Pseudomembranous colitis: causes, symptoms, diagnosis, therapy, complications, prognosis, mortality

By Cristiano Antonino On Mar 20, 2023

Pseudomembranous colitis’ (also called ‘pseudomembranous enterocolitis’, hence the acronyms ‘CPM’ and ‘ECPM’) is an inflammation of the colon (hence the term ‘colitis’) characterised by raised white-yellow plaques that come together to form pseudomembranes on the mucosa

Inflammation of the colon occurs when, under certain circumstances, the bacterium Clostridioides difficile (once known as ‘Clostridium difficile’) damages the organ through its toxin.

It almost always appears in people previously treated with antibiotics and is therefore also often called ‘antibiotic-associated colitis’.

It also occurs most frequently in debilitated persons admitted to hospitals or nursing homes.

The bacterium Clostridioides difficile causes most pseudomembranous colitis, but it is not the only possible aetiological agent.

Pseudomembranous colitis mainly affects adults, but can also affect children and the elderly

It electively affects the most terminal part of the colon: the descending colon, sigma and rectum are affected in 77-80% of cases; the cecum, ascending and transverse colon are affected in 5-19% of cases.

The disease is characterised by diarrhoea, sometimes with a fetid odour, fever, abdominal pain and leucocytosis, and can be severe and in some cases fatal.

Various professionals may be involved in the diagnosis and treatment of the disease, including a gastroenterologist, infectivologist, dietician and general surgeon.

Causes and risk factors

Pseudomembranous colitis is often caused by toxins produced by the bacterium Clostridioides difficile (once known as Clostridium difficile).

This bacterium is normally part of the human microbiota.

The human microbiota (also incorrectly called intestinal flora) is the collection of symbiotic microorganisms that coexist with the human organism without harming it.

The presence of Clostridioides difficile is therefore not a problem, at least not until certain circumstances make it dangerous for the colon that harbours it.

The use of almost all antibiotics, but especially broad-spectrum antibiotics such as quinolones, clindamycin and cephalosporins, is one of the risk factors that make the bacterium a health risk: antibiotics in fact cause a change in the balance of the normal bacterial flora of the intestine, favouring its abnormal spread.

In particular, when the antibiotic destroys the competitive bacteria in the gut, then all remaining organisms will have less competition for space and nutrients in the colon: the net effect is to allow more extensive growth of certain bacteria normally present in the microbiota, including Clostridioides difficile.

This bacterium proliferates abnormally and this causes an increase in the toxin it produces, a toxin responsible for diarrhoea and other symptoms and signs that characterise pseudomembranous colitis.

Pseudomembranous colitis is caused by Clostridioides difficile in 90-95% of cases.

Other causes

Clostridioides difficile is not the only aetiological agent of pseudomembranous colitis: in approximately 5-10% it is caused by other causes, which may be Behçet’s disease, collagenous colitis, inflammatory bowel disease, ischaemic colitis, other infectious organisms (bacteria, parasites and viruses) and certain drugs and toxins.

Bacteria causing pseudomembranous colitis, in addition to Clostridioides difficile, include:

Escherichia coli;
Klebsiella oxytoca;
Clostridium ramosum;
Clostridium perfringens;
Plesiomonas shigelloides
Salmonella enterica;
Shigella;
Staphylococcus aureus;
Yersinia enterocolitica.
Parasites include:
Entamoeba histolytica;
Schistosoma mansoni;
Strongyloides stercoralis;

Among viruses, a possible cause is Cytomegalovirus.

Symptoms and signs

Symptoms and signs of pseudomembranous colitis can vary greatly depending on many factors, including the patient’s age and general state of health, specific cause, mode of onset, part of the colon affected, severity of changes in intestinal flora, and quality of the patient’s immune response.

Pseudomembranous colitis almost always results in:

acute or chronic diarrhoea, often with the presence of traces of blood and a fetid odour;
pain and/or cramps in the abdomen;
fever, even high fever;
mucus or pus in the stool;
nausea;
dehydration;
general malaise.

Symptoms and signs of the fulminant form

Very elderly and/or immunocompromised patients (e.g. with AIDS) may experience the fulminant form of pseudomembranous colitis, which may show, in addition to the symptoms and signs listed above:

arterial hypotension (low blood pressure)
hyperazotemia;
dehydration;
high fever;
high leucocytosis even with a white blood cell count above 40 000/mm3;
coma and death in the most severe and untreated cases.

Diagnosis

Diagnosis is achieved by several means: first of all, the anamnesis is important, in which the patient describes his or her symptoms to the doctor and lists a series of useful information, such as the possible presence of other diseases, tests and operations carried out, the possible presence of conditions causing a state of immunosuppression, previous hospital stays and type of diet.

During the history, the doctor should see an alarm bell ring if the patient describes extensive antibiotic use associated with diarrhoea with mucus and blood and abdominal pain.

The objective test will focus in particular on the abdomen: the doctor will look for signs of pathology e.g. by observing and palpating it.

The diagnostic doubt will be confirmed in most cases by laboratory medicine: the patient collects his stools and the laboratory technician will identify in them the presence of Clostridioides difficile toxins.

In the absence of such toxins and excluding the most probable Clostridioides difficile infection, a colonoscopy is performed that endoscopically detects the pseudomembranes typical of the disease.

