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Cutaneous Lupus Erythematosus Diagnosis, Classification, and Screening for Systemic Disease

David A. Wetter, M.D. Professor of Dermatology, Mayo Clinic (Rochester, MN)

Cutaneous Lupus and Dermatomyositis Management Pearls and Pitfalls for the General Dermatologist, Symposium (S006)

American Academy of Dermatology, Annual Meeting,

Washington, D.C., March 1, 2019

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Disclosure

• I have no conflicts of interest

• Off-label use of systemic medications will be discussed

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The scenario and

clinical conundrum…

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A 36 year-old woman has this generalized eruption of the head, arms, and upper trunk. You are suspicious that this patient has discoid lupus.

1. What are the clinical and microscopic features that can help confirm the diagnosis of cutaneous lupus?

2. How should a patient be

• Initially evaluated for the presence of systemic involvement

• Monitored over time for the presence of systemic involvement

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Overview

• How to diagnose cutaneous lupus

• How to classify the various subtypes of cutaneous lupus

• How to evaluate patients with cutaneous lupus for the possibility of systemic lupus (both at baseline and over time)

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The Incidence of Cutaneous Lupus is

1. Greater than systemic lupus

2. The same as systemic lupus

3. Less than systemic lupus

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Incidence Rate of Cutaneous Lupus is 4.30 per 100,000

Cutaneous lupus

is as common

as SLE

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Incidence of Cutaneous Lupus is 3 Times Higher Than Systemic Lupus in Men

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Which of the Following is an Example of Lupus Erythematosus-Specific Skin Disease?

1. Calcinosis cutis

2. Chilblain lupus

3. Leukocytoclastic vasculitis

4. Livedo reticularis

5. Periungual telangiectasia

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Costner MI and Sontheimer RD

Do not show

characteristic

histopathology

of lupus and can

be seen in other

diseases Show characteristic histopathologic changes of lupus

erythematosus (e.g. interface dermatitis)

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What are the typical clinical

findings of cutaneous lupus?

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ACTIVITY: Erythema, scale/hypertrophy

DAMAGE: Dyspigmentation, scarring, atrophy

*Can help determine

1. How active disease is at time of evaluation (and thus influence your treatment approach)

2. Response to your treatment at follow-up

Arch Dermatol 147(2):203, 2011

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• Note presence of both ACTIVITY (erythema, scale) and DAMAGE (dyspigmentation, scarring) in this patient with discoid lupus

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A few examples of

lupus-specific skin disease…

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Localized acute cutaneous lupus (“malar rash”)

Note:

1. Sparing of nasolabial fold

2. Involvement of malar cheeks extending over nasal dorsum (“butterfly rash”)

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Patient had generalized DLE and

although had 4/11 ACR criteria

(discoid rash, oral ulcers,

photosensitivity, positive ANA), she

did not have clinically relevant SLE

(per rheumatologic evaluation)

Mucosal (oral)

discoid lupus (DLE)

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Hypertrophic/verrucous DLE

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Note violaceous

erythema and

swelling of 2nd toe

Chilblain lupus in setting of

systemic lupus (SLE)

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Cutis 54(6):395, 1994

“Definite” chilblains lupus

requires fulfilling BOTH

major criteria and at least

one of the minor criteria

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Proposed Diagnostic Criteria of Pernio

Major criteria

• Localized erythema and swelling

involving acral sites and persistent for

>24 h

Minor criteria

• Onset and/or worsening in cooler months

(between November and March)

• Histopathologic findings of skin biopsy

consistent with pernio (eg, dermal edema

with superficial and deep perivascular

lymphocytic infiltrate) and without findings

of lupus erythematosus

• Response to conservative treatments

(ie, warming and drying of affected areas)

Pernio (chilblains) – DIFFERENT entity

than chilblain lupus

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Lupus panniculitis

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Which of the following conditions can closely mimic lupus panniculitis both clinically and microscopically?

1. Deep morphea

2. Erythema nodosum

3. Lymphoma

4. Nodular vasculitis

5. Pancreatic panniculitis

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Lupus panniculitis

and subcutaneous

panniculitis-like T-cell

lymphoma (SPTCL)

can present very

similarly both

clinically and

histopathologically

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A few examples of

lupus-nonspecific skin disease...

