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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">A 25-year-old male was admitted to the internal medicine outpatient center for swelling in the legs and periorbital region&#44; general fatigue and recurring bouts of abdominal distension and pain in recent years&#44; with no other accompanying symptoms&#46; Patient stated that he was not taking anti-inflammatory agents or other drugs on a regular basis&#46; He was admitted on several occasions to various emergency departments and was diagnosed with bouts of partial bowel obstruction&#44; which were resolved without surgery&#46; The general laboratory study showed only hypoproteinemia and iron deficiency anemia&#46; There were no inflammatory parameters&#44; and the studies on systemic and intestinal infections&#44; autoimmune diseases&#44; celiac disease&#44; lymphoma and solid tumors were negative&#46; Colonoscopy with ileoscopy and the abdominal computed tomography results were normal&#46; In the oral endoscopy&#44; an ulcerated stenosis was observed in the posterior area of the duodenal bulb&#44; whose pathological study revealed superficial ulceration&#44; along with a slight nonspecific inflammatory infiltrate of the intestinal mucosa&#46; Finally&#44; in the gastrointestinal transit time using barium and capsule endoscopy&#44; we observed several short stenoses of the small intestine and superficial ulcers&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">What disease does this patient have that is causing anemia&#44; anasarca and abdominal pain&#63; What are the diagnostic possibilities in this case&#63; What would be the most beneficial treatment&#63; What could surgery provide&#63;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The clinical problem</span><p id="par0015" class="elsevierStylePara elsevierViewall">Numerous chronic ulcerations of the small intestine with nonspecific etiology were described in the mid to late 1960s by French and Japanese scientists&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a> It is a disease whose incidence and prevalence is unknown&#46; It is currently a rare condition&#44; but its detection is important for clinicians because it presents a number of specific characteristics&#46; The syndrome is defined by the presence of numerous ulcers in the small proximal intestine &#40;ileum&#44; jejunum&#44; and duodenum&#41;&#44; which typically measure less than 4<span class="elsevierStyleHsp" style=""></span>cm and have a geographical or linear form&#46; The predominant symptoms are related to anemia&#44; fatigue&#44; weight loss and&#47;or delayed growth&#44; abdominal pain&#44; bowel obstruction conditions and peripheral edema as manifestations of hypoalbuminemia and protein-losing enteropathy&#46; The ulcers affect the mucosa and submucosa but typically do not affect the muscle layer itself&#46; The mucosa shows a nonspecific inflammatory infiltrate of plasma cells&#44; lymphocytes and scarce eosinophils&#44; with an absence of granulomas&#46; A submucous fibrosis process can also be seen in the ulceration area&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Currently&#44; due to the increasingly extensive use of capsule endoscopy<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and double balloon endoscopy&#44; clinicians can study the small intestine more precisely as a cause of occult gastrointestinal bleeding&#46; In general&#44; vascular causes &#40;telangiectasia&#44; etc&#46;&#41; tend to be the most common&#44; but the presence of ulcers in the intestinal mucosa can also be visualized with these techniques&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Various terms have been used in the scientific literature to name this disease&#46; On occasions some have overlapped others&#44; although all include a number of common characteristics with the terms of cryptogenic enteritis with stenotic ulcers &#40;CMUSE&#44; the term most known in the West&#41; or multiple&#44; nonspecific and chronic ulcers of the small intestine&#44; in its Asian terminology&#46; Its primary differential diagnosis is established with nonsteroidal anti-inflammatory drug &#40;NSAID&#41;-induced enteropathy&#44; Crohn&#39;s disease &#40;CD&#41; and intestinal tuberculosis&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Diagnosis</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Signs and symptoms</span><p id="par0030" class="elsevierStylePara elsevierViewall">The main manifestations of this condition are abdominal pain&#44; fatigue&#44; weight loss&#44; delayed growth and peripheral edema&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7</span></a> It is important to note the lack of inflammatory parameters in laboratory tests &#40;except for a case reported by Kohotov&#225; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#41;&#59; however&#44; hypoalbuminemia&#44; hypoproteinemia and iron deficiency anemia are often found&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The presence of extra-abdominal symptoms &#40;fever&#44; dry syndrome&#44; Raynaud&#39;s phenomenon&#44; polyneuropathy&#41; has only been reported in isolated cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;6&#44;7</span></a> A recessive reticular pigmentary disorder associated with chromosome X &#40;region Xp22-p21&#44; IMO 301220&#41; has been reported in a patient with CMUSE&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In the cases published in the literature&#44; CMUSE has more points in common than phenotypic differences in patients of Eastern and Western descent&#46; The age at diagnosis is younger in Asian patients&#44; and they therefore have longer follow-up periods&#46; In Western cases&#44; reports indicate that men are more frequently affected and that there are a greater number of intestinal stenoses and cases of abdominal pain&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Endoscopy and imaging tests</span><p id="par0045" class="elsevierStylePara elsevierViewall">The development of capsule endoscopy and double balloon endoscopy allows clinicians to examine the small intestine with greater precision in patients with bleeding of uncertain origin&#46; It is therefore expected that in the coming years the visualization of intestinal lesions using these techniques will increase and that CMUSE will require an accurate differential diagnosis&#46; The technique of functional radiology with oral barium contrast is well documented