Molecular diagnostics of psoriasis and eczema a novel ... · • Psoriasis and eczema phenotypes...

Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein

5th Munich Biomarker Conference 2015/12/01

Molecular diagnostics of psoriasis and eczema – a novel approach to

establish personalized therapy

Natalie Garzorz, MD

[email protected]

Center of Allergy and Environment



Inflammatory skin diseases: stigmatizing, devastating, severe diseases

Psoriasis:

20.000.000 European citizens

Atopic eczema:

>20.000.000 European adults

Life-long, un-curable, disfiguring, disabling, stigmatizing diseases

onset <30 years of life

Systemic diseases associated with:

Arthritis, cardiovascular events, metabolic

syndrome, inflammatory bowel diseases

Rhinoconjunctivitis, allergic asthma,

inflammatory bowel diseases

Anxiety, depression, suicidal ideation are common

Hay RJ et al, J Invest Dermatol 2014; Dalgard FJ et al, J Invest Dermatol 2015

Cause Global YLDs YLD rank

Low back pain 80,666,896 1

Major depressive disorder 63,239,334 2

Iron-deficiency anemia 42,505,250 3

Skin conditions 33,717,725 4

Neck pain 32,650,797 5



2015 – a good year for psoriasis patients

Apremilast Secukinumab First biosimilars

Selective PDE4 inhibitor human IL-17A Antibody Infliximab biosimilars

Oral medication

(30mg 1-0-1)

Subcutaneous injection

(300mg every 4 weeks)

No clinical trials in the field of

dermatology

Very good safety profile Safety profile: KI for IBD,

mucocutaneous candidiasis

Implications for Patient –

Prescriber – Payer

Slow response, effectivity

better than classic systemic

therapies, 2nd line label

Most effective approved

therapy, 1st line label

Price decline for example in

Scandinavia



Prediction: impossible!

Psoriasis (Th17):

20.000.000 Europeans

Atopic eczema (Th2):

20.000.000 European adults

Most potent therapy (only symptomatic): secukinumab

EMA approval: 19th January, 2015

Most potent therapy (only symptomatic): dupilumab

EMA approval expected 2017

Non-responders: 20% Non-responders: 30%

Annual costs: 25.000€/ patient Annual costs: estimated 20.000€/ patient

Pa

tie

nts

[%

]

Pa

tie

nts

[%

]

Beck LA et al, N Engl J Med 2014; Langley R et al, N Engl J Med 2014



Is it really all the same?

Fotolia.com

ebalance.com

healthline.com



Self-limited versus non-limited eczema

Biopsies of

eczema and

autologous non-involved skin

Whole genome

expression array

Atopic eczema

Allergic contact

dermatitis

Nummular eczema

Dyshidrotic eczema



Eczema ≠ eczema: Self-limited versus non-limited eczema

Immunology • IL-1b

• AIM2

• Numerous chemokines

(CCL2/3/7/8/17/19/26,

CXCL1/2/8/9/10/11)

• Hyluronic acid/

extracellular matrix

• In total 54 immune

related genes

Significant in naturally

occuring eczema only

Significant in

both

Significant in inducible

eczema only

Quaranta M et al, Sci Transl Med 2014



Overlapping phenoytpes and why we need disease classifiers…

Scalp psoriasis or seborrheic dermatitis? Ear canal psoriasis or

eczema ?

Pretty clear…but:

Psoriasis or nummular eczema?

Palmoplantar psoriasis or

dyshidrotic hand eczema?



Genes Environment: Both diseases in parallel and what they teach us…

Eyerich S, New Engl J Med, 2011 Eyerich S et al, N Engl J Med 2011

Genes Environment in the pathogenesis of eczema and psoriasis



Significant in psoriasis only Significant in both Significant in eczema

only

Psoriasis: Th17, IL-10 and IL36 family Eczema: Th2, IL-6

Quaranta M et al, Sci Transl Med 2014

SERPINB13 ATP12A

SOST PLA2G4D

NOS2 HPSE

Met

abo

lism

Molecular signature of psoriasis and eczema



The molecular classifier separates clear cases of eczema and psoriasis on RNA level

Psoriasis

Ekzem

Psoriasis

Ekzem

Sensitivity and specificity > 95%

n= 88



The molecular classifier identifies subclasses of eczema and psoriasis

Psoriasis

Ekzem

Psoriasis

Ekzem



The molecular classifier identifies psoriasis and eczema on the protein level

Psoriasis

Ekzem

Psoriasis

Ekzem

Psoriasis

Eczema

Psoriasis Eczema Psoriasis Eczema

Sensitivity and specificity > 88%



NOS2 and CCL27 correlate with clinical and histological hallmarks of psoriasis and

eczema

Psoriasis

Ekzem

Psoriasis

Ekzem



The classifier gives a clear prediction in unclear cases

Patient 1: - 20 y old patient, since years slightly

itchy skin lesions - Mother: Psoriasis - Asthma, allergic rhinoconjunctivitis - S. aureus negative - Histology: Psoriasis - Worsening under Fumaderm - Improvement under Alitretinoin



The classifier gives a clear prediction in unclear cases

Patient 2: - 78 y patient, since 1 year itchy skin

lesions - Histology: Eczema - No improvement under steroids

- Improvement under Fumaderm



Financial support

Bayerische

Akademie der

Wissenschaften

Kommission

Klinische Forschung

Take home messages

• Psoriasis and eczema phenotypes may overlap making an

accurate diagnosis impossible in special cases, not to speak

about predicting the clinical outcome of an individual patient.

• Only using the two markers NOS2 and CCL27 our classifier

(MC) diagnosed psoriasis and eczema with a sensitivity and

specificity of > 95 % (> 88 %) on the level of RT-PCR

(immunofluorescence stainings)

• Histologically misdiagnosed patients could be identified by

MC and a clear prediction for therapeutic response in

indistinct patients could be given that was in line with the

subsequent clinical course.

• NOS2 and CCL27 correlate with clinical and histological

hallmarks of psoriasis and eczema in a mutually antagonistic

way, thus highlighting their biological relevance.

Department for dermatology and allergy Biederstein, Munich

Director: Tilo Biedermann

Kilian Eyerich, Johannes Ring, Felix Lauffer, Regina Franz

Thank you for your attention!

Laboratorio di Immunologia (IDI-IRCCS), Rome

Director: Andrea Cavani

Francesca Nasorri, Teresa Carbone, Cristina Albanesi,

Claudia Scarponi, Gianna Zambruno, Francesca Cianfarani

ZAUM – Center of allergy and environment, Munich

Director: Carsten Schmidt-Weber

Stefanie Eyerich

Anne Atenhan, Jenny Thomas, Jana Sänger, Sebastian P. Stark

Dipartimento di Scienze biomediche avanzate, Università

degli Studi di Napoli Federico II, Naples, Italy

Anna Balato

Department for dermatology, allergology and venereology, Kiel

Stephan Weidinger, Hans-Jörg Baurecht, Elke Rodriguez

Helmholtz Center – Institute for Computational Biology, Munich

Director: Fabian Theis

Linda Krause, Nikola S. Müller

Molecular diagnostics of psoriasis and eczema a novel ... · • Psoriasis and eczema phenotypes...

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