Microscopic colitis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Microscopic colitis is an inflammatory disease of the colonic mucosa that typically causes chronic or recurrent watery diarrhoea while leaving little or no visible abnormality at endoscopy. Collagenous and lymphocytic colitis are histological patterns rather than reliably distinct bedside syndromes. Patients may describe many small-volume stools, abrupt urgency, night-time defaecation, abdominal discomfort, weight loss and incontinence. Blood, persistent fever or a palpable mass should prompt a broader explanation. The burden can be substantial even when observations, inflammatory markers and endoscopic appearance look reassuring, so document sleep disruption, continence, hydration, work and nutrition rather than counting stools alone.

Diagnosis depends on clinicopathological agreement. A complete drug and smoking history, stool tests selected for infection risk, coeliac serology and assessment for bile acid diarrhoea help define alternatives or coexisting disease. Flexible sigmoidoscopy with a single distal biopsy strategy can miss patchy or proximal change. Colonoscopy or appropriate lower-GI endoscopy should therefore obtain multiple specimens from right and left colon in separate pots so the pathologist can assess distribution and orientation. Faecal calprotectin may be normal or only moderately raised and cannot rule microscopic colitis in or out. A normal CT also cannot replace mucosal sampling.

Treatment starts with explaining that the inflammation is real but usually non-destructive, correcting fluid and nutritional consequences, and withdrawing a plausible precipitating medicine when the risk-benefit discussion supports it. Budesonide has high local activity and extensive first-pass metabolism, but it remains a glucocorticoid with infection, metabolic, ocular, psychiatric, adrenal and bone risks. The selected formulation matters because release profiles and licensed wording differ. Persistent symptoms after an adequate course require verification of adherence, histology and the original phenotype, then reconsideration of infection, bile acid diarrhoea, coeliac disease, pancreatic insufficiency or another inflammatory disorder before escalation. Refractory disease and repeated relapse belong with gastroenterology rather than serial unsupervised steroid courses.

Key points

Think of microscopic colitis in persistent watery, usually non-bloody diarrhoea with urgency, nocturnal stools or faecal incontinence, particularly in an older adult.
A macroscopically normal colonoscopy does not exclude the diagnosis; histology from appropriately labelled right- and left-colon biopsies is the decisive investigation.
Collagenous colitis shows a thickened subepithelial collagen band, while lymphocytic colitis shows increased intraepithelial lymphocytes; clinical management overlaps substantially.
Review proton-pump inhibitors, NSAIDs, selective serotonin reuptake inhibitors and other temporally related medicines, but describe associations carefully and do not stop essential treatment without agreement.
Exclude infection, coeliac disease and bile acid diarrhoea where the history supports them, because coexistence or a convincing mimic can explain incomplete response.
Oral budesonide is first-line induction for active disease; a relevant UK product licence specifies 9 mg each morning, generally for a time-limited course.
Relapse after withdrawal is common. Reconfirm the diagnosis and competing causes before a specialist uses the lowest effective maintenance strategy.
Microscopic colitis is not managed with the colorectal dysplasia-surveillance programme used for longstanding ulcerative colitis solely because the word colitis appears in its name.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Immune and autoimmune susceptibility

Dysregulated mucosal immunity is associated with coeliac, thyroid and other autoimmune disease, particularly in older adults.

Medicine associations

PPIs, NSAIDs, SSRIs and other temporally related medicines are associated with disease, but causality requires careful review before stopping essential treatment.

Smoking and luminal triggers

Smoking and altered responses to bile acids, microbiota or other luminal factors may promote inflammation in a susceptible colon.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Microscopic mucosal inflammation
Increased intraepithelial lymphocytes and lamina-propria inflammation develop despite a macroscopically normal or near-normal colon on colonoscopy.
2
Collagen or lymphocytic phenotype
Collagenous colitis adds a thickened subepithelial collagen band, while lymphocytic colitis is defined predominantly by epithelial lymphocytosis.
3
Secretory and barrier dysfunction
Inflammation reduces sodium and water absorption and increases permeability, producing persistent watery, often nocturnal diarrhoea without visible ulceration.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Characteristic diarrhoea

Frequent watery stools without visible blood, urgency, nocturnal defaecation and episodes of incontinence form the classic phenotype. Symptoms may fluctuate, and abdominal pain is usually less dominant than stool frequency and urgency.

Deceptively normal endoscopy

The colon often looks normal or near normal, so absence of ulceration does not close the case. Diagnosis requires adequate right- and left-sided biopsies with compatible collagenous or lymphocytic inflammation.

