REVIEW
Treatment of Genital Psoriasis: A Systematic Review
Kristen M. Beck . Eric J. Yang . Isabelle M. Sanchez . Wilson Liao
Received: June 14, 2018 / Published online: August 25, 2018� The Author(s) 2018
ABSTRACT
Genital psoriasis affects approximately 63% ofpsoriasis patients at least once in their lifetime.More than any other area on the body, genitallesions significantly impair patients’ psycho-logic well-being and quality of life. We aimed tosystematically review the published evidence onthe safety, efficacy, and tolerability of treat-ments of genital psoriasis and synthesize theavailable clinical data. A total of 1 randomizedcontrolled trial, 11 open-label studies, and 26case reports were included in our analysis, rep-resenting a total of 458 patients, of which 332were adults and 126 were children. Topicalcorticosteroids were commonly used first-linefor genital psoriasis and were well tolerated.Nonsteroidal agents, such as topical calcineurininhibitors or vitamin D analogs, were also effi-cacious, but were often irritating. One systemicagent, ixekizumab, demonstrated efficacy in
reducing genital psoriasis symptoms in a large,randomized, placebo-controlled trial. Varioussystemic and topical medications may improvegenital psoriasis lesions, but there is a lack ofhigh-quality evidence to guide clinical decision-making. Specific reporting of efficacy for genitalpsoriasis in larger controlled studies of psoriasistreatments are necessary to improve the avail-able evidence regarding the optimal treatmentregimen for genital psoriasis.
Keywords: Genital psoriasis; Psoriasis; Therapy;Treatment
INTRODUCTION
Sixty-three percent of adults with psoriasisdevelop psoriatic lesions in the genital area atleast once during their lifetime [1]. In the pres-ence of inverse psoriasis, the prevalence ofgenital psoriasis increases to approximately 79%[2, 3]. In 2–5% of psoriasis patients, lesions onlyoccur in the genital region [3]. Genital psoriasiscan occur in all age groups, from newborns togeriatric patients, with a slight predilection foryounger male patients with relatively severedisease [4]. In children under 2 years of age,genital psoriasis typically presents as intensewell-demarcated erythema in the diaper area,termed napkin psoriasis [5, 6].
Kristen M. Beck and Eric J. Yang contributed equally tothe work.
Enhanced digital features To view enhanced digitalfeatures for this article go to https://doi.org/10.6084/m9.figshare.6950072.
K. M. Beck (&) � E. J. Yang � I. M. Sanchez � W. LiaoDepartment of Dermatology, UCSF Medical Center,San Francisco, CA, USAe-mail: [email protected]
Dermatol Ther (Heidelb) (2018) 8:509–525
https://doi.org/10.1007/s13555-018-0257-y
Patients with psoriasis lesions in their genitalarea experience significantly worse quality oflife than patients with psoriasis on any otherareas, particularly with respect to pruritus, sex-ual function, sexual health, sexual distress,avoidance of sexual relationships, embarrass-ment, shame, and psychologic depression[4, 7–9].
Despite the high prevalence of genital pso-riasis, almost half of patients with genitallesions do not discuss their symptoms withtheir physician [8, 10, 11]. Lack of communi-cation and awareness about genital psoriasis inthe healthcare environment may result inunderdiagnosed and under-treated genital pso-riasis, subsequently increasing the risk of inap-propriate self-treatment [10].
Although there are many effective treat-ments in the therapeutic armamentarium forpsoriasis, treatment of lesions on the genitaliaand surrounding skin folds remains challeng-ing. Topical treatments have increased pene-tration through the thin, sensitive, and oftenoccluded genital skin, increasing the risk of sideeffects from common psoriasis medications[12]. A review of the literature in 2011 found alack of evidence regarding the efficacy andsafety of various treatments for genital psoriasis[3]. This review summarizes the most currentliterature regarding the efficacy and safety ofavailable therapies for psoriasis affecting thegenital skin.
METHODS
A literature search using the MEDLINE andEmbase health literature databases was con-ducted using the terms (‘‘psoriasis’’) AND (‘‘pe-nile’’ OR ‘‘penis’’ OR ‘‘genital*’’ OR ‘‘glans’’ OR‘‘scrotal’’ OR ‘‘scrotum’’ OR ‘‘anal’’ OR ‘‘diaper’’OR ‘‘napkin’’ OR ‘‘shaft’’ OR ‘‘foreskin’’ OR‘‘prepuce’’ OR ‘‘perianal’’ OR ‘‘vulva*’’ OR ‘‘labia’’OR ‘‘labium’’ OR ‘‘groin’’ OR ‘‘preputial’’ OR‘‘penoscrotal’’). Two independent reviewersidentified the included articles (EY, IS) andextracted information. The review methodswere established prior to the conduct of thereview and did not deviate during the course ofthe study. Articles were included if they
included patients with psoriasis or psoriasiformnapkin dermatitis affecting the genital area,discussed the results of treatment with respectto the genital lesions, and were published priorto 31 July 2018. Studies were excluded if theydid not study genital psoriasis, did not discussthe results of treatment in the genital region,were in a foreign language, were conferenceabstracts, or were a review or meta-analysis.Study results were extracted using a standard-ized data form recording information on thepublication date, type of psoriasis, site, age andgender of patients, and reported efficacy andadverse events. In addition, the quality of allstudies was rated based on the Oxford Centrefor Evidence-Based Medicine Levels of Evidencerating scheme [13].
The article is based on previously conductedstudies and does not contain any studies withhuman participants or animals performed byany of the authors.
RESULTS
A total of 1964 potentially relevant uniquecitations were identified from our literaturesearch (Fig. 1). Of these, 128 articles wereselected for further evaluation based on therelevance of their title and abstract. A total of 32articles examining the treatment of genitalpsoriasis were ultimately included in this study.Table 1 summarizes the data for adults. Table 2summarizes the findings for infants andchildren.
