Skip to textbook content
Doctor’s PassportTextbook
TopicsAll topics

Loading topic navigation…

Textbook navigation
TopicsAll topics

Loading topic navigation…
← Oncology and palliative care indexChapter sections
OverviewAetiologyPathophysiologyClinical features and red flagsInvestigationsDifferential diagnosisManagementComplicationsMonitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
Full textbook13 sectionsOpen only what you need
Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.

Immune-related adverse events

Oncology and palliative care · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

RapidFull
!
Time-critical presentation

Suspect immediately dangerous immune toxicity with hypoxia, chest pain, arrhythmia, severe weakness, dysphagia, seizure, confusion, visual loss, hypotension, severe abdominal pain, blood in stool, jaundice or major biochemical disturbance. Hold immunotherapy, contact acute oncology and the relevant organ specialist, stabilise physiology and treat infection concurrently when plausible.

Overview

Recognise and grade multisystem immune-related adverse events, exclude infection and cancer complications in parallel, deliver organ-specific immunosuppression or hormone replacement, and plan a safe taper and rechallenge decision.

Immune checkpoint blockade can break tolerance against normal tissue. Clinical phenotype varies by organ and can be isolated or multisystem. Skin rash and thyroid dysfunction are common; myocarditis and severe neurological events are less common but disproportionately dangerous. Toxicity can persist because activated immune cells continue after the medicine has cleared.

Diagnosis is syndromic and exclusionary. Chest CT may support pneumonitis but infection and embolism coexist; diarrhoea may be immune colitis or infection; transaminitis may reflect tumour, obstruction, virus or another medicine. Endocrine tests require paired hormone interpretation. Myocarditis work-up integrates symptoms, ECG, troponin, imaging and specialist judgement; one normal early value does not overrule progression.

Treatment begins with holding exposure and supporting physiology. Corticosteroid route and intensity follow organ and grade; prolonged taper reduces relapse. Some steroid-refractory events use infliximab, mycophenolate, intravenous immunoglobulin or other agents, but selection differs by organ and contraindication. Endocrine deficiencies often require lifelong replacement and alert-card education.

Aetiology

01

Checkpoint pathway blockade

PD-1, PD-L1 or CTLA-4 inhibition removes regulatory signals that normally restrain activated T cells and protect self-tissue.

02

Host susceptibility

Pre-existing autoimmunity, organ reserve, microbiome, combination therapy and incompletely understood immune factors influence which toxicity develops.

03

Persistent immune activation

Expanded immune clones and inflammatory signalling can continue after circulating medicine declines, explaining delayed and prolonged adverse events.

Pathophysiology

  1. 1
    Self-tolerance is disrupted

    Activated T cells recognise shared or cross-reactive antigens, recruit inflammatory cells and direct immune injury against previously healthy organ tissue.

  2. 2
    Tissue-specific inflammation develops

    Cellular infiltration, cytokines, autoantibodies and complement produce organ patterns such as colitis, pneumonitis, hepatitis, myocarditis or endocrinopathy.

  3. 3
    Organ reserve determines severity

    Small amounts of inflammation can be catastrophic in myocardium, respiratory muscle or pituitary-adrenal function, while larger skin involvement may remain stable.

  4. 4
    Damage may become permanent

    Destruction of hormone-producing cells, myocardium or neural tissue can leave lasting deficits even after systemic inflammation is suppressed.

Clinical features and red flags

Pneumonitis pattern

New cough, breathlessness, hypoxia or inflammatory CT change requires urgent assessment for immune injury, infection, embolism and progression.

Colitis pattern

Increased stool frequency, abdominal pain, blood, fever or dehydration can progress to toxic dilatation or perforation.

Hepatitis pattern

Rising transaminases or bilirubin may be asymptomatic but requires medicine, viral, obstructive and metastatic assessment before attribution.

Endocrine crisisRed flag

Hypotension, hyponatraemia, hypoglycaemia, severe hyperglycaemia or polyuria can indicate adrenal, pituitary, pancreatic or thyroid emergency.

Cardiac-neuromuscular overlapRed flag

Chest pain, ptosis, dysphagia, proximal weakness and troponin or CK elevation may represent rapidly fatal overlapping myocarditis and myositis.