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Gutierrez Jr. and Wetter: Dermatologic Therapy 25:195, 2012

Ulcerations with focal extrusion of

chalky granules because of calcinosis

cutis in a patient with systemic lupus

erythematosus

Calcinosis cutis

(in a patient with SLE)

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Underlying ACTD Female sex Male sex Total

Age at onset of calcinosis

cutis, mean (range), y

Time to onset of calcinosis cutis after

diagnosis of ACTD, mean (range), mo

Dermatomyositis 23 (77) 7 (23) 30 (38) 31 (4-75) 65 (3-216)

Classic 11 (73) 4 (27) 15 (19) 48 (21-75) 94 (12-216)

Amyopathic 1 (100) 0 1 (1) 52 72

Juvenile 11 (79) 3 (21) 14 (18) 10 (4-21) 35 (3-84)

Systemic sclerosis with limited

cutaneous scleroderma 21 (88) 3 (13) 24 (31) 54 (28-73) 90 (0-372)

Overlap CTD 5 (83) 1 (17) 6 (8) 39 (14-55) 128 (2-312)

Undifferentiated CTD 5 (83) 1 (17) 6 (8) 51 (31-67) 32 (0-84)

Lupus panniculitis 4 (100) 0 4 (5) 60 (39-74) 58 (5-108)

Mixed CTD 2 (50) 2 (50) 4 (5) 50 (39-62) 75 (12-92)

SLE 2 (100) 0 2 (3) 46 (35-57) 258 (228-288)

RA 1 (100) 0 1 (1) 29 24

Polymyositis 1 (100) 0 1 (1) 44 108

• Range of ACTD’s associated with calcinosis

• Dermatomyositis (38%)

• Systemic sclerosis with limited cutaneous scleroderma (31%)

• Lupus panniculitis (4 pts.), SLE (2 pts.)

Characteristics and Prevalence of ACTD Associated with Calcinosis Cutis Patients, No. (%) (n=78)

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• Urticarial vasculitis

• Note “bruise-like” discoloration

• Can be associated with SLE –

particularly if associated with low

complement levels

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Etiologies of Cutaneous Small Vessel Vasculitis

Chung et al: Dermatology, 2008, Ch. 25

Infection (15-20%)

Autoimmune connective tissue disease (15-20%)

Drug (10-15%)

Neoplasm (5%)

Idiopathic (45-55%)

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What other conditions can

appear clinically similar to

cutaneous lupus?

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Differential Diagnosis

Acute cutaneous lupus/malar rash

• Rosacea (including corticosteroid-induced)

• Seborrheic dermatitis (especially photosensitive form)

• Sunburn

• Drug induced photosensitivity (phototoxic and photoallergic)

• Dermatomyositis

• Erysipelas

• Pemphigus erythematosus

• Dermatitis, atopic, contact and photocontact

• Acne vulgaris (rarely)

Subacute cutaneous lupus

• Psoriasis

• Dermatophytosis, including tinea incognito

• Photolichenoid drug eruption

• Granuloma annulare

• Figurate erythemas (e.g. erythema annulare centrifugum)

• Dermatitis, atopic, contact and photocontact

• Permphigus foliaceus

Discoid lesions

• Facial discoid dermatosis

• Tinea faciei, tinea capitis, tinea corporis

• Lichen planus and lichen planopilaris

• Jessner’s lymphocytic infiltrate

• Polymorphous light eruption

• Sarcoidosis

• Lymphocytoma cutis

• Lymphoma cutis

• Granuloma faciale

• Dimorphic fungal infections, lupus vulgaris

• When single lesion, non-melanoma skin cancer

Tumid lupus lesions

• Jessner’s lymphocytic infiltrate

• Polymorphous light eruption

• Reticular erythematous mucinosis

Lupus panniculitis

• Other panniculitides

Lee and Werth: Dermatology, 2012, Ch. 41

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What is the histopathology

of cutaneous lupus?

