REVIEW

Evaluation and management of the patient

with multiple syringomas: A systematic review
of the literature
Kiyanna Williams, BS,a and Kanade Shinkai, MD, PhDb
San Francisco, California

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic
comma (tadpole) shaped tail comprised of dilated, cystic eccrine ducts. Clinically, syringomas typically
present in adolescent females predominantly in the periorbital region. They may present as solitary or
multiple lesions, and more rare sites of involvement include the genitals, palms, scalp, and the chest. Over
the past 50 years, there have been [800 reported cases of syringoma either alone or in conjunction with a
systemic syndrome, most commonly Down syndrome. The primary aim of this systematic review is to
discuss the clinical features and associations of syringomas with a focus on the patient with multiple
syringomas. Its secondary aims are to explore pathophysiology with a focus on multiple syringomas and
provide comprehensive data on both traditional and novel treatments. Importantly, multiple syringomas
present across a broad clinical spectrum. Though noted in many textbooks to be related to tumor
syndromes, the association of syringomas with inherited tumor syndromes is only rarely reported in the
literature. Despite multiple reported cases of syringoma, the pathophysiology remains poorly understood
and treatment continues to pose a significant challenge. ( J Am Acad Dermatol http://dx.doi.org/10.1016/
j.jaad.2015.12.006.)

Key words: eruptive syringoma; familial syringoma; multiple syringomas; syringoma; syringoma
syndromes; syringoma treatment.

S yringomas are benign adnexal tumors with

characteristic histopathologic features deriving
from intraepidermal eccrine ducts. Clinically,
lesions appear as small, firm, flesh-colored or yellow
asymptomatic papules, 1 to 3 mm in diameter, often
in multiples with symmetric distribution. Syringomas
typically present in early adulthood, with a female
predominance. Although the most common site of
localized involvement is periorbital, other affected
sites have been reported, including the vulva, penis,
scalp, and axillae (Fig 1). Less commonly, eruptive
distributions (a form of generalized syringoma) that
occur in successive crops, including the anterior
chest, axillae, neck, abdomen, and extremities, have
also been reported.1
The clinical differential diagnosis of syringomas
includes milia, xanthoma, hidrocystoma, trichoepi-
thelioma, and xanthelasma, especially for lesions on
Abbreviations used:
DM:
DS:
TCA:
diabetes mellitus
Down syndrome
trichloroacetic acid
the eyelids; additional diagnostic considerations
include cutaneous mastocytosis, fibrofolliculomas,
vellus hair cysts, angiofibromas, and fibroelastic
papulosis. Diagnosis is confirmed by distinct histo-
pathologic features (ie, the presence of multiple
small ducts and epithelial cords within the dermis,
and cystic eccrine ducts with a characteristic comma-
shaped tail).
A syringoma classification criterion proposed by
Friedman and Butler 1is based on clinical features
and consists of 4 variants: localized, familial, a form

From the University of California San Francisco School of
Medicinea and the Department of Dermatology,b University
of California San Francisco.
Funding sources: None.
Conflicts of interest: None declared.
Accepted for publication December 5, 2015.
Correspondence to: Kanade Shinkai, MD, PhD, Department of
Dermatology, University of California San Francisco, 1701
Divisadero St, 3rd fl, San Francisco, CA 94115. E-mail: kanade.
shinkai@ucsf.edu.
Published online February 3, 2016.
0190-9622/$36.00
2015 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2015.12.006

