Urticaria and Angioedema

Preface to the First Edition
Preface
Contents
Contributors
1: History of Urticaria
	1.1	 Introduction
	1.2	 The Cellular and Molecular Basis of Urticaria: First Steps
	1.3	 The Enigma of Chronic “Idiopathic” Urticaria
	1.4	 Treatment of Urticaria: Antihistamines
	References
2: Aetiopathogenesis of Urticaria
	2.1	 Lessons Learned from Histopathology
	2.2	 A Central Role for the Mast Cell
	2.3	 Mast Cell Mediators of Urticaria
		2.3.1	 Histamine
		2.3.2	 Cysteinyl Leukotrienes and Platelet Activating Factor
	2.4	 Involvement of Other Inflammatory Cells in Urticaria
	2.5	 The Role of Bradykinin in Angioedema
	2.6	 What Causes Mast Cell Mediator Release in the First Place?
	2.7	 Tests for Autoimmune and Autoallergic Urticaria
		2.7.1	 Autologous Serum Skin Test (ASST)
		2.7.2	 Basophil Activation Assays
		2.7.3	 Immunoassays for Autoantibodies in Autoimmune CSU
	2.8	 Conclusions
	References
3: Classification and Diagnosis of Urticaria
	3.1	 Definition
	3.2	 Histology
	3.3	 Classification of Urticaria on the Basis of Its Symptoms, Duration, Frequency, and Causes
	3.4	 Diagnosis of Urticaria
		3.4.1	 Diagnostic Work Up in Acute Urticaria
		3.4.2	 The Diagnostic Work Up in CU
			3.4.2.1	 Assessment of Disease Activity Impact and Control
	References
4: Impact of Chronic Urticaria and How to Measure It
	4.1	 What Makes Chronic Urticaria a Burdensome Condition
		4.1.1	 Physical, Social, and Emotional Burden in Chronic Spontaneous Urticaria
		4.1.2	 Itch, Sleep Impairment, and Psychiatric Comorbidities in Chronic Spontaneous Urticaria
		4.1.3	 Impairment of Daily Activities and Work Productivity in Chronic Spontaneous Urticaria
		4.1.4	 Disease Burden in Chronic Inducible Urticaria
	4.2	 Extent, Pattern, and Drivers of Disease Burden
		4.2.1	 HRQoL Impairment in Chronic Spontaneous Urticaria
		4.2.2	 Drivers of HRQoL in chronic spontaneous urticaria
		4.2.3	 HRQoL Impairment in Chronic Inducible Urticaria
	4.3	 How to Assess Disease Burden in CSU
		4.3.1	 The Use of PROMs Improves Chronic Urticaria Management
		4.3.2	 What PROMs Should Be Used in Chronic Spontaneous Urticaria
		4.3.3	 What PROMs Should Be Used in Chronic Inducible Urticaria
	References
5: Acute Urticaria
	5.1	 Definition
	5.2	 Epidemiology
	5.3	 Clinical Aspects
	5.4	 Aetiology
	5.5	 Natural Course
	5.6	 Diagnosis
	5.7	 Treatment
	References
6: Chronic Spontaneous Urticaria
	6.1	 Definition
	6.2	 Clinical Picture
	6.3	 Epidemiology
	6.4	 Etiopathogenesis
		6.4.1	 Autoallergy and Autoimmunity, Causes of CSU
		6.4.2	 Autoimmunity
		6.4.3	 Stress, Infections, and Food Intolerance, Modulators of CSU
	6.5	 Diagnostic Workup
	6.6	 Therapy
	References
7: Chronic Spontaneous Urticaria and Comorbidities
	7.1	 Introduction
	7.2	 Chronic Inducible Urticaria
	7.3	 Mental Disorders
	7.4	 Autoimmune Diseases
	7.5	 Infection
		7.5.1	 Bacterial Infection
		7.5.2	 Parasitic Infection
		7.5.3	 Viral Infection
		7.5.4	 Fungal Infection
	7.6	 Allergic Diseases
	7.7	 Malignancy
	7.8	 Metabolic Syndrome
	References
8: Inducible Urticarias
	8.1	 Introduction
	8.2	 Symptomatic Dermographism
		8.2.1	 Definition and Clinical Picture
		8.2.2	 Pathogenesis
		8.2.3	 Diagnosis and Differential Diagnosis
		8.2.4	 Treatment and Prognosis
	8.3	 Cold Urticaria
		8.3.1	 Definition and Clinical Picture
