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

Transcription

1 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, Forum Session (F114) American Academy of Dermatology, Annual Meeting, San Diego, California, February 18, MFMER

2 I have no conflicts of interest Disclosure Off-label use of systemic medications will be discussed 2016 MFMER

3 The scenario and clinical conundrum 2016 MFMER

4 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 2016 MFMER

5 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) 2016 MFMER

6 The Incidence of Cutaneous Lupus is 1. Greater than systemic lupus 2. The same as systemic lupus 3. Less than systemic lupus 2016 MFMER

7 Incidence Rate of Cutaneous Lupus is 4.30 per 100,000 Cutaneous lupus is as common as SLE 2016 MFMER

8 Incidence of Cutaneous Lupus is 3 Times Higher Than Systemic Lupus in Men 2016 MFMER

9 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 2016 MFMER

10 Costner MI and Sontheimer RD Show characteristic histopathologic changes of lupus erythematosus (e.g. interface dermatitis) Do not show characteristic histopathology of lupus and can be seen in other diseases 2016 MFMER

11 What are the typical clinical findings of cutaneous lupus? 2016 MFMER

12 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, MFMER

13 Note presence of both ACTIVITY (erythema, scale) and DAMAGE (dyspigmentation, scarring) in this patient with discoid lupus 2016 MFMER

14 A few examples of lupus-specific skin disease 2016 MFMER

15 Localized acute cutaneous lupus ( malar rash ) Note: 1. Sparing of nasolabial fold 2. Involvement of malar cheeks extending over nasal dorsum ( butterfly rash ) 2016 MFMER

16 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) 2016 MFMER

17 Hypertrophic/verrucous DLE 2016 MFMER

18 Note violaceous erythema and swelling of 2nd toe Chilblain lupus in setting of systemic lupus (SLE) 2016 MFMER

19 Definite chilblains lupus requires fulfilling BOTH major criteria and at least one of the minor criteria Cutis 54(6):395, MFMER

20 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 2016 MFMER

21 Lupus panniculitis 2016 MFMER

22 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 2016 MFMER

23 Lupus panniculitis and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) can present very similarly both clinically and histopathologically 2016 MFMER

24 A few examples of lupus-nonspecific skin disease MFMER

25 Calcinosis cutis (in a patient with SLE) Ulcerations with focal extrusion of chalky granules because of calcinosis cutis in a patient with system lupus erythematosus Gutierrez Jr. and Wetter: Dermatologic Therapy 25:195, MFMER

26 2016 MFMER

27 Characteristics and Prevalence of ACTD Associated with Calcinosis Cutis Patients, No. (%) (n=78) 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) 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 ( ) RA 1 (100) 0 1 (1) Polymyositis 1 (100) 0 1 (1) Range of ACTD s associated with calcinosis Dermatomyositis (38%) Systemic sclerosis with limited cutaneous scleroderma (31%) Lupus panniculitis (4 pts.), SLE (2 pts.) 2016 MFMER

28 Urticarial vasculitis Note bruise-like discoloration Can be associated with SLE particularly if associated with low complement levels 2016 MFMER

29 Etiologies of Cutaneous Small Vessel Vasculitis Infection (15-20%) Autoimmune connective tissue disease (15-20%) Drug (10-15%) Neoplasm (5%) Idiopathic (45-55%) Chung et al: Dermatology, 2008, Ch MFMER

30 What other conditions can appear clinically similar to cutaneous lupus? 2016 MFMER

31 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 MFMER

32 What is the histopathology of cutaneous lupus? 2016 MFMER

33 Low-Power Image Note Perivascular and Periadnexal Lymphocytic Infiltrate as well as Follicular Plugging Photo courtesy of Michael J. Camilleri, M.D. Mayo Clinic 2016 MFMER

34 Medium and High Power Images Note Interface Dermatitis With Basal Vacuolar Degeneration Photo courtesy of Michael J. Camilleri, M.D. Mayo Clinic 2016 MFMER

