Podcast Beta
Questions and Answers
Immune checkpoint inhibitors primarily treat ______.
malignancy
Common immune-related adverse effects include diarrhea, colitis, and ______.
dermatitis
Many adverse effects occur within the first ______ months of starting therapy.
6
Differentiating immune-related adverse effects from other oncologic complications can be ______.
Signup and view all the answers
A detailed history should include signs, symptoms, and the specific ______ the patient is receiving.
Signup and view all the answers
Infection and immune-related adverse effects are often ______ to differentiate.
Signup and view all the answers
Symptoms of immune-related adverse effects may be mild or ______ at onset.
Signup and view all the answers
Fever is ______ likely in an immune-related adverse effect.
Signup and view all the answers
Adrenal insufficiency is one of the ______ diagnoses that can occur.
Signup and view all the answers
Sepsis is classified as a potential ______ emergency.
Signup and view all the answers
Grade 1 immune-related adverse effects are typically ______ but abnormal laboratory values.
Signup and view all the answers
Treatment may involve corticosteroids like ______ for grade 2 immune-related adverse effects.
Signup and view all the answers
Toxic ingestion can involve substances like ______ and salicylates.
Signup and view all the answers
______ storm is a severe endocrine emergency that can occur.
Signup and view all the answers
Grade 5 immune-related adverse effects can result in ______.
Signup and view all the answers
Patients with suspected immune-related adverse effects should receive ______ consultation.
Signup and view all the answers
Endocrinopathy is present in up to ______% of patients, most commonly involving the pituitary, thyroid, or adrenal glands.
Signup and view all the answers
Patients with primary hypothyroidism typically present with fatigue, weight gain, constipation, depression, and ______.
Signup and view all the answers
A full skin exam is essential to assess for findings such as maculopustular rash, vitiligo, and ______.
Signup and view all the answers
For grade 1 immune-related adverse effects, the patient should take oral ______ and a class I topical corticosteroid.
Signup and view all the answers
Patients presenting with nonspecific symptoms such as weakness, fatigue, headache, and ______ may indicate endocrine dysfunction.
Signup and view all the answers
Hyperthyroidism may present with symptoms like diaphoresis, palpitations, tremor, dyspnea, diarrhea, and ______.
Signup and view all the answers
In patients with drug reactions, a differential diagnosis should include atopic dermatitis, viral ______, and drug toxicity.
Signup and view all the answers
Grade 3-4 immune-related adverse effects require systemic corticosteroids and ______ consultation while in the ED.
Signup and view all the answers
The most common finding is new or progressive bilateral pulmonary infiltrates with ground glass ______.
Signup and view all the answers
Bronchoscopy for severe ______ may be needed during hospitalization to differentiate infection from pneumonitis.
Signup and view all the answers
For grade 2 immune-related adverse effects, provide supplemental ______, prednisone, and antibiotics.
Signup and view all the answers
Patients with grade 3-4 immune-related adverse effects may require ______ support.
Signup and view all the answers
Prophylactic therapy for Pneumocystis jirovecii is recommended with trimethoprim-______ in those with radiographic findings of pneumonitis.
Signup and view all the answers
Patients may present with palpitations, shortness of breath, edema, or ______.
Signup and view all the answers
Dysrhythmias such as blocks, supraventricular and ventricular ______ have been described in patients.
Signup and view all the answers
Antifungal therapy should be considered in admitted patients who do not respond to antibiotics and ______.
Signup and view all the answers
Diagnostic tests include ECG, electrolytes, renal and liver function tests, TSH, coagulation panel, troponin, and brain natriuretic ______.
Signup and view all the answers
Management of patients should be based on symptoms and ______ evaluation.
Signup and view all the answers
Patients with unstable tachycardias require ______.
Signup and view all the answers
If pericardial effusion is present with ______, intravenous fluid resuscitation and drainage are recommended.
Signup and view all the answers
Patients with myocarditis may be treated with corticosteroids, and for severe cases, ______ 1,000 mg/day intravenous is recommended.
Signup and view all the answers
Neurologic manifestations are rare, accounting for ______% of immune-related adverse effects.
Signup and view all the answers
Myasthenia gravis typically presents with fluctuating, fatigable ______, especially in the ocular and bulbar muscles.
Signup and view all the answers
Guillain-Barré syndrome presents with ascending weakness and decreased or ______ reflexes.
