Dermatology Update: Latest Findings on Rheumatic Skin Disease Across the Lifespan

Victoria P. Werth, MD Lisa M. Arkin, MDPerelman School of Medicine at the University of Pennsylvania University of Wisconsin School of Medicine

Veterans Affairs Administration American Family Children’s Hospital

ObjectivesRecognize the skin manifestations and mimics of rheumatic disorders in adults, infants and children

Understand the current therapeutic approaches to rheumatic skin disease across the lifespan

Prepare to counsel regarding good sun protection practices

Disclosures• Dr. Werth - Consulting: Celgene, Medimmune, Resolve, Neovacs,

Genentech, Idera, Janssen, Lilly, Pfizer, Biogen, BMS, Gilead, Amgen, Medscape, Nektar, Incyte, EMD Sorona, CSL Behring

• Grants: Celgene, Janssen, Pfizer, Biogen, Gilead, CorbusPharmaceuticals, Genentech, AstraZeneca

• University of Pennsylvania owns the copyright for the CLASI and CDASI

• Dr. Arkin – Investigator for Celgene, Candela

The challenge

Few cross-comparative studies involving children and adults with rheumatic skin disease

Recognize the skin manifestations and mimics of rheumatic disorders in adults, infants and children

Understand the current therapeutic approaches to rheumatic skin disease across the lifespan

Contrast adult vs pediatric presentations:

• Cutaneous Lupus Erythematosus

• Dermatomyositis/Juvenile Dermatomyositis

Cutaneous Lupus Erythematosus:

Classification

Cutaneous Phenotypes/Mimics

Disease Course Treatment

• Adults

• Kids

Cutaneous manifestations of SLE are common

• Up to 85% of patients with SLE

• First sign of the disease in 25% of patients

• Prevalence equivalent to SLE in some populations

• 4/11 ACR are mucocutaneous manifestations

• Isolated skin disease is distinct from SLE

• Treatments may improve skin but not systemic disease, suggesting differences in pathogenesis

Jarukitsopa et al, Arthritis Care Res 2015;67:817-28.

Challenges of Current ACR Classification Criteria for SLE: Issues of case definition of

Cutaneous LE vs SLE

Butterfly rash

Discoid lupus

Photosensitivity: Definition unclear

-Better to have specific terminology for types of skin lesions induced

Oral ulcers: Overlap with Discoid LE

ACR Dermatologic Criteria for SLE

Many dermatologic criteria

- Can meet SLE criteria with only dermatologic criteria or with no significant systemic disease

Parodi and Rebora, Dermatol 194:217, 1997

Albrecht J, et al. Dermatology position paper on the revision of the 1982 ACR criteria for SLE. Lupus, 2004.

Challenges of Current ACR Classification Criteria for SLE: Issues of case definition of

Cutaneous LE vs SLE

Petri M et al, Arthritis Rheumatol 64:2677, 2012

ACR vs SLICC Criteria

• SLICC SLE criteria- Removes photosensitivity criterion

- Accounts for additional cutaneous manifestations

- Adds non-scarring alopecia

- Expands on neurological manifestations

- Includes more immunological markers

- Can diagnose lupus nephritis as lupus with + serologies, but not meeting SLE criteria

SLICC criteria for SLE

•Non-scarring alopecia-Diffuse thinning or hair fragility with visible broken hairs in the absence of other causes such as alopecia areata, drugs, iron deficiency, and androgenic alopecia

Petri M et al, Arthritis Rheumatol 64:2677, 2012

Generalized DLE Patients Are More Likely to Have SLE Than Localized DLE Patients

Presto and Werth, SID poster #143, 2016

•25% with localized disease have moderate to severe skin disease

New proposed ACR Criteria

• Must have +ANA• However 7.4% of our SLE patients have

negative ANA• Lot of disagreement in rheumatology

community about yet another set of criteria

• Focus should be on lupus as a spectrum disease

• Subsets for homogeneity should be defined for study purposes

Skin lesions in LE

LE-specific

- Skin biopsy shows LE-specific histology

- Diagnosis of LE can be confirmed regardless of presence of ACR criteria for SLE

LE-nonspecific

- Not histopathologically distinct for LE and/or may be seen as a feature of another disease process

LE-specific Skin Lesions

• Chronic Cutaneous LE- DLE: localized, generalized,

hypertrophic- Lupus panniculitis

- Tumid LE

• Subacute Cutaneous LE- Psoriasiform,

annular/polycyclic

• Acute cutaneous LE- Malar erythema,

photodistributederythema

Lupus Specific alopecia: DLE

Lupus Specific alopecia: SCLE

Scar Carcinoma in DLE

• Other areas healed and one area persists

• Need biopsy to differentiate from DLE

Lupus Panniculitis

• Overlying DLE in lupus panniculitis

• Need biopsy to rule out panniculitic lymphoma

Tumid Lupus Erythematosus

Subacute Cutaneous Lupus Erythematosus

Annular Polycyclic Psoriasiform

33% triggered by medication

Drug-induced Cutaneous LEThiazide diureticsCalcium channel blockers

AntifungalsTerbinafine (Lamisil),

griseofulvinBeta blockers

oxyprenololNSAIDS: Piroxicam,naproxenAntihistamines: Cinnarizine

Chemotherapy: Taxotere, Paclitaxel

ACE inhibitorsCilazapril, captopril

GI Acid inhibitorsRanitidine, omeprazole

TNF-α inhibit. biologics

Etanercept, infliximabPlatelet inhibitor:TiclopidineMiscellaneous:

Interferon & , statins, procainamide, phenytoin, oxyprenolol, d-penicillamine, fertilizer/pesticides

Attribution to CLE is Critical: Differential Diagnosis:

Tinea, CLE

• Scaly elevated border

• KOH for hyphae when not sure

Clinical features of Acute Cutaneous Lupus Erythematosus (ACLE)

• Photodistributed

• Spares nasolabial fold

• Does not scar

Distribution in LE vs DM

SLE sparesNasolabial fold

Dermatomyositis involvesnasolabial fold

Attribution to CLE is Critical: Differential Diagnosis: Acne, Rosacea, CLE

Inflamed follicular papules

Attribution to CLE is Critical: Differential Diagnosis:

Rosacea, CLE

• Inflammatory papules

• Telangiectasias• H/o

flushing/blushing

Clinical Findings: Lichen Planopilaris(LPP)

• Perifollicular erythema and scale

• Lack of follicular plugging

• Lack of central depigmentation

Pirmez R et al, Br J Dermatol 175:1387, 2016Berliner JG et al, Br J Dermatol JAAD 71:e27, 2014

