J AM ACAD DERMATOL
VOLUME 83, NUMBER 1
independently doing investigator global assessment
scores of all patients, and Dr Jineesh Valakkada, from
Department of Radiology, All India Institute of Medical
Sciences, New Delhi, for radiologic assessment of all
pretreatment and post-treatment x-ray images.
Sujay Khandpur, MD,a Prateek Sondhi, MD,a
Neha Taneja, MD,a Preeti Sharma, MSc,a Day-
asagar Das, MSc,b Alpana Sharma, PhD,b and
Vishnubatla Sreenivas, MDc
From the Departments of Dermatology and Vene-
reology,a Biochemistry,b and Biostatistics,c All
India Institute of Medical Sciences, Ansari Na-
gar, New Delhi, India.
Funding sources: None.
Conflicts of interest: This was an investigator-
initiated trial. The drug adalimumab biosimilar
(Exemptia) was provided by Zydus Biovation
(division of Cadila Health Care) free of cost to all
patients. Zydus Biovation had no interference in
the design, conduct, and analysis of the study.
IRB approval status: Reviewed and approved by All
India Institute of Medical Sciences Ethics Com-
mittee, New Delhi (approval reference number
IEC-83/08.01.2016, RP-11/2016).
Correspondence and reprint requests to: Sujay
Khandpur, MD, Department of Dermatology and
Venereology, All India Institute of Medical
Sciences, New Delhi, India
E-mail: sujay_khandpur@yahoo.com
REFERENCES
1. Jani RH, Gupta R, Bhatia G, et al. A prospective, randomized,
double-blind, multicentre, parallel-group, active controlled
study to compare efficacy and safety of biosimilar adalimu-
mab (Exemptia; ZRC-3197) and adalimumab (Humira) in
patients with rheumatoid arthritis. Int J Rheum Dis. 2016;
19(11):1157-1168.
2. Midha V, Mahajan R, Mehta V, et al. Efficacy and safety of the
adalimumab biosimilar Exemptia as induction therapy in
moderate-to-severe ulcerative colitis. Intest Res. 2018;16(1):83-89.
3. Papp K, Bachelez H, Costanzo A, et al. Clinical similarity of
biosimilar ABP 501 to adalimumab in the treatment of patients
with moderate to severe plaque psoriasis: a randomized,
double-blind, multicenter, phase III study. J Am Acad Dermatol.
2017;76:1093-1102.
4. Campanati A, Orciani M, Lazzarini R, et al. TNF- inhibitors
reduce the pathological Th1-Th17/Th2 imbalance in cuta-
neous mesenchymal stem cells of psoriasis patients. Exp
Dermatol. 2017;26:319-324.
5. Reddy M, Torres G, McCormick T, et al. Positive treatment
effects of ustekinumab in psoriasis: analysis of lesional and
systemic parameters. J Dermatol. 2010;37:413-425.
https://doi.org/10.1016/j.jaad.2019.12.071
Research Letters 251
Prevalence and predictors of pruritus
in pemphigus compared with bullous
pemphigoid: A cross-sectional study
To the Editor: Pemphigus is an autoimmune blis-
tering disease with substantial pain, which affects
quality of life.1-3 Previous reports and anecdotal
clinical observations suggest that patients
with pemphigus with cutaneous involvement
frequently experience pruritus. We sought to eluci-
date the prevalence and predictors of itch in
pemphigus compared with bullous pemphigoid
(BP), for which pruritus has been well documented.
After institutional review board approval, a retro-
spective analysis was performed of visits by adults
with pemphigus and BP with documented itch
scores seen at Emory Clinic from June 2012 through
May 2019 (BP) and July 2017 through May 2019
( pemphigus). The Bullous Pemphigoid Disease
Area Index (BPDAI)4 Pruritus component character-
izes itch on a visual analog scale of 0 to 10 over the
past day, week, and month; the intensity score is the
sum of these subcomponents. The Pemphigus
Disease Area Index (PDAI)5 lacks an itch score, so
the BPDAI Pruritus component was administered to
patients with pemphigus and BP. Categorical and
numeric variables were analyzed in relation to a 24-
hour, standard pruritus VAS and total BPDAI Pruritus
scores by using analysis of variance and Pearson
correlation coefficient (PCC), with significance at P
less than 0.05. All patients could read English and
self-completed the surveys.
Overall, data from 58 patients with pemphigus (91
encounters) and 77 patients with bullous pemphi-
goid (504 encounters) were included. Tables I and II
show participant demographic data and descriptive
statistics. The average BPDAI 24-hour for patients
with pemphigus was 3.25 6 3.03 (out of 10), and the
average BPDAI Pruritus total score was 11.05 6 8.69
(out of 30). Patients with pemphigus with cutaneous-
only involvement had greater BPDAI 24-hour and
total itch scores. Pemphigus foliaceus had greater
itch than pemphigus vulgaris ( pemphigus foliaceus:
BPDAI 24-hour, 4.45 6 2.74; P ¼ .027; BPDAI
Pruritus total, 15.20 6 7.00; P ¼ .007), and
cutaneous-only involvement had greater itch than
mucosal and/or mucocutaneous (cutaneous only:
BPDAI 24-hour, 4.16 6 2.85; P ¼ .028; BPDAI
Pruritus total, 14.20 6 7.49; P ¼ .006) (Tables I and
II). PDAI score was significantly correlated with both
itch scores (24-hour: PCC, 0.331; P ¼ .011; total: PCC,
0.336; P ¼ .010) (Table II). Serum anti-Dsg1 autoan-
tibody levels trended toward significance in relation
to BPDAI Pruritus total score (PCC, 0.305; P ¼ .059)
(Table II). Total immunoglobulin E and eosinophil
252 Research Letters J AM ACAD DERMATOL
JULY 2020

