was no evidence of lymphadenopathy on examination and her The initial upper GI endoscopy showed inflammation and
RI PT
routine blood tests were unremarkable.
ulceration in the distal oesophagus (Figure A), but this did not resolve with standard acid suppression with proton pump inhibitor therapy.
AC C
EP
TE D
M AN U
SC
What is the most likely diagnosis?
ACCEPTED MANUSCRIPT DISCUSSION Endoscopy revealed a 3cm distal oesophageal ulcer (Figure A) and the biopsy was reported as benign oesophagitis. A computer tomography (CT) thorax showed a circumferential thickening in the distal 6.5 cm,
RI PT
suggesting possible malignancy (Figure B). Endoscopic ultrasound (EUS) confirmed thickening of the oesophageal wall supporting the CT thorax findings (Figure C). However, both EUS guided fine needle aspiration and endoscopic mucosal resection revealed no evidence of malignancy, despite suggestive imaging and weight loss. The initial endoscopic oesophageal biopsy from the ulcer edge was therefore re-
SC
examined. Despite the absence of hyphae on haemotoxylin and eosin (H&E), periodic acid schiff diastase (PAS-D) staining was undertaken, as the presence of numerous polymorph infiltrates in the squamous cell
M AN U
layer remained unexplained and unresolved despite proton pump inhibitor treatment. Subsequently, PAS-D confirmed the presence of candida hyphae (arrows, Figure D). The patient was treated with 100 mg fluconazole once daily for 3 weeks and symptoms completely resolved, with 5 kg weight gain (12%). Repeat upper GI endoscopy revealed complete resolution of the oesophageal ulceration (Figure E). Candida is the most common cause of infectious oesophagitis, occurring in 11 and 3% of patients with HIV and non-HIV,
TE D
respectively (1). The main predisposing factors include antibiotic use, inhaled steroids, radiation- or chemotherapy, haematologic malignancies, and compromised immune systems. Other risk factors include
EP
oesophageal dysmotility (i.e. achalasia), diabetes, malnutrition, advanced age and smoking (2). Most cases of oesophageal candidiasis present with odynophagia and if longstanding can result in weight
AC C
loss, however, in the absence of predisposing factors is more likely to be asymptomatic. There is often concomittant oropharyngeal involvement and classical diffuse, raised, linear plaques that can be removed from the oesophageal mucosa on endoscopy. Rarely, as in the current case, candidiasis can cause deep oesophageal ulceration (<3%) in the absence of plaques (3). The differential diagnosis in such cases includes gastrointestinal reflux disease, drug induced, caustic/foreign body injury, herpes simplex virus and malignancy. In the absence of pseudohyphae on high resolution H&E stains, studies have recommended proceeding to PAS-D staining with unexplained ulceration and/or suspicious morphology (prominent
ACCEPTED MANUSCRIPT desquamated or hyper-pink parakeratosis, acute inflammation, and/or intraepithelial lymphocytosis) (1). First-line treatment is fluconazole and the patient’s symptoms should fully resolve.
RI PT
References: 1. Takahashi Y, Nagata N, Shimbo T, Nishijima T, Watanabe K, Aoki T, et al. Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients: An Endoscopy-Based Cross-Sectional Study of 6011 Patients. Medicine (Baltimore) 2015;94:e2138.
SC
2. Alsomali MI, Arnold MA, Frankel WL, Graham RP, Hart PA, et al. Challenges to “Classic” Esophageal Candidiasis. Am J Clin Pathol 2017;147:33-42.
M AN U
3. Rajablou M, Batts KP. Candida infection presenting as multiple ulcerated masses. Gastrointestinal
AC C
EP
TE D
Endoscopy 2017;65:164-165
AC C
EP
TE D
M AN U
SC
RI PT
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