Clinical-Pathologic Correlation: Lichen Planopilaris (LPP)

Nambudiri VE et al. 71:e135, 2014

• Hair loss with absent follicles

• Perifollicular scaling

Disease Course: CLE and the association with SLE

• 1088 Swedish patients with CLE• 4/100,000 incidence• Female/male: 3/1• Mean age of onset: 54 years• DLE (80%)

• 24% with SLE at time diagnosed with CLE• Over 3 years, an additional 18% were

diagnosed with SLE

Groenhagen, et al. Br J Dermatol 164: 1335, 2011

CLE who went on to get SLE in 3 years

• 18% overall progressed to SLE over 3 years

- 68.2% had DLE

- 28% SCLE

- 3.7% other

• DLE: 9.8% (95% CI 7.3-12.3%) after one year; 16.7% after 3 years

• SCLE: 22% for first year; 24.7% after 3 years

Groenhagen, et al. Br J Dermatol 164: 1335, 2011

Cutaneous LE progressing to SLE

Chong BF, et al, Br J Dermatol 166:29, 2012

• Generalized DLE• Arthralgias/arthritis• Anemia/leukopenia• Elevated sedimentation rates• +ANA

CLASI

Albrecht and Werth, JID 125:889, 2005

Validation of the CLASINumber of validation studies since then

- Reliability: Albrecht J, et al. J Invest Dermatol. 2005;125:889-94; Krathen MS, et al. Arthr Care Res. 2008;59:338-44.

- Responsiveness: Bonilla-Martinez ZL, et al. Arch Dermatol. 2008;144(2):173-80; Klein RS, et al. Arch Dermatol. 2011;147(2):203-8.

- Correlation of CLASI with skin-specific QoL (Skindex): Klein RS, et al. Quality of Life in Cutaneous Lupus Erythematosus. J Am Acad Dermatol. 2011;64(5):649-58; Vasquez R, et al. A multi-center, cross-sectional study on quality of life in cutaneous lupus erythematosus patients. Br J Dermatol. 2012;

Treatment of Cutaneous LE

Sunscreens and sun protectionAvoid triggers like smokingTopical SteroidsTopical nonsteroidal T cell inhibitors

- Tacrolimus (Protopic)- Pimecrolimus (Elidel)

Intralesional Steroids

Compliance with topicals in Cutaneous LE

Ro T et al, J Cut Med Surg 22:530, 2018

Treatment of CLE

• Antimalarials

• Immunosuppressives

• Thalidomide and derivatives

• Other: Steroids, Dapsone, Retinoids, Rituximab

Evidence for antimalarial use in CLE

Single center cohort of patients treated with antimalarials

Prospective assessment of disease activity

55% of patients in cohort respond to hydroxychloroquine (HCQ)

Chang A et al, Arch Dermatol 147(11):1261-7, 2011

Antimalarial Concentration Correlates with Response

300 patients with SCLE or chronic CLE

Treated with hydroxychloroquine

Median blood HCQ higher in those with CR (910 ng/ml), PR (692 ng/ml), treatment failure (569 ng/ml)

CR associated with higher blood HCQ concentrations (p = 0.005) and absence of DLE (p = 0.004)

10% had very low blood HCQ, considered non compliant Frances C et al, Arch Dermatol 148:479, 2012

Evidence for antimalarial use in CLE

66% of HCQ-refractory patients responded to addition of quinacrine to HCQ

Chang A et al, Arch Dermatol 147(11):1261-7, 2011

Initiation of HCQ-Qn

Median (IQ range) CLASI

Pre-treatment 1st post-treatment

6.0 (4.8-8.3) 3.0 (1.0-5.0)

Median (IQ range) CLASI

Pre-treatment 1st post-treatment

9.0 (3.5-24) 8.0 (3.0-23)

p=0.004 p=0.27

Chang A et al, Arch Dermatol 2011:[Epub ahead of print]

Antimalarials

Hydroxychloroquine <6.5 mg/kg/day Quinacrine 100 mg/day Chloroquine <3.5 mg/kg/day

Hydroxychloroquine for 8 weeks If no better, add quinacrine 100 mg/day

for 8 weeks Switch from Hydroxychloroquine to

Chloroquine if still not improved

Immunosuppressives in Cutaneous Lupus Erythematosus

Azathioprine, Methotrexate, Mycophenolate mofetil: case reports and case series report efficacy

Callen et al Arch Dermatol 127:515, 1991; Wenzel et al, Br J Dermatol 153:157, 2006; Goyal and Nousari JAAD 45:144, 2001; Gammon et al, J Am Acad Dermatol 65:717, 2011)

Immunosuppressives in Cutaneous Lupus Erythematosus

Open label prospective study of 13 patients- Didn’t respond or tolerate antimalarials

50% of patients responded when treated with immunosuppressives

Methotrexate and Mycophenolate mofetilmore effective than azathioprine

Chang A et al, JAMA Dermatol 2013;149(1):104-6.

Effect of Response to

immunosuppressives on QoL

Pre-Tx 1st Post-Tx64.2 (32.5, 95.8) 39.1 (18.5, 59.8)

Pre-Tx 1st Post-Tx65.4 (41.1, 89.3) 64.6 (43.5, 85.8)

RespondersNon-responders

Chang et al, JAMA Dermatol149:104, 2013

Thalidomide in CLE

Cortes-Hernadez J, Br J Dermatol 2012;166(3):616-23

Before After

Thalidomide Analogues

• Up to 50,000 times more active than thalidomide

• Potentially less neurotoxicity

• Have complex mechanisms of action that need to be evaluated in context of clinical trials for specific subsets of diseases

Lenalidomide Study for CLE

• Open label prospective study• Refractory CLE• 4/5 patients improved >4 points in CLASI • 1/5 not improved• 1/4 with skin improvement had new-onset

proteinuria and arthralgia• Clearly would need much more systematic

study before implementation

Braunstein I et al, J Am Acad Dermatol 66:571-82, 2012

CLASI activity change over time

Cortes-Hernandez J et al, ArthrRes & Ther14:R265, 2012

15 patients86% with CR

Mean Change From Baseline in the CLASI Activity Score in Subjects With a Baseline

CLASI Score ≥10

Intent-to-treat population (data as observed).CLASI=Cutaneous Lupus Erythematosus Disease Area and Severity Index.

