chronic diarrhea and malabsorption syndromes

CChronic diarrheahronic diarrhea

Mihai Rimbaș

DefinitionDefinitionIts definition has traditionally

been based upon the frequency, volume, and consistency of stools.

BUTthe relationship between these

features and patients' perception of diarrhea is variable.

DefinitionDefinitionChronic diarrhea should be defined

as a decrease in fecal consistency lasting for four or more weeks.

The American Gastroenterological Association (AGA) technical review for the evaluation and

management of chronic diarrhea: www.gastro.org/practice/medical-position-statements

EpidemiologyEpidemiologyBased upon a commonly used

definition (ie, the presence of excessive stool frequency) a reasonable approximation is that chronic diarrhea affects approximately 5 percent of the population.

Chronic diarrhea can decrease quality of life.

EtiologyEtiologyIn developing countries, chronic

diarrhea is frequently caused by chronic bacterial, mycobacterial, and parasitic infections, although functional disorders, malabsorption, and inflammatory bowel disease are also common.

In developed countries, common causes are irritable bowel syndrome (IBS), inflammatory bowel disease, malabsorption syndromes, and chronic infections (particularly in patients who are immunocompromised).

Irritable bowel syndrome Irritable bowel syndrome The symptom complex of chronic

lower abdominal pain and altered bowel habits;

Symptoms of IBS often correlate with episodes of psychologic stress.

Irritable bowel syndromeIrritable bowel syndromePatients with IBS complain of

crampy lower quadrant pain with diarrhea, alternating diarrhea and constipation, or normal bowel habits alternating with either diarrhea and/or constipation.

Diarrhea is usually characterized as frequent loose stools of small to moderate volume.

Irritable bowel syndromeIrritable bowel syndromeStools generally occur during

waking hours, most often in the morning or after meals.

Most bowel movements are preceded by extreme urgency and may be followed by a feeling of incomplete evacuation.

Irritable bowel syndromeIrritable bowel syndrome

Approximately one-half of all patients with IBS complain of mucus discharge with stools.

Incontinence of liquid stool may occur during periods of disease activity.

Pain may be relieved with defecation.

Post-infectious IBS Post-infectious IBS Following recovery from C. difficile

and other bacterial infections.May mimic the symptoms of the

original infection with diarrhea and crampy pain.

Patients who develop this condition are more likely to have had mild symptoms of IBS prior to the inciting infection.

Irritable bowel syndromeIrritable bowel syndrome

large volume diarrheabloody stoolsnocturnal diarrheagreasy stools

are not associated with IBS and suggest an organic disease.

Functional diarrhea Functional diarrhea

Continuous or recurrent passage of loose or watery stools without abdominal pain or discomfort

Inflammatory bowel Inflammatory bowel diseasedisease

Primarily refers to ulcerative colitis and Crohn's disease.

Most cases have their onset between ages 15 and 40.

Crohn's disease Crohn's disease

May involve the entire gastrointestinal tract from mouth to perianal area.

Diarrhea, abdominal pain, weight loss, and fever are the typical clinical manifestations for most patients with ileitis, ileocolitis, or Crohn's colitis.

Crohn's disease Crohn's disease

Patients can have symptoms for many years prior to diagnosis.

Although Hemoccult positive stools are common in Crohn's disease, gross bleeding is much less frequent than in ulcerative colitis.

Ulcerative colitis Ulcerative colitis

Mild disease Patients present insidiously with

intermittent rectal bleeding associated with the passage of mucus, and the development of mild diarrhea with fewer than four small loose stools per day.

Mild crampy pain, tenesmus, and periods of constipation are also common.

Ulcerative colitis Ulcerative colitis

Moderate disease Involvement of more than the distal

colon, with the inflammatory process extending to at least the splenic flexure (left-sided colitis).

Frequent loose, bloody stools (up to 10 per day), mild anemia not requiring blood transfusions, abdominal pain that is not severe, and low grade fever.

Ulcerative colitis Ulcerative colitis Severe disease Usually extensive colonic

involvement, often but not always extending to the cecum (pancolitis).

