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10 Differential Diagnosis for Your IBS Diarrhea (IBS-D) Patients

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10 Differential Diagnosis for Your IBS Diarrhea (IBS-D) Patients

Irritable bowel syndrome (IBS) affects millions worldwide. IBS-related health concerns constitute a large percentage of cases seen in both primary care and gastroenterological settings. The symptoms of IBS can be unrelenting, causing many patients with the diagnosis life-long physical and emotional disturbance related to symptom severity and the financial burden of medical care.

IBS can only be diagnosed once all other possible causes of digestive symptoms have been ruled out. Unfortunately, many seek medical care and are given an IBS diagnosis without an extensive evaluation. This article will discuss ten conditions that present similarly to IBS and that must be considered and ruled out by every doctor before they make an IBS diagnosis.


What is IBS-D?

Irritable bowel syndrome-diarrhea subtype (IBS-D) is a functional gastrointestinal disorder (FGID) characterized by normal intestinal anatomy despite recurrent abdominal pain and bowel movement changes. (1, 2)

IBS affects 25-45 million people of all ages in the United States. Up to 10% of the world's population has been diagnosed with IBS. IBS affects women more commonly than men, with up to two-thirds of patients with IBS being female. (3)

IBS symptoms are unpredictable and vary in severity, and up to 80% of people with IBS suffer through their symptoms without seeking medical support. Moderate-to-severe IBS often impairs physical, emotional, economic, and social well-being. (1, 3)

IBS-D Symptoms

IBS is a diagnosis of exclusion, meaning the diagnosis can be made after ruling out all other conditions that could result in similar symptoms. The patient's symptoms must also fit the ROME IV diagnostic criteria for IBS. (1)

The ROME IV criteria state that the patient's abdominal pain must occur at least once daily every week for at least three months and must be associated with at least two of the following:

  • Related to defecation
  • A change in stool frequency
  • A change in stool appearance

The hallmark symptoms of IBS-D are abdominal pain and diarrhea. With IBS-D, at least one-quarter of abnormal bowel movements are loose and watery. Other characteristic symptoms of IBS-D include urgent bowel movements that often feel incomplete, abdominal bloating, and mucus in the stool. (2)

Top 10 Differential Diagnoses for Your IBS-D Patients

IBS shares similar symptoms with many other conditions and diseases. It is up to the provider to do a thorough evaluation to ensure that all possible causes of digestive symptoms are ruled out before making an IBS diagnosis.


SIBO, which stands for small intestinal bacterial overgrowth, is the overgrowth of bacteria in the upper digestive tract, which causes a multitude of digestive symptoms, including:

  • Burping
  • Bloating, often better in the morning and progressively worse throughout the day
  • Gas
  • Constipation and/or diarrhea
  • Reflux
  • Nausea

Despite the evidence indicating that up to 80% of IBS cases are attributed to SIBO, this condition is commonly overlooked in the allopathic community.

Intestinal Fungal Overgrowth

Intestinal fungal overgrowth, often attributed to Candida yeast species, can occur in the small and large intestines. It also frequently occurs alongside SIBO. Approximately 25% of patients with unexplained digestive symptoms have underlying fungal overgrowth. Diets high in refined carbohydrates, antibiotic use, and low stomach acidity are all factors that can increase the risk of intestinal yeast overgrowth.

Common digestive symptoms of yeast overgrowth include burping, bloating, gas, abdominal pain, heartburn, nausea, and diarrhea. Many extraintestinal signs of fungal overgrowth can occur due to intestinal yeast, including:

  • Skin rashes and itching
  • Vaginal yeast infections
  • Toenail fungal
  • Oral thrush - a white coating on the tongue
  • Urinary tract infections

Celiac Disease

Celiac disease is an autoimmune condition in which the immune system attacks the small intestine, causing irreparable damage, after exposure to the gluten protein. Autoimmunity against the nervous system (gluten ataxia) and the skin (dermatitis herpetiformis) are also manifestations of celiac disease.

