Galicia Clínica | Sociedade Galega de Medicina Interna people, being people, 1 000 000 in 1 about affects that syndrome malabsorption the diagnosis the confirm to biopsy tissue the in bacteria the of presence the The polymerase chain reaction (PCR) can be used to identify erosions.mucosal and exudates whitish with folds mucosal performed through endoscopy where there is a thickening of ces ch is taxonomically closely related to the group of Whipple´s disease, araremalabsorption syndrome Cómo citareste artículo: BatistaR, Real A, Nepomuceno J, PimientaM Correspondencia: [email protected] sed by The Whipple´s disease is a rare multisystemic infection cau- Introduction increase reaction) chain (polymerase PCR in and macrophages staining positive tissues.Immunohistochemical Shiff) affected acid- (periodic PAS of detection the is diagnosis concerning method standard The misdiagnosed. often is it rarity and presentation by involvement,multiform Tropherymacaused multisystemic it´s with to whipplei.illness Due bacterial rare, chronic a is disease Whipple´s Abstract Recibido: 02/12/2017; Aceptado: 26/12/2017 Palabras clave: Keywords: progressive stage. cases.of with majority patient a the a in in of disease outcome case Whipple´s favourable a a describe provides autors therapy The antibiotic term Long and anemia rate sedimentation erythrocyte elevated hypoalbuminemia, as:such diagnosis the of suggestive be can combination in that findings nonspecific several provide may tests boratory with systemic repercussions and nonspecific symptoms. La- disease a is it because achieve to difficult is diagnosis Early therapy followed by maintenance regimen for a long period cardiovascular, neurological and pulmonary disfunct hyperpigmentation lymphadenopathy, cachexia, rhea, includes that stagegeneralized (3) lossand;weight weaknes diarrhea, pain, symptoms: abdominal typical in the large joints) that can preceed illness for 1 forillnesspreceed can thatjoints)large the in symptoms,dromalincludingpolyarthralgiamigratory It´s classic clinical course has three stages: (1) small intestineatthejejunumlevelcausingmalabsorption. macrophages thogenesis is linked to a defect of the impared function of the Serviço deMedicinaInterna,Serviço CentroHospitalarMédio Tejo, Abrantes, Portugal Raquel Batista and Tropheryma whipplei Mycobacteria Whipple´s disease. Malabsorptionsyndrome. Tropheryma whipplei 6 . Thus, the specific immediate diagnosis can be Enfermedadde Whipple. Síndromedemalabsorción. Tropheryma whipplei 7 3

. Treatment consists of induction of antibiotic of induction of .Treatmentconsists . affected mainly men 40 to 50 years 50 to 40 men mainly affected , Tropherymawhipplei André Real 1 .It is an important cause of infectious of cause important an is .It

, , a gram positive of latediagnosis. Galicia Clin2018;79(3): 89-91 Jorge Nepomuceno

preferably reaches the reaches preferably

nonspecific pro- bacterium bacterium whi- Whipple´s disease, araremalabsorption 0 years; (2)years; 0 , Actinomy- ions Maria deFátima Pimenta 2 steator- . Its pa- Its . (mainly and s 4,5 and . 4 .

was thin,was weighing(BMI= kg13.3kg/m32 bar pain with mechanical characteristics. At the ad about one year. Her previous medical history includ nia, anemia and intermittent diarrhea without blood emergencyroom for investigation of17akg weight femalecaucasiana oldpatientwasyear four fifty A Case report exposed areas edemaand skin hyperpigmentation of the entire body Fig. 1. Patient beforethetreatmentfor Whipple’s disease. syndrome

(fig 1).

the sensitivity and specificity of conventional methods. conventional of specificity and sensitivity the

of late diagnosis.of late Galicia Clin 2018;79(3):89-91 2 ),

presentedlowerlimb CASO CLÍNICO mission, the patient ed 2 years of lom- , mucus or pus for losswith asthe- mostly the sun mte t the dmitted to |

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PULSE PARA VOLVER AL ÍNDICE CASO CLÍNICO Whipple´s disease, a rare malabsorption syndrome of late diagnosis