Typically have frequent loose stools (greater than 10 per day) with severe cramps, fever up to 39.5ºC, and bleeding often necessitating blood transfusion.

Patients may suffer rapid weight loss, leading to a poor nutritional state.

Microscopic colitisMicroscopic colitisCharacterized by chronic watery

(secretory) diarrhea of up to two liters daily without bleeding, with a mainly intermittent clinical course.

Usually occurs in middle-aged patients.

Lymphocytic colitisCollagenous colitis (the diagnosis is made by histology,

and biopsies obtained from the right colon are optimal)

Malabsorption syndromesMalabsorption syndromesMalabsorption refers to impaired

absorption of nutrients.

The clinical and laboratory features of malabsorption depend upon the cause and severity of the disease

Malabsorption syndromesMalabsorption syndromesThe CLASSIC MANIFESTATIONS of

malabsorption are pale, greasy, voluminous, foul-smelling stools and weight loss despite adequate food intake.

However, this spectrum of findings is relatively uncommon, even in generalized mucosal disease.

Malabsorption syndromesMalabsorption syndromes

The majority of patients with malabsorption have relatively mild gastrointestinal symptoms, which often mimic more common disorders such as irritable bowel syndrome.

Malabsorption syndromesMalabsorption syndromes

In some cases, anorexia, flatulence, abdominal distension, and borborygmi may be the only complaints suggesting malabsorption; other patients may be asymptomatic.

CholecystectomyCholecystectomyDiarrhea following cholecystectomy

has been reported in 5 to 12 percent of patients.

In many cases resolves or significantly improves with time (weeks to months).

The diarrhea is related to excessive bile acids overcoming the terminal ileum’s reabsorptive capacity and entering the colon (cholerheic diarrhea).

Chronic infectionsChronic infectionsSome persisting infectionsC. DifficileAeromonasPlesiomonasCampylobacterGiardiaAmebaeCryptosporidiumWhipple's diseaseCyclospora

can be associated with chronic diarrhea

Chronic infectionsChronic infectionsThese diagnoses should be

considered in patients with specific risk factors such as travel, HIV infection, use of antibiotics, and consumption of potentially contaminated drinking water.

All patients should be asked about use of antibiotics within the last three months!

Chronic infectionsChronic infectionsChronic diarrhea due to Candida

albicans infection has been described in case reports.

Most patients immunosuppressed (in some cases received antibiotics) and malnourished.

Diagnosis established by detection of large numbers of Candida in small bowel aspirates and stool specimens and response to antifungal therapy.

EVALUATIONEVALUATIONOptimal strategies for the

evaluation of patients with chronic diarrhea have not been established.

Recommendations have been derived mostly from expert opinion and from experience in individual clinical centers.

EVALUATIONEVALUATIONHowever, it is generally agreed upon

that a specific diagnosis can be achieved in more than 90 percent of patients.

The selection of specific tests, timing of referral, and the extent to which testing should be performed depend upon an appraisal of the likelihood of a specific diagnosis, the availability of treatment, the severity of symptoms, patient preference, and comorbidities.

Timing of referral Timing of referral The timing of referral to a

subspecialist depends upon the severity of symptoms, the diagnoses being considered and the need for endoscopic procedures.

HistoryHistory

A thorough medical history can guide appropriate evaluation.

HistoryHistoryA clear understanding of what led

the patient to complain of diarrhea;

Stool characteristics;

Duration of symptoms, nature of onset (sudden or gradual)

Travel history

Risk factors for HIV infection

HistoryHistoryWeight loss;

Whether there is fecal incontinence;

Occurrence of diarrhea during fasting or at night (suggesting a secretory diarrhea);

Family history of IBD;

The volume of the diarrhea;

HistoryHistoryThe presence of systemic symptoms;

All medications;

Association of symptoms with specific food ingestion;

A sexual history;

A history of recurrent bacterial infections (eg, sinusitis, pneumonia).

Physical examination Physical examination

The physical examination rarely provides a specific diagnosis.

