British Association for Sexual Health and HIV national guideline for the management of Genital Molluscum in adults (2021)

Objectives

This guideline offers recommendations on diagnosis, treatment regimens and health promotion principles needed for the effective management of genital molluscum, including management of the initial presentation and recurrences. The primary focus is on infection which affects the genital area and has a sexual mode of transmission.

The guideline is aimed primarily at patients aged 16 years or older presenting to healthcare professionals working in departments offering level 3 care in STI management within the United Kingdom. However, the principles of the recommendations should be adopted across all levels; level 1 and 2 providers may need to develop local care pathways where appropriate.

Search strategy

PICO questions were set as:

POPULATIONS: individuals with genital molluscum contagiosum

INTERVENTION: management (including no treatment) for molluscum contagiosum

COMPARISON: no specific comparators were applied to ensure all relevant articles were picked up in the search

OUTCOME: clearance of molluscum, adverse effects

The following reference sources were used to provide a comprehensive basis for the guideline:

➢ Medline and Embase search (from 1980 till end of Dec 2018): the search strategy comprised the following terms in the title or abstract: Molluscum +/− contagiosum +/− genital. Only articles published in English were included in the search.

Methods

Article titles and abstracts were reviewed and if relevant, the full text article obtained. Priority was given to randomised controlled trial and systematic review evidence where available, and recommendations made and graded on the basis of best available evidence.

Piloting and feedback

The document was reviewed by the Clinical Effectiveness Group of the British Association for Sexual Health and HIV (BASHH), and their comments incorporated. The draft guideline was placed on the BASHH website for two months and any comments received during the consultation period were reviewed by the authors and acted on appropriately. The document was also piloted by target users and the public panel of BASHH, and their feedback considered by the authors.

Aetiology

Molluscum infection is a benign epidermal eruption of the skin, caused by molluscum contagiosum, a large DNA virus. Molluscum contagiosum belongs to the Poxviridae family and Molluscipox genus. ¹

Up to four subtypes of molluscum contagiosum have been identified by genotypic analysis^2–5; the commonest is MCV-1, followed by the MCV-2 subtype.^6–8 However, while there appears to be no clinical difference between subtypes,^8–9 MCV-2’s relative frequency appears to increase with age and in the setting of genital infection,⁷ though MCV-1 still remains the commonest subtype. MCV-2 also appears relatively commoner in the setting of immunocompromise and HIV.^10–12 An individual infection usually includes only one subtype of molluscum. ⁷

Molluscum infection may be spread by physical contact between individuals, fomites or autoinoculation. Molluscum incidence appears to be increasing worldwide.

Molluscum infection commonly occurs in one of 3 settings:

➢ Infection acquired through routine physical contact or occasionally fomites is the commonest presentation, and children account for the majority of infections^13–14: In the period 1994–2003, over 90% of molluscum infections presenting to general practitioners in the UK were in children aged under the age of 15 years. ¹⁵ In this setting, the molluscum lesions usually affect face and neck, trunk or limbs.^14,16,17

Clinical features

Molluscum lesions are usually characteristic, presenting as smooth-surfaced, firm, dome-shaped papules with central umbilication. Their colour can vary from pearly-white or pink to yellow. Lesions are usually 2–5 mm diameter, though occasionally much larger (giant mollusca), especially in the setting of immunocompromise.^14,21,22 Other uncommon manifestations include cystic, cellulitis or abscess-like lesions,^14,23–27 cutaneous pseudo-lymphomas,^28–31 folliculitis^32–33 or warty appearances. ³⁴ Destruction of an individual lesion will reveal a cheesy material, containing infectious viral particles.

Commonly, patients have 1–30 individual lesions at a time, ³⁵ occurring as clusters, and these can become Koebnerised. Especially lesions in later stages, at the point of regression, can be surrounded by an inflammatory dermatitis, which is due to a local inflammatory response to the infection.^36–37 Molluscum infection can affect almost any part of the body, rarely even the oral cavity^38–40 or sole of the foot.^41–43 Molluscum infection of the eyes may cause keratitis. ⁴⁴ Autoinoculation of other areas is possible following infection of skin at one region. Individuals with atopic dermatitis may be at higher risk of acquiring infection, due to loss of skin integrity and the immune dysregulation of atopic skin. Molluscum lesions are frequently asymptomatic, though occasionally associated with itch, discomfort or secondary bacterial infection. Molluscum lesions will usually regress spontaneously within 6–18 months on average in immunocompetent individuals, leaving no sequelae. Immunocompetent patients can therefore generally be reassured and asked to adopt a policy of ‘watchful waiting’.

