Advances in Psoriasis. A Multisystemic Guide

Contents
1: Introduction to and History of Psoriasis and Psoriasis Therapy
	History of Psoriasis
		Identification of Psoriasis as a Unique Disease
		History of the Treatment of Psoriasis
		Arsenic, Ammoniated Mercury and Chrysarobin
		Anthralin and Tar
		Corticosteroids
		Methotrexate and PUVA
		Narrowband UVB, Retinoids, Vitamin D
		Systemic Immunosuppressive Medications
2: Pathophysiology of Psoriasis/Novel Pathways
	Principles of Immunity
	Implicating Dysregulation of Immunity
	Intralesional T Lymphocytes
	T-Lymphocyte Stimulation
	T-Lymphocyte Signaling
		NK T Cellss
		Dendritic Cells
	Cytokines
	Tumor Necrosis Factor α
	IL-23/TH17 Axis
	Genetic Basis of Psoriasis
	Conclusion
	References
3: Psoriasis: Clinical Review and Update
	Plaque Psoriasis
	Guttate Psoriasis
	Pustular Psoriasis
	Generalized Pustular Psoriasis
	Impetigo Herpetiformis
	Acute Generalized Exanthematous Pustulosis
	Localized Pustular Forms
	Consensus Statement of Phenotypes of Pustular Psoriasis
	ErythrodermicPsoriasis
	Manifestations of Psoriasis in Specific Locations
		Scalp Psoriasis
		Nail Psoriasis
		Inverse (Flexural, Intertiginous) Psoriasis
		Rare Forms and Some Specific Locations
	Pediatric Psoriasis
	Differential Diagnosis of Psoriasis
	Conclusion
	References
4: Psoriasis: Epidemiology, Potential Triggers, Disease Course
	Epidemiology
	Potential Triggers
		Trauma
		Infections
		Stress
		Medications
		Alcohol and Smoking
		Obesity
		Estrogen
		Disease Course
	References
5: Topical Therapy I: Corticosteroids and Vitamin D Analogues
	Topical Corticosteroids
		Pharmacokinetics/Mechanism of Action
		Vehicle
		Immunologic Mechanisms
		Use in Psoriasis
		Combination with Other Therapies
		Adverse Effects
	Vitamin d Analogues
		Structure, Biosynthesis and Mechanism of Action
		Calcitriol
		Calcipotriene (Calcipotriol)
		Tacalcitol
		Maxacalcitol
		Indication for Psoriasis
		Use with Other Treatment Modalities
		Adverse Effects
	References
6: Topical Therapy II: Retinoids, Immunomodulators, and Others
	Tazarotene
		Mechanism of Action
		Pharmacokinetics
		Toxicology
		Clinical Studies in Plaque Psoriasis
		Clinical Studies in Other Types of Psoriasis (Palmoplantar, Nail)
		Application Tips
	Topical Calcineurin Inhibitors (Immunomodulators) Pimecrolimus and Tacrolimus
		Mechanism of Action
		Toxicity
		Clinical Studies in Psoriasis
		Crisaborole 2% Ointment
	Tar
		Mechanism of Action
		Toxicity
		Clinical Studies in Psoriasis
	Anthralin
		Mechanism of Action
		Toxicity
		Clinical Studies
	Moisturizers and Keratolytics
	Conclusions
	References
7: Topical Therapy II: Retinoids, Immunomuodulators, and Others/Ultraviolet Therapy for Psoriasis
	UVB Phototherapy
		Dosage and Administration
		Efficacy
		Side Effects and Safety
		Photocarcinogenicity of UVB Phototherapy
	PUVA (Psoralen Plus PUVA)
		Dosage and Administration
		Efficacy
		Side Effects
		Photocarcinogenicity of PUVA
	Inpatient Photothearpy
		Goeckerman Therapy
			Dosage and Administration
			Efficacy
			Side Effects and Long-term Safety
		Ingram Therapy
	Non-office-based Phototherapy
		Commercial Tanning Therapy
		Home UVB Therapy
		Heliotherapy
		Climatotherapy at the Dead Sea
	Combination Therapy
		UVB and Retinoid Therapy
		PUVA and Retinoid Therapy
		UVB and Biologics