0 20 40 60 80-30

-25

-20

-15-15

-10

-5

0

Days

CLA

SI A

ctiv

ity S

core

Placebo

0.3 mg QOD

0.3 mg QD

0.3/0.6 MG ALT QD

0.6 MG QD

Werth VP et al, Annals of Rheum Dis 76:870 (abstract), 2017

Bullous Lupus

• Inflammatory cells are neutrophilic• Dapsone blocks neutrophil migration and is

effective for neutrophilic blistering conditions-Safer alternative than systemic steroids for mild bullous LE patients

• Reports of Rituximab helping patients with refractory bullous lupus (Alsanafi S et al, J ClinRheumatol 17:142, 2011)

Rituximab

•82 SLE patients received rituximab-32 with significant skin disease before or after treatment

•10/29 (39%) with baseline skin disease had beneficial skin response at 6 months

-6/14 (43%) with good response in ACLE-0/8 (0%) with CCLE

Vital EM et al, Arthr Rheumatol 67:1586-1591, 2015

Rituximab

•Clinical response associated with negative anti-RNP and anti-Ro serology•Flares of SCLE and CCLE occurred in 12 patients who had no skin disease or ACLE at baseline

Vital EM et al, Arthr Rheumatol 67:1586-1591, 2015

Belimumab (Anti-BLyS Monoclonal Ab)

Manzi et al, Ann Rheum Dis71:1833, 2012

Other New Potential Treatments

• Anti-IFN receptor monoclonal antibody (Anifrolumab)

• Ustekinumab (ongoing)

• Anti-BDCA2 blocks activation of pDCs

Mechanistic Rationale for Targeting IL-12/IL-23 in SLE

• IL-12 is essential for Th1 cell development and cytotoxic T cell activation and function

• IL-23 drives the expansion and survival of pathogenic Th17 cells which promote inflammation in tissues

• IL-12 and the IL-23/IL-17 axis have been implicated in the pathogenesis of SLE

Relle, et al. Autoimmun Rev. 2015.; Fors Nieves and Izmirly. Curr Rheumatol Rep. 2016. Kikawada, et al. J Immunol. 2003.; Dai, et al. Eur J Immunol. 2007.; Dai, et al. J Immunol. 2017.;Martin, et al. Clin Immunol. 2014.;Grammer, et al. Lupus. 2016.; Mesquita, et al. Clin Exp Immunol. 2017.

Phase 2 SLE Study DesignSTUDY POPULATION:

• SLE with SLEDAI ≥6

• At least 1 BILAG A and/or 2 BILAG B

• + ANA, anti-dsDNA, and/or anti-Sm

R

Primary EndpointSRI-4 at Wk 24 (ITT)

Ustekinumab (IV at wk 0, then SC q8 wks) (N=60)

Placebo (N=42) Ustekinumab (SC q8w)

Maintain Standard of CareMedications/steroids controlled*

Medications/steroids controlled;

Some Adjustments for Cause

* Gradual tapering of corticosteroids are allowed for cause beyond Week 28

DBL DBLWeek 0 4 8 12 16 20 24 28 32 36 40 44 48 56

~6 mg/kg or PLWeight-range

Based IV dosing

Study Agent SC at Wks 8 & 16 PL cross-over at Wk 24; all subjects 90 mg SC q8w

Safety F/U

= Randomization = Study Agent Administration PE = Primary EndpointR

Screen

≤ 6 wk

Study Agent Administration

Data to be presentedthrough Wk 24

UST Exhibited a Statistically Significant Improvement in SRI-4 Response at Wk 24 Compared to PBO:

Primary Endpoint Analysis∆ 29%

p=0.0046*

60

31

0

20

40

60

80

100

UST(n=60)

PBO(n=42)

Pe

rce

nt

of

Pa

tie

nts

UST Demonstrated Greater Proportions of Patients with Improvement in Mucocutaneous

Disease Compared to PBO

Post Hoc Exploratory Analysis

4 8 1 2 1 6 2 0 2 4

0

1 5

3 0

4 5

6 0

W e e k

CL

AS

I R

es

po

nd

er

s (

%)

U s t e k i n u m a b ( N = 3 7 )

P l a c e b o ( N = 2 4 )

p = 0 . 0 4 3

*60% of Study Population with

CLASI activity score ≥4 at BLResponder defined as ≥50%

improvement from baseline

pDCBIIB059

Type I IFN ( 13 subtypes, , w, e, k)Type III IFN (IFN )

TLR7,9

BDCA2

Pro-InflammatoryCytokines

(IL-6, TNFα)

Fc-independentFc-dependent

Pro-InflammatoryChemokines

(CCL3, CCL4, CCL5)

BIIB059: a humanized IgG1 anti-BDCA2 mAb specifically targets pDCs

Pellerin et.al. 2015 EMM

MxA Expression in Skin of BIIB059-Treated Subjects

Subject / CLE Subtype

Timepoint

191SCLE

196ACLE

274ACLE

001DLE

002ACLE

007ACLE

185DLE

310DLE

CLASI-A score

D1Week 4Week 12

900

500

624

1066

1482

1887

454

171518

MxAhistology

MxA areaEpidermis

D1Week 4

58.4%0.1%

1.2%0.4%

21.0%2.2%

34.3%1.0%

23.1%2.4%

26.4%3.6%

NDND

57.5%78.4%

CLASI response R R R R R R NR NR

Day 1

Week 4

Cutaneous lupus erythematosus (CLE) affects visible, cosmetically sensitive areas of the body

Untreated, it can alter the way a child grows up feeling about themselves during a formative time.

Klein et al, JAAD. 2011;64(5):849-58

Lupus-specific subsets of CLE

FLO

Acute

Cutaneous

Lupus (ACLE)

Subacute

Cutaneous

Lupus (SCLE)

Chronic

Cutaneous

Lupus (CCLE)

Chillblains

Discoid lupus

Tumid lupus

Neonatal LupusLupus panniculitis/profundus

Hersh et al, Arthritis Care Res. 2010 Aug;62(8):1152-59

Childhood-onset systemic lupus remains a strong predictor for early mortality

Cutaneous lupus is heterogeneous. It may be isolated (skin-limited) or associated with SLE.

