Pseudomembranous Colitis (Clinical)

Overview

Definition

Pseudomembranous colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis is inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy caused by overgrowth of the bacterium Clostridioides difficile.

Epidemiology^[8,10–12]

• In the US in 2011:
  • Approximately 450,000 cases
  • Approximately 14,000 deaths
• Cases of CDI and associated hospitalizations have been decreasing since 2011.^[10]
• Most cases are hospital-acquired.
• Up to 40% of cases of C. difficile colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis are community-acquired.
• Most common in adults > age 65

Etiology^[8,11,12]

• Caused by toxigenic strains of C. difficile: 
  • Spore-forming, gram-positive Gram-Positive Penicillins bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus, obligate anaerobe
  • C. difficile can exist in 2 forms:
    • Spore form Spore form Pneumocystis jirovecii/Pneumocystis Pneumonia (PCP): outside the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy; resistant to heat Heat Inflammation, acid, and antibiotics
    • Vegetative form: in the intestine; the active, toxin-producing form; susceptible to antibiotics
  • Highly contagious
  • Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax transmitted via the fecal–oral route
• Recent antibiotic use is the leading risk factor. CDI can occur with any antibiotic, but the most commonly implicated are:
  • Clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides 
  • Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
  • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
  • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins
• Other risk factors:
  • Proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitors (gastric-acid suppression Suppression Defense Mechanisms)
  • Age > 65
  • Medical comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus
  • Recent or current hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
  • Gastrointestinal surgery
  • Enteral feeding
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Chemotherapy Chemotherapy Osteosarcoma
  • Hematopoietic stem cell transplantation Hematopoietic stem cell transplantation Transfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms. Organ Transplantation
  • Inflammatory bowel disease
  • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis

Pathophysiology and Clinical Presentation

Pathogenesis^[11–13]

• Asymptomatic colonization Colonization Bacteriology:
  • Occurs in 12–20% of hospitalized adults
  • Up to 50% asymptomatic colonization Colonization Bacteriology in long-term care facilities
• Disruption of the normal flora by antibiotics leads to overgrowth of C. difficile.
• Most of the clinical C. difficile infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are observed in newly colonized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
• Intestinal damage is due to toxin release. 
• Toxins released by C. difficile:
  • Enterotoxin A Enterotoxin A Clostridia:
    • Targets brush-border enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
    • Alters fluid secretion Secretion Coagulation Studies
    • Causes watery diarrhea Watery diarrhea Rotavirus
  • Toxin B (10 times more potent):
    • Depolymerizes actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction 
    • Disrupts cytoskeleton Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. The Cell: Cytosol and Cytoskeleton of enterocytes
    • Causes pseudomembranous colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis

Clinical presentation^[8,13]

• Acute diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea with ≥3 loose stools in 24 hours:
  • Mucus and occult blood in stools are possible.
  • Gross bleeding (e.g., melena Melena The black, tarry, foul-smelling feces that contain degraded blood. Gastrointestinal Bleeding, hematochezia Hematochezia Gastrointestinal Bleeding) is rare.
• Lower quadrant or diffuse abdominal pain Abdominal Pain Acute Abdomen
• Abdominal distention Abdominal distention Megacolon
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration
• Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus 
• Fulminant colitis Fulminant colitis Pseudomembranous Colitis: 
  • Acute abdominal distention Abdominal distention Megacolon and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Signs of sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock:
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
    • Change in mental status
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea may be absent owing to colonic ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction.
  • Toxic megacolon Toxic megacolon An acute form of megacolon, severe pathological dilatation of the colon. It is associated with clinical conditions such as ulcerative colitis; Crohn disease; amebic dysentery; or Clostridium enterocolitis. Megacolon:
    • Large bowel dilatation Bowel Dilatation Congenital Duodenal Obstruction > 7 cm; cecum Cecum The blind sac or outpouching area of the large intestine that is below the entrance of the small intestine. It has a worm-like extension, the vermiform appendix. Colon, Cecum, and Appendix: Anatomy > 12 cm
    • Systemic toxicity Toxicity Dosage Calculation (e.g., multisystem organ failure)
  • Colonic perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis, ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage can develop.