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Low-Power Image Note Perivascular and Periadnexal Lymphocytic

Infiltrate as well as Follicular Plugging

Photo courtesy of Michael J. Camilleri, M.D. Mayo Clinic

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Medium and High Power Images Note Interface Dermatitis With Basal Vacuolar Degeneration

Photo courtesy of Michael J. Camilleri, M.D. Mayo Clinic

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Direct Immunofluorescence Microscopy (DIF)

• Photo highlights granular deposits of IgM along basement membrane zone

• “Lupus band” – continuous, strong, granular deposition of IgM, IgG, and complement (C3) along basement membrane zone

Photo courtesy of Michael J. Camilleri, M.D. Mayo Clinic

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Which of the following is associated with worse disease in this patient with discoid lupus?

1. Alcohol use

2. Hepatitis C

3. Malignancy

4. Positive PPD

5. Smoking

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Can medications be

associated with the onset

of cutaneous lupus?

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Subacute Cutaneous Lupus Erythematosus (SCLE)

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SCLE Note Photodistribution in Current and Previous Photo

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Drug-Induced SCLE Drug-Induced SLE (Usually Does Not Have Skin Involvement)

Causes of Drug-Induced Lupus

Drug-induced SCLE

ACE inhibitors

Phenytoin

Hydroxychloroquine

Griseofulvin

Terbinafine

Tetracycline

Beta blockers

Calcium channel blockers

Tamoxifen

Docetaxel

Paclitaxel

Anastrozole

NSAIDS

Thiazide diuretics

Buproprion

Leflunomide

Proton Pump inhibitor

Anti-TNF biologics

Interferon-α

Drug-Induced SLE (typically without skin involvement)

Hydralazine

Isoniazid

Antihyperlipidemic agents

Minocycline

Procainamide

Anti-TNF biologics

Costner and Sontheimer: Dermatology in General Medicine, Ch. 155, 8th ed.

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More than 1/3 of

SCLE cases could

be attributed to drug

exposure

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What is already known about this topic?

• Eighteen cases of proton pump inhibitor (PPI)-induced cutaneous lupus erythematosus (CLE) have been reported in the literature since 2001

What does this study add?

• Nineteen new patients with 24 episodes of PPI-induced subacute CLE (SCLE) are reported

• Cross-reactivity between different PPIs is demonstrated

• Patients with previous CLE or other autoimmune diseases may be particularly prone to PPI-induced or exacerbated SCLE

• The diagnosis is challenged by the variation in time from prescription of the culprit drug to the appearance of SCLE

Sandholdt et al: British Journal of Dermatology 170:342, 2014

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Antihypertensives 40 of 117 reported cases: 34.2%

Calcium channel blockers

Diltiazem 6 cases

Verapamil 5 cases

Nifedipine 3 cases

Nitrendipine 1 case

Diuretics

Hydrochorothiazide 10 cases

Hydrochlorothiazide + triamterene 3 cases

Chlorthiazide 2 cases

Beta blockers

Oxprenolol 4 cases

Acebutolol 1 case

Angiotensin-converting enzyme inhibitors

Enalapril 2 cases

Lisnopril 1 case

Captopril 1 case

Cilazapril 1 case

Antifungals 30 of 117 reported cases: 25.6%

Terbinafine 29 cases

Griseofulvin 1 case

Chemotherapeutics 10 of 117 reported cases: 8.5%

Docetaxel 3 cases

Paclitaxel 3 cases

Tamoxifen 2 cases

Capecitabine 2 cases

Antihistamines 9 of 117 reported cases: 7.7%

Ranitidine 7 cases

Brompheniramine 1 case

Cinnarizine + thiethylperazine 1 case

Immunomodulators 8 of 117 reported cases: 6.8%

Leflunomide 5 cases

Interferon α and β 3 cases

Antiepileptics 3 of 117 reported cases: 2.6%

Carbamazepine 2 cases

Phenytoin 1 case

Statins 3 of 117 reported cases: 2.6%

Simvastatin 2 cases

Pravastatin 1 case

Biologics 2 of 117 reported cases: 1.7%

Etanercept 2 cases

Efalizumab 1 case

Proton pump inhibitors 2 of 117 reported cases: 1.7%

Lansoprazole 2 cases

Nonsteroidal anti-inflammatory drugs 2 of 117 reported cases: 1.7%

Naproxen 1 case

Piroxicam 1 case

Hormone-altering drugs 2 of 117 reported cases: 1.7%

Leuprorelin 1 case

Anastrozole 1 case

Ultraviolet therapy 2 of 117 reported cases: 1.7%

PUVA 1 case

PUVA and UVB 1 case

Others 4 of 117 reported cases: 3.4%

Bupropion 1 case

Tiotropium 1 case

Ticlopidine 1 case

Hay with fertilizer 1 case

Answer: No (according to Lowe et al)