Physical examinationPhysical examinationCLUES:

◦findings suggestive of IBD (eg, mouth ulcers, a skin rash, episcleritis, an anal fissure or fistula, the presence of visible blood on digital examination, abdominal masses or abdominal pain);

◦evidence of malabsorption (such as wasting, physical signs of anemia, scars indicating prior abdominal surgery);

Physical examinationPhysical examinationCLUES:

◦lymphadenopathy (possibly suggesting HIV infection);

◦abnormal anal sphincter pressure or reflexes (possibly suggesting fecal incontinence);

◦palpation of the thyroid and examination for exophthalmos and lid retraction may provide support for a diagnosis of hyperthyroidism.

Specific testing Specific testing A large number of tests are

available for diagnosing specific causes of diarrhea.

There is no firm rule as to what testing should be done.

The history and physical examination may point toward a specific diagnosis for which testing may be indicated.

Minimum evaluationMinimum evaluation

Complete blood count and differential;

Erythrocyte sedimentation rate;Thyroid function tests;Serum electrolytes;Total protein and albumin;Stool occult blood.

Minimum evaluationMinimum evaluation

In addition, most patients require some form of endoscopic evaluation and mucosal biopsy, depending upon the clinical setting

CATEGORIZE THE CATEGORIZE THE SYMPTOMSSYMPTOMSBecause irritable bowel syndrome

is one of the most common causes of chronic diarrhea, it is frequently useful to begin evaluation by attempting to categorize the symptoms and signs of the diarrhea as more likely to be either◦functional (related to IBS)◦or organic (related to an identifiable

bowel pathology).

CATEGORIZE THE CATEGORIZE THE SYMPTOMSSYMPTOMS

The presence of:◦significant weight loss,◦anemia, ◦occult or overt gastrointestinal bleeding, ◦nocturnal awakening with pain or

diarrhea

are inconsistent with IBS and should alert to other diagnoses.

CATEGORIZE THE CATEGORIZE THE SYMPTOMSSYMPTOMS

Another useful way to guide specific testing is to attempt to categorize diarrhea as:◦Watery;◦Inflammatory;or◦Fatty.

SecretorySecretory/osmotic/osmotic diarrhea diarrhea

Secretory diarrhea characteristically:◦continues despite fasting;◦is associated with stool volumes >1

liter/day◦occurs day and night.

SecretorySecretory/osmotic/osmotic diarrhea diarrhea Although usually unnecessary, the

distinction between an osmotic and a secretory diarrhea can also be established by measuring stool electrolytes and calculating an osmotic gap:

290 - 2 ({Na+} + {K+})

◦>125 mOsm/kg suggests an osmotic diarrhea ;

◦<50 mOsm/kg suggests a secretory diarrhea.

SSecretory diarrhea ecretory diarrhea

SSecretory diarrhea ecretory diarrhea Further testing may include:

◦stool cultures to exclude chronic infection;

◦imaging of the small and large bowel;◦selective testing for secretagogues;◦secretory diarrhea occurs in 80% of

patients with carcinoid syndrome.;◦testing for bile-acid malabsorption or

empiric treatment with a bile-acid binding resin may also be helpful.

OOsmotic diarrheasmotic diarrhea

Mg, PO4, SO4 ingestion Carbohydrate malabsorption

OOsmotic diarrheasmotic diarrheaFurther testing in patients may

be unnecessary if the osmotic agent can be identified based upon the history.

Testing the stool for laxatives may occasionally be required if laxative abuse is suspected.

InflammatoryInflammatory//infectious infectious diarrhea diarrhea should be suspected in patients

with clinical features suggesting:◦inflammatory bowel disease;◦C. difficile infection;◦those at risk for opportunistic

infections;◦or those with a pertinent travel

history.

InflammatoryInflammatory//infectious infectious diarrhea diarrhea


Diagnosis can usually be established by sigmoidoscopy or colonoscopy or by analysis of stool specimens (ie, culture or testing for C. difficile toxin).


Serum markers of acute inflammation (such as the sedimentation rate and C-reactive protein levels) have been proposed markers of inflammatory diarrhea.