35 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 2016 MFMER

36 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 2016 MFMER

37 2016 MFMER

38 Can medications be associated with the onset of cutaneous lupus? 2016 MFMER

39 Subacute Cutaneous Lupus Erythematosus (SCLE) 2016 MFMER

40 SCLE Note Photodistribution in Current and Previous Photo 2016 MFMER

41 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, 8 th ed MFMER

42 More than 1/3 of SCLE cases could be attributed to drug exposure 2016 MFMER

43 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, MFMER

44 2016 MFMER

45 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) 2016 MFMER

46 Approximately 80% of Patients With SCLE Will Have Positive Ro/SSA Antibodies (Does Not Differ Between Idiopathic and Drug-Induced Cases) Autoantibodies in drug-induced subacute cutaneous lupus erythematosus 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 Ro/SS-A autoantibody rates were not significantly different between DI-SCLE and idiopathic SCLE 2016 MFMER

47 2016 MFMER

48 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) (14) 18 (25) Outcome Improvement 13/13 (100) 71 (99) Time to improvement (mo) *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, 2 nd ed.]) 2016 MFMER

49 Which laboratory evaluations should be performed in patients with cutaneous lupus? 2016 MFMER

50 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? 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 Callen: Arch Dermatol 145(3):316, MFMER

51 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) 2016 MFMER

52 Approach to newly diagnosed patient with cutaneous lupus 2016 MFMER

53 Costner M and Sontheimer R 2016 MFMER

54 SLICC, MFMER

55 SLICC (2012) criteria were more sensitive than ACR (1997) criteria in classifying a patient as having SLE 2016 MFMER

56 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 2016 MFMER

57 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% 2016 MFMER

58 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) 2016 MFMER

59 2016 MFMER

60 Baseline Patient Characteristics and Symptoms Characteristic or Symptom CLE (n=64) SLE (n=13) P Age, mean (SD), y 51.0 (14.3) (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) Discoid generalized 6 (9) 4 (31) 0.04 SCLE, No. (%) 19 (30) 5 (38) 0.53 Antibody test result, No. (%) Negative baseline ANA titer 54 (84) 5 (38) Baseline ANA titer, 1:80-1:160 3 (5) 4 (31) Baseline ANA titer, 1:320-1: (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) 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) Moderate/severe 0 2 (15) 0.03 P<0.005 = statistically significant 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 2016 MFMER

61 Criteria Met by Patients Who Transitioned to SLE Severity of Systemic Symptoms Developed During the Study 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) Severity of systemic symptoms Musculoskeletal SLE, No. (%) (n=13) SLE (n=13) Mild 1 (2) 0 Moderate/severe 0 3 (23) Renal Mild 0 2 (15) Moderate/severe 0 2 (15) Hematologic Mild 5 (8) 4 (31) Moderate/severe 0 0 Overall severity Mild 64 (100) 8 (62) Moderate/severe 0 5 (38) P < <0.001 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) 2016 MFMER

62 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) 2016 MFMER

63 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, MFMER

64 2016 MFMER

65 *** *** * Follow-up approach to patient with established cutaneous lupus 2016 MFMER

66 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 2016 MFMER

67 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 2016 MFMER

68 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 2016 MFMER

69 Lupus Erythematosus (LE)-Specific Skin Disease SCLE Generalized DLE ACLE Localized DLE Skin disease only Hypertrophic DLE Systemic disease LE-non-specific skin disease LE profundus Risk of systemic lupus: ACLE, LE-non-specific disease >>> SCLE > DLE (generalized > localized) Costner and Sontheimer, Dermatology in General Medicine, Ch. 155, 8 th ed MFMER

