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RESEARCH LETTER

Autoantibodies and Disease Activity in Patients With Discoid Lupus Erythematosus Serologic markers mirroring disease activity in patients with discoid lupus erythematosus (DLE) are unknown. Identifying them would help predict disease course, guide treatSupplemental content at ment, and clarify the etioljamadermatology.com ogy of DLE. Because autoantibodies have been associated with systemic lupus erythematosus (SLE) disease activity,1 we investigated associations between autoantibodies and disease activity measures in patients with DLE. Methods | Patients recruited from University of Texas Southwestern Medical Center outpatient clinics provided written informed consent to this cross-sectional pilot study, which was approved by the university’s institutional review board. Patients with clinicopathologic diagnoses of DLE were included. Patients with other cutaneous lupus erythematosus subtypes (besides acute cutaneous lupus erythematosus) were excluded. Levels of IgG autoantibodies were quantified by means of enzyme-linked immunosorbent assays (antinuclear antibodies [ANAs], antiribonucleoprotein [anti-RNP], anti– double-stranded DNA [anti-dsDNA] [Inova Diagnostics], anti–single-stranded DNA [anti-ssDNA] [ORGENTEC Diagnostika]) or QUANTAPlex fluorescent immunoassays (antiScl-70, anti-Smith, anti-SS-A [52 kDa], anti-SS-A [60 kDa], anti-SS-B) (Inova). The Cutaneous Lupus Disease Area and Severity Index (CLASI) activity score was the primary disease activity measure. Secondary disease activity indices included CLASI damage score, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, numbers of oral lupus medications prescribed, SLE criteria,2 concentrations of C3 and C4, erythrocyte sedimentation rate, and level of C-reactive protein. All indices except C3, C4, erythrocyte sedimentation rate, and Creactive protein, which were recorded if measured within 3 months of serum collection, were collected at study visits. Correlations were calculated by means of the Spearman rank correlation. The DLE subgroup analyses (eg, DLE with SLE or positive for ANAs) were preplanned. P < .005 was declared significant to account for multiple comparisons. Results | Characteristics of patients with DLE and their subsets are presented in Table 1. In all patients with DLE, level of jamadermatology.com

anti-RNP IgG correlated strongly with CLASI activity scores (Table 2, eFigure in Supplement). Results of tests for ANA, anti-RNP, anti-dsDNA, and anti-ssDNA IgG significantly correlated with SLEDAI scores, numbers of SLE criteria and oral medications used, C3, and C4, except anti-ssDNA IgG and SLEDAI scores. Patients with DLE who tested positive for ANA or who also had SLE demonstrated significant associations between the levels of anti-RNP IgG and CLASI activity scores, and between the levels of ANA, anti-RNP, antidsDNA, and anti-ssDNA IgG and several systemic disease activity measures (Table 2). Discussion | Results of anti-RNP IgG tests correlated with skin disease activity in patients with DLE. Because patients with DLE who were positive for ANA or who also had SLE demonstrated similar findings, we postulate that when circulating anti-RNP IgG levels surpass a threshold amount, they parallel skin disease activity in patients with DLE. Whereas anti-RNP antibody levels have not been associated with DLE, patients with DLE with SLE have shown upregulated anti-RNP antibody levels.3 Our observation of anti-RNP antibody levels trending with DLE skin disease activity raises the question of whether they contribute to skin disease progression or are byproducts of inflammation. Mechanistic studies investigating whether anti-RNP antibodies exacerbate skin disease in lupusprone mice are being planned. There were multiple correlations of levels of ANA, antiRNP, anti-dsDNA, and anti-ssDNA IgG with systemic disease activity measures in all patients with DLE with or without ANA positivity or SLE. Elevated levels of ANA, anti-RNP, antidsDNA, or anti-ssDNA IgG in patients with DLE could prompt initiation of oral medication use, which can diminish their levels. Use of quinacrine hydrochloride decreased anti-dsDNA antibody levels in patients with SLE.4 Prospective studies tracking autoantibody levels and disease activity in patients with DLE receiving oral lupus medications may validate this hypothesis. Limitations of this study include collection of complement levels, erythrocyte sedimentation rate, and C-reactive protein levels, which were not always collected at study visits. Because they fluctuate often, levels may not be accurately reflected. Enzyme-linked immunosorbent assays and fluorescent immunoassays are very sensitive, leading to high false-positive rates.5 However, they were selected because they provided continuous values used in correlation analyses. Because of the study’s cross-sectional design, a causal relationship between autoantibody level and disease progression cannot be determined. JAMA Dermatology June 2014 Volume 150, Number 6