Disease subsets are helpful in prognosticating risk of SLE in adults. But few studies exist in children

Clinical features of Acute Cutaneous Lupus Erythematosus (ACLE)

• Photodistributed

• Contrast JDM, more mid-facial edema

• Violaceous = histopathologiccorrelate of interface

• Does not scar

Courtesy of Yvonne Chiu, MD Pearls to differentiate generalized ACLE from PMLE:

ColorTiming of onset (1-3 weeks)Duration (weeks)

ACLE

Courtesy of Yvonne Chiu, MD

Spares the joints when located on the hands (contrast DM)

Attribution is critical in CLE

Often with keratoticpapules on the arms

Not photo distributed, waxes and wanes with heat

ACLE mimic: keratosis pilaris rubrum

ACLE mimic: vesicular polymorphous light eruption

• Vesicles and bullae, often localized to the face

• Blistering develops within hours of sun exposure

• Resolves within a few days (vs weeks for ACLE)

Attribution is critical in CLE

ACLE mimic: airborne allergic contact dermatitis

• Scaly, crusted (often superinfected with staph)

• NOT photo-distributed

• Acute onset

• Intensely itchy

Attribution is critical in CLE

Disease Course in pediatric ACLE

• Commonly adolescents• Nearly all develop SLE• May precede systemic

symptoms by months to years

• Highest incidence of SLE manifestations

Photo courtesy of J. Teng, MD PhDDickey BZ et al, Br J Dermatol. 2013;169(2):428-33.Szczech et al, Postep DermatolAlergol2016;33(1):13-7

Clinical Features of Subacute Cutaneous Lupus

Photodistributed

Does not scar, but dyspigmentation is common

Variants:

1. Papulosquamous (annular)

2. Psoriasiform (fine white scaling)

Courtesy of Yvonne Chiu, MD

Psoriasiform variant of SCLE

Courtesy of Megan Curren, MD

Annular variant of SCLE

Neonatal Lupus: a subset of SCLE

• Passive immunologic injury, maternal +SSA, SSB, U1RNP

• Affects offspring of 1-2% of antibody positive mothers, 20-25% risk for recurrence

• Cardiac, hematologic, neurologic, hepatic complications

SCLE mimic: tinea

Annular (ring like)

Active scaly border

KOH if any doubt

Attribution is critical in CLE

Disease course in children with SCLE• Rarely medication triggered,

in contrast to adults

• Often associated with early complement deficiency (C2 & C4)– 66-100% develop SLE

– More likely to be widespread– Severe manifestations of

pediatric SLE– Make sure you order a CH50

Photo courtesy of Ben Chong, MD PhD

Lowe et al, Br J Dermatol2011;164(3):465-72Lipsker et al, Arch Dermatol. 2000;136(12):1508-14.

Courtesy of Yvonne Chiu, MD

Familial and sporadic variants differentiated by age of onset, inheritance pattern

Mutations described in genes involved in detection of intracellular DNA, deficiency results in type I interferon signature

JAK inhibitors treatment of choice

Chillblain Lupus: A Monogenic Form of CLE

TREX1 associated familial chillblain lupus

Lee-Kirsh et al, Am J Hum Genet. 2006 Oct;79(4):731-7Rice G et al, Am J Hum Genet. 2007 Apr;80(4):811-5. Lee-Kirsh et al, Nat Genet. 2007 Sep;39(9):1065-7.

• TREX1 (DNA specific 3’ 5’ exonuclease) deficiency accumulation of ssDNA

• Type I interferon response• Shared locus: Aicardi –Goutieres Syndrome (elevated IFN- in

CSF); 40% with chillblains

SAMHD1 associated chillblain lupus

• Similar clinical phenotype

• Shared locus with AGS

• Type I IFN signature

Ravenscraft et al, Am J Med Genet A. 2011 Jan;155A(1):235-7.

STING Associated Vasculopathy of Infancy

• Early onset systemic inflammation, cutaneous vasculopathy, SEVERE interstitial lung disease

• Constitutively active STING leads to increased transcription of IFN-

Liu et al, N Engl J Med. 2014 Aug 7;371(6):507-518.Fremond et al, J Allergy Clin Immunol. 2016 Dec;138(6):1752-1755.

STING associated familial chillblain lupus

Konig et al, Ann Rheum Dis. 2017 Feb;76(2):468-472.

• Exists on a common disease spectrum with Sting Associated Vasculopathy of Infancy (SAVI)

• Gain of function mutation causing constitutive type I IFN• Treatment with JAK inhibitor suppresses systemic type I IFN

Clinical features of DLE in children

• Violaceous dyspigmentedplaques with scarring

• Conchal bowls, scalp

• Previous literature: <3% present before age 10 years

3 colors – red/purple, brown, white

Pearls for diagnosis:• Disease activity:

annular plaques, follicular plugging

• Disease damage: scarring and atrophy

• Location:scalp/ears

• Few studies with <40 patients: • Progression to SLE in 25-30%• Risk factors poorly understood• Children who meet ACR

classification criteria for SLE without skin manifestations at higher risk for organ disease

Arkin LM t al, J Am Acad Dermatol. 2015 Cherif F et al, Pediatric Dermatol. 2003..Sampaio et al, Pediatr Dermatol. 2008. Chiewchengal et al, Rheumatology (Oxford). 2014.

Disease course in pediatric DLE

Courtesy of Heather Brandling-Bennett, MD

What does CLE look like in children?

Are there risk factors and biomarkers to accurately sub-

stratify these patients?

CLECLE with auto-antibodies and/or systemic features

CLE with SLE and organ disease

Baseline features and outcomes in

pediatric-onset DLE

SLE diagnosis atbaseline visit using

ACR/SLICC

18 international sites:

pediatric rheumatology and

dermatology

Demographics of all

comers with DLE

Follow up data collected

at every visit

305 patients enrolled to date

Interim analysis on 205 with 9/18 sites reporting

DLE only

followed for SLE using

ACR/SLICC

JHO-0135-2DA-4N

Gender Race/Ethnicity

Most patients were female and black with localized disease

70% Female30% Male

40% Black23% Caucasian21% Hispanic7% Asian9% Unknown

76% localized (head/neck only)22% generalized (above/neck)2% lower body only

Baseline data (n = 205 patients)9/18 sites reporting

Distribution of

lesionsFamily history

of SLE

20% with first degree family member

Median delay in DLE diagnosis was 6 months. Most patients did not have SLE at presentation

Age at DLE diagnosis: median 11.8 years

Baseline data (n = 205 patients)9/18 sites reporting

5 years 10 years0 years 15 years 20 years

>73% presented with DLE without SLE:>4 ACR classification (n = 56, 27%)>4 SLICC classification (n = 46, 22%)

There was a low cumulative incidence of SLE in DLE-only patients through study follow up

Baseline data (n = 205 patients)9/18 sites reporting

14% with SLE

by >4 ACR

22% with

SLE by

>4 SLICC

DLE

without SLE

78-86% remained

DLE only (without SLE)

Median follow up:

3.1 years (range 0.1-12.5 years, 393

total patient-years).