Investigations

  1. 01
    Organ-focused blood panelFirst step
    Why
    Detect injury in the symptomatic system and screen multisystem involvement.
    Interpretation and limitations
    Use blood count, renal, hepatic, glucose, electrolytes, thyroid, cortisol, troponin and CK selectively but broadly when overlap is possible.
  2. 02
    Cultures and infection testing
    Why
    Identify infection before and during immunosuppression.
    Interpretation and limitations
    Take samples promptly without delaying treatment of severe immune physiology; negative tests do not instantly exclude infection.
  3. 03
    Chest CT and oxygenation
    Why
    Characterise suspected pneumonitis and competing thoracic disease.
    Interpretation and limitations
    Pattern and distribution support but do not prove immune toxicity; embolism, infection and progression need parallel consideration.
  4. 04
    Stool studies and bowel assessment
    Why
    Separate infection from colitis and identify severe complications.
    Interpretation and limitations
    Grade from baseline, test pathogens and involve gastroenterology for imaging or endoscopy when severe, persistent or atypical.
  5. 05

Differential diagnosis

01

Infection

Bacterial, viral, fungal and opportunistic infection can reproduce fever, lung, bowel, liver and neurological syndromes and may coexist during immunosuppression.

02

Cancer progression

New metastasis, obstruction, lymphangitic disease or paraneoplastic effects can mimic organ inflammation and require imaging or tissue correlation.

03

Other treatment toxicity

Chemotherapy, targeted therapy, radiotherapy and supportive medicines can injure the same organs through distinct non-immune mechanisms and overlapping clinical presentations.

04

Thrombosis or unrelated disease

Pulmonary embolism, acute coronary syndrome, inflammatory bowel disease and endocrine illness remain active alternatives during cancer treatment.

Management

01RecogniseHold and gradeFirst stepA new organ symptom or biochemical abnormality occurs after checkpoint exposure.+
  1. 1Hold immunotherapy when clinically important toxicity is plausible and assess ABCDE stability, baseline function and all involved organs.
  2. 2Notify acute oncology and the relevant specialist early for cardiac, neurological, pulmonary, hepatic, bowel or endocrine concern.
  3. 3Investigate infection, progression, thrombosis and other medicines concurrently rather than waiting to prove an immune mechanism.
02SuppressTreat the threatened organModerate, severe or rapidly progressive immune toxicity is likely.+
  1. 1Start the protocol's organ- and grade-specific corticosteroid promptly, using intravenous treatment and critical care for unstable disease.
  2. 2Give hormone replacement for endocrine failure, including emergency hydrocortisone before thyroid hormone when ACTH deficiency is possible.

Complications

01

Organ failure

Pneumonitis, myocarditis, hepatitis, colitis and neurological inflammation can progress rapidly to respiratory, circulatory, hepatic or cerebral failure.

02

Endocrine crisis

ACTH deficiency, insulin deficiency and severe thyroid dysfunction can cause shock, hypoglycaemia, ketoacidosis or dangerous electrolyte disturbance.

03

Immunosuppression harm

Prolonged corticosteroid and second-line immunosuppression increases infection, dysglycaemia, muscle, bone, psychiatric and gastrointestinal morbidity during recovery.

04

Permanent treatment loss

Severe toxicity may preclude further checkpoint therapy and leave persistent disability, changing both cancer control and quality of life.

Monitoring and follow-up

  • Trend the organ-specific clinical and laboratory endpoint frequently until recovery is secure, not merely until symptoms first improve.
  • Monitor infection and corticosteroid complications throughout treatment and taper, including glucose, blood pressure, mood, muscle and bone risk.
  • Repeat endocrine testing and maintain permanent replacement and emergency identification when recovery does not occur.
  • Record maximal grade, treatment, taper, residual deficit and rechallenge decision in every relevant care record.
  • After rechallenge, use a pre-agreed surveillance and stop plan with rapid access for recurrence in the same or a new organ.

Special situations

Diagnosis can coexist

Immune pneumonitis and bacterial infection, or colitis and enteric infection, can occur together and may need simultaneous treatment.

Grade is organ-specific

A small biochemical change can be critical in myocarditis, while a visible rash may be extensive but physiologically stable.

Endocrine toxicity persists

Inflammation may settle while hormone-producing cells remain destroyed, creating lifelong replacement and emergency-planning needs.

Steroid response is evidence

Improvement supports immune inflammation but does not prove it; infection can temporarily appear better and recur under immunosuppression.

Rechallenge is a new decision

Previous consent does not cover every later risk after severe toxicity; benefit and alternatives must be revisited.

Common pitfalls

  1. 01

    Excluding toxicity because the last dose was months ago.

  2. 02

    Assuming one organ explains all symptoms.

  3. 03

    Starting thyroid replacement before cortisol protection.

  4. 04

    Giving the same second-line agent for every organ.

  5. 05

    Tapering corticosteroid after symptom improvement alone.

  6. 06

    Rechallenging without documented multidisciplinary review.

Practice

Two practice questions

Your practice draft is saved in this browser.

Question 1 of 2
0 correct
Oncology and palliative careOriginal SBA

Steroid-refractory toxicity

A patient with suspected severe immune-mediated hepatitis does not improve after initial protocol corticosteroid treatment. What is the safest next principle?

