Molluscum contagiosum

 

MC is a common, self-limited cutaneous viral infection in children caused by a member of the poxvirus family (Molluscum contagiosum virus, or MCV). Two molecular subtypes of the virus, MCV I and MCV II, result in indistinguishable skin lesions. MCV colonizes the epidermis and infundibulum of hair follicle.

 

 

Epidemiology

 

Incidence and prevalence

 

The virus occurs throughout the world, most commonly causing disease in childhood. In small children virtually all infections are caused by MCV-1 and in patients infected with HIV and in adults, however, MCV-2 causes the majority of infections. The virus is highly epidermotropic and is most easily transmitted by direct skin-to skin contact, especially if the skin is wet via swimming pools as well as via fomites such as sponges and towels and in beauty parlors.

 

Age

 

Three groups are primarily affected: young children with a peak age between 2 and 5 years, sexually active young adults (ages 20-29), and immunosuppressed persons, especially those with HIV infection.

 

 

Predisposing factors

 

Autoinoculation of the virus is a common mode of spread in affected patients. Children with atopic dermatitis (AD), either active or inactive are four times more likely than nonatopic children to have more than 50 lesions because lesions tend to spread more rapidly, possibly related to suppressed Th-cell responses. Topical steroids and also topical calcineurin inhibitors have been suspected as a contributing factor for spread of infection in atopic eczema.

Unusually widespread lesions have been reported in patients with immune compromise, such as HIV disease, hematological malignancy, sarcoidosis, and in those receiving immunosuppressive therapy suggesting that cell‐mediated immunity is significant in the control and elimination of the infection. In spite of profound immunosuppression following organ transplantation, the incidence of molluscum contagiosum infection is not greatly increased in this group and is not as common as other infections such as warts and herpes simplex.

 

 

Pathology

A subclinical carrier state of MCV probably exists in many healthy adults. Unique among poxviruses, MCV infection results in epidermal tumor formation. The virus seems first to enter the basal epidermis where an early increase in cell division extends into the suprabasal layer. Virus multiplication occurs in the cytoplasm of affected cells and produce large intrcytoplasmic eosinophilic inclusion bodies called molluscum bodies or Handerson- Peterson bodies within epidermal keratinocytes, which increase in size as they move toward the skin surface. The inclusion bodies measure 35um in diameter and tend to displace the nucleus to the periphery of the cells. Inclusion bodies are more evident in stratum granulosum and stratum corneum of the epidermis. Rupture and discharge of infected cells occur in the umbilication/crater of the lesion.

 

 

Clinical features

 

The incubation period lasts 2 weeks to 6 months.  The individual lesion is a firm, shiny, pearly white, hemispherical papule with a waxy surface, averaging 3-5 mm in diameter that then enlarge, occasionally reaching sizes of up to 3 cm (“giant molluscum”). As they enlarge, they may become flat topped, dome-shaped and opalescent. A central dell or umbilication is characteristic, within which a white curd-like substance can be seen that can be expressed with pressure. Lesions may be grouped in clusters or appear in a linear array. The latter often results from koebnerization or development of lesions at sites of trauma.

 

In approximately 20% of patients, after trauma, or spontaneously after several months, inflammatory changes result in suppuration, crusting and eventual destruction of the lesion. The development of inflammation within MC lesions suggests a robust immune response and tends to be associated with a subsequent decline in the number of lesions.

It has described a phenomenon called “beginning of the end” (BOTE) sign which refers to clinical erythema and swelling of an MC skin lesion when the regression phase begins. This phenomenon is likely due to an immune response towards the MC infection rather than a bacterial super infection.

 

Clinical variants

 

The clinical pattern depends on the risk group affected. In young children the lesions can occur anywhere on the skin surface but are most common on the exposed sites like face and extremities or in naturally occluded sites (e.g. axillae, neck, antecubital, popliteal fossae, and groin) and number from a few to more than 100. Genital lesions, as a part of a wider distribution, occur in 10% of childhood cases. When molluscum is restricted to the genital area in a child, the possibility of sexual abuse must be considered.