in the diagnosis of these patients and can be an easier and more economical initial diagnostic&#44; although it probably does not preclude the implementation of other techniques for obtaining tissue samples&#46; However&#44; intestinal lesions can be difficult to recognize&#44; since the ulcers can be very narrow&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The terminal ileum is usually spared&#44; although there are reported cases of its involvement&#46; The involvement of the small intestine at several levels is the most frequently reported&#46; Abdominal CT results are not conclusive for this disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;12</span></a> Although capsule endoscopy can diagnose more patients with this disorder&#44; this technique also has potential complications&#44; given that the stenoses are very narrow and short and the capsule can be retained in them&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The endoscopic appearance of the CMUSE lesions has been well characterized&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;13</span></a> These are linear or triangular erosions or ulcers that occasionally fuse and acquire a geographical configuration&#46; The general rule is to find multiple short&#44; narrow ulcers separated by more than 4<span class="elsevierStyleHsp" style=""></span>cm from each another&#46; The ulcers are also more distal in the small intestinal tract in comparison with NSAID-induced disease&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The ulcers do not reach the lamina propria&#46; Sometimes the stenoses are not only concentric but can also be oblique or spiral&#46; Finally&#44; findings compatible with a healing phase of the stenoses can be found&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Histology</span><p id="par0055" class="elsevierStylePara elsevierViewall">Mucosal ulcers are accompanied by a mild inflammatory infiltrate of plasma cells&#44; lymphocytes and eosinophils&#46; Occasionally&#44; lymphoid follicles can be observed&#46; The margins of the ulcer are clearly defined and surrounded by mucosa with no disorders in the villi&#46; A certain submucosal fibrosis can also be observed&#46; The inflammatory infiltrate reaches up to the submucosa but characteristically does not affect the deepest layers&#46; Granulomas&#44; fissures&#44; thrush type ulcers and local adenopathies are not observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7&#44;8&#44;15</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Differential diagnosis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Small bowel diaphragm disease &#40;DD or NSAID-associated enteropathy&#41; is an uncommon condition characterized by the presence of numerous circumferential stenotic lesions in a diaphragm shape in the small intestine of patients undergoing prolonged use of NSAIDs&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> These are short annular ulcers&#44; with superficial involvement of the apex of the villi&#44; reactive enterocytes&#44; mild to moderate inflammatory infiltrate and submucosal fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Cryptitis&#44; lymphoplasmacytic infiltrate of the lumen and the presence of eosinophils in the mucosal layer can also be observed&#46; Pathology studies have not identified transmural inflammation&#44; fistulized ulcers or lymphocytic aggregates throughout the muscularis propria layer&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The clinical and radiological presentation is similar in both conditions&#46; The differential diagnosis with CMUSE can be established by anamnesis &#40;in the absence of taking NSAIDs&#41;&#44; the possible involvement of the colon<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and the greater age of patients with DD&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Ulcerative and stenotic lesions of the small intestine can also be interpreted as involvement by Crohn&#39;s disease &#40;CD&#41;&#46; Although the lack of laboratory inflammatory parameters is very suggestive of CMUSE&#44; persistently low CRP levels have been reported in patients with CD&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> above all in ileal involvement&#46; The arrangement of CMUSE stenoses is circular or oblique&#44; geographical or linear&#44; and the stenoses are short &#40;less than 4<span class="elsevierStyleHsp" style=""></span>cm&#41; and are surrounded by healthy mucosa&#46; However&#44; in CD&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> the ulcers begin as small red points or depressions in the mucosa&#44; which can deepen and acquire a star distribution or merge into longitudinal ulcers&#44; surrounded by edematous mucosa with a cobblestone appearance&#46; Transmural involvement&#44; fistulization&#44; fissures&#44; giant-cell granuloma<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and cryptitis have not been observed in the histopathology of CMUSE&#46; The involvement of other gastrointestinal areas and extraintestinal manifestations &#40;uveitis&#44; episcleritis&#44; erythema nodosum&#44; pyoderma gangrenosum&#44; etc&#46;&#41; are more typical of CD&#46; In terms of treatment&#44; CMUSE rarely responds &#40;and then only for a few months&#41; to corticosteroid therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Intestinal infections&#44; especially by <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;21</span></a> can cause chronic inflammation of the ileum&#46; Unlike CMUSE&#44; these ulcers have irregular margins&#44; a dense mucosal exudate and several inflammatory stages&#46; These lesions can be accompanied by ascites and&#47;or locoregional adenopathies&#46; Histopathology usually reveals the presence of epithelioid granulomas with central caseous necrosis&#46; The presence of fever and sweating should make us further consider an infectious cause&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> CMUSE lesions do not respond to treatment with tuberculosis drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">In certain patients&#44; ulcerative jejunitis associated with celiac disease<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a> and intestinal infections by <span class="elsevierStyleItalic">Campylobacter</span> or <span class="elsevierStyleItalic">Shigella</span> spp&#46; can be also included in the differential diagnosis with CMUSE&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Moreover&#44; vasculitis<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> can