ARTHRALGIA, WEIGHT LOSS, ANEMIA, AND SUSPECTED PANNICULITIS: A PROLONGED DIAGNOSTIC JOURNEY TO WHIPPLE DISEASE

Abstract

Introduction. Whipple disease (WD) is an extremely rare systemic infectious disease caused by Tropheryma whipplei, with an estimated prevalence of approximately one case per million people. Due to its multisystem involvement and nonspecific clinical manifestations, WD can mimic a wide range of gastrointestinal, rheumatological, infectious, and other disorders, often resulting in substantial diagnostic delay. The aim of this report was to describe and analyze a case of classical WD with a prolonged diagnostic course and several atypical manifestations and to identify factors that may have contributed to the delayed diagnosis.

Materials and Methods. We present the clinical case of a 45-year-old woman with chronic diarrhea, arthralgia, progressive weight loss, anemia, systemic inflammation, lymphadenopathy, and clinically suspected panniculitis. The approximately 3.5-year clinical course was analyzed together with laboratory findings, computed tomography, upper and lower gastrointestinal endoscopy, and histological examination of duodenal biopsy specimens. Cardiac and neurological assessments, including echocardiography and brain magnetic resonance imaging, were performed to evaluate possible extraintestinal involvement.

Results. The initial manifestation was persistent non-bloody diarrhea, which was subsequently accompanied by fever, arthralgia, painful subcutaneous nodules, marked weight loss, and progressive iron-deficiency anemia. Computed tomography revealed retroperitoneal and mesenteric lymphadenopathy. Initial upper gastrointestinal endoscopy, performed without duodenal biopsy, did not establish the diagnosis. Repeat esophagogastroduodenoscopy revealed duodenal mucosal edema, granularity and hyperemia, thickening of the mucosal folds, and marked villous alterations. Histological examination of duodenal biopsy specimens demonstrated focal aggregates of macrophages with abundant eosinophilic cytoplasm containing PAS-positive granules. In combination with the characteristic clinical presentation, these findings supported the diagnosis of classical WD. Cardiac and central nervous system involvement was not detected. Panniculitis was clinically suspected but was not confirmed by histological or other specific investigations. Treatment was initiated with intravenous ceftriaxone for 14 days, followed by oral doxycycline and hydroxychloroquine. After four weeks of therapy, the patient reported substantial symptomatic improvement.

Discussion. The approximately 3.5-year diagnostic delay was likely related to the extreme rarity of WD, the nonspecific and multisystem nature of its manifestations, the patient’s female sex, which is less typical of classical WD, previous courses of antimicrobial therapy associated with partial and temporary improvement, and the absence of duodenal biopsy during the initial endoscopic examination. This case demonstrates that the absence of characteristic macroscopic duodenal abnormalities on endoscopy does not exclude WD. The combination of persistent diarrhea, arthralgia, weight loss, manifestations suggestive of malabsorption, anemia, and lymphadenopathy should increase clinical suspicion of the disease.

Conclusions. Whipple disease should be considered in the differential diagnosis of patients with prolonged, unexplained gastrointestinal and systemic manifestations, particularly when diarrhea, arthralgia, weight loss, malabsorption, anemia, and lymphadenopathy occur in combination. Duodenal biopsy remains a cornerstone of diagnosis and should be considered even when the endoscopic appearance of the duodenal mucosa is normal or nonspecific.