Table 7.

Grading of hypersensitivity reactions, anaphylaxis, acute infusion reactions, and cytokine-release syndrome

Reaction	Grade I	Grade II	Grade III	Grade IV	Grade V
HSR [165]	Transient flush, rash or exanthema, drug-induced fever <38 °C	Flush, rash, exanthema, urticaria, and dyspnea, drug-induced fever ≥38 °C	Symptomatic bronchospasm with or without urticaria, hypotension, and angioedema	Anaphylaxis	Death
Anaphylaxis [166]	Pruritus, flush, urticaria, angioedema	Pruritus, flush, urticaria, angioedema, nausea, cramping, rhinorrhea, hoarseness, dyspnea, tachycardia, blood pressure change, arhythmia, vomiting	Pruritus, flush, urticaria, angioedema, vomiting, defecation, laryngeal edema, bronchospasm, cyanosis, shock	Pruritus, flush, urticaria, angioedema, vomiting, defecation, respiratory arrest, cardiac arrest	Death
Acute IR [165]	Mild reaction	Requires therapy interruption, prophylactic medication indicated for ≥24 h	Prolonged symptoms or not rapidly responsive to intensive medication	Life-threatening Need for vasopressor or ventilatory support	Death
	Grade I and II reactions: chills, dizziness, dyspnea, fever, flushing, headache, myalgia, rigors, and mild hypotension		Grades III and IV: anaphylaxis, bronchospasms, cardiac dysfunction, severe hypotension requiring medication, and other symptoms
CRS [167]	Fever, constitutional symptoms	Hypotension responding to fluids or low dose vasopressors, grade 2 organ toxicities	Schock requiring high dose/multiple vasopressors, Hypoxia requiring ≥ 40% Fractional Inspired O2 Concentration (FiO2), grade 3 organ toxicities, grade 4 transaminases	Mechanical ventilation, grade 4 organ toxicities (excl. transaminases)	–
	Mild cases may show flu-like symptoms. Grade III and IV shows life-threatening hematologic, cardiovascular, neurological, pulmonary, and renal involvement and symptoms. Unspecific: anorexia, fever, fatigue, nausea, vomiting Extremity: arthralgia, edema, myalgia, rash, and rigor Gastrointestinal: diarrhea, hepatomegaly, splenomegaly Hematologic: coagulopathy, elevated liver enzyme, febrile neutropenia, disseminated intravascular coagulation, liver failure Neurologic: aphasia, confusion, headache, delirium, paresis, seizures Respiratory: hypoxia, pulmonary edema, respiratory failure, tachypnea Cardiac: acute heart failure, arrhythmia, hypotension, stress cardiomyopathy, tachycardia, QT prolongation Renal: acute kidney injury, acute renal failure

HSR hypersensitivity reaction, IR infusion reaction, CRS cytokine release syndrome