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Images in Dermatology
September 28, 2022

Netherton Syndrome

Author Affiliations
  • 1Vestfold Hospital Trust, Tønsberg, Norway
  • 2Department of Clinical Genetics, Odense University Hospital, Clinical Institute, University of Southern Denmark, Odense, Denmark
JAMA Dermatol. 2022;158(11):1315. doi:10.1001/jamadermatol.2022.3796

A 7-year-old girl with presumed atopic dermatitis was evaluated at our institution’s department of dermatology. She had a history of erythroderma at birth and later showed signs of delayed growth. During her first years of life, she developed multiple food allergies, allergic asthma, and rhinitis. Her skin was dry, with marked redness of her face and hands (Figure 1A). Because of her sparse and brittle hair and thin eyebrows, Netherton syndrome (NS) was suspected. Examination of her hair using light microscopy showed invagination of the hair at several points along the shaft, which was consistent with trichorrhexis invaginata (“bamboo hair”) (Figure 1B). Immunohistochemistry performed on a skin biopsy showed absent staining for lymphoepithelial Kazal-type-related inhibitor. The diagnosis was confirmed by molecular genetic analysis, which showed 2 heterozygous pathogenic variants in the SPINK5 gene.

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Allergological contribution to Netherton syndrome diagnosis and management
Roberto Paganelli, M.D. | UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy*, roberto.paganelli@unicamillus.org
Dear Editor
We read with great interest the text of the Images in Dermatology on Netherton syndrome (NS) (JAMA Dermatology Sept.28, 2022) and in particular the conclusion that “early diagnosis is crucial to engage correct management, which involves a multidisciplinary approach. This includes specialists in allergology, dermatology, immunology […]”(1). We would like to underscore the contribution of molecular allergology with multiplex proteomic micro- and macroarrays to both diagnosis and management of these patients, who, at variance with Hyper IgE syndrome, are at risk of anaphylaxis due to environmental and food allergens. As described in our recent paper(2), the traditional allergological
diagnostic approach in NS is problematic due to both the skin conditions which prevent the use of in vivo tests, and the extremely high levels of total IgE which can alter the results of current singleplex tests. The multiplexed approach offers the advantage of obtaining hundreds of results using minimal amount of serum, and ensures the reliability of the results despite the presence of very high levels of IgE(3, 4). In a series of 10 patients affected by NS, aged 3 to 43 years, we found two positive to Hev b 6 and Hev b 5 and with history of severe reactions to latex, and five others showed strong IgE responses to molecules from cow’s milk, hen’s egg and fish parvalbumin(2), Avoidance of the foods that scored positive in the microarray test determined an immediate and marked improvement in both skin and gastrointestinal symptoms, preventing anaphylactic episodes, with a great improvement in the perceived quality of life. The new methods based on molecular micro- or macro-arrays greatly advance their diagnostic value and allow to distinguish true and potentially harmful sensitizations even in the presence of high IgE levels in rare diseases, thus improving diagnosis and management(5).

Enrico Scala, M.D.
Clinical and Laboratory Molecular Allergy Unit | IDI-IRCCS | FLMM - Rome, Italy. E.scala@idi.it
Roberto Paganelli, M.D.
UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy*, roberto.paganelli@unicamillus.org

References
1. Drivenes JL, Bygum A. Netherton Syndrome. JAMA Dermatol. 2022;158(11):1315.
2. Scala E, Condorelli AG, Scala A, Caprini E, Didona B, Paganelli R, et al. IgE Sensitization Profile in Patients with Netherton Syndrome. Int Arch Allergy Immunol. 2022:1-6.
3. Scala E, Caprini E, Abeni D, Meneguzzi G, Buzzulini F, Cecchi L, et al. A qualitative and quantitative comparison of IgE antibody profiles with two multiplex platforms for component-resolved diagnostics in allergic patients. Clin Exp Allergy. 2021;51(12):1603-12.
4. Matricardi PM, Kleine-Tebbe J, Hoffmann HJ, Valenta R, Hilger C, Hofmaier S, et al. EAACI Molecular Allergology User's Guide. Pediatr Allergy Immunol. 2016;27 Suppl 23:1-250.
5. Scala E, Abeni D, Asero R. Disease-Specific Molecular Profiles Highlighted by Radar Graphic Display. Int Arch Allergy Immunol. 2020;181(7):536-9.
CONFLICT OF INTEREST: ES has received consultant arrangements and speakers’ bureau participation from Stallergenes, Thermo Fisher Scientific, and DASIT S.p.A. and non-financial support from Macroarray Diagnostics, Vienna, all outside the submitted work. RP has no potential conflicts of interest.
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