dermatology update: latest findings on rheumatic skin ...€¦ · acr dermatologic criteria for sle...
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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
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