Table I. Descriptive statistics and univariate association of categorical variables with BPDAI Pruritus scores for
patients with pemphigus
BPDAI 24-hour BPDAI pruritus total
(out of 10) (out of 30)*
ANOVA ANOVA
Category Covariate Subvariate n (%) Mean (SD) P value Mean (SD) P value
Disease Diagnosis Pemphigus vulgaris 38 (65.5) 2.62 (3.01) .027 8.87 (8.77) .007
characteristics Pemphigus foliaceus 20 (34.5) 4.45 (2.74) 15.20 (7.00)
Disease site Mucocutaneous 28 (48.3) 2.95 (3.10) .028 9.93 (8.97) .006
Cutaneous 25 (43.1) 4.16 (2.85) 14.20 (7.49)
Mucosal 5 (8.6) 0.40 (0.89) 1.60 (3.58)
Disease severityy PDAI total score 0.0-8.9 37 (63.8) 2.61 (2.73) .083 9.35 (8.25) .066
(out of 250) 9.0-24.9 18 (31.0) 4.22 (3.37) 13.11 (9.20)
$25.0 3 (5.2) 5.33 (2.89) 19.67 (2.31)
Demographics Race African American 26 (44.8) 3.79 (2.97) .565 13.35 (8.29) .239
Asian including Indian 9 (15.5) 2.44 (3.47) 8.11 (10.01)
Other 7 (12.1) 3.57 (3.05) 12.00 (9.50)
White 20 (34.5) 2.69 (2.96) 8.56 (7.84)
Sex Male 20 (34.5) 3.80 (2.86) .320 13.30 (7.66) .155
Female 38 (65.5) 2.96 (3.11) 9.87 (9.06)
Laboratory Dsg1, U/mlz \20 19 (48.7) 3.42 (3.13) .838 11.95 (8.75) .709
markers $20 20 (51.3) 3.63 (3.06) 13.00 (8.72)
Dsg3, U/mlz \20 19 (48.7) 3.05 (3.10) .353 11.58 (8.41) .529
$20 20 (51.3) 3.98 (3.03) 13.35 (8.98)
IgE, IU/mlx 0-179 6 (10.3) 3.83 (3.71) .469 12.50 (8.80) .365
$180 2 (3.4) 6.00 (1.41) 19.00 (2.83)
Absolute eosinophils, \0.36 25 (43.1) 4.12 (3.07) .827 13.36 (9.13) .333
103/mlk $0.36 4 (6.8) 4.50 (4.12) 18.00 (4.55)
Treatment and Previous rituximab No 17 (29.3) 4.00 (3.10) .228 12.59 (9.53) .391
disease status treatment Yes 41 (70.7) 2.94 (2.98) 10.41 (8.36)
Current prednisone No 36 (62.1) 3.13 (2.89) .691 11.42 (8.16) .686
treatment Yes 22 (37.9) 3.45 (3.31) 10.45 (9.66)
Current adjuvant No 37 (63.8) 3.18 (2.90) .807 11.35 (8.56) .731
therapy{ Yes 21 (36.2) 3.38 (3.31) 10.52 (9.10)
In remission# No 33 (56.9) 3.61 (3.29) .308 12.06 (9.42) .314
Yes 25 (43.1) 2.78 (2.64) 9.72 (7.60)