Diagnosis

History^[3,8]

• Acute onset of diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea without alternative explanations
• Antibiotic use in the past 6 months
• Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
• Recent abdominal surgery
• Chronic medical conditions

Physical exam^[3,8]

• Findings may be minimal in mild cases
• Severe colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis:
  • Diffuse abdominal tenderness/distention
  • Signs of dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration/ sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock:
    • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Low urine output
• Signs of colonic perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis in fulminant colitis Fulminant colitis Pseudomembranous Colitis ( peritonitis Peritonitis Inflammation of the peritoneum lining the abdominal cavity as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the peritoneal cavity via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the abdominal cavity itself through rupture or abscess of intra-abdominal organs. Penetrating Abdominal Injury/ acute abdomen Acute Abdomen Acute abdomen, which is in many cases a surgical emergency, is the sudden onset of abdominal pain that may be caused by inflammation, infection, perforation, ischemia, or obstruction. The location of the pain, its characteristics, and associated symptoms (e.g., jaundice) are important tools that help narrow the differential diagnosis. Acute Abdomen):
  • Abdominal rigidity Abdominal Rigidity Acute Abdomen
  • Rebound tenderness Rebound Tenderness Acute Abdomen
  • Involuntary guarding
  • Diminished bowel sounds

Laboratory studies^[3,4,8,13]

Stool studies:^[3,4]

• Indication for testing (per the Infectious Diseases Society of America [IDSA]):^[4]
  • Unexplained new-onset diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea with ≥ 3 unformed stools in 24 hours
  • People > 2 years of age with a history of diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea following antimicrobial use or those with healthcare-associated diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • May be considered:
    • Persistent diarrhea Persistent Diarrhea Entamoeba spp./Amebiasis without an etiology
    • Testing asymptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship for colonization Colonization Bacteriology (e.g., on admission to transplant or oncology units)
• Types of tests:
  • Nucleic acid amplification Nucleic acid amplification Laboratory techniques that involve the in-vitro synthesis of many copies of DNA or RNA from one original template. Septic Arthritis test (NAAT)/ polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)) for C. difficile genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure:
    • Pro: identifies the presence of toxigenic C. difficile strains; highly sensitive (about 96%)
    • Con: unable to distinguish patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea due to toxigenic C. difficile from asymptomatic colonized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea from other causes ( positive predictive value Positive predictive value The positive predictive value is the percentage of people with a positive test result who actually have the disease among all people with a positive result, regardless of whether or not they have the disease. Epidemiological Values of Diagnostic Tests [ PPV PPV The positive predictive value is the percentage of people with a positive test result who actually have the disease among all people with a positive result, regardless of whether or not they have the disease. Epidemiological Values of Diagnostic Tests] about 45%)
  • Enzyme immunoassay Enzyme immunoassay HIV Infection and AIDS ( EIA EIA HIV Infection and AIDS) for C. difficile glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids dehydrogenase (GDH) antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination:
    • Detects the presence of GDH, which is produced by both toxigenic and nontoxigenic strains (test can not distinguish between the 2)
    • PPV PPV The positive predictive value is the percentage of people with a positive test result who actually have the disease among all people with a positive result, regardless of whether or not they have the disease. Epidemiological Values of Diagnostic Tests is about 35%; sensitivity is about 95.
    • Rapid, widely available
  • EIA EIA HIV Infection and AIDS for C. difficile toxins A and B:
    • Detects endotoxins Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Bacteriology produced by C. difficile with high specificity (99%)
    • Lower sensitivity (60%‒80%)
  • Toxigenic stool culture or cell cytotoxicity neutralization assays: highly sensitive but impractical for use outside of research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest settings
• Only liquid stools should be sent for testing.
• A 2-step testing algorithm is preferred:
  • Step 1:
    • NAAT for C. difficile toxin B gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics, or
    • EIA EIA HIV Infection and AIDS for GDH
  • Step 2: If either NAAT or GDH is positive → proceed with EIA EIA HIV Infection and AIDS for C. difficile toxin
• Interpreting the results:
  • If both steps are positive, this is diagnostic.
  • If only step 1 is positive, possibilities include:
    • Colonization Colonization Bacteriology without active infection 
    • Toxins below the threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction for detection 
    • False negative False negative An FN test result indicates a person does not have the disease when, in fact, they do. Epidemiological Values of Diagnostic Tests EIA EIA HIV Infection and AIDS for C. difficile toxin 
  • If both GDH and toxin EIA EIA HIV Infection and AIDS are negative, the diagnosis is unlikely.
  • Note: Treatment may still be appropriate despite negative test results if there is high clinical suspicion
• The same approach is recommended for suspected recurrent infections Recurrent infections Common Variable Immunodeficiency (CVID) with symptoms.
• Do not repeat lab testing to check for cure in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship without symptoms (tests remain positive).