However, their test-characteristics have not been well validated for this purpose; thus, their role in patients presenting with chronic diarrhea is unclear.


Several stool studies have also been evaluated for identifying patients with inflammatory diarrhea:◦Fecal leukocytes (Se 70%, Sp only 50%);◦Fecal calprotectin (Se 93%, Sp 96% for

IBD);◦Fecal lactoferrin.

Fatty diarrhea Fatty diarrhea (steatorrhea) (steatorrhea)

should be suspected:◦in patients who report greasy,

malodorous stools◦and those who are at risk for fat

malabsorption, such as patients with chronic pancreatitis.


The gold standard for diagnosis of steatorrhea is quantitative estimation of stool fat.

Colonoscopy versus Colonoscopy versus sigmoidoscopy sigmoidoscopy

An endoscopic evaluation should be considered if there are persistent symptoms, inconclusive diagnosis, or failure to respond to therapy.

Colonoscopy versus Colonoscopy versus sigmoidoscopy sigmoidoscopy An advantage of colonoscopy is that

it permits examination and biopsy of the entire colon and the terminal ileum (in many patients).

However, flexible sigmoidoscopy (to 60 cm) is often sufficient for establishing the diagnosis, is less expensive, and is associated with fewer risks.

Symptomatic therapy Symptomatic therapy Symptomatic therapy is indicated

when the diagnosis has been made but definitive treatment is unavailable, when diagnosis has eluded diagnostic evaluation, and as a temporizing measure during evaluation. ◦Loperamide;◦Intraluminal adsorbents.

Intestinal malabsorptionIntestinal malabsorption

Mihai Rimbaș

FAT ABSORPTION FAT ABSORPTION Most dietary lipids are absorbed in

the proximal two thirds of the jejunum.

Normally, more than 94 percent of dietary fat is absorbed. As a result, the presence of >6 grams of fecal fat in a 24-hour collection indicates fat malabsorption.

FAT ABSORPTION FAT ABSORPTION

Central to the mechanism of fat absorption is the problem of solubilizing lipids in an aqueous environment.

Lipids must be emulsified to expose a large surface area to lipolytic enzymes◦mastication◦gastric mixing◦bile salts

FAT ABSORPTION FAT ABSORPTION

Enzymes◦salivary lipase◦pancreatic lipase and colipase

2-monoglycerides and fatty acids are then absorbed across the apical membrane of the enterocyte.

FAT ABSORPTION FAT ABSORPTION Disease, or resection, of greater than

100 cm of terminal ileum commonly results in severe impairment of the enterohepatic circulation of bile salts resulting in fat malabsorption.

Similarly, deconjugation of bile acids by florid small bowel bacterial overgrowth defunctionalizes the bile acids, and can also result in fat malabsorption.

CARBOHYDRATE CARBOHYDRATE ABSORPTION ABSORPTION Dietary starch and disaccharides

must be broken down into their constituent monosaccarides prior to absorption.

Enzymes◦salivary and pancreatic amylase◦brush border enzymes

(disaccharidases)

CARBOHYDRATE CARBOHYDRATE ABSORPTION ABSORPTION Carbohydrates that are not

digested and absorbed in the small intestine undergo bacterial degradation in the colon.

Excessive bacterial fermentation is the reason for acidic stools, abdominal distension, and flatulence in patients with carbohydrate malabsorption.

PROTEIN ABSORPTION PROTEIN ABSORPTION

Protein digestion begins in the stomach by the action of gastric pepsins, which are released as proenzymes (pepsinogen 1 and 2), and undergo autoactivation at low pH.

PROTEIN ABSORPTION PROTEIN ABSORPTION In the duodenum, several proteases

act together to digest proteins into amino acids, or dipeptides and tripeptides.

Central to this process is enterokinase, which converts trypsinogen to trypsin, which then catalyzes the conversion of all other pancreatic proteases to their active forms.


Following pancreatic enzyme digestion, amino acids, dipeptides, and tripeptides can be absorbed through highly efficient sodium-dependent amino acid co-transporters at the brush border membrane.