 

In young adults, molluscum is sexually transmitted and other STDs may coexist. There are usually fewer than 20 lesions; these favor the lower abdomen, upper thighs, and the penile shaft in men. Pubic hair removal by shaving, clipping, or waxing is a risk factor for acquiring MC by sexual contact. Mucosal involvement is very uncommon. In otherwise healthy subjects, occasional facial lesions are seen, particularly on the eyelids.

 

Multiple facial mollusca suggest host defense defect. Between 10 and 30% of AIDS patients not receiving antiretroviral therapy develop molluscum contagiosum. Virtually all HIV-infected patients with molluscum contagiosum already have an AIDS diagnosis with helper T-cell count of less than 100. AIDS patients may develop widespread, large, and occasionally deforming lesions involving both face and genitalia. Cutaneous cryptococcosis may resemble molluscum contagiosum in AIDS patients. Involvement of oral and genital mucosa can occur, virtually always indicative of advanced AIDS (helper T-cell count less than 50).

 

 

Complications and co‐morbidities

 

In at least 10% of cases, particularly in atopic children, a patchy eczema, often very irritable, develops around one or more of the lesions a month or more after their onset, known as molluscum dermatitis. Unilateral chronic conjunctivitis may similarly complicate lesions on or near the eyelids. The eczema and the conjunctivitis subside spontaneously when the lesion resolves or is removed.

 

 

Disease course and prognosis

 

Most cases are self‐limiting and clear spontaneously in 6–9 months; it is not unusual for some to persist for 3 or 4 years. Individual lesions are unlikely to persist for more than 2 months, but some lesions, particularly if solitary, may persist for up to 5 years. In HIV disease, mollusca persist and proliferate even after aggressive local therapy.

 

Depressed scars or anetoderma‐like lesions can remain when mollusca clear. In individuals with dark skin, significant post inflammatory hyper pigmentation may occur after treatment or spontaneous regression.

 

 

 

Investigations

 

The diagnosis of molluscum contagiosum is usually obvious when multiple typical umbilicated papules are present. The distinctive umbilication may be enhanced by light cryotherapy that leaves the umbilication appearing clear against a white (frozen) background. For confirmation, express the pasty core of a lesion, squash it between two microscope slides (or a slide and a coverglass) and stain it with Wright, Giemsa, or Gram stains shows intracytoplasmic inclusion bodies called Henderson-Patterson bodies, which appear as ovoid eosinophilic structures.

On electron microscopy: characteristic brick-shaped poxvirus particles are seen in the epidermis.

 

 

Treatment

 

In many instances, therapy is not necessary and natural resolution can be awaited. The risk of dissemination of the infection can be minimized by reducing scratching, which can both damage adjacent skin and spread virus from mature papules. Associated dry skin should be treated with emollients. Transfer of infection to another individual may be reduced by avoidance of shared towels, contact sports and swimming pool bathing.

MC resolves spontaneously in immunocompetent children, with the time interval between onset and clearance of the lesions ranging from several months to several years. However, treatment may be requested when there are numerous or cosmetically significant lesions. The choice of treatment will depend on the age of the patient, and the number and position of the lesions. Treatments aim to destroy the infected epidermal cells, stimulate an immunological response or act directly against the virus.

In young immunocompetent children, especially those with numerous lesions, the most practical course may be not to treat or to use only topical tretinoin. Aggressive treatment may be emotionally traumatic and can cause scarring. Spontaneous resolution is virtually a certainty in this setting, avoiding these sequelae. Individual lesions last 2–4 months each; the duration of infection are about 2 years. Continuous application of surgical tape to each lesion daily after bathing for 16 weeks led to cure in 90% of children so treated. Topical cantharidin, applied for 4–6 h to approximately 20 lesions per setting, led to resolution in 90% of patients. This therapy is well tolerated, has a very high satisfaction rate for patients and their parents, and has rare complications. If lesions are limited and the child is cooperative, nicking the lesions with a blade to express the core (with or without the use of a comedo extractor), light cryotherapy, application of trichloroacetic acid (35–100%), or removal by curettage are all alternatives. The application of EMLA cream for 1 h before any painful treatments has made the management of molluscum in children much easier. 