Treatments for Genital Psoriasis in Adults
A total of 21 articles examined treatment out-comes for adults with genital psoriasis (Table 1),including 1 randomized controlled trial (grade1), 8 open-label studies (grade 4), and 16 casereports (grade 5), representing a total of 332patients. Of these, topical corticosteroids wereused in the regimen of 201 patients for suc-cessful treatment (Table 2). Low-potency topicalsteroids were used in 132 patients, moderate-potency steroids were used in 120 patients, andhigh-potency steroids were used in 15 patients.Antifungal medications were used as part of
510 Dermatol Ther (Heidelb) (2018) 8:509–525
successful treatment in 3 patients, while coal tarpreparations were effective in clearing genitallesions in 126 patients. Topical tacrolimus 0.1%ointment resulted in significant improvementin genital lesions in 38 patients across 4 open-label studies (grade 4) and 2 case reports (grade5). Tacrolimus was fairly well tolerated by mostpatients, with side effects of mild pruritus and/or burning sensation of limited duration.However, use precipitated extreme irritation inone case report, requiring discontinuation oftherapy [14]. Other agents used for successfultreatment of genital psoriasis include topicalcyclosporine, which was well tolerated in threepatients [15].
Vitamin D preparations were used success-fully in 40 patients, often in combination withtopical corticosteroids for genital psoriasis[16–18]. Additional reports of vitamin D prepa-ration use in genital psoriasis patients exist inthe literature; these studies often do not report
outcomes specifically for the genital area. Arandomized, double-blind, head-to-head com-parison (grade 1) of calcitriol ointment 3 lg/gtaken twice daily was compared with tacrolimusointment 0.3 mg/g taken twice daily for 6 weeksin 49 patients with either facial or gen-itofemoral psoriasis [19]. Of these patients, fivehad genital psoriasis; two were treated withcalcitriol, and three were treated with tacroli-mus. Both treatments were well tolerated in thestudy, and tacrolimus treatment resulted in amore significant reduction of target lesion size,but results were not stratified for lesions on theface and genitalia.
In addition to topical treatments, severalinjectable and oral medications have beenreported to successfully clear genital lesions ofpsoriasis (Table 3). Ixekizumab, an IL-17A inhi-bitor approved for the treatment of moderate-to-severe psoriasis and active psoriatic arthritis[20], is the first biologic to report formal clinical
Fig. 1 Genital psoriasis: study selection for treatment
Dermatol Ther (Heidelb) (2018) 8:509–525 511
Table1
Studieson
treatm
entsforgenitalpsoriasisin
adults
Sources
Stud
ycharacteristics
Treatments
andou
tcom
es
Stud
ydesign,
levelof
evidence
Typeof
psoriasis
Site
Age
(years)
Coh
ort
(M/F)
Successful
(sideeffects)
Unsuccessful(sideeffects)
Notes
JFam
Pract
2016
[41]
Casereport,5
Plaque
psoriasis
Groin
451M
Triam
cinolone
cream,
clobetasol
ointment
1%hydrocortisone
cream,topicalantifungals,
oralantifungals
90%
improvem
entafter
1month,95%
improvem
ent
after2months
Albertet
al.
[14]
Casereport,5
Plaque
psoriasis
Anogenital
area,
genitocrural
folds
711F
Oraldoxepin,
methotrexate
7.5–
10mg/week(G
Idisturbance)
Mild
toultra-potent
topicalcorticosteroids,
topicaltacalcitol,topicaldoxepin,
twice
weeklyPU
VAfor2months,topical0.1%
tacrolim
us(extremeirritation,w
orsening
ofpruritus)
Oraldoxepinpartially
helpful
inalleviatingitching,
methotrexateim
proved
genitocruralfoldsbut
abandonedbecauseof
GI
disturbance
Albertet
al.
[14]
Casereport,5
Plaque
psoriasis
Groin,genitalia
extend
ingto
perianaland
natalcleft
771F
–Clomitrazole1%
,hydrocortisone1%
Minimalim
provem
ent
Bissonn
ette
etal.[33]
Open-label
case
series,
4
Plaque
psoriasis
Penis,scrotum
42(29–
70)
12M
Topical0.1%
tacrolim
ustwice
daily
(mild
pruritus
orburningsensationof
limited
duration)
–MeangenitalPA
SIdecreased
from
15.8
to1.2after
8weeks
Cassano
etal.[26]
Open-label
case
series,
4
Plaque
psoriasis
Genitalia
18?
9cEfalizum
ab1mg/kg
weekly
–Considerableim
provem
entin
genitallesionsafter
12weeks
Fischeret
al.
[16]
Open-label
case
series,
4
Plaque
psoriasis
Vulva
33(15–
56)
8F
TCS,
2%LPC
,topical
calcipotriol
–Resolutionof
vulvitis
Foureuretal.
[39]
Casereport,5
Napkin
psoriasis
Diaperarea
771F
Betam
ethasone
0.05%
cream
Bifo
nazolecream
daily
Cured
in1month
Foureuretal.
[39]
Casereport,5
Napkin
psoriasis
Diaperarea
871M
Bifo
nazolecream
daily
–Im
proved
in1month
Foureuretal.
[39]
Casereport,5
Napkin
psoriasis
Diaperarea
100
1F
Betam
ethasone
0.05%
cream
–Cured
in1month
Foureuretal.
[39]
Casereport,5
Napkin
psoriasis
Diaperarea
871F
Bifo
nazolecream
daily,o
ral
fluconazole100mgdaily
–Im
proved
withfluconazole
after1month
Guglielmetti
etal.[23]
Casereport,5
Plaque
psoriasis
Vulva,groin,
perianal
region
421F
Dapsone
100gdaily,
mycophenolate
mofetil
500mgtwicedaily
20mgmethotrexateweekly(U
TI)
Com
pleteclearanceafter
4weeks
ofdapsone,
remission
for2yearsusing
topicaltacrolim
us0.1%
and
calcipotriol.Slow
improvem
entwith
mycophenolate
mofetilafter
2months,partial
therapeuticresponse
with
methotrexate,stoppedat
4months
512 Dermatol Ther (Heidelb) (2018) 8:509–525
Table1
continued
Sources
Stud
ycharacteristics
Treatments
andou
tcom
es
Stud
ydesign,
levelof
evidence
Typeof
psoriasis
Site
Age
(years)
Coh
ort
(M/F)
Successful
(sideeffects)
Unsuccessful(sideeffects)
Notes
Jemec
etal.
[15]
Open-label
case
series,
4
Plaque
psoriasis
Glans
penis,
innerfold
ofprepuce
433M
Topicalcyclosporine
solution
100mg/mlthreetimes
daily
–Meanbaselin
escorea
decreased
from
4.8to
0.8after
8weeks,cyclosporinewell
tolerated
Jese
etal.
