Molluscum contagiosum: The importance of early

diagnosis and treatment

Stephen K. Tyring, MD, PhD

Galveston, Texas

Molluscum contagiosum is a viral infection that is becoming an increasing problem in sexually active individuals

and in patients with human immunodeficiency virus. Although molluscum contagiosum lesions are generally

self-limiting, it may take 6 months to 5 years for lesions to disappear. Furthermore, patients with weakened

immune systems have increased difficulty in clearing lesions; therefore lesions typically persist for prolonged

periods. Although there has been continued debate about whether molluscum contagiosum lesions should be

treated or allowed to resolve spontaneously, many clinicians recommend treatment of genital molluscum

contagiosum lesions to reduce the risk of sexual transmission, prevent autoinoculation, and increase patient

quality of life. Treatment options for molluscum contagiosum include physician-administered and patient-

administered therapies. Novel patient-administered treatment options allow administration in the privacy of

a patient’s home, providing added convenience and reducing patient embarrassment or stress. With the novel

treatment opportunities currently available or in development, physicians are able to improve patient quality of

life while providing patients with a convenient, well-tolerated, easily administered treatment regimen. This

review summarizes the clinical diagnosis of molluscum contagiosum and provides a critical assessment of

several current and emerging treatment options. (Am J Obstet Gynecol 2003;189:S12-S16.)

Key words: Imiquimod, immune response modifier, molluscum contagiosum, poxvirus, sexuallytransmitted disease

Molluscum contagiosum is a viral infection that

produces raised, umbilicated lesions (ie, papules or

nodules) in the epidermal layer of the skin. Once

considered a benign disease usually observed in children,

molluscum contagiosum has also been recognized—

during the last 25 years—as a sexually transmitted disease

(STD) in adults. Although current statistics are lacking in

the United States, the overall incidence of molluscum

contagiosum accounts for approximately 1% of all

diagnosed dermatologic conditions.1 Furthermore, the

frequency of molluscum contagiosum appears to be

increasing. From 1966 to 1983, the number of mollus-

cum contagiosum-related visits to private physicians

by patients older than 15 years increased 11-fold.2 In

addition, patients 15 to 29 years were more likely than any

other age group to present with molluscum contagiosum

in STD clinics and private physician offices. Moreover, 5%

to 18% of patients with human immunodeficiency virus

(HIV) are infected with themolluscum contagiosum virus

(MCV).3

From the University of Texas Medical Branch.Received for publication January 30, 2003; accepted March 31, 2003.Reprint requests: Stephen K. Tyring, MD, PhD, Professor of Dermatol-ogy, Microbiology and Immunology, and Internal Medicine, Director,UTMB Center for Clinical Studies, University of Texas Medical Branch,301 University Blvd, Route 1070, Galveston, TX 77555. E-mail:styring@utmb.edu� 2003, Mosby, Inc. All rights reserved.0002-9378/2003 $30.00 + 0doi:10.1067/S0002-9378(03)00793-2

S12

The virus (genus Molluscipoxvirus) that causes

molluscum contagiosum is a member of the family

Poxviridae, of which smallpox is also a member. Three

subtypes of MCV have been identified, all of which have

a similar clinical presentation and are not localized to

a particular region of the body (eg, genital).4,5 Molluscum

contagiosum virus type 1 (MCV-1) is the most common

subtype detected in patients, whereas MCV-3 is rare.4,5

For example, an analysis of 106 MCV clinical isolates

indicated the occurrence of MCV-1, -2, and -3 as 80:25:1.5

In adolescents and adults, molluscum contagiosum is

most commonly transmitted by sexual contact.6 However,

MCV may be transmitted by casual contact, fomites, or

self-inoculation. The incubation time and communicabil-

ity of MCV have not been determined; however, the

average incubation period for MCV in humans ranges

from approximately 14 to 50 days.7 Molluscum contagio-

sum lesions are generally self-limiting, but it may take 6

months to 5 years for lesions to disappear.3 In addition,

patients with weakened immune systems (eg, patients with

HIV) have increased difficulty clearingMCVandmay thus

exhibit lesions for prolonged periods.

Because molluscum contagiosum is considered an STD

in adolescents and adults, obstetricians and gynecologists

should be aware of the clinical features of genital

molluscum contagiosum. Therefore, the clinical diag-

nosis of genital molluscum contagiosum is discussed and

a critical assessment of several current and emerging

treatment options is presented.

