Differentials
Common
Ulcerative colitis
History
Exam
generally nonspecific; extraintestinal manifestations, such as erythema nodosum, pyoderma gangrenosum, uveitis, iritis, episcleritis, and arthritis
1st investigation
Microscopic colitis (lymphocytic colitis and collagenous colitis)
History
Exam
generally nonspecific
1st investigation
- colonoscopy with colonic biopsies:
collagenous colitis: thickened subepithelial collagenous band >7 micrometer; lymphocytic colitis: prominent subepithelial lymphocytic infiltrate
More
Other investigations
- IgA-tissue transglutaminase (tTg):
elevated, if celiac disease also present (check local reference values)
- esophagogastroduodenoscopy with duodenal biopsies:
increased intraepithelial lymphocytes, villous atrophy, and crypt hyperplasia, if celiac disease also present
Viral, bacterial, parasitic, HIV enteropathy
History
Exam
usually nonspecific; specific infections may have systemic manifestations (e.g., rash in typhoid)
Irritable bowel syndrome
History
long history of diarrhea, constant or intermittent, without alarm features or night waking; bouts of diarrhea coincide with anxiety/stress, family history of irritable bowel syndrome; bloating, flatulence, and crampy abdominal pain relieved by defecation may be present; diarrhea may coexist with periods of constipation; Rome criteria (set of guidelines that outlines symptoms and applies parameters such as frequency and duration to make possible a more accurate diagnosis) useful when considering irritable bowel syndrome[33][34][35]
Exam
mild abdominal distention or tenderness; patients may demonstrate hyperalgesia and allodynia (pain with nonpainful stimuli, e.g., on light palpation or touching the abdominal wall)
Drug effects
History
on a medication that is known to cause diarrhea; typically proton pump inhibitors, nonsteroidal anti-inflammatory drugs, metformin, and quinine; in many cases, patients on multiple medications; possible laxative use/abuse; ingestion of candy sweetened with a nonabsorbable sugar such as sorbitol;[36][37][38][39] time of onset can be very variable, so can be difficult to pinpoint offending agent[1][40][41]
Exam
generally nonspecific
1st investigation
- trial of discontinuation of suspected medication:
improvement in symptoms upon discontinuation of drug
More
Other investigations
Fecal impaction
History
colonic obstruction due to malignancy or severe motility disorder causing fecal impaction and overflow diarrhea, usually history of severe or worsening constipation; cramping, gas, and abdominal pain common[1]
Exam
hard fecal mass may be noted on rectal exam
1st investigation
- plain abdominal x-ray:
large amount of feces
Other investigations
Celiac disease
History
family history of celiac disease or personal history of other autoimmune diseases, especially type 1 diabetes mellitus or autoimmune thyroid disease; presenting symptoms, especially in adults, are highly variable; classic symptoms include diarrhea, abdominal pain, weight loss, fatigue or lethargy, nausea or vomiting, bloating or excess intestinal gas[42][43][44][45]
Exam
nonspecific; dermatitis herpetiformis (a pruritic, vesicular rash over the extensor surfaces) if found, highly suggestive; aphthous mouth ulceration
1st investigation
- IgA-tissue transglutaminase (tTG):
elevated (>20 units)
More
Other investigations
- duodenal biopsy:
increased intraepithelial lymphocytes, villous atrophy, and crypt hyperplasia
More - capsule endoscopy:
villous atrophy, mosaic mucosal pattern, scalloping of folds, micronodularity
Crohn disease
History
Exam
generally nonspecific; may include distention consistent with a stricture and obstruction, abdominal masses secondary to abscess or phlegmon, abdominal or perirectal fistulae, or skin lesions including erythema nodosum or less commonly pyoderma gangrenosum
1st investigation
Other investigations
- small bowel follow through:
strictures, lesions in small bowel
- capsule endoscopy:
inflammation, ulceration
- fecal calprotectin:
elevated
More
Bile salt malabsorption
History
surgical history of resection of a section of ileum usually >50 cm; can occur in the absence of surgery and ileal disease (termed idiopathic bile salt malabsorption, it is believed to be due to abnormalities of the apical bile salt transporter located in ileal enterocytes)[1][46][47][48][49][50][51]
Exam
surgical scars on abdomen may be present
1st investigation
- 75-selenium-23-selena-25-homotaurocholic acid test (SeHCAT):
abnormally low retention level at 7 days is suggestive of bile salt malabsorption
More
Other investigations
- trial of low-fat, medium-chain triglyceride-supplemented diet:
significant and lasting improvement of symptoms suggests cause related to bile salt deficiency or advanced liver disease
- serum 7-hydroxycholesterol:
elevated
- trial of cholestyramine:
diarrhea resolves
Brush border enzyme deficiency (lactose, fructose, sucrose, isomaltase)
History
