Whipple's disease

 

Whipple's disease:

Whipple's disease is a bacterial infection of jejunum manifest as malabsorption of fat, fat soluble vitamins and protein.

Dr. George Whipple, in 1907, described the first case in a 36 yr old man presented with malabsorption associated with lymph nodes enlargement of the mesentery and increased skin pigmentation. He found a small rod-shaped organism in the tissue stained by silver stain but could nor grow it in any artificial media to make a positive identification but predicted the possibility of a bacterial infection. In 1992 a gram positive coccobacillus was identified in the biopsy tissue by electron microscopy. The bacteria were PAS (periodic acid-Schiff stain) positive and Acid-fast stain negative, The organism is named- Tropheryma whipplei (T. whipplei). T. whipplei belongs to Actinomycetes group and its pathology has many similarities with Mycobacterium avium intercellari infection.

The natural habitat of T. whipplei is in the soil, and farmers are three times more likely to develop clinical signs of infection over people in other professions. 51% of world population are positive for T. whipplei antibodies, however, only 3 in 1 million develop clinical signs of illness. This is due to cellular immune deficiency contributes to the development of illness. Farmers who are haplotype for HLA B27, having phagocytes which fail to digest engulfed bacteria because of lack of activation of CD 11b (integrin alpha) by TH1 lymphocytes.

Mode of infection and incubation period.

The mode of infection and the incubation period are not known preciously, but oral route is most likely. These bacteria have a three layered outer membrane and that helps them to withstand digestion by the strong Hydrochloric acid (HCl) in the stomach. Once T. whipplei are in the duodenum and Jejunum, they infect the surface cells of the villi. The cellular infiltration follows, and it produces edema of the villi and this is the beginning of abdominal symptoms of bloating, cramps and diarrhea. The macrophages engulf the T. whipplei but unable to kill and the bacteria. Macrophages move to lymph follicles in the lamina propria. Nodularity of lymph follicles develop in lamina propria and also in the mesentery. These two features – edema of villi and enlarged lymph follicles - are characteristics of Whipple's disease.

The second most frequent clinical feature is a reactive type of arthritis of the finger joints and metacarpal phalangeal joints resembling Rheumatoid arthritis but Rh factor is negative and erosion of bones does not develop. Similar symptoms is also occur in the sacroiliac joints, ankles and knees but less frequently. Other feature are anemia, low grade fever, lymph node enlargement, increased skin pigmentation. Occasionally cerebellar ataxia, peripheral neuropathy, headaches, oculomotor palsy and seizures may be present. These, non-GI symptoms are due to increased production of acute-phase reactants as a result of infection of the GI tact by T. whipplei.

Diagnosis.

Investigation of Malabsorption syndrome includes an upper GI endoscopy with biopsy and the T. whipplei infection can be identified by histopathology, electron microscopy, PAS and Acid fast staining and also by PCR identification of bacterial DNA.

Treatment:

T. whipplei, not unlike Mycobacterium avium intercellari, requires prolonged antibacterial therapy followed by a year or two of chemoprophylaxis.

For acute phase infection.

The standard regimen. Ceftriaxone 1 gm IV every 12 hrs., or, high dose of Penicillin IV for 2 to 4 weeks. Followed by one to two years of Sulfamethoxazole Trimethoprim 800 mg/160mg tablet twice a day for 1 to 2 years.

Alternate regimen. Doxycycline 200 mg, by mouth daily every12 hrs. plus Hydroxychloroquine 600 mg orally, once daily for 18 months, followed by Doxycycline 200 mg orally daily for life time.

For CNS symptoms. Ceftriaxone  2 gm IV every 12 hrs. for 6 weeks followed by Sulfamethoxazole Trimethoprim twice a day for 1 to 2 years.

Whipple's disease is a bacterial disease due to immune system's failure in eliminating the pathogenic organism from the body. Articles presented earlier, dealt with a virus that remains in hibernation after an infection and  subsequently causes new disease - Burkitt lymphoma virus. Similarly, a fungus -Pneumocystis jirovecii, and a protozoa – Toxoplasma gondii were discussed. This article on Whipple's disease concludes this section.

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