[24]
Casereport,5
Plaque
psoriasis
Glans,foreskin,
glutealfold
371M
Adalim
umab
40mgevery
2weeks
Topicalpimecrolim
us,topicalcorticosteroids,
methotrexate15
mgweekly(nausea,
vomiting,headache,insom
nia)
Nearcompleteregression
at90
days,com
pleteclearance
at6months
Kapila
etal.
[18]
Open-label
case
series,
4
Plaque
psoriasis
Vulva
30(2–8
4)145F
Methylpredn
isoloneaceponate
0.1%
(110),2%
LPC
(118),
hydrocortisone
1%(94),
calcipotriol
0.05%
(10),
betamethasone
dipropionate
0.05%
(7),betamethasone
dipropionate
0.05%
?calcioptriol
0.05%
(4),UVBphototherapy
(3),
clioquinol
1%(1),clobetasol
propionate
0.05%
(1),
methotrexate(1)
Methylpredn
isoloneaceponate0.1%
(7),2%
LPC
(5),hydrocortisone
1%(6)
93.8%respondedto
topical
treatm
ent
Martin-
Ezquerra
etal.[46]
Open-label
case
series,
4
Plaque
psoriasis
Intertriginous
folds
18?
8M/7
F0.1%
tacrolim
usointmenttwice
daily
–Im
provem
entas
earlyas
day
15,m
eantotalscoreb
from
6.88
to0.37
after60
days
Meeuw
iset
al.[17]
Open-label
case
series,
4
Plaque
psoriasis
Genitalia
50(20–
80)
25M/
17F
Low
-potency
corticosteroid
cream
with(18)
andwithout
(16)
vitamin
Danalog
ointment,moderate-potency
corticosteroid
cream
(5),
daily
tacrolim
uswithlow-
potencycorticosteroid
cream
(2),alternatingmild
and
higher
potencycorticosteroid
cream
(1)
–Significant
improvem
entin
PASI,IA,SUM,D
LQI,
FSDS,sQ
oL-M
Quanet
al.
[43]
Casereport,5
Pustular
psoriasis
Glans
penis,
penileshaft
231M
Oralitraconazole200mgbid,
triamcinolone,d
esonide,
mom
etasonefuroate,baking
soda
preparation
Hydrocortisone1%
,coaltar2%
,naftifin
ehydrochloride
Someim
provem
entwith
itraconazole,m
inim
alim
provem
entwith
hydrocortisone
andcoaltar
Rallis
etal.
[47]
Open-label
case
series,
4
Plaque
psoriasis
Glans
penis,
scrotum
37(22–
72)
7M
0.1%
tacrolim
usointmenttwice
daily
for10
days,thenevery
7days
thereafter
–Com
pleteclearanceafter
3weeks,4
3%still
clearat
12weeks
Dermatol Ther (Heidelb) (2018) 8:509–525 513
Table1
continued
Sources
Stud
ycharacteristics
Treatments
andou
tcom
es
Stud
ydesign,
levelof
evidence
Typeof
psoriasis
Site
Age
(years)
Coh
ort
(M/F)
Successful
(sideeffects)
Unsuccessful(sideeffects)
Notes
Ryanet
al.
[50]
Randomized,
placebo-
controlled
phaseIII
clinical
trial,1
Plaque
psoriasis
Genitalia
43(19–
77)
56M/
19F
Ixekizum
ab160mgat
week0,
then
80mgevery2weeks
thereafter
–Significant
improvem
entin
genitalpsoriasissymptom
scomparedwithplaceboas
measuredby
sPGA-G
0/1
(74%
vs.8
%),GenPS
-SFQ
item
2score0/1(78%
vs.
21%),andC
3point
reductionin
genitalitch
NRS(60%
vs.8
%)
Sezeret
al.
[51]
Casereport,5
Plaque
psoriasis
Glans
penis,
penileshaft
261M
Betam
ethasone
valerate,topical
5%salicylicacid
–Markedregression
ofthe
lesions
Shim
amoto
etal.[25]
Casereport,5
Pustular
psoriasis
Groin
801M
Oralchlorpromazine
125mg/day
Corticosteroids,antibiotics,griseofulvin
Resolutionof
skin
symptom
sseveralw
eeks
afterinitiation
oftreatm
ent,associated
with
reductionin
manic
symptom
s
Singhet
al.
[22]
Casereport,5
Pustular
psoriasis
Glans
penis
371M
Dapsone
100mgdaily,
doxycycline,metronidazole,
penicillin,
topicalsteroid
ointments
–Com
pleteclearancein
4weeks
withdapsone,maintenance
withdapsone50
mgdaily
Winrauch
etal.
Casereport,5
Plaque
psoriasis
Labium
majus
221F
Betam
etasone17-valeratethree
times
daily
–Clearance
oflesions
Yao
etal.
[40]
Casereport,5
Plaque
psoriasis
Glans
penis
371M
Tacrolim
us0.1%
ointment
twicedaily
Topicalketoconazolecream
for2weeks
Resolutionof
lesionsafter
3weeks
Zam
petti
etal.[48]
Casereport,5
Plaque
psoriasis
Glans
penis
451M
Topicaltacrolim
us0.1%
ointmentdaily
–Com
pleteresolution
after
3weeks
PASI
PsoriasisAreaandSeverityIndex,IA
investigator’sassessmentof
affected
genitalskin,SU
Msumof
severityscoreforerythema,desquamation,andinduration,D
LQIDermatologicalLife
QualityIndex,
FSDSFemaleSexualDistressScale,SQ
oL-M
SexualQualityof
Life
questionnaireforusein
men,sPG
A-G
staticPh
ysician’sGlobalA
ssessm
entof
Genitalia,G
enPS
-SFQ
GenitalPsoriasisSexualFrequency
Questionn
aire,N
RSnu
mericrating
scale
aMeasuredon
a6-pointscalegradingredn
ess,scaling,andmaceration
bMeasuredon
a9-pointscalegradingerythema,infiltration,
anddesquamationof
face,genitalia,and
intertriginous
areas
cUnspecifiedsex
514 Dermatol Ther (Heidelb) (2018) 8:509–525
Table2
Evidenceon
topicaltreatm
entsforgenitalpsoriasisby
medication
Medication
Successful
Unsuccessful
Zincpaste
Fergussonet
al.[35]
And
ersenet
al.[28],Baggioet
al.[36],Greco
etal.[37]
Salicylicacid
And
ersenet
al.[28]
Anilin
edye
And
ersenet
al.[28]
Topicalantibiotics
Cretu
etal.[37]
Topicalantifungals
Watanabeet
al.[38],Foureuret
al.[39]
Baggioet
al.[36],Greco
etal.[37],Foureuret
al.[39],Yao
etal.[40],JFam
Pract2016
[41]
Topicalcorticosteroids
Low
potency
Cretu
etal.[37],Kapila
etal.[18],Meeuw
iset
al.[17],Kam
er
etal.[42]
And
ersenet
al.[28],Baggioet
al.[36],Cretu
etal.[37],
Fergussonet
al.[35],Greco
etal.[37],Albertet
al.[14],
Meeuw
isetal.[17],Quanetal.[43],Singhetal.[22],JFam
Pract2016
[41]
Mid
potency
Afsar
etal.[6],B
aggioet
al.[36],Kapila
etal.[18],Meeuw
is
etal.[17],Weinrauch
etal.[44],JFam
Pract2016
[41]
Amichaiet
al.[29],Hernand
ezet
al.[45],Albertet
al.[14],
Meeuw
iset
al.[17],Jese
etal.[24]
Highpotency
Hernand
ezetal.[45],Foureuretal.[39],JFam
Pract2016
[41]
Albertet
al.[14],Meeuw
iset
al.[17]
Topicalcalcineurininhibitors
Amichaietal.[29],Bissonn
etteetal.[33],Martin-Ezquerraetal.