Non-celiac gluten sensitivity (NCGS), or gluten sensitivity, has similar digestive symptoms to those with celiac disease when they eat gluten but don't have measurable autoantibodies or small intestinal damage.

Common symptoms of celiac disease and NCGS, similar to IBS, include abdominal pain, bloating, gas, constipation, and diarrhea. An itchy skin rash and neurological symptoms, including numbness/tingling and involuntary movements, are more severe presentations of celiac disease that don't typically accompany IBS.

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD), ulcerative colitis (UC), and microscopic colitis. Chronic, recurrent inflammation of the gastrointestinal tract causes IBD. The location and depth of inflammation within the intestines differentiate between these conditions. Chronic, persistent, and often bloody diarrhea with abdominal pain and weight loss are IBD's most common gastrointestinal symptoms. Gastrointestinal symptoms associated with IBD are typically more severe than those with IBS and may accompany additional symptoms like joint pain, mouth sores, and eye pain. (1)


The pancreas is an abdominal organ responsible for secreting insulin and glucagon to regulate blood sugar and enzymes to support digestion and absorption of carbohydrates, proteins, and fats. If these digestive enzymes act on the pancreatic tissues, they will cause tissue injury and inflammation, known as pancreatitis. Pancreatitis can be acute or chronic, depending on how long pancreatic damage and inflammation persist.

Upper abdominal pain is the most characteristic symptom of pancreatitis, which can last hours to years, depending on the chronicity of the disease. Acute pancreatitis can also present with nausea, vomiting, and fever. Chronic pancreatitis can appear more similar to IBS with the development of loose, greasy stools due to the maldigestion of fat that occurs.

Mast Cell Activation Syndrome

Mast cells are a type of immune cell that release inflammatory mediators responsible for allergy-type symptoms when activated. In an overactive state, called mast cell activation syndrome (MCAS), significant systemic symptoms occur in nearly every body system. Gastrointestinal, neurologic, and cardiac symptoms are very common in MCAS. The abdominal pain, diarrhea, and bloating accompanying MCAS appear very similar to IBS.

Lactose Intolerance

Lactose intolerance develops due to a deficiency in lactase, an enzyme that digests the milk sugar lactose in the small intestine. Lactose maldigestion causes gastrointestinal symptoms like pain, diarrhea, gas, and bloating after ingesting lactose-containing foods. The severity of symptoms depends upon the amount of lactose consumed and the degree of lactase deficiency.  


Endometriosis is a gynecologic condition affecting up to 10% of American women of reproductive age. Endometriosis occurs when endometrial tissue, the inner lining of the uterus, begins to grow outside the uterus. Endometrial lesions can occur on the ovaries, fallopian tubes, behind the uterus, bladder, and bowels. The most common endometriosis symptom is pain at the site of implanted endometrial tissue. Gastrointestinal symptoms similar to IBS, like bowel movement changes, pain with defecation, and bloating, can occur when endometriosis involves the bowels.


IBS is closely associated with anxiety, a mental health condition characterized by persistent feelings of worry and dread that interfere with daily living. Nearly 40% of patients with IBS also suffer from anxiety symptoms, and anxiety is a risk factor for developing and progressing IBS.

The physical expression of psychological and emotional factors, called somatization, is common in anxiety disorders and commonly includes symptoms like abdominal pain, diarrhea, indigestion, chest pain, fatigue, and headache.


Hyperthyroidism, most commonly caused by autoimmunity, is the overproduction of thyroid hormones, resulting in a hypermetabolic state. Frequent, loose bowel movements, abdominal pain, and anxiety can all occur from a hyperactive thyroid.

Functional Medicine Labs to Rule Out Differential Diagnosis

Functional lab testing can help a practitioner rule out or confirm diagnosis. Lab results can also help practitioner individualize treatment options.