Blood tests:

• CBC may show leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus or leukopenia
• Chemistries for hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia (due to diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea)
• Findings in fulminant colitis Fulminant colitis Pseudomembranous Colitis:
  • Serum creatinine ≥ 1.5 mg/dL ( acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury due to dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration)
  • Lactic acidosis Lactic Acidosis Oxazolidinones
  • Serum albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests < 2.5 g/dL
  • Bandemia

Imaging^[3,8]

• Abdominal X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests (if CT is not available):
  • Can show colonic dilatation 
  • Free air seen with perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
• Computed tomography (CT) of the abdomen and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy with oral and IV contrast:
  • Findings consistent with colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis:
    • Pronounced colonic wall thickening
    • Concentric rings of different attenuation indicating mucosal and submucosal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema (“ target sign Target sign Pseudomembranous Colitis” or “double halo sign Halo sign Aspergillus/Aspergillosis”)
    • Oral contrast trapped between thickened haustral folds (“ accordion sign Accordion sign Pseudomembranous Colitis”) showing alternating bands of high and low attenuation
  • Can detect ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction or toxic megacolon Toxic megacolon An acute form of megacolon, severe pathological dilatation of the colon. It is associated with clinical conditions such as ulcerative colitis; Crohn disease; amebic dysentery; or Clostridium enterocolitis. Megacolon (> 7 cm dilatation)
  • Can reveal complications such as perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis

Flexible sigmoidoscopy Sigmoidoscopy Endoscopic examination, therapy or surgery of the sigmoid flexure. Colorectal Cancer Screening^[3,8]

• Not necessary if the diagnosis is confirmed based on stool studies
• Needed only if an alternative diagnosis is considered
• Full colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening is not recommended because of the risk of perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis.
• Findings:
  • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
  • Friable mucosa
  • Bowel-wall edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Pseudomembranes Pseudomembranes Raised yellow or off-white plaques up to 2 cm in diameter that form as a result of mucosal ulceration Pseudomembranous Colitis:
    • Raised yellow or off-white plaques up to 2 cm in diameter
    • Form as a result of mucosal ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers

Management

• US guidelines:
  • Click here for the American College of Gastroenterology (ACG) Guidelines for prevention, diagnosis, and treatment of Clostridioides difficile infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.^[3]
  • Click here for the clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults.^[4]
• UK guidelines:
  • Click here for National Institute for Health and Care Excellence (NICE) guideline NG199 on Clostridioides difficile infection and antimicrobial prescribing.^[5]
  • Click here for the joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines on the use of fecal microbiota transplant for Clostridium [Clostridioides] difficile infection.^[6]

Classifying disease severity and predicting unfavorable outcomes^[3,4,9]

Classifying CDI into nonsevere, severe, or fulminant disease helps guide treatment and predict outcomes. The IDSA recommends using the following definitions/criteria:

• Severe CDI:
  • WBC ≥ 15,000 cells/µL, or
  • Serum creatinine > 1.5 mg/dL
• Fulminant CDI: severe CDI plus hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock, ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction, or megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon

Other predictors of poor outcomes:

• High fecal calprotectin Calprotectin Irritable Bowel Syndrome (> 2,000 µg/g)
• Hypoalbuminemia Hypoalbuminemia A condition in which albumin level in blood (serum albumin) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (albuminuria). Nephrotic Syndrome in Children
• Low or undetectable peripheral eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever > 38.5 °C (seen in only 1%)
• Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease with the hypervirulent strain NAP/027/BI C. difficile

Medical management^[3,4,7]

