Cutaneous granulomas in ataxia telangiectasia and other primary immunodeficiencies: reflection of inappropriate immune regulation?

Abstract

Background: Non-infective cutaneous granulomas with unknown pathogenesis occur in various primary immunodeficiencies (PIDs) including ataxia telangiectasia (A-T).

Objective: To find a common immunological denominator in these cutaneous granulomas.

Methods: The dermatological and immunological features of 4 patients with A-T and cutaneous granulomas were described. The literature on skin granulomas in A-T and in other PIDs is reviewed.

Results: All 4 A-T patients had progressive granulomas on their limbs and showed decreased IgG and IgA concentrations with normal IgM levels. They had a marked decrease in B cells and naïve T cells coinciding with the appearance of the cutaneous granulomas. Similar B- and T-cell abnormalities were described in patients with other PIDs with skin granulomas.

Conclusions: We hypothesize that the pathogenesis of these skin granulomas is related to immune dysregulation of macrophages due to the absence of naïve T cells with an appropriate T-cell receptor repertoire and the unopposed activity of γδ T cells and/or natural killer cells.