Medication-associated presentation

A recent start or dose change involving an NSAID, PPI, SSRI or another reported association increases suspicion, but chronology and clinical necessity must guide supervised withdrawal because association does not establish causation.

Physiological complicationRed flag

Orthostatic symptoms, oliguria, confusion, tachycardia or muscle weakness suggest volume or electrolyte depletion from high stool output. Assess urgently and correct deficits while determining whether an acute alternative is present.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Colonoscopy with segmental biopsiesFirst step
Why
Obtain diagnostic tissue and exclude macroscopic colitis, neoplasia or another lower-gastrointestinal cause.
Interpretation and limitations
Normal-looking mucosa remains compatible with microscopic colitis. Separate right- and left-colon specimens showing a thickened collagen band or increased intraepithelial lymphocytes establish the subtype in the correct clinical setting.
02
Stool microbiology
Why
Exclude infectious diarrhoea when onset, exposure, travel, antibiotics, immunosuppression or local epidemiology makes infection plausible.
Interpretation and limitations
A pathogen redirects treatment and may make steroid exposure unsafe. Negative testing does not diagnose microscopic colitis; it simply removes selected infectious mimics.
03
Coeliac serology
Why
Identify coeliac disease, which can coexist with microscopic colitis or independently cause chronic diarrhoea and deficiency.
Interpretation and limitations
Test total IgA with IgA tissue transglutaminase while gluten is being eaten; IgA deficiency needs an IgG-based route. Positive results require confirmation through the coeliac pathway.
04
Full blood count, renal profile and inflammatory markers
Why
Measure dehydration, electrolyte loss, anaemia and inflammatory burden while looking for discordant severe disease.
Interpretation and limitations
Kidney injury or hypokalaemia requires prompt correction. Anaemia or a striking CRP response is not typical proof of microscopic colitis and should widen investigation.
05
Assessment for bile acid diarrhoea
Why
Detect a common treatable cause of watery diarrhoea when symptoms persist or risk factors coexist.
Interpretation and limitations
Use the locally commissioned diagnostic route rather than relying on an unstructured therapeutic trial. A positive result may explain partial or absent budesonide response and supports targeted treatment.
06
Bone and adrenal risk assessment
Why
Establish safety needs when repeated or maintenance glucocorticoid exposure is being considered.
Interpretation and limitations
Review fracture risk, calcium and vitamin D context, diabetes, blood pressure, infection, eye disease and interacting CYP3A medicines; monitoring is individualised by cumulative exposure and comorbidity.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Irritable bowel syndrome with diarrhoea

IBS may cause watery stool and urgency, but nocturnal diarrhoea and diagnostic right- and left-colon biopsies support microscopic colitis.

Bile-acid diarrhoea

Post-ileal disease, cholecystectomy context or positive specialist testing supports bile-acid loss; coexistence with microscopic colitis is possible.

Coeliac, infection or IBD

Serology, stool studies, calprotectin and histology distinguish small-bowel enteropathy, infection and conventional macroscopic colitis in persistent diarrhoea.

Additional chapter-specific clues

Inflammatory or malignant alternativeRed flag

Visible bleeding, progressive iron deficiency, marked inflammatory response, abdominal mass or persistent unexplained weight loss is atypical and requires investigation for cancer, conventional IBD, ischaemia or another organic disorder.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DiagnosisConfirm histology before chronic treatmentFirst stepWatery diarrhoea persists and initial assessment has not shown an obvious infectious or structural cause.

1Characterise frequency, nocturnal symptoms, blood, urgency, weight change, exposures, previous surgery and medicines, while checking hydration and warning features.
2Send targeted stool and blood tests, including coeliac serology, and arrange lower-GI endoscopy when microscopic colitis remains plausible.
3Request multiple right- and left-colon biopsies even if mucosa appears normal, clearly stating the clinical suspicion to endoscopy and pathology teams.
4AlternativeReconcile histology with symptoms and exclude a stronger alternative before attaching a durable diagnosis or starting recurrent steroid treatment.

02Active diseaseInduce remission safelyBiopsy-confirmed microscopic colitis is causing clinically important watery diarrhoea.

1Correct dehydration, discuss smoking and nutrition, and review potentially contributory medicines with the original prescriber rather than stopping necessary therapy automatically.
2Use an appropriately licensed oral budesonide formulation under the current SmPC and local formulary, commonly 9 mg in the morning for an induction course.
3Explain expected stool improvement and glucocorticoid cautions, including infection, mood, glucose, blood pressure, eye, bone and adrenal effects despite high first-pass metabolism.
4Review during and at the end of induction, recording stool frequency, nocturnal symptoms, continence and functional recovery rather than relying on a global impression.

