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

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.

Netherton syndrome; neuropsychological and psychosocial functioning of child and adult patients and their parents.

BACKGROUND: Netherton syndrome is a rare severe skin disease. Clinical experience showed considerable psychosocial burdens among Netherton syndrome patients/families. Their (neuro)psychological functioning has never been investigated. OBJECTIVE: To investigate neuropsychological/psychosocial functioning of Netherton syndrome patients and parents. METHODS: A total of 12 Netherton syndrome patients and/or parents completed neuropsychological tests, semi-structured-interviews, and psychological-questionnaires. RESULTS: Intelligence results showed disharmonic profiles, with below-average scores on processing speed. Neuropsychological problems and unfavorable outcomes on health-related quality of life, illness-appearance-related problems, and negative social consequences among patients/parents were found. Psychopathological (emotional) problems were reported; stigmatization, bullying was common among Netherton syndrome patients. CONCLUSION: Compared with normative data, Netherton syndrome patients showed neuropsychological and psychosocial problems. Standard follow-up is necessary to identify problems at early stage.