Managing Immunotherapy Related Organ Toxicities: A Practical Guide

Preface
Introduction
Contents
Contributors
Chapter 1: Anesthesia
	General Recommendations
	Organ-Specific Treatment Strategies
	References
Chapter 2: Cardiology (Heart)
	Available Immune Checkpoint Inhibitors
	Cardiac Side Effect Profile of Immune Checkpoint Inhibitors
	Mechanisms of Myocardial Toxicity
	ICI-Associated Myocarditis
	Timing Onset of Myocarditis
	Diagnostic Testing Considerations in ICI-Associated Myocarditis
	Troponin
	Natriuretic Peptide
	Electrocardiogram (ECG)
	Echocardiography
	Cardiac Magnetic Resonance (CMR) Imaging
	Endomyocardial Biopsy (EMB)
	Management
	Advanced Management
	Conclusion
	References
Chapter 3: Dermatology (Skin)
	Epidemiology
	Clinical Characteristics
		Morbilliform/Maculopapular Rash (MPR)
		Pruritus
		Eczematous Dermatitis
		Urticaria
		Lichenoid/Lichen Planus-Like Eruption
		Psoriasiform Dermatitis
		Vitiligo
		Granulomatous Dermatitis
		Xerosis
		Autoimmune Bullous Disorders
		Severe Cutaneous Adverse Reactions
		Erythema Multiforme (EM)
		Neutrophilic Dermatoses
		Sweet’s Syndrome (Acute Febrile Neutrophilic Dermatosis)
		Pyoderma Gangrenosum
		Follicular Eruptions
		Rheumatologic Disease
		Dermatomyositis and polymyositis
		Mucosal Toxicities
		Hair Toxicities
		Nail irCAEs
		Less Common irCAEs
			Grover’s Disease
			Keratoacanthoma/Cutaneous Squamous Cell Carcinoma
	Evaluation
		Diagnostic Tests for Specific irCAEs
			Bullous Pemphigoid
			Dermatitis Herpetiformis
			Pemphigus Vulgaris-Like Lesions
			Urticaria
			Hair Toxicities
			Rheumatologic Diseases
	Treatment
		Treatment Pearls
			Pruritus
			Eczematous
			Urticaria
			Lichenoid
			Psoriasiform
			Vitiligo
			Bullous Pemphigoid
			Alopecia
			Mucosal Toxicities (Including Lichenoid Eruptions)
			Nail Toxicities
			Neutrophilic Dermatoses
			Granulomatous
			SCARs
			Erythema Multiforme
			Sarcoidosis
		Treatment Recommendations
	Long-Term Complication and Follow-Up
	References
Chapter 4: Endocrine
	Introduction
	Checkpoint Inhibitor-Induced Hypophysitis
		Epidemiology
		Clinical Characteristics
		Evaluation
		Treatment
		Long-Term Complications and Follow-Up
	Thyroid Dysfunction
		Epidemiology
		Clinical Characteristics
		Evaluation
		Treatment
		Long-Term Complications and Follow-Up
	Primary Adrenal Insufficiency
		Epidemiology
		Clinical Presentation
		Treatment
	Checkpoint Inhibitor-Induced Diabetes
		Epidemiology
		Clinical Characteristics
		Evaluation
		Treatment
		Long-Term Complications and Follow-Up
	References
Chapter 5: Gastroenterology (GI)
	Epidemiology and Risk Factors
		Type of ICI Agent
		Type of Cancer
		The Patient
	Clinical Presentation and Evaluation
		Clinical Presentation
		Clinical Evaluation
		Biochemical and Stool Evaluation
		IMC, Infections, and Its Management
		Imaging
		Endoscopic Evaluation
		Histologic Evaluation
	Treatment of IMC
	Recurrence of IMC
	Surveillance
	Maintenance Therapy
	IMC and Its Impact on Cancer Outcomes
	Future Direction and Scope
	Conclusion
	Immune-Mediated Upper GI Toxicity (from the Mouth to the Ligament of Treitz)
		ICI Mucositis (IMM)
		ICI-Related Esophagitis
