Purpose of review
To show that skin symptoms help in the recognition of primary immunodeficiencies (PIDs). To analyze whether recent molecular data help in understanding genotype/phenotype relations.
Erythroderma in Omenn syndrome may be caused by either mutations in genes associated with severe combined immunodeficiency (SCID) in which the generation of some T cells is possible, which results in potentially autoreactive lymphoid clones, or by selective proliferation of revertant CD8+ T cells in the skin due to clonal expansion in response to infections or autoantigens.
The newborn eczematous eruption, which occurs mainly in the signal-transducer-and-activator-of-transcription-3 (STAT3) variant, helps to differentiate STAT3 from Dedicator of Cytokinesis 8-related Hyper-IgE-syndrome (HIES).
Impaired T helper 17 cell (TH17) immunity [HIES and defects of autoimmune regulator element (AIRE), STAT-1, and interleukin17 receptor(IL17(R))] may give rise to localized chronic mucocutaneous candidiasis, whereas a defective innate immune system predisposes to systemic candidiasis [congenital neutropenia, neutrophil dysfunction, and caspase recruitment domain 9 (CARD9) deficiency].
Noninfectious granulomas may be the presenting symptom in innate immunity defects [such as chronic granulomatous disease (CGD) or in predominantly humoral immunodeficiencies such as common variable immunodeficiency], as well as ataxia teleangiectasia or rare recombination-activating gene-deficient cases.
The skin is important in the diagnosis of PIDs. In particular eczematous lesions, erythroderma, noninfectious granuloma, and microbial manifestations may help to direct further diagnostic laboratory analysis.