[46],R
allis
etal.[47],Zam
pettiet
al.[48],Jemec
etal.[15],
Yao
etal.[40]
Albertet
al.[14],Jese
etal.[24]
Vitam
inD
analogs
Amichaiet
al.[29],Albertet
al.[14]
Coaltar
And
ersenet
al.[28]
Quanet
al.[43]
Topicaldoxepin
Albertet
al.[14]
Com
bination
therapies
Topicalantifungalandtar
Kapila
etal.[18]
Low
-potency
TCS?
topical
antifungals
And
ersenet
al.[28],Rattetet
al.[49],Kapila
etal.[18]
Albertet
al.[14]
Low
-potency
TCS?
TCIs
Kapila
etal.[18]
Low
-potency
TCS?
tar
Kapila
etal.[18]
Kapila
etal.[18]
Dermatol Ther (Heidelb) (2018) 8:509–525 515
Table2
continued
Medication
Successful
Unsuccessful
Low
-potency
TCS?
topical
vitamin
Danalog
Meeuw
iset
al.[17]
Low
-potency
TCS?
tar?
vitamin
D
analog
Fischeret
al.[16]
Low
-potency
TCS?
mid-
potencyTCS?
tar
Kapila
etal.[18]
Kapila
etal.[18]
Low
-potency
TCS?
mid-
potency
TCS?
tar?
vitamin
D
analog
Kapila
etal.[18]
Mid-potency
TCS?
tar
Kapila
etal.[18]
Kapila
etal.[18]
Mid-potency
TCS?
tar?
vitamin
D
analog
Kapila
etal.[18]
High-potency
TCS?
vitamin
D?
tar
Kapila
etal.[18]
516 Dermatol Ther (Heidelb) (2018) 8:509–525
trial data for the treatment of genital psoriasis[21]. In this randomized, double-blind, placebo-controlled phase III trial (grade 1), adult sub-jects with moderate-to-severe genital psoriasiswere randomized to receive either placebo(n = 74) or ixekizumab 160 mg subcutaneouslyat week 0 followed by 80 mg every 2 weeksthereafter (n = 75). The primary outcome ofpatients achieving static Physician’s GlobalAssessment of Genitalia score of ‘‘clear’’ or‘‘minimal’’ (sPGA-G 0/1) by week 12 was met bysignificantly more subjects on ixekizumabtreatment than placebo (74% vs. 8%). Addi-tionally, significantly more patients treatedwith ixekizumab reported improved sexualactivity as measured by Genital Psoriasis SexualFrequency Questionnaire (GenPS-SFQ) item 2score 0/1 (78% vs. 21%) and clinically mean-ingful reduction in genital itch as measured bythe genital itch numeric rating scale (NRS) (60%
vs. 8%) compared with placebo. Safety out-comes were similar to the overall safety profileof ixekizumab, with the most common adverseevents including diarrhea, injection site reac-tions, nasopharyngitis, upper respiratory tractinfections, and headaches.
Two cases (grade 5) reported that oral dap-sone given 100 mg daily was found to be suc-cessful in clearing psoriasis lesions within4 weeks, without any reported adverse events[22, 23]. Mycophenolate mofetil and oral dox-epin have both been reported as successfultreatments for genital psoriasis in one case eachas well [14, 23]. Methotrexate 7.5–20 mg weeklyimproved genital symptoms in two of fourgenital psoriasis patients [14, 18, 23, 24]. How-ever, methotrexate use was associated withgastrointestinal disturbance, headache, insom-nia, and urinary tract infections. There is onereport of genital pustular psoriasis clearance
Table 3 Evidence on systemic treatments for genital psoriasis by medication
Medication Successful Unsuccessful
Phototherapy
UVB phototherapy Kapila et al. [18]
PUVA Albert et al. [14]
Immunosuppressants
Mycophenolate mofetil Guglielmetti et al. [23]
Methotrexate Albert et al. [14], Kapila et al. [18] Guglielmetti et al. [23], Jese et al. [24]
Biologics
Adalimumab Jese et al. [24]
Ixekizumab Ryan et al. [50]
Efalizumaba Cassano et al. [26]
Oral antifungals Foureur et al. [39], Meeuwis et al. [17] J Fam Pract 2016 [41]
Oral antibiotics Quan et al. [43] Singh et al. [22]
Dapsone Guglielmetti et al. [23], Singh et al. [22]
Doxepin Albert et al. [14]
Antihistamines Cretu et al. [37]
Antipsychotics Shimamoto et al. [25]
Calcium gluconate Cretu et al. [37]
a Formerly available treatment
Dermatol Ther (Heidelb) (2018) 8:509–525 517
after initiation of chlorpromazine for treatmentof a concurrent manic episode [25]. Adali-mumab has also been shown in one case reportto result in clearance of genital psoriasis by6 months without adverse effects [24]. Efal-izumab considerably improved genital pruritusin 9 patients (grade 4) given at a dose of 1 mg/kgweekly for 12 weeks [26]. However, 2 of 55patients in this study experienced adverseevents requiring treatment discontinuationwithin 12 weeks (psoriasis flare and neurologicsymptoms), and 7 patients described self-lim-ited treatment-associated papular psoriasis.Efalizumab has since been removed from themarket because of safety concerns [27].