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Approximately 80% of Patients With SCLE Will Have Positive Ro/SSA Antibodies (Does Not Differ Between Idiopathic and Drug-Induced Cases)

Ro/SS-A,

n/N (%)

La/SS-B

n/N (%)

Antinuclear

antibodies,

n/N (%)

Histone, n/N

(%)

Number reported

positive at

diagnosis

87/107 (81) 35/73 (48) 84/103 (82) 19/57 (33)

Number reported

positive after

resolution of rash

28/42 (67) 5/9 (56) 19/23 (83)

3/6 (50): in one

case antibody

appeared after

resolution

Autoantibodies in drug-induced subacute cutaneous lupus erythematosus

Ro/SS-A autoantibody rates were not significantly different between DI-SCLE and idiopathic SCLE

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SLE criteria

ANA 14 (100) 57 (79)

Arthritis 13 (93) 22 (31)

Anti-dsDNA 10 (71) 52 (72)

Cutaneous features 4 (29) 48 (67)

Serositis 4 (29) 9 (12)

Hematologic disorder 4 (29) 16 (22)

Oral ulcers 4 (29) 3 (4)

Antiphospholipid antibodies 1 (7) 8 (11)

Renal disorder 0 (0) 5 (7)

Neurologic disorder 0 (0) 2 (3)

Anti-Smith antibodies 0 (0) 7 (10)

Other features

Hypocomplementemia 3 (21) 17%

Antihistone antibodies 3 (21) NA

Fever or general symptoms 11 (79) 23%

Number of SLE critieria fulfilled

≥4 9 (64) 37 (51)

3 3 (21) 17 (24)

1-2 2 (14) 18 (25)

Outcome

Improvement 13/13 (100) 71 (99)

Time to improvement (mo) 2.9 9.9

*High rate of arthritis and low rate of skin findings in our study

*Do not need to fulfill ACR criteria to have an important lupus-like syndrome (ACR criteria

developed more for clinical study classification, rather than establishing SLE diagnosis in

given patient [Cutaneous Manifestations of Rheumatic Diseases, 2nd ed.])

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Which laboratory evaluations

should be performed in patients

with cutaneous lupus?

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Clinically Relevant Information About Cutaneous Lupus Eythematosus

“The development of systemic disease in patients with what seems to be a strictly cutaneous disease at diagnosis has been highlighted in this issue of the Archives. What is needed is a clear statement of how to monitor patients for this possibility. Is there predictive value of obtaining immunoflurescence microscopic findings on patients at diagnosis? Should we be performing repeated serologic testing in our patients, or should we only follow patients with a careful clinical history along with complete blood cell counts and urinalyses?”

Callen: Arch Dermatol 145(3):316, 2009

How should patients with cutaneous lupus be monitored for

systemic disease at (1) time of diagnosis and (2) over time?

A CLEAR CONSENSUS DOES NOT YET EXIST

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My Typical Workup for Cutaneous Lupus (CLE)

• Goal: confirm diagnosis and assess for systemic involvement

• Thorough review of systems (use ACR criteria as guide)

• Skin biopsy: H&E and lesional DIF (I personally find the H&E to be the most helpful)

• Basic labs: CBC, LFT’s, creatinine, inflammatory markers (ESR, CRP), urinalysis

• Autoimmune serologies, etc: ANA, ENA panel, dsDNA, complement (C3, C4, total), anti-phospholipid Abs (anti-cardiolipin, beta-2-glycoprotein-1, lupus anticoagulant)

• If considering systemic therapy: Eye exam (antimalarials), hepatitis serologies (methotrexate), thiopurine methyltransferase (TPMT; azathioprine)