ANOVA, Analysis of variance; BPDAI, Bullous Pemphigoid Disease Area Index; Dsg, desmoglein; IgE, immunoglobulin E; PDAI, Pemphigoid
Disease Area Index; SD, standard deviation. Values found to be significant (P less than .05) in bold.
*BPDAI Pruritus total has a maximum score of 30 and is the sum of BPDAI 24-hour itch (0-10), past week itch (0-10), and past month itch (0-
10) scores.
y
This table describes demographic data and descriptive statistics of only patients with pemphigus. Patients with bullous pemphigoid
experienced a similar mild to moderate severity, with a mean total BPDAI of 9.97 6 15.45. Data were included from 482 encounters.
z
Of the 58 patients with pemphigus, data for Dsg1 and Dsg3 levels from 19 patients were not available at the time of itch score collection.
x
IgE levels were available for 8 patients.
k
Absolute eosinophil levels were available for 29 patients.
{
Includes mycophenolate, methotrexate, dapsone, azathioprine, doxycycline, and minocycline.
#
Includes those in complete remission off and/or on minimal therapy and partial remission off and/or on minimal therapy, as defined by the
International Pemphigus Committee consensus statement (Murrell et al. Consensus statement on definitions of disease, end points, and
therapeutic response for pemphigus. J Am Acad Dermatol. 2008:58(6):1043-1046).

levels did not correlate to either itch score. The
percentage of all patient encounters with docu-
mented itch and average BPDAI Pruritus total score
did not differ between pemphigus and BP (Itchy
Encounters: parametric P ¼ .935; average BPDAI
Pruritus total score: P ¼ .926) (Table III).
Our results indicate that patients with pemphigus
with cutaneous involvement itch as frequently and
as severely as those with BP. Cutaneous involve-
ment, diagnosis of pemphigus foliaceus, and dis-
ease severity predicted pruritus. Lack of significance
in treatment variables suggests that disease activity
does not fully explain pruritus, although these
results are limited by small sample size and high
proportion of patients with mild to moderate dis-
ease. Further limitations include performance at a
J AM ACAD DERMATOL Research Letters 253
VOLUME 83, NUMBER 1

Table II. Descriptive statistics and univariate association of numeric variables with BPDAI pruritus scores for
patients with pemphigus
BPDAI 24-hour (out of 10) BPDAI Pruritus total (out of 30)*
Variable Mean (SD) n PCC Pearson P value PCC Pearson P value
Age, y 54.17 (15.49) 58 0.005 .968 0.045 .739
PDAI total (out of 250) 9.46 (8.68) 58 0.331 .011 0.336 .010
Dsg1, U/mly 49.62 (62.35) 39 0.154 .348 0.305 .059
Dsg3, U/mly 46.92 (61.61) 39 -0.036 .829 0.031 .853
IgE, IU/mlz 277.94 (434.54) 8 0.369 .368 0.415 .306
Absolute eosinophils, 103/mlx 0.20 (0.14) 29 0.272 .153 0.341 .070

BPDAI, Bullous Pemphigoid Disease Area Index; Dsg, desmoglein; IgE, immunoglobulin E; PCC, Pearson correlation coefficient; PDAI,
Pemphigoid Disease Area Index. Values found to be significant (P less than .05) in bold.
*BPDAI Pruritus total has a maximum score of 30 and is the sum of BPDAI 24-hour itch (0-10), past week itch score (0-10), and past month
itch score (0-10).
y
Of the 58 patients with pemphigus, data for Dsg1 and Dsg3 levels from 19 patients were not available at that time of itch score collection.
z
IgE levels were available for 8 patients.
x
Absolute eosinophil levels were available for 29 patients.