1
2 Williams and Shinkai J AM ACAD DERMATOL
n 2016

associated with Down syndrome (DS), and a gener- patient needed to have clinical or biopsy-confirmed
alized variant, including multiple and eruptive sy- syringoma with a reported family history of similar
ringomas. Lau et al2 recently proposed the lesions in $1 family members; 29 familial cases were
classification of familial syringomas based on hered- included in this review. For treatment cases, reports
itary pattern and clinical presentation, including needed to provide data on method of treatment,
factors such as distribution, syringoma type, and number of cases, anatomic sites treated, and results
anatomic location. of treatment; 215 cases met the inclusion criteria.
Multiple syringomas are
seen in several clinical con- Data sources
texts, including familial CAPSULE SUMMARY Case reports, systematic
syringomatosis and tumor reviews, and research letters
d Syringomas are benign adnexal tumors
syndromes, but little is known published in PubMed and
deriving from intraepidermal eccrine
about the clinical spectrum of Scopus between 1964 and
ducts.
syringoma presentations and 2013 were included.
effective treatments. The aim d Multiple syringomas occur in several
of this review is aim to clinical contexts, including familial Data extraction
describe the clinical features, syringomatosis, and rarely as a feature of Comprehensive data,
systemic associations, and tumor syndromes. including age, age at presen-
effective treatment strategies d This review outlines an evidence-based tation, sex, anatomic involve-
for multiple syringomas. approach to the diagnosis and ment, family history, and
management of a patient presenting treatments were obtained
METHODS with multiple syringomas. from 46 reports. Percentages
Search strategies were calculated from avail-
A systematic literature able reported data from these
search was conducted on the PubMed and Scopus select cases. Anatomic location and syndrome asso-
databases using the following search terms: familial ciation demographics were obtained from 826 cases
syringoma, hereditary syringoma, familial eruptive from 204 reports.
syringoma, hereditary eruptive syringoma, syrin-
goma, familial generalized syringoma, generalized RESULTS
syringoma, multiple syringoma, eruptive syrin- Eight hundred twenty-six cases of syringomas
goma, vulvar syringoma, periorbital syringoma, were reported in the literature between 1964 and
penile syringoma, scalp syringoma, axilla syrin- 2013. Comprehensive data were obtained from 239
goma, milia AND syringoma, lichen AND syrin- cases of syringoma identified from 46 reports2-47 that
goma, plaque AND syringoma, syringoma AND met the inclusion criteria. Two hundred fifteen cases
syndrome, syringoma AND diabetes mellitus, sy- described treatment,17-47 24 cases were familial,2-17
ringoma AND Down syndrome, syringoma AND and 5 cases were familial with reported treatment
NicolaueBalus, syringoma AND BrookeeSpiegler, attempts.18,19 Of the 239 cases, 92% were women,
syringoma treatment, syringoma laser, syringoma and 70%, 20%, and 10% presented during adoles-
removal, syringoma destruction, syringoma cence, childhood, and adulthood, respectively.
argon, syringoma CO2, syringoma isotretinoin, Localized syringomaddefined as multiple syringo-
and syringoma Accutane. Bibliographies of select mas confined to 1 anatomic sitedwas more
publications were reviewed for additional eligible commonly reported than the eruptive form.
studies. Based on available data, cases were grouped Specifically, 212 (88.7%) cases were localized, with
as comprehensive, familial cases, or treatment the most frequent type being located in the peri-
cases, as described in Supplemental Fig 1 (available orbital region (81%), followed by the vulva (17%)
online at http://www.jaad.org). Please note that addi- and face (2%). Ten (5.8%) of the localized periorbital
tional references appear online only and include cases were plaque type. Eruptive cases (11.3%) were
results of the search criteria described. Papers contain- largely distributed over the trunk, neck, and extrem-
ing comprehensive data, including age, sex, anatomic ities (92.6%), with some distributed over the face and
involvement, family history, and treatments were neck (7.4%).
included as comprehensive; a diagnosis of syrin- Case reports of familial syringomatosis (ie, multi-
goma confirmed by biopsy specimen or clinical pre- ple syringomas present in familial cohorts) were rare,
sentation was also used as inclusion criteria. Two with only 29 reported cases2-19 that are summarized
hundred thirty-nine comprehensive cases were in Supplemental Table I (available online at http://
included in this review. For familial cases, the reported www.jaad.org). Of the 29 cases described, 15
J AM ACAD DERMATOL Williams and Shinkai 3
VOLUME jj, NUMBER j

Fig 1. Familial syringomatosis. A 35-year-old healthy woman presented with a history of

periocular, neck (A), axillary, and vulvar (B) syringomas that had been confirmed by obtained
biopsy specimens. Her family history was notable for a mother with multiple syringomas with
similar periocular (but not neck, axillary, or vulvar) lesions. The patient had minimal
improvement with laser, surgical incision and drainage, and isotretinoin treatment.

(51.7%) were localized, with eyelid involvement
being most common, presenting in 65.5% of patients.
Other commonly involved locations included the
cheeks (37.9%), vulva (28.6%), neck (14.3%), face
(10.3%), and palms (7.1%). A single case of a clinical
variant of familial syringomas presenting as milia-
like lesions was described, representing 3.4% of
familial cases.14 Almost half (48.2%) of cases of
familial syringoma described a broader distribution
of lesions and are classified as familial eruptive
syringoma.2-5,9-11,13,15 Most patients developed skin
lesions during adolescence (87%).
Of the 826 reported cases studied, varying pri-
mary morphologies were seen in a number of cases,
including rare cases that present with a plaque/
lichen planusetype appearance (2.4%)4,28,48-55 or
milia-like papules, differing from the classic appear-
ance of syringoma (3.5%).14,56-63 Clear cell cases
(2.2%) were reported,64-74 including an extremely
rare variant: generalized eruptive clear cell syrin-
goma associated with diabetes mellitus (DM;
0.5%).70-74
Multiple systemic associations of syringomas have
been discussed in textbooks, but their true incidence
is sparsely reported. There were 183 (22.2%) cases of
syringoma associated with DS4,21,58,75-88 and 17
(2.1%) cases of syringomas associated with
DM.55,64-68,70-73 Syringomas in the context of tumor
syndromes were rarely reported, with only 1 (0.1%)
case of BrookeeSpiegler syndrome,89 characterized
by cylindromas, trichoepitheliomas, and spiradeno-
mas and 1 (0.1%) case of NicolaueBalus syndrome,
characterized by milial cysts and atrophoderma
vermiculata.90 Syringoma was reported in 1 (0.1%)
case of Costello syndrome, characterized by cranio-
facial, musculoskeletal, and neurologic abnormal-
ities with cutaneous manifestations, including
hyperkeratosis, hyperpigmentation, papillomas,
and deep palmoplantar creases.91
A total of 215 cases from 30 reports described
treatment modalities (Supplemental Table II; avail-
able online at http://www.jaad.org).18-47 Traditional
treatment options for syringoma included destruc-
tive methods (eg, laser, chemical peel, and electro-
desiccation) and surgical excision, all of which were
associated with postprocedural adverse events. More
recent treatment options included topical retinoids,
dermabrasion, and topical atropine. One hundred
sixty-nine cases (78.6%) described the use of a CO2
laser, either alone or in conjunction with trichloro-
acetic acid (TCA), temporary tattooing and alexan-
drite laser, or in vaporization mode.18-33 Of these 169
reported cases, 71 (33%) resulted in moderate
improvement; 51 (23.7%) cases achieved total reso-
lution, 31 (14.4%) cases had near total resolution,
and 16 (7.4%) cases had a poor to fair response.
Argon laser was used in 1 (0.5%) case with vulvar
syringoma, resulting in resolution.34 Fractional pho-
tothermolysis provided high patient satisfaction in 2
(1%) reported cases.47
Additional destructive methods were described.
In a case series of 18 patients (8.4%), low-voltage
electrocoagulation resulted in marked improvement
([70% resolution) in 11 (5.1%) patients and moder-
ate improvement (50-70% resolution) in 7 (3.3%)
patients.36 Each patient underwent 3 sessions
with progressive clinical improvement with
each subsequent visit and few adverse events. The
4 Williams and Shinkai
use of intralesional insulated needles with electro-
coagulation was shown to provide satisfactory lesion
resolution in 2 (1%) cases.35 Intralesional electrodes-
iccation was described in 12 (5.6%) cases, with
complete resolution and no cases of recurrence.39
Surgical excision was described in 2 (1%) case
reports, with total satisfaction and cosmetically
acceptable results noted.45,46 Whole-face dermabra-
sion in 1 (0.5%) case resulted in little recurrence and
good repigmentation.44
Medical therapies were rarely reported (7 cases
[3.3%]). Topical tretinoin was reported in 1 (0.5%)
case of eruptive syringoma resulting in flatter lesions
with reduced erythema.37 Oral isotretinoin was
reported as a successful treatment in 2 (1%) cases
and ineffective in 1 (0.5%) reported case.40,41
Similarly, 1 (0.5%) case of topical atropine resulted
in significant relief of pruritus with reduction of
syringoma lesion size.38 Oral tranilast was cited in 2
(1%) case reports with good improvement after 3 and
8 months of daily tranilast.42,43
Many adverse side effects of treatment were
reported, with dyspigmentation and erythema being
the most common, occurring in 52 (24.2%) and 50
(23.2%) cases, respectively. Less common side ef-
fects included pain (18 cases [8.4%]), swelling (18
cases [8.4%]), and blistering (1 case [0.5%]). Adverse
side effects were most commonly seen using a CO2
laser in combination with TCA (32.3%), followed by
low voltage electrocoagulation (27.7%), CO2 laser
(20%), intralesional desiccation (18.5%), and argon
laser (1.5%). The duration of follow-up varied with
each study from 2 weeks to 29 months; however,
adverse side effects resolved in nearly all cases at the
time of follow-up.
DISCUSSION
Clinical presentation, prevalence, and
systemic associations
This systematic review highlights important pat-
terns that may be relevant in the assessment of a
patient presenting with multiple syringomas,
including unusual presentations, familial cases, and
rare associated syndromes. The common occurrence
of syringomas on the genitalia, scalp, and axilla and
eruptive cases with lesions distributed over the trunk
and extremities necessitate a total body skin exam-
ination. The anatomic distribution in familial cases
and nonfamilial cases varied slightly, with an
increased prevalence of unusual sites in familial
cases, including the vulva, neck, and palms.
Distinct pathophysiology may underlie unusual
primary morphologies of syringomas, including
plaque/lichen planusetype or milia-type syringo-
mas. It is thought that the fibrotic stroma of
J AM ACAD DERMATOL
n 2016
syringoma along with chronic scratching likely
causes epidermal thickening, resulting in lichenoid
plaques seen in lichen planuselike syringoma and
therefore should be considered as a diagnosis in
patients with suspected lichen planus not respond-
ing to topical steroids, especially of the genitalia.19,48
In milia-like syringoma, histopathologic evidence
suggests that the milia derive from the underlying
eccrine duct tumor.60 These less commonly seen
variants can pose a challenge in clinical diagnosis
and should be considered during the differential
diagnosis when encountered. Obtaining a skin bi-
opsy specimen is recommended to confirm the
diagnosis.
Syringoma has been found in association with
several systemic syndromes, especially DS. The
incidence of syringoma among patients with DS has
been reported to be between 18.5% and 39.2%.73,74
While calcium deposition is an uncommon feature of
syringoma in general, it is most commonly seen in
patients with DS and necessitates prompt treatment
because it may herald progression to calcinosis
cutis.21 The association with DM is weaker, reported
in 2.1% cases. Aberrations in glucose metabolism
leading to characteristic changes of clear cell syrin-
goma may link this distinct histopathologic subtype
to patients with DM.16,66,68 It is not known if glycemic
control affects the incidence or resolution of syrin-
goma in patients with DM. The association of
syringomas in tumor syndromes is exceptionally
rare, and common tumorigenesis leading to syrin-
goma and other cutaneous neoplasms have not been
clearly elucidated. A personal and family medical
history is essential to rule out additional systemic
associations or a putative genetic basis.
Several groups have proposed pathophysiologic
mechanisms by which multiple syringomas arise,3,92-94
including in the setting of systemic syndromes. The
most widely accepted theory is that syringomas
are benign neoplasms arising from intraepidermal
portion of eccrine ducts.92 Staining with anti-keratin
antibodies EKH4 and EKH6 suggest that syringomas
arise within basal layers of the epidermis and possess
eccrine secretory and ductal structures.3 The concept
of syringomas as eccrine duct reactive hyperplasia
rather than true neoplasms93 is supported by the
finding of associated lymphocytic infiltrates and case
reports of syringoma developing after maculopapular
or eczematous eruptions, suggesting inflammation as a
precipitating factor.93 A localized or generalized
hamartomatous process could explain eruptive
syringoma, based on the observation of budding of
eccrine germs from epidermis overlying syringoma
lesions.3 Finally, a strong genetic component is sus-
pected, with inheritance patterns in familial cases
J AM ACAD DERMATOL
VOLUME jj, NUMBER j
typically following an autosomal dominant distribu-
tion and genetic aberrations (ie, a loss of heterozygos-
ity on chromosome 16q22) associated with syringoma
development.94 Though earlier studies and a female
predominance in common cases suggested a role for
hormonal factors, the lack of female predominance in
familial cases and immunohistochemical studies of
progesterone and estrogen receptors have not been
consistent in confirming hormonal involvement.19,72
Treatment
The goal of syringoma treatment is to improve
cosmetic appearance, because these lesions are
considered benign, nonprogressive, and typically
asymptomatic. Both medical and surgical interven-
tions have been described in the literature with
variable success. Lack of histopathologic confirma-
tion in almost 50% of available studies limits their
interpretation. No single treatment has proven to be
consistently efficacious. Importantly, recurrence,
scarring, and dyspigmentation commonly compli-
cate destructive interventions. Medical therapies
have been reported to be a successful modality,
with near-complete lesion resolution in case reports
or small case series, limiting generalizability.
While CO2 therapy has been shown to be moder-
ately effective, nonspecific thermal damage may result
in scarring of the adjacent tissue. Alternative tech-
niques may mitigate unwanted scarring. CO2 laser
methods with a pinhole drilling technique may reduce
the degree of tissue damage and resulted in near
complete to complete resolution in 2 small patient
cohorts.23,28 Combining CO2 laser with TCA peels may
synergistically stimulate type I collagen synthesis,
promoting tissue regeneration.31 The use of intrale-
sional insulated needles for electrocoagulation de-
creases the size and number of lesions while sparing
epidermal damage, such as scarring and hyperpig-
mentation.35 However, this time-consuming method
requires multiple sessions for the best results, and
long-term efficacy has not yet been determined. Other
treatment optionsdie, intralesional desiccation, sur-
gical excision, entire face dermabrasion, argon laser,
and fractional photothermolysisdoffer modest clin-
ical improvement; however, there are few reported
cases with limited generalizability.
The value of medical therapy in the management
of syringomas will require validation by larger
studies. The precise rationale for the use of most
current medical therapies for syringoma treatment
remains poorly defined. Retinoids target cellular
proliferation, differentiation, and keratinization;
atropine inhibits sweat production; tranilast may
suppress the proliferation of stromal connective
tissue in syringoma lesions by inhibiting the release
Williams and Shinkai 5
of interleukin-1 beta from eccrine ducts.43
Isotretinoin therapy (3 cases) using variable dosing
regimens had mixed results.
Given the currently available data, treatment with
CO2 laser is likely the most efficacious treatment
modality with tolerable side effects. While it does not
consistently offer complete resolution and is most
commonly associated with dyspigmentation, most
side effects resolve with time. Combining this tradi-
tional therapy with newer techniques, such as TCA
peels or using CO2 lasers in vaporization mode, may
be the most promising methods to increase efficacy
and minimize side effects. While some cases of the
newer medical therapies appear promising, there are
not enough data to use these methods with great
confidence.
In conclusion, multiple syringomas are common
and occur in diverse settings, including in sporadic
and familial cases, with heterogeneous distributions
and presentations. Whereas familial syringomatosis
is a rare condition with an autosomal dominant
pattern of inheritance, multiple syringomas may be
associated with systemic conditions, primarily DS,
and only in rare cases is it a presenting sign of tumor
syndromes. Treatment remains a challenge, though
destructive methodsdspecifically CO2 laser and
possibly intralesional electrocoagulationdmay
represent the best current options for surgical man-
agement; comparative studies, especially of newer
methods, are still needed. Additional research is
needed to substantiate the best medical and surgical
treatment options for cosmetic improvement.
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200. Janniger CK, Brodkin RH. Eruptive syringomas. Cutis. 1990;46:
247-249.
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201. Dvall-Smith DJ, Connors TJ, Scurry J. Generalised eruptive
syringomada popular dermatosis. Australas J Dermatol.
1990;31:95-98.
202. Pruzan DL, Esterly NB, Prose NS. Eruptive syringoma. Arch
Dermatol. 1989;125:1119-1120.
203. Hashimoto K, DiBella RJ, Borsuk GM, Lever WF. Eruptive
hidradenoma and syringoma. Histological, histochemical, and
electron microscopic studies. Arch Dermatol. 1967;96:500-519.
204. Ceulen RP, Van Marion AM, Steijlen PM, Frank J,
Poblete-Gutierrez P. Multiple unilateral skin tumors suggest
type 1 segmental manifestation of familial syringoma. Eur J
Dermatol. 2008;18:285-288.
205. Seth J, Saha A, Rajesh Sarkar T, Jain N, Sarkar P. Eruptive
syringoma-a report of two cases. J Pakistan Assoc Dermatol.
2013;23:461-464.
206. Mondal AK, Kumar P, Chowdhury SN, Pal S, Barbhuiya JN.
Multiple asymptomatic papules over neck and upper ex-
tremities. J Pakistan Assoc Dermatol. 2012;22:79-81.
207. Aktu AS, Ozturk B, Ozturk T, Bayramgurler D. Generalized
eruptive syringoma. Turk Dermatol. 2011;5:104-106.
208. Hassan S, Rizvi N, Bhengra MP, Chaudhary SS. Generalized
eruptive syringoma. J Pakistan Assoc Dermatol. 2012;22:
153-156.
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Supplemental Fig 1. Flow diagram of methods for systematic review (references 95-208 are
available online at http://www.jaad.org).
 7.e5 Williams and Shinkai
Supplemental Table I. Familial cases of syringoma
Anatomic site of
Age, y/sex (age at Anatomic site of involvement of
No. of cases presentation, y) involvement Family member(s) affected family member Reference
1 16/F (13) Axillae and abdomen Brother and mother Brother: arms, axillae, Lau and Haber2
(eruptive) abdomen, groin, and
periorbital (eruptive);
mother: periorbital
1 55/M (5-10) Eyelids, chest, and back Father and sister Periorbital Hashimoto et al3
(eruptive)
6 NR Widespread involvement NR NR Patrizi et al4
(eruptive)
2 33/F (10); 16/F (12) Neck and eyelid; neck Father and brother; Neck and eyelid; NR Soler-Carrillo et al5
and anterior trunk father
(eruptive)
1 54/M (puberty) Eyelids Father and sister Eyelids Draznin6
3 20/F (15), 45/F (33), and Eyelids and cheeks (all Mother, grandmother, Eyelids and cheeks (all Gupta and Raman7
30/M (15) cases) and aunt; daughter, cases)
sister, and brother; and
brother, aunt, uncle,
cousin, and
grandmother,
respectively
1 19/M (18) Eyelids and neck Brother NR Yesudian and Thambiah8
1 16/F (NR) Anterior neck and chest Mother and brother Mother: anterior aspect Patrone and Patrizi9
(eruptive) of the neck and chest;
brother: anterior
aspect of the neck,
chest, and axillae
1 52/F (puberty) Face, neck, trunk, and Mother and daughter NR Metze et al10
extremities (eruptive)
1 23/F (puberty) Neck, axillae, and Father, 2 sisters, and 2 NR Elsayed and Assaf11
abdomen (eruptive) brothers
1 65/F (teens) Face and palms Mother NR Baden12