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Approach to newly diagnosed patient

with cutaneous lupus

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Costner M and Sontheimer R

American College of

Rheumatology (ACR)

criteria for diagnosis of

SLE

• 4 of 11 criteria

• Simultaneously or

serially (over time)

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• Diagnosis of SLE requires 4 of 17 criteria

• At least 1 (of 11) clinical and 1 (of 6)

immunologic

• OR, biopsy-proven lupus nephritis in presence of

positive ANA or anti-dsDNA

• Criteria are cumulative (and do not need to be

present concurrently)

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SLICC (2012) criteria were

more sensitive than ACR

(1997) criteria in classifying

a patient as having SLE

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How can ACR and SLICC criteria of SLE be helpful for dermatologists?

• Helpful for review of systems to determine possible internal organ (systemic) manifestations in patients with cutaneous lupus

• HOWEVER: Do not provide a comprehensive listing of internal organ involvement of SLE

• For example, do not include nonspecific symptoms and signs such as fever, fatigue, weight loss, myalgias, and lymphadenopathy

• Such findings may be important markers for progression to SLE in patient with cutaneous lupus

• (Lee LA and Werth VP. “Lupus Erythematosus.” Chapter 41 in “Dermatology,” 4th ed. Page 672)

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How Do I Monitor Patients With (Clinically Quiescent/Stable) CLE Over Time?

• Chronic CLE (CCLE) [DLE most common subtype]

• Annual skin exam and review of systems

• Laboratory studies based on: skin findings, review of systems (and if any abnormal baseline labs at time of diagnosis that are more concerning for higher chance of progression to SLE)

• SCLE

• Annual skin exam and review of systems

• For first 1-2 years consider annual labs (CBC, Cr, ESR, urinalysis, ENA panel, dsDNA, complement levels); thereafter only if review of systems or skin exam concerning for SLE

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In those with isolated discoid lupus, what is the risk of progression to systemic lupus over time?

1. 2%

2. 10%

3. 25%

4. 50%

5. 75%

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• 13 of 129 patients (10.1%) with DLE progressed to SLE

• Mean time from cutaneous lupus diagnosis to progression to SLE was 8.2 years (this included all 19 [of 156 pts.] with cutaneous lupus that progressed to SLE)

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• Nationwide registry-based

cohort study in Denmark

• 2380 patients with

cutaneous lupus, including:

• 62% discoid lupus

• 20% SCLE

• Median time of 2.05 years

from cutaneous lupus

diagnosis to progression to

SLE – implications for

monitoring (see later slides)

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Characteristic or Symptom CLE (n=64) SLE (n=13) P

Age, mean (SD), y 51.0 (14.3) 50.35 (14.80) 0.88

Time from CLE diagnosis to first visit, mean (SD), y 7.64 (8.52) 6.62 (6.10) 0.68

Follow-up time, mean (SD), y 2.33 (1.21) 2.81 (1.34) 0.20

No. of visits, median [range] 4 [2-12] 7 [2-13)

Female sex, No. (%) 44 (69) 12 (92) 0.10

White race/ethnicity, No. (%) 46 (72) 12 (92) 0.18

CCLE, No. (%) 45 (70) 8 (62) 0.53

Discoid localized 22 (34) 1 (8) 0.04

Discoid generalized 6 (9) 4 (31)

SCLE, No. (%) 19 (30) 5 (38) 0.53

Antibody test result, No. (%)

Negative baseline ANA titer 54 (84) 5 (38)

0.002 Baseline ANA titer, 1:80-1:160 3 (5) 4 (31)

Baseline ANA titer, 1:320-1:1280 7 (11) 4 (31)

Positive for anti-dsDNA 5 (8) 2 (15) 0.35

Positive for anti-Smith 0 1 (8) 0.17

Positive for anti-cardiolipin or lupus anticoagulant 3 2 (15) 0.20

Therapeutic agent, No. (%)

Topical or IL corticosteroid 18 (28) 2 (15) 0.50

Prednisone 6 (8) 1 (8) NA

Antimalarials or dapsone 49 (77) 7 (54) 0.17

Immunomodulators 4 (6) 1 (8) NA

Thalidomide 4 (6) 1 (8) NA

No. of ACR criteria at baseline, mean (SD) 1.62 (0.92) 2.38 (0.78) 0.007

Musculoskeletal, No. (%) 2 (3) 1 (8) 0.43

Renal, No. (%) 1 (2) 11 (8) 0.31

Hematologic, No. (%) 2 (3) 0 NA

Overall severity, No. (%)