		ICI-Related Gastroenteritis
	References
Chapter 6: Hematology
	Autoimmune Hemolytic Anemia
		Epidemiology
		Clinical Characteristics
		Evaluation
		Treatment
			ICI-Related Warm AIHA
			ICI-Related Cold AIHA
		Long-Term Complications and Follow-Up
	Immune Thrombocytopenic Purpura
		Epidemiology
		Clinical Characteristics
		Evaluation
		Treatment
		Long-Term Complications and Follow-Up
	Autoimmune Neutropenia
		Epidemiology
		Clinical Characteristics
		Evaluation
		Treatment
		Long-Term Complication and Follow-Up
	Bone Marrow Failure Syndromes
		Epidemiology
		Clinical Characteristics
		Evaluation
		Treatment
		Long-Term Complications and Follow-Up
	Macrophage Activation Syndrome/Hemophagocytic Lymphohistiocytosis
		Epidemiology
		Clinical Characteristics
		Evaluation
		Treatment
		Long-Term Complications and Follow-Up
	Thrombophilia and Hemostasis Complications
		Epidemiology
		Clinical Characteristics
		Evaluation
		Treatment
		Long-Term Complications and Follow-Up
	References
Chapter 7: Hepatology (Liver and Bile Duct)
	Introductions
	Nomenclature
	Epidemiology
	Pathophysiology
	Clinical Characteristics
	Evaluation
		Initial Assessment
		Imaging
		The Role of Liver Biopsy and Histopathologic Features
	Management and Treatment Options
		Summary of Initial Management Recommendations
		Commentary on Steroid Treatment Strategies
		Cholangiopathic Phenotypes: Immune-Mediated Cholangiopathy or Cholangiohepatitis
		Adjunctive Treatments
		Kinetics of Biochemical Improvement
		Approach to Suspected or Confirmed IMH in the Context of Intrahepatic Primary Tumors or Metastatic Liver Lesions
	Outcomes and Follow-Up
		Overview
		The Risk of Relapse or Flare During the Management of IMH
		Re-challenging with ICI After Recovery from Grade 3–4 IMH
		Mortality in IMH
	Evaluation for Pre-existing Liver Disease and Viral Infections Before Initiating ICI
	Conclusions
	References
Chapter 8: Infectious Diseases
	Overview
		Background
		Sources of Infection
		Impact of the Underlying Malignancy
		Risk Factors
		Timing of Infection (Prior, During, and After Checkpoint Inhibitor Therapy)
		Microbiome Signatures Associated with Response Cancer Therapy and ICIs-Related Toxicity
		Use of Antibiotics in Patients on ICIs
	Screening for Infectious Diseases Prior to Initiation of ICIs and Potential Use of Immunosuppressants
	Antimicrobial Prophylaxis
		Indications
	Management and Outcomes of Common Infections in the Patient Receiving ICIs
		Infections Related to ICIs Use
			Combination Therapy Versus Monotherapy
			As Adjuvants to Chemotherapy
			Overlap Between Clinical Presentation of Infection and Immune Adverse Events
			Organ-Specific Considerations
				Pneumonitis
				Colitis
				Encephalitis
	Sepsis
	Mucositis
		Infections that Can Trigger ICIs Toxicity
	Infection with SARS-CoV-2 in Patients Receiving ICIs
	Vaccination of Patients Receiving ICIs
	Knowledge Gaps and Other Areas of Uncertainty (Table 8.4)
		Adjuvant Use of ICIs to Treat Infection
		Biomarkers That Can Help Differentiate irAEs from Infection
		Tailoring Immunosuppression to Least Dose Effective
			Objective Markers of Net Immunosuppression
