- Email: [email protected]
Clinicopathologic comparison of Rowell syndrome, erythema multiforme, and subacute cutaneous lupus erythematosus
Accepted Manuscript Clinicopathologic comparison of Rowell syndrome, erythema multiforme, and subacute cutaneous lupus erythematosus Mitch Herold, BS, Colton B. Nielson, MD, Diana Braswell, MD, Kimberly Merkel, MD, Addie Walker, MD, Jena Auerbach, DO, Jyoti Kapil, MD, Kiran Motaparthi, MD PII:
S0190-9622(19)30968-5
DOI:
https://doi.org/10.1016/j.jaad.2019.06.008
Reference:
YMJD 13529
To appear in:
Journal of the American Academy of Dermatology
Received Date: 11 February 2019 Revised Date:
17 May 2019
Accepted Date: 7 June 2019
Please cite this article as: Herold M, Nielson CB, Braswell D, Merkel K, Walker A, Auerbach J, Kapil J, Motaparthi K, Clinicopathologic comparison of Rowell syndrome, erythema multiforme, and subacute cutaneous lupus erythematosus, Journal of the American Academy of Dermatology (2019), doi: https:// doi.org/10.1016/j.jaad.2019.06.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
1
Clinicopathologic comparison of Rowell syndrome, erythema multiforme, and subacute
2
cutaneous lupus erythematosus
RI PT
Mitch Herold1, BS Colton B Nielson1, MD Diana Braswell1, MD Kimberly Merkel1, MD Addie Walker1, MD Jena Auerbach2, DO Jyoti Kapil3, MD Kiran Motaparthi1, MD
SC
3 4 5 6 7 8 9 10 11
1: Department of Dermatology, University of Florida College of Medicine 2: Department of Pathology, University of Florida College of Medicine 3: Inform Diagnostics Research Institute
35 36 37
Conflicts of interest: None to disclose Sources of funding: None to disclose Prior presentation or publication: None to disclose
38 39 40
Keywords: Rowell syndrome, CD123, plasmacytoid dendritic cells, subacute cutaneous lupus erythematous, erythema multiforme
41
M AN U
12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
TE D
Corresponding author: Kiran Motaparthi, MD Department of Dermatology University of Florida College of Medicine 4037 NW 86 Terrace, 4th Floor Room 4123 Springhill Gainesville, FL 32606 [email protected] 352-594-1930 (p) Reprint requests: Kiran Motaparthi, MD [email protected]
EP
Word count: 500
AC C
Tables: 1 Figures: 1 (2 additional online only at https://data.mendeley.com/datasets/bwswc4h9yb/1) References: 6
ACCEPTED MANUSCRIPT 2 To the editor: Rowell syndrome (RS) is characterized by erythema multiforme (EM)-like lesions
43
with serologic and historical evidence of lupus erythematosus (LE).1 Classification of RS
44
remains controversial given overlapping clinical features of EM and cutaneous lupus
45
erythematosus (CLE).2 Our objective was to identify histologic and immunohistochemical
46
findings that support classification of RS; current definitions lack these criteria.3 CD123, which
47
labels pathogenic plasmacytoid dendritic cells (PDCs) in LE, may be useful in this context.4,5
RI PT
42
SC
48
Following Institutional Review Board approval, the archives of the University of Florida and
50
Inform Diagnostics were queried for diagnoses of RS (8 biopsies from 5 patients), SCLE (7
51
biopsies from 4 patients), and EM (5 biopsies from 5 patients) rendered between November 2016
52
and June 2018; an additional single indeterminate case was also identified. Clinical features,
53
serology, histology, and CD123 antibody staining for plasmacytoid dendritic cells were
54
compared between RS, SCLE, and EM cases following a blinded retrospective histologic review.
55
A Fisher exact test was used to compare histologic variables and CD123 staining patterns
56
between RS, SCLE, and EM. Two tailed p-values less than 0.05 were deemed statistically
57
significant.
TE D
EP
AC C
58
M AN U
49
59
RS and SCLE were characterized by female predominance, antecedent history of LE, lack of
60
causative medication, absence of mucosal involvement, positivity for rheumatoid factor (RF),
61
and speckled ANA pattern with anti-Ro (SS-A) positivity (Table 1). Targetoid plaques were
62
observed in RS (4/4) but not SCLE (0/4). Conversely, anti-La (SS-B) positivity was observed in
63
SCLE (2/3) but not in RS (0/4), which may reflect assays with variable sensitivity of detection
ACCEPTED MANUSCRIPT 3 for this autoantibody.6 DIF was positive in RS (1/1) and SCLE (1/1) but negative in EM (0/1).