imitate CMUSE &#40;or have an undemonstrated direct relationship&#41; and&#44; in these cases&#44; can respond well to corticosteroids &#40;both immediately and over time&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Etiology</span><p id="par0090" class="elsevierStylePara elsevierViewall">Until a few years ago&#44; data were scarce on the origin and pathogenesis of CMUSE&#46; Perlemuter et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> described a case with a type I heterozygous deficiency of the C2 component of complement &#40;genetic deletion of 28 base pairs&#41; in a patient with CMUSE&#44; extraintestinal symptoms and mesenteric aneurysms&#46; These authors proposed the hypothesis that CMUSE is a form of expression of vasculitis &#40;itself or as a variant of polyarteritis nodosa&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The first genetic evidence of the cause of this disease was reported by Adler et al&#46; in 2008&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> The authors presented the case of a 45-year-old male of Italian descent&#44; with chronic iron deficiency anemia&#44; recurring abdominal pain from childhood and gastrointestinal bleeding of uncertain origin&#46; The patient had multiple stenoses in the jejunum and ileum&#46; The authors suspected that the patient had an inherited prostanoid biosynthesis deficiency&#44; given that the platelet COX-1 activity was normal&#46; In the laboratory studies&#44; they demonstrated a marked deficit of thromboxane A2&#44; leukotriene E4 and B4 and 12-hydroxyeicosatetraenoic acid &#40;12-HETE&#41; in the presence of whole blood activated by calcium ionophore&#46; These findings were consistent with the virtual absence of arachidonic acid &#40;AA&#41; liberation during platelet activation &#40;and&#44; therefore&#44; the platelets also showed reduced total activity&#41;&#46; Platelet aggregation and degranulation in response to adenosine diphosphate &#40;ADP&#41; was virtually absent and was corrected by adding AA to the patient&#39;s platelets&#46; Following these studies&#44; the authors identified a heterozygous missense mutation in the patient&#39;s cPLA2&#945; gene &#40;PLA2G4A&#59; OMIM 600522&#41;&#58; S11P &#40;600522&#46;0001&#41; &#40;a rare allele inherited from the mother&#41; and R485H &#40;600522&#46;0002&#41; &#40;a rare variant&#41; and&#44; in the same allele as R485H&#44; a known variant of the SNP allele K651R &#40;inherited from the father&#41;&#46; The patient&#39;s sister and mother &#40;who were asymptomatic&#41; had intermediate levels of thromboxane B2 and low levels &#40;or at the lower limit of normality&#41; of 12-HETE&#46; Both were heterozygous for one of the mutations found in the patient&#46; An interesting conclusion of this study is that the synthesis of eicosanoids<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> by human platelets and leukocytes results entirely from the cPLA2&#945; pathway and suggests that this phospholipase contributes decisively to the integrity of the small intestine&#46; Other authors have suggested that consanguinity can play a role in CMUSE&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Recently&#44; Brooke et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> in 2012&#44; reported 2 new cases with a homozygous mutation of the PLA2G4A gene &#40;deletion of 4 base pairs &#91;g&#46;155574&#95;77delGTAA&#93;&#44; in exon 17&#41; in 2 siblings &#40;1 male and 1 female&#41; with signs and symptoms of CMUSE&#46; They also demonstrated that the activity of cPLA2&#945; was virtually absent&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Treatment and prognosis</span><p id="par0105" class="elsevierStylePara elsevierViewall">Medical therapy &#40;corticosteroids and immunosuppressants&#41; is seldom effective<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7&#44;28&#44;29</span></a> in patients affected by this disease&#46; Occasionally&#44; control of the disease can be achieved for a few months&#44; although sustained remission for more than 1 year is not common&#46; Surgery can resolve the symptoms in a considerable number of cases&#44; although relapses are not rare&#44; and new laparotomies are required during follow-up of these cases&#46; Nutrition support therapy and treatment of the symptomatic anemia are therapeutic strategies that should always be maintained&#46; NSAIDs should be avoided as they theoretically can cause new outbreaks of this disease&#46; Immunosuppressants and corticosteroids should be used prudently because the side effects &#40;infections&#44; metabolic&#44; etc&#46;&#41; can subject patients to increased morbidity and mortality&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The long-term prognosis is good&#46; The mortality directly attributable to CMUSE is low&#44; although it is unknown whether CMUSE predisposes patients to increased frequency of tumors and other morbidity&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Areas of uncertainty</span><p id="par0115" class="elsevierStylePara elsevierViewall">There is currently no specific therapy for this condition and to date&#44; we have found no study underway on this topic&#46; Although it has been reported in isolated cases&#44; it is possible that the condition is caused by mutations in the PLA2G4A gene&#44; which cause dysfunction in eicosanoid biosynthesis&#46; Moreover&#44; the terms &#8220;cryptogenic&#8221; and &#8220;nonspecific&#8221; do not seem appropriate at present&#46; The scientific terms are confusing in many cases and can also be confused with other diseases&#46; The terminology of chronic&#44; multiple&#44; recurrent and stenosing ulcers of the small intestine is probably more exact for defining CMUSE&#44; in light of current knowledge of this disease&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusions</span><p id="par0120" class="elsevierStylePara elsevierViewall">After the case was studied&#44; the diagnosis was CMUSE&#44; and the hypoproteinemia and iron deficiency anemia were interpreted as secondary to intestinal losses due to the superficial mucosal ulcers typical of this disease&#46; The type of short stenoses&#44; the lack of inflammation and the histological findings were not consistent with Crohn&#39;s disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#8211;32</span></a> Adequate nutrition&#44; iron replacement therapy and low-dose steroid