Treatment of Genital Psoriasisin the Pediatric Population
A total of 12 articles examined treatments forgenital psoriasis in infants and children(Table 4). Three of these articles were open-labelstudies (grade 4), while the remaining ten werecase reports (grade 5) describing the effects oftreatment on pediatric patients. Treatmentoutcomes were described for a total of 126patients. Mild, topical coal tar preparationswere effective in clearing genital lesions among91 pediatric patients from two case series[16, 28].
Topical corticosteroid-based regimens led tosuccessful treatment outcomes in 37 cases. Low-potency topical steroids were used in 26patients; moderate- and high-potency steroidswere used in 6 patients and 1 patient, respec-tively. Successful treatment in six patients alsoincluded topical antifungal medications, pri-marily ketoconazole cream and clotrimazolecream. There was one case report (grade 5) ofcomplete resolution of psoriatic lesions withtopical pimecrolimus 1% ointment treatment[29]. All of the therapies used in children werewell tolerated, without any significant adverseevents reported.
DISCUSSION
In the past several years, there has been amoderate increase in studies assessing
treatments for genital psoriasis. At the time ofthe last published review on this topic in 2011,only 6 case reports and 1 open-label studydescribed the effects of therapies for genitalpsoriasis, while 24 articles reflected expertonion on treatment for this disease [3]. In ouranalysis, we found 1 randomized controlledtrial (grade 1), 11 open-label studies (grade 4),and 26 case reports (grade 5) describing theefficacy and safety of topical and systemictreatments for genital psoriasis. Various thera-pies have been shown to be effective for genitalpsoriasis in case reports and case series, buthigh-quality evidence in the form of random-ized controlled trials remains inadequate forgenital psoriasis treatments.
Low-to-mid-potency topical corticosteroidsare recommended as the first-line treatment forgenital psoriasis [30] (grade of recommenda-tion: D) and are commonly reported in the lit-erature to be a critical component of treatmentfor these lesions. However, topical corticos-teroids are generally approached with greatcaution for genital psoriasis patients because ofthe unique environment of the genitalia [31].The thin skin and constant occlusion of thisenvironment cause topical medications to haveincreased penetration in the groin area, which isa particular problem for infants, who have ahigh surface area-to-body mass ratio, predis-posing them to systemic side effects. Mildtopical corticosteroids may not be potentenough to induce a clinically significantresponse in some patients [11, 32] and are oftenused in combination with second-line topicaltherapies to yield clinical benefit (Table 2).Moderate-to-high-potency corticosteroids havebeen used effectively in adults and childrenwith genital psoriasis, both as monotherapy andin combination with other topical agents,without reports of significant adverse effects(Table 2). There was a lack of reporting onadverse effects from topical corticosteroids instudies included our analysis; therefore, there isnot enough evidence to determine whetherthere were no side effects with these therapies orif they simply were not mentioned. From theexisting evidence, topical corticosteroids con-tinue to be recommended as first-line treatment
518 Dermatol Ther (Heidelb) (2018) 8:509–525
Table4
Studieson
treatm
entsforgenitalpsoriasisin
childrenandinfants
Sources
Stud
ycharacteristics
Treatments
andou
tcom
es
Stud
ydesign,
levelof
evidence
Typeof
psoriasis
Site
Age
Coh
ort
(M/F)
Successful
Unsuccessful
Result
Afsar
etal.
[6]
Case
report,
5
Napkin
psoriasis
Diaperarea
5.5 months
1M
0.05%
clobetasone17-butyrate
cream
daily,emollient
cream
–Overallregression
with
interm
ittent
mild
flares
Amichai
etal.[29]
Case
report,
5
Plaque
psoriasis
Glans
penis,
distal
partsof
shaft
10years
1M
1%pimecrolim
uscream
Betam
ethasone
1%
cream,
calcipotriol
ointment
Resolutionof
psoriatic
lesionsafter3weeks
of
topicalpimecrolim
us,
recurrence
treated
successfully
And
ersen
etal.[28]
Open-
label
case
series,
4
Psoriasiform
napkin
derm
atitis
Diaperarea
2.1 months
(0–2
1)
35M/
32F
Tar
(64),corticosteroid-
vioform
ointment(3)
Zincpaste,salicylic
ointment,
steroid
ointment,or
aniline
dye
solutions
Tar
effectivein
64patients,
corticosteroid-vioform
ointmenteffectivein
3
patients
Baggioetal.
[36]
Case
report,
5
Psoriasiform
napkin
derm
atitis
Diaperarea
18
months
1F
Fluticasonepropionate
cream
Zincoxide-based
ointments,
antifungal
creams,desonide
cream
Com
pleteresolution
at
1week
Cretu
etal.
[37]
Case
report,
5
Napkin
psoriasis
Anogenital
area,
buttocks,
upper
1/3
thighs
4months
1M
System
icantihistam
ines,
nonspecific
desensitization
treatm
ent,rigorous
hygiene,
non-fluorinated
topical
corticosteroids
Antibiotic
ointmentfor
5days,calcium
gluconate,
topical
corticosteroids
Significant
improvem
entby
day2of
treatm
ent
Dermatol Ther (Heidelb) (2018) 8:509–525 519
Table4
continued
Sources
Stud
ycharacteristics
Treatments
andou
tcom
es
Stud
ydesign,
levelof
evidence
Typeof
psoriasis
Site
Age
Coh
ort
(M/F)
Successful
Unsuccessful
Result
Fergusson
etal.[35]
Open-
label
case
series,
4
Psoriasiform
napkin
derm
atitis
Diaperarea
Infants
22a
Zinc-oxidepaste
Topicalsteroids
Com
pleteclearance
Fischer
etal.[16]
Open-
label
case
series,
4
Plaque
psoriasis
Vulva
6years
(2–1
2)
27F
LPC
andtopicalcalcipotriol
with1%
hydrocortisone
(23)
ormethylpredn
isolone
aceponate0.1%
ointment(4)
–Symptom
remission,L
PC
welltolerated
Greco
etal.
