Autoinflammation: From monogenic syndromes to common skin diseases

Abstract

Autoinflammation is characterized by aberrant regulation of the innate immune system and often manifests as periodic fevers and systemic inflammation involving multiple organs, including the skin. Mutations leading to abnormal behavior or activity of the interleukin 1 beta (IL-1ß)-processing inflammasome complex have been found in several rare autoinflammatory syndromes, for which anticytokine therapy such as IL-1 or tumor necrosis factor-alfa inhibition may be effective. It is becoming clear that features of autoinflammation also affect common dermatoses, some of which were previously thought to be solely autoimmune in origin (eg, vitiligo, systemic lupus erythematosus). Recognizing the pathogenetic role of autoinflammation can open up new avenues for the targeted treatment of complex, inflammatory dermatoses.

Inflammasomes and dermatology

“…These syndromes result from mutations in tbe NLRP3 gene and in the 1q44 chromosome, with dominant autosomal inheritance and variable penetrance, but with some new mutation cases, especially in the syndrome's more serious spectrum. 26,28,29,30 Over 90 mutations have been reported. 31 This disease's physiopathology is characterized by excessive IL-1β production by macrophages, monocytes, and chondrocytes.…”

Pyoderma gangrenosum: challenges and solutions

“…Systemic symptoms may result from IL1β elevation due to inflammasome activation, and consequent signal cascades maintaining systemic inflammation. 28 Very rarely, as in SS, extracutaneous neutrophilic infiltrates can be observed, namely in the bones, liver, lungs, pancreas, spleen, kidneys, and central nervous system. 29,30 Particularly, in the classic ulcerative type, two distinct stages are described: the active ulcerative stage and the wound healing stage.…”

“…Furthermore, the inflammatory cascades activated by IL1β, can be responsible for chronic inflammation and sterile neutrophilic inflammation, which may result in arthritis, a common feature in auto-inflammatory diseases. 28,39 PG has also been associated with HIV, hepatitis, systemic lupus erythematous, PAPA syndrome and the associated syndromes (PAPASH and PASH), Takayasu's arteritis, solid tumors, and pregnancy. 23,29,33 Furthermore, drugs such as propylthiouracil, isotretinoin, pegfilgrastim, TNF inhibitors, and gefitinib have been reported to induce PG.…”

“…8 Relapses may occur in patients who responded rapidly and completely to the chosen drug regimen. 28 Unfortunately, despite advances in the therapeutic management, PG is still a potentially lifethreatening disease, and the risk of death was shown to be three times higher than the general population.…”

Treatment Patterns and Annual Drug Costs of Biologic Therapies Across Indications from the Humana Commercial Database

“…Although these diseases are systemic in nature, tissue destruction is the result of dysregulation of innate and adaptive immunity in specific organs, such as joints and skin. 1,2 In addition to symptoms of tissue destruction, these autoimmune diseases have substantial negative impact on health-related quality of life. [3][4][5] Several biologic therapies that target specific components of the immune system are approved by the U.S. Food and Drug Administration (FDA) for the treatment of autoimmune diseases, including agents that target tumor necrosis factor (TNF; adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab); Cluster of Differentiation (CD) 20 (rituximab); interleukin (IL)-12 and IL-23 (ustekinumab); and CD80 and CD86 (abatacept; Table 1).…”