therapy were begun&#44; which did not substantially change the symptoms&#46; The patient was not subjected to any abdominal surgery&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Therefore&#44; CMUSE is a disease with unique characteristics&#44; probably caused by mutations in the PLA2G4A gene&#44; and whose prevalence is unknown&#46; CMUSE should be included in the differential diagnosis of patients with abdominal pain of unknown etiology &#40;both with and without prior surgeries&#41;&#44; iron deficiency anemia with intestinal bleeding of unknown origin&#44; malnutrition&#44; edema and protein-losing enteropathy&#46; Medical treatment with corticosteroids and immunosuppressants is seldom effective&#44; and patients require nutrition support measures and&#44; occasionally&#44; surgery to control the symptoms of this disease&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Authorship</span><p id="par0130" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Concept and design of the manuscript&#58; P&#46; Guisado and G&#46; Fraile Rodr&#237;guez&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Data collection&#58; P&#46; Guisado and G&#46; Fraile Rodr&#237;guez&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Data analysis and interpretation&#58; P&#46; Guisado and G&#46; Fraile Rodr&#237;guez&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Drafting&#44; review and approval of the submitted manuscript&#58; P&#46; Guisado and G&#46; Fraile Rodr&#237;guez&#46;</p></li></ul></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "identificador" => "xres307807"
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          "titulo" => "Background"
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          "titulo" => "The clinical problem"
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          "titulo" => "Diagnosis"
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              "titulo" => "Signs and symptoms"
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            1 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Endoscopy and imaging tests"
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            2 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Histology"
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        7 => array:2 [
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          "titulo" => "Differential diagnosis"
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          "titulo" => "Etiology"
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          "titulo" => "Areas of uncertainty"
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    "fechaRecibido" => "2013-04-24"
    "fechaAceptado" => "2013-07-26"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec290887"
          "palabras" => array:5 [
            0 => "Cryptogenic multifocal ulcerous stenosing enteritis"
            1 => "Protein-losing enteropathy"
            2 => "Abdominal pain"
            3 => "Gastrointestinal bleeding of obscure origin"
            4 => "Weight loss"
          ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec290888"
          "palabras" => array:5 [
            0 => "Enteritis ulcerosa criptog&#233;nica estenosante y multifocal"
            1 => "Enteropat&#237;a pierde prote&#237;nas"
            2 => "Dolor abdominal"
            3 => "Sangrado digestivo de causa oculta"
            4 => "P&#233;rdida de peso"
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We studied a patient with edema secondary to protein losing enteropathy&#44; and recurrent bouts of bloating and abdominal pain secondary to intestinal subocclusion episodes&#46; After the clinical study&#44; the patient was diagnosed of cryptogenic multifocal ulcerous stenosing enteritis &#40;CMUSE&#41;&#44; that is a rare disease&#44; probably caused by mutations in the gene PLA2G4A&#44; and characterized by multiple short stenosis of the small bowel with superficial ulcers&#44; which do not exceed the submucosa layer&#46; Inflammatory bowel disease &#40;Chron&#39;s disease&#41;&#44; intestinal tuberculosis and intestinal ulcers secondary to non-steroidal anti-inflammatory drugs are the main differential diagnosis&#46; To sum up&#44; physicians should included CMUSE in the differential diagnosis of recurrent abdominal pain&#44; iron deficiency anemia&#44; occult intestinal bleeding&#44; edema and protein losing enteropathy&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prop&#243;sito del estudio de un paciente con anasarca&#44; enteropat&#237;a pierde prote&#237;nas y dolor abdominal recurrente secundario a episodios de suboclusi&#243;n intestinal&#44; al que se le diagnostica de enteritis ulcerosa criptog&#233;nica&#44; estenosante y multifocal &#40;CMUSE&#41;&#44; se revisa esta enfermedad rara y poco conocida&#44; probablemente causada por mutaciones en el gen de PLA2G4A&#44; que se caracteriza por m&#250;ltiples estenosis cortas del intestino delgado con ulceraciones que no sobrepasan la submucosa&#46; La enfermedad inflamatoria intestinal &#40;enfermedad de Crohn&#41;&#44; la tuberculosis intestinal y las ulceraciones intestinales asociadas a la toma de antiinflamatorios no esteroides son los principales diagn&#243;sticos diferenciales&#46; En conclusi&#243;n&#44; CMUSE deber&#237;a ser incluida en el diagn&#243;stico diferencial del dolor abdominal recurrente&#44; anemia ferrop&#233;nica con sangrado intestinal oculto&#44; edemas y enteropat&#237;a pierde prote&#237;nas&#46;</p>"
      ]
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Guisado Vasco P&#44; Fraile Rodr&#237;guez G&#46; &#218;lceras estenosantes&#44; m&#250;ltiples&#44; recurrentes y cr&#243;nicas del intestino delgado&#58; una entidad propia como causa de dolor abdominal&#44; anemia ferrop&#233;nica y enteropat&#237;a pierde prote&#237;nas&#46; Rev Clin Esp&#46; 2014&#59;214&#58;26&#8211;30</p>"
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                        0 => array:2 [
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Clinical up-date
Cryptogenia multifocal ulcerous stenosing enteritis: An entity on its own as a cause of abdominal pain, iron deficiency anemia and protein-losing enteropathy
Úlceras estenosantes, múltiples, recurrentes y crónicas del intestino delgado: una entidad propia como causa de dolor abdominal, anemia ferropénica y enteropatía pierde proteínas
P. Guisado Vasco
Corresponding author
pablogvasco@gmail.com

Corresponding author.