Unremarkable pulmonary, cardiac and abdominal examination.La- ganism from samples of saliva, gastric juice and duodenal boratory tests showed iron deficiency anemia (hemoglobin = 6.5 biopsies of patients without Whipple´s disease 8. There seems g/dL, ferritin = 26.6 ug/L, transferrin saturation = 4%, serum iron to be a failure of the immune response to Tropheryma whipplei , =7 ug/dL), hypokaliemia of 2.4 mmol/L,hypoalbuminemia (1.3 sugesting that such deficiency has a role in the occurence of mg/dL), a deficiency of folat acid (3.06 nmol/L)and an elevated this disease. erythrocyte sedimentation rate of 75 mm/h. In relation to the ima- ging studies an abdominal ultrasond showed a small amount of Gastrointestinal manifestations typically of a malabsorption free fluid in the abdominal cavity. Anti-HIV antibodies, antinuclear syndrome, occur in about 70% of the cases of Whipple´s antibodies, rheumatoid factor, serum cortisol and thyroid-stimula- disease.The weight loss is on average 11 kg (range : 3-36 ting hormone ( TSH) were investigated and showed to be negative kg) 9 and diarrhea is usually watery and occurs episodically or within the normal limit ranges. Stool search for parasites was with colic pain. A pure statorrhea is rather rare 10 . negative, and steatocrit was normal. The antibodies for celiac di- The most frequent extra-intestinal manifestations are joint sease were negative. The patient underwent a colonoscopy which was normal. An upper endoscopy showed a focal duodenal whitish disease and constituicional symptoms ,mainly weight loss, exsudad. Biopsies were performed and revealed many spongy ma- as verified in this patient and that is present in more than crophages in the lamina propria, with difuse and nodular distribu- 2/3 of cases in some series. The following systems may tion and positive citoplasmatic staining with periodic acid- Schiff also be affected in some way during the course of the di- (PAS) staining with negative Ziehl Neelson staining, compatible sease in order of frequency : central nervous system, car- with Whipple`s disease. In the absence of molecular biology test diovascular system, mucocutaneous system, pleuropulmo- to further confirm the diagnosis, it was began treatment with in- nary system and vison 11 . travenous ceftriaxone 2g/ day for two weeks, with normalization of the bowel habits and progressive improvement of the general Therefore the Whipple´s disease should be considered a condition of the patient. After discharge, the patient was continued differential diagnosis in many clinical situations: malabsorp- on sulfamethoxazol and trimethoprim for a year and suplements of tion with envolvement of the small intestine (celiac disease, folat acid and iron. The medication was discontinued after a year sarcoidosis and lymphoma), inflamatory rheumatic disease and the patient nowadays is asymptomatic, with normal albumin (seronegative arthritis), Addison´s disease, conjunctive tissue level, Hb level of 11.2 g/dL and weighing 65 kg (fig 2). disease and a variety of neurological disease. Discussion Because of its broad spectrum of clinical manifestations ad- ded to its low incidence in the general population makes the Whipple disease is a rare disorder that affects more men diagnosis difficult, usually leading to a late diagnosis. In this than women, generally middle aged 1. There is evidence that case the diagnosis was only estabilished in a progressive the Tropheryma whipplei may be ubitiquitous in humans, stage with a malabsorption syndrome and skin pigmentation since there are studies using PCR amplication of this or- which suggests a severe case of Whipple`s disease. Skin hyperpigmentation is present in about 40% of the patients, Fig. 2. Patient after a year of treatment for Whipple’s disease. it may occur as a consequence of vitamine D malabsorp- tion, which may induce compensatory secondary hyperpara- thyrodism leading to enhaced MSH and ACTH production 12 . In addition to this Tropheryma whipplei infection may induce hypothalamic disfunction and adrenal gland insufficiency 13 . Upper endoscopy with intestinal biopsy and PCR, if neces- sary, are the most effective method of investigation. Histolo- gically, there are infiltrates comprised by macrophages with granular cytoplasma, showing inclusions which stain positive with periodic acid- Schiff (PAS), and phagocytosed bacteria. The presence of macrophages with postive PAS material is not pathognomonic of the disease and can occur in cases of infection of Mycobacterium avium complex, Rhodococcus equi, Bacillus cereus, Corinebacterium and Histoplasma. The Ziehl –Neelsen staining is useful for differentiation of infec- tions caused by alcohol resistant acid bacilli. The PCR tecnique has a high sensivity but low specificity, therefore it is only indicated for people who have characte- ristic symptoms of Whipple´s disease. Whipple`s disease was invariably fatal before the advent of antibiotics 6. However the recommendations are not based on therapeutic trials or the susceptibility of Tropheryma whipplei to various antimicrobial agents, they favour antibiotics that are capable of crossing