Volume 189, Number 3SAm J Obstet Gynecol

Tyring S13

Diagnosis

Diagnosis of genital molluscum contagiosum is gener-

ally made by clinical examination of lesions (Fig 1).8

Lesions caused by MCV typically appear as white, pink, or

flesh-colored, umbilicated, raised papules (1 to 5 mm in

diameter) or nodules (6 to 10 mm in diameter).9

Molluscum contagiosum lesions may occur as single or

multiple lesions (usually <30 papules). Key characteristics

are summarized in Table I. Although patients are usually

asymptomatic, theymay present with eczema surrounding

the lesion andmay experience pruritus or tenderness. On

rare occasions, in addition to the presence of lesions in

the genital region or on the lower abdomen, sexual

transmission may also result in intraoral or perioral

clinical manifestations, particularly in immunocompro-

mised patients.10

Immunocompromised patients may present with atyp-

ical manifestations of molluscum contagiosum, includ-

ing differences in morphology and growth patterns. For

example, patients with HIV tend to develop giant (>1

cm) lesions (Fig 2) or may have clustering of hundreds of

small lesions.6,9 Furthermore, molluscum contagiosum

lesions in patients with HIV do not resolve quickly, are

spread easily to other locations (eg, face), and are typically

refractory to common treatments.

Differential diagnosis includes condylomata acuminata

and vulvar syringoma for multiple small MCV lesions and

Fig 1. Classic pink umbilicated genital molluscum contagiosumpapule. Reprinted with permission from Diven.8

squamous or basal cell carcinoma for large, solitary

lesions. Analysis of biopsy specimens of lesions with

hematoxylin and eosin staining to identify epidermal

changes may facilitate a more definitive diagnosis. If geni-

tal molluscum contagiosum is identified, patients should

also be tested for other STDs as a precautionary measure.

Treatment options

Because molluscum contagiosum is considered a self-

limiting disease, debate continues about whether lesions

associated with this disease (MCV lesions) should be

treated or allowed to resolve spontaneously. Many clini-

cians recommend treatment of genital MCV lesions to

reduce the risk of sexual transmission and to prevent

autoinoculation. Although MCV lesions will generally

resolve if left untreated, the resolution rate is extremely

variable3and immunocompromisedpatientsareatgreater

risk for secondary inflammation and bacterial infection.

In addition to the risk for transmission to sexual

partners, some patients may experience pain and discom-

fort that adversely affect theirquality of life. Emotional and

psychological discomfort, particularly embarrassment,

Fig 2. Giant molluscum contagiosum lesion in HIV-infectedpatient.

Table I. Genital molluscum contagiosum

Epidermal viral infectionGenus Molluscipoxvirus3 subtypes

TransmissionDirect bodily contact (eg, sexual activity)Fomites (eg, underwear)Self-inoculation

14- to 50-d incubation period

Clinical presentationWhite, pink, or flesh-colored, umbilicated, raised papules(1-5 mm in diameter) or nodules (6-10 mm in diameter).

Lesions are self-limitingMay take 6 months to 5 years for lesion disappearance in theabsence of therapeutic intervention.

September 2003Am J Obstet Gynecol

S14 Tyring

mayalsobeassociatedwithgenitalMCVlesions.Therefore,

it would be advantageous in most cases for physicians to

treat MCV lesions, provided the treatment was safe,

effective, painless, and convenient to administer. Several

treatment options, both physician-administered and

patient-administered, for genitalMCV lesions are available

(Table II).

Physician-administered treatment options. Physicians

usually treat MCV lesions as they would treat warts caused

by human papillomavirus. Small lesions are commonly

removed by physical ablation of infected tissue and may

involve local excision by electrocautery, curettage, or

cryotherapy.11 Unfortunately, even with application of

a local anesthetic, these ablative procedures are associated

with pain, irritation, soreness, and mild scarring. Fur-

thermore, repeated treatments requiring additional office

visits may be necessary. The success of these physical

ablative procedures for genital MCV lesions has not been

rigorously evaluated, and high-quality, placebo-controlled

studies are lacking.12,13

Physician-administered chemical ablation has also been

used to treat genital MCV lesions. Acids such as

trichloroacetic acid have been applied to lesions.