, G. Fraile Rodríguez
Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, Madrid, Spain
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      "titulo" => "Comprehensive care program for elderly patients over 65 years with hip fracture"
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        "titulo" => "&#218;lceras estenosantes&#44; m&#250;ltiples&#44; recurrentes y cr&#243;nicas del intestino delgado&#58; una entidad propia como causa de dolor abdominal&#44; anemia ferrop&#233;nica y enteropat&#237;a pierde prote&#237;nas"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">A 25-year-old male was admitted to the internal medicine outpatient center for swelling in the legs and periorbital region&#44; general fatigue and recurring bouts of abdominal distension and pain in recent years&#44; with no other accompanying symptoms&#46; Patient stated that he was not taking anti-inflammatory agents or other drugs on a regular basis&#46; He was admitted on several occasions to various emergency departments and was diagnosed with bouts of partial bowel obstruction&#44; which were resolved without surgery&#46; The general laboratory study showed only hypoproteinemia and iron deficiency anemia&#46; There were no inflammatory parameters&#44; and the studies on systemic and intestinal infections&#44; autoimmune diseases&#44; celiac disease&#44; lymphoma and solid tumors were negative&#46; Colonoscopy with ileoscopy and the abdominal computed tomography results were normal&#46; In the oral endoscopy&#44; an ulcerated stenosis was observed in the posterior area of the duodenal bulb&#44; whose pathological study revealed superficial ulceration&#44; along with a slight nonspecific inflammatory infiltrate of the intestinal mucosa&#46; Finally&#44; in the gastrointestinal transit time using barium and capsule endoscopy&#44; we observed several short stenoses of the small intestine and superficial ulcers&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">What disease does this patient have that is causing anemia&#44; anasarca and abdominal pain&#63; What are the diagnostic possibilities in this case&#63; What would be the most beneficial treatment&#63; What could surgery provide&#63;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The clinical problem</span><p id="par0015" class="elsevierStylePara elsevierViewall">Numerous chronic ulcerations of the small intestine with nonspecific etiology were described in the mid to late 1960s by French and Japanese scientists&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a> It is a disease whose incidence and prevalence is unknown&#46; It is currently a rare condition&#44; but its detection is important for clinicians because it presents a number of specific characteristics&#46; The syndrome is defined by the presence of numerous ulcers in the small proximal intestine &#40;ileum&#44; jejunum&#44; and duodenum&#41;&#44; which typically measure less than 4<span class="elsevierStyleHsp" style=""></span>cm and have a geographical or linear form&#46; The predominant symptoms are related to anemia&#44; fatigue&#44; weight loss and&#47;or delayed growth&#44; abdominal pain&#44; bowel obstruction conditions and peripheral edema as manifestations of hypoalbuminemia and protein-losing enteropathy&#46; The ulcers affect the mucosa and submucosa but typically do not affect the muscle layer itself&#46; The mucosa shows a nonspecific inflammatory infiltrate of plasma cells&#44; lymphocytes and scarce eosinophils&#44; with an absence of granulomas&#46; A submucous fibrosis process can also be seen in the ulceration area&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Currently&#44; due to the increasingly extensive use of capsule endoscopy<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and double balloon endoscopy&#44; clinicians can study the small intestine more precisely as a cause of occult gastrointestinal bleeding&#46; In general&#44; vascular causes &#40;telangiectasia&#44; etc&#46;&#41; tend to be the most common&#44; but the presence of ulcers in the intestinal mucosa can also be visualized with these techniques&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Various terms have been used in the scientific literature to name this disease&#46; On occasions some have overlapped others&#44; although all include a number of common characteristics with the terms of cryptogenic enteritis with stenotic ulcers &#40;CMUSE&#44; the term most known in the West&#41; or multiple&#44; nonspecific and chronic ulcers of the small intestine&#44; in its Asian terminology&#46; Its primary differential diagnosis is established with nonsteroidal anti-inflammatory drug &#40;NSAID&#41;-induced enteropathy&#44; Crohn&#39;s disease &#40;CD&#41; and intestinal tuberculosis&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Diagnosis</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Signs and symptoms</span><p id="par0030" class="elsevierStylePara elsevierViewall">The main manifestations of this condition are abdominal pain&#44; fatigue&#44; weight loss&#44; delayed growth and peripheral edema&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7</span></a> It is important to note the lack of inflammatory parameters in laboratory tests &#40;except for a case reported by Kohotov&#225; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#41;&#59; however&#44; hypoalbuminemia&#44; hypoproteinemia and iron deficiency anemia are often found&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The presence of extra-abdominal symptoms &#40;fever&#44; dry syndrome&#44; Raynaud&#39;s phenomenon&#44; polyneuropathy&#41; has only been reported in isolated cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;6&#44;7</span></a> A recessive reticular pigmentary disorder associated with chromosome X &#40;region Xp22-p21&#44; IMO 301220&#41; has been reported in a patient with CMUSE&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In the cases published in the literature&#44; CMUSE has more points in common than phenotypic differences in patients of Eastern and Western descent&#46; The age at diagnosis is younger in Asian patients&#44; and they therefore have longer follow-up periods&#46; In Western cases&#44; reports indicate that men are more frequently affected and that there are a greater number of intestinal stenoses and