DOI: 10.12890/2026_007539
Tropheryma whipplei infection mimicking sarcoidosis with an atypical course: a molecularly confirmed diagnosis without PAS-positive intestinal disease
Authors
lucka.bohinikova@gmail.com
Keywords
Whipple’s disease, Tropheryma whipplei, sarcoidosis, fever of unknown origin, granulomaAbstract
Introduction: The bacterium Tropheryma whipplei causes Whipple’s disease, a rare chronic infection that can involve virtually any organ, especially in the late phase, and mimic inflammatory or neoplastic conditions. The interval from first symptoms to diagnosis is typically several years.
Case description: A 68-year-old man was referred for pulmonary re-evaluation 2 years after a non-caseating hilar lymph-node granuloma had led to a diagnosis of stage I (nodal) sarcoidosis. His records revealed a 3-year history of lymphadenopathy with persistently elevated C-reactive protein and a two-year history of recurrent fever and fatigue. Corticosteroid therapy for ankle synovitis caused symptomatic worsening, prompting further investigation. Extensive infectious, oncological, rheumatological and tropical-medicine workup was unrevealing. Detailed history-taking revealed a 6 kg weight loss and epigastric discomfort, and a prior short antibiotic course for incipient pneumonia had produced transient improvement, making an atypical infectious aetiology, specifically Whipple’s disease, plausible. An endobronchial ultrasound–guided lymph-node aspirate and subsequently a stool sample were both positive for T. whipplei by quantitative polymerase chain reaction (qPCR), whereas cerebrospinal fluid PCR was negative, establishing systemic disease without central nervous system involvement. Oral doxycycline plus hydroxychloroquine produced fast and sustained clinical and biochemical remission at 1 year. Surveillance duodenal histology was periodic acid–Schiff -negative and structured clinical follow-up was arranged.
Conclusion: Whipple’s disease is a great mimicker, but a treatable one, and should be considered in cases of chronic inflammation without evidence of a pathogen in primary microbiological analysis and in cases of sarcoidosis with an atypical course, particularly if symptoms do not improve or worsen while on corticosteroids.
References
- Boumaza A, Ben Azzouz E, Arrindell J, Lepidi H, Mezouar S, Desnues B. Whipple’s disease and Tropheryma whipplei infections: from bench to bedside. Lancet Infect Dis. 2022;22(10):e280-e291. doi: 10.1016/S1473-3099(22)00128-1.
- Dolmans RA, Boel CH, Lacle MM, Kusters JG. Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections. Clin Microbiol Rev. 2017;30(2):529-555. doi: 10.1128/CMR.00033-16.
- Lagier JC, Lepidi H, Raoult D, Fenollar F. Systemic Tropheryma whipplei: clinical presentation of 142 patients with infections diagnosed or confirmed in a reference center. Medicine (Baltimore). 2010;89(5):337-345. doi: 10.1097/MD.0b013e3181f204a8.
- Fenollar F, Puéchal X, Raoult D. Whipple’s disease. N Engl J Med. 2007;356(1):55-66. doi: 10.1056/NEJMra062477.
- Moos V, Krüger J, Allers K, Moter A, Kikhney J, Kühl AA, et al. Oral treatment of Whipple’s disease with doxycycline and hydroxychloroquine versus intravenous therapy with ceftriaxone followed by oral trimethoprim-sulfamethoxazole in Germany: a phase 2/3, prospective, open-label, randomised, controlled, non-inferiority trial. Lancet Infect Dis. 2025;25(7):788-800. doi: 10.1016/S1473-3099(24)00797-7.
- Roy-Chowdhuri S, Dacic S, Ghofrani M, Illei PB, Layfield LJ, Lee C, et al. Collection and Handling of Thoracic Small Biopsy and Cytology Specimens for Ancillary Studies: Guideline From the College of American Pathologists in Collaboration With the American College of Chest Physicians, Association for Molecular Pathology, American Society of Cytopathology, American Thoracic Society, Pulmonary Pathology Society, Papanicolaou Society of Cytopathology, Society of Interventional Radiology, and Society of Thoracic Radiology. Arch Pathol Lab Med. 2020. doi: 10.5858/arpa.2020-0119-CP.
- Feurle GE, Junga NS, Marth T. Efficacy of ceftriaxone or meropenem as initial therapies in Whipple’s disease. Gastroenterology. 2010;138(2):478-86; quiz 11-2. doi: 10.1053/j.gastro.2009.10.041.
- Bakkali N, Fenollar F, Biswas S, Rolain JM, Raoult D. Acquired resistance to trimethoprim-sulfamethoxazole during Whipple disease and expression of the causative target gene. J Infect Dis. 2008;198(1):101-8. doi: 10.1086/588706.
- Boulos A, Rolain JM, Mallet MN, Raoult D. Molecular evaluation of antibiotic susceptibility of Tropheryma whipplei in axenic medium. J Antimicrob Chemother. 2005;55(2):178-81. doi: 10.1093/jac/dkh524.
- Lagier JC, Fenollar F, Lepidi H, Giorgi R, Million M, Raoult D. Treatment of classic Whipple’s disease: from in vitro results to clinical outcome. J Antimicrob Chemother. 2014;69:219–227. doi: 10.1093/jac/dkt310.
