title: Topical application of a vitamin D analogue exacerbates atopic dermatitis and induces the atopic dermatitis-like phenotype in Stat6VT mice.
abstract: Calcipotriene is a topical vitamin D3 analogue approved for the treatment of plaque and scalp psoriasis. We report the case of a 2-year-old boy whose atopic dermatitis (AD) flared in response to application of calcipotriene 0.005% cream and solution for a mistaken diagnosis of plaque and scalp psoriasis. We investigated whether the patient's eruption was secondary to an allergic contact dermatitis. In the Stat6VT mouse model of AD we tested whether calcipotriene could induce the otherwise-spontaneous AD-like phenotype. Closed patch testing was done on the patient with calcipotriene solution and cream, moisturizing cream, and 51% isopropanol. Stat6VT and wild-type (WT) mice were treated for 7 days with calcipotriene solution or vehicle (isopropanol) applied to the right and left upper back skin, respectively, after which mice were followed longitudinally for 10 weeks. Biopsy specimens from prior treatment sites were then collected for histology and RNA isolation. RNA was analyzed for interleukin (IL-4) expression using quantitative polymerase chain reaction. Patch testing was negative. Stat6VT mice, in contrast to WT mice, developed a persistent eczematous dermatitis at sites of calcipotriene application. Clinical and histologic features and high IL-4 transcript levels were consistent with the spontaneous AD-like phenotype seen in Stat6VT mice. At sites of active disease, calcipotriene can worsen a flare of AD. In Stat6VT mice, calcipotriene can induce the AD-like phenotype.
authors.affiliation: Department of Dermatology, Indiana University, Indianapolis, Indiana.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Turner
authors.forename: Sonia C
authors.initials: SC
authors.lastname: Dasilva-Arnold
authors.forename: Qiaofang
authors.initials: Q
authors.lastname: Yi
authors.forename: Purvi
authors.initials: P
authors.lastname: Mehrotra
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Travers
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002117:Calcitriol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D002675:Child, Preschool; D017449:Dermatitis, Allergic Contact / Q000473:pathology; D003876:Dermatitis, Atopic / Q000139:chemically induced* / Q000473:pathology*; D003879:Dermatologic Agents / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D005148:Facial Dermatoses / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010328:Patch Tests; D010641:Phenotype; D050800:STAT6 Transcription Factor / Q000235:genetics
chemical_list: D003879:Dermatologic Agents; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C055085:calcipotriene; D015847:Interleukin-4; D002117:Calcitriol
references.citation: Clin Immunol. 2008 Mar;126(3):332-7
references.pmid: 18166499
references.citation: Br J Dermatol. 2008 Jul;159(1):245-7
references.pmid: 18489598
references.citation: N Engl J Med. 2008 Apr 3;358(14):1483-94
references.pmid: 18385500
references.citation: Crit Rev Immunol. 2008;28(1):15-43
references.pmid: 18298382
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11736-41
references.pmid: 16880407
references.citation: J Immunol. 2010 Mar 15;184(6):3186-90
references.pmid: 20147633
references.citation: J Allergy Clin Immunol. 2009 Sep;124(3 Suppl 2):R7-R12
references.pmid: 19720210
references.citation: Clin Rev Allergy Immunol. 2011 Dec;41(3):245-53
references.pmid: 21222175
references.citation: J Invest Dermatol. 2009 Feb;129(2):498-502
references.pmid: 18650845
references.citation: Immunol Allergy Clin North Am. 2010 Aug;30(3):397-409
references.pmid: 20670821
references.citation: Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2495-503
references.pmid: 20930170
references.citation: J Immunol. 2003 Apr 1;170(7):3478-87
references.pmid: 12646608
references.citation: J Immunol. 2001 Aug 15;167(4):1945-53
references.pmid: 11489974