title: PCR analysis is superior to histology for diagnosis of Whipple's disease mimicking seronegative rheumatic diseases.
abstract: OBJECTIVE
  The diagnosis of Whipple's disease (WD) is commonly confirmed by histology demonstrating Periodic Acid Schiff (PAS)-positive macrophages in the duodenal mucosa. Analysis of intestinal tissue or other specimens using polymerase chain reaction (PCR) is a more sensitive method. However, the relevance of positive PCR findings is still controversial. Therefore, we evaluated the relevance of histology and PCR findings to establishing the diagnosis of WD in a series of WD patients initially presenting with suspected rheumatic diseases.
  
  
  METHODS
  Between 2006 and 2014, 20 patients with seronegative rheumatic diseases tested positive for Tropheryma whipplei (Tw) by PCR and/or histology and were enrolled in a retrospective analysis of the diagnostic value of both procedures.
  
  
  RESULTS
  Seven of the 20 cases (35%) were diagnosed with 'classic' WD as indicated by PAS-positive macrophages. In the remaining 13 patients, the presence of Tw was detected by intestinal (n = 10) or synovial PCR analysis (n = 3). Two of the 20 patients (10%) with evidence of Tw did not respond to antibiotic therapy. They were not considered to suffer from WD. Therefore, relying only on histological findings of intestinal biopsies would have missed 11 (61%) of the 18 patients with WD in our cohort. In comparison, PCR of intestinal biopsies detected Tw-DNA in 14 (93%) of the 15 WD patients evaluated. Patients with a positive histology did not differ from PCR-positive patients with regard to sex, age, or duration of disease, but more often presented with gastrointestinal symptoms.
  
  
  CONCLUSIONS
  A substantial number of WD patients present without typical intestinal histology findings. Additional PCR analysis of intestinal tissue or synovial fluid increased the sensitivity of the diagnostic evaluation and should be considered particularly in patients presenting with atypical seronegative rheumatic diseases and a high-risk profile for WD.
authors.affiliation: a Department of Rheumatology and Clinical Immunology , Asklepios Medical Centre , Bad Abbach , Germany.
authors.forename: P
authors.initials: P
authors.lastname: Lehmann
authors.affiliation: a Department of Rheumatology and Clinical Immunology , Asklepios Medical Centre , Bad Abbach , Germany.
authors.forename: B
authors.initials: B
authors.lastname: Ehrenstein
authors.affiliation: a Department of Rheumatology and Clinical Immunology , Asklepios Medical Centre , Bad Abbach , Germany.
authors.forename: W
authors.initials: W
authors.lastname: Hartung
authors.affiliation: a Department of Rheumatology and Clinical Immunology , Asklepios Medical Centre , Bad Abbach , Germany.
authors.forename: C
authors.initials: C
authors.lastname: Dragonas
authors.affiliation: b Institute of Clinical Microbiology and Hygiene, University Medical Centre Regensburg , Regensburg , Germany.
authors.forename: U
authors.initials: U
authors.lastname: Reischl
authors.affiliation: a Department of Rheumatology and Clinical Immunology , Asklepios Medical Centre , Bad Abbach , Germany.|c Department of Internal Medicine I , University Medical Centre Regensburg , Regensburg , Germany.
authors.forename: M
authors.initials: M
authors.lastname: Fleck
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D012189:Retrospective Studies; D012216:Rheumatic Diseases / Q000175:diagnosis*; D008061:Whipple Disease / Q000175:diagnosis* / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents