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Molluscum Contagiosum: An Update

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Recent Patents on Inflammation & Allergy Drug Discovery 2017, 11, 22-31
REVIEW ARTICLE
ISSN: 1872-213X
eISSN: 2212-2710

Inflammation
& Allergy
Drug Discovery

Molluscum Contagiosum: An Update

Alexander K.C. Leung1,*, Benjamin Barankin2 and Kam L.E. Hon3

Recent Patents on Inflammation & Allergy Drug Discovery

1
Department of Pediatrics, The University of Calgary, Alberta Children’s Hospital, Calgary, Alberta, Canada; 2Toronto
Dermatology Centre, Toronto, Ontario, Canada; 3Department of Paediatrics, The Chinese University of Hong Kong,
Shatin, Hong Kong

ARTICLE HISTORY
Received: February 28, 2017
Revised: May 15, 2017
Accepted: May 16, 2017
DOI:
10.2174/1872213X11666170518114456
Keywords: Cantharidin, central umbilication, cryotherapy, dome-shaped papules, poxvirus, epidemiology.
Abstract: Background: Molluscum contagiosum is a viral cutaneous infection in childhood that occurs
worldwide. Physicians should familiarize themselves with this common condition.
Objective: To review in depth the epidemiology, pathophysiology, clinical manifestations, complica-
tions and, in particular, treatment of molluscum contagiosum.
Methods: A PubMed search was completed in Clinical Queries using the key term “molluscum conta-
giosum”. Patents were searched using the key term “molluscum contagiosum” from
www.google.com/patents, http: //espacenet.com, and www.freepatentsonline.com.
Results: Molluscum contagiosum is caused by a poxvirus of the Molluscipox genus. Preschool and
elementary school-aged children are more commonly affected. The virus is transmitted by close physi-
cal contact, autoinoculation, and fomites. Typically, molluscum contagiosum presents as asymptomatic,
discrete, smooth, flesh-colored, dome-shaped papules with central umbilication from which a plug of
cheesy material can be expressed. Some authors suggest watchful waiting of the lesions. Many authors
suggest active treatment of lesions for cosmetic reasons or concerns of transmission and autoinocula-
tion. Active treatments may be mechanical (e.g. cryotherapy, curettage, pulsed dye laser therapy),
chemical (e.g. cantharidin, potassium hydroxide, podophyllotoxin, benzoyl peroxide, tretinoin,
trichloroacetic acid, lactic acid, glycolic acid, salicylic acid), immune-modulating (e.g. imiquimod,
interferon-alpha, cimetidine) and anti-viral (e.g. cidofovir). Recent patents related to the management
of molluscum contagiosum are also retrieved and discussed. These patents comprise of topical compo-
sitions and herbal Chinese medicine with limited documentation of their efficacy.
Conclusion: The choice of treatment method should depend on the physician’s comfort level with the
various treatment options, the patient’s age, the number and severity of lesions, location of lesions, and
the preference of the child/parents. In general, physical destruction of the lesion, in particular, cryother-
apy with liquid nitrogen and chemical destruction with cantharidin are the methods of choice for the
majority of patients.

1. INTRODUCTION to the management of molluscum contagiosum are also

Molluscum contagiosum is a common cutaneous infec-
tious disease caused by a poxvirus and generally observed
in children [1-3]. The condition was first described by
Bateman in 1817 [4]. Spontaneous resolution of the lesions
is the norm in individuals with a normal immune system,
although the condition can last for many months. A variety
of treatment options are available, including watchful wait-
ing [1]. Active treatments may be mechanical, chemical,
immunomodulatory, and anti-viral. Recent patents related
*Address correspondence to this author at The University of Calgary,
Alberta Children’s Hospital, #200, 233 - 16th Avenue NW, Calgary, Alberta,
Canada, T2M 0H5; Tel: (403) 230 3300; Fax: (403) 230-3322;
E-mail: aleung@ucalgary.ca
discussed.
2. ETIOLOGY
Molluscum contagiosum is caused by a poxvirus of the
molluscipox genus in the Poxviridae family [5]. Molluscum
contagiosum virus (MCV) is a large brick-shaped, double-
stranded deoxyribonucleic acid (DNA) virus 200 to 3000 nm
in length [6]. The virus genome is covalently linked at both
ends and encodes 182 proteins, of which 105 have direct coun-
terparts in orthopoxviruses [7, 8]. MCV has 4 major subtypes:
MCV-1 being the most common subtype (75 to 96% of cases),
followed by, in the order of decreasing frequency, MCV-2,
MCV-4, and MCV-3 [5, 9-11]. Virtually all pediatric cases are
caused by MCV-1 [12]. On the other hand, MCV-2 affects

2212-2710/17 $100.00+.00 © 2017 Bentham Science Publishers

Molluscum Contagiosum Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 23
teenagers and adults and is mainly sexually transmitted [13].
In patients with human immunodeficiency virus (HIV) infec-
tion, MCV-2 accounts for approximately 60% of MCV infec-
tions [12]. Thus, molluscum contagiosum associated with HIV
does not represent recurrence of childhood MCV infection
[12]. In general, an individual infection is usually caused by
only one subtype of the virus [14].
