abdominal pain, diarrhea, orbleeding. lation. offever,There wasnohistory arthralgia, nausea, vomiting, ofhypertension,referred ahistory hyperuricemia, andatrialfibril infection, buttheweightlosscontinued. Hewasaretiredmanand doing someexercise. Hestoppedbothafter sufferinganinfluenza of three months. The patient tried to lose weight on a diet and because ofunintentionalweightloss. Hehadlost10kginaperiod A 68 years old man was referred to the outpatient consultation CASE REPORT PET-CT scanningasadiagnostictool. weight lossandreviewtheliteraturefocusingonroleof The authors describe a case of W.D. presented as isolated “Eryma” (barrier), thatmeansobstacletoabsorptionoffood etiological agentcomesfromtheGreek “Trophy” (food), and of thelaminapropria the intestinalmucosadeterminesanextensiveinvolvement with PAS. The foamyrosyappearanceofmacrophagesinside fast negative actinomycete, periodic acid-Schiff-positive (PAS) andacid- ( system nervous systems like the joints, cardiovascular system and central tion fromgastrointestinalinvolvementbutalsoaffectsother per 1.000.000 inhabitants ple disorder first described in 1907 by Dr. George Hoyt Whip Whipple’s disease(W.D.) isamultisystemicchronicinfectious INTRODUCTION Department ofInternalMedicineand(*)Pathology. HospitalClínicoUniversitario. SantiagodeCompostela. Spain. Páez-Guillán E, García-Villafranca A, Lazaré-IglesiasH(*), Díaz-Peromingo JA. Role ofPET-CT scanningandreviewoftheliterature Unintentional weightlossaspresentingformof Whipple’s disease. Recibido: 22/04/2019; Aceptado: 27/05/2019// Unintentional weight lossaspresentingform of Whipple’s disease. RoleofPET-CT scanningandreviewofthe literature. GaliciaClin2020;81 (3): 90-92 Cómo citaresteartículo: Páez-Guillán E, García-Villafranca A, Lazaré-IglesiasH, Díaz-PeromingoJA. Correspondencia: CASO CLÍNICO T. whipplei Figure 1. PET-CT scan. Panel A showsenlargedmesentericlymphnodesandPanelB an inguinalenlargedlymphnode. Biopsyoftheinguinallymph 1 . rare,The disease is very with an annual incidence of 1 [email protected] ) wasfirstdescribedin1992. Itisagram-positive 4 . Itcontainspolysaccharidesthatstainpositive 3 . The etiological agent, 2 and, inthissense, thenameof 2 http://doi.org/10.22546/57/1959 . It not only involves malabsorp Tropheryma whipplei node wasmadeshowingnopathologicalfindings.

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inguinal lymph node was reported as normal. Duodenal biopsy with mesenteric lymphnodesyndrome. A coreneedlebiopsyfromthe lymph nodessuggestingtheradiologicappearanceofcavitating showing enlargement of several abdominal and inguinal hypodense computed tomography(PET-CT) scanwasperformed(Figure1) toms butcontinuedlosingweight. A positronemissiontomography/ After thisinitialevaluationthepatientreferrednoassociatedsymp sonographic study, upperendoscopyandcolonoscopywerenormal. glutaminase antibodies(ATGT) werenegative. An abdominalultra with normal serum ferritinlevel, and iron level. Anti-tissue trans coagulation wasnormal. Mildanemia(Hb12.8g/L)wasfound Serum biochemistry, leucocytecount, plateletcount, aswellblood were normal. were normal. Neurologicalexamination, digestivesystemandjoints On physicalexamination, thepatientwasafebrileandvitalsigns regular basis. mg twice a day). Currently he continues to take TMP-SMZ on a long term trimethoprim-sulfamethoxazole (TMP-SMZ; 160/800 home) wasgivenfor2weeks. This initialtherapywasfollowedby Antibiotic treatmentusingceftriaxone(2g/dayintravenouslyat positive resultintheduodenalbiopsy. (PCR) assaytargetingthe16SrRNAgeneof There was no evidence of malignancy. Polymerase chain reaction 2). Special staining for acid-fast bacilli and fungi were negative. numerous granularintracytoplasmicinclusionsPAS positive(Figure thickening oftheintestinalvilliandfoamymacrophagescontaining investigation ofcoeliacdiseaseand W.D. wasperformedshowing T. whipplei

