Whipple Hastalığı
Özet
Whipple Hastalığı (WH), Tropheryma whipplei adlı bakterinin neden olduğu, özellikle 40-60 yaş arası erkekleri etkileyen, tedavi edilmediğinde ölümcül olabilen nadir ve multisistemik bir enfeksiyondur. Hastalık patogenezinde konakçıya özgü immün yetmezliklerin ve genetik yatkınlığın rol oynadığı düşünülmektedir. Genellikle gastrointestinal malabsorpsiyon semptomları (kronik ishal, kilo kaybı) ortaya çıkmadan yıllar önce gezici poliartralji, ateş ve halsizlik gibi spesifik olmayan bulgularla başlar. Tanıda ince bağırsak biyopsisinde PAS-pozitif makrofajların gösterilmesi, PCR testleri ve immünohistokimyasal boyamalar temel alınır. Standart tedavi, seftriakson veya meropenem ile intravenöz indüksiyonun ardından bir yıllık ko-trimoksazol idamesini ya da alternatif olarak doksisiklin ve hidroksiklorokin kombinasyonunu içerir. Tedavinin ilk aylarında gelişebilen İmmün Yeniden Yapılanma İnflamatuar Sendromu (IRIS) ise kortikosteroidlerle yönetilmesi gereken ciddi bir komplikasyondur.
Whipple Disease (WD) is a rare, chronic, and potentially fatal multisystemic infectious disorder caused by the bacterium Tropheryma whipplei, primarily affecting middle-aged men. The pathogenesis is linked to host-specific immune deficiencies and genetic susceptibility rather than bacterial virulence. Patients often suffer from non-specific prodromal symptoms like migratory polyarthralgia and fever for years before classic malabsorption signs, such as chronic diarrhea and weight loss, manifest. Diagnosis relies on detecting PAS-positive macrophages in small bowel biopsies, PCR genetic analysis, and immunohistochemical staining. Standard antimicrobial regimens involve intravenous induction with ceftriaxone or meropenem followed by a one-year oral maintenance of trimethoprim/sulfamethoxazole, or a long-term combination of doxycycline and hydroxychloroquine. Immune Reconstitution Inflammatory Syndrome (IRIS) is a severe complication that can arise during the early months of therapy, often requiring corticosteroid management.
Referanslar
Dolmans RA, Boel CE, Lacle MM, Kusters JGJCmr. Clinical manifestations, treatment, and diagnosis of Tropheryma whipplei infections. 2017;30(2):529-55.
Moos V, Schmidt C, Geelhaar A, Kunkel D, Allers K, Schinnerling K, et al. Impaired immune functions of monocytes and macrophages in Whipple's disease. 2010;138(1):210-20.
Whipple GHJBJHH. A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. 1907;18:382-91.
JH Y, TR HJBotJHH. Combined electron and light microscopy in Whipple's disease. Demonstration of" bacillary bodies" in the intestine. 1961;109:80-98.
Wilson K, Frothingham R, Wilson J, Blitchington RJTL. Phylogeny of the Whipple's-disease-associated bacterium. 1991;338(8765):474-5.
Raoult D, Birg ML, Scola BL, Fournier PE, Enea M, Lepidi H, et al. Cultivation of the bacillus of Whipple's disease. 2000;342(9):620-5.
Schöniger-Hekele M, Petermann D, Weber B, Müller CJA, microbiology e. Tropheryma whipplei in the environment: survey of sewage plant influxes and sewage plant workers. 2007;73(6):2033-5.
Ehrbar H-U, Bauerfeind P, Dutly F, Koelz H-R, Altwegg MJTL. PCR-positive tests for Tropheryma whippelii in patients without Whipple's disease. 1999;353(9171):2214.
Street S, Donoghue HD, Neild GJTL. Tropheryma whippelii DNA in saliva of healthy people. 1999;354(9185):1178-9.
Maibach RC, Dutly F, Altwegg MJJoCM. Detection of Tropheryma whipplei DNA in feces by PCR using a target capture method. 2002;40(7):2466-71.
Marth T, Roux M, von Herbay A, Meuer SC, Feurle GEJCi, immunopathology. Persistent reduction of complement receptor 3 α-chain expressing mononuclear blood cells and transient inhibitory serum factors in Whipple's disease. 1994;72(2):217-26.
Marth T, Neurath M, Cuccherini BA, Strober WJG. Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease. 1997;113(2):442-8.
Marth T, Kleen N, Stallmach A, Ring S, Aziz S, Schmidt C, et al. Dysregulated peripheral and mucosal Th1/Th2 response in Whipple's disease. 2002;123(5):1468-77.
