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The concept of autoinflammation includes a heterogeneous group of monogenic and polygenic diseases. These are characterized by excessive activation of the innate immune system without antigen-specific T cells or autoantibodies. The diseases are characterized by periodic episodes of fever and increased inflammation parameters. Monogenic diseases include familial Mediterranean fever (FMF) and the newly described VEXAS (vacuoles, E1 enzyme, X‑linked, autoinflammatory, somatic) syndrome. Heterogeneous diseases include adult-onset Still's disease and Schnitzler syndrome. Treatment is aimed at preventing the excessive inflammatory reaction in order to avoid long-term damage, such as amyloid A (AA) amyloidosis., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Systemic autoinflammatory diseases are characterized by a spontaneous chronic inflammatory reaction mediated by the innate immunity. The inflammatory processes involve many organs including the skin. Diagnosis remains a challenge despite new molecular genetic methods, but early diagnosis is crucial for the prevention of long-term complications such as amyloidosis. Skin manifestations are often observed early in the course of the disease and can be decisive in the diagnosis.

Autoinflammatory diseases comprise a group of chronic disabling entities characterized by inflammation without the presence of infectious agents, auto-antibodies or antigen-specific T-cells. Many autoinflammatory diseases are caused by monogenic defects, which lead to disturbed immune signalling with release of proinflammatory mediators. In addition to interleukin-1β and interleukin-18, interferons play a key role in the pathophysiology of these disorders. Patients with autoinflammatory diseases show a broad variety of clinical symptoms, including skin involvement. Wheals, pustules and ulcerative lesions are the most common cutaneous findings observed. Knowledge of the clinical presentation of autoinflammatory diseases is crucial for establishing the diagnosis and guiding appropriate treatment. This review focuses on the dermatological findings in selected autoinflammatory disorders based on their distinct pathomechanisms.

Hereditary autoinflammatory diseases are caused by gene mutations of the innate immune pathway, e.g. nucleotide receptor protein 3 (NLRP3). Here, we report a four-generation family with cold-induced urticarial rash, arthralgia, chills, headache and malaise associated with an autosomal-dominant inheritance. Genetic studies identify a substitution mutation in gene F12 (T859A, resulting in p.W268R) which encodes coagulation factor XII (FXII). Functional analysis reveals enhanced autocatalytic cleavage of the mutated protein and spontaneous FXII activation in patient plasma and in supernatant of transfected HEK293 cells expressing recombinant W268R-mutated proteins. Furthermore, we observe reduced plasma prekallikrein, cleaved high molecular weight kininogen and elevated plasma bradykinin. Neutrophils are identified as a local source of FXII. Interleukin-1β (IL-1β) is upregulated in lesional skin and mononuclear donor cells exposed to recombinant mutant proteins. Treatment with icatibant (bradykinin-B2-antagonist) or anakinra (interleukin-1-antagonist) reduces disease activity in patients. In conclusion, our findings provide a link between contact system activation and cytokine-mediated inflammation.