Neuro: dysimmune neuropathy Weight loss Tumor progression Mechanical obstruction digestive tumor/ENT Oral thrush, bad dental status Digestive surgery: derivation/short bowel syndrome Radiation-induced esophagitis Mucositis in chemotherapy Long-term corticosteroid Toxic: nausea/vomiting in opiates Pain Depression Hypercatabolism related to inflammatory syndrome Loss of autonomy for food Dysimmune gastritis Dysimmune enterocolitis Celiac disease Dysimmune hyperthyroidism Dysimmune hypophysitis Dysimmune adrenal insufficiency Dysimmune diabetes Induced systemic diseases Influenza syndrome, fever Sepsis: infection of the catheter, pneumonia, urinary tract infection, cholangitis, erysipelas, deep infection Thrombosis phlebitis Tumor-specific inflammation (elimination diagnosis) Paraneoplastic ILI reaction to immunotherapy Dysimmune colitis Hyperthyroidism Thrombosis Vasculitis Neurologic Sensory loss Medullary compression/metastatic evolution Carcinomatous meningitis Neurotoxicity previous treatments Paraneoplastic Dysimmune mononeuritis Dysimmune Encephalitis Myelitis Vasculitis Motor deficit Medullary compression/metastatic evolution Carcinomatous meningitis Neurotoxicity previous treatments Paraneoplastic Dysimmune mononeuritis Dysimmune Encephalitis Myelitis Vasculitis Myasthenia Myositis Seizure Brain metastasis and carcinomatous meningitis Infectious encephalitis Neurotoxicity previous Dysimmune encephalitis
treatment Paraneoplastic Cutaneous Rash Anaphylactic or anaphylactoid urticarial (off target effects of conventional drugs) Immune-related hives, eczema (on-target off tumor effects of drugs) Pemphigus Pruritus Cholestasis secondary to liver/pancreatic metastasis Dysimmune hypo/hyperthyroidism Immune-related eczema Respiratory Acute Pneumonia/pleurisy infectious, aspiration pneumonia Thoracic tumor invasion Bronchial tumor compression/ specific pleurisy/lymphangitis carcinomatosis Rib fractures on bone metastases Tumoral hemoptysis Pneumothorax Anemia Overdose of morphine, benzodiazepines Anxiety Dysimmune interstitial lung disease Hydrops, pleurisy autoimmune Dysimmune pericarditis Dysimmune myocarditis Dysimmune myasthenia Acute autoimmune polyradiculoneuropathy Rheumatic Arthralgia Bone metastasis Referred pain of visceral metastasis Thrombosis pathological fracture Dysimmune arthritis Digestive Abdominal pain Tumor compression of the biliary tract, urinary tract, pancreatic ducts Peritoneal tumor invasion Tumor or iatrogenic bowel obstruction Intra-abdominal infection (cholecystis … ) Hypercalcemia Pancreatitis (lithiasis, alcohol … ) Thrombosis Dysimmune enterocolitis Dysimmune pancreatitis Dysimmune gastritis Dysimmune pericarditis Dysimmune myocarditis Dysimmune pleurisy Occlusive syndrome of enteric neuropathy Occlusive syndrome in dysimmune hypothyroidism Acute adrenal insufficiency Ketoacidosis due to dysimmune diabetes Diarrhea Secondary to antibiotic use Enteropathy due to cancer Dysimmune enterocolitis Celiac disease
Clostridium difficile Exocrine pancreatic insufficiency on compression Dysimmune hyperthyroidism Nausea vomiting obstruction by the tumor Carcinomatous peritonitis Carcinomatous meningitis Intracranial hypertension Hypercalcemia Hyponatremia Dysimmune meningitis Dysimmune enterocolitis Ketoacidosis due to dysimmune diabetes Dysimmune adrenal insufficiency Dysimmune nephropathy Dysimmune pancreatitis Dysimmune hepatitis Hepatic Liver Enzymes Elevation Hepatic cancer progression Sepsis Concurrent medication Dysimmune hepatitis Dysimmune myocarditis (AST) Dysimmune myositis (AST) Dysimmune hemolytic anemia (AST) Jaundice, bilirubin elevation GGT and ALP elevation Intrinsic cancer progression, gall, locoregional tumor or extrinsic compression Sepsis Medication, parenteral nutrition Dysimmune hepatitis Sclerosing cholangitis Primary biliary cirrhosis Dysimmune granulomatosis Dysimmune hemolytic anemia (unconjugated bilirubin) Hematologic Anemia chemotherapy toxicity Tumor bleeding Marrow involvement Deficiency Vitamin B9, B12 or martial inflammatory anemia false anemia: hemodilution, splenomegaly, monoclonal peak Dysimmune hemolytic anemia Dysimmune hypothyroidism Dysimmune pancytopenia Immune thrombocytopenic purpura Thrombotic microangiopathy: TTP, HUS Evans syndrome Thrombocytopenia Marrow involvement chemotherapy toxicity Disseminated intravascular coagulation due to tumor progression Myelodysplasia Heparin-induced thrombocytopenia Immune thrombocytopenic purpura (ITP) syndrome Autoimmune pancytopenia Thrombotic microangiopathy: Thrombotic thrombocytopenic purpura (TTP)