[37]
Case
report,
5
Napkin
psoriasis
Diaperarea
18
months
1F
–Zincoxidepaste,
nystatin,
hydrocortisone
acetate2.5%
ointment
Minim
alim
provem
ent
Hernand
ez
etal.[45]
Case
report,
5
Vulvar
psoriasis
Vulva,
perianal
area
5years
1F
Clobetasol0.05%
ointment
twicedaily
Triam
cinolone
0.1%
ointment
twicedaily
Significantlyim
proved
erythemaon
innerlabial
andperianalareasat
2weeks,com
plete
resolution
at4weeks
Kam
eretal.
[42]
Case
report,
5
Napkin
psoriasis
Diaperarea
10weeks
1F
Low
-potency
topical
corticosteroids
–Clearance
oflesionsat
2weeks
520 Dermatol Ther (Heidelb) (2018) 8:509–525
Table4
continued
Sources
Stud
ycharacteristics
Treatments
andou
tcom
es
Stud
ydesign,
levelof
evidence
Typeof
psoriasis
Site
Age
Coh
ort
(M/F)
Successful
Unsuccessful
Result
Rattetet
al.
[49]
Case
report,
5
Psoriasiform
napkin
derm
atitis
Diaperarea
12
months
1F
Clomitrazole1%
cream,
hydrocortisone
1%cream
threetimes
daily
–Clearance
oflesionsat
2weeks
withmild
erythema
Rattetet
al.
[49]
Case
report,
5
Psoriasiform
napkin
derm
atitis
Diaperarea
5weeks
1M
Clomitrazole1%
cream,
hydrocortisone
1%cream
threetimes
daily
–Clearance
oflesionsat
4weeks
Watanabe
etal.[38]
Case
report,
5
Pustular
psoriasis
Diaperarea
4months
1M
0.2%
ketoconazolecream
daily
–Com
pleteclearanceat
1month
LPC
liquorpiciscarbonis
aUnspecifiedsex
Dermatol Ther (Heidelb) (2018) 8:509–525 521
for genital psoriasis (grade of recommendation:C).
The data in this analysis do not show supe-rior efficacy for nonsteroidal topical treatmentscompared with topical corticosteroids for thetreatment of genital psoriasis (Table 2). Topicalcalcineurin inhibitors did improve genital pso-riasis in several patients and were fairly welltolerated. Mild burning or pruritus can beassociated with using these treatments in thesensitive groin region, but these symptoms areoften manageable and limited in duration [33].Topical coal tar preparations demonstrate effi-cacy in both adults and children with genitallesions and are not associated with significantadverse effects. Vitamin D analogs are some-times recommended for patients with generalpsoriasis (grade of recommendation: D), but thisis less reported in the literature [11, 30]. How-ever, these nonsteroidal topical therapies mayincrease the risk for lymphoma, be more irri-tating, and be more costly than topical corti-costeroids [34]. Topical calcineurin inhibitors,coal tar preparations, and vitamin D analogsmay thus be used as second-line therapies forpsoriasis lesions in the genital area (grade ofrecommendation: C).
Systemic therapies such as dapsone andmethotrexate can work well for patients withgenital lesions and should be considered forpatients with debilitating quality of lifeimpairment (grade of recommendation: C) [30].Our analysis did not find any evidence on theuse of other traditional systemic agents, such asoral cyclosporine, acitretin, or apremilast,specifically for genital psoriasis. Althoughnumerous effective biologics are available forthe treatment of psoriasis, there is only onepublished clinical trial result on the efficacy ofcurrently approved biologics specifically forgenital psoriasis.
A recent study has shown ixekizumab tohave high efficacy specifically for genital psori-asis, with rapid improvement seen as early as1 week into treatment [21]. This medicationsignificantly improves genital lesion appear-ance, genital itch, sexual health, and quality oflife and may be a promising solution forpatients suffering from recalcitrant genital pso-riasis. Ixekizumab is currently the only
medication with FDA labeling specificallymentioning genital psoriasis (grade of recom-mendation: B).
Although not specifically addressed in themajority of articles in our analysis, goodhygiene and reduction of friction are essentialfirst-line measures for the treatment of genitalpsoriasis patients (grade of recommendation: D)[11]. Gentle, non-soap cleansers are recom-mended to keep the genitals clean withoutirritating the area, and patients should beadvised to wear loose-fitting, unrestrictiveclothing to avoid koebnerization and furtherirritation [30]. Patients with genital psoriasisshould always use lubricant or lubricated con-doms with any sexual activity to avoid exacer-bation of genital symptoms. In combinationwith proper pharmacologic therapy, these sup-portive measures are necessary for minimizingthe impact of genital psoriasis.
Despite increased research into genital pso-riasis in recent years, the optimal treatmentapproach for affected patients remains unclear.Overall, available evidence is limited, especiallyregarding the efficacy of systemic agents forgenital psoriasis. This is most likely becausesystemic treatments are indicated for moderate-to-severe psoriasis, and efficacy evaluationstypically do not specifically assess genitalsymptoms. Genital psoriasis is ill defined, variesin characterization throughout the literature,and is not distinguished from inverse psoriasisin several studies. The existing literature thususes various different measures to evaluatetreatment efficacy or assess symptom improve-ment qualitatively so studies can be difficult tocompare. The introduction of novel assessmenttools for genital psoriasis will facilitate a greaterunderstanding of how various treatmentscompare.
Additionally, most studies included in ouranalysis did not assess or report safety data orside effects with treatment, which is especiallyimportant for the sensitive genital area. Mostrecommendations for treating genital psoriasisare based on case reports or expert opiniononly, and randomized controlled trials for thisdisease are lacking [3, 11]. Larger sample sizesand controlled studies are needed to properlyassess the safety and efficacy of treatments for
522 Dermatol Ther (Heidelb) (2018) 8:509–525
genital psoriasis to better understand the opti-mal management approach for these patients.
CONCLUSIONS
Recently, a growing number of studies haveevaluated the efficacy of various treatmentsspecifically for genital psoriasis, including onerandomized clinical trial for a biologic agent [3].A variety of topical therapies have shown vary-ing success for treatment of genital psoriasis,while far fewer systemic and biologic therapieshave been evaluated for genital psoriasis. Fur-ther inquiry into the optimal treatment regi-men for genital psoriasis is necessary.
ACKNOWLEDGEMENTS
Funding. No funding or sponsorship wasreceived for this study or publication of thisarticle. Wilson Liao is funded in part by grantsfrom the National Institutes of Health(R01AR065174, U01AI119125).
Authorship. All named authors meet theInternational Committee of Medical JournalEditors (ICMJE) criteria for authorship for thisarticle, take responsibility for the integrity ofthe work as a whole, and have given theirapproval for this version to be published.
