DIARRHEA AND abdominal pain

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Presentation transcript:

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

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

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

Laboratory findings

Imaging findings

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

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

Endoscopic findings

Biopsy - duodenum

Residents… Differential diagnosis???

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

AFB stain

PAS stain

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

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

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)

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

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

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

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)

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

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?