Impaired digestion and absorption of dietary protein occurs when pancreatic protease secretion and/or activity is impaired, as in chronic pancreatitis or cystic fibrosis.

Protein malabsorption can also occur in diseases associated with a generalized reduction of the intestinal absorptive surface.

VITAMIN, MINERAL, AND VITAMIN, MINERAL, AND TRACE ELEMENT TRACE ELEMENT ABSORPTION ABSORPTION The fat-soluble vitamins (A, D, E,

and K) require solubilization in a mixed micellar phase in order to be absorbed.

The proximal half of the small intestine is the predominant site for the absorption of most vitamins and minerals.

VITAMIN, MINERAL, AND VITAMIN, MINERAL, AND TRACE ELEMENT TRACE ELEMENT ABSORPTION ABSORPTION The excess fatty acids present in the

intestinal lumen of patients with untreated fat malabsorption bind divalent cations, such as calcium and magnesium, creating soaps and causing undue losses of these minerals.

Clinically significant deficiencies of these minerals are common in untreated fat malabsorption and create a substantial risk for metabolic bone disease.

MALABSORPTIONMALABSORPTIONRefers to impaired absorption of

nutrients.

Results from:◦congenital defects in the membrane

transport systems;◦acquired defects in the epithelial

absorptive surface.Maldigestion (due to impaired

digestion of nutrients).

CLINICAL FEATURES CLINICAL FEATURES

The clinical features of malabsorption depend upon the cause and severity of the disease.

Malabsorption may either be global or partial (isolated).

CLINICAL FEATURES CLINICAL FEATURES The classic manifestations of

global malabsorption are diarrhea with pale, greasy, voluminous, foul-smelling stools and weight loss despite adequate food intake.

However, this spectrum of findings is relatively uncommon, even with generalized mucosal disease.


Clinical manifestations related to a specific micronutrient deficiency can predominate in some patients.


Partial or isolated malabsorption results from diseases that interfere with the absorption of specific nutrients.

Signs and symptoms of Signs and symptoms of malabsorptionmalabsorption

TESTSTESTS

Because symptoms may be absent or mimic other diseases, a routine battery of blood tests is often helpful as an initial step when malabsorption is suspected.

TESTSTESTSThe malabsorption of fat is the most

commonly used indicator of global malabsorption for two reasons:◦ (1) among the macronutrients (fat,

carbohydrates, and protein), the process by which fat is absorbed is the most complex and, therefore, it tends to be the most sensitive to interference from disease processes;

◦ (2) it is the most calorically dense macronutrient and, therefore, its malabsorption is a critical factor in the weight loss that often accompanies malabsorptive disorders.

TESTS for fat TESTS for fat malabsorptionmalabsorptionQualitative assessment of fecal

fat on a single specimen, since it is easier to perform.

Quantitative assessment of a 72 hour stool collection on a 100 gram fat/day diet if the qualitative is negative and clinical suspicion remains high.

TESTS for carbohydrate TESTS for carbohydrate malabsorption malabsorption

D-xylose test - measures the absorptive capacity of the proximal small intestine;◦Low blood levels and urinary excretion

suggests mucosal disease such as celiac sprue.

◦Absorption is usually normal in pancreatic insufficiency since pancreatic enzymes are not required for xylose absorption.


Lactose tolerance test ◦Following oral administration of a 50

g test dose, blood glucose levels are monitored at 0, 60, and 120 minutes.

◦An increase in blood glucose by less than 20 mg/dL plus the development of symptoms is diagnostic.

or◦An increase in breath hydrogen by

more than 20 ppm is diagnostic.


Breath tests using H2 or (13)CO2 can be used to diagnose specific forms of carbohydrate malabsorption

BUTRely on bacterial fermentation of

nonabsorbed carbohydrate

TESTS for TESTS for protein protein malabsorption malabsorption Technically difficult

◦Enteral protein loss should be directly demonstrable by measurement of the alpha-1 antitrypsin clearance.