None to mild 64 (100) 11 (85) 0.03

Moderate/severe 0 2 (15)

• 13 of 77 patients with cutaneous lupus (CLE) progressed to systemic disease (SLE): 16.8%

• 5/24 SCLE (20.8%)

• 8/53 DLE (15.1%)

• Those developing SLE were more likely to have

• ANA >1:80 at baseline (P=0.002)

• Mean time from CLE diagnosis to SLE diagnosis (n=13) was 8.03 years

Baseline Patient Characteristics and Symptoms

P<0.005 = statistically significant

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Criteria SLE, No. (%) (n=13)

Photosensitivity 12 (92)

ANA 9 (69)

Discoid rash 8 (62)

Oral ulcers 7 (54)

Arthritis 6 (46)

Malar rash 4 (31)

Hematologic 4 (31)

Antibodies 3 (23)

Renal 2 (15)

Pleuritis 0

Neurologic 0

Mucocutaneous criteria only 1 (8)

Mucocutaneous criteria and antibodies 3 (23)

Criteria Met by Patients Who Transitioned to SLE

Severity of systemic

symptoms

SLE, No.

(%) (n=13)

SLE

(n=13) P

Musculoskeletal

Mild 1 (2) 0 0.004

Moderate/severe 0 3 (23)

Renal

Mild 0 2 (15) <0.001

Moderate/severe 0 2 (15)

Hematologic

Mild 5 (8) 4 (31) 0.04

Moderate/severe 0 0

Overall severity

Mild 64 (100) 8 (62) <0.001

Moderate/severe 0 5 (38)

Severity of Systemic Symptoms Developed During the Study

• Most patients that developed SLE did so via mucocutaneous ACR criteria (Table 2)

• Of the 13 that developed SLE, only 5 (38.5%) developed new moderate to severe

systemic disease (Table 3)

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• Wieczorek et al. concluded:

• Few patients with newly diagnosed CLE will go on to develop SLE (17%)

• Those that progress to SLE are likely to have mild systemic symptoms/disease (62%)

Note: the 2 patients that developed renal involvement had the following baseline criteria (1 – photosensitivity, ANA, discoid lesions; 2 – photosensitivity, discoid lesions, and arthritis [patient 2 later developed positive ANA and other autoantibodies]) (Personal correspondence with Victoria Werth, M.D., 3/26/14)

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• A new SLE diagnosis in CLE may not require rheumatologic referral if primarily skin disease

• 31% of SLE patients only had mucocutaneous +/- ANA and other autoantibody titers

• Proposed monitoring

1. CBC with differential and urinalysis annually

2. Complete review of systems at each visit

3. Additional serologic tests based on positive review of systems (eg, ANA, anti-dsDNA, anti-Sm)

Chong: JAMA Dermatology, 2014

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*** ***

Follow-up approach to patient

with established cutaneous lupus

*

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• 20% (18 of 90) SCLE patients met ACR

criteria for SLE

• HOWEVER, only 1 with SLE had

lupus nephritis (which developed 8.5

years prior to SCLE) and none of the

others had renal, neurologic, or

notable hematologic sequelae

• 14% (13 of 90) SCLE patients also had

Sjögren syndrome

• 3 of 13 (23%) had systemic

manifestations of Sjögren syndrome:

pulmonary interstitial fibrosis,

peripheral neuropathy, and

inflammatory myopathy

• (1) Importance of evaluating SCLE patients

not only for SLE, but also for Sjögren

syndrome

• (2) Only rare serious systemic sequelae

in SCLE patients with SLE – may help

guide clinicians on how to monitor their

patients over time for SLE development

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Not all patients that have “SLE” are

managed the same

• Those that manifest SLE mainly due to

mucocutaneous features are typically

managed much differently than those

with serious sequelae of SLE such as

nephritis, cerebritis, or significant

cytopenias

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In a patient with lupus, which of the following cutaneous findings is associated with the highest risk of systemic involvement?

