Diarrhea — Chronic

Last posting was Acute Diarrhea.  Today’s is the Chronic version, defined as either >1 month duration, or history of recurrent episodes.  Remember that acute diarrhea can tail-away into low-grade chronic symptoms for 1-2 months after resolution, sometimes a result of transient lactase deficiency.  If you get a compatible history, simply reassure the patient, & perhaps counsel milk avoidance.

The differential for Chronic Diarrhea is much broader than for Acute Diarrhea; the following is abbreviated:

CAUSES OF CHRONIC DIARRHEA

WORK-UP  —  This is the main clinical question, since many / most patients will wind up having IBS or other functional disorder.  But IBD, i.e. Crohn’s, Ulcerative Colitis, or the newly identified Microscopic Colitis, requires timely diagnosis, as do other entities above.  Note the enormous difference between Inflammatory vs. “Irritable”, between Disease vs. “Syndrome”

So who do we work-up, then who do we refer?  Unfortunately, there’s little solid data around, and the American Gastroenterological Association’s last position statement was in 1999.  I tend to proceed as follows.

Perform a basic H&P.  Certainly, if you find tachycardia, for example, order a TSH.  But let’s say the H&P, including the abdominal exam (with appropriate distraction to evaluate tenderness) is normal.

Seek Red Flags / Key Clues  —  These direct specific work-up.  They include:

Weight loss is hard to evaluate without a baseline.  People can have exaggerated misperceptions of weight trends in all directions.  A useful objective parameter in the absence of firm numbers is to look at their belt — are tighter notches being used; do looser ones look worn?  Are their pants looser?  [though I’ve had occasional patients explain how they had to seek other clothes due to the weight loss, which is convincing].

Inflammatory Bowel Disease occasionally presents with extra-intestinal manifestations.  If these are present in a patient with Chronic Diarrhea, they warrant G-I referral for colonoscopy.  They include:

• Oligoarthritis, Ankylosing Spondylitis
• Eye Pain (iritis, episcleritis, scleritis)
• Erythema nodusum
• Elevated Alkaline Phosphatase
• Aphthous ulcers

Digression — In 1995, a 33-year-old woman, typical immigrant from rural Mexico with husband & baby, sought care in San Francisco for chronic diarrhea.  Got worked-up for every possible bowel disease, infectious & otherwise, to no avail.  Frustrated, she returned to Mexico — doctors there heard, “Lady from San Francisco, chronic diarrhea!” & nailed the HIV diagnosis without further thought.

HIV isn’t a common cause of chronic diarrhea, but everyone should get tested.

If there are no Red Flags or Key Clues noted at your first visit, make a tentative diagnosis of either Lactose Intolerance and/or, if there’s any abdominal pain/discomfort, Irritable Bowel Syndrome (IBS).  Treat with dietary manipulation, psyllium, and/or anti-motility agents.

That was quick!?!?  Well, we didn’t find anything, & the above 2 conditions are awfully common.  Lactose Intolerance has no good simple test to document, & is best addressed through therapeutic trial of milk avoidance or adding commercial “lactase” products.

IBS has the Manning Criteria — 2 or more of the following 6:

• Pain relieved with defecation
• ↑ Stool frequency at time of pain
• Diarrheal stools at time of pain
• Mucus in stool
• Sensation of incomplete defecation
• Abdominal distention on PE

Accuracy for IBS depends on sex, age, & number of criteria.  For example:

• 20 y.o. women: 2/6 (50% accuracy) to 6/6 (>90%)
• 60 y.o. man:  2/6 (25%) to 6/6 (70%)

Accuracy for men is always less than for women, and accuracy for everyone decreases after 40 y.o.  IBS is a condition of younger people; personally, I’d never diagnose it if new onset ≥50 y.o. without a decent work-up (including colonoscopy).  Treat IBS if you suspect it, reserving further work-up for non-responders.

If the diarrhea began right after starting a new medication, look up its side effects.  Consider a substitution or trial of discontinuation if feasible.

If onset correlated with gall bladder surgery, suspect Post-Cholecystectomy Syndrome due to bile being dumped directly into the small intestine.  It may occur after 10% of operations.  Titrate a trial of cholestyramine to the highest dose tolerated for diagnosis; the syndrome may eventually resolve on its own.