◦Plasma citrulline and arginine concentrations are highly correlated to small bowel length

ADDITIONAL TESTS ADDITIONAL TESTS Schilling test - can also be used

to determine the restoration of the functional integrity of the ileal mucosa after treatment of ileal Crohn's disease

ADDITIONAL TESTS ADDITIONAL TESTS 75SeHCAT (selenium-

homotaurocholic acid) test serum test for 7 alpha-hydroxy-4-

cholesten-3-one BUTquantitative measurement of bile

acids in stool in patients who did not respond to cholestyramine may be the method of choice to diagnose cholerheic enteropathy.

Tests for bacterial Tests for bacterial overgrowth overgrowth The gold standard for diagnosis of

bacterial overgrowth is the direct quantitative measurement of bacterial counts from aspirated intestinal fluid.

BUTHydrogen breath tests carbohydrate

substrates have replaced bacterial cultures for the diagnosis of small bowel bacterial overgrowth.

Tests for pancreatic Tests for pancreatic insufficiency insufficiency

DIRECT (duodenal fluid is collected and analyzed to quantify normal pancreatic secretory content (ie, enzymes, and bicarbonate)

INDIRECT (measure the consequences of pancreatic insufficiency )

Endoscopy and pancreatic Endoscopy and pancreatic imagingimagingA cobblestone appearance of the

duodenal mucosa is seen in Crohn's disease, while reduced duodenal folds and scalloping of the mucosa may be evident in celiac disease.

The unusual finding of multiple jejunal ulcers may indicate the presence of jejunoileitis or lymphoma

Endoscopy and pancreatic Endoscopy and pancreatic imagingimagingSmall bowel biopsy is safe and can

help establish the diagnosis.Tissue should be obtained distal to

the ampulla of Vater using biopsy forceps passed through a gastroduodenoscope or enteroscope.

Obtaining four biopsies at different sites optimizes the likelihood of obtaining a diagnosis

Endoscopy and pancreatic Endoscopy and pancreatic imagingimagingImaging of the pancreas by CT,

ERCP, MRCP, or ultrasonography may be helpful in the diagnosis of chronic pancreatitis and may be critical for distinguishing benign from malignant causes.

Barium studies Barium studies

An upper gastrointestinal series with small bowel follow-through or enteroclysis (a double contrast study performed by passing a tube into the proximal small bowel and injecting barium and methylcellulose) can provide important information about the gross morphology of the small intestine.

Wireless capsule Wireless capsule endoscopy endoscopy Wireless capsule endoscopy

allows for visualization of the entire small bowel and allows for much more detailed evaluation of small bowel mucosal disease than barium studies.

CCeliac disease eliac disease gluten-sensitive

enteropathy/nontropical sprue

frequent intrafamilial occurrence;remarkably close association with

the HLA-DQ2 and/or DQ8 gene loci;

immune disorder that is triggered by an environmental agent (the gliadin component of gluten) in genetically predisposed individuals

EpidemiologyEpidemiologyCeliac disease occurs primarily in

whites of northern European ancestry.

Prevalences of 1:300 to 1:500 in most countries.

Although classically a disease of infants, celiac disease now often presents later, between the ages of 10 and 40 years.

CLASSIFICATIONCLASSIFICATIONClassic disease:

◦villous atrophy◦symptoms of malabsorption such as

steatorrhea, weight loss, or other signs of nutrient or vitamin deficiency

◦resolution of the mucosal lesions and symptoms upon withdrawal of gluten-containing foods.

CLASSIFICATIONCLASSIFICATIONAtypical celiac disease - patients

exhibit only minor gastrointestinal complaints:◦anemia, ◦dental enamel defects,◦osteoporosis, ◦arthritis, ◦increased transaminases, ◦neurological symptoms, ◦or infertility.