1. Generalized DLE

2. Leukocytoclastic vasculitis

3. Lupus panniculitis

4. SCLE

5. Tumid lupus

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Risk of SLE stratified by cutaneous lupus subtypes

Costner and Sontheimer, Dermatology in General Medicine, Ch. 155, 8th ed.

LE-non-specific

skin disease

Systemic disease Skin disease

only

SCLE

Generalized DLE

Localized DLE

Hypertrophic DLE

LE profundus

ACLE

Risk of systemic lupus:

ACLE, LE-non-specific disease >>> SCLE > DLE (generalized > localized)

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Risk factors for both: (1) progression of DLE to SLE and (2) SLE patients with DLE

• Widespread DLE lesions

• Arthralgias/arthritis

• Nail changes (eg, periungual telangiectasia)

• Anemia

• Leukopenia

• High ESR (sedimentation rate)

• High-titer ANA

2012;166:29

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Summary of Studies Comparing DLE-Only Patients and SLE Patients With DLE

Study, year Groups studied Clinical Laboratory

Cardinali et al., 2000 116 DLE only, 19 DLE with SLE • Generalized DLE

• Nail changes

(i.e. periungual telan

giectasias)

None mentioned

Ng et al., 2000 63 DLE only, 10 DLE with SLE • Generalized DLE • ANA (≥1:160)

• (+) C1q deposits

Scott and Rees, 1959 16 SLE without DLE, 14 DLE with SLE, 11 DLE

with systemic findings but no SLE, 77 DLE only

• Generalized DLE • (+) LE test

Callen, 1982, Callen, 1985 56 DLE only, 17 DLE with SLE • Generalized DLE

• Periungual telangiectasias

• Arthritis

• (+) Anti-nDNA

• Elevated ESR

• Hypocomplementemia

• (+) ANA

• Leucopenia

• Anemia

Vera-Recabarren et al., 2010 148 CCLE only, 10 CCLE with SLE • Generalized DLE

• Arthralgias/arthritis

• Nephropathy

• Xerophthalmia

• Leucopenia

• (+) ANA (≥1:80)

• (+) Anti-Ro

• Lymphopenia

• (+) Anti-dsDNA

Prystowsky and Gilliam, 1975 80 DLE without SLE, 15 DLE with systemic

involvement, 13 SLE with proliferative

glomerulonephritis

• None mentioned • (+) ANA

• Low CH50

• (+) LBT

Characteristics associated with systemic involvement

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Summary of Studies Comparing DLE-Only Patients and Patients With DLE Who Progress to SLE

Study, year Groups studied Clinical Laboratory

Callen et al., 1982 56 DLE only, 4 DLE → SLE • Widespread DLE

• Periungual telangiectasias

• Arthralgias/arthritis

• Anemia

• High ANA titres

• Leucopenia

• High ESR

Healy et al., 1995 26 localized DLE, 27 widespread DLE, 7

SLE, 3 DLE → SLE

• Progression of localized DLE to

generalized DLE

• Persistently anemia

• Persistently (+) ANA (≥1:80)

• Persistently abnormal ESR

• Persistently abnormal serum

immunoglobins

Insawang et al., 2010 71 DLE only, 59 DLE with SLE (including

27 DLE → SLE)

• Arthralgia/arthritis

• Generalized DLE

• Presence of ANA

• Abnormal urinalysis

Millard and Rowell, 1979 67 localized DLE, 19 disseminated DLE,

6 DLE → SLE

None mentioned • Persistently (+) ANF titre (>1:50)

• Persistently low hemoglobin

Risk factors for systemic spread

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SLE manifestation

(n=positive finding of

1043)

SLE without

DLE (n=926),

n(%)

SLE with DLE

(n=117), n (%)

Unadjusted OR

(95% CI)

Adjusted OR

(95%)

Adjusted OR

(95%)

Anti-Smith 201(21.7) 45 (38.5) 2.25 (1.50-3.38) 2.27 (1.50-3.45) 2.41 (1.58-3.69)

Photosensitivity 374 (40.4) 60 (51.3) 1.55 (1.06-2.28) 1.71 (1.15-2.55) 1.63 (1.09-2.44)