		Photocarcinogenicity of Combination Therapy
	Conclusion
	References
8: Laser Therapy in Psoriasis
	Introduction
	Excimer Laser
		Background
		Mechanism of Action
		Efficacy
		Safety
		Dosing/Protocols
		Other Morphologies and Special Populations
		Adjuvant Therapies
	Pulsed Dye Laser
		Background
		Mechanism of Action
		Efficacy
		Safety
		Other Morphologies
	Nd:YAG Laser
		Background
		Efficacy
	Carbon Dioxide Laser
		Background
		Efficacy
		Safety
	Comparative Studies
	References
9: Traditional Systemic Therapy I: Methotrexate and Cyclosporine
	Introduction
	Methotrexate
		Introduction
		Mechanism of Action
		Absorption and Bioavailability
		Use in Psoriasis
		Dosing
		Monitoring Guidelines
			Liver Biopsy
		Adverse Effects
			Hepatotoxicity
			Myelosuppression
			Pulmonary Fibrosis
		Drug Interactions
	Cyclosporine
		Introduction
		Mechanism of Action
		Absorption and Bioavailability
		Use in Psoriasis
		Dosing
		Monitoring Guidelines
		Adverse Effects
			Nephrotoxicity
			Hypertension
		Drug Interactions
	Summary
	References
10: Traditional Systemic Therapy II: Retinoids and Others
	Acitretin
		FDA-Approved Indication(s)
		Mechanism of Action
		When Best to Use
		Dosage
		Adverse Events
		Recommended Monitoring
		Perils and Pitfalls
		Strength of Evidence
	Hydroxyurea
		FDA-Approved Indication(s)
		Mechanism of Action
		When Best to Use
		Dosage
		Adverse Events
		Recommended Monitoring
		Perils and Pitfalls
		Strength of Evidence
	Mycophenolate Mofetil (MMF)
		FDA-Approved Indication(s)
		Mechanism of Action
		When Best to Use
		Dosage
		Adverse Events
		Recommended Monitoring
		Perils and Pitfalls
		Strength of Evidence
	6-Thioguanine (6TG)
		FDA-Approved Indication(S)
		Mechanism of Action
		When Best to Use
		Dosage
		Adverse Events
		Recommended Monitoring
		Perils and Pitfalls
		Strength of Evidence
	Systemic Tacrolimus
		FDA-Approved Indication(s)
		Mechanism of Action
		When Best to Use
		Dosage
		Adverse Events
		Recommended Monitoring
		Perils and Pitfalls
		Strength of Evidence
	Leflunomide
		FDA-Approved Indication(s)
		Mechanism of Action
		When Best to Use
		Dosage
		Adverse Events
		Recommended Monitoring
		Perils and Pitfalls
		Strength of Evidence
	Penicillin V and Erythromycin
		FDA-Approved Indication(S)
		Mechanism of Action
		When Best to Use
		Dosage
		Adverse Events
		Recommended Monitoring
		Perils and Pitfalls
		Strength of Evidence
	Apremilast
		FDA-Approved Indication(s)
		Mechanism of Action
		When Best to Use
		Dosage
		Adverse Events
		Recommended Monitoring
		Perils and Pitfalls
		Strength of Evidence
	Conclusion
	References
		Recommended Reading
11: Apremilast
	Bibliography
12: Etanercept
	Introduction
	Background
	Structure and Mechanism of Action
	Etanercept in the Treatment of Psoriatic Arthritis
	Etanercept in the Treatment of Psoriasis
	Combination Therapy
	Safety
	Malignancies
	References
13: Adalimumab for Psoriasis
	Introduction
	Adalimumab
	Adalimumab in Clinical Trials for Psoriasis and Psoriatic Arthritis
	REVEAL
	Champion
	ADEPT
	Adalimumab for Special Populations
		Pregnancy and Lactation
		Pediatric
		Elderly
		Fingernail Psoriasis
		Hidradenitis Suppurativa
		Generalized Pustular Psoriasis
		Inflammatory Bowel Disease (IBD)
		Hemodialysis
		Biologic Comparator Trials
		Practical Considerations for TNF-Inhibitors
