Autoinflammatory keratinization diseases: An emerging concept encompassing various inflammatory keratinization disorders of the skin.

Abstract

Classifying inflammatory skin diseases is challenging, especially for the expanding group of disorders triggered by genetic factors resulting in hyperactivated innate immunity that result in overlapping patterns of dermal and epidermal inflammation with hyperkeratosis. For such conditions, the umbrella term "autoinflammatory keratinization diseases" (AIKD) has been proposed. AIKD encompasses diseases with mixed pathomechanisms of autoinflammation and autoimmunity, and includes IL-36 receptor antagonist (IL-36Ra)-related pustulosis, CARD14-mediated pustular psoriasis, pityriasis rubra pilaris (PRP) type V, and familial keratosis lichenoides chronica (KLC). Mechanistically, the entities include generalized pustular psoriasis (GPP) without psoriasis vulgaris, impetigo herpetiformis and acrodermatitis continua, which are IL-36Ra-related pustuloses caused by loss-of-function mutations in IL36RN; GPP with psoriasis vulgaris and palmoplantar pustular psoriasis which are CARD14-mediated pustular psoriasiform dermatoses with gain-of-function variants of CARD14; PRP type V which is caused by gain-of-function mutations in CARD14; and, familial KLC in which mutations in NLRP1, an inflammasome sensor protein predominantly expressed in skin, have been identified. It is likely that further inflammatory keratinization disorders will also fall within the concept of AIKD, as elucidation of novel pathogenic mechanisms of inflammatory keratinization diseases emerges. A better understanding of the pathophysiology of AIKD is likely to lead to innovative, targeted therapies that benefit patients.

• Authors: Masashi Akiyama, Takuya Takeichi, John A McGrath, Kazumitsu Sugiura
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 90 Issue 2 Pg. 105-111 (May 2018) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 29422292 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• CARD Signaling Adaptor Proteins
• IL36RN protein, human
• Interleukins
• Membrane Proteins
• NLR Proteins
• NLRP1 protein, human
• CARD14 protein, human
• Guanylate Cyclase

Topics

• Adaptor Proteins, Signal Transducing (genetics, immunology)
• Apoptosis Regulatory Proteins (genetics, immunology)
• Autoimmune Diseases (genetics, immunology)
• CARD Signaling Adaptor Proteins (genetics, immunology)
• Dermatitis (genetics, immunology)
• Guanylate Cyclase (genetics, immunology)
• Humans
• Immunity, Innate
• Interleukins (genetics, immunology)
• Membrane Proteins (genetics, immunology)
• Mutation
• NLR Proteins
• Skin (immunology, pathology)
• Skin Diseases, Papulosquamous (genetics, immunology)