However, controlling the depth of acid penetration can

be difficult and—as observed with physical ablation—

pain, irritation, and mild scarring are common.14 As an

illustration of the limitations in currently available

physician-administered chemical ablative procedures,

podophyllum resin (podophyllin) must be applied only

for a minimal period (eg, 1 to 4 hours) and then

thoroughly washed off. Because podophyllin is caustic

and may cause significant irritation, only a small number

of warts or limited area of skin should be treated at one

time. Furthermore, an increasing number of physicians

are no longer recommending this form of therapy

because of its low efficacy and significant toxicity.15,16

Patient-administered treatment options. In addition to

physician-administered treatments, several treatment

alternatives that may be self-administered in the privacy

of the patient’s home are available to patients with genital

MCV lesions. Podofilox (podophyllotoxin) is the active

component in podophyllum resin. Although not

indicated in the treatment of MCV lesions, podofilox is

Table II. Treatment options for molluscum

contagiosum lesions

Physician administeredElectrosurgeryCurettageCryosurgeryTrichloroacetic acidPodophyllin

Patient administeredPodofilox (podophyllotoxin)Retinoic acidImiquimod cream (immune response modifier)

approved in gel form for the treatment of cutaneous

(external) genital and perianal warts and as a topical

solution in the treatment of external warts. Several clinical

trials in patients with warts have demonstrated varied

response (clearance) rates (in 38% to 50% of patients)

after 2 to 4 weeks of treatment with podofilox. Common

adverse events have included burning, pain, inflamma-

tion, erosion, and itching.14 Retinoic acid (tretinoin) is

another form of chemical ablation that can be self-

administered and has been used topically to remove MCV

lesions.17 However, application of retinoic acid may cause

skin drying, peeling, irritation, and soreness.14

In addition to therapies that involve physical or

chemical ablation of MCV lesions, a novel patient-

administered topical treatment that uses localized

immune response modification has been used. Imi-

quimod is a member of a new class of drugs known as

immune response modifiers and is approved as a 5%

cream for the treatment of external genital and perianal

warts/condylomata acuminata in adults. Although the

mechanism of action of imiquimod has not been fully

elucidated, published studies indicate that imiquimod

indirectly activates antiviral activity by inducing cytokines,

including interferon alpha.18,19 The proposed mecha-

nism of action and demonstrated efficacy of imiquimod

against human papillomavirus (the causative agent for

genital warts) suggest that it might also be effective against

poxvirus, which causes molluscum contagiosum.

To determine the efficacy and safety of imiquimod

in the treatment of molluscum contagiosum, a small

number of clinical trials have been performed

(Table III).20-22 In 1 open-label study, 7 children and 8

adults with molluscum contagiosum (including 3 patients

with lesions in the anogenital region and 3 patients with

HIV) resistant to standard therapeutic treatment (eg,

salicylic acid, local surgery, and cryotherapy) self-admin-

istered 5% imiquimod cream once daily, 5 days per week,

for 4 to 16 weeks.20 After completion of therapy, 12 of 15

(80%) patients achieved either a complete clearance of

MCV lesions (8 patients) or a greater than 50% reduction

in lesion size (4 patients). There was no correlation of

response to HIV serostatus, gender, or atopic predis-

position. Furthermore, during the 32-week follow-up

period, only 1 patient had a recurrence develop at

a treated location, which occurred 10 weeks after

a complete clearance of initial lesions. Forty percent of

patients did not report any adverse events. In the

remainder of patients, the most commonly reported

adverse events were local inflammatory reactions, which

were generally mild and transient and included 7 (47%)

episodes of erythema, 5 (33%) cases of erosions, and 5

(33%) cases of pruritus. However, no patient discon-

tinued treatment because of adverse events.

An additional open-label study evaluated the safety

and activity of 5% imiquimod cream in the treatment of

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Tyring S15

Table III. Imiquimod therapy in the management of molluscum contagiosum

Study Patients, n TreatmentClearance of >50%reduction, n (%)

Hengge et al20 15 5% imiquimod cream, once daily, 5 d per wk, for 4-16 wks 12 (80)Liota et al21 23* 5% imiquimod cream, once daily, 3 times per wk, for maximum of 16 wks 18 (78)Syed et al22 50 1% imiquimod cream, 3 times daily for 5 d, for maximum of 4 wks 41 (82)

*Number of adult patients who completed the study.

molluscum contagiosum in adults and children.21

Focusing on the adult study population, 28 patients with

10 or more MCV lesions were treated with 5% imiquimod

cream 3 times a week for a maximum of 16 weeks. Of the

23 patients who completed the study, 18 (78%) exhibited

clearance of MCV lesions by week 16, with 10 (43%)

patients achieving clearance of MCV lesions by week 4.