Schneider T, Stallmach A, von Herbay A, Marth T, Strober W, Zeitz MJAoIM. Treatment of refractory Whipple disease with interferon-γ. 1998;129(11_Part_1):875-7.
Ectors NL, Geboes KJ, de Vos RM, Heidbuchel HP, Rutgeerts PJ, Desmet VJ, et al. Whipple's disease: a histological, immunocytochemical, and electron microscopic study of the small intestinal epithelium. 1994;172(1):73-9.
Bai J, Sen L, Diez R, Niveloni S, Maurino E, Estévez ME, et al. Impaired monocyte function in patients successfully treated for Whipple's disease. 1996;26(2):85-9.
Schinnerling K, Geelhaar-Karsch A, Allers K, Friebel J, Conrad K, Loddenkemper C, et al. Role of dendritic cells in the pathogenesis of Whipple's disease. 2015;83(2):482-91.
Desnues B, Lepidi H, Raoult D, Mege JLJJoID. Whipple disease: intestinal infiltrating cells exhibit a transcriptional pattern of M2/alternatively activated macrophages. 2005;192(9):1642-6.
Desnues B, Ihrig M, Raoult D, Mege J-LJC, Immunology V. Whipple's disease: a macrophage disease. 2006;13(2):170-8.
Desnues B, Raoult D, Mege J-LJTJoI. IL-16 is critical for Tropheryma whipplei replication in Whipple’s disease. 2005;175(7):4575-82.
Moos V, Kunkel D, Marth T, Feurle GE, LaScola B, Ignatius R, et al. Reduced peripheral and mucosal Tropheryma whipplei-specific Th1 response in patients with Whipple’s disease. 2006;177(3):2015-22.
Martinetti M, Biagi F, Badulli C, Feurle GE, Müller C, Moos V, et al. The HLA alleles DRB1* 13 and DQB1* 06 are associated to Whipple's disease. 2009;136(7):2289-94.
Lagier J-C, Lepidi H, Raoult D, Fenollar FJM. Systemic Tropheryma whipplei: clinical presentation of 142 patients with infections diagnosed or confirmed in a reference center. 2010;89(5):337-45.
Marth T, Raoult DJTL. Whipple's disease. 2003;361(9353):239-46.
Marín M, Muñoz P, Sánchez M, del Rosal M, Rodríguez-Créixems M, Bouza EJJocm. Tropheryma whipplei infective endocarditis as the only manifestation of Whipple's disease. 2007;45(6):2078-81.
Brouqui P, Raoult DJCmr. Endocarditis due to rare and fastidious bacteria. 2001;14(1):177-207.
Lepidi H, Fenollar F, Dumler JS, Gauduchon V, Chalabreysse L, Bammert A, et al. Cardiac valves in patients with Whipple endocarditis: microbiological, molecular, quantitative histologic, and immunohistochemical studies of 5 patients. 2004;190(5):935-45.
He YT, Peterson K, Crothers J, Dejace J, Hale AJJI. Endocarditis and systemic embolization from Whipple’s disease. 2021;24:e01105.
Rickman LS, Freeman WR, Green WR, Feldman ST, Sullivan J, Russack V, et al. Uveitis caused by Tropheryma whippelii (Whipple's bacillus). 1995;332(6):363-6.
Razonable R, Pulido J, Deziel P, Dev S, Salomão D, Walker RJTID. Chorioretinitis and vitreitis due to Tropheryma whipplei after transplantation: case report and review. 2008;10(6):413-8.
Damaraju D, Steiner T, Wade J, Gin K, FitzGerald JMJNEJoM. A Surprising Cause of Chronic Cough. 2015;373(6):561-6.
Zhang WM, Xu LJOM. Pulmonary parenchymal involvement caused by Tropheryma whipplei. 2021;16(1):843-6.
Riemer H, Hainz R, Stain C, Dekan G, Feldner-Busztin M, Schenk P, et al. Severe pulmonary hypertension reversed by antibiotics in a patient with Whipple's disease. 1997;52(11):1014-5.
Wang L, Su P, Song L, Sai LJEid. Subcutaneous Nodules Caused by Tropheryma whipplei Infection. 2022;28(3):761-3.
Sanchez A, Del Giudice P, Mantion C, Mazellier S, Boukari F, Roger P, et al. Erythematous skin nodules during treatment of Whipple's disease. 2021;51(4):397-9.
Cremniter J, Bauer T, Lortat-Jacob A, Vodovar D, Le Parc J-M, Emile J-F, et al. Prosthetic hip infection caused by Tropheryma whipplei. 2008;46(4):1556-7.