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Galicia Clínica | Sociedade Galega de Medicina Interna Galicia Clínica | Sociedade Galega de Medicina Interna symptoms but isolated weight loss is very rare.symptoms butisolated weightlossisvery A patientwith important manifestation ated withmalabsorption complaint inpatientsaffected from W.D. intestinal system(75-95%) The most frequent and common symptoms involve the gastro classical W.D. a protectiveimmuneresponsearepronetodevelopmentof the pathogenesis bacterial, andenvironmentalfactorsmayallcontribute to of carriersdevelop W.D. Inthissense, itseemsthathost, terium is acquiredduring childhood vironmental source transmission or because they are infected by the same en the bacterium either because of human to human carrying Relatives ofchronic W.D. patients haveahigherchanceof and cerebrospinalfluid bowel, colon, larynx, sinus, maxillary aqueoushumor, brain, valve, lung, bronchoalveolarfluid, liver, spleen, stomach, small node, synovial fluid, skeletalmuscle, myocardium, cardiac cal samplesincludingurine, blood, saliva, stool, skin, lymph years bacterium throughthebody, butcarriagecanlastforseveral riers develop protective response that prevents spread of the voir fromwhichotherhumansmightbecolonized. Mostcar Asymptomatic carriersof new casesper10.000.000personsyearworldwide incidence ratehasbeenestimatedtobebetween1and6 ing PCRtestingasatoolfordiagnosisof W. D., theannual in thenative African and Asian populations mainly patients from Europe and North America. rare It is very particularly in male patients that work with animals Epidemiologically, W.D. islinkedtoafecal-oraltransmission, like W.D. areapossibleunderlyingetiology. cause ofunintentionalweightloss disorders, mainly digestive diseases are the mostfrequent plained unintentionalweightloss. Non-malignantorganic This casedealswithararediseasepresentingunex DISCUSSION Figure 2. Duodenalbiopsy. Panel A showsthickeningoftheintestinalvilliandfoamymacrophages(H&E, originalmagnificationx20). PAS stain(Panel B) revealsthepresenceofnumerousgranularintracytoplasmicinclusionsPAS positive, diastaseresistant(PAS-D, originalmagnificationx40). 10 . T. whipplei 1 . 14 . Probably, subjectswhodonotdevelop 13 hasbeenfoundinnumerousbiologi . Although itisassumedthatthe bac 11,12 17 18 T. whipplei commonly associated with other . Weight lossisthesecondmost . 2,16 . Diarrheaisthe mostcommon 6 . Malabsorptivediseases 14 representalargereser , only a limited number 17 frequentlyassoci 8 .introduc After 7 affecting affecting 9 . ------Clinical presentationishighlypolymorphic. There has been malabsorption result bothfromanorexiaandnutritionaldeficiencydueto loss isapredominantfeatureofthedisease, cachexiamay most common in males 40-50 years old Weight loss is less common in patients under 40 years. It is W.D. associatedweightlosscanloseupto15Kginoneyear. disease, lymphoma, Crohn’s diseaseoramyloidosis differentiation withmalabsorptive disorderssuchasceliac Both diagnostictests, PCRandPAS positive, allowalsothe teria such as therapy andperformadifferential diagnosiswithotherbac lows toevaluatethedegreeofpatientresponseantibiotic depending fromthePCRassayperformed a highsensitivity(59-95%)butlowspecificity(45-71%), sequence ofthe16SRNAgene diagnosis withPCRgivingadeterminationofthenucleotide Important diagnostic support is provided by the molecular neurological symptom neurological involvement in untreated W.D., or an isolated be theresultofarelapsepreviouslytreatedclassic W.D., 10-43% inpatientswith W.D. Neurologicalmanifestationscan feature 17-55% ofthecasesbeingendocarditismostfrequent to spondylitis volvement ofdistaljointsiscommon(65-90%)andcanevolve Polyarthralgia duetochronicpolyarthritiswithmigrantin and mucosa and diffuseedemaexudatesinsidetheintestinalwall of gastrointestinalaffectationisduetobacterialovergrowth eyes, heart, system andcentralnervous organcanbeinvolved,phase wherealmostevery mostlythe gia. A middle phase with diarrhea and weight loss, and alate with symptomsofinfectionsuchasfever, arthritisorarthral Symptoms tendtodevelopinthreephases. An earlyphase localized chronic infections, acute infections, and carriage described fourcommonlyrecognizedpatterns: classic W.D., 2,22 . system can be involved around The central nervous 22 complex 5,23 . 16 . . The cardiovascular system is affected in , or 24 Histoplasma sp . T. whipplei Galicia Clin 2020;81(3):90-92 , 16 spp Corynebacterium . 21 7,19 . Pathophysiology 11,16 . This testhave .weight When . PCRalsoal Páez-Guillán E, etal 25 . Never |