Molluscum infection in immunocompromised states can be significantly more aggressive and widespread, presenting with 100 or more lesions in one individual,^45–48 and progressing as confluent, coalescing plaques. ⁴⁹ As described, these individual lesions can be atypical in appearance, are frequently significantly larger than average^50–52 and fail to spontaneously resolve with time. Extensive molluscum infection has been described in many different settings of immunocompromise, including malignancy, ⁴⁷ hereditary/congenital immunosuppressive conditions^53–56 and with immunosuppressant treatments.^{36,52,57–59}

Severe molluscum infections were also common in people living with HIV in the pre-HAART era,^60–61 estimated to affect 5–18% of positive individuals.^62–65 Extensive disease usually occurs in the setting of late HIV, with CD4 counts significantly under 200 and concurrent illnesses related to advanced HIV infection.^{46,63,66–74} Extensive molluscum can be the first indication of HIV infection. ⁴⁶

Lesions occur commonly on the face and neck,^50,75 but can also commonly affect the genital regions, indicating both non-sexual and sexual transmission routes in this scenario. ⁴⁶ Particularly in immunocompromise, molluscum lesions can affect the eyelids^76–78 and cause chronic conjunctivitis due to a foreign body type reaction.^{14,77,79–81} Molluscum infection can be particularly difficult to treat in late-stage HIV using conventional means,^64,82 though it usually responds to HIV antiretroviral treatment (ARV) initiation ⁸³ However, an immune reconstitution inflammatory syndrome (IRIS) reaction to molluscum may occur with the starting of ARVs,^84–86 and molluscum may occasionally first present in the setting of IRIS.^87–89

Diagnosis

Diagnosis is predominantly clinical, on the basis of characteristic lesions.

Occasionally, clinical diagnosis can be challenging, and dermatoscopy may be of some additional benefit,^90–91 as appearances are usually distinctive. ⁹² However, dermatoscopy is not routinely available in a sexual health setting. Rarely, biopsy maybe useful for atypical infections, as the histopathology will usually identify characteristic molluscum bodies.^36,93

While molecular methods such as PCR now exist for molluscum, ⁹⁴ these are not routinely used in clinical practice. Electron microscopic appearance of molluscum is again characteristic but not routinely utilised in everyday practice.

Management

Treatments (please see Table 1)

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Table 1.

Summary of recommendations for the treatment of genital molluscum contagiosum.

		GRADE recommendation
Treatments for MC for people without HIV
1.1	Expectant management (i.e. no treatment) for immunocompetent individuals with molluscum contagiosum (MC)	1B
2.1	Liquid nitrogen treatment in immunocompetent individuals with MC	2C
2.1	Podophyllotoxin 0.5% treatment in immunocompetent individuals with MC	2C
2.1	Emollients and mild topical steroid for severe dermatitis associated with MC lesions	2C
3.1	Imiquimod in immunocompetent individuals with MC	Not recommended
4.1	Treatments for MC for people living with HIV1. Liquid nitrogen2. Podophyllotoxin 0.5%	2D2D
4.2	For extensive MC lesions in immunosuppressed patients, the introduction of antiretroviral therapy (ART) is recommended	1C

Recommended

Expectant management (no treatment) is recommended for immunocompetent patients (although this recommendation is guided by a Cochrane review of molluscum treatments at non-genital sites). ¹¹⁹ (GRADE 1B) Patients should be warned that new lesions may appear while old ones disappear, and it will usually take 12–18 months for infection to completely resolve, though occasionally even longer (up to a few years).

Patients seek treatment from various motives, including for cosmetic reasons, stigma, symptoms (pruritus, secondary infection), extensive lesions, lesion persistence and concerns regarding transmission and autoinoculation. Some treatments may shorten the disease course, but this requires to be balanced against possible side-effects. Molluscum infection itself, resolving naturally, usually leaves no long-term sequelae, and it is important therefore that any therapy chosen, especially for delicate genital skin, is also gentle and has minimal side-effects. It is difficult to advocate one single treatment above others and choice is influenced by a number of factors, including site and number of lesions, comparative efficacy, side-effects, cost and ease of use. The patient’s views should be considered in the decision-making process. If patients opt for treatment, they must be informed that new lesions can appear for a while, necessitating more than one treatment course.