		8.3.2	 Pathogenesis
		8.3.3	 Diagnosis and Differential Diagnosis
		8.3.4	 Treatment and Prognosis
	8.4	 Delayed Pressure Urticaria
		8.4.1	 Definition and Clinical Picture
		8.4.2	 Pathogenesis
		8.4.3	 Diagnosis and Differential Diagnosis
		8.4.4	 Treatment and Prognosis
	8.5	 Solar Urticaria
		8.5.1	 Definition and Clinical Picture
		8.5.2	 Pathogenesis
		8.5.3	 Diagnosis and Differential Diagnosis
		8.5.4	 Treatment and Prognosis
	8.6	 Heat Urticaria
		8.6.1	 Definition and Clinical Picture
		8.6.2	 Pathogenesis
		8.6.3	 Diagnosis and Differential Diagnosis
		8.6.4	 Treatment and Prognosis
	8.7	 Vibratory Angioedema
		8.7.1	 Definition and Clinical Picture
		8.7.2	 Pathogenesis
		8.7.3	 Diagnosis and Differential Diagnosis
		8.7.4	 Treatment and Prognosis
	8.8	 Cholinergic Urticaria
		8.8.1	 Definition and Clinical Picture
		8.8.2	 Pathogenesis
		8.8.3	 Diagnosis and Differential Diagnosis
		8.8.4	 Treatment and Prognosis
	8.9	 Contact Urticaria
		8.9.1	 Definition and Clinical Picture
		8.9.2	 Pathogenesis
		8.9.3	 Diagnosis and Differential Diagnosis
		8.9.4	 Treatment and Prognosis
	8.10	 Aquagenic Urticaria
		8.10.1	 Definition and Clinical Picture
		8.10.2	 Pathogenesis
		8.10.3	 Diagnosis and Differential Diagnosis
		8.10.4	 Treatment and Prognosis
	References
9: Angioedema
	9.1	 Introduction
	9.2	 Differential Diagnosis
		9.2.1	 Pseudo Angioedema (Figs. 9.2 and 9.3)
		9.2.2	 Angioedema Associated with Systemic Syndromes
		9.2.3	 Diagnostic Strategy for Isolated Angioedema (Table 9.1)
	9.3	 Mast Cell Angioedema (Histaminergic, …)
		9.3.1	 Isolated Allergic Angioedema
		9.3.2	 Spontaneous MC-AE (More Frequent)
		9.3.3	 Non-steroid Anti-inflammatory Drugs Induced AE (NSAID-AE)
	9.4	 Bradykinin Mediated AE (Fig. 9.4)
		9.4.1	 Clinical Description
			9.4.1.1	 Abdominal Localization
			9.4.1.2	 Upper Airways Localization
			9.4.1.3	 Erythema Marginatum (Photo 9.2)
		9.4.2	 Pathophysiology (Fig. 9.2)
		9.4.3	 BK-AE with C1Inh Deficiency (Fig. 9.4)
			9.4.3.1	 Hereditary Angioedema (HAE Type I/II)
			9.4.3.2	 Acquired AE (Type I/II)
		9.4.4	 BK-AE with Normal C1Inh (Fig. 9.4)
			9.4.4.1	 Hereditary AE with Normal C1Inh (Previously Type III) [44]
			9.4.4.2	 Drug Induced BK-AE (Mainly Angiotensin-Converting Enzyme Inhibitor (ACEi))
	9.5	 Conclusion
	References
10: Management Principles in Urticaria
	10.1	 Identification and Elimination of Underlying Causes
	10.2	 Drugs
	10.3	 Infection
	10.4	 Food Intolerance
	10.5	 Physical Stimuli
	10.6	 Lifestyle Adjustments
	10.7	 Inducing Tolerance
	10.8	 Pharmacological Treatment
11: Antihistamines
	11.1	 Introduction
	11.2	 The Histamine H1-Receptor
	11.3	 H1-Antihistamines and the Central Nervous System
	11.4	 H1-Antihistamines and Cardiotoxicity
	11.5	 H1-Antihistamines in Urticaria
		11.5.1	 Speed of Onset of Action and Duration of Action
		11.5.2	 Efficacy
		11.5.3	 Clinical Usage
	11.6	 Conclusions
	References
12: Omalizumab in the Treatment of Urticaria
	12.1	 Bioavailability, Metabolism and Elimination
	12.2	 Mechanisms of Action of Omalizumab in CSU
	12.3	 Common Adverse Effects
	12.4	 Omalizumab in the Treatment of Chronic Spontaneous Urticaria: Clinical Trials
	12.5	 Omalizumab in the Treatment of Chronic Spontaneous Urticaria: Real-world Data
	12.6	 Markers that Predict and Tools that Help to Monitor Treatment Responses to Omalizumab in Patients with CSU