Choose one answer, then submit
← Rapid synopsisBack to overviewAll Oncology and palliative care topics →
Sources and review status7 sources · checked 27 Aug 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

  • MHRA Safety Roundup: checkpoint inhibitor overlap syndromesCurrent warning on potentially fatal myocarditis with myositis or myasthenia gravis overlap.
  • NHS England adult cancer chemotherapy service specificationCurrent requirements for safe, protocol-governed systemic anticancer treatment services.
  • NHS England cancer programmeAcute oncology and multispecialty management of serious immune adverse events.
  • NICE shared decision making recommendationsRechallenge, permanent toxicity and alternative-treatment decisions.
  • ESMO immune-related adverse-event guidelineOrgan-specific grading, corticosteroid ranges, escalation, taper and rechallenge principles.
  • Society for Endocrinology adrenal-crisis guidanceImmediate hydrocortisone and fluid doses for adult adrenal crisis.
  • Society for Endocrinology checkpoint endocrine emergenciesCortisol-first sequencing and emergency replacement for checkpoint-induced endocrine failure.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem ·

Key points

  • Immune-related adverse events follow checkpoint activation and may affect skin, bowel, liver, lung, endocrine, kidney, nervous, cardiac, eye, joint or blood systems.
  • Timing ranges from days after the first dose to months after treatment ends, so previous immunotherapy remains relevant in every acute history.
  • Grade from the patient's baseline and organ threat, not symptom count alone; mild fatigue can precede adrenal crisis, myocarditis or neurological overlap.
  • Hold checkpoint treatment for clinically important suspected toxicity and investigate immune injury, infection, progression, thrombosis and other medicines together.
  • Corticosteroid is first-line for many moderate and severe events, with organ-specific dosing and taper; endocrine failure usually needs hormone replacement rather than high-dose steroid alone.
  • Myocarditis, pneumonitis, severe colitis, hepatitis and neuromuscular overlap require early specialist and often critical-care involvement.
  • Failure to improve at the protocol-defined interval prompts diagnostic reassessment and organ-specific second-line immunosuppression rather than indefinite steroid escalation.
  • Rechallenge is not automatic after recovery; severity, organ, residual deficit, cancer benefit and alternative therapy are reviewed in MDT.
ECG, troponin, CK and cardiac imaging
Why
Investigate possible myocarditis and neuromuscular overlap.
Interpretation and limitations
Escalate early to cardio-oncology and neurology; serial change and clinical trajectory matter when initial tests are equivocal.
  • 3Second lineIf response is inadequate, reassess diagnosis and use organ-specific second-line immunosuppression rather than a generic agent across all toxicities.
    • 03RecoverTaper and decide future therapyObjective organ recovery begins after treatment.+
    1. 1Taper corticosteroid over the recommended period while monitoring the relevant organ marker and infection or steroid complications.
    2. 2Document permanent deficits, sick-day rules and long-term follow-up, especially for adrenal, pituitary, thyroid, pancreatic or cardiac injury.
    3. 3AlternativeDiscuss rechallenge in MDT with explicit recurrence risk, previous cancer benefit, alternative treatment and the patient's informed preference.
    Key medicines and prescribing safety2 treatments · regimens, roles and cautions+
    Suppresses clinically important checkpoint-induced inflammation while infection, progression, thrombosis and other causes are investigated in parallel.

    Systemic corticosteroid for significant immune toxicity

    Many grade 2 toxicities start oral prednisolone 0.5–1 mg/kg/day; many grade 3–4 toxicities use intravenous methylprednisolone or equivalent 1–2 mg/kg/day. The threatened organ can require a different or pulse regimen, so use the current organ-specific protocol and taper commonly over at least 4–6 weeks after objective improvement.

    Myocarditis, neurological overlap, pneumonitis, colitis and hepatitis need early specialist input and may require different rescue therapy. Monitor infection, glucose, blood pressure, mood, myopathy, gastrointestinal and bone harm; rapid taper risks relapse.

    Life-saving glucocorticoid replacement for adrenal crisis from checkpoint-related adrenal or pituitary failure; draw cortisol first only if doing so causes no treatment delay.

    Hydrocortisone for suspected adrenal crisis

    Give 100 mg intravenously or intramuscularly immediately, then 200 mg over 24 hours by continuous intravenous infusion or 50 mg intravenously or intramuscularly every 6 hours, with rapid 0.9% sodium chloride resuscitation and endocrine input.

    Do not delay treatment for diagnostic certainty. Protect cortisol before levothyroxine when ACTH deficiency is possible, monitor glucose and electrolytes, then convert to maintenance replacement with sick-day rules and emergency identification.

    Content changes
    Authoring stateComplete draftClinical stateAwaiting reviewJurisdictionUnited Kingdom