diarrhea often occurs along with bloating, cramping, and gas; onset usually within 1 hour of ingesting offending substance; only lactose is typically easily identifiable as discrete exposures; symptoms often gradual, becoming increasingly severe in early adulthood; may present more suddenly after an acute insult (infectious gastroenteritis)[52][53][54]
Exam
usually nonspecific; signs of weight loss and anemia should not be present
1st investigation
- diet record with elimination diet:
prompt resolution of symptoms with avoidance of offending substance
Small intestinal bacterial overgrowth
History
Exam
generally nonspecific
1st investigation
Other investigations
Pancreatic insufficiency
History
Exam
generally nonspecific
1st investigation
- fecal elastase:
positive if approximately ≤200 micrograms/g
More
Other investigations
- fecal chymotrypsin:
positive if approximately ≤6 units/g
More - MRI abdomen:
may reveal pancreatic calcifications
More - CT abdomen:
may reveal pancreatic calcifications
More - ultrasound of pancreas:
may reveal pancreatic calcifications
More - therapeutic trial with pancreatic enzyme replacement:
significant and lasting improvement of symptoms suggests pancreatic insufficiency
More
Alcohol
History
history of excessive alcohol ingestion
Exam
smell of alcohol present or intoxication evident; clinical features of liver disease (e.g., jaundice, spider angiomata, Dupuytren contractures, palmar erythema, gynecomastia, ascites)
1st investigation
- blood alcohol level:
may be elevated
- LFTs:
all parameters may be elevated
Other investigations
- hepatic ultrasound:
may show hepatomegaly, fatty liver, liver cirrhosis, liver mass, splenomegaly, ascites, evidence of portal hypertension
Hyperthyroidism
History
Exam
fine tremor, goiter, exophthalmos, tachycardia, or hypertension in severe cases
1st investigation
- thyroid stimulating hormone:
suppressed
More
Other investigations
- free thyroid hormones:
increased
- thyroid radioactive iodine or technetium-99 uptake scan:
diffuse increased uptake in Graves disease, reduced uptake in subacute thyroiditis
Diabetes mellitus
History
Exam
generally nonspecific; in patients with diabetes, neuropathy, nephropathy, retinopathy are often present by the time gastrointestinal (GI) symptoms manifest
1st investigation
- HbA1c:
48 mmol/mol (6.5%) or greater
- plasma glucose:
elevated
- motility studies: gastric emptying, small intestinal transit time, colonic (sitz marker study, anorectal manometry):
evidence of abnormally fast or slow intestinal transit
More
Other investigations
Radiation enteritis/colitis
History
Exam
generally nonspecific
1st investigation
Other investigations
- small bowel follow through:
areas of thickening, stenosis, adhesions, and occasional fistula
More
Eosinophilic enteritis
History
Exam
generally nonspecific
1st investigation
Other investigations
- CT or small bowel follow through:
areas of thickening can occur in any area of the intestinal tract
More - serum eosinophil count:
may be elevated
Chronic ischemic colitis
History
Exam
generally nonspecific; abdominal tenderness may be present and blood may be seen on rectal examination
1st investigation
- colonoscopy:
mucosal congestion/hemorrhage in the area of the splenic flexure
More
Other investigations
- CT abdomen/pelvis:
thickening of the colon in the area of the splenic flexure
More
Surgical bypass or resection
History
Exam
scars should be notable on the abdomen from prior surgery; otherwise, exam is generally nonspecific
1st investigation
- no initial test:
diagnosis is based on history
More
Uncommon
Nonsteroidal anti-inflammatory drug enteropathy
Infiltrating malignancy
History
Exam
usually nonspecific; cachexia and signs of anemia (e.g., pallor) may be present
1st investigation
- CT abdomen/pelvis:
may reveal mucosal thickening or mass lesion
Other investigations
- endoscopy/colonoscopy:
may be targeted for biopsy if lesion seen on prior imaging
Protein-losing enteropathy
History
leg swelling, abdominal pain, weight loss, rectal bleeding, history immune deficiency with recurrent infections; history of the underlying disease (connective tissue disease, amyloidosis, congestive heart failure, constrictive pericarditis, ulcerative colitis)[92]
Exam
cachexia, pallor, edema; features of underlying disease (connective tissue disease, amyloidosis, congestive heart failure, constrictive pericarditis, ulcerative colitis)
1st investigation
- stool alpha-1-antitrypsin:
present
Other investigations
- endoscopy/colonoscopy:
evidence of underlying mucosal disease
Graft versus host disease
History
Exam
generally nonspecific; patients will often have a maculopapular skin rash that may progress to generalized erythroderma and in severe cases bullous formation with desquamation
1st investigation
- biopsy of affected area (skin/liver/intestine):
active colitis or enteritis with increased crypt apoptosis, degenerated crypts, and epithelial regeneration
More
Other investigations