Signup and view all the answers
Study Notes
Immune Checkpoint Inhibitors
- Immunotherapy using checkpoint inhibitors has become a primary treatment option for malignancy.
- These medications often produce an excessive inflammatory response, leading to immune-related adverse effects, impacting nearly every organ system.
- Immune-related adverse effects (iRAEs) differ from those observed with standard chemotherapy or radiation.
- Common iRAEs affect the gastrointestinal, dermatologic, pulmonary, and endocrine systems.
- iRAEs are often seen within the first 6 months of starting therapy and can occur even after therapy discontinuation.
Gastrointestinal iRAEs
- The most common gastrointestinal iRAEs include diarrhea and colitis.
Dermatologic iRAEs
- Dermatitis is a common dermatologic iRAE.
Pulmonary iRAEs
- Pneumonitis is a common pulmonary iRAE.
- Bronchoscopy for severe pneumonitis may be needed during hospitalization to differentiate infection from pneumonitis.
Endocrine iRAEs
- Hypophysitis (inflammation of the pituitary gland) is a common endocrine iRAE.
- Endocrinopathies, including thyroid disorders and adrenal insufficiency, may require temporary discontinuation of immune checkpoint inhibitors.
Severity of iRAEs
- The severity of iRAEs is graded on a scale of 1 to 5, with grade 1 being asymptomatic and grade 5 being death.
- Less severe iRAEs (grades 1 and 2) are more frequent, while more severe iRAEs (grades 3 and 4) are life-threatening but rare.
- All patients with suspected iRAEs should be referred to oncology.
Management of iRAEs
- Treatment depends on the specific complication and grade of the iRAE.
- For most grade 1 iRAEs, the immune checkpoint inhibitor should be continued with close monitoring, except in cases of specific organ toxicities like adrenal, renal, neurologic, microangiopathic hemolytic anemia, hemophilia, and cardiac, where discontinuation should be considered.
- For grade 2 iRAEs, the immune checkpoint inhibitor should be held and may be resumed when symptoms and studies return to grade 1.
- Corticosteroids, such as prednisone (0.5-1 mg/kg/day), may be considered.
- Grade 2 endocrinopathies may require temporary cessation of immune checkpoint inhibitors until acute symptoms have resolved.
Dermatologic iRAE Assessment
- A complete skin exam is essential.
- Assess medication list, systemic symptoms and hemodynamics, total body surface area involved, presence of bullae, and mucosal involvement.
- Inquire concerning the duration of the skin changes, involved skin areas, and how the rash has changed.
- Patients may present with maculopustular rash, vitiligo, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis, bullae, or drug reaction with eosinophilia and systemic symptoms.
Dermatologic iRAE Differential Diagnosis
- Atopic or contact dermatitis, viral exanthem, drug toxicity, erythema multiforme, or infection should be considered.
Dermatologic iRAE Diagnostic Tests
- Laboratory assessment should include CBC with differential, electrolytes, liver and renal function tests, creatine kinase (CK), inflammatory markers, and coagulation panel.
- Dermatology consultation is recommended.
Dermatologic iRAE Grading
- Grade 1: Nonlocalized rash involving 30% of total body surface area; intense pruritis limiting activities of daily living; SJS or toxic epidermal necrolysis present; full thickness dermal ulceration, necrotic bullae, or hemorrhagic findings.
Dermatologic iRAE Treatment
- For grade 1 iRAEs: oral antihistamines, class I topical corticosteroid, oncology follow-up, and dermatology referral.
- For grade 2 iRAEs: oral antihistamines, topical corticosteroids, systemic corticosteroids, oncology, and dermatology follow-up.
- For grades 3-4 iRAEs: systemic corticosteroids, dermatology consultation, admission, and potential burn center care if SJS or toxic epidermal necrolysis is diagnosed.
Endocrine iRAE Clinical Presentation
- Endocrinopathy occurs in up to 10% of patients, most commonly after 9-10 weeks of therapy.
- Commonly affects the pituitary, thyroid, or adrenal glands, 9-10 weeks after therapy initiation
- Patients present with nonspecific symptoms like weakness, fatigue, headache, nausea, and vomiting, making diagnosis difficult.
- Primary hypothyroidism is the most common endocrinopathy, presenting with fatigue, weight gain, constipation, depression, and cold intolerance.