• General management:
  • Fluid resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome, electrolyte correction
  • Stop the offending antibiotic, if possible.
  • Regular Regular Insulin, low-residue diet as tolerated
  • Antimotility agents are typically avoided.
• Infection control measures:
  • Contact precautions/gloves
  • Hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy washing with soap (alcohol-containing hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy gels are not sporicidal) 
  • Isolation of the patient, with designated bathroom facilities
  • Avoid using contaminated electronic thermometers and stethoscopes.
  • Use of hypochlorite (bleach) solution to decontaminate patient rooms
  • Restrict the use of specific antibiotics:
    • Clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides
    • 2nd- and 3rd-generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
• Antibiotic therapy for initial episodes: indicated for all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship diagnosed with CDI
  • Nonsevere and severe CDI:
    • Oral fidaxomicin (preferred if available): 200 mg twice daily for 10 days
    • Oral vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides: 125 mg 4 times daily for 10 days
    • If neither of the above is available: oral or IV metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess 500 mg 3 times daily for 10–14 days (for nonsevere disease only, higher failure rates)
  • Fulminant CDI:
    • Oral vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides 500 mg every 6 hours plus 
    • IV metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess 500 mg every 8 hours
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction: can also add rectal vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides (retention enema) 500 mg in 100 mL saline every 6 hours (or a fecal microbiota transplant)
• Initial recurrent episodes:
  • Fidaxomicin (preferred in US guidelines)^[4]
    • Standard regimen: 200 mg twice daily for 10 days
    • Extended-pulsed regimen: 200 mg twice daily for 5 days, then every other day for 20 days 
  • Alternative: oral vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides in a tapered and pulsed regimen (preferred in UK guidelines, acceptable alternative per IDSA)^[4-6]
    • 125 mg 4 times daily for 10–14 days, then 
    • 125 mg twice daily for 7 days, then 
    • 125 mg once daily for 7 days, then 
    • 125 mg every 2–3 days for 2–8 weeks
  • Bezlotoxumab:
    • Monoclonal antibody targeting toxin B
    • Indicated as an adjunctive therapy for a recurrent CDI episode within 6 months
    • Dosing: 10 mg/kg IV given once during antibiotic regimen
• ≥ 2nd recurrence options:
  • Same antibiotic options as for an initial recurrence
  • Additional potential regimen: vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides 125 mg 4 times a day for 10 days, then rifaximin Rifaximin A synthetic rifamycin derivative and anti-bacterial agent that is used for the treatment of gastroenteritis caused by Escherichia coli infections. It may also be used in the treatment of hepatic encephalopathy. Hepatic Encephalopathy 400 mg 3 times a day for 20 days
  • Fecal microbiota transplantation
• Consider fecal microbiota transplantation (FMT):
  • Instilling processed stool from healthy donors into the patient’s intestinal tract via oral capsules, upper GI routes (e.g., nasojejunal tube), or lower GI routes (e.g., colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening, retention enema)
  • Indications:
    • Severe or fulminant initial episode refractory to antibiotic therapy, especially those who are poor surgical candidates (ACG, BSG guidelines)^[3,6]
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 2 episodes of CDI and risk factors for additional episodes (BSG guidelines)^[6]
    • 3rd episode of CDI (IDSA guidelines)^[4] 
  • Benefits of FMT:
    • Improved cure rates
    • Decreased rates of CDI-related colectomy and sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
  • FDA safety alerts:
    • Potential for transmission of pathogenic Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli  from donor to recipient, causing illness or death
    • Potential for transmission of SARS-CoV-2, which causes COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems).
• Special considerations:^[3]
  • If continuing antibiotics for another infection is essential: Continue CDI treatment for 1 week after completion of other antibiotics.
  • Cost constraints with fidaxomicin or bezlotoxumab: best for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at greatest risk of recurrence:
    • Age > 65 years
    • Severe CDI
    • Immunosuppression
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with inflammatory bowel disease: Extend vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides treatment to 14 days.
  • Pregnant and breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: ACG recommends vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides.
  • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: ACG recommends either vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides or fidaxomicin, as above. 
  • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe or fulminant disease: Consider monitoring serum vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides levels (because of the possibility of systemic absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption).

Surgical consultation^[3,7]

Indications:

• Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever > 38.5ºC (101.3ºF)
• Ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction or significant abdominal distention Abdominal distention Megacolon
• Peritonitis Peritonitis Inflammation of the peritoneum lining the abdominal cavity as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the peritoneal cavity via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the abdominal cavity itself through rupture or abscess of intra-abdominal organs. Penetrating Abdominal Injury
• Altered mental status Altered Mental Status Sepsis in Children
• Serum lactate > 2.2 mmol/L
• Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus ≥ 15,000 cells/µL
• ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus admission
• Failure to improve after 3–5 days of medical therapy
• Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis

Surgical interventions:

