View source for Protein losing enteropathy

__NOTOC__
{{SI}} 
{{CMG}} ; {{AE}} {{Zamani}} {{EH}} 

{{SK}} Protein loss, protein deficiency, GI protein loss, gastrointestinal protein loss, protein-losing gastroenteropathy, protein-losing gastroenteropathy, gastroenteropathy, gastric protein loss, helicobacter pylori, H pylori, giant hypertrophic gastropathy, menetrier disease, ménétrier, disease, loss of plasma proteins from the gastrointestinal tract, excessive leakage of plasma proteins into the lumen of the gastrointestinal tract, lymphatic obstruction, mucosal disease with erosions, ulcerations, swelling of the legs, peripheral edema, decreased plasma oncotic pressure

==Overview==
[[Protein]] losing [[enteropathy]] is the loss of [[plasma proteins]] from the [[gastrointestinal tract]] caused by an array of [[abnormalities]], such as primary [[gastrointestinal diseases]] and [[lymphatic obstruction]]. Protein losing [[enteropathy]] is not a separate disease entity but a complication of different [[pathological]] conditions leading to [[hypoproteinemia]]. Treatment is tailored towards the underlying [[etiology]] leading to protein losing [[enteropathy]] as a complication. 

==Historical Perspective==

*There is no historical significance associated with protein losing enteropathy.
 
==Classification==

*There is no classification for protein losing enteropathy according to recent updates.

==Pathophysiology==
Normally there is a balance between the [[synthesis]] and [[degradation]] of [[proteins]] maintained by a series of interconnected processes in the body. Any condition which disrupts the normal protein [[stasis]] where the loss of [[protein]] through the [[gastrointestinal tract]] exceeds the body’s ability to synthesize [[Protein|proteins]] failing to compensate for the loss leads to the development of a state of low serum protein called [[hypoproteinemia]].<ref name="CravenWashabau2019">{{cite journal|last1=Craven|first1=Melanie D.|last2=Washabau|first2=Robert J.|title=Comparative pathophysiology and management of protein‐losing enteropathy|journal=Journal of Veterinary Internal Medicine|volume=33|issue=2|year=2019|pages=383–402|issn=0891-6640|doi=10.1111/jvim.15406}}</ref><ref name="pmidhttps://www.ncbi.nlm.nih.gov/pubmed/31194423">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=https://www.ncbi.nlm.nih.gov/pubmed/31194423 | doi= | pmc= | url= }} </ref> <ref name="WaldmannWochner1969">{{cite journal|last1=Waldmann|first1=T.A.|last2=Wochner|first2=R.D.|last3=Strober|first3=W.|title=The role of the gastrointestinal tract in plasma protein metabolism|journal=The American Journal of Medicine|volume=46|issue=2|year=1969|pages=275–285|issn=00029343|doi=10.1016/0002-9343(69)90011-4}}</ref>

*Primary [[gastrointestinal]] diseases such as [[inflammatory bowel disease]] and [[malignancies]] initiates a series of abnormal changes leading to the disruption of the protective [[mucosal layer]] of the [[gut]] resulting in [[inflammation]], [[erosions]] and [[ulcerations]] of the normal [[mucosa]] leading to:
**Alteration in the [[mucosal]] lining of the [[gut]].
**An increase in the [[permeability]] for the previously [[Semi-permeable membrane|semi-permeable]] and non-permeable [[proteins]], leading to excessive [[protein]] leakage through [[gastrointestinal tract]].
**Decrease surface area for [[protein]] [[reabsorption]] leading to poor [[reabsorption]].
*Non-erosive [[gastrointestinal]] conditions such as [[connective tissue disorders]] and [[infectious diseases]] affecting the [[mucosa]] of the [[gastrointestinal tract]] causes the leakage of [[proteins]] into the [[lumen]] of [[gastrointestinal tract]] in a similar manner as erosive [[gastrointestinal diseases]].
*Conditions leading to [[lymphatic obstruction]] such as [[lymphomas]] and other [[benign]] or [[malignant]] masses causes an increase in the pressure inside the [[lymphatic system]] which forces the [[lymph]] to leak out of the [[lymphatic vessels]] into the [[lumen]] of [[gastrointestinal tract]] leading to protein loss. <ref name="pmid30762910">{{cite journal| author=Craven MD, Washabau RJ| title=Comparative pathophysiology and management of protein-losing enteropathy. | journal=J Vet Intern Med | year= 2019 | volume= 33 | issue= 2 | pages= 383-402 | pmid=30762910 | doi=10.1111/jvim.15406 | pmc=6430879 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30762910  }} </ref>