65
Summarized in Table 1, common and unifying histologic features of RS (Figure 1) and SCLE
66
(Figure 2) include periadnexal lymphocytic infiltrates (p=1), absence of dermal eosinophils
67
(p=1), and CD123 positivity representing 10% or more of the inflammatory infiltrate (p=1).
68
Distinction of RS from EM (Figure 3) is supported by periadnexal lymphocytic infiltrates
69
(p=0.003) and periadnexal CD123+ PDCs (p=0.049). Using these features, the indeterminate
70
case was reclassified as RS. Several features did not aid classification (1 > p > 0.05), including
71
interface tissue reaction subtype (lichenoid or cell-poor), deep perivascular lymphocytic
72
infiltrate, periadnexal plasmacellular aggregates, mucin deposition by Alcian blue, and the
73
predominant CD123 staining pattern (epidermal or dermal).
M AN U
SC
RI PT
64
74
This series is limited by its small sample size, retrospective nature, and lack of complete clinical
76
data for all patients. Previously dependent on clinical history, serology, and nonspecific clinical
77
morphology, diagnosis of RS may be improved by histologic detail and CD123. Unifying
78
features of RS and SCLE include antecedent history of LE, absence of mucosal involvement,
79
serology (ANA, anti-Ro/SS-A, and RF), DIF positivity, periadnexal lymphocytic infiltrates,
80
absence of dermal eosinophils, and CD123+ inflammatory cells only when comprising 10% or
81
more of the inflammatory infiltrate. In the context of targetoid clinical morphology, these
82
features aid in distinction from EM. These clinicopathologic findings support inclusion of RS
83
in the spectrum of CLE and may provide therapeutic or prognostic benefit to patients with
84
diagnoses previously identified as RS or EM.
85 86
AC C
EP
TE D
75
ACCEPTED MANUSCRIPT
88
RS
Rowell syndrome
89
EM
erythema multiforme
90
LE
lupus erythematosus
91
CLE
cutaneous lupus erythematosus
92
SCLE
subacute cutaneous lupus erythematosus
93
PDC
plasmacytoid dendritic cell
94
ANA
antinuclear antibody
95
SS-A
Sjögren syndrome antibody A
96
SS-B
Sjögren syndrome antibody B
97
IHC
immunohistochemistry
98
DIF
direct immunofluorescence
99
RF
rheumatoid factor
101 102 103 104 105
TE D
EP
AC C
100
SC
Abbreviations
M AN U
87
RI PT
4
ACCEPTED MANUSCRIPT 5 References:
107
1. Torchia D, Romanelli P, Kerdel FA. Erythema multiforme and Stevens-Johnson
108
syndrome/toxic epidermal necrolysis associated with lupus erythematosus. J Am Acad
109
Dermatol. 2012;67(3):417-21. doi: 10.1016/j.jaad.2011.10.012.
110
RI PT
106
2. Rowell NR, Beck JS, Anderson JR. Lupus erythematosus and erythema multiforme-like
112
lesions. A syndrome with characteristic immunological abnormalities. Arch Dermatol.
113
1963;88:176-80. doi: 10.1001/archderm.1963.01590200064012
SC
111
M AN U
114 115
3. Zeitouni NC, Funaro D, Cloutier RA, et al. Redefining Rowell’s syndrome. Br J Dermatol.
116
2000;142(2):343-6. doi: 10.1046/j.1365-2133.2000.03306.x
117
4. Swiecki M, Colonna M, The multifaceted biology of plasmacytoid dendritic cells. Nat Rev
119
Immunol. 2015;15(8):471-85. doi: 10.1038/nri3865.
120
TE D
118
5. Vermi W, Lonardi S, Morassi M, et al. Cutaneous distribution of plasmacytoid dendritic cells
122
in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage.
123
Immunobiology. 2009;214(9-10):877-86. doi: 10.1016/j.imbio.2009.06.013.
AC C
124
EP
121
125
6. Franceschini F, Cavazzana I. Anti-Ro/SSA and La/SSB antibodies. Autoimmunity.
126
2005;38(1):55-63. doi: 10.1080/08916930400022954.