		The Need for Antimicrobial and Microbiome Stewardship
	References
Chapter 9: Nephrology (Kidney)
	Introduction
	Incidence and Risk Factors
	Clinical Characteristics of Renal Adverse Events
	Electrolyte and Acid-Base Disturbances
	Renal Pathologies Associated with irAEs
		ATIN
		Proposed Mechanisms of ATIN
		ATN
		GN
		Re-Challenge of ICI in GN Cases
		Proposed Mechanisms of Glomerular Diseases and Vasculitis
	ICI Use in Solid Organ Transplant Recipients
	Long-Term Complications and Follow-Up
	References
Chapter 10: Neurology
	Epidemiology
	Clinical Characteristics
	Evaluation
	Treatment Principles
	Long-Term Complication and Follow-Up
	References
Chapter 11: Ophthalmology (Eye)
	Introduction
	Epidemiology
	Mechanism of IRAEs
	Clinical Characteristics
		Conjunctiva/Cornea
			Keratoconjunctivitis
			Peripheral Ulcerative Keratitis
		Sclera and Episclera
			Episcleritis
			Scleritis
		Uvea (Choroid, Ciliary Body, Iris)
			Uveitis
			Choroidal Neovascularization
		Retina/Optic Nerve
			Cystoid Macular Edema
			Retinal Vasculitis
			Retinal Detachment
			Optic Neuropathy
		Orbital Inflammation
			Orbital Inflammatory Syndrome
			Thyroid Eye Disease
			Giant Cell Arteritis
		Myasthenia Gravis
	Evaluation
	Treatment Algorithm
	Long-Term Complication and Follow-Up
	Prognosis
	Summary
	References
Chapter 12: Pancreas and Gallbladder
	Immune Checkpoint Inhibitor-Mediated Pancreas Injury (ICI-PI)
		Definition and Background
		Grading and Severity
		Epidemiology and Risk Factors
		Clinical Presentation and Management
		Overall Survival and Prognosis
		Is ICI-PI a Third Type of Autoimmune Pancreatitis (AIP)?
	Immune Checkpoint Inhibitor-Mediated Cholecystitis (ICICC)
	References
Chapter 13: Pathology
	Introduction
	Pathological Features of ICIs-Induced Toxicities by Organ/System
	Luminal Gastrointestinal Tract Toxicity
		Hepatobiliary Toxicity
		Pancreatic Toxicity
		Pulmonary Toxicity
		Cardiac Toxicity
		Neuromuscular Toxicity
		Renal Toxicity
	References
Chapter 14: Pulmonology (Lung)
	ICI Pneumonitis
		Introduction
		Clinical Presentation
		Diagnostic Approach
			Imaging Patterns
			Pulmonary Function Testing
			Bronchoscopy
			Lung Biopsy
			Assessment of Severity
		Epidemiology and Risk Factors
			Type of ICI
			Monotherapy vs. Combination Therapy
			Prior Treatment History
			Prior Radiation Therapy
			Type of Malignancy
			Tumor Mutational Burden
			Prior Lung Disease
		Treatment
			Corticosteroids
			Steroid-Refractory Pneumonitis
			IVIg
			Infliximab
			Mycophenolate Mofetil
			Cyclophosphamide
			Aviptadil
		Outcomes After ICIP
			ICI Re-challenge
	ICI Pleural Effusions
	Sarcoidosis-Like Reactions
	ICI-Related Eosinophilic Lung Diseases
	Conclusion
	References
Chapter 15: Rheumatology (Arthritis and Myositis)
	Articular irAE
		Epidemiology
		Clinical Characteristics
		Management
		Long-Term Complications and Follow-Up
	Muscular irAEs
		Epidemiology
		Clinical Characteristics
		Management
		Long-Term Complications and Follow-Up
	Polymyalgia Rheumatica-Like Syndrome
		Epidemiology
		Clinical Characteristics
		Management
		Long-Term Complications and Follow-Up
	Conclusion
	References
Index