| 90 | Galicia Clin 2018; 79 (3): 89-91 Galicia Clínica | Sociedade Galega de Medicina Interna two weeks ded by parenteral admnistration ceftriaxone (2 g daily during sulfamethoxazole twice a day during a yeara during day a twice sulfamethoxazole is oral administration of 160 mg trimethoprim and 800 mg of the antibiotic treatment. The mostly recommended treatment disease relapses and very frequently ned for 10 years because the risk of late recurrenc after diagnosis. commended treatment. re- the after life of quality her improving and improvement se, confirmed with endoscopy and biopsies with progressive compatible disea- had Whipple´s suggesting tests patient aditional and the symptoms report, case present the In xazole trimethoprim-sulfametho- as barrier,such –brain blood the at 6 and 12 months of treatment of months 12 and 6 at with the realization of upper endoscopy with duodenal biopsy prognosis should be carried out from monitoring the patients For some authors, the control of the disease progression and 6,10 . There is no consensus on the type and duration of 6,10 .

Therefore clinical follow-up should be maintai-

14 . Weknow that Whipple´s

may occur several years , usually prece- usually e is high 15 . 15. Thomas M, DidierR.15. Whipple´s diseaseseminaron. Lancet. 2003;361:239-46. Muller N,14. Schneider T, Zeitz M, Marth T. Whipple´s disease: new aspects in pathogen- disease. Whipple of manifestations Neurological H. Rousset A,DV, Gérard Durand 13. asympto- by masked hyperparathyroidism primary Severe M. Sheef AS, Alzahrani 12. Iqbal 11.T, Karovitch, Veinot J, Saginur R, Beauch Obst W,10. Ulrike A,P.Malfertheiner article.review disease- Whipple´s Viszeralmedizin. . aut , gt H ui S Rbr C She , rnor M e al. et M, Drancourt K, Suhre C, Robert S, Audic H, Ogata D, Raoult 1. Bibliography . air , epd H Rol D Fnla F Systemic F. Fenollar D, Raoult H, Leipidi J, Lagier 9. Med Acta diagnóstico. desafio Whipple: de Doença I.P, Barbosa Lima A, Carneiro 8. disease: Whipple´s tal. e H, VogelsangH, Riemer C, Stain D, Petermann C, Muller 7. Fenollar 6. Jackuliak P, Koller T, Baqi L, Plank 5.L, Lasabova Z, Minarik G, et al. Whipple´s disease- Freeman HJ. 4. Whipple´s classical of patogenesis the in cells T of role T.V,Schneider The Moos 3. M. Romano M, Zucchelli G, Stevenato D, Bucca C, Barbarino M, Almendolara 2. esis anddiagnosis. Acta Endoscopica. 2001;31: 243-53. Rev Neurol;158: 988-92. matic celiacdisease. Endoc Pract. 2008;14: 347-50. 2014; 30: 167-72. center. Medicine(Baltimore). 2010;89: 337-45. reference a in confirmed dor diagnose infections with patients 142 of presentation pericarditis: a rare disease with a rare presentati Port. 2004;17:742-8. consecutive cases. Gut. 1997;40: 425-7. four in reaction chain polymerase on based diagnosis with histology of comparison 2007; 356: 55-66. generalized stage. DigDisSci. 2008;53: 3250-8; disease. Expert Ver Anti Infect Ther. 2012;10: 253-255. erature review. G. Chir. 2013;34: 117-121. lit- and case rare a of presentation treatment: surgical infection disease Whipple´s Res whipplei . 2003; 13: 1800-9. Twist: a human pathogenic Actinobacteria with reduced genoma. Genome genoma. reduced with Actinobacteria pathogenic Twist: human a F, Puéchal Xavier, Raoult D. Whipple´s disease- review article. N Eng J Med. Tropheryma whipplei infection. World J Gastroenterol. 2009; 15:2078-80 esne L. Whipple´s disease with constritive Galicia Clin 2018;79(3):89-91 on. Can J Cardiol. 2009; 25:89-91. rpeya whippleiTropheryma Batista R, Tropheryma clinical : |

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