cases of abdominal pain&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Endoscopy and imaging tests</span><p id="par0045" class="elsevierStylePara elsevierViewall">The development of capsule endoscopy and double balloon endoscopy allows clinicians to examine the small intestine with greater precision in patients with bleeding of uncertain origin&#46; It is therefore expected that in the coming years the visualization of intestinal lesions using these techniques will increase and that CMUSE will require an accurate differential diagnosis&#46; The technique of functional radiology with oral barium contrast is well documented in the diagnosis of these patients and can be an easier and more economical initial diagnostic&#44; although it probably does not preclude the implementation of other techniques for obtaining tissue samples&#46; However&#44; intestinal lesions can be difficult to recognize&#44; since the ulcers can be very narrow&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The terminal ileum is usually spared&#44; although there are reported cases of its involvement&#46; The involvement of the small intestine at several levels is the most frequently reported&#46; Abdominal CT results are not conclusive for this disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;12</span></a> Although capsule endoscopy can diagnose more patients with this disorder&#44; this technique also has potential complications&#44; given that the stenoses are very narrow and short and the capsule can be retained in them&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The endoscopic appearance of the CMUSE lesions has been well characterized&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;13</span></a> These are linear or triangular erosions or ulcers that occasionally fuse and acquire a geographical configuration&#46; The general rule is to find multiple short&#44; narrow ulcers separated by more than 4<span class="elsevierStyleHsp" style=""></span>cm from each another&#46; The ulcers are also more distal in the small intestinal tract in comparison with NSAID-induced disease&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The ulcers do not reach the lamina propria&#46; Sometimes the stenoses are not only concentric but can also be oblique or spiral&#46; Finally&#44; findings compatible with a healing phase of the stenoses can be found&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Histology</span><p id="par0055" class="elsevierStylePara elsevierViewall">Mucosal ulcers are accompanied by a mild inflammatory infiltrate of plasma cells&#44; lymphocytes and eosinophils&#46; Occasionally&#44; lymphoid follicles can be observed&#46; The margins of the ulcer are clearly defined and surrounded by mucosa with no disorders in the villi&#46; A certain submucosal fibrosis can also be observed&#46; The inflammatory infiltrate reaches up to the submucosa but characteristically does not affect the deepest layers&#46; Granulomas&#44; fissures&#44; thrush type ulcers and local adenopathies are not observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7&#44;8&#44;15</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Differential diagnosis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Small bowel diaphragm disease &#40;DD or NSAID-associated enteropathy&#41; is an uncommon condition characterized by the presence of numerous circumferential stenotic lesions in a diaphragm shape in the small intestine of patients undergoing prolonged use of NSAIDs&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> These are short annular ulcers&#44; with superficial involvement of the apex of the villi&#44; reactive enterocytes&#44; mild to moderate inflammatory infiltrate and submucosal fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Cryptitis&#44; lymphoplasmacytic infiltrate of the lumen and the presence of eosinophils in the mucosal layer can also be observed&#46; Pathology studies have not identified transmural inflammation&#44; fistulized ulcers or lymphocytic aggregates throughout the muscularis propria layer&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The clinical and radiological presentation is similar in both conditions&#46; The differential diagnosis with CMUSE can be established by anamnesis &#40;in the absence of taking NSAIDs&#41;&#44; the possible involvement of the colon<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and the greater age of patients with DD&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Ulcerative and stenotic lesions of the small intestine can also be interpreted as involvement by Crohn&#39;s disease &#40;CD&#41;&#46; Although the lack of laboratory inflammatory parameters is very suggestive of CMUSE&#44; persistently low CRP levels have been reported in patients with CD&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> above all in ileal involvement&#46; The arrangement of CMUSE stenoses is circular or oblique&#44; geographical or linear&#44; and the stenoses are short &#40;less than 4<span class="elsevierStyleHsp" style=""></span>cm&#41; and are surrounded by healthy mucosa&#46; However&#44; in CD&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> the ulcers begin as small red points or depressions in the mucosa&#44; which can deepen and acquire a star distribution or merge into longitudinal ulcers&#44; surrounded by edematous mucosa with a cobblestone appearance&#46; Transmural involvement&#44; fistulization&#44; fissures&#44; giant-cell granuloma<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and cryptitis have not been observed in the histopathology of CMUSE&#46; The involvement of other gastrointestinal areas and extraintestinal manifestations &#40;uveitis&#44; episcleritis&#44; erythema nodosum&#44; pyoderma gangrenosum&#44; etc&#46;&#41; are more typical of CD&#46; In terms of treatment&#44; CMUSE rarely responds &#40;and then only for a few months&#41; to corticosteroid therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Intestinal infections&#44; especially by <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;21</span></a> can cause chronic inflammation of the ileum&#46; Unlike CMUSE&#44; these ulcers have irregular margins&#44; a dense mucosal exudate and several inflammatory stages&#46; These lesions can be accompanied by ascites and&#47;or locoregional