70 2012;166:29 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 2016 MFMER

71 Summary of Studies Comparing DLE-Only Patients and SLE Patients With DLE Characteristics associated with systemic involvement Study, year Groups studied Clinical Laboratory Cardinali et al., DLE only, 19 DLE with SLE Generalized DLE Nail changes (i.e. periungual telan giectasias) None mentioned Ng et al., DLE only, 10 DLE with SLE Generalized DLE ANA ( 1:160) (+) C1q deposits Scott and Rees, 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, DLE only, 17 DLE with SLE Generalized DLE Periungual telangiectasias Arthritis Vera-Recabarren et al., CCLE only, 10 CCLE with SLE Generalized DLE Arthralgias/arthritis Nephropathy Xerophthalmia (+) Anti-nDNA Elevated ESR Hypocomplementemia (+) ANA Leucopenia Anemia Leucopenia (+) ANA ( 1:80) (+) Anti-Ro Lymphopenia (+) Anti-dsDNA Prystowsky and Gilliam, DLE without SLE, 15 DLE with systemic involvement, 13 SLE with proliferative glomerulonephritis None mentioned (+) ANA Low CH 50 (+) LBT 2016 MFMER

72 Summary of Studies Comparing DLE-Only Patients and Patients With DLE Who Progresses to SLE Risk factors for systemic spread Study, year Groups studied Clinical Laboratory Callen et al., DLE only, 4 DLE SLE Widespread DLE Periungual telangiectasias Arthralgias/arthritis Anemia High ANA titres Leucopenia High ESR Healy et al., 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., DLE only, 59 DLE with SLE (including 27 DLE SLE) Arthralgia/arthritis Generalized DLE Presence of ANA Abnormal urinalysis Millard and Rowell, localized DLE, 19 disseminated DLE, 6 DLE SLE None mentioned Persistently (+) ANF titre (>1:50) Persistently low hemoglobin 2016 MFMER

73 2016 MFMER

74 Associations between discoid lupus erythematosus and other American College of Rheumatology criteria for systemic lupus erythematosus and end-stage renal disease 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 ( ) 2.27 ( ) 2.41 ( ) Photosensitivity 374 (40.4) 60 (51.3) 1.55 ( ) 1.71 ( ) 1.63 ( ) Leukopenia 301 (32.5) 50 (42.7) 1.55 ( ) 1.50 ( ) 1.55 ( ) Pleuritis 349 (37.7) 31 (26.5) 0.59 ( ) 0.56 ( ) 0.56 ( ) Arthritis 738 (79.7) 79 (67.5) 0.53 ( ) 0.51 ( ) 0.49 ( ) Lupus nephritis 281 (30.3) 38 (32.5) 1.10 ( ) 1.09 ( ) 1.33 ( ) Pericarditis 112 (12.1) 10 (8.6) 0.68 ( ) 0.68 ( ) 0.68 ( ) Proteinuria 256 (27.7) 27 (23.1) 0.78 ( ) 0.70 ( ) 0.77 ( ) Casts 117 (12.6) 9 (77) 0.56 ( ) 0.53 ( ) 0.57 ( ) End-stage renal 48 (5.1) 7 (6.0) 1.16 ( ) 0.96 ( ) 1.24 ( ) disease Oral ulcers 240 (25.9) 37 (31.6) 1.32 ( ) 1.35 ( ) 1.32 ( ) Malar rash 406 (43.8) 46 (39.3) 0.82 ( ) 0.86 ( ) 0.88 ( ) Seizure 100 (10.8) 14 (12) 1.12 ( ) 1.14 ( ) 1.20 ( ) Psychosis 16 (1.7) 3 (2.6) 1.50 ( ) 1.45 ( ) 1.50 ( ) Anemia 181 (19.5) 26 (22.2) 1.17 ( ) 1.12 ( ) 1.15 ( ) Lymphopenia 340 (36.7) 51 (43.6) 1.33 ( ) 1.32 ( ) 1.38 ( ) Thrombocytopenia 110 (11.9) 18 (15.4) 1.35 ( ) 1.45 ( ) 1.54 ( ) Anti-dsDNA 610 (65.9) 83 (70.9) 1.27 ( ) 1.25 ( ) 1.33 ( ) Antiphospholipid antibodies 225 (24.3) 24 (20.5) 0.80 ( ) 0.85 ( ) 0.87 ( ) 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 2016 MFMER

75 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 2016 MFMER