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31-08-2018 | Immune checkpoint inhibitor-induced rheumatic disease | Review | Article

Rheumatic immune-related adverse events from cancer immunotherapy

Journal: Nature Reviews Rheumatology

Authors: Leonard H. Calabrese, Cassandra Calabrese, Laura C. Cappelli

Publisher: Nature Publishing Group UK

Abstract

Immunotherapy has revolutionized the treatment of cancer, but a rapid rise in the use of the family of therapeutic agents known as checkpoint inhibitors (CPIs) is associated with a new group of immune-related adverse events (irAEs) in almost any organ system. Among these irAEs, rheumatic complications are common and seem to have features that are distinct from irAEs in other organ systems, including a highly variable time of clinical onset and the capacity to persist, possibly indefinitely, even after cessation of CPI therapy. In this Review, mechanisms of action of CPIs and how they might cause rheumatic irAEs are described. Also covered are epidemiology and clinical descriptions of rheumatic irAEs, plus guiding principles for managing irAEs. Finally, we outline future directions that must be taken in response to a series of unanswered questions and unmet needs that now confront rheumatologists who are, or will be, engaged in this new area of rheumatology.

Immune-related adverse events

(irAEs). A term now used commonly to describe the range of toxic effects in one or more organs after exposure to checkpoint inhibitors.

Antimetabolites

Chemicals that inhibit the function of a metabolite, for example, the DMARDs methotrexate or azathioprine.

Amaurosis fugax

A temporary loss of vision in one eye or both eyes owing to lack of blood flow to the retina.

Parotitis

Inflammation of the parotid salivary glands.

Eosinophilic fasciitis

A rare scleroderma-like disorder that involves inflammation, thickening and tethering of the skin and underlying fascia.

Hypophysitis

A general term used to describe inflammation of the pituitary gland. Before checkpoint inhibitor therapy, hypophysitis was exceedingly rare in medical practice, but it is now one of the most well described and common immune-related adverse events, especially with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) therapy.

Cross presentation

In immunology, this term refers to the capacity of professional antigen-presenting cells to take up antigens of extracellular origin and present these in the context of MHC class I molecules to cytotoxic CD8⁺ T cells. This phenomenon is believed to occur in the tumour microenvironment when tumour cells and nearby host cells of non-cancerous origin are destroyed, and might be important in the pathogenesis of off-target autoimmune responses mediated by T cells.

Sialagogues

Drugs that cause salivation

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Medicine Matters Rheumatology

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