3. EPIDEMIOLOGY
Molluscum contagiosum occurs worldwide but is more
common in areas with tropical and humid climates [1, 15, 16].
The only known host for MCV is humans [5, 9, 17]. Epidemi-
ologic data on the incidence of molluscum contagiosum are
few and most have focused on rates of molluscum contagio-
sum infection or risk factors for infection in specific popula-
tion subgroups. It is estimated that the infection accounts for
approximately 1% of all diagnosed dermatological conditions
[8, 11, 18]. Reynolds et al. analyzed data of outpatient visit
records listing molluscum contagiosum as a diagnosis in the
Indian Health Service National Patient Information Reporting
System in the United States during 2001 to 2005 [19]. The
authors found that the average annual rate of molluscum con-
tagiosum-associated outpatient visits was 20.15 per 10,000
American Indian and Alaska Native persons. Kyriakis et al.
carried out an 8-year comparative study on 50,237 consecu-
tive, self-referred, Greek patients aged 35 days to 96 years
seen in a general state hospital dermatology teaching clinic
[18]. The authors found that approximately 60% of cases oc-
curred in individuals less than 20 years of age. Yearly detec-
tion rates fluctuated significantly (range, 2.3 to 6.3%, p =
0.01). In a study of 332,330 patients in Netherlands, approxi-
mately 17% of children aged 15 years had visited their doctor
for molluscum contagiosum at least once [20]. More recently,
Olsen et al. performed a systematic review of 8 articles
(n = 12,627) that reported the prevalence of molluscum conta-
giosum [21]. The authors found an overall reported prevalence
in the pediatric age group between 5.1% and 11.5%.
Molluscum contagiosum is rare in children under one
year of age [22]. Congenital molluscum contagiosum, in
particular, has very rarely been reported [23, 24]. The condi-
tion is most common in preschool and elementary school-
aged children [1-3, 9, 18, 25]. The sex ratio is approximately
equal [21]. Molluscum contagiosum is associated with pov-
erty, poor hygiene, and over-crowded conditions [26]. The
virus is transmitted by close physical contact, autoinocula-
tion, and, occasionally, contaminated fomites (e.g., clothing,
bath sponges, towels), especially if the skin is wet [1, 6, 12,
27, 28]. However, it is unclear whether the disease can be
transmitted by simple contact of seemingly intact lesions or
whether breaking of a lesion is essential for the transmission.
Children are particularly susceptible to autoinoculation, for
example, via rubbing or scratching. This may explain why
the lesions are often found in clusters. In adults, the disease
is spread mainly by sexual contact and is typically found in a
bathing-trunk distribution [29]. The virus can also be trans-
mitted by tattoos [30]. Swimming in community swimming
pools has been implicated as a source of infection [21, 31].
Vertical transmission of the virus from mother to infant
has also been reported, although it is not common [13, 32].
MCV infection may occur during delivery via an infected
birth canal or via an ascending infection after premature rup-
ture of membranes [7, 13, 22]. Vertical transmission of MCV
accounts for the majority of molluscum contagiosum cases
seen in the first 6 weeks of life [9, 22].
Although molluscum contagiosum is seen primarily in
healthy individuals, individuals with immunodeficiency (es-
pecially those with HIV infection) and atopic dermatitis are
at increased risk [1-3, 10, 15, 33-35]. Between 5 and 18% of
individuals with HIV infection are coinfected with MCV
[16]. The disease is also more common in sexually active
individuals [12].
4. PATHOPHYSIOLOGY
Histological examination shows a lobulated circum-
scribed lesion with epithelial hyperplasia with accelerated
keratinization and downward displacement of the basement
membrane [36]. Perilesional stroma shows fibroedematous to
fibromyxoid changes in many cases [37]. Immunohisto-
chemical studies with anti-CD34 monoclonal antibodies
show a tightly enclosing fine vasculature around lesions of
molluscum contagiosum [38]. Within the area of epithelial
hyperplasia, keratinocytes contain numerous discrete, ovoid,
large eosinophilic intracytoplasmic inclusion bodies
(Henderson-Patterson bodies or molluscum bodies), com-
pressing the nucleus against the cell membrane, resulting in a
signet-ring appearance [8, 15, 36-39]. Prominent nucleoli
and amphophilic cytoplasm with clear vacuolization are
common [37]. Electronic microscopy shows the characteris-
tic brick-shaped viral particles inside the intracytoplasmic
inclusion bodies [31].
MCV infects epithelial cells and replicates in the stratum
spinosum of the epidermis [9]. Replication of the virus within
the cytoplasm of keratinocytes leads to proliferation and hy-
pertrophy of keratinocytes with the characteristic viral intracy-
toplasmic inclusion bodies [39]. The intracytoplasmic inclu-
sion bodies contain large number of virions sealed off intracel-
lularly by a collagen and lipid-rich sac-like structure [39].
These eosinophilic intracytoplasmic inclusion bodies can best
be demonstrated with hematoxylin-eosin stain [5, 10, 35].