==Causes==
Most cases of [[protein]] losing [[enteropathy]] are caused as a result of:

#Primary [[gastrointestinal]] diseases
#[[Lymphatic obstruction]]

===Primary Gastrointestinal Diseases===
=====Mucosal Erosions/Ulcerations=====
Primary [[gastrointestinal]] diseases causing erosion or [[ulceration]] of the [[mucosa]] of the [[gut]] leading to [[fecal]] loss of [[proteins]] such as:<ref name="CravenWashabau2019">{{cite journal|last1=Craven|first1=Melanie D.|last2=Washabau|first2=Robert J.|title=Comparative pathophysiology and management of protein‐losing enteropathy|journal=Journal of Veterinary Internal Medicine|volume=33|issue=2|year=2019|pages=383–402|issn=0891-6640|doi=10.1111/jvim.15406}}</ref><ref name="pmid30408010">{{cite journal| author=Akkelle BS, Tutar E, Sengul OK, Celikel CA, Ertem D| title=A Rare Complication of Giardiasis in Children: Protein-losing Enteropathy. | journal=Pediatr Infect Dis J | year= 2018 | volume= 37 | issue= 12 | pages= e345-e347 | pmid=30408010 | doi=10.1097/INF.0000000000002025 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30408010  }}</ref><ref name="pmid30834767">{{cite journal| author=Zubiaga Toro L, Ruiz-Tovar J, Castro MJ, Ortiz de Solórzano FJ, Luque de León E, Jiménez JM | display-authors=etal| title=Whipple disease after bariatric surgery: from malabsorption to malnutrition status. | journal=Nutr Hosp | year= 2019 | volume= 36 | issue= 1 | pages= 238-241 | pmid=30834767 | doi=10.20960/nh.02258 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30834767  }}</ref>

*[[Inflammatory bowel diseases]] ([[Crohn disease]], [[Ulcerative colitis]])
*[[Malignancies]] involving the [[gut]] [[mucosa]]
*[[Graft vs. host disease]]
*[[Esophageal]] and [[gastric]] erosions or [[Ulceration|ulcerations]]
*[[Carcinoid syndrome]]
*[[Bacterial infection]] with [[Clostridium difficile]] causing [[pseudomembranous colitis]]
*[[Parasitic]] infection with [[Giardia]]

=====Non-Erosive/Ulcerative Mucosal involvement=====

*[[Celiac disease]]
*[[Eosinophilic gastritis]]
*[[Hypertrophic gastritis]]
*[[Connective tissue disorders]]: [[Systemic lupus erythematosus]]
*[[Cutaneous]] [[burns]]<ref name="VenkateshGough2004">{{cite journal|last1=Venkatesh|first1=Balasubramanian|last2=Gough|first2=Jenny|last3=Ralston|first3=David R.|last4=Muller|first4=Michael|last5=Pegg|first5=Stuart|title=Protein losing enteropathy in critically ill adult patients with burns: a preliminary report|journal=Intensive Care Medicine|volume=30|issue=1|year=2004|pages=162–166|issn=0342-4642|doi=10.1007/s00134-003-2050-2}}</ref>

