The Skin Tells the Story: Early Signs of Inborn Errors of Immunity

Inborn errors of immunity (IEIs) comprise a heterogeneous group of more than 500 genetic disorders, often presenting with recurrent infections, autoimmunity, malignancies, allergic inflammation, and various skin manifestations.

To evaluate the prevalence, phenotypes, and treatment responses of skin manifestations in IEIs.

Patient data from 2018 to 2024 were retrospectively analyzed in a single-center cohort from Turkey and classified according to the 2024 report of the International Union of Immunological Societies. Recorded skin manifestations included atopic dermatitis-like lesions, infections, granulomas, pigmentary abnormalities, vascular changes, and autoimmune lesions.

Among 389 patients with IEIs, 155 (39.8%) exhibited skin manifestations, with 48.3% presenting as an initial symptom. The median (interquartile range) age at onset of skin manifestations was 8.5 (2.2-84) months, whereas the median age at referral was 84 (19-174) months. The predominant IEI categories were combined immunodeficiencies with associated or syndromic features (21%) and immunodeficiencies affecting cellular and humoral immunity (20.5%). Cutaneous manifestations were most frequent in congenital phagocyte defects (56.8%). Predominant skin manifestations included infections (59.3%), atopic dermatitis-like lesions (37.4%), and chronic mucocutaneous candidiasis (16.7%). During the median follow-up period of 44 (17-68) months, the most common comorbidities were recurrent sinopulmonary infections (67.3%) and growth delay (50.6%). Biological agents were administered to 11.6% of patients, whereas 20% underwent hematopoietic stem cell transplantation.

Skin manifestations are common and often early indicators of IEIs. Their coexistence with recurrent infections or growth delay should prompt immunologic evaluation. Early recognition may facilitate timely diagnosis, targeted treatment, and improved long-term outcomes.