adenopathies&#46; Histopathology usually reveals the presence of epithelioid granulomas with central caseous necrosis&#46; The presence of fever and sweating should make us further consider an infectious cause&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> CMUSE lesions do not respond to treatment with tuberculosis drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">In certain patients&#44; ulcerative jejunitis associated with celiac disease<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a> and intestinal infections by <span class="elsevierStyleItalic">Campylobacter</span> or <span class="elsevierStyleItalic">Shigella</span> spp&#46; can be also included in the differential diagnosis with CMUSE&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Moreover&#44; vasculitis<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> can imitate CMUSE &#40;or have an undemonstrated direct relationship&#41; and&#44; in these cases&#44; can respond well to corticosteroids &#40;both immediately and over time&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Etiology</span><p id="par0090" class="elsevierStylePara elsevierViewall">Until a few years ago&#44; data were scarce on the origin and pathogenesis of CMUSE&#46; Perlemuter et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> described a case with a type I heterozygous deficiency of the C2 component of complement &#40;genetic deletion of 28 base pairs&#41; in a patient with CMUSE&#44; extraintestinal symptoms and mesenteric aneurysms&#46; These authors proposed the hypothesis that CMUSE is a form of expression of vasculitis &#40;itself or as a variant of polyarteritis nodosa&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The first genetic evidence of the cause of this disease was reported by Adler et al&#46; in 2008&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> The authors presented the case of a 45-year-old male of Italian descent&#44; with chronic iron deficiency anemia&#44; recurring abdominal pain from childhood and gastrointestinal bleeding of uncertain origin&#46; The patient had multiple stenoses in the jejunum and ileum&#46; The authors suspected that the patient had an inherited prostanoid biosynthesis deficiency&#44; given that the platelet COX-1 activity was normal&#46; In the laboratory studies&#44; they demonstrated a marked deficit of thromboxane A2&#44; leukotriene E4 and B4 and 12-hydroxyeicosatetraenoic acid &#40;12-HETE&#41; in the presence of whole blood activated by calcium ionophore&#46; These findings were consistent with the virtual absence of arachidonic acid &#40;AA&#41; liberation during platelet activation &#40;and&#44; therefore&#44; the platelets also showed reduced total activity&#41;&#46; Platelet aggregation and degranulation in response to adenosine diphosphate &#40;ADP&#41; was virtually absent and was corrected by adding AA to the patient&#39;s platelets&#46; Following these studies&#44; the authors identified a heterozygous missense mutation in the patient&#39;s cPLA2&#945; gene &#40;PLA2G4A&#59; OMIM 600522&#41;&#58; S11P &#40;600522&#46;0001&#41; &#40;a rare allele inherited from the mother&#41; and R485H &#40;600522&#46;0002&#41; &#40;a rare variant&#41; and&#44; in the same allele as R485H&#44; a known variant of the SNP allele K651R &#40;inherited from the father&#41;&#46; The patient&#39;s sister and mother &#40;who were asymptomatic&#41; had intermediate levels of thromboxane B2 and low levels &#40;or at the lower limit of normality&#41; of 12-HETE&#46; Both were heterozygous for one of the mutations found in the patient&#46; An interesting conclusion of this study is that the synthesis of eicosanoids<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> by human platelets and leukocytes results entirely from the cPLA2&#945; pathway and suggests that this phospholipase contributes decisively to the integrity of the small intestine&#46; Other authors have suggested that consanguinity can play a role in CMUSE&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Recently&#44; Brooke et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> in 2012&#44; reported 2 new cases with a homozygous mutation of the PLA2G4A gene &#40;deletion of 4 base pairs &#91;g&#46;155574&#95;77delGTAA&#93;&#44; in exon 17&#41; in 2 siblings &#40;1 male and 1 female&#41; with signs and symptoms of CMUSE&#46; They also demonstrated that the activity of cPLA2&#945; was virtually absent&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Treatment and prognosis</span><p id="par0105" class="elsevierStylePara elsevierViewall">Medical therapy &#40;corticosteroids and immunosuppressants&#41; is seldom effective<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7&#44;28&#44;29</span></a> in patients affected by this disease&#46; Occasionally&#44; control of the disease can be achieved for a few months&#44; although sustained remission for more than 1 year is not common&#46; Surgery can resolve the symptoms in a considerable number of cases&#44; although relapses are not rare&#44; and new laparotomies are required during follow-up of these cases&#46; Nutrition support therapy and treatment of the symptomatic anemia are therapeutic strategies that should always be maintained&#46; NSAIDs should be avoided as they theoretically can cause new outbreaks of this disease&#46; Immunosuppressants and corticosteroids should be used prudently because the side effects &#40;infections&#44; metabolic&#44; etc&#46;&#41; can subject patients to increased morbidity and mortality&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The long-term prognosis is good&#46; The mortality directly attributable to CMUSE is low&#44; although it is unknown whether CMUSE predisposes patients to increased frequency of tumors and other morbidity&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Areas of uncertainty</span><p id="par0115" class="elsevierStylePara elsevierViewall">There is currently no specific therapy for this condition and to date&#44; we have found no study underway on this topic&#46; Although it has been reported in isolated cases&#44; it is possible that the condition is caused by mutations in the PLA2G4A gene&#44; which cause dysfunction in eicosanoid biosynthesis&#46; Moreover&#44; the terms &#8220;cryptogenic&#8221; and &#8220;nonspecific&#8221; do not seem appropriate at