TY - JOUR
T1 - Comel-Netherton syndrome
T2 - A local skin barrier defect in the absence of an underlying systemic immunodeficiency
AU - Stuvel, Kira
AU - Heeringa, Jorn J.
AU - Dalm, Virgil A.S.H.
AU - Meijers, Ruud W.J.
AU - van Hoffen, Els
AU - Gerritsen, Susan A.M.
AU - van Zelm, Menno C.
AU - Pasmans, Suzanne G.M.A.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - allergy
KW - Comel-Netherton syndrome
KW - dermatitis
KW - immunodeficiency
KW - SPINK5
UR - http://www.scopus.com/inward/record.url?scp=85088064639&partnerID=8YFLogxK
U2 - 10.1111/all.14197
DO - 10.1111/all.14197
M3 - Article
C2 - 31975472
AN - SCOPUS:85088064639
SN - 0105-4538
VL - 75
SP - 1710
EP - 1720
JO - Allergy
JF - Allergy
IS - 7
ER -