With the death and rupture of the host cell, MCV particles are
released which may infect new epithelial cells [40].
5. CLINICAL MANIFESTATIONS
The incubation period ranges from 2 to 7 weeks, but can
be as long as 26 weeks [5, 10, 11]. Typically, molluscum
contagiosum presents as discrete, smooth, firm, dome-
shaped, waxy papules with characteristic central dell or um-
bilication from which a plug of cheesy material which con-
tains dead epithelial cells and virus particles can be ex-
pressed (Fig. 1) [1, 2, 41]. The color can be pearly white,
yellow, flesh-colored, translucent, pink or red (especially
when irritated) [1, 5, 29]. The lesions are most common in
areas of skin rubbing or moist regions [25]. In children, le-
sions most commonly affect the extremities (particularly the
intertriginous areas), trunk, and less commonly, face [5, 29].
In adults, lesions are more common on the lower abdomen,
upper thighs, pubic area, anus, and genital area [12, 37].
Atypical locations include the nipples [42, 43], areolae [42],
conjunctiva [44], oral mucosa [14], lips [45], eyelids [46],
scalp [47], and soles [48].
24 Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 Leung et al.

Fig. (2). Examination of a molluscum contagiosum lesion under a

Fig. (1). Note the flesh-colored, pearly, umbilicated papules of
magnifying lens shows a dome-shaped papule with central umbili-
molluscum contagiosum lesions on the right axilla and chest.
cation.

Lesions are usually 1 to 5mm in diameter and the number shows a central umbilication with well-defined polylobular,
is usually less than 20 [6]. They often appear in clusters or in roundish or four-leaved clover-like, white to yellowish
a linear pattern (e.g. autoinoculated) [25, 49]. Less com- amorphous structures surrounded by a peripheral crown of
monly, the lesion can be solitary at the time of presentation reddish, linear or branched vessels (Fig. 3) [61-63]. Although
[50]. Central umbilication can be hard to observe in small molecular methods such as polymerase chain reaction (PCR)
lesions and young children [1, 8]. The lesions are usually may be of great value for clinical and epidemiological stud-
asymptomatic but may sometimes itch or become irritated ies of MCV infections, they are not routinely used in clinical
[16]. In congenital cases, the lesions appear in a halo-like practice. Excision and histopathologic examination should be
ring around the scalp [7]. Rarely, a pale, hypopigmented halo reserved for those with atypical morphology which renders
or ring (Woronoff ring) around molluscum contagiosum le- the diagnosis difficult. Histopathologic examination shows
sions has been described (halo phenomenon) [51]. the characteristic large intracytoplasmic eosinophilic inclu-
sion bodies with hematoxylin-eosin staining [6, 10]. Re-
At point of regression, the lesion may appear inflamed cently, it has been shown that hand-held reflectance confocal
characterized by erythema and swelling, a finding which microscopy allows in vivo horizontal scans of the superficial
signifies pending resolution of the lesion [9, 14, 52]. The layers of the skin, with a resolution comparable to histopa-
acronym "BOTE" sign (for beginning of the end) has been thology [62]. Thus, the hand-held reflectance confocal mi-
proposed to help underscore the significance of the inflamed croscopy is a fast, non-invasive tool that can be used for the
lesion as an expected variation in the evolution of immune diagnosis of molluscum contagiosum.
response to the MCV rather than bacterial superinfection
[53]. In one study, patients with inflamed molluscum conta-
giosum lesions were less likely to have an increased number
of lesions over the next 3 months than patients without in-
flamed lesions [52]. Likewise, an id reaction to MCV may
herald immunological clearance of molluscum contagiosum
lesion in an immunocompetent individual [54].
In individuals with immunodeficiency, the lesions can be
extensive and of a large size [5, 55-58]. Occasionally, it may
reach a size greater than 1 cm in diameter (giant molluscum
contagiosum) [59]. Also, the lesions may occur in atypical
locations and may be atypical in appearance such as verru-
cous and hypertrophic [36, 58]. The lesions tend to be rap-
idly progressive, disseminated, recalcitrant to treatment, and
frequently recurring [36, 60].
Fig. (3). Dermatoscopic examination of a molluscum contagiosum
6. DIAGNOSIS lesion shows a discrete, non follicular, pearly white papule. The
epidermal papule has distorted skin surface markings.
The diagnosis is predominantly clinical. The discrete,
smooth, flesh-colored, dome-shaped papules with central 7. DIFFERENTIAL DIAGNOSIS
umbilication are pathognomonic. A magnifying lens or der-
moscopy aids visualization of the central umbilication which Molluscum contagiosum should be differentiated from
may not be obvious to the naked eye (Fig. 2). Dermoscopy acne vulgaris, chickenpox, common warts (verruca vulgaris),
Molluscum Contagiosum Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 25
papular acrodermatitis of childhood (Gianotti-Crosti syn-
drome), milia, syringomas, Fordyce spots, papular urticaria,
eruptive xanthomas, steatocystoma multiplex, folliculitis,
condyloma acuminatum, lichen striatus, and lichen planus [1,
11, 64]. A giant molluscum contagiosum may mimic an
acantholytic acanthoma, epidermoid cyst, and subepidermal
calcified nodule [65, 66].