Of course, if the Diarrhea has been bothersome for quite a while, it’s fine to order a few basic tests at the first visit.  Certainly order them if your initial treatment doesn’t help.  I start with:

• CBC — Normocytic Anemia suggests IBD; Microcytic suggests iron deficiency from Cancer, IBD, Celiac Disease
• ESR / CRP — significant elevation suggests IBD, maybe cancer metastases
• Total Protein & Albumin  —  serum globulin >4 g/dL suggests systemic inflammation (how to calculate); low albumin suggests nutritional deficiency)
• Tissue-Transglutaminase Antibody (TTG), IgA fraction (for Celiac Disease)
• Stool for Giardia Antigen
• TSH (hyperthyroidism is unlikely, but a one-time cheap test rules it out)

Other tests to consider:

• Ova & Parasites (O&P) [need to order at least 3 separate specimens]
• Stool for C. difficile (if antibiotic use preceded onset of Sx; also in immunocompromised patients)
• Stool C&S (esp. in immunocompromised persons)
• Fecal Fat for malabsorption, esp. if greasy stools.  Ask you lab about single-stool options, before ordering a 72-hour stool collection.  You could let G-I deal with this, since they’d be the ones to work-up positive results anyway.

NEVER perform or order an Occult Blood test for Diarrhea.  Only use it for colon cancer screening on asymptomatic people >50.  On a person with diarrhea, a positive would have no specificity, and a negative no sensitivity.  Screening only!!!!

Parasites  —  We already noted last posting how the yield is low for O&Ps, and you need 3 of them.  But if acute diarrhea doesn’t resolve, it becomes chronic.  It’s hard to avoid a parasite work-up for patients with Chronic Diarrhea.  AIDS-related parasites need separate tests, not the preserved O&P.

Stool for Giardia Antigen, as opposed to O&Ps, identifies the most common cause.  Other pathogens to be found are Ameba and Trichuris, not endemic in the US.  Strongyloides can persist for decades, worth seeking if any history of 3^rd World travel.  But O&P’s are notoriously poor for it; order an ELISA serology for immunocompetent persons.

Entamoeba histolytica can cause serious illness years down the line from initial infection.  However, you can’t distinguish it from non-pathogenic (& thus no-need-to-treat) E. dispar or E. moshkovskii strains on the basis of an O&P.  Lots of gay men in the US are colonized with E. dispar.  So if you find “Ameba,” send a fresh stool for Antigen Detection to distinguish.  Can also order serology for E. histolytica; most useful if negative (positive remains so for life).

What about Blastocystis hominis (now called “Blastocystis spp” since there are many species)?  It’s often identified on an O&P.  There’s no good evidence at all as to it being a pathogen.  Thus, it’s hard to know how to treat in case you think it’s pathogenic.  Some clinicians like to treat, because that’s all they found, & don’t know what else to do for the patient.  I’m skeptical.

One regimen I saw, Metronidazole 750 mg T.I.D. x10 days, is not easy to tolerate.  I might be inclined to offer 250 mg T.I.D. x5 days, which cures any Giardia that might not have been found.  One study found some clinical success with 500 mg T.I.D. x10 days (vs. placebo).  Tinidazole 2 gm daily (50 mg/kg) x3 days is much better tolerated & cures lots of organisms (may be expensive).

Follow-Up  —  I schedule follow-up depending on how long the illness had been going on.  Diarrhea for a little over a month I see back in 3-4 weeks.  Diarrhea 1-2 years can return to clinic in 2 months.  But BEWARE  —  be sure that the “Diarrhea on & off for 2 years,” didn’t suddenly get worse a month ago, which would completely change the equation.

At every follow-up, Compare Weights.  Weight loss is the main parameter mandating extensive work-up.

G-I Referral  —  Certainly refer anybody with findings suggestive of:

• IBD (normocytic Anemia, High ESR / CRP, or history of Bloody Diarrhea); they need a colonscopy.
• Microcytic Anemia, send also after documenting iron deficiency & ruling-out Celiac Disease (negative TTP).  Maybe don’t send young women with very heavy periods (low likelihood GI pathology, more probably IBS with anemia due to menorrhagia).
• Certainly send anyone >50 y.o.; they’d benefit from colonscopy anyway (colon cancer screening).
• Malabsorption, even if you obtained a fecal fat & it was negative, send if stools are really greasy & malodorous.
• Weight Loss  —  Send for sure.

What’s the difference between colonoscopy & flexible sigmoidoscopy?  The latter is certainly cheaper, but doesn’t reach the cecum (where Crohn’s often lurks).  Some studies show comparable yields for chronic diarrhea.  The Flex Sig is said to be safer, but the rare morbidity/mortality from colonoscopy tends to occur >75 y.o., when chronic diarrhea would need need one anyway.

If you refer to G-I, they’ll pick up the work-up and address the obscure etiologies in our Table, like intestinal TB or carcinoid, as indicated.  If you have Open Access colonoscopy, and ordered the test for a red flag, send to G-I anyway, even if the scope was negative.

Also send to G-I if you or the patient get tired.  I try never to refer for IBS.  But if all tests are negative, I offer treatment after treatment; even if the weight remains stable, you can refer.  G-I won’t mind (i.e. public sector indigent-care G-I won’t mind; private sector never minds).

That’s it for Chronic Diarrhea.  No pictures with this posting, probably just as well.