- Hyperthyroidism may present with diaphoresis, palpitations, tremor, dyspnea, diarrhea, and weight loss.
Pulmonary iRAE Clinical Presentation
- The most common finding is new or progressive bilateral pulmonary infiltrates with ground glass changes.
- Infiltrates are often bilateral but usually asymmetric.
- Imaging may demonstrate cryptogenic organizing pneumonia, nonspecific interstitial pneumonitis, hypersensitivity pneumonitis, and usual interstitial pneumonitis with pulmonary fibrosis.
Pulmonary iRAE Grading
- Grade 1: Asymptomatic
- Grade 2: Mild to moderate hypoxia, symptoms limit activities of daily living
- Grades 3-4: Severe symptoms, worsening/severe hypoxia
Pulmonary iRAE Treatment
- For grade 1 iRAEs: monitor symptoms and oxygen saturation, return if either worsen, pulmonology referral, and oncology follow-up.
- For grade 2 iRAEs: supplemental oxygen, prednisone (1-2 mg/kg/day), antibiotics, admission, pulmonology consultation, and potential bronchoscopy with biopsy.
- For grades 3-4 iRAEs: methylprednisolone (2 mg/kg/day intravenous), antibiotics, respiratory support, potential intravenous immunoglobulin, cyclophosphamide, infliximab, or mycophenolate if corticosteroids do not result in improvement, pulmonology, infectious disease, and oncology consultation, admission, and often ICU care.
- Prophylactic therapy for Pneumocystis jirovecii with trimethoprim-sulfamethoxazole is recommended in those with radiographic findings of pneumonitis.
- Antifungal therapy should be considered in admitted patients who do not respond to antibiotics and corticosteroids.
Cardiac iRAE Clinical Presentation
- Patients may present with palpitations, shortness of breath, edema, or chest pain.
- Dysrhythmias (e.g., blocks, supraventricular and ventricular tachycardias), myocarditis, takotsubo cardiomyopathy, and pericarditis/myopericarditis have been described.
Cardiac iRAE Diagnostic Tests
- ECG, electrolytes, renal and liver function tests, TSH, coagulation panel, troponin, and brain natriuretic peptide are recommended.
- Imaging should include chest x-ray and bedside echocardiography to evaluate ventricular function, wall abnormalities, and the presence of an effusion.
Cardiac iRAE Treatment
- Management is based on patient symptoms and ED evaluation.
- If positive biomarkers and/or an abnormal ECG are found, cardiology should be consulted.
- Patients with unstable tachycardias require cardioversion, while those with unstable bradycardias should be treated with chronotropic agents.
- Severe dysrhythmias may require pacemaker insertion.
- Heart failure should be treated with standard therapies based on hemodynamics and volume states.
- If pericardial effusion is present with tamponade, intravenous fluid resuscitation and drainage are recommended.
- Corticosteroids are recommended for those with myocarditis and ventricular dysrhythmias due to iRAEs.
- For mild/moderate disease, prednisone (1-2 mg/kg/day) is recommended, but for severe disease or those not responsive to previous regimens, methylprednisolone (1,000 mg/day intravenous) is recommended.
- Further immunosuppression (e.g., mycophenolate, infliximab) may be needed.
- Most patients with cardiac iRAEs will require admission for monitoring and oncology and cardiology consultation.
Neurologic iRAE Clinical Presentation
- Neurologic manifestations are rare, accounting for 1%-6% of iRAEs.
- Patients may present with a variety of neurologic signs and symptoms, including weakness or Bell’s palsy.
- Myasthenia gravis typically presents with fluctuating, fatigable muscles, especially the ocular and bulbar muscles.
- Guillain-Barré syndrome presents with ascending weakness and decreased/absent reflexes but may begin with pain and sensory changes in the lower extremities.
- Respiratory muscle involvement may result in respiratory failure.
- Transverse myelitis presents with bilateral acute/subacute weakness and sensory changes, typically at a specific spinal level but preserved/increased reflexes.
- Encephalitis presents with altered mental status, headache, focal neurologic deficits, and/or seizures.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
This quiz covers the essential aspects of immune checkpoint inhibitors in immunotherapy, focusing on immune-related adverse effects (iRAEs) across various organ systems. Discover the common iRAEs associated with gastrointestinal, dermatologic, pulmonary, and endocrine systems, and understand their implications during treatment.