Hodgkin lymphoma
History
abdominal pain, nausea, vomiting, weight loss, anemia, fever, night sweats; history prolonged celiac disease, or clinical relapse of celiac disease after prolonged period of good response to gluten avoidance[96]
Exam
nonspecific; occasionally cachexia, pallor, lymphadenopathy, rash
1st investigation
- CT scan:
staging tool; may show a mass, lymphadenopathy, or metastases
- lymph node biopsy:
diagnostic histology
Other investigations
- endoscopy/colonoscopy:
may show ulceration, nodules
- polymerase chain reaction:
clonal Ig and T-cell receptor gene rearrangement
- capsule endoscopy:
abnormal mucosal features
- deep small bowel biopsy:
diagnostic histology
Non-Hodgkin lymphoma
History
abdominal pain, nausea, vomiting, weight loss, anemia, fever, night sweats; history prolonged celiac disease, or clinical relapse of celiac disease after prolonged period of good response to gluten avoidance[96]
Exam
nonspecific; occasionally cachexia, pallor, lymphadenopathy, rash
1st investigation
- CT scan:
staging tool; may show a mass, lymphadenopathy, or metastases
- lymph node biopsy:
diagnostic histology
Other investigations
- endoscopy/colonoscopy:
may show ulceration, nodules
- polymerase chain reaction:
clonal Ig and T-cell receptor gene rearrangement
- capsule endoscopy:
abnormal mucosal features
- deep small bowel biopsy:
diagnostic histology
Tropical sprue
History
Exam
generally nonspecific
1st investigation
- stool culture and serologic testing for infections:
negative for common pathogens
More
Other investigations
- endoscopy with duodenal biopsy:
macroscopic scalloping may be seen; histology reveals villous blunting, crypt hyperplasia, and increased intraepithelial lymphocytes
More
Lymphangiectasia/impaired lymphatic drainage
History
diarrhea with or without steatorrhea and nausea/vomiting in childhood or early adulthood; may be history of infection (e.g., tuberculosis), lymphoma, cardiac disease, or use of certain chemotherapeutic agents; easy bruising or night blindness may be noted[100]
Exam
peripheral edema may be present
1st investigation
- alpha-1 antitrypsin excretion in 24-hour stool collection:
>24 mL/day without diarrhea or >56 mL/day with significant diarrhea
More
Other investigations
- CT scan with lymphangiography:
imaging constant with intestinal lymphangiectasia
Hypoparathyroidism
History
fatigue, poor sleep, myalgias, unsteady gait, anxiety, depression, memory loss, constipation, muscle cramps, paresthesias, abdominal pain; may be a history of osteopenia or osteoporosis and kidney stones
Exam
hyper-reflexia, tetany, surgical scars of thyroidectomy
1st investigation
- serum intact parathyroid hormone:
low
- serum calcium:
low
- serum phosphate:
low or normal
Other investigations
- bone radiography:
hyperostosis, soft tissue calcification
- brain CT:
may show basal ganglia calcification
Addison disease
History
fatigue, weakness, weight loss, anorexia
Exam
skin hyperpigmentation, hypotension, hair loss in females
1st investigation
- synthetic ACTH stimulation test:
low basal cortisol and/or failure to raise endogenous cortisol appropriately
Other investigations
- adrenal CT:
normal or atrophy, calcification, or enlargement due to infiltration
- serum electrolytes:
low sodium, elevated potassium, elevated calcium
- insulin hypoglycemia test:
abnormal
Gastrinoma
History
Exam
hypertension, wheezing indicative of bronchospasm
1st investigation
Carcinoid tumors
History
Exam
hypertension, wheezing indicative of bronchospasm
1st investigation
VIPomas
History
Exam
hypertension, wheezing indicative of bronchospasm
1st investigation
Abetalipoproteinemia
History
Exam
physical exam may reveal ataxia, visual impairment, and other neurologic abnormalities
1st investigation
- serum beta-lipoprotein:
absent
Other investigations
- chylomicron level:
low
- MTTP gene testing:
presence of gene mutation
Advanced liver disease
History
history of advanced liver disease from any cause including alcohol, fatty liver, autoimmune, and infectious; although the diarrhea associated with advanced liver disease is rarely life threatening, it often portends end-stage liver disease and evaluation and treatment should be expedited[1][46][47][48][49][50]
Exam
stigmata of chronic liver disease may be present, including spider angioma, palmar erythema, jaundice, and ascites
1st investigation
- trial of low-fat, medium-chain triglyceride-supplemented diet:
significant and lasting improvement of symptoms suggests cause related to bile salt deficiency or advanced liver disease
Other investigations
Common variable immune deficiency
Amyloidosis
History
Exam
generally nonspecific; however, macroglossia, enlargement of the anterior shoulder, ecchymoses, or subcutaneous nodules may be seen[111]
1st investigation
- urine/serum protein analysis:
presence of monoclonal protein in the serum or urine (Bence Jones proteins)
Use of this content is subject to our disclaimer