CLASSIFICATIONCLASSIFICATIONAsymptomatic (silent) celiac

disease◦recognized incidentally based upon

screenings for antibodies against gliadin or tissue transglutaminase

CLASSIFICATIONCLASSIFICATIONLatent celiac disease

◦patients who have normal jejunal mucosa and minor symptoms or no symptoms at one or more time points while on a normal, gluten-containing diet

Clinical manifestationsClinical manifestationsdiarrhea with bulky, foul-smelling,

floating stools due to steatorrhea and flatulence

the consequences of malabsorption:◦growth failure in children, ◦weight loss, ◦severe anemia, ◦neurologic disorders from deficiencies of

B vitamins, ◦osteopenia from deficiency of vitamin

D and calcium.

Nongastrointestinal Nongastrointestinal manifestations manifestations Neuropsychiatric disease (peripheral

neuropathy, ataxia, depression, anxiety, or epilepsy)

ArthritisIron deficiency Metabolic bone disease HyposplenismKidney disease -glomerular IgA

depositionIdiopathic pulmonary

hemosiderosis

ASSOCIATED ASSOCIATED CONDITIONS CONDITIONS Dermatitis herpetiformis (up to

24%)

ASSOCIATED ASSOCIATED CONDITIONS CONDITIONS

Diabetes mellitus - type 1Down syndrome Liver disease Autoimmune thyroid disease InfertilityMyocarditis and cardiomyopathy Atrophic glossitis Pancreatitis

DIAGNOSTIC APPROACH DIAGNOSTIC APPROACH

All testing should be performed while patients are on a gluten-rich diet.

Serologic evaluation (IgA anti tissue transglutaminase and IgA endomysial antibody)


Small bowel biopsy


Symptoms resolve subsequently on a gluten-free diet

Principles of a gluten-free Principles of a gluten-free diet diet

Wheat, rye, and barley – avoided.

Soybean or tapioca flours, rice, corn, buckwheat, and potatoes are safe.

Nutritional considerations Nutritional considerations

Specific dietary deficiency such as iron, folic acid, calcium, vitamin D and, rarely, vitamin B12 deficiency should be corrected.

Monitoring the response to a Monitoring the response to a gluten-free diet gluten-free diet

The rapidity of the response to a gluten-free diet is variable. Approximately 70 percent of patients have noticeable clinical improvement within two weeks;

Symptoms improve faster than histology;

Decline in the titer of antiendomysial antibodies.

NonrespondersNonrespondersThe most common reasons for a

lack of response are poor compliance or inadvertent gluten ingestion

Other disorders Refractory sprue (type 1 and 2)Ulcerative jejunitis or intestinal

lymphoma

Refractory sprueRefractory sprueCan be severe and associated with

progressive malabsorption and death.

A subset of patients develops subepithelial collagen deposition, a condition referred to as "collagenous sprue.“

The dose of glucocorticoids required varies among patients, and not all patients respond.

Ulcerative jejunitis and Ulcerative jejunitis and intestinal lymphoma intestinal lymphoma Considered in patients with refractory

sprue unresponsive to corticosteroids;

Aberrant T-cell monoclonality;

Clinical manifestations are similar to severe celiac disease; lassitude, anorexia, weight loss, abdominal pain, diarrhea, and fever.

Intestinal stricturing can develop with resulting small bowel obstruction.

Ulcerative jejunitisUlcerative jejunitisUlcerative jejunitis responds

poorly to a gluten-free diet

Associated with an unfavorable prognosis. Up to one-third of patients die from complications.

The prognosis can be improved if the ulcerated or strictured segment can be resected.

EEnteropathy-associated T-nteropathy-associated T-cell lymphomacell lymphoma

Lymphomas are almost always of high-grade histology and the prognosis is poor.

Five-year survival is approximately 10%.

Whipple's diseaseWhipple's disease

etiologic agent was identified in 1991

Tropheryma whippleigram-positive, non-acid-fast,

periodic acid-Schiff (PAS) positive bacillus

EPIDEMIOLOGYEPIDEMIOLOGYThe spectrum of infections due to

T. whipplei is wide.

In Europe, the prevalence of the bacterium in fecal samples from the healthy adult population is estimated to be 1 to 11 percent.

