Autoinflammatory keratinization diseases: An emerging concept encompassing various inflammatory keratinization disorders of the skin. Issue 2 (May 2018)

• Record Type: Journal Article
• Authors: Akiyama, Masashi; Takeichi, Takuya; McGrath, John A.; Sugiura, Kazumitsu
• Is Part Of: Journal of dermatological science. Volume 90:Issue 2(2018)
• Page Start: 105
• Page End: 111
• Publication Date: 2018-05
• Subjects: AIKD autoinflammatory keratinization diseases -- CAPS cryopyrin-associated periodic syndrome -- CARD14 caspase recruitment domain family member 14 -- FMF familial Mediterranean fever -- GPP generalized pustular psoriasis -- IL-36Ra IL-36 receptor antagonist -- KLC keratosis lichenoides chronica -- NLRP1 NLR family Pyrin domain-containing protein 1 -- PAPA syndrome syndrome of pyogenic arthritis with pyoderma gangrenosum and acne -- PRP pityriasis rubra pilaris -- PV psoriasis vulgaris -- TLR4 toll-like receptor 4 -- TRAPS TNF receptor-associated periodic fever syndrome; Autoinflammation -- CARD14 -- IL-36 receptor antagonist -- Keratinization -- Keratosis lichenoides chronica -- NLRP1 -- Pityriasis rubra pilaris -- Psoriasis -- Psoriatic arthritis -- Pustular psoriasis; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2018.01.012
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: Autoinflammatory keratinization diseases have autoinflammatory pathomechanisms. The clinical entity "autoinflammatory keratinization diseases" includes IL36Ra-related pustulosis. CARD14-mediated pustular psoriasis falls within the concept of autoinflammatory keratinization diseases. Pityriasis rubra pilaris type V and keratosis lichenoides chronica are included in autoinflammatory keratinization diseases. Improved understanding of disease pathophysiology may lead to innovative targeted therapies. 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.