Frequency of Skin Diseases in Children with Inborn Errors of Immunity

The immune system is a complex network of cells and organs which cooperate to protect individuals against infectious microorganisms. B- and T- lymphocytes, phagocytic cells, and soluble factors such as complement are some of the major components of the immune system and have specific critical functions in immune defense. When part of the immune system is missing or does not work correctly, immunodeficiency occurs; it may be either congenital (primary) or acquired (secondary). Primary immunodeficiency diseases (PIDs), also known as inborn errors of the immune system (IEI), are a heterogeneous group of inherited disorders caused by genetic mutations that alter the immune system.

Individual IEI are rare, IEIs as a group are not, and they represent a significant health burden. The updated classification of Inborn Errors of Immunity (IEI), encompassing a total of 555 IEIs, and 17 phenocopies due to mutations in 504 different genes. IEIs are currently categorized into 10 categories, with overlapping phenotypes. These categories are Combined immunodeficiencies, Combined immunodeficiencies with syndromic features, Predominantly antibody deficiencies, Diseases of immune dysregulation, Congenital defects of phagocytes, Defects in intrinsic and innate immunity, Autoinflammatory diseases, Complement deficiencies, Bone Marrow Failure, and Phenocopies of inborn errors of immunity.

IEIs present clinically as increased susceptibility to infections, autoimmunity, autoinflammation, allergy, bone marrow failure, and/or malignancy. IEI is to be suspected if there is recurrent or opportunistic infections, organ specific inflammation, autoimmunity, or continuous systemic immune activation and/or benign or malignant, potentially virally induced lymphoproliferation or tumors are seen together, in various combinations.

The skin is an organ of great importance at the immunological level and is commonly affected in IEI. Although infections are the most common cutaneous finding in IEI patients, noninfectious skin diseases are also quite frequent among those patients. These include allergic, inflammatory autoimmune, and malignant manifestations. Also, pigmentary changes, angioedema, urticaria, vasculitis along with nonspecific findings of eczema, erythroderma, granuloma, and ectodermal dysplasia are among the early presenting symptoms in IEI.

Severe combined immunodeficiency (SCID) patients present with severe, recurrent viral and bacterial infections as well as opportunistic infections very early in life (before 6 months of age). IEI is associated with atopy commonly include severe atopic dermatitis as a distinctive characteristic of the disease due to an immune dysregulation that affects skin barrier function.