Immunomodulators and Biologics in Dermatologic Treatment: Turning Theory into Practice

Contents
Introduction
	1 Immunomodulation
		1.1 Small Molecule Inhibitors
	2 Janus Kinase Inhibitors
	3 Phosphodiesterase-4 Inhibitors
		3.1 Safety
	4 Biologics
	References
Mechanism of Action of Immunomodulators in Dermatologic Disease
	1 Introduction
	2 Basic Concepts of the Immune System
		2.1 Types of Immunity
		2.2 Innate Immunity
		2.3 Adaptive Immunity
		2.4 The Skin’s Role in the Immune System
		2.5 Immunomodulatory Strategies to Treat Skin Disease
	3 Traditional Immunodulatory Strategies
		3.1 Glucocorticoids
		3.2 Calcineurin Inhibitors
		3.3 Methotrexate
		3.4 Mycophenolate Mofetil
		3.5 Azathioprine
		3.6 Dapsone
		3.7 Cyclophosphamide
		3.8 Chloroquine and Hydroxychloroquine
		3.9 Immunoglobulin Therapy
		3.10 Vitamin D
		3.11 Retinoids
	4 Targeted Immunomodulatory Strategies
		4.1 Phosphodiesterase 4
		4.2 Aryl Hydrocarbon Receptor (AhR)
		4.3 Cytokines
		4.4 IgE
		4.5 JAK-STAT Signaling
		4.6 Immunologic Checkpoints
	5 Conclusion
	6 Conflicts of Interest
	References
Steroid and Non-steroid Immunomodulators
	1 Introduction
	2 Corticosteroids
		2.1 Topical Steroids (TCS)
		2.2 Systemic Steroids
	3 Calcineurin Inhibitors
		3.1 Topical Calcineurin Inhibitors (TCIs)
	4 Phosphodiesterase 4 (PDE4) Inhibitors
		4.1 Apremilast
		4.2 Crisaborole
		4.3 Roflumilast
	5 Aryl Hydrocarbon Receptor (AhR) Agonist
	6 Conclusion
	References
Biologics as Immunomodulators
	1 What Are Biologics and What Are They Made of?
	2 Biologic Development
	3 Historical Clinical Use of Biologics
	4 Pharmacokinetics of Biologics
	5 Immunogenicity
	6 Common Biologic Types
	7 Common Biologic Mechanisms
	8 Applications of Biologics in Dermatology
	9 Psoriasis
	10 Other Applications of Biologics in Dermatology
	11 IL-1 and Autoinflammation
	12 Other Biologics
	13 Conclusion
	References
JAK Inhibitors as Immunomodulators
	1 IMIDs Pathogenesis
		1.1 Cellular Components of the Immune Response in Autoimmunity
		1.2 Soluble Components of Immune Responses: Cytokines
	2 Treatment of IMIDs
		2.1 Conventional Immunosuppressants
		2.2 Molecularly Targeted Therapies
		2.3 Monoclonal Antibodies
		2.4 Small Molecule Inhibitors
	3 JAK-STAT Signaling
		3.1 JAK-STAT Pathway
		3.2 Cytokines that Use JAK-STAT
		3.3 Genetic Inactivation of JAK-STAT Signaling Causes Immunodeficiency
		3.4 Overactivation of JAK-STAT Signaling Is Associated with Cancer and Autoimmunity
	4 JAK Inhibitors
		4.1 FDA Approved JAK Inhibitors
		4.2 JAK Inhibitor Selectivity/Specificity
		4.3 JAK Inhibitor Safety: A Boxed Warning
	5 Conclusions
	References
Combinations of Topical and Systemic Immunomodulators
	1 Inflammatory Myopathy
	2 Cutaneous Vasculitis
	References
Nanoparticles as Immunomodulators
	1 Introduction
	2 Skin Penetration with Nanoformulation
	3 Immunomodulatory Applications in Dermatology
		3.1 Cutaneous Infection and Wound Healing
		3.2 Cutaneous Endocannabinoid System
	4 Future Trends
	5 Summary
	References
Antibiotics and Antimicrobials as Immunomodulators
	1 Introduction
	2 Antibiotics
		2.1 Clindamycin
		2.2 Clofazimine
		2.3 Dapsone
		2.4 Macrolides
		2.5 Metronidazole
		2.6 Rifampicin
		2.7 Tetracyclines
	3 Antifungals
		3.1 Azoles