Acne vulgaris is characterized by noninflammatory fol-
licular papules or comedones and by inflammatory papules,
pustules, and nodules in its more severe forms [67]. The
pathognomonic lesion is the comedo, which may be either
open or closed [67]. Acne lesions tend to occur on the face,
and to a lesser extent, on the upper chest and back [67]. The
condition is most common during adolescence.
The lesions of chickenpox start as rose-colored macules,
and progress rapidly to become papules, vesicles with the
classic “dew drop on a rose petal” appearance, pustules and,
finally, crusts [68, 69]. New lesions appear in successive
crops every one or two days, with two to four crops develop-
ing over the course of the illness. The total number of lesions
typically varies between 250 and 500. Characteristically,
lesions in different stages of development are present
throughout the first week of illness. The skin rash is usually
intensely pruritic. The distribution of the lesions is typically
central, with the greatest concentrations on the trunk. Scar-
ring may result from chickenpox but usually not from mol-
luscum contagiosum [68].
Common warts (verruca vulgaris) are asymptomatic,
well-circumscribed, small papule/nodule with a hyperkera-
totic and verrucous surface [70]. The lesions are usually yel-
low, grayish brown or flesh-colored. When the surface is
pared away, characteristic punctate black dots which repre-
sent thrombosed capillaries become visible [64]. Sites of
predilection include the fingers, dorsum surfaces of hands,
toes, elbows, knees, and face [70].
Papular acrodermatitis of childhood (Gianotti-Crosti syn-
drome) is characterized by an acute onset of multiple,
monomorphous, flat-topped, pink to red-brown papules or
papulovesicles [71]. Typically, the lesions are symmetrically
distributed on the extensor surfaces of the extremities [71].
Truncal lesions, when present, are usually mild and transient.
Milia are small (generally less than 3mm), white, benign,
dome-shaped, superficial keratinous cysts. While congenital
primary milia favor the nose, benign primary milia of chil-
dren and adults favor the eyelids.
Typically, syringomas present as small, soft to firm, skin-
colored to slightly yellowish papules [72]. The papules are
usually 1 to 3mm in diameter, asymptomatic, and symmetri-
cally distributed. The lesions may be solitary or, most often,
multiple. The distribution may be localized or generalized.
Localized syringomas are the most common clinical variant
and the lesions are usually found in the periorbital areas [72].
Generalized syringomas are found mainly on the chest and
neck, followed by the forearms.
Clinically, Fordyce spots appear as asymptomatic, iso-
lated or grouped, minute (pinhead-sized), creamy yellow,
discrete papules [73]. They occur most commonly and most
conspicuously on the vermilion border of the lips and oral
mucosa and, less commonly, on the penis, scrotum, and labia
[73]. The lesions are usually bilateral and symmetrical. On
the penile shaft, these papules are more obvious when the
foreskin is stretched or during penile erection. A thick,
chalky or cheesy material can sometimes be expressed by
squeezing the lesion.
Papular urticaria is characterized by intensively pruritic
grouped or disseminated urticarial papules caused by hyper-
sensitivity to insect bites or stings. Some lesions have a cen-
tral punctum. The condition is most commonly seen in chil-
dren 3 to 10 years of age and is most common in the summer
and late spring.
Eruptive xanthomas are characterized by an abrupt onset
of yellow-orange papules that appear in crops [74]. Sites of
predilection include the extensor surfaces of extremities and
buttocks. Eruptive xanthomas are highly suggestive of hy-
perlipidemia [74].
Clinically, steatocystoma multiplex is characterized by
multiple, asymptomatic, smooth, round, soft, movable, yel-
low to skin-colored papules and nodules [75]. Lesions tend
to be a few millimeters to a centimeter in diameter and are
slow growing. Superficial lesions are usually yellowish
while deeper lesions skin-colored. The overlying epidermis
is normal with no central punctum present. The content is
usually oily or creamy. Sites of predilection include the
chest, and less often the neck, axillae, proximal extremities,
and groin where high numbers of sebaceous glands are
found.
Folliculitis typically presents as small, discrete, pustules
with an erythematous base, located at follicular orifices. Hair
growth is unimpaired.
The lesions of condyloma acuminata usually begin as
soft, flesh-colored, flat or ragged papules. They may coa-
lesce to form velvety plaques, discrete warty papules, or cau-
liflower growths. Condyloma acuminata typically occur in
the perianal areas.
Lichen striatus is characterized by an abrupt onset of dis-
crete, flesh-colored, pink, tan, or erythematous, flat-topped
papules, 1 to 3mm in diameter [76]. Papules often coalesce
to form a continuous or interrupted linear band over a few
weeks. The linear band may develop a curved appearance as
it follows Blaschko lines.
Cutaneous lichen planus is characterized by 6 Ps: planar
(flat-topped), purple (violaceous), polygonal, pruritic, pap-
ules/plaques that affect the skin [77]. Lesions of lichen
planus are often superimposed by lacy, reticular, white lines
known as 'Wickham striae'. Sites of predilection include the
flexor aspects of the wrists and ankles, dorsa of hands, trunk,
shins, and glans penis. The distribution is often symmetric.