===Lymphatic Obstruction===
Conditions responsible for causing [[lymphatic]] obstruction leading to the leakage of [[lymph]] into the [[lumen]] of [[gut]] such as:

*[[Lymphoma]]
*[[Congenital]] or acquired [[lymphatic diseases]]
*Lymphatic [[filariasis]]
*[[Sarcoidosis]]
*Cardiovascular diseases: [[Congestive heart failure]], Restrictive [[pericarditis]]
*[[Intestinal]] [[Tuberculosis]]
*[[Fontan surgical procedure|Fontan surgical procedure]]
*[[Cirrhosis]] with [[portal hypertension]]
*[[Retroperitoneal fibrosis]]<ref name="pmid26446687">{{cite journal| author=Furfaro F, Bezzio C, Maconi G| title=Protein-losing enteropathy in inflammatory bowel diseases. | journal=Minerva Gastroenterol Dietol | year= 2015 | volume= 61 | issue= 4 | pages= 261-5 | pmid=26446687 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26446687  }} </ref> <ref name="pmid25618488">{{cite journal| author=Amiot A| title=[Protein-losing enteropathy]. | journal=Rev Med Interne | year= 2015 | volume= 36 | issue= 7 | pages= 467-73 | pmid=25618488 | doi=10.1016/j.revmed.2014.12.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25618488  }} </ref> <ref name="pmid31194423">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31194423 | doi= | pmc= | url= }} </ref>

==Complete Differential Diagnosis Of Underlying Causes==
Protein losing [[enteropathy]] must be differentiated from any condition causing hypoproteinemia. Some common condition are listed below:<ref name="TsochatzisBosch2014">{{cite journal|last1=Tsochatzis|first1=Emmanuel A|last2=Bosch|first2=Jaime|last3=Burroughs|first3=Andrew K|title=Liver cirrhosis|journal=The Lancet|volume=383|issue=9930|year=2014|pages=1749–1761|issn=01406736|doi=10.1016/S0140-6736(14)60121-5}}</ref> <ref name="RiederHuber2019">{{cite journal|last1=Rieder|first1=Simone C.|last2=Huber|first2=Lars C.|last3=Trachsler|first3=Johannes|last4=Herberger|first4=Elisabeth|title=CME: Das nephrotische Syndrom beim Erwachsenen: Präsentation,                     Abklärung, Therapie|journal=Praxis|volume=108|issue=5|year=2019|pages=347–355|issn=1661-8157|doi=10.1024/1661-8157/a003223}}</ref>
<ref name="GroverEe2009">{{cite journal|last1=Grover|first1=Zubin|last2=Ee|first2=Looi C.|title=Protein Energy Malnutrition|journal=Pediatric Clinics of North America|volume=56|issue=5|year=2009|pages=1055–1068|issn=00313955|doi=10.1016/j.pcl.2009.07.001}}</ref> <ref name="ClarkJohnson2018">{{cite journal|last1=Clark|first1=Ricketta|last2=Johnson|first2=Ragan|title=Malabsorption Syndromes|journal=Nursing Clinics of North America|volume=53|issue=3|year=2018|pages=361–374|issn=00296465|doi=10.1016/j.cnur.2018.05.001}}</ref> <ref name="Hazenberg2013">{{cite journal|last1=Hazenberg|first1=Bouke P.C.|title=Amyloidosis|journal=Rheumatic Disease Clinics of North America|volume=39|issue=2|year=2013|pages=323–345|issn=0889857X|doi=10.1016/j.rdc.2013.02.012}}</ref>

*Acute [[gastroenteritis]]
*[[Bacterial overgrowth]]
*[[Carcinoid Syndrome]]
*[[Clostridium Difficile]]
*[[Heart Failure]]
*[[Connective tissue disorders]]
*[[Chronic liver disease]]<nowiki/>s
*[[Nephrotic syndrome]]
*Severe protein calorie [[malnutrition]]
*[[Malabsorptive syndromes|Malabsorption syndromes]]
*[[Graft vs. Host Disease]]
*[[Intestinal parasites]]
*[[Lymphoma]]
*[[Menetrier's Disease]]
*[[Pseudomembranous colitis]]
*[[Retroperitoneal fibrosis]]
*[[Amyloidosis]]