	12.7	 Use in Pregnancy and Breast Feeding
	12.8	 Home Therapy
	12.9	 Future Developments
	12.10	 Current Positioning of Omalizumab in Local and International Guidelines
	References
13: Other Interventions for Chronic Urticaria
	13.1	 Low-Evidence Pharmacological Interventions in Chronic Urticaria
		13.1.1	 Anti-inflammatory Sulphones
			13.1.1.1	 Dapsone
				Evidence for Dapsone in Urticaria
				Dose and Length of Treatment
				Interactions with Other Medicines
				Checks During Treatment
				Contraindications to Treatment
				Possible Side Effects of Treatment
				Summary
			13.1.1.2	 Sulphasalazine
				Evidence for Sulphasalazine in Urticaria
				Dose and Length of Treatment
				Possible Side Effects of Treatment
				Interactions with Other Medicines
				Checks During Treatment
				Reasons for Avoiding It
				Summary
		13.1.2	 Tranexamic Acid
			13.1.2.1	 Evidence for Tranexamic Acid in Urticaria
			13.1.2.2	 Dose and Length of Treatment
			13.1.2.3	 Possible Side Effects of Treatment
			13.1.2.4	 Interactions with Other Medicines
			13.1.2.5	 Checks During Treatment
			13.1.2.6	 Contraindications to Treatment
			13.1.2.7	 Summary
		13.1.3	 Montelukast
			13.1.3.1	 Evidence for Using Montelukast in Urticaria
			13.1.3.2	 Dose and Length of Treatment
			13.1.3.3	 Possible Side Effects of Treatment
			13.1.3.4	 Interactions with Other Medicines and Reasons for Avoiding It
			13.1.3.5	 Checks During Treatment
			13.1.3.6	 Summary
		13.1.4	 H2 Antihistamines
			13.1.4.1	 Evidence for Using H2 Antihistamines in Urticaria
		13.1.5	 Immunosuppressives
			13.1.5.1	 Ciclosporin
				Evidence for Using Ciclosporin in Urticaria
				Dose and Length of Treatment
				Possible Side Effects of Treatment
				Checks Before and During Treatment
				Interactions with Other Medicines
				Cautions and Contraindications
				Summary
			13.1.5.2	 Methotrexate
				Evidence for Using Methotrexate in Urticaria
				Dose and Length of Treatment
				Possible Side effects of Treatment
				Checks Before and During Treatment
				Interactions with Other Medicines
				Cautions and Contraindications
				Summary
			13.1.5.3	 Mycophenolate Mofetil
				Evidence for Using Mycophenolate in Urticaria
				Dose and Length of Treatment
				Possible Side effects of Treatment
				Interactions with Other Medicines
				Checks During Treatment
				Contraindications to Treatment
				Summary
			13.1.5.4	 Azathioprine
				Evidence for Using Azathioprine in Urticaria
				Dose and Length of Treatment
				Possible Side Effects of Treatment
				Interactions with Other Medicines
				Checks During Treatment
				Contraindications to Treatment
				Summary
		13.1.6	 Miscellaneous
			13.1.6.1	 Doxepin
				Evidence for Using Doxepin in Urticaria
				Dose and Length of Treatment
				Possible Side Effects of Treatment
				Interactions with Other Medicines
				Cautions and Contraindications
				Checks During Treatment
				Summary
			13.1.6.2	 Epinephrine
				Evidence for Using Epinephrine in Histaminergic Angioedema
				Dose and Method of Administration
				Possible Side Effects of Treatment
				Interactions with Other Medicines
				Summary
		13.1.7	 Steroids
			13.1.7.1	 Anabolic Steroids
			13.1.7.2	 Danazol
				Evidence for Danazol in Cholinergic Urticaria
				Details and Length of Treatment