Just like with psoriasis, the Koebner phenomenon is particu-
larly characteristic [77].
Acantholytic acanthoma is a benign tumor of the skin
characterized histologically by prominent acanthosis and
acantholysis [78]. Clinically, acantholytic acanthoma pre-
sents as an asymptomatic, keratotic papule or nodule, usually
on the trunk [78]. The condition occurs mainly in elderly
patients with a male to female ratio of 2: 1 [78].
Typically, an epidermoid cyst presents as a fluctuant to
firm, dome-shaped lesion that is attached to the skin but not
26 Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1
attached to the underlying structure. A punctum may be
noted. It has a tendency to grow slowly.
A subepidermal calcified nodule typically presents as a
dome-shaped, firm, well-circumscribed papule or nodule
with a smooth or verrucous surface [65]. The color can be
yellow-white or erythematous. The lesion is usually solitary
and occurs more often in the head and neck area [65].
In immunocompromised individuals, the differential di-
agnosis would also include: cryptococcosis, histoplasmosis,
penicilliosis, aspergillosis, and coccidomycosis [14, 15, 79].
8. COMPLICATIONS
Molluscum lesions can be cosmetically unsightly and
embarrassing and may cause undue parental anxiety [80].
This is especially so for giant or extensive lesions on ex-
posed areas [81]. Other complications include secondary
bacterial infection, irritation, inflammation, conjunctivitis,
and superficial punctate keratitis [1,7, 82, 83]. Secondary
bacterial infection is often secondary to scratching-induced
impetiginization [1]. Approximately 10% of affected patients
develop eczematous dermatitis around the molluscum conta-
giosum lesions [84]. The eczematous dermatitis usually sub-
sides spontaneously with the eradication of the molluscum
contagiosum lesions [7]. In some cases, the id reactions may
appear at sites distant from the molluscum contagiosum le-
sions [54]. Folliculitis and erythema multiforme due to mol-
luscum contagiosum are rare [85, 86]. Infection of an epi-
dermoid cyst by MCV is rare but has been described [87,
88]. Molluscum contagiosum-induced erythema annulare
centrifugum has also rarely been reported [89, 90].
9. TREATMENT
9.1. General Measures
To avoid spread of the infection, the importance of
avoidance of sharing of bed linen, towels, sponges, and bath-
tubs cannot be over-emphasized [10, 15]. Swimming in
pools and participation in contact sports can spread the virus
and should be discouraged [10, 15]. However, there is no
reason to keep these children home from daycare or school
[1, 3, 29]. Patients/parents should be advised not to scratch,
rub, pick or squeeze the lesions with their fingernails be-
cause the central plugs are laden with MCV particles that can
easily spread to uninfected skin.
9.2. Watchful Waiting
Some authors suggest watchful waiting of the lesions and
to await spontaneous resolution [6, 64, 91, 92]. This is espe-
cially so for those patients with mild disease and who are not
bothered by the lesions, as well as in cases where lesions
affect delicate areas such as the face or groin in young chil-
dren.
9.3. Active Treatments
In spite of the fact that molluscum contagiosum is self-
limiting, many authors suggest active treatment of lesions for
cosmetic reasons, social stigma associated with visible le-
sions, alleviation of discomfort including itching, or con-
cerns of transmission and autoinoculation [1, 16, 25, 27, 28,
Leung et al.
93, 94]. One major parental concern is that their child might
not be able to participate on various physical or team-based
activities such as gymnastics and swimming for a long time
till all lesions are resolved [93]. Active treatments may be
mechanical, chemical, immunomodulatory, and anti-viral [1,
2, 5, 26, 94].
9.3.1. Mechanical Methods
Mechanical methods (e.g. cryotherapy with liquid nitro-
gen, curettage, pulsed dye laser therapy) are generally quite
effective, but they subject children to a potentially painful
and traumatic experience [1, 80, 95]. Topical anesthesia such
as with a eutectic mixture of local anesthetics (EMLA) ap-
plied over the lesions with occlusion for an hour or Nanorap
(a hydrogel with 2.5% lidocaine and 2.5% prilocaine with
50% of active products in nanocapsules) applied over the
lesions without occlusion 20 minutes before the procedures
should be considered [96, 97]. Topical anesthetics help to
reduce the discomfort/pain which can be disturbing for some
children.
Cryotherapy is an effective treatment for molluscum con-
tagiosum. Liquid nitrogen can be applied by spray or a cot-
ton-tip applicator directly to and 2 mm surrounding the le-
sion [31]. Adverse effects include pain, erythema, vesicle
formation, and dyspigmentation [9].
Curettage which involves the physical removal of the
lesion with a curette is an effective method of treating mol-
luscum contagiosum [17]. In one study, 70% of 1,878 chil-
dren treated with curettage were cured after one session of
treatment [97]. The success rate depends on the skill and
experience of the operator, as well as the number and distri-
bution of the lesions. Adverse effects include pain, minor
bleeding, and scarring [17]. Curettage is not advisable for
those with atopic dermatitis because of the increasing num-
ber of molluscum contagiosum lesions and the greater risk
for scar formation.