03Relapse or non-responseRecheck mechanism before escalationEscalationSymptoms recur after withdrawal or fail to improve during a credible induction course.

1Confirm adherence, exact formulation, treatment duration and whether the current stools still match the original watery phenotype.
2Revisit histology and test for infection, bile acid diarrhoea, coeliac disease or another malabsorptive cause selected by the revised history.
3Refer to gastroenterology for lowest-effective-dose maintenance when relapse is frequent, with a planned review of continuing benefit and steroid toxicity.
4Use specialist multidisciplinary advice for genuinely refractory disease; avoid indefinite empirical prednisolone, repeated antibiotics or unsupported immunosuppression in primary care.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

First-line anti-inflammatory induction treatment that often reduces watery stool frequency and urgency while limiting, not eliminating, systemic steroid exposure.

Oral budesonide

For active microscopic colitis, use the selected licensed formulation at 9 mg each morning for the SmPC-defined induction course, usually up to eight weeks.

Check the formulation, hepatic impairment, infection, diabetes, hypertension, osteoporosis, glaucoma, cataract, psychiatric history and CYP3A interactions. Tapering and maintenance differ by product and specialist plan.

Maintains symptom control in selected relapsing disease when repeated withdrawal produces important recurrence and alternative causes have been addressed.

Maintenance budesonide

For frequent relapse after successful induction, a gastroenterologist may use 6 mg each morning or the lowest effective licensed regimen with scheduled reassessment.

Do not regard long-term budesonide as risk free. Reassess need by twelve months or sooner under the relevant SmPC, minimise exposure and monitor systemic glucocorticoid complications.

Treats coexisting bile acid malabsorption and can reduce watery stool output when that mechanism contributes to persistent symptoms.

Bile acid sequestrant

Use the locally recommended preparation and titration only when bile acid diarrhoea is established or specialist assessment supports a monitored therapeutic trial.

Constipation, bloating and binding of other oral medicines are important; separate administration as product guidance requires and do not let response substitute for appropriate colonic biopsies.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Dehydration and electrolyte loss

Frequent watery stool can cause volume depletion, kidney injury and potassium or magnesium abnormalities, particularly in frailty.

Weight loss and social impairment

Urgency, nocturnal stool and incontinence reduce intake, sleep and confidence, producing weight loss and major quality-of-life restriction.

Relapsing or treatment-dependent disease

Symptoms often recur after successful induction, requiring maintenance decisions that balance disease burden with cumulative corticosteroid and bone risk.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Track daily stool frequency, Bristol form, night-time episodes, urgency and incontinence so response and relapse are measured consistently.
Recheck weight, hydration, renal function and electrolytes when output is high, particularly in frail adults or those taking diuretics.
During repeated or maintenance budesonide, review blood pressure, glucose, infection, mood, eyes, skin and bone or adrenal risk according to cumulative exposure.
Record every proposed medicine withdrawal, the prescriber agreement and whether symptoms changed, avoiding a permanent inaccurate allergy or causality label.
Escalate new bleeding, anaemia, fever, progressive pain or weight loss as a changed presentation rather than assuming another routine relapse.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Normal mucosa can inflame

Conventional endoscopic appearance mainly reflects surface architecture. Microscopic immune and collagen changes can produce severe secretory diarrhoea without the ulcers or friability expected in ulcerative colitis.

Biopsy geography matters

Histological changes may vary across the colon. Labelled proximal and distal samples improve detection and help the pathologist judge a borderline collagen band or lymphocyte count.

Association is not attribution

Commonly implicated medicines are also common in the age group affected. A careful temporal dechallenge can inform causality, whereas indiscriminate cessation may remove necessary gastroprotection or mental-health treatment.

Relapse asks two questions

First decide whether inflammation has returned; then decide whether repeated treatment benefit outweighs cumulative steroid harm. Stool recurrence alone does not automatically answer either question.

Cancer surveillance differs

Microscopic colitis does not carry the same chronic dysplasia pathway as extensive ulcerative colitis. Routine bowel-cancer screening and any separate polyp or family-history schedule still apply.

11Common pitfallsFrequent interpretation and management errors.

01
Rejecting microscopic colitis because colonoscopy reports normal mucosa and no biopsies were taken.
02
Sampling only the rectum or sigmoid and missing more proximal diagnostic histology.
03
Labelling a bloody, febrile or peritonitic presentation as a harmless flare of microscopic colitis.
04
Stopping an essential PPI or antidepressant solely because it appears on an association list.
05
Repeating budesonide indefinitely without checking formulation, relapse mechanism or systemic steroid toxicity.
06
Assuming a mildly raised or normal faecal calprotectin either proves or excludes microscopic colitis.