 

Treatment of molluscum dermatitis with a weak topical corticosteroid may help to reduce associated pruritus and prevent autoinoculation from scratching.

 

In adults with genital molluscum, removal by cryotherapy or curettage is very effective. Sexual partners should be examined; screening for other coexistent STDs is mandatory.

 

In patients with atopic dermatitis, application of EMLA followed by curettage or cryotherapy is most practical. Caustic chemicals should not be used on atopic skin. Topical steroid application to the area should be reduced to the minimum strength possible. A brief course of antibiotic therapy should be considered after initial treatment, since dermatitic skin is frequently colonized with S. aureus.

 

In immunosuppressed patients, especially those with AIDS, management of molluscum can be very difficult. Aggressive treatment of the HIV infection with HAART, if it leads to improvement of the helper T-cell count, is predictably associated with a dramatic resolution of the lesions. This response is delayed 6–8 months from the institution of the treatment. Molluscum occurs frequently in the beard area, so shaving with a blade razor should be discontinued to prevent its spread. If lesions are few, curettage or core removal with a blade and comedo extractor is most effective. EMLA application may permit treatment without local anesthesia. Cantharidin or 100% trichloroacetic acid may be applied to individual lesions. Temporary dyspigmentation and slight surface irregularities may occur. Cryotherapy may be effective but must be used with caution in persons of pigment. When lesions are numerous or confluent, treatment of the whole affected area may be required because of the possibility of latent infection. Trichloroacetic acid peels above 35% concentration (medium depth) or daily applications of 5-fluorouracil (5-FU) to the point of skin erosion may eradicate lesions, at least temporarily. At times, removal by curette is required. In patients with HIV infection, continuous application of tretinoin cream once nightly at the highest concentration tolerated seems to reduce the rate of appearance of new lesions. Topical 1–3% cidofovir application and systemic infusion of this agent have been reported to lead to dramatic resolution of molluscum in patients with AIDS.

Treatment must be individualized. Conservative nonscarring methods should be used for children who have many lesions. Genital lesions in adults should be definitively treated to prevent spread by sexual contact. New lesions that are too small to be detected may appear after treatment and may require additional attention. Topical corticosteroids are used to treat both nearby dermatitis and dermatitis involving the lesions.

Curettage

Small papules can be quickly removed with a curette and without local anesthesia in adults. Children might tolerate curettage after a lidocaine/prilocaine cream (EMLA) is applied for analgesia. The cream is applied 30 to 60 minutes before treatment. Bleeding is controlled with gauze pressure. Curettage is useful when there are a few lesions because it provides the quickest, most reliable treatment. A small scar may form; therefore this technique should be avoided in cosmetically important areas.

Cryosurgery

Cryosurgery is the treatment of choice for patients who do not object to the pain. Most children will not tolerate cryosurgery. The papule is touched lightly with a nitrogen-bathed cotton swab or spray until the advancing, white, frozen border has progressed to form a 1-mm halo on the normal skin surrounding the lesion. This should take approximately 5 seconds. This conservative method destroys most lesions in one to three treatment sessions at 1- or 2-week intervals and rarely produces a scar.