127 128
ACCEPTED MANUSCRIPT 6 129
Figure legend
130
Figure 1:
132
Rowell syndrome. A: Targetoid plaques with dusky centers and peripheral erythema. B:
133
Lichenoid interface dermatitis with keratinocyte necrosis, perivascular lymphocytic infiltrates,
134
and mucin (H&E, 100x magnification). C: Perifollicular and intraepithelial plasmacytoid
135
dendritic cells, representing greater than 10% of the inflammatory infiltrate (CD123 with red
136
chromagen, 200x magnification). D: Perieccrine plasmacytoid dendritic cells (CD123 with red
137
chromagen, 200x magnification).
M AN U
138
SC
RI PT
131
Figure 2 (online only – available at https://data.mendeley.com/datasets/bwswc4h9yb/1):
140
Subacute cutaneous lupus erythematosus. A: Polycyclic erythematous plaques with peripheral
141
scale. B and C: Cell-poor interface dermatitis, epidermal atrophy, and sparse lymphocytic
142
infiltrate with abundant dermal mucin (B: H&E, 40x magnification; C: H&E, 200x
143
magnification). D: Perieccrine plasmacytoid dendritic cells highlighted by CD123 (CD123 with
144
red chromagen, 400x magnification).
EP
145
TE D
139
Figure 3 (online only – available at https://data.mendeley.com/datasets/bwswc4h9yb/1):
147
Erythema multiforme. A: Typical target with three zones of color change and central
148
vesiculation. B: Orolabial erosions. C: Lichenoid interface dermatitis with partial epidermal
149
necrosis. D: Absence of perieccrine plasmacytoid dendritic cells (CD123 with red chromagen,
150
200x magnification).
151
AC C
146
ACCEPTED MANUSCRIPT 7 152 153 154
RI PT
155 156 157
SC
158 159
M AN U
160 161 162 163
EP
166
AC C
165
TE D
164
ACCEPTED MANUSCRIPT
8 Table 1: Comparison of RS, SCLE, and EM by clinical, serologic, histologic and immunohistochemical findings SCLE (4 patients; 7 biopsies)
EM (5 patients; 5 biopsies)
Mean Age (years)
53 ± 23.15
62.8 ± 16.44
52.8 ± 16.07
Gender
80% F (4/5)
100% F (4/4)
80% F (4/5)
100% (4/4)
75% (3/4)
0% (0/5)
Targetoid lesions
100% (4/4)
0% (0/4)
100% (5/5)
Mucosal involvement
0% (0/4)
0% (0/4)
Implicated medication
0% (0/4)
0% (0/4)
ANA pattern
50% Speckled (2/4)
67% Speckled (2/3)
Lesional DIF3
100% (1/1)
100% (1/1)
Full-thickness epidermal necrosis
50% (4/8)
0% (0/7)
Parakeratosis
25% (2/8)
85.7% (6/7)
Dermal eosinophils
0%
0%
Periadnexal lymphocytic infiltrate4
RS, SCLE, and EM (p-value)
1
1
0.0047
0.0286
0.0028
40% (2/5)
1
0.2821
20% (1/5)
1
1
0% Speckled (0/2)
1
0.5238
0% (0/1)
1
1
80% (4/5)
0.077
0.017
20% (1/5)
0.041
0.034
20% (1/5)
1
0.250
SC
1
M AN U
2
TE D
History of LE1
RS and SCLE (p-value)
RI PT
RS (5 patients; 8 biopsies)
85.7% (6/7)
0%
1
0.003
62.5% (5/8)
57.1% (4/7)
20% (1/5)
1
0.395
Dermal predominant CD123 pattern
42.9% (3/7)
83.3% (5/6)
40% (2/5)
0.266
0.292
Intraepidermal CD123-positive PDCs
100% (7/7)
66.7% (4/6)
100% (5/5)
0.192
0.163
Periadnexal CD123-positive PDCs
100% (7/7)
66.7% (4/6)
40% (2/5)
0.192
0.049
10% or greater CD123-positive cells
EP
87.5% (7/8) 5
AC C
ANA: Antinuclear antibody; DIF: direct immunofluorescence; EM: erythema multiforme; LE: lupus erythematosus; PDC: plasmacytoid dendritic cell; RS: Rowell syndrome; SCLE: subacute cutaneous lupus erythematosus 1. History of systemic or cutaneous lupus erythematosus 2. Two or more zones of color 3. IgG: granular deposition in the lower epidermis, along the basement membrane zone, and ANA pattern in keratinocytes; C3, IgM, IgA, C3, and C5b-9: granular deposition along the basement membrane zone 4. Perifollicular or perieccrine 5. Percentage of inflammatory cells positive for antibody staining in a single histologic section
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S0190-9622(19)30968-5
DOI:
https://doi.org/10.1016/j.jaad.2019.06.008
Reference:
YMJD 13529
To appear in:
