Pustular diseases and keratinocyte-myeloid synergy

Area of Science:

• Dermatology
• Immunology
• Pathology

Background:

• Pustules are common skin lesions caused by infections, drugs, or immune responses.
• Recent focus on immune-mediated pustular diseases highlights the need for better classification.
• Understanding the underlying pathology is crucial for managing these conditions.

Purpose of the Study:

• To propose a classification system for pustular diseases based on initiating events and sites.
• To elucidate the unifying pathological mechanisms in different pustular disease categories.
• To explore the role of keratinocyte-myeloid synergy (KMS) in pustule formation.

Main Methods:

• Classification of pustular diseases into epidermal, follicular, or autoinflammatory categories.
• Analysis of the role of key cytokines (IL-17, IL-23, IL-36, IL-1) and pathways (inflammasomes, caspase activation).
• Investigation of keratinocyte-myeloid synergy (KMS) and the influence of interferons (IFNα, IFNβ) and chemoattractants (IL-8, LTB4).

Main Results:

• A proposed classification identifies purely epidermal pustules, follicular pustules, and pustules in autoinflammatory syndromes.
• Neutrophil microinvasion into epithelia is a unifying pathological feature.
• Keratinocyte-myeloid synergy (KMS) plays a significant role, involving cytokines like IL-17/IL-23 and IL-36/IL-36RN, or IL-1/caspase-activated inflammation.
• Non-infectious pustules are influenced by IFNα, IL-1-regulated inflammasomes, and caspase/IFNβ-induced chemotaxins.
• Follicular KMS-driven disorders show neutrophil toxicity leading to ulcerating diseases with elevated circulating IgA.

Conclusions:

• Pustular diseases can be classified based on initiating events and affected sites.
• Keratinocyte-myeloid synergy (KMS) is a central mechanism in pustule formation.
• Specific inflammatory pathways and the role of IgA are critical in the pathogenesis of these skin conditions.