FLI-0875-3DA-4N

Consensus:

Hydroxychloroquine 1st

line systemic treatment

Pediatric Rheumatologists and Dermatologists: Screening and Therapy

Web-based survey of

492 pediatric

dermatologists

& rheumatologistsConsensus:

Baseline

laboratory

evaluationConsensus agreement pre-defined as >70% from both subspecialties.

CBC with diff, Complete metabolic panel, complement,U/A, ESR, ANA, dsDNA, SSA, SSB, RNP

No consensus on 2nd or 3rd line agents for systemic disease

Some areas of consensus but significant practice-based differences in management

No baseline

demographic risk

factors altered

screening for SLE

Disease modifying risk factors

Laboratory screening

Treatment

Antimalarials in children

Hydroxychloroquine <6.5 mg/kg/day (can be compounded in solution, but only good for 2 weeks)

Quinacrine 100 mg/day or approximate fractionated weight (using 60 kg as IBW for adults)

Chloroquine <3.5 mg/kg/day

Hydroxychloroquine for 8 weeks If no better, add quinacrine 100 mg/day for 8 weeks Switch from Hydroxychloroquine to Chloroquine if still not

improved

Lenalidomide for refractory cutaneous

manifestations of SLE• 10 adolescents with

skin findings of SLE• All with “complete or

near resolution” by 6 months

• Decreased prednisone dosage

• Well toleratedWu et al, Lupus. 2017 May;26(6):646-649.

Therapeutic studies for CLE require a

validated outcomes instrument

Anti-malarials

Combination

therapy

Topical therapies

Novel IFN

targeted

agents

Thalidomide

& derivatives

Systemic

corticosteroids

CLASI

Activity scale:ErythemaScaleHypertrophyMucous Membrane Disease

Damage Scale:Hyperpigmentation AtrophyScarring alopecia

Bonilla-Martinez et al, Arch Dermatol. 2008 February ; 144(2): 173–180.

Immuno

modulatory

Agents

The CLASI is now a validated instrument in pediatric CLE

• 11 pediatric patients with active CLE• 12 Pediatric rheumatologists and

dermatologists• Excellent inter-and intra-rater reliability

between dermatologists and rheumatologists (ICC > 0.90)

• Opens the door to performing clinical trials in pediatric CLE

Kushner et al. Br J Dermatol, July 2018

Emerging targets for CLE will make their way

to pediatric patients

Bakers KF and Issacs JD. Ann Rheum Dis 77:175-187, 2018

Upstream targets: Plasma DC

BII059Talacotuzumab

Downstream targets: JAK/STAT inhibition:

TofacitinibBaricitinibRuxolitinib

Dermatomyositis/Juvenile

Dermatomyositis

Clinical phenotypes

Distinguishing features and biomarkers

Treatment for refractory disease

• Adults

• Kids

Dermatomyositis Patient

Erythema on skin ten years Diagnosed as psoriasis for ten years Treated with UVB, ustekinumab,

apremilast, Ixekizumab (last injection August 2018)

All failed +ANA, high sed rate No muscle symptoms, no dysphagia, no

joint pain, +dry cough for a year Normal chest x-ray

Dermatomyositis Patient

DM Diagnostic Criteria (Bohan and Peter’s)

• Symmetric proximal weakness with or without dysphagia or respiratory muscle involvement

• Abnormal muscle biopsy specimen• Elevation of skeletal muscle-derived enzymes• Abnormal electromyogram• Typical skin rash

- Definite DM: rash and 3 or 4 criteria- Probable DM: rash and 2 criteria- Possible DM: rash and 1 criterion

Clinically Amyopathic DM

• Amyopathic DM and hypomyopathicDM.

• Predominantly clinical problem is skin disease.

Diagnosis of Amyopathic DM

Problems in getting a diagnosis

Often misdiagnosed with SLE

SLE criteria often positive (malar rash, photosensitivity, +ANA, oral ulcers)

Skin biopsy indistinguishable between CLE and DM

Diagnoses of Dermatomyositis Patients

Da Silva D and Werth VP. J Am Acad Dermatol 79, 371-373.

Confirmed DM cases (n=232)

Originally diagnosed with DM (n=103)44.4%

Different diagnosis prior to DM (n=129)55.6%

SLE or CLE (n=48)37.2%

UCTD (n=38)29.5%

Undiagnosed (n=10)7.8%

Other (n=33)25.5%

Anti-MDA5 Autoantibodies 10/77 (13%) of patients with DM skin

lesions had anti-MDA5 Abs in serum Higher incidence:

- Lung Disease (67 vs 18%)- Cutaneous ulceration (80 vs 18%)- Palmar papules (60 vs 1.6%)- Mechanics hands (67% vs 15.5%)- Oral lesions (50% vs 7.3%)- Alopecia (78 vs 27%)

Fiorentino D et al, JAAD 65:25-34, 2011

Ulcers

Mechanics Hands

Mechanics Hands

Palmar papules

• Contact dermatitis

• Hand Eczema

• Psoriasis• Dyshidrosis

Clues:

ViolaceousColor

Location

Association between clinical findings and ILD (n=101)

Clinical Signs

Low DLCO and/or ILD

N=38N (%)

No ILD(n=63)N (%)

OR (95%CI)

P-value

Gottronspapules

25 (66) 53 (84) 0.36 (0.14-0.94)

0.05

Mechanic’s hands

28 (74) 29 (46) 3.28 (1.37-7.88)

0.01

Ang CC, Br J Dermatol 176:321, 2017

Mechanics Hands and Antibodies

26/43 had mechanics hands

71% with anti-TIF1-g had mechanics hands

52% had no detectable antibodies

Ang CC, Fujimoto M, and Werth VP, Br J Dermatol 176:231-322, 2017

Mechanics Hands Anti-synthetase syndrome

Polymyositis

Classic DM and CADM

Classic DM and CADM not associated with anti-synthetase antibody

Biopsy of mechanics hands frequently shows interface dermatitis

Concha J et al, JAAD 78:769-775, 2018

Anti-TIF1

More extensive skin involvement Palmar hyperkeratotic papules, psoriasis-

like lesions, hypopigmented and ‘red on white’ telangiectatic patches

Less calcinosis Correlates with malignancy Less ILD, Raynaud phenomenon,

arthritis/arthralgia Mild myositis

Fiorentino DF et al, JAAD 72:449, 2015

Anti-p155/140 Antibody (TIF-1g)

• Poikiloderma

• Flagellate erythema

• Bullae formation

Ikeda N et al. J Dermatol 38:973, 2011

Anti-TIF1

Higher antibody levels on ELISA correlate with presence of cancer (Aggarwal R et al, Rheumatology 53:433, 2014)

Fiorentino DF et al, JAAD 72:449, 2015

Anti-TIF1

Fiorentino DF et al, JAAD 72:449, 2015

Psoriasiform Hyperkeratotic Gottron’s

Anti-TIF1

Fiorentino DF et al, JAAD 72:449, 2015

Red on White Hyperkeratotic palmar

papules

Anti-NXP-2

NXP-2 is nuclear matrix protein involved in the regulation of p53-induced cell senescence in response to oncogenic signals

11% of one cohort

Rogers A et al, Arthritis Care &

Research, 2017.