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1 36/F (16) Neck, chest, and arms Son, mother, 2 brothers, Son: trunk and Marzano et al13
(eruptive) 2 sisters, and 2 extremities
nephews
Continued

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Supplemental Table I. Contd

VOLUME jj, NUMBER j

J AM ACAD DERMATOL
Anatomic site of
Age, y/sex (age at Anatomic site of involvement of
No. of cases presentation, y) involvement Family member(s) affected family member Reference
1 14/F (childhood) Lower eyelids and cheeks Mother Periorbital Ribera et al14
(milia-type)
1 19/M (adolescence) Anterior trunk (eruptive) Mother Left side anterior trunk Smith and Skelton15
1 70/F (60) Eyelids and cheeks Mother Eyelids and cheeks Headington et al16
1 42/F (childhood) Periorbital Paternal aunts, uncles, Periorbital Castro et al18
grandfather,
grandmother, great
aunts, and great
grandparents
4 NR Vulvar NR Periorbital Huang et al19

NR, Not reported.

Williams and Shinkai 7.e6

Supplemental Table II. Reported treatment of syringomas

7.e7 Williams and Shinkai

Anatomic site of
No. of cases (sex) Treatment modality involvement treated Results of treatment Adverse side effects Reference
7 (F) CO2 laser Vulva Resolution of lesions at NR Huang et al19
9 mos F/U
1 (F) CO2 laser Periorbital Not satisfactory NR Cho et al20
1 (F) CO2 laser with pinhole Periorbital Satisfactory at 2 mos F/U NR Cho et al20
method
1 (F) CO2 laser Perioral, periorbital, Resolution at 8 mos F/U None Seo et al21
bilateral axillae
(Eruptive)
10 (8F, 2M) CO2 laser Periorbital Complete resolution at Prolonged erythema in Wang and Roenigk22
1-24 mos F/U all patients (6-12
weeks)
11 (8F, 3M) CO2 laser with pinhole, 10 periorbital, 1 vulvar 7 excellent (80-100%) No erythema or scarring Park et al23
multiple drilling improvement, 4 great at 1-29 months
method (60-80%) improvement
1 (F) CO2 laser Periorbital Resolution at 6 mos F/U Erythema with resolution Nerad and Anderson24
at 6 months
2 (F) CO2 laser Periorbital Resolution at 2 year F/U None Nerad and Anderson24
1 (F) CO2 laser (superpulsed) Periorbital Resolution at 2 year F/U Erythema with resolution Castro et al18
at 1 month F/U
8 (7F, 1M) CO2 laser (superpulsed Periorbital 2 excellent, 3 good, 2 NR Apfelberg et al25
and continuous) poor, and 1 fair
response
4 (3F, 1M) CO2 laser (superpulsed) Infraorbital cheek 2 complete responses, 1 1 case with Sajben et al26
80% response, and 1 hypopigmentation
incomplete ([50% that resolved
lesions present)
35 (34F, 1M) CO2 laser (superpulsed) Periorbital 3 near total ([75%), 15 NR Cho et al27
marked (51-75%), 12
moderate (26-50%),
and 5 minimal (0-25%)
29 (NR) CO2 laser (drilling Periorbital 7 near total ([75%), 10 NR Lee et al28
method) marked (51-75%), 8