Blood Work

A comprehensive blood evaluation that includes a complete blood count (CBC), comprehensive metabolic panel (CMP), thyroid panel, C-reactive protein (CRP), pancreatic enzymes (amylase and lipase), and iron panel is fairly standard for both an allopathic and functional medicine workup of abdominal pain and IBS-like symptoms. The results of this panel can indicate signs of infection, inflammation, hyperthyroidism, and nutrient deficiencies causing and resulting from IBD, celiac disease, hyperthyroidism, MCAS, pancreatitis, and anxiety.

Blood work screening for immune reactions to gluten (e.g., Array 3X) and specific genetic mutations can help rule out celiac disease and NCGS. Celiac blood panels are most accurate when patients have been actively incorporating gluten-containing grains into their diet for 4-6 weeks before the blood draw.

Elevations in tryptase and histamine can indicate mast cell involvement in IBS-like symptoms.

Breath Testing

SIBO can be diagnosed by elevations in hydrogen, methane, and/or hydrogen sulfide gas levels in the breath after the patient drinks a lactulose-containing solution. The SIBO 3-Hour Breath Test is a popular breath test that measures only hydrogen and methane levels. The trio-smart breath test is the latest advancement in SIBO testing and can measure all three gas levels associated with SIBO.

Like SIBO, lactose intolerance can be diagnosed via a lactose malabsorption breath test if hydrogen gas levels measured through breath samples exceed a certain level after the patient drinks an oral dose of lactose.

Stool Testing

A comprehensive stool analysis provides an extensive assessment of gastrointestinal health, measuring a variety of biomarkers pertaining to digestion, intestinal inflammation, and dysbiosis. Markers included on a comprehensive stool test of particular importance when ruling out gastrointestinal conditions include:

  • Elastase: a marker of pancreatic digestive function
  • Calprotectin and Lactoferrin: intestinal inflammatory markers often elevated in active IBD and celiac disease
  • Microbiome assessment: dysbiosis can contribute to the development of SIBO, fungal overgrowth, anxiety, autoimmunity contributing to gastrointestinal and thyroid conditions, hormone imbalances contributing to anxiety and endometriosis, and MCAS
  • Yeast culture with KOH prep is one of the most accurate ways to detect intestinal yeast overgrowth.


Imaging is often indicated to make definitive medical diagnoses. Depending on patient symptoms and lab results, commonly ordered imaging methods for additional evaluation and diagnosis include:

  • Endoscopy and colonoscopy to directly visualize and biopsy the small and large intestines; required for definitive diagnosis of celiac disease and IBD
  • Abdominal and/or endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) for pancreatic assessment
  • A diagnosis of endometriosis is often made presumptively based on medical history, lab results, and imaging methods like pelvic/abdominal ultrasounds, MRIs, and CT scans. A confirmed diagnosis must be made with surgical laparoscopy and tissue biopsy.

Other Testing

The GAD-7 is a quick screening questionnaire utilized in office for anxiety disorders. It can be used to objectively determine the presence and severity of initial anxiety symptoms and monitor symptom changes over time.

The NutrEval is a comprehensive nutritional test that measures vitamins, minerals, antioxidants, omega-3 fatty acids, amino acids, and organic acids. Imbalances can indicate the presence of or contribute to developing any of the diagnoses discussed above.

A comprehensive hormonal panel, like the DUTCH Complete, measures sex and adrenal hormones to screen for imbalances contributing to digestive symptoms, endometriosis, hyperthyroidism, and anxiety.


Many gastrointestinal and extraintestinal health conditions are responsible for causing digestive symptoms shared with IBS. To definitively make an IBS diagnosis, a patient must meet the ROME IV criteria, and all other possible diagnoses must first be excluded. Constructing a comprehensive differential diagnosis is an important first step for doctors making an IBS diagnosis to ensure a complete and thorough patient diagnostic evaluation is performed.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
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