1. DIARRHEA AND abdominal pain
Bart Kenney, MD
Middlesex Hospital
DIARRHEA AND abdominal pain

2. Clinical history 61 yo female
Developed chronic diarrhea and weight loss
Progressive over 10 months
Malabsorption/protein losing enteropathy

3. Clinical history Past medical history: Medication: Physical exam:
10 year history of sarcoidosis and PMR
Medication:
Oral steroids
Physical exam:
Unremarkable

4. Laboratory findings

5. Imaging findings

6. Laboratory findings Infectious Autoimmune Hematologic
EBV, CMV, HIV, HBV, HCV negative
Stool culture/O&P negative
Mycobacterial QFT negative
Babesia smear negative
Lyme serology negative
Autoimmune
Lymphocyte subsets wnl
No change in rheumatologic parameters
Hematologic
Peripheral blood flow cytometry negative
SPEP negative

7. Lymph node biopsy Inguinal and mesenteric nodes sampled
Granulomatous inflammation c/w sarcoid
AFB/PAS/GMS negative
Bacterial, fungal, mycobacterial cx negative
Flow cytometry negative

8. Endoscopic findings

9. Biopsy - duodenum

12. Residents…
Differential diagnosis???

13. Differential diagnosis
Mycobacterium Avium Intracellulare
Whipple’s disease
Other infection (pneumocystis, histoplasma, leishmania)
Xanthoma
Metabolic storage disease
Histiocytosis
Non-specific/reactive

14. AFB stain

15. PAS stain

17. Additional studies Discussion with GI and PMD
Tissue sent for T. whipplei PCR

18. Additional studies Discussion with GI and PMD
Tissue sent for T. whipplei PCR

19. Whipple’s disease Described in 1907 by George Whipple
"gradual loss of weight and strength, stools consisting chiefly of neutral fat and fatty acids, indefinite abdominal signs, and a peculiar multiple arthritis"
Named in 1949 after discovery of characteristic accumulation of PAS+ macrophages in LP
Although infectious etiology was suspected, first successful rx with antibiotics wasn’t until 1952
Causative agent identified in 1991 (using 16S rRNA sequencing)

20. Whipple’s disease Tropheryma whipplei
Greek “trophe” nourishment and “eryma” barrier (nutrient malabsorption)
Gram positive bacillus related to soil-borne actinomycetes
Ubiquitous in the environment – host immune deficiency may be important factor

21. Whipple’s disease
Uptake of the bacillus is widespread (intestinal epithelium, macrophages, endothelium, liver, kidney, marrow, skin)
Lack of inflammatory response to the organism
No visible cytotoxic effects on host cells
Allows for massive accumulation of bacillus at sites of infection  GI = malabsorption

22. Whipple’s disease Can be highly variable, but classic features…
Diarrhea
Weight loss
Abdominal pain
Arthralgias
Other features…
Fever (25-40%)
Lymphadenopathy (~50%)
CNS findings

23. Whipple’s disease Rule out more common alternatives Small bowel biopsy
IBD, infectious diarrhea, advanced HIV, TB, CTD, hyperthyroidism
Small bowel biopsy
Even if no obvious GI involvement (many pt’s have normal endo)
H&E and PAS
PCR
Small bowel biopsy material
Other sites (CSF, synovial tissue, vitreous fluid)

24. Whipple’s disease Uniformly fatal before antibiotic era Regimen:
Initial phase: IV ceftriaxone x 2 weeks
Maintenance: TMP-SMX or doxycycline/hydroxychloroquine x 1 year
Response monitored by symptom resolution and weight gain
Some advocate repeat endoscopic bx every year for several years to r/o relapse

25. Follow-up Patient on TMP-SMX for 8 months Marked improvement
Less diarrhea
Weight gain
Will reassess after 1 year of treatment
Repeat endoscopy
Repeat CT (adenopathy from sarcoid or WD?)
Patient works in landscaping – soil exposure?