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

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.