		Safety Update
	Black Box Warnings: Infection and Malignancy
	Post-Marketing Safety Information
	Adalimumab Pearls
	Complications of Not Treating Psoriasis
	Conclusion
	References
14: Infliximab, Golimumab, and Certolizumab Pegol
	Introduction
	Mechanism of Action
	Efficacy for Psoriasis and Psoriatic Arthritis
		Infliximab
		Combination Therapy
		Golimumab
		Certolizumab
	Safety Considerations
		Infusion-Reactions
		Infection
		Malignancy
		Laboratory Data/Autoimmune Disease
		Dermatologic
		Treatment Switches
	Conclusion
	References
15: Ustekinumab
	Introduction
	Pharmacokinetics
	Pharmacodynamics
	Clinical Efficacy
		Psoriatic Arthritis
		Adolescent Patients
	Adverse Effects
		Serious Infections
		Malignancy
		Major Adverse Cardiovascular Events
		Other Adverse Events
	Laboratory Abnormalities
	Pregnancy and Lactation
	Cautions for Patients Treated with Anti-IL-12p40 Agents
	Conclusions
	References
16: Guselkumab
	Introduction
	Structure and Mechanism
		Pharmacodynamics and Pharmacokinetics
	Clinical Efficacy
		VOYAGE 1
		VOYAGE 2
		Maintenance and Recapture
		NAVIGATE
		ECLIPSE
		Other Studies
	Safety/Adverse Events
		Pediatrics and Breastfeeding
		Tuberculosis, HIV, and Live Vaccines
		Malignancy
		Inflammatory Bowel Disease
	Psoriatic Arthritis
	Hidradenitis Suppurativa
	Patient Controlled Injector
	Conclusion
	References
17: Tidrakizumab
	Introduction
	Rationale of Targeting IL-23
	Pharmacokinetics/Pharmacodynamics
	Clinical Efficacy
	Psoriatic Arthritis
	Safety/Adverse Events
	Immunogenicity
	Considerations in Treatment Approach
		Speed of Onset
		Prior Treatment with Biologics
		Inflammatory Bowel Disease
		Metabolic Syndrome
		Withdrawal and Retreatment
		Pregnancy
	Conclusions
	References
18: Risankizumab
	Introduction
	Pharmacology
	Dosing and Monitoring
	Clinical Efficacy
	Safety
	Pregnancy and Lactation
	Conclusion
	References
19: Secukinumab for the Treatment of Inflammatory Skin and Joint Disease
	Introduction
	Secukinumab: Background and Pivotal Clinical Trial Data
		Plaque Psoriasis
		Difficult to Treat Psoriasis Subtypes: Palmoplantar, Nail, and Scalp Psoriasis
		Psoriatic Arthritis
		Ankylosing Spondylitis
	Pharmacologic Properties and Safety
	Future Direction of IL-17 Blockade for Chronic Inflammatory Conditions
	Conclusion
	References
20: Ixekizumab
	Introduction
	Pharmacodynamics
	Pharmacokinetics
	Clinical Efficacy
	Bodyweight
	Psoriatic Arthritis
	Nail Psoriasis
	Scalp
	Palmoplantar Psoriasis
	Genital Psoriasis
	Body Regions
	Erythrodermic and Pustular Psoriasis
	Adverse Effects
	Adverse Events of Special Interest
	Infections
	IBD
	Malignancy
	Depression
	Summary
	References
21: Brodalumab
	Introduction
	Role of IL-17 in Psoriasis
	Brodalumab
		Dosing, Storage, Administration, and Pharmacokinetics
		Clinical Efficacy in Plaque Psoriasis
			Phase I Clinical Trials
			Phase II Clinical Trials
			Phase III Clinical Trials
		Clinical Efficacy in Psoriatic Arthritis
		Clinical Efficacy in Difficult-to-Treat Psoriasis
		Improvements in Quality of Life
	Safety and Tolerability
		Common Adverse Events
		Inflammatory Bowel Disease
		Serious Infections
		Immunizations
		Pregnancy
		Elderly
		Suicidal Behavior
		Contraindications and Cautions
	Initiation of Therapy
	Conclusion
	References
22: Biosimilars for Psoriasis
