Indian Journal of Pathology and Microbiology
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Year : 2015  |  Volume : 58  |  Issue : 3  |  Page : 398-399
Atypical presentation of Whipple disease with no diarrhea

1 Department of Pathology, University of California at San Diego, San Diego, California, USA
2 Department of Pathology, University of California at San Diego, San Diego, California; Department of VA San Diego Healthcare System, San Diego, California, USA

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Date of Web Publication14-Aug-2015

How to cite this article:
Perez-Alvarez I, Yekezare S, Zhao X F, Xu X. Atypical presentation of Whipple disease with no diarrhea. Indian J Pathol Microbiol 2015;58:398-9

How to cite this URL:
Perez-Alvarez I, Yekezare S, Zhao X F, Xu X. Atypical presentation of Whipple disease with no diarrhea. Indian J Pathol Microbiol [serial online] 2015 [cited 2022 Jan 22];58:398-9. Available from: https://www.ijpmonline.org/text.asp?2015/58/3/398/162930

The present case is that of a 47-year-old Caucasian man who presented with fevers, decreased appetite, weakness, and abdominal pain for 1 month and 10 pound weight loss. There was no significant history of diarrhea. Further review of the charts identified a prior history of multi-joint disease for 3 years. Laboratory tests revealed iron deficiency anemia. Other abnormal laboratory findings included hypoalbuminemia (2.3 g/dL), elevated C-reactive protein (4.63 mg/dL), and elevated erythrocyte sedimentation rate (47 mm/h). Computed tomography of the abdomen showed mesenteric and retroperitoneal lymphadenopathy. Multiple laboratory tests for infectious etiologies, including HIV, Epstein-Barr virus, cytomegalovirus, hepatitis viruses, and tuberculosis, were all negative. An upper gastrointestinal endoscopy revealed prominent villi in the first and second parts of the duodenum. Biopsies from the duodenum and an enlarged axillary lymph node were submitted for histologic examination.

The duodenal biopsy revealed club-shaped, blunted small intestinal villi with dilated lacteals, and packed with foamy histiocytes [Figure 1]a and b. Periodic acid-Schiff (PAS) stain revealed numerous magenta-colored, rod-shaped organisms within the histiocytes [Figure 1]c. Acid-fast bacillus stain was negative [Figure 1]d. The findings were consistent with Tropheryma whipplei infection.
Figure 1: The morphologic features of the duodenal biopsy. (a) Low magnification shows blunted villi with lipid droplets. (b) There are many foamy histiocytes within the lamina propria. (c) Periodic acid-Schiff stain shows numerous magenta-colored microorganisms. (d) Acid-fast stain is negative

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Sections of the lymph node revealed preserved nodal architecture with sinusoidal expansion, containing many histiocytes [Figure 2]a and b. PAS stain highlighted the same microorganisms within the histiocytes as those in the duodenal biopsy [Figure 2]c and d.
Figure 2: Lymph node morphology (a) Low magnification shows dilated sinusoids (b) The sinusoids contain many histiocytes with granular eosinophilic cytoplasm (c and d) Periodic acid-Schiff stain highlights Tropheryma whipplei organisms

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The differential diagnoses include Whipple disease (WD) and other infectious diseases. A portion of the lymph node specimen was sent for T. whipplei ribosomal RNA test by polymerase chain reaction (PCR), which confirmed the diagnosis of WD.

Whipple disease is a rare, potentially lethal, infectious disease involving multiple organs. The culprit is a Gram-positive bacillus, T. Whipplei. Since the first case reported by Dr. George Hoyt Whipple in 1907, there are approximately 1000 cases reported in the literature. [1] Majority of the patients are middle-aged Caucasian men with a history of exposure to soil and animals. Typically, WD starts with the prodromal stage of arthralgia and arthritis (73-85% of total cases). [1],[2] Often years later, the disease progresses to the steady stage and shows some typical symptoms include diarrhea (75-81% cases), abdominal pain (60% cases), weight loss (90-93% cases), and lymphadenopathy (45-52% cases). [1],[2] It is important to be aware that WD may have atypical presentations. Our patient had an atypical non-diarrheic presentation, and the correct diagnosis was 3 years later than the onset of arthropathy.

Even with the major scientific discoveries of T. whipplei in the past several decades, including cultivation methods, the genome, and new diagnostic methods, [1] timely diagnosis of WD is still a challenge due to its rarity and nonspecific clinical presentations. The initial workup of WD includes identification of PAS-positive organisms in tissue biopsies. It is important to be aware that PAS positivity is not specific for T. whipplei, and could also be seen in, for example, mycobacterial infection. Acid-fast stain is negative in WD and is useful to exclude mycobacteria. Lymph nodes, especially of the mesenteric region, are involved in approximately half of WD cases. There are two common histologic patterns of involved lymph nodes: "lipodystrophy" with ill-defined noncaseating lipogranulomas and "sinusoid histiocytosis." The lymph node of our case demonstrated the second pattern.

The best confirmatory test of WD is PCR amplifying the 16S ribosomal RNA of the organism, which can be done on either fresh tissue or formalin fixed paraffin embedded tissue. Alternative confirmatory tests of WD include immunohistochemistry, [3] electron microscopy, [4] and culture. [3] Immunohistochemistry has great sensitivity and specificity and can detect the organisms in tissues, body fluids, and infected monocytes. Electron microscopy reveals the trilaminar wall as a distinctive feature of T. whipplei. However, electron microscopy is used less frequently and has gradually lost its popularity to aforementioned new methods. Culture of T. whipplei can be performed only in a specialized laboratory and has very limited accessibility.

WD is universally lethal before the advent of antibiotics. The current recommended therapy initiate with streptomycin induction, plus either ceftriaxone or penicillin G for 2 weeks. Maintenance therapy use antibiotics crossing the blood-brain barrier (such as trimethoprim-sulfamethoxazole) for 1-2 years. [5] Our patient was started on Ceftriaxone 2 g daily and had prompt responses of increased appetite and weight gain within 2 weeks. Long-term follow-up is needed to ensure bacterial eradication.

   References Top

Fenollar F, Puéchal X, Raoult D. Whipple's disease. N Engl J Med 2007;356:55-66.  Back to cited text no. 1
Marth T. New insights into Whipple's disease - A rare intestinal inflammatory disorder. Dig Dis 2009;27:494-501.  Back to cited text no. 2
Raoult D, Birg ML, La Scola B, Fournier PE, Enea M, Lepidi H, et al. Cultivation of the bacillus of Whipple's disease. N Engl J Med 2000;342:620-5.  Back to cited text no. 3
Chears WC Jr, Ashworth CT. Electron microscopic study of the intestinal mucosa in Whipple's disease. Demonstration of encapsulated bacilliform bodies in the lesion. Gastroenterology 1961;41:129-38.  Back to cited text no. 4
Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D. Whipple's disease: New aspects of pathogenesis and treatment. Lancet Infect Dis 2008;8:179-90.  Back to cited text no. 5

Correspondence Address:
Dr. Xiangdong Xu
VA San Diego Healthcare System, 3350 La Jolla Village Drive, 113, San Diego, CA 92161
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.162930

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