At this point, the diagnosis must discriminate the possible causes, looking for pathogens that, less frequently than Clostridioides difficile, can cause this type of colitis.

Thanks to colonoscopy, a biopsy can be performed, which allows a histological sample to be sent to the laboratory.

For the differential diagnosis, various tests may be useful, including blood tests, urine tests, abdominal ultrasound, X-rays and CT scans.

The differential diagnosis arises from diseases and conditions that result in more or less similar symptoms and signs, including:

chemotherapy colitis;
HIV infection;
Crohn’s disease;
colon cancer;
diverticular disease;
celiac disease;
indigestion;
gallstones;
post-cholecystectomy syndrome;
non-gastrointestinal endocrine diseases;
food intolerances;
ischaemic colitis;
ulcerative colitis;
other types of colitis.

Complications of colitis

Possible complications include:

massive fluid loss;
dehydration;
destruction of the affected intestinal mucosa;
hypovolaemia and arterial hypotension with possible hypovolaemic shock;
electrolyte depletion;
sepsis;
toxic megacolon;
intestinal perforation;
intestinal haemorrhage;
death.

Very rapid treatment is required in these cases, as such complications could quickly lead to death (fulminant colitis), especially in debilitated and frail individuals.

Therapy

In the presence of numerous diagnostic clues (use of antibiotics, abdominal pain, severe diarrhoea with mucus and blood), empirical treatment should be started before the results of the Clostridioides difficile toxin search arrive from the laboratory.

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Treatment consists of discontinuing, if possible, any antibiotic therapy the patient may be taking and administering a specific antibiotic against Clostridioides difficile, usually metronidazole, vancomycin, linezolid or bacitracin, orally.

More recently, rifaximin and fidaxomicin are also available.

Therapy must also be aimed at rapidly restoring hydro-electrolyte balance and correcting any ionic alterations, with fluid replenishment to avoid hypovolaemia and severe hypotension.

Lactic ferments and/or other oral formulations (tablets, suspensions and/or powders) containing spores, bacteria or yeasts must be taken concurrently with antibiotic therapy and then prolonged for a long period following treatment in order to re-establish the normal human microbiota.

In severe forms, emergency surgery is not ruled out, e.g. in the case of a perforated colon with haemorrhage.

In recent years, the use of ‘faecal microbiota transplantation’ (also known as ‘faecal transplantation’) to restore the normal bacterial balance of the colon has become increasingly popular.

If testing for Clostridioides difficile proves negative (5-10% of cases) and symptoms persist despite empirical treatment, the underlying cause must be urgently ascertained (with coloscopy, biopsy and other possible tests) and therapy tailored to it.

Colitis, the recommended diet

Certain foods can increase the symptoms and signs of any type of colitis, so – even in the case of pseudomembranous colitis – it may be advisable to avoid them or at least limit their intake.

These include:

coffee;
chocolate;
beverages containing caffeine;
spirits and spirits;
carbonated drinks;
dairy products (if lactose intolerance is present);
foods containing gluten in the case of coeliac disease (pasta, bread, breadsticks, crackers, rusks, bread loaves, focaccia, pizza, gnocchi, sweet biscuits, etc.);
beans, peas, broad beans and dried legumes in general;
dried fruit, fruit with pulp or seeds;
foods containing sulphur or sulphates;
foods with a lot of fibre, including whole grain products;
nuts and dried fruits, oils and butters extracted from them;
products containing sorbitol (gum and sugar-free sweets);
chilli peppers.

Conversely, it may be beneficial to consume certain foods, including:

steamed white meat;
boiled fish;
boiled potatoes;
boiled carrots;
yoghurt rich in lactic ferments;
cooked fruit;
oat, barley and rice soups;
vegetable broth;
non-fermented cheeses.

Prognosis and relapse

Prognosis varies depending on the cause.

If pseudomembranous colitis is associated with the administration or exposure to specific causative agents, e.g. antibiotic drugs that disrupt the balance of intestinal bacterial flora, cessation of exposure may result in a rapid remission, especially in otherwise healthy, young and immunocompetent individuals.

Treatment with metronidazole and vancomycin generally resolves, although relapses are observed in about 20-25% of cases.

If colitis is caused by Clostridioides difficile, the risk of further recurrence after the first recurrence increases by up to 60%

The prognosis with regard to the risk of recurrence of pseudomembranous colitis caused by Clostridioides difficile is linked to the presence or absence of the appendix, as this probably plays an active role in restoring normal intestinal microflora after a course of antibiotic therapy.

The probability of infection with a Clostridioides difficile is 11% in patients with an appendix, compared to 48% in appendectomised subjects.

Mortality

The disease can be severe and in some cases fatal (some estimates cite a mortality rate of between 6 and 30%).

Mortality increases with increasing diagnostic and therapeutic delay, and is usually related to megacolon, intestinal perforation and massive internal haemorrhage.

Sepsis and hypovolaemic shock are possible causes of death.

The highest risk occurs in fulminant cases, which often occur in frail individuals (people who have undergone transplants, the elderly, the immunosuppressed, etc.).

The presence of the appendix decreases the risk of death, while its absence (appendectomy) increases it.

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