Disclosures. Kristen M Beck, Eric J Yang,Isabelle M Sanchez, and Wilson Liao havenothing to disclose.
Compliance with Ethics Guidelines. Thearticle is based on previously conducted studiesand does not contain any studies with humanparticipants or animals performed by any of theauthors.
Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommer-cial use, distribution, and reproduction in any
medium, provided you give appropriate creditto the original author(s) and the source, providea link to the Creative Commons license, andindicate if changes were made.
REFERENCES
1. Meeuwis KAP, Potts Bleakman A, van de KerkhofPCM, Dutronc Y, Henneges C, Kornberg LJ, MenterA. Prevalence of genital psoriasis in patients withpsoriasis. J Dermatol Treat. 2018:1–7.
2. Wang G, Li C, Gao T, Liu Y. Clinical analysis of 48cases of inverse psoriasis: a hospital-based study.Eur J Dermatol. 2005;15:176–8.
3. Meeuwis KA, de Hullu JA, Massuger LF, van deKerkhof PC, van Rossum MM. Genital psoriasis: asystematic literature review on this hidden skindisease. Acta Derm Venereol. 2011;91:5–11.
4. Ryan C, Sadlier M, De Vol E, Patel M, Lloyd AA, DayA, Lally A, Kirby B, Menter A. Genital psoriasis isassociated with significant impairment in quality oflife and sexual functioning. J Am Acad Dermatol.2015;72:978–83.
5. Morris A, Rogers M, Fischer G, Williams K. Child-hood psoriasis: a clinical review of 1262 cases.Pediatr Dermatol. 2001;18:188–98.
6. Afsar FS, Uysal SS, Salis FM, Calli AO. Napkin pso-riasis. Pediatr Int. 2016;58:420–2.
7. Meeuwis KA, de Hullu JA, van de Nieuwenhof HP,Evers AW, Massuger LF, van de Kerkhof PC, vanRossum MM. Quality of life and sexual health inpatients with genital psoriasis. Br J Dermatol.2011;164:1247–55.
8. Zamirska A, Reich A, Berny-Moreno J, Salomon J,Szepietowski JC. Vulvar pruritus and burning sen-sation in women with psoriasis. Acta Derm Vener-eol. 2008;88:132–5.
9. Cather JC, Ryan C, Meeuwis K, Potts Bleakman AJ,Naegeli AN, Edson-Heredia E, Poon JL, Jones C,Wallace AN, Guenther L, Fretzin S. Patients’ per-spectives on the impact of genital psoriasis: aqualitative study. Dermatol Ther (Heidelb).2017;7:447–61.
10. Meeuwis KA, van de Kerkhof PC, Massuger LF, deHullu JA, van Rossum MM. Patients’ experience ofpsoriasis in the genital area. Dermatology.2012;224:271–6.
Dermatol Ther (Heidelb) (2018) 8:509–525 523
11. Menter A, Korman NJ, Elmets CA, Feldman SR,Gelfand JM, Gordon KB, Gottlieb A, Koo JY, Leb-wohl M, Leonardi CL, Lim HW, Van Voorhees AS,Beutner KR, Ryan C, Bhushan R. Guidelines of carefor the management of psoriasis and psoriaticarthritis: section 6. Guidelines of care for the treat-ment of psoriasis and psoriatic arthritis: case-basedpresentations and evidence-based conclusions.J Am Acad Dermatol. 2011;65:137–74.
12. Farage M, Maibach HI. The vulvar epithelium dif-fers from the skin: implications for cutaneous test-ing to address topical vulvar exposures. ContactDermatitis. 2004;51:201–9.
13. Howick J, Chalmers I, Glasziou P, Greenhalgh T,Heneghan C, Liberati A, Moschetti I, Phillips B,Thornton H. The 2011 Oxford CEBM levels of evi-dence (introductory document). Oxford Centre forEvidence-Based Medicine. 2011.
14. Albert S, Neill S, Derrick EK, Calonje E. Psoriasisassociated with vulval scarring. Clin Exp Dermatol.2004;29:354–6.
15. Jemec GB, Baadsgaard O. Effect of cyclosporine ongenital psoriasis and lichen planus. J Am AcadDermatol. 1993;29:1048–9.
16. Fischer G. Chronic vulvitis in pre-pubertal girls.Aust J Dermatol. 2010;51:118–23.
17. Meeuwis KA, de Hullu JA, IntHout J, Hendriks IM,Sparreboom EE, Massuger LF, van de Kerkhof PC,van Rossum MM. Genital psoriasis awareness pro-gram: physical and psychological care for patientswith genital psoriasis. Acta Derm Venereol.2015;95:211–6.
18. Kapila S, Bradford J, Fischer G. Vulvar psoriasis inadults and children: a clinical audit of 194 cases andreview of the literature. J Lower Genit Tract Dis.2012;16:364–71.
19. Liao YH, Chiu HC, Tseng YS, Tsai TF. Comparisonof cutaneous tolerance and efficacy of calcitriol 3microg g(-1) ointment and tacrolimus 0.3 mg g(-1)ointment in chronic plaque psoriasis involvingfacial or genitofemoral areas: a double-blind, ran-domized controlled trial. Br J Dermatol.2007;157:1005–12.
20. TALTZ (ixekizumab) [package insert]. Indianapolis:Eli Lilly and Company. 2017.
21. Ryan C, Menter A, Guenther L, Blauvelt A, Bisson-nette R, Yang F, Potts Bleakman A. Efficacy andsafety of ixekizumab in a randomized, double-blinded, placebo-controlled, phase 3b clinical trialin patients with moderate-to-severe genital psoria-sis. J Sexual Med. 2018;15:S6–7.
22. Singh N, Thappa DM. Circinate pustular psoriasislocalized to glans penis mimicking ‘circinate bal-anitis’ and responsive to dapsone. Indian J Derma-tol Venereol Leprol. 2008;74:388–9.
23. Guglielmetti A, Conlledo R, Bedoya J, Ianiszewski F,Correa J. Inverse psoriasis involving genital skinfolds: successful therapy with dapsone. DermatolTher (Heidelb). 2012;2:15.
24. Jese R, Perdan-Pirkmajer K, Dolenc-Voljc M, TomsicM. A case of inverse psoriasis successfully treatedwith adalimumab. Acta Dermatovenerol Alp Pan-nonica Adriat. 2014;23:21–3.