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PULSE PARA VOLVER AL ÍNDICE CASO CLÍNICO Galicia Clin 2020;81(3): |

92 should beinvestigated. thy andunintentionalweightloss, apossibleunderlying W.D. In patientswithmesentericorretroperitoneal lymphadenopa research isnegative, antibiotictreatmentcanbestopped. therapy shouldbemade. When the PAS-positive macrophages with duodenalbiopsywithin6to12monthsfromtheonsetof symptoms in1-4weeks. Regardingtofollowup, gastroscopy and preventsrelapse oxazole for 1 to 2 years guarantees the remission of the disease prolonged antibiotictherapywith Trimethoprim andSulfometh Treatment withparenteralceftriaxone, 2grdaily, followedby positive for contain bacteriaorremnantsofbacteria. PCRtestingcanbe and foamymacrophageswithvesiclesPAS-positive thatcan occlusion ofvessels, lipiddepositinthelaminaofwall, opsy thatevidencesthickeningoftheintestinalwall, lymphatic Diagnostic toolsincludeupperendoscopywithduodenalbi intestinal mucosaleadingtomalabsorptionanddiarrhea aggravate thelymphaticstasisandassociatededemaof The mesentericandretroperitoneallymphadenopathycan to chronicconstipationandeventuallyintestinalobstruction Mesenteric lymphadenopathyisalsocommonandcanevolve lymphoma or other infectious diseases such as . indistinguishable fromlymphadenopathyduetosarcoidosis, 40 to60%ofcases Peripheral lymphadenopathyisfrequentin W.D. rangingfrom mas omas, tuberculosis, metastaticgermcelltumors, orlympho be madewithcysticlymphangiomas, mesentericlymphangi of themesentericlymphnode presence of fluid and/or adipose material in the central cavity masses withacentrallowattenuationareacausedbythe ism. Computedtomographyshowsmultiplecysticmesenteric findings of hyposplen sociated to clinical signs and laboratory to treatment,loss that is refractory fatigue, and diarrhea as understood. PatientswithCMLNSoftenpresentweight intolerance togluteningestion)thatisdocumentedbutpoorly tion ofceliacdisease(chronicenteropathycharacterizedby mesenteric lymphnode syndrome (CMLNS) is a complica nancy, orintheevaluationofmetastaticdisease. Cavitating patients withsuspectedoccultinflammation, malig primary PET-CT scanningiscommonlyusedintheassessmentof cording toclinicalfindingsshouldbepreformed positive, more invasive samples such as blood, or others ac diagnosing W. D. usingPCRinstoolorsalivasamples. When blood such as synovial fluid, cerebrospinal fluid, cardiac tissue or disease, itcanbealsoperformedinnondigestivesamples test after ordered as a confirmatory PAS stainingin classical gut related toanunevendistributionofthebacteriumwithin histology. A possibleexplanationforthisdiscrepancyhasbeen ant resultsespeciallybecausePCRsensitivityishigherthan theless, histology(PAS positive)andPCRmayshowdiscord Role ofPET-CT scanningandreviewoftheliterature Unintentional weightlossaspresentingformof Whipple’s disease.

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16,25,30 . Although intestinaltissuePCRhasbeentraditionally 27 . Ofnote, someauthorshaveproposedastrategyfor . T.whipplei 90-92 31 . Fromaclinicalpointofview, theyare 5. DNA. Antibiotic treatmentreducesclinical 29 . Differentialdiagnosisshould

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