Pulsed dye laser therapy is a safe, effective, and well-
tolerated method for treating molluscum contagiosum [98,
99]. Because pulsed dye laser is not readily available and the
treatment is costly, the procedure is usually reserved for the
treatment of recalcitrant molluscum contagiosum.
9.3.2. Chemical Methods
Chemical agents (e.g. cantharidin, potassium hydroxide,
podophyllotoxin, benzoyl peroxide, tretinoin, trichloroacetic
acid, lactic acid, glycolic acid, salicylic acid) work by pro-
ducing a local inflammatory response [25, 84].
Cantharidin, a phosphodiesterase inhibitor derived from
blister beetles (Lytta vesicatoria), has been shown to be safe,
effective, and relatively painless and is often the preferred
method for young children [25, 80, 100, 101]. It is recom-
mended that the medication be applied carefully to the center
of individual lesions usually with the blunt end of a cotton
swab and covered for 2 to 6 hours (or much less time with
stronger preparations such as Cantharidin plus) after which it
should be washed off with soap and water [35, 29]. The pro-
cedure can be repeated every 2 to 4 weeks until all lesions
have resolved [35]. Treatment with cantharidin has been
found to be effective and has a high parental satisfaction rate
Molluscum Contagiosum Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 27
[9, 94, 100-102]. Although the use of cantharidin is not pain-
ful at the time of application, it may lead to later discom-
fort/pain, pruritus, blister formation, and postinflammatory
dyspigmentation (especially in dark skinned individuals) [9,
95, 102]. Occlusion or use in intertriginous areas should be
avoided because of the risk of increased inflammatory reac-
tions [31].
Potassium hydroxide, in concentrations of 5 or 10%, is a
safe, efficient, and inexpensive treatment of molluscum con-
tagiosum [17, 26, 103-106]. The medication is applied di-
rectly on the lesion twice a day or every other day for about
7 days or until an inflammatory response has developed [17,
103]. Adverse effects include burning/stinging and dyspig-
mentation at the site of application [17].
Podophyllotoxin (Podofilox), a plant resin that causes
tissue necrosis by arresting mitosis, can also be used in the
treatment [31]. The recommended treatment is topical appli-
cation twice daily for three consecutive days per week for up
to 6 weeks [14, 17, 31]. The medication can be applied at
home. Adverse effects include burning, pruritus, irritation,
xerosis, erythema, erosion, and postinflammatory pigmen-
tary changes [7, 17, 31]. The medication is not recommended
for pregnant women because of potential toxicity to the fe-
tus.
Other chemical preparations that have been used in the
treatment of molluscum contagiosum include benzoyl perox-
ide, tretinoin, trichloroacetic acid, lactic acid, glycolic acid,
and salicylic acid [14, 106]. These agents are applied directly
to the lesion.
9.3.3. Immunomodulatory Methods
Immunomodulatory agents (e.g. imiquimod, interferon-
alpha, cimetidine) work by enhancing the local release of
cytokines such as -interferon, which promote destruction
and regression of viral infections [10, 60, 80, 107].
Topical imiquimod was once considered beneficial in the
treatment of molluscum contagiosum. However, two large,
well designed, randomized, double-blind, vehicle-controlled
trials (n = 702; age 2 to 12 years) failed to demonstrate the
efficacy of 5% imiquimod over placebo in the treatment of
molluscum contagiosum [108, 109]. As such, imiquimod is
no longer recommended for the treatment of molluscum con-
tagiosum.
Interferon-alpha, a glycoprotein cytokine, is typically
reserved for immunocompromised patients with severe, re-
fractory lesions [17, 31]. It is usually given subcutaneously,
although it can also be given intralesionally [17, 31].
Oral cimetidine, a H2-receptor antagonist, presumably
works by enhancing cell-mediated immunity against MCV
[31]. The recommended dose is 25 to 40 mg/kg/day. The
medication is safe, painless, and well tolerated. Lesions on
the face do not respond as well compared with lesions else-
where on the body.
9.3.4. Anti-Viral Therapy
Anti-viral therapy with topical or intravenous cidofovir
has also been used for immunocompromised patients with
severe, refractory lesions [7, 17, 110]. Because intravenous
cidofovir may lead to nephrotoxicity, topical cidofovir is
preferred [7, 17]. The medication, in the form of 1 to 3% gel
or cream, can be applied to the lesion daily 5 days per week
until resolution, typically 6 to 8 weeks [31]. Adverse effects
of topical cidofovir include irritation, erosion, post-
inflammatory pigmentary changes, and superficial scars at
the site of application [17].
A Cochrane systematic review in 2009 of 11 randomized
controlled trials (n = 495) examining the effects of topical (9
studies), systemic (1 study), and homoeopathic (1 study)
interventions showed that there was insufficient evidence to
suggest superiority of any particular treatment [16]. A more
updated systematic review is needed as there have been more
studies showing effectiveness of many therapeutic agents
since the publication of the Cochrane systematic review.
