Ask The Expert
September 15, 2020
When should a child with repeated skin infection of moderate to severe atopic dermatitis (4 to 6 courses of antibiotics annually), but with no infections elsewhere, be investigated for immunodeficiency?
Primary immunodeficiencies (PIDs), also known as inborn errors of immunity, are a group of more than 450 diseases characterized by an increased susceptibility to infections, immune dysregulation, and malignancies. Early diagnosis and adequate treatment of affected patients usually lead to an improved quality of life, lower impact to the healthcare system, and ultimately less mortality.
Skin complaints, both infectious and noninfectious, are common in patients with PIDs. However, not every skin disorder is a manifestation of PID, and not all PIDs include skin affection. Nevertheless, we should be trained to suspect or recognize an underlying PID in patients with common skin diseases such as atopic dermatitis.
Some characteristic skin lesions in particular PIDs include:
- Skin telangiectasia and cafe au lait macules in ataxia-telangiectasia.
- Abscesses and granulomas in chronic granulomatous disease.
- Recurrent boils and cold abscesses in hyper-IgE syndrome due to dominant-negative mutations in STAT3 (signal transducer and activator of transcription 3) gene.
- Alopecia, vitiligo, mucocutaneous candidiasis and nail dystrophy in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) due to AIRE pathogenic variants.
- Ectodermal dysplasia in NEMO (NF-kappa B Essential Modulator) deficiency.
- Severe eczema in Wiskott-Aldrich syndrome (WAS) and Netherton syndrome.
On the other hand, atopic dermatitis (AD) per se generates a local state of immunodeficiency in the skin (barrier defect, innate immune dysregulation, increased TH2 and TH22 inflammation, defective TH1 and TH17 immunity), which increases the risk for cutaneous infections, especially by Staphylococcus aureus and certain herpes virus (herpes simplex virus, varicella zoster virus). Additionally, severe atopic dermatitis can be associated to variants in several genes including DSG1, FLG, TLR2, TLR4, and SPINK.
There are no established clinical criteria that can absolutely exclude PID in patients with AD. However, every patient with AD, especially when moderate or severe, should have a thorough evaluation regarding family history of PID, personal history of recurrent, severe or opportunistic infections, and other clinical details suggesting PID (e.g., coarse facial features, pneumatoceles, skeletal abnormalities, delayed shedding of primary teeth, low TH17 numbers and NIH score ≥40 in STAT3-defective HIES; thrombocytopenia with microplatelets in WAS; ‘bamboo hair’ in Netherton syndrome). Even more, we must consider that the clinical manifestations of PID are highly variable depending on the type of gene mutation, the degree of protein affection, gene-gene interactions, and the effect of environmental factors.
- de Wit, J., Brada, R. J. K., van Veldhuizen, J., Dalm, V. A. S. H., & Pasmans, S. G. M. A. (2019). Skin disorders are prominent features in primary immunodeficiency diseases: A systematic overview of current data. Allergy, 74(3), 464–482. https://doi.org/10.1111/all.13681
- Kabashima, K. (Ed.). (2016). Immunology of the Skin: Basic and Clinical Sciences in Skin Immune Responses. Springer Japan. https://doi.org/10.1007/978-4-431-55855-2
- Lehman, H. (2014). Skin Manifestations of Primary Immune Deficiency. Clinical Reviews in Allergy & Immunology, 46(2), 112–119. https://doi.org/10.1007/s12016-013-8377-8
- Yamazaki, E., Kikuchi, K., Sasahara, Y., Kono, M., Akiyama, M., & Aiba, S. (2020). Atopic dermatitis without serum immunoglobulin E elevation or loss‐of‐function filaggrin gene mutation in a patient with X‐linked agammaglobulinemia. The Journal of Dermatology, 47(1), 58–60. https://doi.org/10.1111/1346-8138.15154
Andrés Hernandez, MD
Allergy and Clinical Immunology
Hospital Nacional Guillermo Almenara Irigoyen
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