• Total abdominal colectomy with end ileostomy Ileostomy Surgical creation of an external opening into the ileum for fecal diversion or drainage. This replacement for the rectum is usually created in patients with severe inflammatory bowel diseases. Loop (continent) or tube (incontinent) procedures are most often employed. Large Bowel Obstruction 
• Segmental colectomy is usually not recommended.
• Alternative to colectomy:
  • Diverting-loop ileostomy Ileostomy Surgical creation of an external opening into the ileum for fecal diversion or drainage. This replacement for the rectum is usually created in patients with severe inflammatory bowel diseases. Loop (continent) or tube (incontinent) procedures are most often employed. Large Bowel Obstruction with colonic lavage and intraluminal vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
  • Not an option if perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis or necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage is present

Prevention^[3] 

• The ACG guidelines recommend against probiotics for the prevention of CDI in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship taking antibiotics or for the prevention of CDI recurrence.
• Evidence does not support discontinuing proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitors (PPIs) in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with CDI.
• Suppressive oral vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides:
  • Dosing: 125 mg once daily
  • Indications:
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who require ongoing (or frequent) courses of antibiotics for other infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a history of CDI and high risk of recurrence who require systemic antibiotics

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas^[4,9]

• Up to 25% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship experience recurrence within 30 days:
  • Defined by the resolution of symptoms and then reappearance within 2–8 weeks after treatment has been stopped.^[4]
  • May be due to a relapse Relapse Relapsing Fever of the initial strain or reinfection with a new strain
  • Less commonly, it can occur up to 2 months after completing treatment
  • Can be mild, severe, or fulminant
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship experiencing recurrence are at a higher risk of further recurrence.
  • Risk factors for recurrence:
    • Age > 65
    • Severe underlying medical disorders
    • Need for ongoing therapy with concomitant antibiotics during treatment for C. difficile colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis
    • Lack of an antibody-mediated immune response to toxin B
• Note: Recurrent symptoms may also be due to postinfectious irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome or another inflammatory colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis.
• Mortality Mortality All deaths reported in a given population. Measures of Health Status in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship > age 65:
  • Primary CDI: 2.7%
  • Recurrent CDI: 25% (almost 10 times higher)^[9]

Differential Diagnosis

• Crohn disease (CD): a chronic, recurrent condition that causes patchy transmural inflammation Transmural inflammation Crohn’s Disease in the terminal ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy and proximal colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with CD typically present with intermittent non-bloody diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and crampy abdominal pain Abdominal Pain Acute Abdomen. Management is with corticosteroids Corticosteroids Chorioretinitis, azathioprine Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen. Immunosuppressants, antibiotics, and anti-tumor necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF)) agents. Complications include malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion, intestinal obstruction Intestinal obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis or fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula, and an increased risk of colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer. 
• Ulcerative colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis ( UC UC Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis): an idiopathic Idiopathic Dermatomyositis inflammatory condition that involves the mucosal surface of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy. Diffuse friability, erosions Erosions Corneal Abrasions, Erosion, and Ulcers with bleeding, and loss of haustra Haustra Colon, Cecum, and Appendix: Anatomy are observed in UC UC Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with bloody diarrhea Bloody diarrhea Diarrhea, colicky abdominal pain Abdominal Pain Acute Abdomen, tenesmus, and fecal urgency. Diagnosis is established based on endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Management is with topical mesalamine, an oral 5-aminosalicylic acid (5-ASA) agent, or an oral glucocorticoid (e.g., budesonide Budesonide A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. Asthma Drugs). Colectomy is sometimes necessary for severe cases.
• Infectious diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea ( Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess, Clostridium perfringens Clostridium perfringens The most common etiologic agent of gas gangrene. It is differentiable into several distinct types based on the distribution of twelve different toxins. Gas Gangrene, Salmonella Salmonella Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Salmonellae are flagellated, non-lactose-fermenting, and hydrogen sulfide-producing microbes. Salmonella enterica, the most common disease-causing species in humans, is further classified based on serotype as typhoidal (S. typhi and paratyphi) and nontyphoidal (S. enteritidis and typhimurium). Salmonella, among others): presents with clinical manifestations similar to those of C. difficile infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease. The diagnosis is distinguished based on stool culture. Management is primarily supportive and requires antibiotics in some cases.
• Diarrheagenic Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli: causes enteritis Enteritis Inflammation of any segment of the small intestine. Lactose Intolerance, enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis, and colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship usually present with watery/ bloody diarrhea Bloody diarrhea Diarrhea, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Diagnosis is established based on culture and/or PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) using stool samples. The treatment consists of supportive therapy (fluids and electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes). Although antibiotics are reserved for severe/persistent cases, they are contraindicated in some instances.