9.4. Treatments of Choice
The choice of the treatment method should depend on the
physician’s comfort level with the various treatment options,
the patient’s age, the number and severity of lesions, location
of lesions, and the preference of the child/parents [1, 64].
The comparative efficacy, cost, adverse effects, ease of use,
and availability of the treatment method should be taken into
consideration [14]. In general, physical destruction of the
lesion, in particular, cryotherapy with liquid nitrogen and
chemical destruction with cantharidin are the methods of
choice for the majority of patients [31]. Anti-viral therapy is
usually reserved for recalcitrant molluscum contagiosum in
immunocompromised patients [1, 2, 5, 25, 60, 80].
10. PROGNOSIS
Most lesions resolve spontaneously without sequelae; the
mean duration of spontaneous resolution ranges from 6.5 to
13 months but may occasionally persist for years [3, 80,
111]. In a prospective community cohort study of 269 chil-
dren aged 4 to 15 years with molluscum contagiosum in the
UK, the mean time to resolution was 13.3 months [111]. In
30% of cases, lesions had not resolved by 18 months and in
13% of cases, lesions had not resolved by 24 months of age
[111]. In another study, the mean duration of spontaneous
resolution was 6.5 months in 205 (95%) of 217 Japanese
children with molluscum contagiosum [93]. Lesions tend to
last longer in those with coexisting atopic dermatitis [9]. In
those with immunodeficiency, lesions tend to persist [112].
CURRENT & FUTURE DEVELOPMENTS
A recent case report showed the successful use of topical
application of sinecatechins ointment in the treatment of re-
calcitrant molluscum contagiosum [113]. Padilla España et
al. treated a 5-year-old girl with a two years history of more
than 40 molluscum contagiosum lesions on her abdomen and
back with 10% sinecatechins ointment. The ointment was
applied to the top of the lesion twice a day for 4 weeks. All
the lesions had resolved when the patient was seen in one
month follow-up. Prior to that, the patient had been treated
with 10% potassium hydroxide for one month with minor
improvement. The main components of sinecatechins are tea
polyphenols, in particular flavonoids, 85% of which are
catechins. It is postulated that the therapeutic effects can be
attributed to the immunomodulatory, antiviral, antitumor,
28 Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1
and antioxidative properties of sinecatechins [113]. This new
finding warrants further investigations in randomized, pla-
cebo-controlled trials to further elucidate its clinical efficacy.
Another case report demonstrated that a topical solution
of 1% povidone-iodine in a dimethylsulfoxide vehicle is very
effective in the treatment molluscum contagiosum [114]. The
finding needs to be confirmed by future studies.
Recently, Gao et al. used a patented hyperthermia device
with an infrared emitting source to treat 21 patients with
molluscum contagiosum [115]. The targeted lesions received
local hyperthermia at a skin surface temperature of 44°C via
a heating probe once a week, with each treatment lasting 30
minutes, for a maximum of 12 weeks. Treatment was discon-
tinued when there were no lesions left. Of the 18 patients
who completed the study, 12 patients had complete resolu-
tion of all lesions, 2 patients had
50 % clearance of lesions,
and 4 patients had < 50% clearance of lesions. Adverse ef-
fects were negligible and consisted mainly of a mild burning
sensation at the time of treatment. Further studies are neces-
sary to confirm these new findings.
More recently, Viswanath et al. reported the successful
use of intralesional 5-fluorouracil in the treatment of recalci-
trant and/or extensive molluscum contagiosum [116]. 5-
fluorouracil is an antimetabolite with cytotoxic activity and
has an immunostimulatory mechanism [116]. Adverse ef-
fects of intralesional 5-fluorouracil therapy include pain,
erythema/hyperpigmentation, and ulceration [116].
Guan et al. have cloned and identified a novel and essen-
tial molluscum contagiosum target gene, mD4, which is es-
sential for processive DNA synthesis in vitro and which can
be inhibited by a small chemical compound that binds to
mD4 [117]. The authors have also engineered a hybrid vac-
cina virus (mD4-VV) in which the natural vaccinia D4 (vD4)
gene is replaced by the mD4 target gene. This hybrid virus is
dependent on mD4 for viral growth and is inhibited by the
small chemical compound that binds to mD4. This target
system provides a platform and approach for the discovery of
additional viral targets that can be used for the treatment of
molluscum contagiosum.
Johnson disclosed an anti-infective composition compris-
ing at least one anti-infective agent in a liquid carrier, such
as an organohalide for the treatment of molluscum contagio-
sum [118]. The liquid carrier includes a tissue penetrating
component for rapid penetration of the anti-infective agent
into the molluscum contagiosum lesion. The author claims
that topical application of the anti-infective composition to
molluscum contagiosum lesion causes the lesion to turn
black and fall off from the skin in less than about 5 days.
Shanler et al. patented a stable composition comprising
stabilized hydrogen peroxide and 2-propanol [119]. The
authors claimed that such composition may be used topically
to treat molluscum contagiosum.