Gérard A, Rousset HJRN. Neurological manifestations of Whipple disease. 2002;158(10 Pt 1):988-92.
Panegyres P, Edis R, Beaman M, Fallon MJJotAoP. Primary Whipple's disease of the brain: characterization of the clinical syndrome and molecular diagnosis. 2006;99(9):609-23.
Bally JF, Méneret A, Roze E, Anderson M, Grabli D, Lang AEJMD. Systematic review of movement disorders and oculomotor abnormalities in Whipple's disease. 2018;33(11):1700-11.
de Oliveira Santana MA, Butt S, Nassiri MJC. Central Nervous System Whipple Disease Presenting as Hypersomnolence. 2022;14(3).
Günther U, Moos V, Offenmüller G, Oelkers G, Heise W, Moter A, et al. Gastrointestinal diagnosis of classical Whipple disease: clinical, endoscopic, and histopathologic features in 191 patients. 2015;94(15).
Rijke AM, Falke T, de Vries RJJocat. Computed tomography in Whipple disease. 1983;7(6):1101-2.
Santos JG, Costa P, Galzerano A, Matos C, Lourenço JJRCR. Challenging case of Whipple's disease: The contribution of radiology. 2022;17(3):1008-12.
Louis E, Lynch T, Kaufmann P, Fahn S, Odel JJAoNOJotANA, Society tCN. Diagnostic guidelines in central nervous system Whipple's disease. 1996;40(4):561-8.
Dobbins III WOJNEJoM. The diagnosis of Whipple's disease. Mass Medical Soc; 1995. p. 390-2.
Mönkemüller K, Fry LC, Von Arnim U, Neumann H, Evert M, Malfertheiner PJD. Whipple’s disease: an endoscopic and histologic study. 2008;77(3-4):161-5.
Moter A, Schmiedel D, Petrich A, Wiessner A, Kikhney J, Schneider T, et al. Validation of an rpoB gene PCR assay for detection of Tropheryma whipplei: 10 years' experience in a National Reference Laboratory. 2013;51(11):3858-61.
Lowsky R, Archer GL, Fyles G, Minden M, Curtis J, Messner H, et al. Diagnosis of Whipple's disease by molecular analysis of peripheral blood. 1994;331(20):1343-6.
Fenollar F, Amphoux B, Raoult DJCid. A paradoxical Tropheryma whipplei western blot differentiates patients with whipple disease from asymptomatic carriers. 2009;49(5):717-23.
von Herbay A, Ditton HJ, Schuhmacher F, Maiwald MJG. Whipple's disease: staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid. 1997;113(2):434-41.
Masselot F, Boulos A, Maurin M, Rolain J, Raoult DJAa, chemotherapy. Molecular evaluation of antibiotic susceptibility: Tropheryma whipplei paradigm. 2003;47(5):1658-64.
Boulos A, Rolain J-M, Raoult DJAa, chemotherapy. Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells. 2004;48(3):747-52.
Feurle GE, Junga NS, Marth TJG. Efficacy of ceftriaxone or meropenem as initial therapies in Whipple's disease. 2010;138(2):478-86.
Feurle GE, Moos V, Bläker H, Loddenkemper C, Moter A, Stroux A, et al. Intravenous ceftriaxone, followed by 12 or three months of oral treatment with trimethoprim-sulfamethoxazole in Whipple's disease. 2013;66(3):263-70.
Bakkali N, Fenollar F, Biswas S, Rolain J-M, Raoult DJTJoid. Acquired resistance to trimethoprim-sulfamethoxazole during Whipple disease and expression of the causative target gene. 2008;198(1):101-8.
Fenollar F, Rolain J-M, Alric L, Papo T, Chauveheid M-P, Van de Beek D, et al. Resistance to trimethoprim/sulfamethoxazole and Tropheryma whipplei. 2009;34(3):255-9.
Lagier J-C, Fenollar F, Lepidi H, Giorgi R, Million M, Raoult DJJoAC. Treatment of classic Whipple's disease: from in vitro results to clinical outcome. 2014;69(1):219-27.
Foteinogiannopoulou K, Mouzas I, Tzardi M, Orfanoudaki E, Theodoraki E, Kofteridis DJG. First case of Whipple’s disease successfully treated with tigecycline. 2021;11(1):105.
Durand DV, Lecomte C, Cathébras P, Rousset H, Godeau PJM. Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Societe Nationale Francaise de Medecine Interne. 1997;76(3):170-84.
Feurle GE, Moos V, Schinnerling K, Geelhaar A, Allers K, Biagi F, et al. The immune reconstitution inflammatory syndrome in whipple disease: a cohort study. 2010;153(11):710-7.