EPIDEMIOLOGYEPIDEMIOLOGYThe disorder has a predilection for

white males of European ancestry, suggesting an underlying genetic predisposition that leads to colonization of T. whipplei throughout the intestinal tract, lymphoreticular system, and central nervous system upon exposure to soil microbes

the annual incidence since 1980 has been approximately 30 cases per year

PATHOGENESISPATHOGENESISInvasion or uptake of the bacillus is

widespread throughout the body.

All of these sites show a remarkable lack of inflammatory response to the bacillus.

In addition, the organism exerts no visible cytotoxic effects upon host cells, thereby allowing massive accumulation of T. whipplei at sites of infection.

CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONS

ArthralgiasWeight lossDiarrheaAbdominal pain

progress to a severe wasting syndrome

CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONSThere may also be symptoms or

signs related to cardiac disease (dyspnea, pericarditis, culture-negative endocarditis), pleuropulmonary (pleural effusion), or mucocutaneous disease;

CNS disease (cognitive dysfunction, oculomasticatory or oculofacial myorhythmia , cerebellar ataxia, dementia, myoclonus, hemiparesis, peripheral neuropathy, seizures, upper motor neuron disorders)

EVALUATIONEVALUATIONEndoscopy with small bowel

biopsy (extensive PAS-positive material in the lamina propria and villous atrophy )

EVALUATIONEVALUATIONConfirmatory electron microscopy

to demonstrate T. whipplei should be performed if the diagnosis is in doubt

PCR techniques

TREATMENT TREATMENT

parenteral ceftriaxone followed by oral trimethoprim-sulfamethoxazole (TMP-SMX, one double-strength tablet twice daily) maintenance therapy for one year

TREATMENT TREATMENT

Several reported cases of Jarisch-Herxheimer reactions one to two hours after initial therapy of Whipple's disease with intravenous antibiotics, especially penicillin.

The reaction consists of fever of 39º to 40ºC, chills, headache, hypotension, and severe abdominal pain or pleuritic chest pain

RelapseRelapseRelapses have been reported in as

many as 17 to 35 percent of patients.

Relapses should be treated with initial ceftriaxone (2 g IV twice daily for four weeks) followed by one year or more of oral doxycycline (100 mg twice daily) or TMP-SMX (one double strength tablet twice daily).

Lactose intoleranceLactose intolerance

Intolerance to lactose-containing foods (primarily dairy products) is a common problem:◦the prevalence is 7 to 20 percent in

Caucasian adults;◦65 to 75 percent among Africans and

African Americans;◦50 percent in Hispanics.

Clinical symptoms Clinical symptoms

diarrhea, abdominal pain, and flatulence after ingestion of milk or milk-containing products

ETIOLOGY OF LACTOSE ETIOLOGY OF LACTOSE MALABSORPTIONMALABSORPTION

primary lactase deficiencylactase deficiency induced by

underlying intestinal disease

PPrimary lactose rimary lactose malabsorptionmalabsorptionRacial or ethnic lactose

malabsorption (lactase nonpersistence)

Developmental lactase deficiency (a consequence of prematurity)

Congenital lactase deficiency (rare autosomal recessive disorder)

Secondary lactose Secondary lactose malabsorptionmalabsorptionBacterial overgrowth or stasis

syndromes Any form of mucosal injury of the

gastrointestinal tract that causes villus flattening or damage to the intestinal epithelium

DIAGNOSISDIAGNOSISLactose tolerance test (sensitivity

of 75 percent and a specificity of 96 percent )

Has largely been replaced by the lactose breath hydrogen test - measures lactose nonabsorption.

Values of breath hydrogen over 20 ppm are considered diagnostic of lactose malabsorption

TREATMENT TREATMENT

focuses on eliminating symptoms, while helping the patient adapt to a gradual increase in lactose intake.

correctable underlying disease?

TREATMENT TREATMENT

Reduced dietary lactose intakeSubstitution of alternative nutrient

sources to maintain energy and protein intake

Administration of a commercially available enzyme substitute (beta-galactosidases)

Maintenance of calcium and vitamin D intake

chronic diarrhea and malabsorption syndromes

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