Chen et al. disclosed an ointment mainly prepared from
six Chinese medicinal raw materials, namely radix scutel-
lariae, herba portulacae, fructus bruceae, peach kernel and
the like [120]. The authors claimed that the ointment is con-
venient to apply, safe and effective in the treatment of mol-
luscum contagiosum. Chen et al. also disclosed another topi-
cal liquid traditional Chinese medicine for external use
Leung et al.
which is effective and safe in the treatment of molluscum
contagiosum [121]. The liquid medicine is mainly formed by
rhizoma drynariae, isatis root, brucea javanica, safflower,
Pseudobulbus cremastrae seu pleiones and honeysuckle
flower.
Yang disclosed a traditional Chinese medicine for topical
treatment of molluscum contagiosum [122]. The medicine
composition is prepared from raw materials in parts by
weight as follows: 1 to 5 parts of honeysuckle, 5 to 10 parts
of indigowoad roots, 10 to 12 parts of raw coix seeds, 10 to
15 parts of poria cocos, 2 to 8 parts of radix arnebiae and 5 to
7 parts of erythrocin. The authors claimed that the medicine
is safe and convenient to use, free of toxic and side effects,
and not expensive.
Ma disclosed a topical traditional Chinese medicine for
treating molluscum contagiosum. The traditional Chinese
medicine comprises nidus vespae, a scallion juice, fructus
ulmi, yellow lycoris bulb, toad, resin of Garcinia hamburgy,
tobacco, chaulmoogra oil, orpiment, maritime dock, vervain,
Buchnera cruciata Ham., Portulaca grandiflora, Ardisia
japonica, roughhaired holly root, sunflower receptacles, Stel-
laria media, Clinopodium herb, Caulis fici tikouae and field
Sowthistle herb [123]. The author claimed that this tradi-
tional Chinese medicine has definite therapeutic effects, no
adverse effects effect, and a low recurrence rate.
Mechanical methods such as cryotherapy and curettage
for the treatment of molluscum contagiosum can be painful.
If using these modalities, it is desirable to apply topical anes-
thetics before the procedure to reduce the pain. Wang et al.
patented a topical traditional Chinese medicine that has a
good analgesic effect [124]. The traditional Chinese medi-
cine comprises Terminalia chebula Retz, Uncaria, Pagoda
tree pod, tuber fern, Elecampane inula root, Cudrania tricus-
pidata stem leaf, Chinese wampee leaf, Morus alba, Cala-
mint, Radix trichosanthis, Viola japonica, Alectoria asiatica
du Rietz, Reddish beautyberry leaf and Salvia. Huang
et al. patented another traditional Chinese medicine surface
anesthesia preparation for molluscum contagiosum treatment
[125]. The traditional Chinese medicine comprises the fol-
lowing raw materials: Halenia elliptica, Iindera glauca
leaves, Evodia lepta, Blumea lacera, Oenanthe javanica,
Aconitum taipeicum, Vernonia cinerea, Eragrostis minor,
Clinopodium chinense, Fordia cauliflora and Macleaya cor-
data.
CONCLUSION
Molluscum contagiosum is a common cutaneous viral
infection that is most common in preschool and elementary
school-aged children. Although some authors suggest watch-
ful waiting of the lesions and to await spontaneous resolu-
tion, many authors suggest active treatment of lesions. How-
ever, the literature on the efficacy of treatment of molluscum
contagiosum is very scarce and is based mainly on anecdotal
evidence and open studies. There are only a few published
head to head or randomized placebo-controlled trials. The
latter may be, in part, due to the difficulties of blinding cer-
tain treatments such as cryotherapy and laser therapy. So far,
none of the currently available therapy is Food and Drug
Administration (FDA)-approved for the treatment of mollus-
cum contagiosum. In addition, conclusive data regarding the
Molluscum Contagiosum Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 29
most effective treatment do not exist. It is hoped that future
well-designed, large-scaled, randomized, double-blind, and
ideally placebo-controlled studies will provide us with more
information on the efficacy and optimal regimen of the vari-
ous treatment methods including the present ones and those
in development. Until then, physical destruction of the le-
sion, in particular, cryotherapy with liquid nitrogen (espe-
cially in adults) and chemical destruction with cantharidin
(especially in children) are the methods of choice for the
majority of patients with molluscum contagiosum.
DISCLOSURE
This is an update of the article" Molluscum contagiosum"
which was published in Current Pediatric Reviews, with
permission from Bentham Science Publishers. [Leung AK,
Davies HD. Molluscum contagiosum. Curr Pediatr Rev
2012; 8(4): 346-9] [1].
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
Prof. Leung, Dr. Barankin, and Prof. Hon disclose no
relevant financial relationship. The authors confirm that this
article content has no conflict of interest.
ACKNOWLEDGEMENTS
Professor Alexander K.C. Leung is the principal author.
Dr Benjamin Barankin and Prof. Kam L. Hon are co-authors
who contributed and helped with the drafting of this manu-
script. The authors would like to thank Dr. Kin Fon Leong
for providing them with a magnifying view and a derma-
toscopic view of a molluscum contagiosum lesion.
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