A novel molecular disease classifier for psoriasis and eczema

Novel specific therapies for psoriasis and eczema have been developed, and they mark a new era in the treatment of these complex inflammatory skin diseases. However, within their broad clinical spectrum, psoriasis and eczema phenotypes overlap making an accurate diagnosis impossible in special cases, not to speak about predicting the clinical outcome of an individual patient. Here, we present a novel robust molecular classifier (MC) consisting of NOS2 and CCL27 gene that diagnosed psoriasis and eczema with a sensitivity and specificity of >95% in a cohort of 129 patients suffering from (i) classical forms; (ii) subtypes; and (iii) clinically and histologically indistinct variants of psoriasis and eczema. NOS2 and CCL27 correlated with clinical and histological hallmarks of psoriasis and eczema in a mutually antagonistic way, thus highlighting their biological relevance. In line with this, the MC could be transferred to the level of immunofluorescence stainings for iNOS and CCL27 protein on paraffin‐embedded sections, where patients were diagnosed with sensitivity and specificity >88%. Our MC proved superiority over current gold standard methods to distinguish psoriasis and eczema and may therefore build the basis for molecular diagnosis of chronic inflammatory skin diseases required to establish personalized medicine in the field.

[1]  K. Reich,et al.  Oral alitretinoin treatment in patients with palmoplantar pustulosis inadequately responding to standard topical treatment: a randomized phase II study , 2016, The British journal of dermatology.

[2]  M. Kelson,et al.  Oral fumaric acid esters for psoriasis. , 2015, The Cochrane database of systematic reviews.

[3]  Michael Hölzel,et al.  IL-36γ (IL-1F9) is a biomarker for psoriasis skin lesions. , 2015, The Journal of investigative dermatology.

[4]  J. Krueger,et al.  The translational revolution and use of biologics in patients with inflammatory skin diseases. , 2015, The Journal of allergy and clinical immunology.

[5]  Matteo Pellegrini,et al.  Comparison of Molecular Signatures from Multiple Skin Diseases Identifies Mechanisms of Immunopathogenesis , 2014, The Journal of investigative dermatology.

[6]  C. Ryan,et al.  Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities. , 2015, Dermatologic clinics.

[7]  M. Schön,et al.  The plot thickens while the scope broadens: a holistic view on IL‐17 in psoriasis and other inflammatory disorders , 2014, Experimental dermatology.

[8]  B. Elewski,et al.  Secukinumab in plaque psoriasis--results of two phase 3 trials. , 2014, The New England journal of medicine.

[9]  Fabian J Theis,et al.  Intraindividual genome expression analysis reveals a specific molecular signature of psoriasis and eczema , 2014, Science Translational Medicine.

[10]  T. Bieber,et al.  Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. , 2014, The New England journal of medicine.

[11]  A. Anichini,et al.  Towards combinatorial targeted therapy in melanoma: From pre-clinical evidence to clinical application (Review) , 2014, International journal of oncology.

[12]  Jon Emery,et al.  Risk Prediction Models for Melanoma: A Systematic Review , 2014, Cancer Epidemiology, Biomarkers & Prevention.

[13]  D. Fisher,et al.  Current status of diagnostic and prognostic markers in melanoma. , 2014, Methods in molecular biology.

[14]  Rosa Parisi,et al.  Global epidemiology of psoriasis: a systematic review of incidence and prevalence. , 2013, The Journal of investigative dermatology.

[15]  S. Werner,et al.  Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk. , 2012, The Journal of clinical investigation.

[16]  A. Peserico,et al.  Erythroderma in the era of biological therapies. , 2012, European journal of dermatology : EJD.

[17]  T. Lotti,et al.  Dimethyl fumarate contact dermatitis of the foot: an increasingly widespread disease , 2012, International journal of dermatology.

[18]  Matti Pirinen,et al.  Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity , 2012 .

[19]  M. Sculpher,et al.  Alitretinoin for Severe Chronic Hand Eczema , 2012, PharmacoEconomics.

[20]  C. Johansen,et al.  Kinetics and differential expression of the skin‐related chemokines CCL27 and CCL17 in psoriasis, atopic dermatitis and allergic contact dermatitis , 2011, Experimental dermatology.

[21]  J. Ring,et al.  Mutual antagonism of T cells causing psoriasis and atopic eczema. , 2011, The New England journal of medicine.

[22]  J. Rutledge,et al.  A tale of two plaques: convergent mechanisms of T‐cell‐mediated inflammation in psoriasis and atherosclerosis , 2011, Experimental dermatology.

[23]  L. Settimi,et al.  A case of contact dermatitis to dimethylfumarate in shoes identified in Italy. , 2010, Annali dell'Istituto superiore di sanita.

[24]  Mayte Suárez-Fariñas,et al.  Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis. , 2009, The Journal of allergy and clinical immunology.

[25]  Frank O. Nestle,et al.  Mechanisms of Disease: Psoriasis. , 2009 .

[26]  S. Baratchi,et al.  Recent advances on the roles of NO in cancer and chronic inflammatory disorders. , 2009, Current medicinal chemistry.

[27]  Koichiro Nakamura,et al.  CCL27‐transgenic mice show enhanced contact hypers ensitivity to Th2, but not Th1 stimuli , 2008, European journal of immunology.

[28]  C. Demirkesen,et al.  Non‐pustular palmoplantar psoriasis: is histologic differentiation from eczematous dermatitis possible? , 2007, Journal of cutaneous pathology.

[29]  G. Schuler,et al.  Infliximab in the treatment of moderate to severe atopic dermatitis. , 2005, Journal of the American Academy of Dermatology.

[30]  J. Travers,et al.  Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. , 2003, The Journal of allergy and clinical immunology.

[31]  Koichiro Nakamura,et al.  Increased serum cutaneous T cell-attracting chemokine (CCL27) levels in patients with atopic dermatitis and psoriasis vulgaris. , 2003, The Journal of allergy and clinical immunology.

[32]  H. Soto,et al.  CCL27–CCR10 interactions regulate T cell–mediated skin inflammation , 2002, Nature Medicine.

[33]  Altmeyer,et al.  Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study , 1998, The British journal of dermatology.

[34]  R. Weller,et al.  Detection of nitric oxide and nitric oxide synthases in psoriasis , 1998, Archives of Dermatological Research.

[35]  C. Suschek,et al.  A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes , 1996, The Journal of experimental medicine.

[36]  I I Lelis,et al.  [Atopic dermatitis]. , 1980, Vestnik dermatologii i venerologii.

[37]  O. Braun-falco,et al.  [Histological differential diagnosis of psoriasis vulgaris and seborrheic eczema of the scalp]. , 1979, Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete.