Abstract:The patient was a 26-year-old male. He had red and scaling skin of the entire body since birth, as well as an elevated level of serum IgE. Genetic testing revealed a mutation in the SPINK5 gene, which had confirmed the diagnosis with Netherton syndrome. He has had significant pruritis since birth, and subsequently had symptoms of sleeping disorders and concentration difficulty throughout the day. Since treatment with various antihistamines were not effective, we administered dupilumab and found that it was eff… Show more
“…To our knowledge, a total of ten cases including ours have been described, highlighting the encouraging effects of dupilumab in NS (Table 2) [4][5][6][7][8][9][10] . In seven out of ten patients, dupilumab achieved a sustained response.…”
“…To our knowledge, a total of ten cases including ours have been described, highlighting the encouraging effects of dupilumab in NS (Table 2) [4][5][6][7][8][9][10] . In seven out of ten patients, dupilumab achieved a sustained response.…”
“…Other typical findings are ichthyosis (type linearis circumflexa) and hair abnormalities (trichorrhexis invaginata). Dupilumab treatment for patients with Netherton syndrome was reported in a total of 16 cases ( Table 6 ) [ 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 ]. All cases showed prompt resolution of itch measured by NRS and an improvement of skin lesions evaluated by EASI or BSA within 3 months.…”
Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks the signaling of interleukin (IL)-4 and -13. Several other chronic skin conditions share mechanistic overlaps with AD in their pathophysiology, i.e., are linked to type 2 inflammation. Most recently, dupilumab was approved by the U.S. Food and Drug Administration for prurigo nodularis (PN). Given its relatively good safety profile, effective off-label use of dupilumab has been reported for a multitude of dermatologic diseases and several clinical trials for dermatologic skin conditions are currently ongoing. We conducted a systematic review of applications of dupilumab in dermatology other than AD and PN by searching the databases PubMed/Medline, Scopus, Web of Science and Cochrane Library as well as the clinical trial registry ClinicalTrials.gov. We found several reports for effective treatment of bullous autoimmune diseases, eczema, prurigo, alopecia areata, chronic spontaneous urticaria, Netherton syndrome and a variety of other chronic inflammatory skin diseases.
“…Mutations in SPINK5 could increase the expression level of kallikrein 5, which can activate Th2 immune responses via stimulating the production of various proinflammatory molecules. 78 8 NS patients were reported to successfully treated with dupilumab [79][80][81][82][83][84][85][86] : four patients got significant improvement within several days after the first loading dose of 600 mg especially for pruritus. All the patients were reported to have a clearance of all the lesions after an average treatment duration of 6.1 months.…”
Section: Dupilumab In Netherton Syndrome Treatmentmentioning
Type 2 immune response refers to a complicated series of immune responses characterized by Th2 polarization and Th2 cytokines secretion. The IgE secretion, airway hypersensitivity, and effector cell recruitment (eosinophils, mast cells, basophils) in skin lesion and peripheral blood stream could be upregulated during the activation of type 2 immune response. Th1/Th2 ratio, also referred as Th1/Th2 balance, represent the T lymphocytes immune pattern to a certain degree: Th1-dominated responses are often involved in intracellular infections (e.g., mycobacterium tuberculosis) and autoimmune diseases (e.g., Graves' disease) while Th2-dominated responses are involved in allergic conditions (e.g., atopic dermatitis, eczema), IgE mediated diseases (e.g., urticaria), and fibrotic dermatoses (e.g., keloids). Dupilumab, as one of the most widely applied Th2 cytokine inhibitors, could block the bioactivity of IL-14/IL-13 via competitively binding to the common IL-4Rα subunit shared by IL-4 and IL-13 receptors. In addition to the direct inhibition of type 2 response, dupilumab is also effective in autoimmune and some infectious skin diseases through indirect regulation of type 1 immune response. The pathological mechanism of Th2 responses and advanced clinical application of dupilumab in skin diseases will be summarized and discussed in the review.
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