Whipple's Disease: Our Own Experience and Review of the Literature

Abstract

Whipple's disease is a chronic infectious systemic disease caused by the bacterium Tropheryma whipplei. Nondeforming arthritis is frequently an initial complaint. Gastrointestinal and general symptoms include marked diarrhoea (with serious malabsorption), abdominal pain, prominent weight loss, and low-grade fever. Possible neurologic symptoms (up to 20%) might be associated with worse prognosis. Diagnosis is based on the clinical picture and small intestinal histology revealing foamy macrophages containing periodic-acid-Schiff- (PAS-) positive material. Long-term (up to one year) antibiotic therapy provides a favourable outcome in the vast majority of cases. This paper provides review of the literature and an analysis of our 5 patients recorded within a 20-year period at a tertiary gastroenterology centre. Patients were treated using i.v. penicillin G or amoxicillin-clavulanic acid + i.v. gentamicin for two weeks, followed by p.o. doxycycline (100 mg per day) plus p.o. salazopyrine (3 g per day) for 1 year. Full remission was achieved in all our patients.

Figure 1

Whipple's disease: severe involvement of the distal duodenum (D4). Folds are low, and mucosa is swollen and grey-yellowish with multiple reddish spots (small mucosal haemorrhages).

Figure 2

Whipple's disease: jejunal mucosa is swollen and grey-pink with small whitish areas and multiple tiny mucosal haemorrhages.

Figure 3

Whipple's disease: endoscopic view of the proximal jejunum. Characteristic whitish areas protrude a little the above surrounding relief.

Figure 4

Whipple's disease: detailed view on whitish plaques on the top of fold.

Figure 5

Whipple's disease: picture of the jejunum. Characteristic whitish areas protrude the above surrounding relief.

Figure 6

Whipple's disease: endoscopic view of the proximal jejunum. Transverse folds are low, reduced, and swollen.

Figure 7

Whipple's disease: irregular rugged surface of the jejunal mucosa with an appearance like being dusted with flour.

Figure 8

Whipple's disease: jejunal mucosa is grey-pink with small whitish areas.

Figure 9

Whipple's disease: no folds are seen in the jejunum. Surface of mucosa is irregular; there are several tiny haemorrhages in mucosa with an appearance like being dusted with flour.

Figure 10

Whipple's disease: control enteroscopy after two-month treatment (with doxycycline and salazopyrine). Picture of the distal duodenum. Folds are still lower with chaotic disarrangement but macroscopically picture of mucosa has significantly improved.

Figure 11

Whipple's disease: control enteroscopy after two-month treatment. Detail view of the jejunal mucosa. Mucosa is still swollen with tiny granular pattern.

Figure 12

Whipple's disease: control enteroscopy after one-year treatment. Morphology of jejunal folds has normalised, surface is still rough, mucosa has fine granular pattern, and small areas of grey-yellowish colour still persist.

Figure 13

Whipple's disease: obvious enlargement of the villi filled by foamy macrophages. Hematoxylin-eosin staining. Courtesy of Jan Nožička, MD, PhD. Reproduced with permission from Bureš and Rejchrt [42].

Figure 14

Whipple's disease: intensely PAS-positive macrophages occupying the lamina propria mucosae. Goblet cells are positively stained, too. Brush border of enterocytes is also marked (as a deep purple line). PAS staining. Courtesy of Jan Nožička, MD, PhD. Reproduced with permission from Bureš and Rejchrt [42].

Figure 15

Whipple's disease: detailed view of macrophages in the lamina propria mucosae. Hematoxylin-eosin staining. Courtesy of Jan Nožička, MD, PhD. Reproduced with permission from Bureš and Rejchrt [42].

Figure 16

Accumulation of large lipid droplets (asterisk) in the lamina propria of intestinal villi. Semi-thin resin section, scale = 0.1 mm. Courtesy of Ladislav Kubeš, MD, PhD. Reproduced with permission from Bureš and Rejchrt [42].

Figure 17

Groups of microbes (arrow) and characteristic lysosomes (asterisk) present in an intestinal histiocyte in Whipple's disease. Electron micrograph, scale = 2 μm. Courtesy of Professor Josef Špaček, MD, DSc. Reproduced with permission from Bureš and Rejchrt [42].

Figure 18

Whipple's disease: partial disappearance of PAS positive macrophages from the lamina propria mucosae following the therapy. PAS staining. Courtesy of Jan Nožička, MD, PhD. Reproduced with permission from Bureš and Rejchrt [42].