25. Shimamoto Y, Shimamoto H. Annular pustularpsoriasis associated with affective psychosis. Cutis.1990;45:439–42.
26. Cassano N, Mastrandrea V, Buquicchio R, Mira-capillo A, Loconsole F, Filotico R, Vena GA. Efal-izumab in moderate-to-severe plaque psoriasis: aretrospective case series analysis from clinicalpractice. J Biol Regul Homeost Agents.2008;22:185–93.
27. Talamonti M, Teoli M, Botti E, Spallone G, Chi-menti S, Costanzo A. Patients with moderate tosevere plaque psoriasis: one year after the EuropeanMedicines Agency recommendation of efalizumabsuspension. Dermatology. 2011;222:250–5.
28. Andersen SL, Thomsen K. Psoriasiform napkin der-matitis. Br J Dermatol. 1971;84:316–9.
29. Amichai B. Psoriasis of the glans penis in a childsuccessfully treated with Elidel (pimecrolimus)cream. J Eur Acad Dermatol Venereol.2004;18:742–3.
30. Menter A, Korman NJ, Elmets CA, Feldman SR,Gelfand JM, Gordon KB, Gottlieb AB, Koo JY, Leb-wohl M, Lim HW, Van Voorhees AS, Beutner KR,Bhushan R. Guidelines of care for the managementof psoriasis and psoriatic arthritis: section 4.Guidelines of care for the management and treat-ment of psoriasis with traditional systemic agents.J Am Acad Dermatol. 2009;61:451–85.
31. Kivelevitch D, Frieder J, Watson I, Paek SY, MenterMA. Pharmacotherapeutic approaches for treatingpsoriasis in difficult-to-treat areas. Expert OpinPharmacother. 2018;19:561–75.
32. Czuczwar P, Stepniak A, Goren A, Wrona W, Pasz-kowski T, Pawlaczyk M, Piekarska-Myslinska D,Wozniak S, Pietrzak A. Genital psoriasis: a hiddenmultidisciplinary problem—a review of literature.Ginekol Pol. 2016;87:717–21.
33. Bissonnette R, Nigen S, Bolduc C. Efficacy and tol-erability of topical tacrolimus ointment for the
524 Dermatol Ther (Heidelb) (2018) 8:509–525
treatment of male genital psoriasis. J Cutan MedSurg. 2008;12:230–4.
34. Broeders JA, Ahmed Ali U, Fischer G. Systematicreview and meta-analysis of randomized clinicaltrials (RCTs) comparing topical calcineurin inhibi-tors with topical corticosteroids for atopic der-matitis: a 15-year experience. J Am Acad Dermatol.2016;75:410–419 (e413).
35. Fergusson AG, Fraser NG, Grant PW. Napkin der-matitis with psoriasiform ‘‘ide’’. A review of fifty-two cases. Br J Dermatol. 1966;78:289–96.
36. Baggio R, Le Treut C, Darrieux L, Vareliette A, SafaG. Psoriasiform diaper rash possibly induced by oralpropranolol in an 18-month-old girl with infantilehemangioma. Case Rep Dermatol. 2016;8:369–73.
37. Greco M, Chamlin SL. An 18-month-old girl withchronic diaper dermatitis. Psoriasis presenting inthe diaper area. Pediatr Ann. 2006;35(79):82–3.
38. Watanabe M, Tabata N, Tagami H. Explosive diaperpustular psoriasis. Pediatr Dermatol. United States.2002;19:564–5.
39. Foureur N, Vanzo B, Meaume S, Senet P. Prospectiveaetiological study of diaper dermatitis in theelderly. Br J Dermatol. 2006;155:941–6.
40. Yao XJ, Zhang TD. Psoriasis localized to the glanspenis in a 37-year-old man. CMAJ. 2018;190:E747.
41. Usatine RP. Itchy rash in groin. J Fam Pract.2016;65(11).
42. Kamer B, Pyziak K, Krawczyk T, Socha-Banasiak A,Rotsztejn H. A rare case of psoriasis resemblingdiaper dermatitis. Przeglad Pediatryczny.2012;42:160–1.
43. Quan MB, Ruben BS. Pustular psoriasis limited tothe penis. Int J Dermatol. 1996;35:202–4.
44. Weinrauch L, Katz M. Psoriasis vulgaris of labiummajus. Cutis. 1986;38:333–4.
45. Hernandez M, Simms-Cendan J, Zendell K. Guttatepsoriasis following streptococcal vulvovaginitis in afive-year-old girl. J Pediatr Adolesc Gynecol.2015;28:e127–9.
46. Martin Ezquerra G, Sanchez Regana M, HerreraAcosta E, Umbert Millet P. Topical tacrolimus forthe treatment of psoriasis on the face, genitalia,intertriginous areas and corporal plaques. J DrugsDermatol. 2006;5:334–6.
47. Rallis E, Nasiopoulou A, Kouskoukis C, Roussaki-Schulze A, Koumantaki E, Karpouzis A, Arvanitis A.Successful treatment of genital and facial psoriasiswith tacrolimus ointment 0.1%. Drugs Exp ClinRes. 2005;31:141–5.
48. Zampetti A, Gnarra M, Linder D, Digiuseppe MD,Carrino N, Feliciani C. Psoriatic pseudobalanitiscircinata as a post-viral koebner phenomenon. CaseRep Dermatol. 2010;2:183–8.
49. Rattet JP, Headley JL, Barr RJ. Diaper dermatitis withpsoriasiform ID eruption. Int J Dermatol.1981;20:122–5.
50. Ryan C, Menter A, Guenther L, Blauvelt A, Bisson-nette R, Meeuwis K, Sullivan J, Cather JC, Yosipo-vitch G, Gottlieb AB, Merola JF, Callis Duffin K,Fretzin S, Osuntokun OO, Burge R, Naegeli AN,Yang FE, Lin CY, Todd K, Potts Bleakman A. Efficacyand safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase 3b study ofpatients with moderate-to-severe genital psoriasis.Br J Dermatol. 2018.
51. Sezer E, Lehman JS, Yalcın O, Tufek I, Keskin S,Durmaz EO, Sahin S. Oyster-shaped hyperkeratoticplaques on the penis. Dermatol Pract Concept.2015;5(4):37–8. https://doi.org/10.5826/dpc.0504a09.
Dermatol Ther (Heidelb) (2018) 8:509–525 525