Where molluscum lesions are associated with dermatitis (either due to background atopy or as an immune reaction to lesions), we suggest considering emollients and possibly mild topical steroid to settle inflammation, reduce the risk of scratching and further autoinoculation. ¹²⁰ (GRADE 2C)Where active treatment for genital molluscum is required, we suggest that liquid nitrogen therapy or topical podophyllotoxin may be used. (GRADE 2C)

Liquid nitrogen therapy has been successfully used to treat molluscum,^121–124 although there are no reported trials in genital disease. Discomfort during application and local site reactions, uncommonly including hypopigmentation, are among the side-effects.

Podophyllotoxin 0.5%, commonly used to treat genital warts, may also be used in the treatment of molluscum contagiosum. We note evidence on efficacy is somewhat limited,^121,125,126 however in one randomised controlled trial (RCT) which demonstrated success, the majority of patients had genital lesions. ¹²⁵ Podophyllotoxin has the advantage of self-application and should be used twice daily for three consecutive days every week, for up to a duration of 4 weeks [net price 3 ml solution £12.38].

Alternative regimens

Cautery of genital molluscum is possible, especially if lesion numbers are not large. ¹¹⁹ Side-effects of scarring is unlikely if it is performed expertly and only to the raised dome of the lesions. However, cautery is often painful, though discomfort may be lessened by the prior application of local anaesthetic cream (e.g. EMLA cream). In addition, equipment necessary for cautery is unlikely to be easily accessible within most sexual health services.

Curettage is a conventional and well-recognised treatment for molluscum affecting non-facial, non-genital skin, ¹²⁷ but is frequently painful, ¹²⁸ impractical if a very large number of lesions are present, may cause scarring and evidence for its efficacy is relatively sparse.^129–130 It is thus less suitable for treating genital lesions.

Light-emitting and pulsed dye lasers have been tried with some success in both HIV-positive and -negative patients with non-genital molluscum, though there are no randomised controlled trials. Reported side-effects are few; mild discomfort and usually, temporary, pigment changes.^131–138 However, such treatment is costly, requires special equipment and is impractical for routine use at the genital region.

Imiquimod 5% cream has demonstrated some limited efficacy in the treatment of molluscum contagiosum, in both HIV-positive^48,139–141 and -negative patients.^142–146 There is also some experience in the use of imiquimod to treat genital infection.^147,148 However, the most recent Cochrane review of molluscum therapies ¹¹⁹ considered previously unpublished data from three large manufacturer sponsored trials, including a total of over 800 patients, enquiring into the efficacy of imiquimod as treatment for cutaneous molluscum. The trials failed to demonstrate any superiority of imiquimod above placebo in the treatment of molluscum but did note an increased incidence of local application site reactions. Taking these data into account, we therefore no longer recommend imiquimod as a treatment option for genital molluscum infection.

There is a very extensive list of other chemical preparations that have been tried for treating molluscum on the trunk and limb areas of the body. These include varying strength topical preparations of salicylic acid,^127,149,150 lactic acid, glycolic acid, ¹²⁷ trichloroacetic acid,^151,152 carbolic acid, benzoyl peroxide, ¹⁵³ iodine, ¹⁵⁰ phenol, sodium nitrite, ¹⁵⁴ potassium hydroxide,^155–159 silver nitrate, ¹⁶⁰ tretinoin,^153,159 tea tree oil ¹⁶¹ and lemon myrtle oil ¹⁶² However, there is little robust trial evidence generally for these treatments and none related to their use in genital infection, to recommend any above the policy of ‘watchful waiting’. Additionally, many of these topical therapies are too irritant for application on delicate genital skin and thus, are not recommended for use at this site. There is more experience in the use of cantharidin for non-genital molluscum, but this treatment is not routinely available in the UK and, again, would be expected to cause significant soreness at genital skin.^163–170

Oral cimetidine has also been attempted as an antiviral treatment for molluscum with mixed success^171–173 and cannot be recommended due to lack of evidence.

In summary, there are a paucity of good-quality trial data for effective and well-tolerated treatments for genital molluscum. We recommend that expectant management is suitable for most immunocompetent patients. Where there is a strong individual patient or clinician preference for active treatment, liquid nitrogen and topical podophyllotoxin can be attempted as easily accessible therapies in most UK sexual health clinic settings. Cautery may also be considered but the required equipment and experience may not be as readily available in regular sexual health service settings. We no longer recommended imiquimod use for genital molluscum.