Vitamin B12 or folate deficiency Hemolytic uremic syndrome (HUS) Abnormal hemostasis Hepatocellular insufficiency: decreased PT, aPTT, decreased factors II, VII, X and factor V, fibrinogen decreased. Vitamin K deficiency: decreased PT, aPTT, factors of the vitamin K-dependent consumption: II, VII, IX, X, proteins C and S; Factor V is normal DIC: decreased PT, APTT prolongation, thrombocytopenia, hypofibrinogenemia, reduction of factors V, PDF and increased D-dimer. Immune thrombocytopenic purpura (ITP) Evans syndrome Dysimmune pancytopenia Thrombotic microangiopathy (MAT): Thrombotic thrombocytopenic purpura (TTP) Hemolytic uremic syndrome (HUS) Acquired hemophilia A Thrombosis tumor compression Cancer relapse Endovascular Tumor progression Heparin-induced thrombocytopenia Iatrogeny due to other drugs (revlimid, bortezomib) Antiphospholipids antibody syndrome (APLS) Renal Elevated serum creatinine Tumor obstruction Renal toxicity related to intercurrent medicines, an iodinated contrast agent injection Tumor lysis syndrome Dysimmune nephropathy Thrombotic thrombocytopenic purpura (TTP) Hemolytic uremic syndrome (HUS) Hypokalemia Deficiency of potassium intake: anorexia, vomiting, taking laxatives, diuretics, exclusive artificial nutrition Excess extrarenal losses: Acute diarrhea, digestive fistulas Dysimmune nephropathy Colitis, autoimmune enterocolitis Hyponatremia SiADH due to tumor in lung, brain … Iatrogenic: diuretics, potomania Excess of hypotonic perfusions False hyponatremia: hyperglycemia … Dysimmune nephropathy Dysimmune colitis, dysimmune enterocolitis Dysimmune hypothyroidism Dysimmune adrenal failure (central or peripheral) Dysimmune diabetes
example, a decrease of hemoglobin value below laboratory normal values (13 and 12 g/l for men and women, respectively) is often minimized until it falls below 10 g/dl because oncologists usually reason according to classic transfusion threshold. In the case of patients treated by immunotherapies, oncologists should always consider patients on a case-by-case basis: patient's values at baseline are each patient's reference values. Alert for monitoring or exploration should be triggered according to baseline variations. Also physicians should be aware that irAE can slowly alter biological parameters over time and a decrease or increase of such parameters should be envisioned over multiple time points. In case of a nonsevere and nonspecific symptom, close monitoring should be conducted to evaluate its evolution and easily repeat proper laboratory or imaging tests. Treat Key Points of Immune-related Adverse Events Management Here are the key points to be handled when a patient is developing an irAE: close monitoring ambulatory versus inpatient care symptomatic treatment immunotherapy suspension or termination corticotherapy and associated measures immunosuppressive drugs patient information on how to self-monitor clinical elements The typical clinical management of irAEs is described in . Table 4. Typical management of irAEs grade Ambulatory versus inpatient care Corticosteroids Other immunosuppressive drugs Immunotherapy 1 Ambulatory Not recommended Not recommended Continue 2 Ambulatory Topical steroids or Systemic steroids oral 0.5–1 mg/kg/day Not recommended Suspend temporarilya 3 Hospitalization Systemic steroids Oral or i.v. 1–2 mg/kg/day for 3 days then reduce to 1 mg/kg/day To be considered for patients with unresolved symptoms after 3–5 days of steroid course Organ Specialist referral advised Suspend and discuss resumption on risk/benefit ratio with patient 4 Hospitalization consider Systemic steroids i.v. To be considered for patients with Discontinue permanently