Anti-NXP-2 Associated with

- Male gender

- Dysphagia- Myalgia- Peripheral edema- Calcinosis- Less clinically amyopathic, milder skin- Decreased Gottron’s sign- Increased risk of malignancy

Rogers A et al, Arthritis Care & Research, 2017

Anti-Small Ubiquitin-like Modifier Activating Enzyme (SAE)

• 1.5-8% of adult DM cohorts

• Skin disease first

• Then progress to systemic (muscle, dysphagia)

Anti-Mi-2

20% of adult DM Classic skin eruptions in sun-exposed areas

(heliotrope, Gottron’s , V-neck sign, shawl sign, cuticular overgrowth, photosensitivity)

Myositis (mild to moderate) Low lung and joint involvement Steroid responsive and monophasic disease

Rate of Autoantibodies in clinical practice

378 patients with myositis panel

- 10% +MSA

- 20% +MAA

Those categorized with probably or definite dermatomyositis, polymyositis, or CADM

- 14% +MSA

- 21% +MAA

Gandiga P, Zhang J, et al. Arthritis Rheumatol (abstract #2589), 2017

Rate of positive myositis specific antibody (MSA) by final diagnosis

Gandiga P, Zhang J, et al. Arthritis Rheumatol (abstract #2589), 2017

Dermatomyositis

Gottron’s papules and shawl sign

Gottron’s off the hands

V neck

• Cuticular

Overgrowth

• Nailfold

telangiectasias

• Nailfold

hemorrhage

• Capillary drop-out

Proximal Nailfold Changes

Multicentric Reticulohistiocytosis

Hsuing and Werth, JAAD 48:S11-S14, 2003

Multicentric Reticulohistiocytosis

Fett and Liu, Dermatology 222:102, 2011

Multicentric Reticulohistiocytosis

Hsuing and Werth, JAAD 48:S11-S14, 2003

CDASI• Rate disease activity and

damage at 15 anatomical sites• Separate activity and damage

scores• Mild DM: CDASI activity score

< 14 • Moderate – Severe DM: CDASI

activity score ≥ 14• Clinically relevant

improvement: 5-point change in CDASI

• Validated outcome measureKlein RQ, et al. Br J Dermatol. 2008;159(4):887-894.

Goreshi R, et al. J Invest Dermatol. 2012;132(4):1117-1124.Anyanwu CO, et al. Arthritis Rheum, Br J Derm 173: 969-74, 2015

CDASI Response correlates with IFN and CXCL10

.

Huard C et al, Br J Dermatol, 2016

CDASI Response correlates with QoL

.

Robinson E et al, Br J Dermatol, 172:169-174, 2015

Treatment of Dermatomyositis

Therapy determined by whether there is underlying muscle or pulmonary disease

Interstititial lung disease in 25% of patients with amyopathic dermatomyositis (steroids ±Mycophenolate mofetil or Cyclophosphamide)

Treatment of skin in Dermatomyositis

First Line Therapies

-Sunscreens

-Topical Steroids

-Intralesional Steroids

-Elidel or Protopic

-Antimalarials (Hydroxychloroquine, Quinacrine, Chloroquine)

Simplify topical regimen

Antimalarial Reactions in DM

• Skin rashes in 20%

• Skin eruptions were approximately 3 times more common in patients with anti-SAE-1/2 autoantibodies

• (7 of 14 [50.0%]) compared with those without the autoantibody (16 of 97 [16.5%]).

Wolstencroft et al, JAMA Derm 154:1199, 2018

Treatment of Skin in Dermatomyositis

Second-line therapies

Immunosuppressives (Methotrexate, Mycophenolate mofetil, Azathioprine, Cyclosporine, Tacrolimus)

Gluocorticoids

IVIG

Other Treatments of Skin in DM

• Third-line therapies

- Rituximab

- JAK inhibitors

• Investigational

- Anakinra

- Anti-IFN

- Lenabasum

- Subcutaneous IVIG

- Abetacept- Interferon-k

Experimental Therapies in Dermatomyositis

• Avoid TNF inhibitors: May exacerbate or activate DM

Potential new treatment for Dermatomyositis: Lenabasum

• Lenabasum, a non-psychoactive cannibinoid• Binds to cannibinoid receptor 2 on pDCs,

lymphocytes• Suppressed the secretion of TNFα, IFN-α, and

IFN- from the PBMCs of dermatomyositis patients in vitro

(Robinson E, J Invest Dermatol 77:374-377, 2017)

Lenabasum (Non-psychoactive) cannabinoid)

Robinson E and Werth VP, J Invest Dermatol 77:374-377, 2017

Lenabasum Trial Placebo-controlled, randomized trial: First

for skin-predominant dermatomyositis 22 patients with skin-predominant DM 1 month half dose, 2 months full dose, one

month off drug Primary outcomes (CDASI) with p=0.02 with

2x/day dosing with drug vs placebo Many patient reported outcomes tracked

improvement of disease activity

Werth et al, Arthritis Rheum (late-breaking abstract), 2017

Lenabasum skin outcomes (CDASI)

Werth VP et al, Arthr Rheumatol (abstract), 2017

Clinical response to Lenabasum

Baseline Week 12

Patient Reported Outcomes

Patient Activity

VAS

Skindex

SymptomsPROMIS-29 pain

interference

Adults and children with DM demonstrate

similar frequencies of photodistributed shawl-

sign, v-sign, cuticular overgrowth, & feverShah et al, Medicine (Baltimore). 2013 Jan;92(1):25-41

Relative to adults with DM, JDM patients are…

…More likely to have distal weakness, falling episodes, and muscle atrophy

…Less likely to have “mechanic’s hands,” Raynaud phenomenon, dyspnea, interstitial lung disease, palpitations

… Less likely to die from their disease

… But over 50% have active disease nearly 2 decades after diagnosis

Shah et al, Medicine (Baltimore). 2013 Jan;92(1):25-41Sanner et al, Rheumatology (Oxford). 2014 Sep;53(9):1578-85.