Table III. Comparing bullous pemphigoid and pemphigus: Prevalence of itchy patient encounters and itch
intensity scores
Diagnosis
Covariate Statistics Bullous pemphigoid (N = 504) Pemphigus (N = 91) Parametric P value*
Itchy encountersy n (%) 408 (80.95) 74 (81.31) .935
BPDAI Pruritus totalz Mean 11.06 10.97 .926
Median 10 9
Minimum 0 0
Maximum 31 30
SD 9.29 8.53

BPDAI, Bullous Pemphigoid Disease Area Index; SD, standard deviation.

*Calculated by analysis of variance for numeric covariates and chi-square test for categorical covariates.
y
Defined as any patient encounter where BPDAI Pruritus total score [ 0 out of the total patient encounters 3 100%.
z
BPDAI Pruritus total has a maximum score of 30 and is the sum of BPDAI 24-hour itch (0-10), past week itch (0-10), and past month itch (0-
10) scores.

single academic center and failure to control for
comorbid pruritic conditions. Future research with
a larger patient population and prospective design
is needed to confirm these trends and to elucidate
the role of T helper type 2emediated pathways in
comparing itch in pemphigus and BP. Our study
suggests the need for development of a patient-
reported itch score for pemphigus patients or
validation of the BPDAI Pruritus component in
other blistering diseases.
Robin Rolader, BS,a Lauren N. Daugherty, MD,b
Yuan Liu, PhD, MS,c and Ron J. Feldman, MD,
PhDb
From the Emory University School of Medicinea;
Emory University Department of Dermatologyb;
and Department of Biostatistics and Bioinfor-
matics, Rollins School of Public Health, Emory
University, Atlanta, Georgia.c
Funding sources: None.
Conflicts of interest: None disclosed.
Abstract accepted for ePoster presentation at the
American Academy of Dermatology Annual
2020 Meeting, Boulder, Colorado, March 20-
24, 2020.
IRB approval status: Approved by the Emory Univer-
sity Institutional Review Board (IRB00054860).
Reprint requests: Ron J. Feldman, MD, PhD, Emory
University, Department of Dermatology, 1525
Clifton Rd NE, 1st Floor, Atlanta, GA 30322
E-mail: ron.j.feldman@emory.edu
REFERENCES
1. Zeidler C, Pereira MP, Huet F, Misery L, Steinbrink K, St€ander S.
Pruritus in autoimmune and inflammatory dermatoses. Front
Immunol. 2019;10:1303.
2. Schr€
oder L, Hertl M, Chatzigeorgakidis E, Phan NQ, St€ander S.
Chronic pruritus in autoimmune dermatoses: results of a
comparative survey. Hautarzt. 2012;63(7):558-566.
254 Research Letters
3. Woldegiorgis S, Swerlick RA. Pemphigus in the southeastern
United States. South Med J. 2001;94(7):694-698.
4. Wijayanti A, Zhao CY, Boettiger D, et al. The reliability, validity
and responsiveness of two disease scores (BPDAI and ABSIS)
for bullous pemphigoid: which one to use? Acta Derm
Venereol. 2017;97(1):24-31.
5. Rahbar Z, Daneshpazhooh M, Mirshams-Shahshahani M, et al.
Pemphigus disease activity measurements: pemphigus dis-
ease area index, autoimmune bullous skin disorder intensity
score, and pemphigus vulgaris activity score. JAMA Dermatol.
2014;150(3):266-272.
https://doi.org/10.1016/j.jaad.2020.01.025
Adequacy of conservative 2- to 3-mm
surgical margins for complete
excision of biopsy-proven severely
dysplastic nevi: Retrospective case
series at a tertiary academic
institution
The management of biopsy-proven severely dysplastic
nevi (SDN) remains controversial because of a lack of
long-term outcomes data and controversy regarding
the malignant potential of SDN.1-3 We performed a
retrospective case series to investigate outcomes of
conservative-margin (2-3 mm) surgical excision
for biopsied SDN with either negative/excised or
positive/transected histologic margins on initial biopsy
to determine the presence of residual dysplastic nevi,