Cantharidin

Cantharidin, a chemovesicant extract from the blister beetle, is very effective, well tolerated, and safe in children. It penetrates the epidermis and induces vesiculation through acantholysis. Cantharidin is sparingly applied to each non facial lesion with the blunt wooden end of a cotton-tipped applicator. Apply single small droplet (sufficient to cover lesion) to each molluscum.  Avoid “painting”. Contact with surrounding skin is avoided, and a maximum of 20 lesions are treated per visit. Let area dry for 3 to 5 minutes before patient gets dressed. Treat initial lesion in a location that can be easily visualized by patient (to calm anxiety about the therapy). The treated areas are washed with soap and water after 4 to 6 hours, or sooner if burning, discomfort, or vesiculation occurs; therapy is repeated at 2- to 4-week intervals. Lesions blister and may clear without scarring. Blistering and pain are mild to moderate. Acetaminophen or ibuprofen may be administered by parent, if needed, for pain. Bacitracin ointment applied to blisters twice daily until areas heal. Pitted shallow depressions sometimes occur.

Imiquimod

Nightly application of the immunomodulatory drug imiquimod cream is applied to individual lesions once each day (5 days a week) for up to a maximum of 16 weeks has been reported to be safe and effective in both immunocompromised and immunocompetent children and adults.

Potassium hydroxide 5%

Parents are instructed to apply the pharmacist-prepared solution twice daily with a cotton swab. A brief stinging may occur shortly after the application. Most lesions clear in 4 weeks.

Hypoallergenic surgical adhesive tape

Tape is applied once each day after showering and is used each day until the lesion ruptures and the core is discharged. The average time to clearance is 16 weeks.

Salicylic acid

Salicylic acid solution applied each day without tape occlusion may cause irritation and encourage resolution.

Laser therapy

Lesions on the genital area may be treated with the carbon dioxide laser.

Trichloroacetic acid peel in immunocompromised patients

Patients with HIV infection who have extensive facial molluscum contagiosum infection are treated with trichloroacetic acid peels. Peels are performed with 25% to 50% trichloroacetic acid (average, 35%) and are repeated every 2 weeks as needed. A total of 15 peels are performed with an average reduction in lesion counts of 40.5% (range, 0% to 90%).

 

Therapeutic ladder

First line

·        Caustic destruction: cantharidin, trichloroacetic acid, diluted liquefied phenol

·        Irritant: salicylic acid, adapalene, potassium hydroxide, benzoyl peroxide

·        Surgical irritation

Second line

·        Immunological:  imiquimod

·        Surgical removal

Third line

·        Cidofovir

·        Paclitaxel

 

 

First line

 

Stimulation of the immune response may occur after destructive or inflammatory therapies. Many topical agents can be used to produce mild to moderate inflammation and hence potentially stimulate the development of an immune response against the virus. Cantharidin, trichloroacetic acid and diluted liquefied phenol are strong irritants which can cause pain, blistering and scarring but with careful application and appropriate dilution can increase lesion clearance. Topical salicylic acid preparations, tretinoin, adapalene, and 5–10% potassium hydroxide solution and benzoyl peroxide cream all lead to an irritant reaction but if the strength of preparation and the frequency of application are adjusted, individuals can tolerate repeated treatments until resolution occurs.

Damage to the lesions by squeezing the contents or insertion of a pointed cocktail stick may stimulate inflammation and clearance.

 

Second line

 

Other treatments have been used for molluscum contagiosum with the explicit aim of enhancing the immune response. Efficacy has been reported with imiquimod cream.

Compared to cryotherapy, lesions clear more slowly with imiquimod, but the treatment is painless and well tolerated in children. In two large unpublished randomized trials, imiquimod was of no benefit when compared to placebo.

 

Cryotherapy is effective and commonly used in older children and adults, but needs to be repeated at 3–4 weekly intervals. The carbon dioxide or pulsed dye lasers have produced useful effects but can cause scars.

Surgical removal of molluscum contagiosum by curettage has been used for many years. Children will usually need prior application of topical anesthetic cream with strict observance of the maximum safe dose.

  

Third line

 

The antiviral agent cidofovir has been shown to effectively resolve molluscum lesions (used either intravenously or topically as a 1–3% ointment or cream). It should be considered for treating extensive lesions in, for example, immunocompromised patients where eradication has proved difficult with standard treatment regimens.

A recent report has also suggested efficacy of intravenous paclitaxel in severe disease in immunocompromise.