==Diagnosis==
As [[hypoproteinemia]] is the key factor in evaluating a patient for protein losing [[enteropathy]], other common causes of [[hypoproteinemia]] such as [[nephrotic syndrome]], impaired protein synthesis due to [[chronic liver disease]] and [[malnutrition]] must be excluded first.<ref name="UmarDiBaise2010">{{cite journal|last1=Umar|first1=Sarah B|last2=DiBaise|first2=John K|title=Protein-Losing Enteropathy: Case Illustrations and Clinical Review|journal=American Journal of Gastroenterology|volume=105|issue=1|year=2010|pages=43–49|issn=0002-9270|doi=10.1038/ajg.2009.561}}</ref>

==='''Laboratory Studies'''===
As the most prominent laboratory finding is a decrease in serum concentration of [[albumin]] and [[globulin]], the diagnostic work up protein losing [[enteropathy]] consist of quantitative measurements of [[Alpha-1 antitrypsin]] or <sup>51</sup>Cr-albumin.<ref name="LevittLevitt2017">{{cite journal|last1=Levitt|first1=David|last2=Levitt|first2=Michael|title=Protein losing enteropathy: comprehensive review of the mechanistic association with clinical and subclinical disease states|journal=Clinical and Experimental Gastroenterology|volume=Volume 10|year=2017|pages=147–168|issn=1178-7023|doi=10.2147/CEG.S136803}}</ref>

*[[Alpha-1 antitrypsin]] (A1AT) used as an [[endogenous]] [[marker]] is a sensitive and inexpensive laboratory test performed to diagnose protein losing [[enteropathy]] and has become the current standard for quantitating [[protein]] losing [[enteropathy]].<ref name="pmid2475983">{{cite journal| author=Karbach U, Ewe K| title=Enteric protein loss in various gastrointestinal diseases determined by intestinal alpha 1-antitrypsin clearance. | journal=Z Gastroenterol | year= 1989 | volume= 27 | issue= 7 | pages= 362-5 | pmid=2475983 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2475983  }} </ref>  Measurement of fecal volume and fecal loss of [[alpha-1 antitrypsin]] depicts the [[Plasma (blood)|plasma]] concentration of [[alpha-1 antitrypsin]] as;

*Alpha 1-AT plasma concentration = ((stool volume) x (stool alpha 1-AT)) / (serum alpha-1 AT)

*[[Gastrointestinal]] loss of [[alpha-1 antitrypsin]] is measured in feces and a clearance greater than 27mL/day is considered diagnostic for protein losing [[enteropathy]].<ref name="pmid6973500">{{cite journal| author=Florent C, L'Hirondel C, Desmazures C, Aymes C, Bernier JJ| title=Intestinal clearance of alpha 1-antitrypsin. A sensitive method for the detection of protein-losing enteropathy. | journal=Gastroenterology | year= 1981 | volume= 81 | issue= 4 | pages= 777-80 | pmid=6973500 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6973500  }} </ref>

*51Cr-labeled [[albumin]] can also be measured followed by stool collection to determine the amount of protein loss into the [[Gastrointestinal tract|gastrointestinal]] tract.

==='''Imaging Studies'''===
Following the detection of abnormal amounts of [[alpha-1 antitrypsin]] in the stool, the following tests can be performed to detect the specific etiology for the protein loss into the [[gastrointestinal]] lumen.<ref name="LevittLevitt2017">{{cite journal|last1=Levitt|first1=David|last2=Levitt|first2=Michael|title=Protein losing enteropathy: comprehensive review of the mechanistic association with clinical and subclinical disease states|journal=Clinical and Experimental Gastroenterology|volume=Volume 10|year=2017|pages=147–168|issn=1178-7023|doi=10.2147/CEG.S136803}}</ref>

*Administration of [[technetium-99]] labeled [[macromolecules]] such as [[albumin]]. [[Imaging]] is required to localize the primary site of [[protein]] leakage with no requirement for fecal collection. [[Scintigraphy]] is becoming popular in the diagnosis and localization of the site of protein leakage.  

