Comel-Netherton syndrome: A local skin barrier defect in the absence of an underlying systemic immunodeficiency

Kira Stuvel, Jorn J. Heeringa, Virgil A.S.H. Dalm, Ruud W.J. Meijers, Els van Hoffen, Susan A.M. Gerritsen, Menno C. van Zelm, Suzanne G.M.A. Pasmans

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Comel-Netherton syndrome (NS) is a rare autosomal disease, characterized by severe skin disease, hair shaft defects, atopic diathesis, and increased susceptibility for skin infections. Since patients with NS suffer from recurrent infections, it has been hypothesized that an underlying immunodeficiency attributes to this. Here, we studied clinical and immunological characteristics of the cohort of NS patients in the Netherlands in order to identify whether potential immunodeficiencies result in the increased risk of infectious complications. Methods: Phenotypes were scored for severity of skin condition, specific hair shaft defects, atopy, and recurrent infections. Patients’ blood samples were collected for quantification of serum immunoglobulin (Ig) levels, specific antibodies against Streptococcus pneumoniae, and allergen-specific IgE, as well as detailed immunophenotyping of blood leukocyte and lymphocyte subsets by flow cytometry. Results: A total of 14 patients were included with age range 3-46 years and varying degrees of skin involvement. All patients presented with atopic symptoms (food allergy, n = 13; hay fever, n = 10; asthma, n = 7). Recurrent skin infections were common, particularly in childhood (n = 12). Low levels of specific antibodies against S pneumoniae were found in 10 of 11 evaluated patients. Detailed immunological analysis was performed on 9 adult patients. Absolute numbers of lymphocyte subsets and serum immunoglobulin levels were all within normal ranges. Conclusion: Multidisciplinary evaluation of our national cohort showed no evidence for a severe, clinically relevant systemic immunodeficiency. Therefore, we conclude that in Dutch NS patients the increased risk of infections most likely results from the skin barrier disruption and that increased allergen penetration predisposes to allergic sensitization.

Original languageEnglish
Pages (from-to)1710-1720
Number of pages11
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume75
Issue number7
DOIs
Publication statusPublished - 1 Jul 2020

Keywords

  • allergy
  • Comel-Netherton syndrome
  • dermatitis
  • immunodeficiency
  • SPINK5

Cite this

Stuvel, K., Heeringa, J. J., Dalm, V. A. S. H., Meijers, R. W. J., van Hoffen, E., Gerritsen, S. A. M., van Zelm, M. C., & Pasmans, S. G. M. A. (2020). Comel-Netherton syndrome: A local skin barrier defect in the absence of an underlying systemic immunodeficiency. Allergy: European Journal of Allergy and Clinical Immunology, 75(7), 1710-1720. https://doi.org/10.1111/all.14197