What can inherited immunodeficiencies reveal about pyoderma gangrenosum?

Abstract

Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that is occasionally associated with primary immunodeficiency. Though contributions from dysregulation of the innate immune system, neutrophil dysfunction and genetic predisposition have been postulated, the precise pathogenesis of PG has not yet been elucidated. This article reviews reported cases of coexisting PG and primary immunodeficiency in order to gain insight into the complex pathophysiology of PG. Our findings suggest that variations in genes such as RAG1, ITGB2, IRF2BP2 and NFκB1 might play a role in genetically predisposing patients to develop PG. These studies support the feasibility of the role of somatic gene variation in the pathogenesis of PG which warrants further exploration to guide targeted therapeutics.

Keywords: autoimmunity; immunodeficiency; neutrophil; pathogenesis; pyoderma gangrenosum; scholarly review.

Figure 1.

Potential shared features in the pathogenesis of primary immunodeficiencies and pyoderma gangrenosum. IL, Interleukin; NFkB, nuclear factor kappa B; CVID, common variable immunodeficiency; SCID, severe combined immunodeficiency; IgA, immunoglobulin A; IgB, immunoglobulin B CGD, chronic granulomatous disease; IRF2BP2, Interferon regulatory factor 2 binding protein 2; RAG1, recombinase activating gene 1; IBD, inflammatory bowel disease; NADPH, nicotinamide adenine dinucleotide phosphate; LAD, leukocyte adhesion deficiency; NK, natural killer; ITGB2, integrin subunit beta2; CD, cluster of differentiation