present&#46; The scientific terms are confusing in many cases and can also be confused with other diseases&#46; The terminology of chronic&#44; multiple&#44; recurrent and stenosing ulcers of the small intestine is probably more exact for defining CMUSE&#44; in light of current knowledge of this disease&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusions</span><p id="par0120" class="elsevierStylePara elsevierViewall">After the case was studied&#44; the diagnosis was CMUSE&#44; and the hypoproteinemia and iron deficiency anemia were interpreted as secondary to intestinal losses due to the superficial mucosal ulcers typical of this disease&#46; The type of short stenoses&#44; the lack of inflammation and the histological findings were not consistent with Crohn&#39;s disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#8211;32</span></a> Adequate nutrition&#44; iron replacement therapy and low-dose steroid therapy were begun&#44; which did not substantially change the symptoms&#46; The patient was not subjected to any abdominal surgery&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Therefore&#44; CMUSE is a disease with unique characteristics&#44; probably caused by mutations in the PLA2G4A gene&#44; and whose prevalence is unknown&#46; CMUSE should be included in the differential diagnosis of patients with abdominal pain of unknown etiology &#40;both with and without prior surgeries&#41;&#44; iron deficiency anemia with intestinal bleeding of unknown origin&#44; malnutrition&#44; edema and protein-losing enteropathy&#46; Medical treatment with corticosteroids and immunosuppressants is seldom effective&#44; and patients require nutrition support measures and&#44; occasionally&#44; surgery to control the symptoms of this disease&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Authorship</span><p id="par0130" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Concept and design of the manuscript&#58; P&#46; Guisado and G&#46; Fraile Rodr&#237;guez&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Data collection&#58; P&#46; Guisado and G&#46; Fraile Rodr&#237;guez&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Data analysis and interpretation&#58; P&#46; Guisado and G&#46; Fraile Rodr&#237;guez&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Drafting&#44; review and approval of the submitted manuscript&#58; P&#46; Guisado and G&#46; Fraile Rodr&#237;guez&#46;</p></li></ul></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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              "titulo" => "Endoscopy and imaging tests"
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            2 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Histology"
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          "titulo" => "Differential diagnosis"
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          "titulo" => "Etiology"
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    "fechaRecibido" => "2013-04-24"
    "fechaAceptado" => "2013-07-26"
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          "clase" => "keyword"
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            0 => "Cryptogenic multifocal ulcerous stenosing enteritis"
            1 => "Protein-losing enteropathy"
            2 => "Abdominal pain"
            3 => "Gastrointestinal bleeding of obscure origin"
            4 => "Weight loss"
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            0 => "Enteritis ulcerosa criptog&#233;nica estenosante y multifocal"
            1 => "Enteropat&#237;a pierde prote&#237;nas"
            2 => "Dolor abdominal"
            3 => "Sangrado digestivo de causa oculta"
            4 => "P&#233;rdida de peso"
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We studied a patient with edema secondary to protein losing enteropathy&#44; and recurrent bouts of bloating and abdominal pain secondary to intestinal subocclusion episodes&#46; After the clinical study&#44; the patient was diagnosed of cryptogenic multifocal ulcerous stenosing enteritis &#40;CMUSE&#41;&#44; that is a rare disease&#44; probably caused by mutations in the gene PLA2G4A&#44; and characterized by multiple short stenosis of the small bowel with superficial ulcers&#44; which do not exceed the submucosa layer&#46; Inflammatory bowel disease &#40;Chron&#39;s disease&#41;&#44; intestinal tuberculosis and intestinal ulcers secondary to non-steroidal anti-inflammatory drugs are the main differential diagnosis&#46; To sum up&#44; physicians should included CMUSE in the differential diagnosis of recurrent abdominal pain&#44; iron deficiency anemia&#44; occult intestinal bleeding&#44; edema and protein losing enteropathy&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prop&#243;sito del estudio de un paciente con anasarca&#44; enteropat&#237;a pierde prote&#237;nas y dolor abdominal recurrente secundario a episodios de suboclusi&#243;n intestinal&#44; al que se le diagnostica de enteritis ulcerosa criptog&#233;nica&#44; estenosante y multifocal &#40;CMUSE&#41;&#44; se revisa esta enfermedad rara y poco conocida&#44; probablemente causada por mutaciones en el gen de PLA2G4A&#44; que se caracteriza por m&#250;ltiples estenosis cortas del intestino delgado con ulceraciones que no sobrepasan la submucosa&#46; La enfermedad inflamatoria intestinal &#40;enfermedad de Crohn&#41;&#44; la tuberculosis intestinal y las ulceraciones intestinales asociadas a la toma de antiinflamatorios no esteroides son los principales diagn&#243;sticos diferenciales&#46; En conclusi&#243;n&#44; CMUSE deber&#237;a ser incluida en el diagn&#243;stico diferencial del dolor abdominal recurrente&#44; anemia ferrop&#233;nica con sangrado intestinal oculto&#44; edemas y enteropat&#237;a pierde prote&#237;nas&#46;</p>"
      ]
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Guisado Vasco P&#44; Fraile Rodr&#237;guez G&#46; &#218;lceras estenosantes&#44; m&#250;ltiples&#44; recurrentes y cr&#243;nicas del intestino delgado&#58; una entidad propia como causa de dolor abdominal&#44; anemia ferrop&#233;nica y enteropat&#237;a pierde prote&#237;nas&#46; Rev Clin Esp&#46; 2014&#59;214&#58;26&#8211;30</p>"
      ]
    ]
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Original language: English
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