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Table 1. Clinical Characteristics of Patients With Discoid Lupus Erythematosus (DLE) and Their Subgroups All DLE (N = 95)

Characteristic Age at visit, mean (SD), y

DLE With ANA Positivity (n = 77)

DLE With SLE (n = 45)

45 (12)

45 (12)

44 (12)

Male

16 (17)

11 (14)

5 (11)

Female

79 (83)

66 (86)

40 (89)

6 (7)

6 (7)

7 (7)

Sex, No. (%)

Disease duration, mean (SD), ya Ethnicity, No. (%) African American

58 (61)

48 (62)

27 (60)

White

23 (24)

18 (23)

9 (20)

Asian

6 (6)

5 (6)

5 (11)

Hispanic

7 (7)

5 (6)

4 (9)

Mixed

1 (1)

1 (1)

0 (0)

Activity

7 (6)

7 (7)

8 (7)

Damage

9 (7)

10 (7)

11 (8)

2 (3)

2 (3)

3 (3)

46 (48)

46 (60)

45 (100)

Malar rash

21 (22)

21 (27)

19 (42)

Discoid rash

95 (100)

77 (100)

45 (100)

Photosensitivity

73 (77)

61 (79)

41 (91)

Oral ulcers

29 (31)

28 (36)

21 (47)

Arthritis

32 (34)

30 (39)

26 (58)

Serositis

5 (5)

5 (6)

5 (11)

Renal disorder

9 (9)

9 (12)

9 (20)

Neurologic disorder

0

0

CLASI, mean (SD)

SLEDAI, mean (SD) SLE diagnosis, No. (%) SLE criteria No. (%)

0

Hematological disorder

34 (36)

30 (39)

29 (64)

Positive for ANAb

56 (59)

53 (70)

44 (98)

Immunological disorder

34 (36)

34 (44)

31 (69)

4 (2)

4 (2)

6 (1)

Total, mean (SD), No. Current lupus medications No. (%) None

12 (13)

9 (12)

3 (7)

Topical/intralesional steroids

54 (57)

42 (55)

26 (58)

6 (6)

6 (8)

1 (2)

Prednisone

20 (21)

19 (25)

19 (42)

Hydroxychloroquine sulfate

55 (58)

45 (58)

27 (60) 5 (11)

Topical immunomodulators

Chloroquine phosphate

9 (9)

7 (9)

11 (12)

10 (13)

7 (16)

4 (4)

4 (5)

2 (4)

11 (12)

11 (14)

10 (22)

Efalizumab

1 (1)

1 (1)

1 (2)

Azathioprine

2 (2)

2 (3)

2 (4)

Quinacrine hydrochloride Methotrexate Mycophenolate mofetil

Methylprednisolone sodium succinate

1 (1)

1 (1)

1 (2)

Cyclosporine

1 (1)

1 (1)

1 (2)

1 (2)

1 (1)

2 (1)

Total oral medications, mean (SD), No.

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Abbreviations: ANA, antinuclear antibody; CLASI, Cutaneous Lupus Disease Area and Severity Index; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Erythematosus Disease and Activity Index. a

Disease duration was not available for 10 patients with DLE, 9 ANA-positive patients with DLE, and 7 patients with DLE with SLE.

b

Antinuclear antibody positivity was determined by history of ANA titers ⱖ1:160 as determined by indirect immunofluorescence and/or positive enzyme-linked immunosorbent assay result.

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Table 2. Correlation Analysis of Autoantibodies and Disease Activity Markers in Subsets of Patients With Discoid Lupus Erythematosus (DLE) Autoantibodya Marker

ANA

Anti-RNP

Anti-dsDNA

Anti-ssDNAb

All DLE (N = 95) No. (%)

77 (81)

41 (43)

21 (22)

22 (24)

CLASI activity score, r (P value)

0.21 (.04)

0.32 (.002)

0.24 (.02)

0.06 (.55)

SLEDAI score, r (P value)

0.37 (

Autoantibodies and disease activity in patients with discoid lupus erythematosus.

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