Leukopenia 301 (32.5) 50 (42.7) 1.55 (1.05-2.29) 1.50 (1.01-2.24) 1.55 (1.03-2.32)

Pleuritis 349 (37.7) 31 (26.5) 0.59 (0.39-0.92) 0.56 (0.36-0.88) 0.56 (0.36-0.76)

Arthritis 738 (79.7) 79 (67.5) 0.53 (0.35-0.80) 0.51 (0.33-0.79) 0.49 (0.31-0.76)

Lupus nephritis 281 (30.3) 38 (32.5) 1.10 (0.73-1.66) 1.09 (0.71-1.68) 1.33 (0.83-2.14)

Pericarditis 112 (12.1) 10 (8.6) 0.68 (0.35-1.34) 0.68 (0.34-1.36) 0.68 (0.34-1.36)

Proteinuria 256 (27.7) 27 (23.1) 0.78 (0.50-1.23) 0.70 (0.43-1.13) 0.77 (0.47-1.27)

Casts 117 (12.6) 9 (77) 0.56 (0.28-1.17) 0.53 (0.26-1.09) 0.57 (0.27-1.20)

End-stage renal

disease 48 (5.1) 7 (6.0) 1.16 (0.51-2.64) 0.96 (0.41-2.22) 1.24 (0.50-3.05)

Oral ulcers 240 (25.9) 37 (31.6) 1.32 (0.87-2.00) 1.35 (0.88-2.07) 1.32 (0.86-2.03)

Malar rash 406 (43.8) 46 (39.3) 0.82 (0.56-1.23) 0.86 (0.57-1.30) 0.88 (0.58-1.32)

Seizure 100 (10.8) 14 (12) 1.12 (0.61-2.03) 1.14 (0.62-2.09) 1.20 (0.65-2.21)

Psychosis 16 (1.7) 3 (2.6) 1.50 (0.43-5.21) 1.45 (0.41-5.14) 1.50 (0.42-5.38)

Anemia 181 (19.5) 26 (22.2) 1.17 (0.74-1.87) 1.12 (0.69-1.80) 1.15 (0.71-1.86)

Lymphopenia 340 (36.7) 51 (43.6) 1.33 (0.90-1.96) 1.32 (0.88-1.97) 1.38 (0.91-2.08)

Thrombocytopenia 110 (11.9) 18 (15.4) 1.35 (0.79-2.31) 1.45 (0.83-2.54) 1.54 (0.87-2.71)

Anti-dsDNA 610 (65.9) 83 (70.9) 1.27 (0.83-1.93) 1.25 (0.81-1.93) 1.33 (0.86-2.07)

Antiphospholipid

antibodies 225 (24.3) 24 (20.5) 0.80 (0.50-1.29) 0.85 (0.52-1.37) 0.87 (0.54-1.43)

Capsule Summary

• Prior studies suggest that discoid lupus erythematosus among patients with systemic lupus erythematosus is a marker for less severe disease, often offered as reassurance

• We did not observe any associations (either positive or negative) with discoid lupus erythematosus and severe lupus manifestations (ie, renal or neurologic)

• These findings have important implications for counseling our patients with systemic lupus erythematosus and discoid lupus erythematosus regarding prognosis

DLE in SLE (compared to SLE without DLE):

• Increased risk of photosensitivity, leukopenia, and anti-Smith antibodies

• Decreased risk of pleuritis and arthritis

• No association (positive or negative) with nephritis or neurologic disease

Associations between discoid lupus erythematosus and other American College of

Rheumatology criteria for systemic lupus erythematosus and end-stage renal disease

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Summary of Cutaneous Lupus (CLE)

• Diagnosis of CLE requires clinicopathologic correlation

• CLE classified as

• Lupus-specific skin disease (multiple subtypes)

• Lupus-nonspecific skin disease

• Risk of systemic disease varies according to the type of skin disease present

• Smoking is associated with worse CLE

• Medications can trigger CLE (particularly SCLE)

• Patients with CLE should be monitored for progression to systemic disease, but consensus guidelines lacking

• Risk factors for SLE in those with DLE include

• Widespread DLE, arthralgias/arthritis, periungual telangiectasias, anemia, leukopenia, high ESR, high-titer ANA