				Possible Side Effects of Treatment
				Checks Before and During Treatment
				Interactions with Other Medicines
				Cautions and Contraindications
				Summary
			13.1.7.3	 Corticosteroids (Steroids)
				Evidence for Using Corticosteroids in Chronic Urticaria
				Dose and Length of Treatment
				Possible Side Effects of Treatment
				Interactions with Other Medicines and Reasons for Being Careful
				Checks During Treatment
				Summary
		13.1.8	 Anticoagulants
			13.1.8.1	 Heparin
			13.1.8.2	 Warfarin
		13.1.9	 Antineutrophilic Drugs
			13.1.9.1	 Colchicine
			13.1.9.2	 Biologicals
			13.1.9.3	 Anakinra
			13.1.9.4	 Anti-TNFs
			13.1.9.5	 Rituximab
		13.1.10 Immunosuppressives (Other than Ciclosporin, Methotrexate, Azathioprine and Mycophenolate Mofetil)
			13.1.10.1	 Tacrolimus
			13.1.10.2	 Cyclophosphamide
		13.1.11 Immunomodulators
			13.1.11.1	 Hydroxychloroquine
			13.1.11.2	 Intravenous Immunoglobulins
			13.1.11.3	 Plasmapheresis
		13.1.12 Vitamin D
	13.2	 Non-drug Interventions
		13.2.1	 Diet
			13.2.1.1	 Low Pseudoallergen Diet
				Evidence for Low Pseudoallergen Diets in Urticaria
				Details and Length of Treatment
				Compatibility with Other Diets
				Summary
			13.2.1.2	 Low Histamine Diet
				Evidence for a Low Histamine Diet
				Phototherapy and Photochemotherapy
				Evidence for Phototherapy in Urticaria
				Dose and Length of Treatment
				Interactions with Other Medicines
				Checks During Treatment
				Reasons for Avoiding Ultraviolet Treatment
				Possible Side Effects of Treatment
				Summary
			13.2.1.3	 Psychological Therapies
				Evidence for Psychotherapy in Chronic Urticaria
			13.2.1.4	 Psychotherapy
			13.2.1.5	 Desensitization
	References
14: Urticaria in Pediatrics and During Pregnancy and Lactation: Highlights on Epidemiology, Diagnosis, and Management
	14.1	 Introduction
		14.1.1	 Acute Urticaria in Children
			14.1.1.1	 Differential Diagnosis of Acute Urticaria in Children
		14.1.2	 CU in Children
			14.1.2.1	 Burden
			14.1.2.2	 Clinical Presentation
			14.1.2.3	 Classification
			14.1.2.4	 Differential Diagnosis of CU
			14.1.2.5	 The Natural History of Pediatric CU
			14.1.2.6	 CU—Diagnostic Approach
			14.1.2.7	 Pathogenesis
			14.1.2.8	 Drug Management of CSU in Childhood
		14.1.3	 CU in Pregnancy and Lactation
	References
15: Urticaria Therapy and Management. Looking Forward
	15.1	 Looking Forward, Clinical Knowledge of Chronic Urticaria (CU)
	15.2	 Emerging Biomarkers in CU, Looking Forward
		15.2.1	 Biomarkers for Disease Activity
		15.2.2	 Biomarkers for Response to Treatment
		15.2.3	 Biomarkers for Disease Course
	15.3	 Treatments for Chronic Urticaria, Looking Forward
		15.3.1	 Mast Cells/Basophils
			15.3.1.1	 Anti-IgEs
				Ligelizumab (QGE031)
				UB-221
			15.3.1.2	 Other Anti-IgE Strategies
			15.3.1.3	 Molecules that Target Intracellular Signalling Pathways in Mast Cells
			15.3.1.4	 Other Targets on Mast Cells
		15.3.2	 T Cells
			15.3.2.1	 Abatacept
			15.3.2.2	 Anti-IL-4/IL-13
			15.3.2.3	 Anti-IL-1 Therapies
		15.3.3	 B Cells
			15.3.3.1	 Bruton’s Tyrosine Kinase (BTK) Inhibitor GDC-0853
		15.3.4	 Eosinophils
			15.3.4.1	 Anti- IL-5 Pathway
		15.3.5	 Other Targets that Might have Implications for the Future
	15.4	 Unmet Needs for Chronic Urticaria, Looking Forward
	References
Index