Furthermore, all HIV-infected patients (n = 4) and 9 of 10

(90%) patients with genital MCVhad complete resolution

of MCV lesions. Of all the patients who had a response to

imiquimod immunotherapy, no patient experienced

a recurrence at a 3-month or longer follow-up examina-

tion. Imiquimod was also safe and well tolerated. No

patient discontinued treatment because of adverse events.

Only 5 (22%) of 23 patients required treatment for

pruritus, which resolved with 1% hydrocortisone (n = 4)

or 0.1% triamcinolone (n = 1).

In addition to open-label studies, a double-blind,

randomized, parallel-group study was conducted to

compare 1% imiquimod cream with placebo in the

treatment of MCV lesions.22 One hundred male adults

and adolescents had a total of 733 MCV lesions (mean,

7.3; majority on thighs or genitalia) of 2 to 5 mm in

diameter per lesion. These patients applied 1%

imiquimod cream or placebo at home 3 times daily for

5 consecutive days for a total of 4 weeks (maximum

60 topical applications). Patients were followed weekly for

12 weeks, then followed monthly for an additional

9 months. At week 4, treatment with 1% imiquimod

cream resulted in a complete response in 82% (41 of 50)

of patients and eliminated 86% (309 of 358) of MCV

lesions compared with a complete response in 16% (8 of

50) of patients and 17% (63 of 375) of lesions treated with

placebo (P < .0001; Fig 3).22 In addition, the MCV lesion

responses to imiquimod therapy were durable. Only 1 of

the 41 patients successfully treated with imiquimod cream

relapsed (at month 10).

Imiquimod cream was also well tolerated; only 18%

(9 of 50) of patients treated with imiquimod cream

experienced an adverse event and no patient discon-

tinued from the study. All 9 of these patients experienced

mild fever, and 6 patients also experienced mild pruritus.

Although this study administered imiquimod 1% cream,

which contains less active agent than the imiquimod 5%

cream approved for the treatment of warts, the results

of this study suggest that imiquimod therapy is safe

and highly effective for the treatment of molluscum

contagiosum.

Additional studies in small numbers of patients have

also suggested that imiquimod therapy may be useful in

the treatment of molluscum contagiosum. In an open-

label safety study, 13 children were treated with 5%

imiquimod cream nightly for 4 weeks.23 Although the

studywasnot designed to test efficacy, complete resolution

of the target lesions occurred in 33% (4 of 12) of patients

by the end of week 4. In addition, case studies have indi-

cated that imiquimod can clear MCV lesions in special

patient populations (eg, HIV-infected patients).24-26

These studies indicate that both 1% and 5% imiquimod

cream (only 5% cream is currently available) are well

tolerated, may be useful in the treatment of mollus-

cum contagiosum, and provide a novel treatment

opportunity—particularly in patients who experience

adverse reactions or who are refractory to other forms of

treatment.

Patient education. In addition to treatment for MCV

lesions, it is important for patients to receive guidance on

Fig 3. Percentage of patients cured andmolluscum contagiosumviral lesions cleared by week 4. Data from Syed et al.22

September 2003Am J Obstet Gynecol

S16 Tyring

MCV transmission. Patients should be reminded that after

treatment there is a risk for recurrence and a risk for

reinoculation/transmission between sexual partners.

Latex condoms may help prevent some skin-to-skin

contact, but patients should recognize that MCV does

not require mucous membrane contact to be transmitted

and that other areas, such as the anal region, will not be

protected. Furthermore, patients should be counseled

that the occurrence of genital molluscum contagiosum

might indicate the presence of other STDs.

Conclusions

Genital molluscum contagiosum is a viral infection of

which the incidence in sexually active adults is increasing.

Because molluscum contagiosum is not life-threatening,

debate continues regarding the value of therapeutic

intervention. Therefore, health care practitioners,

including obstetricians and gynecologists, should work

with each patient to determine whether and how

treatment should be administered. However, it is

recommended that physicians treat this contagion,

particularly in light of the availability of safe, efficacious,

and convenient treatment options. Novel patient-admin-

istered treatment options allow administration in the

privacy of a patient’s home, providing added convenience

and reducing patient embarrassment or stress. With the

novel treatment opportunities currently available,

physicians have the appropriate tools to improve patient

quality of life while providing patients a convenient,

well-tolerated, easily administered treatment regimen.

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