	Background
	Generics Versus Biosimilars
	Naming of Biosimilars
	Development of Biosimilars
	Approval Process
		Analysis of Structure and Function
		Nonclinical (Animal) Studies
		Clinical Studies
		Pharmacovigilance Studies
		Interchangeability
	Biosimilars in Dermatology
	Economic Advantage of Biosimilars
	Barriers to Use and Future Directions
		Patent Disputes and Extended Patents for Branded Drugs
		Prescriber Considerations
		Patient Factors
	Conclusion
	References
23: Research Pipeline I: Oral Therapeutics for Psoriasis
	Introduction
	JAK Inhibitors
	Tyk2 Inhibitor
	PDE4 Inhibitors
	RORγt Inhibitors
	Fumarate Esters
	S1P Receptor Antagonists
	Neurokinin-1 Receptor Antagonists
	Adenosine A3 Receptor Agonists
	H4 Receptor Antagonists
	IL-20/PRINS Inhibitor
	SYK Inhibitors
	Conclusion
	References
24: Research Pipeline II: Upcoming Biologic Therapies
	Introduction
	Overview of Pathogenesis
	Overview of Biologic Treatments
	Clinical Trial Background
	Psoriasis Biologics Pipeline
		IL-17
		IL-12/23
	Miscellaneous
	Summary
	References
25: Pediatric Psoriasis
	Introduction
	Epidemiology (Table 25.1)
	Pathogenesis
	Obesity and Metabolic Syndrome
	Diagnosis and Clinical Characteristics (Tables 25.1 and 25.3)
	Differential Diagnosis (Table 25.5)
	Biopsy and Histology
	Therapeutic Management (Table 25.2 and Fig. 25.6) [62]
	Topical Therapies
	Systemic Therapies (Table 25.2 and Fig. 25.6)
	Phototherapy
	Natural Supplements
	Dietary Recommendations
	Conclusions
	References
26: Challenges in Psoriasis Treatment: Nail, Scalp, and Palmoplantar Involvement
	Nail Psoriasis
		Treatment of Nail Psoriasis
		Treatment Approach to Nail Disease
	Scalp Psoriasis
		Clinical Presentation of Scalp Psoriasis
		Measuring Scalp Disease
		Management of Scalp Psoriasis: Topical Therapies
		Procedural Therapies for Scalp Psoriasis
		Systemic Therapy for Scalp Psoriasis
		Biologic Therapy for Scalp Psoriasis
		Treatment Algorithm for Scalp Psoriasis
		TNF Induced Psoriasis
	Palmoplantar Psoriasis
	References
27: Psoriasis and Comorbidities
	Introduction
	Obesity
	Dyslipidaemia
	Hypertension
	Non-alcoholic Fatty Liver Disease (NAFLD)
	Insulin Resistance and Type 2 Diabetes Mellitus
	Metabolic Syndrome
	Cardiovascular Disease (CVD)
		Heart Disease
			Evidence for an Association Between CVD and Psoriasis
			Evidence Against an Association Between CVD and Psoriasis
			Effect of Treatment of Psoriasis on CVD Risk
		Stroke and Atrial Fibrillation
	Cancer and Lymphoma
		Skin Cancer
		Lymphoma
		General Cancer Risk
	Autoimmune Disease
	Psychiatric Illness
	Conclusions
	References
28: Summary of Published Treatment Guidelines
	Introduction
	Methods
	Overview of Treatment Guidelines
		General Principles
		Topicals
		Corticosteroids
		Vitamin D Derivatives
		Tazarotene
		Topical Calcineurin Inhibitors
		Anthralin
		Coal Tar
		Phototherapy and Photochemotherapy
	Systemics
		Non-biologic systemics
			Acitretin
		Cyclosporine A
		Methotrexate
		Apremilast
		Systemic Corticosteroids
		Other Systemic Medications
		Biologics
		Adalimumab
		Etanercept
		Infliximab
		Ustekinumab
		Secukinumab
	Considerations for Less Common Psoriasis Types
		Pustular
		Erythrodermic
		Flexural/Inverse
	Considerations for Specific Patient Populations
		Pregnancy
		Children
	Limitations
	Conclusion
	References
Index