Fiorentino et al, Curr Rheumatol Rep. 2018 Apr 10;20(5):28.

How common are auto-antibodies in clinical practice?

430 children in a nationwide registry

253 single MSA (59%)

121 no identified MSA (28%)

Mi-2 32%

NXP-2 20%

Rider et al, Medicine (Baltimore). 2013 July;92 (3):223-242

Fiorentino et al, Curr Rheumatol Rep. 2018 Apr 10;20(5):28.Rider et al, Medicine (Baltimore). 2013 July;92 (3):223-242

Mi-2+ JDM

Prevalence 3-10% of JDM

High titer ANAs, Hispanic ethnicity

Mi-2+ Antibodies in JDM

Classic findings- heliotrope, gottron’s papules, malar rash, cuticular overgrowth similar to adults

Associated with good response to therapy in spite of more severe muscle disease and histopathology Deakin et al, Arthritis Rheumatol. 2016;68(11):2806–16

JDM Mimic:

Allergic

Contact

dermatitis

Pink or red – not

violaceous or

telangiectatic

No other findings to

suggest vasculopathy

Anti-Mi2 antibodies

• 4-10% JDM

Classic Gottron’s

JDM mimic: SLE psoriasis overlap

Likes extensor surfaces

White micaceousscaling

Broader areas of involvement than classic Gottron’s

PLAN A: Hydroxychloroquine

PLAN B: Hydroxychloroquine + MTX

PLAN C: Hydroxychloroquine + MTX + Corticosteroids

CARRA CTP for Skin-Predominant

JDM

Kim et al, Pediatric Rheumatology (2017) 15:1

CARRA CTP for Refractory Skin

Disease in JDM

Patients should have previously received MTX + Corticosteroids

PLAN A: Add IVIG

PLAN B: Add Mycophenolate Mofetil

PLAN C: Add Cyclosporine

Huber et al, J Rheumatol. 2017 Jan;44(1):110-116.

Mi-2+ Antibodies predict responsiveness

to rituximab in refractory JDM

Aggarwal et al, Arthritis Rheumatol. 2014 Mar;66(3):740-9.

Fiorentino et al, Curr Rheumatol Rep. 2018 Apr 10;20(5):28.Tanley et al, Arhtirits Res Ther. 2014;16(4):R138.

MDA-5+ JDM

Prevalence 7-12% of JDM

Increased prevalence & severity in Asian cohorts with JDM

Cutaneous ulcerations

Painful scaly palmar papules - vasculopathy

Diffuse hair loss

Oral erosions

Sometimes calcinosis

Sometimes mechanic’s hands

Cutaneous phenotype in children with MDA5+

JDM is similar to adults

Fiorentino et al, JAAD 2011 Jul; 65(1): 25–34..

Ulcerations associated with MDA5+ JDM

Elbows, knees, lateral nailfolds

Ulcerated Gottron’s papules

Ulcerated plaques on the elbows and knees

Deakin et al, Arthritis Rheumatol. 2016;68(11):2806–16Tansley et al, Arthritis Res Ther. 2014;16(4):R138.

Mechanic’s Hands in MDA-5+ JDM

Anti-synthetase antibodies uncommon in JDM (<5%)Hall et al, Arthritis Care Res. 2013 Aug; 65(8): 1307–1315.Rider et al, Medicine (Baltimore). 2013 July;92 (3):223-242

Tansley et al, Arthritis Res Ther 2014 Jul 2;16(4):R138.

Conflicting data on prognosis in MDA5+ JDM

1. Less destructive histopathologic changes on muscle biopsy compared to other antibodies, but increased likelihood of remaining on treatment

2. Less severe myositis, 20% with ILD but none rapidly progressive, associated with improved prognosis and disease remission at 2 years

Deakin et al, Arthritis Rheumatol. 2016;68(11):2806–16

Interstitial lung disease in MDA5+ JDM may reflect

genetic and environmental influences

Small East Asian cohorts have described rapidly progressive ILD in MDA5+ JDM associated with high mortality

In this population, high serum levels of ferritin and anti-MDA5 antibodies may be an indication for early aggressive treatment

Kobayashi I et al, J Pediatr. 2011 Apr;158(4):675-7.Kobayashi et al, Rheumatology (Oxford). 2015 May;54(5):784-91.

Fiorentino et al, Curr Rheumatol Rep. 2018 Apr 10;20(5):28Rider et al, Medicine (Baltimore). 2013 July;92 (3):223-242.

NXP-2+ JDM

Prevalence 20-25% of JDM

Synonymous with anti-MJ antibody

Caucasian patients

Younger age at onset/diagnosis

NXP-2+ is a marker for increased JDM severity

Strongly associated with calcinosis

Contractures, atrophy, proximal muscle weakness, increased muscle cramps

Severe muscle damage at disease onset

Intestinal vasculitis– GI bleeding and ulcers

Rider et al, Medicine (Baltimore). 2013;92(4):223–43Iwata et al, Mod Rheumatol. 2018 Sep 10;1-6Oddis et al, Arthritis Rheum-Us. 1997;40(9):652-.Espada et al, J Rheumatol. 2009 Nov;36(11):2547-51.

Intensified immunosuppression favored as

1st line treatment for calcinosis in JDM Orandi et al, Pediatr Rheumatol Online J. 2017; 15: 71.

Experienced pediatric rheumatologists

were more likely to use alternative agents

Definition: experience with >10 cases

Anti-Tif-1 g+ JDM

Synonymous with p-155/140

No association with malignancy in children (contrast adults)

Prevalence 20-35% of JDM

Most are Caucasian (80%)

Fiorentino et al, Curr Rheumatol Rep. 2018 Apr 10;20(5):28Rider et al, Medicine (Baltimore). 2013 July;92 (3):223-242.

