Sicca syndromes

Abstract

Biologic agents that block immune checkpoints have significantly advanced cancer therapy. However, treatment with these agents frequently leads to inflammation in specific organ systems not necessarily affected by the cancer, including the salivary and lacrimal glands with resultant hypofunction. Collectively, these are termed "immune-related adverse events. " When the salivary and/or lacrimal glands are involved, this condition is referred to as immune checkpoint inhibitor-induced sicca (ICI-induced sicca). "Sicca syndrome" is a loosely defined entity that encompasses dryness of more than one mucosal surface, generally that of the eyes and mouth. We discuss the epidemiology and postulate on the pathogenesis of ICI-induced sicca. We then review the literature on ICI-induced sicca and detail the clinical findings from 89 reported cases. One defining feature of ICI-induced sicca is that the condition often develops abruptly and is objectively quite severe. Within the reported cases, we highlight marked clinical heterogeneity with three potential patient subsets: (i) those with de novo sicca without systemic symptoms, (ii) those with de novo sicca with systemic symptoms, and (iii) and those with a flare of a preexisting rheumatic disease with sicca. The clinical workup of ICI-induced sicca is described, including the engagement of multiple specialists, and a management algorithm for treating ICI-induced sicca. Despite the involvement of the activation of T cells and secretion of cytokines in the affected tissues, the pathophysiology underlying ICI-induced sicca remains poorly understood.