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moderate (26-50%),
and 4 minimal (0-25%)
1 (F) CO2 laser (vaporization Forehead No lesions at 2 year F/U None Wheeland et al29
mode)
Continued

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Supplemental Table II. Contd

VOLUME jj, NUMBER j

J AM ACAD DERMATOL
Anatomic site of
No. of cases (sex) Treatment modality involvement treated Results of treatment Adverse side effects Reference
25 (NR) CO2 laser (vaporization Facial No lesions with no None at 6 month-4 yr F/U Wheeland et al29
mode) recurrence at 6 mos to
4 years of F/U
1 (F) CO2 laser with Eruptive facial Good results but not Hyper- and Frazier et al30
trichloroacetic acid resolved at 9 mos F/U hypopigmentation at
9 month F/U
20 (F) CO2 laser with Periorbital 11 excellent, 6 good, and Erythema and Kang et al31
trichloroacetic acid 3 fair-initial hyperpigmentation
which cleared by
3 mos
6 (F) CO2 laser with temporary Periorbital Good to excellent at No scarring or erythema Park et al32
tattooing and Q- 1 wk F/U
switched alexandrite
laser
5 (4F, 1M) CO2 laser with Periorbital Good results significant No scarring or Hasson et al33
radiofrequency improvement in size dyspigmentation at
and number at 24 month F/U
24 mos F/U
1 (F) Argon laser Vulvar Resolution at 2 mos F/U Initial blistering which Kopera et al34
healed within a week
2 (F) Intralesional insulated Periorbital High satisfaction No ASE with no Hong et al35
needles recurrence at
6 months
18 (F) Low voltage Periorbital 11 marked ([70%) and 7 Redness, pain, swelling Al Aradi36
electrocoagulation moderate (50-70%) and
improvement of hyperpigmentation at
lesions at 6 wks 2 weeks.
1 (F) Topical tretinoin Neck, trunk, arms Flattened, flesh-colored NR Gomez et al37

Williams and Shinkai 7.e8

(eruptive)
1 (F) Topical atropine Chest, neck (eruptive) Improvement in pruritus None Sanchez et al38
and discrete reduction
in size of lesions
12 (10F, 2 M) Intralesional Periorbital Complete resolution with Hyperpigmentation Karam and Benedetto39
electrodesiccation no recurrence F/U 12- which resolved in
48 mos 3 months
2 (F) Oral isotretinoin Eruptive Flattened, softened, skin NR Mainitz et al40
colored at 6 mos F/U
Continued
Supplemental Table II. Contd

7.e9 Williams and Shinkai

Anatomic site of
No. of cases (sex) Treatment modality involvement treated Results of treatment Adverse side effects Reference
1 (F) Oral isotretinoin Eruptive No change NR Janniger and Brodkin41
2 (F) Oral tranilast Eruptive Good improvement with Bladder irritation in 1 Horie et al42
no deterioration after case
discontinuation of
drug
1(F) Oral tranilast Vulvar Remarkable NR Iwao et al43
improvement with no
recurrence at 6 mos
postmedication
completion
1 (F) Dermabrasion Eyelids, lips, scattered Very little recurrence NR Roenigk Jr44
face 6 mos F/U
1 (F) Surgical excision Periorbital Total satisfaction at None at 6 months F/U Moreno-Gonzales and
6 mos F/U Rios-Arizpe45
1 (F) Surgical excision Periorbital Cosmetically acceptable NR Maloney46
appearance
2 (F) Fractional Periorbital Positive clinical results NR Akita et al47
photothermolysis with high patient
satisfaction

F, Female; F/U, follow-up; M, male; NR, not reported.

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