*For the diagnosis of [[lymphatic obstruction]], [[computed tomography]], [[lymphangiography]] or [[magnetic resonance imaging]] can be used.

*[[Radiographic]] contrast studies and [[endoscopy]] can be performed to evaluate the [[ulcerative]] or erosive [[gastrointestinal]] causes of the protein loss.

*For detecting [[cardiac]] diseases causing loss of protein, [[echocardiography]] or [[radionuclide]] scanning of the heart can be performed.

==='''Other tests:'''===

*All patients should undergo basic laboratory tests such as complete blood test, [[Liver function tests|liver]] and [[renal function tests]].

*Work up for [[autoimmune diseases]] such as [[systemic lupus erythematosus]] should be ordered if there is a suspicion of [[connective tissue disorder]] causing protein loss in the [[gastrointestinal tract]].

*[[Biopsy]] samples of the [[mucosa]] and stool cultures for [[ova]] and [[parasites]] should be performed if there is a suspicion of ulcerative or erosive [[Gastrointestinal diseases|gastrointestinal disease]] and [[parasitic infection]], respectively.

==Treatment==

*[[Symptomatic treatment|Symptomatic]] relief can be achieved with dietary modifications and medications.

*Supplementation with [[proteins]] with 2 to 3 g/kg a day as well as [[micronutrients]], [[Electrolyte|electrolytes]] and [[vitamins]] to compensate for the loss of [[proteins]] plays a critical role.

*Treatment with [[steroids]] or [[heparin]] to stop protein leak via the [[intestines]] could also provide [[Symptomatic treatment|symptomatic relief.]]

*However, protein losing [[enteropathy]] is not a separate disease entity but a complication of different [[pathological]] conditions and hence the mainstay of treatment depends upon the underlying etiology of the disease causing protein losing [[enteropathy]].

*Effectual treatment depends on a better understanding of the [[pathophysiology]] of the disease, for instance, if the underlying [[pathology]] involves [[inflammation]] or [[autoimmune]] condition such as; [[inflammatory bowel disease]] or [[connective tissue disorder]], treatment strategy is tailored towards treating the underlying pathology with [[immunosuppressive]] medications.

*Similarly, if [[cardiovascular disease]] is the underlying [[pathology]] of protein losing [[enteropathy]], the mainstay of treatment would be optimization of the medications for [[heart failure]]. [[Diuretics]] can be used for [[symptomatic]] relief.

*[[Lymphatic obstruction]] can be relieved according to the underlying [[etiologies]] such as; treatment of the [[parasitic]] or [[Bacteria|bacterial]] infection causing protein losing [[enteropathy]], increased [[lymphatic pressure]] can be relieved with [[octreotide]] and [[surgical resection]] should be considered in case of refractory [[inflammatory bowel disease]]. <ref name="RychikSpray2002">{{cite journal|last1=Rychik|first1=Jack|last2=Spray|first2=Thomas L.|title=Strategies to treat protein-losing enteropathy|journal=Seminars in Thoracic and Cardiovascular Surgery: Pediatric Cardiac Surgery Annual|volume=5|issue=1|year=2002|pages=3–11|issn=10929126|doi=10.1053/pcsu.2002.31498}}</ref> <ref name="pmidhttps://www.ncbi.nlm.nih.gov/pubmed/31194423">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=https://www.ncbi.nlm.nih.gov/pubmed/31194423 | doi= | pmc= | url= }} </ref>

==References==
{{reflist|2}}
[[Category:Gastroenterology]]