Paraproteinemia in Autoinflammatory Diseases

Autoinflammatory diseases represent clinical entities characterized by recurrent episodes of systemic and organ-specific inflammation determined by the primary deregulation of the innate immune system. In addition to monogenic diseases, caused by gene mutations of specific genes involved in the innate immunity, other disorders have been recently classified as multifactorial autoinflammatory diseases on the basis of clinical, pathogenic, and treatment features shared with the monogenic entities. Both in relation to monogenic and multifactorial diseases, a specific chapter referring to autoinflammatory disorders associated with paraproteinemia and other bone marrow disorders is emerging. Considering that many of the innate immunity cells involved in autoinflammatory diseases pass through the bone marrow at some point in their life lends support to this concept. Therefore, recent scientific research is trying to identify bone marrow disorders as a possible cause of autoinflammatory diseases. This would probably allow a considerable diagnostic improvement for adult patients with acquired autoinflammatory conditions currently classified as undifferentiated. Among autoinflammatory diseases related to paraproteinemia and bone marrow disorders, particular attention has to be paid to Schnitzler’s syndrome, but also to Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS) syndrome, and other recently described clinical entities, especially VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, which represents an intriguing bridgehead for future scientific research on the field of bone marrow-associated autoinflammatory diseases.