	4 Antiparasitics
		4.1 Antimalarials
		4.2 Levamisole
		4.3 Ivermectin
	5 Conclusion
	References
Integrative Therapies as Immunomodulators
	1 Herbs, Probiotics, Nutrition and Inflammatory Disease
		1.1 Acne
	2 Psoriasis
		2.1 Low Calorie Diet and Weight Loss
		2.2 Dietary Supplements for Psoriasis
		2.3 Topical Botanical Agents
		2.4 Hidradenitis Suppurativa (HS)
		2.5 Rosacea
		2.6 Atopic Dermatitis
	3 Key Takeaways and Summary
	References
Immunomodulators and Biologics for Follicular and Neutrophilic Cutaneous Disorders
	1 Introduction
	2 Hidradenitis Suppurativa
	3 Immune Dysregulation in Hidradenitis Suppurativa
	4 Current Guidelines
	5 Biologic Medications
		5.1 Anti-TNF Biologics
		5.2 IL-17 Inhibitors
		5.3 IL-12 and 23 Inhibitors
		5.4 IL-1 Inhibitors
		5.5 Other Inhibitors
	6 Small Molecule Inhibitors
		6.1 JAK Inhibitors
		6.2 Other Immunomodulators
	7 Special Populations
		7.1 Pediatric
		7.2 Pregnancy
	8 Laboratory Testing
		8.1 Screening
		8.2 Monitoring
	9 Surgery and Biologics
	10 Future Directions
	11 Pyoderma Gangrenosum
		11.1 Pathophysiology
		11.2 Treatment
	12 Special Populations
		12.1 Pediatric
		12.2 Pregnancy
	13 Cutaneous Vasculitis
		13.1 Small Vessel Vasculitis
		13.2 Medium Sized Vessel Vasculitis
		13.3 Other Vasculitides
		13.4 Future Directions
	References
Immunomodulators for Common Dermatologic Disorders: A Focus on Acne, Rosacea, Seborrheic Dermatitis
	1 Acne
	2 Rosacea
	3 Seborrheic Dermatitis
	References
Prescribing and Advocating for Immunomodulators in Dermatology Practice
	1 Overview of Small Molecule and Biologics in Dermatologic Treatment
	2 Significance and Evolution of These Therapies in Dermatology
	3 Bridge from Theoretical Concepts to Practical Applications
	4 Types of Biologics and Small Molecules in Dermatology Biologics
	5 Current Available Medications and Their Efficacy
	6 Small Molecules
	7 Comparative Analysis with Biologics
	8 Challenges in Clinical Implementation
		8.1 Physician’s Constraints in Prescribing
	9 Geographic Distribution Challenges
	10 Role of Biologic Coordinators in Patient Management
	11 Impact of Prior Authorizations on Patient Care
	12 Understanding Medication Cost: Considerations and Terminology
		12.1 Formulary and Its Implications
	13 Advocacy and Its Role in Medication Access
	14 Specialty Pharmacies: Navigating Their Significance
	15 Patient Support Programs
	16 Copay Cards: Facilitating Cost-Sharing
	17 Patient Assistance Programs/Advocacy Programs: Bridging Financial Gaps
	18 Bridge Programs: Ensuring Uninterrupted Treatment
	19 Additional Challenges in Dermatological Treatment
		19.1 Impact of Accumulators and Maximizers on Patients and Practices
	20 Challenges Posed by Step Therapy
	21 Navigating Buy-and-Bill Procedures
	22 Conclusion
		22.1 Summary of Key Findings
	23 Bridge Between Theory and Practice
	24 Future Implications and Areas for Further Research
	References
Conclusions
	1 Lebrikizumab
	2 Tezepelumab—Anti-TSLP Ab
	3 Amlitelimab—Anti-OX 40 Antibody
	4 Bruton Tyrosine Kinases
	5 Ritlecitinib: TEC Non-receptor Kinases
	6 Tyrosine Kinase 2 Inhibitors
	7 SAR441566: An Oral TNF Inhibitor?
	8 Fumaric Acid and Etrasimod: Will They Come Back to Dermatology?
	9 Conclusions
	References
Index