TIF-1g is the most common antibody in JDM and is associated with characteristic cutaneous findings

Ovoid palatal patch not reported in children

Malar RashGottron’s papulesHeliotrope rashShawl SignV-shaped SignCuticular OvergrowthLinear extensor erythema

Feldman B et al, Lancet. 2008 Jun 28;371(9631):2201-12Rider et al, Medicine (Baltimore). 2013 July;92 (3):223-242

Associated with high titer ANAs

Lower prevalence of severe muscle manifestations

Severity of muscle biopsy histopathology alone predicts the risk for remaining on treatment

TIF-1g is associated with low mortality but chronic disease course in JDM

Rider et al, Medicine (Baltimore). 2013 July;92 (3):223-242Deakin et al, Arthritis Rheumatol. 2016;68(11):2806–16

Photosensitivity in Dermatomyositis and Lupus

Practice advice for photo protective counseling in a busy clinic

Thank you to Heather Brandling-Bennett, MD for use of some slides

Prepare to counsel regarding good sun protection practices

UVB and UVA2 are inducers of skin disease in photosensitizing conditions

In contrast, longer wavelength UVA1 may be beneficial .

Cripps et al, Arch Dermatol. 1975 Apr;107(4):563-7.Nived et al, Lupus. 1993 Aug;2(4);247-50.McGrath, J Investig Dermatol Symp Proc. 1999 Sept;4(1):79-84.

Windows block UVB but almost no UVA

69 year old truck driver for 28 years

Chronic, low dose UV exposure from indoor

lamps can induce cumulative skin damage

• Halogen lamps >> incandescent bulbs >> fluorescent bulbs emit varying levels of UVR

Rihner et al, Arthritis Rheum. 1992 Aug;35(8):949-52Klein et al, Autoimmun Rev. 2009 Feb; 8(4):320-24.Klein et al, Photochem Photobiol. 2009 Jul-Aug;85(4):1004-10

Some computer screens may be a risk…

LED (light emitting diode)

CFL (compact fluorescent lamp)

EEH(energy-efficient halogen)

Fenton et al. Br J Dermatol 2014;170:697-8.

?

Photosensitivity impacts QoL

• Limited ability to play outdoors

• School & work absences

• Missed holidays

Moorthy et al. Lupus 2017;26:255-65.

Sunscreen prevents photo-induced cutaneous lupusKuhn et al. J Am Acad Dermatol 2011;64:37-48.

*P<.001

What happened to waterproof sunscreen?

• New FDA requirements summer 2012

• “Broad Spectrum SPF” test to measure UVA protection relative to UVB protection

• No “waterproof,” “sweatproof” or “sunblock”

• “Water resistance” claims for 40 or 80 minutes

• Since 1978, sunscreen regulated as an OTC non prescription drug

• New innovations require extensive testing before market

• No new FDA-approved sunscreen ingredients since 1999!

• Sunscreen Innovation Act, November 2014 established an expedited process for approval of OTC sunscreens

“New chemicals that could prevent skin

cancer are languishing in the FDA purgatory”Newsweek Magazine, 4/12/19

Simple recommendations in a busy clinic:

1. Pick a sunscreen that says “broad spectrum UVA/UVB” of at minimum SPF >60

2. Reapply every 90 minutes, and within 40 minutes of getting out of the water

3. Nickel-sized amount of sunscreen for the face. Medicine cup-sized amount of sunscreen for the body

4. Sun protective clothing is good for broad areas (hats, tops, bottoms)

5. Handouts help (I’m happy to share these – email me)6. Samples help (ask your derm colleagues for supplier)

Don’t forget to supplement vitamin D…

Sun avoidance and chronic corticosteroids worsen vitamin D insufficiency

Screen (with 25-hydroxyvitamin D) and supplement orally

Threshold to treat: 25 OH D <20 (children); <20-30 (adults)

Lee et al, J Pediatr Pharmacol Ther. 2013 Oct-Dec;18(4):277-291

Questions?

Werth@mail.med.upenn.edu

Larkin@dermatology.wisc.edu

UV radiation promotes development of cutaneous lupus

through lymphocyte recruitment and antibody-mediated

cytotoxicity

Kim & Chong. Photodermatol Photoimmunol Photomed 2013;29:4-11.

Patients with DM/JDM and LE have lower minimal

erythema dose testing than normal controls

~50% of DM and CLE/SLE patients demonstrated reduced MEDs to UVB compared to 19% of controls (p<0.05)

Dourmishev et al. Photodermatol Photoimmunol Photomed 2004;20:230-4.

UV radiation modulates the clinical and immunologic

expression of DM in women

Love et al. Arthritis Rheum 2009;60:2499-504.

Higher UV intensity associated with increasing odds of DM (OR 2.3) AND anti Mi-2 antibodies in US

Association only significant for women, not men

Not significant for other auto-antibodies

Higher mean UV index increased odds for JDM (vs PM) AND anti-p155/140 autoantibodies

No association with anti-MJ antibodies (NXP2) or those with negative myositis antibodies

Shah et a. Arthritis Rheum 2013;65:1934-41.

Short-term UVR exposure modulates the clinical and immunologic expression of JDM

What is photosensitivity?ACR definition:

(1982 SLE classification criteria)

Skin rash as a result of unusual reaction to sunlight, by patient history or physician

observation

But most lupus reactions are delayed (1-3 weeks) and durable (>3 weeks) Sanders et al, Br J Dermatol. 2003 Jul;149(1):131-7.

Kuhn et al, JAAD 2001 Jul; 45(1):86-95.Hasan et al, Br J Dermatol. 1997 May;136(5):699-704

Patients with CLE have reproducible, delayed

responses to photo testing

Kuhn et al, J Invest Dermatol. 2011 Aug;13 (18):1622-30

47 CLE and 13 controls photo-tested using a standardized protocol across 7 sites (UVA and UVB)

47% of CLE patients and none of the healthy volunteers developed photo-induced lesions

(86%) histopathologically confirmed as lupus

1-2 week delay in appearance of the lesions

QoL in Photosensitivity

Foering et al, JAAD 69:205-218, 2013

QoL in Photosensitivity

Foering et al, JAAD 69:205-218, 2013

5 clinical photosensitivity phenotypes identified

Percentages of photosensitivity phenotypes

Foering et al, JAAD 69:205-218, 2013

Development & resolution of reactions

Foering et al, JAAD 69:205-218, 2013

Photosensitivity phenotype associated with SLE diagnosis

Foering et al, JAAD 69:205-218, 2013

Stannard & Kahlenberg. Curr Opin Rheumatol 2016;28:453-9.

UVR triggers an inflammatory response in CLE

Mouse models support a link between cutaneous inflammation and systemic disease activity

Questions?

Werth@mail.med.upenn.edu

Larkin@dermatology.wisc.edu