Journal of the American Academy of Dermatology
Received Date: 11 February 2019 Revised Date:
17 May 2019
Accepted Date: 7 June 2019
Please cite this article as: Herold M, Nielson CB, Braswell D, Merkel K, Walker A, Auerbach J, Kapil J, Motaparthi K, Clinicopathologic comparison of Rowell syndrome, erythema multiforme, and subacute cutaneous lupus erythematosus, Journal of the American Academy of Dermatology (2019), doi: https:// doi.org/10.1016/j.jaad.2019.06.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
1
Clinicopathologic comparison of Rowell syndrome, erythema multiforme, and subacute
2
cutaneous lupus erythematosus
RI PT
Mitch Herold1, BS Colton B Nielson1, MD Diana Braswell1, MD Kimberly Merkel1, MD Addie Walker1, MD Jena Auerbach2, DO Jyoti Kapil3, MD Kiran Motaparthi1, MD
SC
3 4 5 6 7 8 9 10 11
1: Department of Dermatology, University of Florida College of Medicine 2: Department of Pathology, University of Florida College of Medicine 3: Inform Diagnostics Research Institute
35 36 37
Conflicts of interest: None to disclose Sources of funding: None to disclose Prior presentation or publication: None to disclose
38 39 40
Keywords: Rowell syndrome, CD123, plasmacytoid dendritic cells, subacute cutaneous lupus erythematous, erythema multiforme
41
M AN U
12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
TE D
Corresponding author: Kiran Motaparthi, MD Department of Dermatology University of Florida College of Medicine 4037 NW 86 Terrace, 4th Floor Room 4123 Springhill Gainesville, FL 32606 [email protected] 352-594-1930 (p) Reprint requests: Kiran Motaparthi, MD [email protected]
EP
Word count: 500
AC C
Tables: 1 Figures: 1 (2 additional online only at https://data.mendeley.com/datasets/bwswc4h9yb/1) References: 6
ACCEPTED MANUSCRIPT 2 To the editor: Rowell syndrome (RS) is characterized by erythema multiforme (EM)-like lesions
43
with serologic and historical evidence of lupus erythematosus (LE).1 Classification of RS
44
remains controversial given overlapping clinical features of EM and cutaneous lupus
45
erythematosus (CLE).2 Our objective was to identify histologic and immunohistochemical
46
findings that support classification of RS; current definitions lack these criteria.3 CD123, which
47
labels pathogenic plasmacytoid dendritic cells (PDCs) in LE, may be useful in this context.4,5
RI PT
42
SC
48
Following Institutional Review Board approval, the archives of the University of Florida and
50
Inform Diagnostics were queried for diagnoses of RS (8 biopsies from 5 patients), SCLE (7
51
biopsies from 4 patients), and EM (5 biopsies from 5 patients) rendered between November 2016
52
and June 2018; an additional single indeterminate case was also identified. Clinical features,
53
serology, histology, and CD123 antibody staining for plasmacytoid dendritic cells were
54
compared between RS, SCLE, and EM cases following a blinded retrospective histologic review.
55
A Fisher exact test was used to compare histologic variables and CD123 staining patterns
56
between RS, SCLE, and EM. Two tailed p-values less than 0.05 were deemed statistically
57
significant.
TE D
EP
AC C
58
M AN U
49
59
RS and SCLE were characterized by female predominance, antecedent history of LE, lack of
60
causative medication, absence of mucosal involvement, positivity for rheumatoid factor (RF),
61
and speckled ANA pattern with anti-Ro (SS-A) positivity (Table 1). Targetoid plaques were
62
observed in RS (4/4) but not SCLE (0/4). Conversely, anti-La (SS-B) positivity was observed in
63
SCLE (2/3) but not in RS (0/4), which may reflect assays with variable sensitivity of detection
ACCEPTED MANUSCRIPT 3 for this autoantibody.6 DIF was positive in RS (1/1) and SCLE (1/1) but negative in EM (0/1).