upgrading to melanoma on the excision specimen, and
local nevus recurrence or subsequent development of
primary melanoma at the surgical site.
The study was approved by the Stanford
University institutional review board. Cases were
consecutively identified from January 1, 2000,
through July 31, 2017, and followed through
January 1, 2018; SDN were excluded if there was
ambiguity in histopathologic diagnosis, including
diagnosis of possible or evolving melanoma in situ
(MIS). Histopathologic evaluation was performed by
the academic dermatopathologists for all cases,
with uniform criteria used for histopathologic
classification of dysplastic nevi over the study period.
A total of 426 biopsy-proven SDN were identified
in 381 patients (mean age, 49.7 years; median age,
50 years; range, 27-85 years) who underwent
conservative re-excision with 2- to 3-mm surgical
margins, regardless of whether the severely
dysplastic nevus was histologically excised or
transected on biopsy (Table I); 271 cases (63.6%)
had negative margins on initial biopsy, and 155
(36.3%) had positive margins. There was a tendency
for 2-mm surgical margins for SDN completely
excised on initial biopsy versus those histologically
transected; 3-mm margins were more commonly
used in patients with history of prior melanoma.
J AM ACAD DERMATOL
JULY 2020
Surgical excision specimens showed 301 of
426 cases (70.6%) with no residual DN and 123
(28.9%) with residual DN excised. Only 2 cases
(histologically transected on initial biopsy)
showed residual SDN involving the surgical
re-excision margin and required a second surgery
for negative margins. Of 271 cases histologically
excised on initial biopsy, only 3 (1.1%) showed
residual DN in the re-excision specimen, whereas
122 of 155 (78.7%) cases histologically transected
on biopsy showed residual DN in the excision
specimen, with 33 (21.2%) negative for residual
tumor. No excision specimens resulted in
upstaging of SDN to MIS or invasive melanoma,
and no subsequent local nevus recurrence or
development of melanoma at the excision site
was observed with a mean dermatologic follow-
up of 28 months.
Our study of histologic SDN showed no cases of
upstaging to melanoma after re-excision with
conservative 2- to 3-mm surgical margins, or local
nevus recurrence or progression to melanoma at a
mean follow-up of only 28 months, which is a study
limitation. However, conservative excision appeared
to provide comprehensive histopathologic margin
analysis to exclude melanoma while allowing for
greater tissue preservation. Because only 1.1% of
re-excised SDN that were histologically excised on
initial biopsy showed residual DN, additional
surgical resection may not be necessary when
complete biopsy is performed at the outset,1,3,4
although prospective outcome studies with larger
sample sizes are needed to corroborate this
observation, particularly given the high degree of
histopathologic interobserver variability in DN
diagnosis and management.5 Longer follow-up
is also necessary to determine whether any
histologically undetected SDN eventuates in local
melanoma recurrence.
Teo Soleymani, MD,a Susan M. Swetter, MD,b
S. Tyler Hollmig, MD,a and Sumaira Z. Aasi, MDa
Department of Dermatology, Stanford University
Medical Center, Redwood City, Californiaa; and
Department of Dermatology, Pigmented Lesion
and Melanoma Program, Stanford University
Medical Center and Cancer Institute, Stanford,
California.b
Dr Hollmig is currently affiliated with the Depart-
ment of Internal Medicine (Dermatology),
University of Texas Dell Medical Center, Austin.
Funding sources: None.
Conflicts of interest: None disclosed.