Primary immunodeficiency and chronic mucocutaneous candidiasis: pathophysiological, diagnostic, and therapeutic approaches.

Abstract

Chronic mucocutaneous candidiasis (CMC) is characterized by a chronic or recurrent non invasive infection, mainly due to Candida albicans , in skin, nails, and mucous membranes, associated in some cases with autoimmune manifestations. The key immune defect is disruption of the action of cytokine IL-17, whose most common genetic etiology is STAT1 gene gain-of function (GOF) mutations. The initial appropriate treatment for fungal infections is with azoles. However, frequent occurrence of drug resistance is the main limitation. Therefore, identification of the underlying inborn error if immunity in CMC may allow widening therapeutic options aimed at restoring immunological function. Type I and II Janus Kinase -inhibitors have been shown to control CMC in cases associated with STAT1 GOF. In this review, we delve into the pathogenesis of CMC and the underlying immune mechanisms. We describe the reported genetic defects in which CMC is the main manifestation. Diagnostic and therapeutic approaches for these patients are also offered.

Case for diagnosis. Disseminated erythematous and scaly plaques: chronic mucocutaneous candidiasis

“…Finally, AIDS is differentiated from CMCC by positive HIV serology, reduced CD4+ T-cell count, and occurrence of opportunistic infections. 6 , 7 …”

Infections in Inborn Errors of Immunity with Combined Immune Deficiency: A Review

“…Defective IL - 17 responses have been found to underlie most cases of mucocutaneous candidiasis, but in immunocompetent individuals intact Th17 responses are protective against infection despite colonization of skin and other surfaces [ 106 ]. Identification of the underlying inborn error of immunity is important to decide on therapeutic options since azole resistance is not uncommon [ 107 ]. STAT1 gain of function mutations have been found to result in impaired STAT3 responses resulting in mucocutaneous candidiasis [ 108 ].…”

Host, pathogenic fungi and the microbiome: A genetic triangle in infection

“…For example, invasive aspergillosis has been linked with inborn errors in patients with chronic granulomatous disease, severe congenital neutropenia or leukocyte adhesion deficiency type I ( 31 , 32 ). Moreover, other less common congenital immunodeficiencies (e.g., CARD9 immunity, IL-12/interferon (IFN)-γ axis or IL-17 immunity) have been described to increase susceptibility risk to invasive candidiasis, dermatophytosis, chronic mucocutaneous candidiasis or endemic mycoses ( Figure 1 ) ( 33 – 36 ).…”