65
Summarized in Table 1, common and unifying histologic features of RS (Figure 1) and SCLE
66
(Figure 2) include periadnexal lymphocytic infiltrates (p=1), absence of dermal eosinophils
67
(p=1), and CD123 positivity representing 10% or more of the inflammatory infiltrate (p=1).
68
Distinction of RS from EM (Figure 3) is supported by periadnexal lymphocytic infiltrates
69
(p=0.003) and periadnexal CD123+ PDCs (p=0.049). Using these features, the indeterminate
70
case was reclassified as RS. Several features did not aid classification (1 > p > 0.05), including
71
interface tissue reaction subtype (lichenoid or cell-poor), deep perivascular lymphocytic
72
infiltrate, periadnexal plasmacellular aggregates, mucin deposition by Alcian blue, and the
73
predominant CD123 staining pattern (epidermal or dermal).
M AN U
SC
RI PT
64
74
This series is limited by its small sample size, retrospective nature, and lack of complete clinical
76
data for all patients. Previously dependent on clinical history, serology, and nonspecific clinical
77
morphology, diagnosis of RS may be improved by histologic detail and CD123. Unifying
78
features of RS and SCLE include antecedent history of LE, absence of mucosal involvement,
79
serology (ANA, anti-Ro/SS-A, and RF), DIF positivity, periadnexal lymphocytic infiltrates,
80
absence of dermal eosinophils, and CD123+ inflammatory cells only when comprising 10% or
81
more of the inflammatory infiltrate. In the context of targetoid clinical morphology, these
82
features aid in distinction from EM. These clinicopathologic findings support inclusion of RS
83
in the spectrum of CLE and may provide therapeutic or prognostic benefit to patients with
84
diagnoses previously identified as RS or EM.
85 86
AC C
EP
TE D
75
ACCEPTED MANUSCRIPT
88
RS
Rowell syndrome
89
EM
erythema multiforme
90
LE
lupus erythematosus
91
CLE
cutaneous lupus erythematosus
92
SCLE
subacute cutaneous lupus erythematosus
93
PDC
plasmacytoid dendritic cell
94
ANA
antinuclear antibody
95
SS-A
Sjögren syndrome antibody A
96
SS-B
Sjögren syndrome antibody B
97
IHC
immunohistochemistry
98
DIF
direct immunofluorescence
99
RF
rheumatoid factor
101 102 103 104 105
TE D
EP
AC C
100
SC
Abbreviations
M AN U
87
RI PT
4
ACCEPTED MANUSCRIPT 5 References:
107
1. Torchia D, Romanelli P, Kerdel FA. Erythema multiforme and Stevens-Johnson
108
syndrome/toxic epidermal necrolysis associated with lupus erythematosus. J Am Acad
109
Dermatol. 2012;67(3):417-21. doi: 10.1016/j.jaad.2011.10.012.
110
RI PT
106
2. Rowell NR, Beck JS, Anderson JR. Lupus erythematosus and erythema multiforme-like
112
lesions. A syndrome with characteristic immunological abnormalities. Arch Dermatol.
113
1963;88:176-80. doi: 10.1001/archderm.1963.01590200064012
SC
111
M AN U
114 115
3. Zeitouni NC, Funaro D, Cloutier RA, et al. Redefining Rowell’s syndrome. Br J Dermatol.
116
2000;142(2):343-6. doi: 10.1046/j.1365-2133.2000.03306.x
117
4. Swiecki M, Colonna M, The multifaceted biology of plasmacytoid dendritic cells. Nat Rev
119
Immunol. 2015;15(8):471-85. doi: 10.1038/nri3865.
120
TE D
118
5. Vermi W, Lonardi S, Morassi M, et al. Cutaneous distribution of plasmacytoid dendritic cells
122
in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage.
123
Immunobiology. 2009;214(9-10):877-86. doi: 10.1016/j.imbio.2009.06.013.
AC C
124
EP
121
125
6. Franceschini F, Cavazzana I. Anti-Ro/SSA and La/SSB antibodies. Autoimmunity.
126
2005;38(1):55-63. doi: 10.1080/08916930400022954.
127 128
ACCEPTED MANUSCRIPT 6 129
Figure legend
130
Figure 1:
132
Rowell syndrome. A: Targetoid plaques with dusky centers and peripheral erythema. B:
133
Lichenoid interface dermatitis with keratinocyte necrosis, perivascular lymphocytic infiltrates,
134
and mucin (H&E, 100x magnification). C: Perifollicular and intraepithelial plasmacytoid
135
dendritic cells, representing greater than 10% of the inflammatory infiltrate (CD123 with red
136
chromagen, 200x magnification). D: Perieccrine plasmacytoid dendritic cells (CD123 with red
137
chromagen, 200x magnification).
M AN U
138
SC
RI PT
131
Figure 2 (online only – available at https://data.mendeley.com/datasets/bwswc4h9yb/1):
140
Subacute cutaneous lupus erythematosus. A: Polycyclic erythematous plaques with peripheral
141
scale. B and C: Cell-poor interface dermatitis, epidermal atrophy, and sparse lymphocytic
142
infiltrate with abundant dermal mucin (B: H&E, 40x magnification; C: H&E, 200x
143
magnification). D: Perieccrine plasmacytoid dendritic cells highlighted by CD123 (CD123 with
144
red chromagen, 400x magnification).
EP
145
TE D
139
Figure 3 (online only – available at https://data.mendeley.com/datasets/bwswc4h9yb/1):
147
Erythema multiforme. A: Typical target with three zones of color change and central
148
vesiculation. B: Orolabial erosions. C: Lichenoid interface dermatitis with partial epidermal
149
necrosis. D: Absence of perieccrine plasmacytoid dendritic cells (CD123 with red chromagen,
150
200x magnification).
151
AC C
146
ACCEPTED MANUSCRIPT 7 152 153 154
RI PT
155 156 157
SC
158 159
M AN U
160 161 162 163
EP
166
AC C
165
TE D
164
ACCEPTED MANUSCRIPT
8 Table 1: Comparison of RS, SCLE, and EM by clinical, serologic, histologic and immunohistochemical findings SCLE (4 patients; 7 biopsies)
EM (5 patients; 5 biopsies)
Mean Age (years)
53 ± 23.15
62.8 ± 16.44
52.8 ± 16.07
Gender
80% F (4/5)
100% F (4/4)
80% F (4/5)
100% (4/4)
75% (3/4)
0% (0/5)
Targetoid lesions
100% (4/4)
0% (0/4)
100% (5/5)
Mucosal involvement
0% (0/4)
0% (0/4)
Implicated medication
0% (0/4)
0% (0/4)
ANA pattern
50% Speckled (2/4)
67% Speckled (2/3)
Lesional DIF3
100% (1/1)
100% (1/1)
Full-thickness epidermal necrosis
50% (4/8)
0% (0/7)
Parakeratosis
25% (2/8)
85.7% (6/7)
Dermal eosinophils
0%
0%
Periadnexal lymphocytic infiltrate4
RS, SCLE, and EM (p-value)
1
1
0.0047
0.0286
0.0028
40% (2/5)
1
0.2821
20% (1/5)
1
1
0% Speckled (0/2)
1
0.5238
0% (0/1)
1
1
80% (4/5)
0.077
0.017
20% (1/5)
0.041
0.034
20% (1/5)
1
0.250
SC
1
M AN U
2
TE D
History of LE1
RS and SCLE (p-value)
RI PT
RS (5 patients; 8 biopsies)
85.7% (6/7)
0%
1
0.003
62.5% (5/8)
57.1% (4/7)
20% (1/5)
1
0.395
Dermal predominant CD123 pattern
42.9% (3/7)
83.3% (5/6)
40% (2/5)
0.266
0.292
Intraepidermal CD123-positive PDCs
100% (7/7)
66.7% (4/6)
100% (5/5)
0.192
0.163
Periadnexal CD123-positive PDCs
100% (7/7)
66.7% (4/6)
40% (2/5)
0.192
0.049
10% or greater CD123-positive cells
EP
87.5% (7/8) 5
AC C
ANA: Antinuclear antibody; DIF: direct immunofluorescence; EM: erythema multiforme; LE: lupus erythematosus; PDC: plasmacytoid dendritic cell; RS: Rowell syndrome; SCLE: subacute cutaneous lupus erythematosus 1. History of systemic or cutaneous lupus erythematosus 2. Two or more zones of color 3. IgG: granular deposition in the lower epidermis, along the basement membrane zone, and ANA pattern in keratinocytes; C3, IgM, IgA, C3, and C5b-9: granular deposition along the basement membrane zone 4. Perifollicular or perieccrine 5. Percentage of inflammatory cells positive for antibody staining in a single histologic section
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT