MCV causes the characteristic skin lesions consisting of single or, more often, multiple, rounded, dome-shaped, pink, waxy papules 2-5 mm (rarely up to 1 cm) in diameter. The papules are umbilicated and contain a caseous plug. MCV is an unclassified member of the Poxviridae family, with features intermediately between the Orthopoxvirus and Parapoxvirus genera. It cannot be grown in tissue culture or eggs. It has been grown in human foreskin grafted to athymic mice but has not been transmitted to other laboratory animals.

By restrictive endonuclease analysis of the genomes of isolates, the following 4 types have been identified: MCV I, II, III, and IV. In one study of 147 patients, MCV I caused 96.6% of infections, and MCV II caused 3.4%; however, no relationship was observed between virus type and lesional morphology or anatomical distribution. MCV III and IV are rare.

Bateman first described the disease in 1817, and Paterson demonstrated its infectious nature in 1841. In 1905, Juliusburg proved its viral nature. Infection follows contact with infected persons or contaminated objects, but the extent of epidermal injury necessary is unknown. Lesions may spread by autoinoculation. MCV may be inoculated along a line of minor skin trauma, resulting in lesions arranged in a linear pattern. This process, termed autoinoculation, is different from the Koebner phenomenon, which also is called an isomorphic response. In the Koebner phenomenon, new lesions develop along a line of trauma in which the etiology of the underlying condition is unknown. Psoriasis and lichen planus are examples of skin conditions that commonly koebnerize.

Methods of MCV transmission between patients have been reported with direct skin contact by children sharing a bath and by athletes sharing gymnasium equipment and benches.

Three distinct disease patterns are observed in 3 different patient populations—children, adults who are immunocompetent, and patients who are immunocompromised (children or adults). The prognosis and therapy are different for each situation.

Molluscum contagiosum (MC) is encountered most commonly in children who become infected through direct skin-to-skin contact or indirect skin contact with fomites, such as bath towels, sponges, and gymnasium equipment. Lesions typically occur on the chest, arms, trunk, legs, and face. Hundreds of lesions may develop in intertriginous areas, such as the axillae and intercrural region. Lesions may rarely occur on the mucous membranes of the lip, tongue, and buccal mucosa. The palms are spared. Patients with atopic dermatitis may develop large numbers of lesions.

In adults, MC most commonly is a sexually transmitted disease. Healthy adults tend to have few lesions, which are limited to the perineum, genitalia, lower abdomen, or buttocks. MC in healthy children and adults is usually a self-limited disease.

Widespread, persistent, and atypical MC may occur in patients who are significantly immunocompromised or have acquired immunodeficiency syndrome (AIDS) with low CD4 T-lymphocyte counts. MC may be the presenting complaint in patients with AIDS. MCV infection in immunocompromised patients may be particularly resistant to therapy. Other opportunistic infections in these patients may closely resemble MC.

Pathophysiology: The virus replicates in the cytoplasm of epithelial cells, producing cytoplasmic inclusions and enlargement of infected cells. This virus only infects the epidermis. Infection follows contact with infected persons or contaminated objects, but the extent of necessary epidermal injury is unknown. The initial infection seems to occur in the basal layer, and the incubation period is usually 2-7 weeks. This is suggested by the fact that, while viral particles are noted in the basal layer, it is not until the spindle and granular layers of the epidermis are involved that viral DNA replication and the formation of new viral particles occur. Infection may be accompanied by a latent period of up to 6 months.

Following infection, cellular proliferation produces lobulated epidermal growths that compress epidermal papillae, while fibrous septa between the lobules produce pear-shaped clumps with the apex upwards. The basal layer remains intact. Cells at the core of the lesion show the greatest distortion and are ultimately destroyed, resulting in large hyaline bodies (ie, molluscum bodies, Henderson-Paterson bodies) containing cytoplasmic masses of virus material. These bodies are present in large numbers and appear as a white depression at the center of fully developed lesions. Occasionally, the lesions can progress beyond local cellular proliferation and become inflamed with attendant edema, increased vascularity, and infiltration by neutrophils, lymphocytes, and monocytes.

As with other poxviruses, MCV does not appear to develop latency but evades the immune system through the production of virus-specific proteins. Cell-mediated immunity is most important in modulating and controlling the infection. Children and HIV-infected patients generally have more widespread lesions. Prevalence of MCV in patients with HIV may be as high as 5-18%, and the severity of infection is inversely related to the CD4 T-lymphocyte count. More extensive and resistant infections also are noted in patients receiving prednisone and methotrexate.

The virus is not strongly immunogenic, as it induces antibody formation infrequently. Specific antibodies have been found in approximately 80% of patients and in about 15% of control subjects. A role for humoral immunity in regression of lesions is not established. Reinfection is common.

Frequency:

• In the US: Molluscum contagiosum is a common infection throughout the United States and accounts for approximately 1% of all skin disorders diagnosed. Data reported from 1969-1983 by the National Disease and Therapeutic Index Survey show an increasing number of patient visits. The prevalence rate in patients with HIV is reported to be 5-18%, and, if the CD4 cell counts are less than 100 cells/mm³, the prevalence of MC is reported to be as high as 33%.

• Internationally: The virus occurs throughout the world, and its incidence in most areas is not reliably known. In Mali, MC is among the most frequent dermatoses in children, with an incidence of 3.6%. In Australia, an overall seropositivity rate of 23% exists. The lowest antibody prevalence was in children aged 6 months to 2 years (3%), and seropositivity increased with age to reach 39% in persons aged 50 years or older.

  Childhood MC is common in Papua, New Guinea, and Fiji and certain parts of Africa. During a regional outbreak in East Africa, it was estimated that 17% of the village population and up to 52% of children older than 2 years developed lesions. Epidemiological studies suggest that transmission may be related to poor hygiene and climatic factors such as warmth and humidity. In England and Wales at sexually transmitted disease (STD) clinics, incidence increased approximately 10-fold from 1971-1978.

Mortality/Morbidity:

• MC generally is a benign and self-limited infection.

• For the most part, morbidity is caused by temporary adverse cosmetic results. Morbidity is higher in immunocompromised patients because they tend to have more lesions and more widespread infection. Most lesions resolve with no permanent residual skin defect; however, occasional lesions may produce a slightly depressed scar. This may represent deeper skin damage in lesions that were particularly inflammatory or secondarily infected.

Race:

• During a US longitudinal study performed from 1977-1981, 2-4 times as many cases were found in whites than in persons of other races. It is unclear if the noted difference was secondary to differences in access to medical care, other socioeconomic factors, or genetic predisposition.

Sex:

• Several studies have shown that males are affected more commonly than females.

• In STD clinics in England and Wales, slightly more than twice as many men are diagnosed as women.

Age:

• The disease is rare in children younger than 1 year, perhaps because of maternally transmitted immunity and a long incubation period; otherwise, incidence seems to reflect exposure to others. The greatest incidence is in children younger than 5 years and young adults. The peak among the pediatric age group correlates with casual contact, whereas the peak in young adults correlates with sexual contact.

• Spread of the virus among households is common in warm-climate countries where children are lightly dressed and in close contact with one another and where personal hygiene may be poor. The age of peak incidence is reported to be 2-3 years in Fiji and 1-4 years in the Congo (formerly Zaire). In New Guinea, the annual infection rate for children younger than 10 years was 6%. In cooler climates, spread within households is less common, and infection is more common at a later age. Use of school swimming pools is correlated with childhood infections, with a peak incidence in children aged 10-12 years in Scotland and 8 years in Japan. Prevalence appears to be increasing in all age groups.

History:

• MC is usually asymptomatic; however, individual lesions may be tender or pruritic.
• In general, the patient does not experience systemic symptoms, such as fever, nausea, or malaise.
• The patient may recall contact with an infected sexual partner, family member, or other person.
• Patients who report having multiple sexual partners or unprotected sex have an increased risk of infection.
• Contact may be reported in children sharing a bath or in athletes sharing gymnasium equipment and benches.

• If the patient has skin conditions that disrupt the epidermal layer, molluscum tends to spread more rapidly.

• The patient may notice new lesions developing along a scratch in areas of involved skin.
• Patients with atopic dermatitis may have more extensive disease. Patients with atopic dermatitis may have a positive family history of atopy (eg, eczema, asthma, hayfever).

• Duration of the individual lesion and of the attack is variable. Although most cases resolve without therapy within 6-9 months, some persist for 3-4 years. Individual lesions seldom persist more than 2 months.

• Patients with HIV or those receiving prednisone, methotrexate, or other immunosuppressive medications may have more extensive and resistant infections.

Physical:

• Lesions are discrete, nontender, flesh-colored, dome-shaped papules that show a central umbilication (more apparent when lesion is frosted with liquid nitrogen).

• Lesions are usually 2-6 mm in diameter (rarely up to 3 cm) and may be present in groups or widely disseminated. Immunocompetent children and adults usually have fewer than 20 lesions. Larger lesions may have several distinct clumps of molluscum bodies. Beneath the umbilicated center is a white curdlike core that contains molluscum bodies. Some lesions become confluent to form a plaque (agminate form).

• Lesions may be located anywhere; however, a predilection exists for the face, trunk, and extremities of children and in the groin and genitalia of adults. Lesions are seldom found on palms and rarely are documented on the soles, oral mucosa, and conjunctiva.

• In sexually active individuals, the lesions may be confined to the penis, pubis, and inner thighs.

• Distribution is influenced by the mode of infection, type of clothing worn, and climate.

• Hundreds of lesions may develop in intertriginous areas, such as the axillae and intercrural region.

• Patients with atopic dermatitis occasionally develop large numbers of lesions, which are confined to areas of lichenified skin.

• Widespread and persistent MC may occur in patients with AIDS and may be the presenting complaint.

• Approximately 10% of patients develop eczema around the lesions. This is attributed to toxic substances produced by the virus or to a hypersensitivity reaction to the virus.

• Eczema that is associated with molluscum lesions subsides spontaneously following removal.

• Lesions may resolve spontaneously or following minor trauma. Inflammatory changes result in suppuration, crusting, and eventual resolution of the lesion. This inflammatory stage does not usually represent secondary infection and seldom requires antibiotic therapy.

• MC may be randomly associated with other lesions, such as epidermal cysts, nevocellular nevi, sebaceous hyperplasias, and Kaposi sarcoma. Pseudocystic MC, giant MC, and MC associated with other lesions are responsible for frequent clinical misdiagnosis.

• Disfiguring lesions may occur in patients with the following conditions:

• AIDS– (Facial and perioral molluscum contagiosum are most commonly observed as a manifestation of HIV infection, particularly in homosexual men with HIV. At the time of MC diagnosis, the CD4 count is low.)
• Sarcoidosis
• Lymphocytic leukemia
• Congenital immunodeficiency
• Selective immunoglobulin M (IgM) deficiency
• Thymoma
• Treatment with prednisone and methotrexate
• Disseminated malignancy
• Refractory atopic dermatitis
• Immunocompromise (Lesions are especially common and extensive on the face and neck.)

Causes:

• MC is a viral disease caused by a DNA poxvirus and is largely, if not exclusively, a disease of humans. It is an unclassified member of the Poxviridae family (ie, poxviruses), with features intermediately between the Orthopoxvirus and Parapoxvirus groups. The poxviruses are a large group of viruses with a high molecular weight. They are the largest animal viruses, only slightly smaller than the smallest bacteria, and are just visible by light microscopy. They are complex DNA viruses that replicate in the cytoplasm and are especially adapted to epidermal cells. They cannot be grown in tissue culture or eggs. MCV has been grown in human foreskin grafted to athymic mice but not in other laboratory animals.

• Man is host for the following 3 types of MCV:

• Orthopoxvirus: This resembles variola (smallpox) and vaccinia, which are ovoid (300X250 nm).
• Parapoxvirus: These are orf and milkers nodule viruses, which are cylindrical (260X160 nm).
• Unclassified (with features that are intermediately between the orthopox and parapox groups): These are intermediate in structure (275X200 nm). They include MCV and tanapox.

• In 1996, the primary structure and coding capacity of MCV was determined by Senkevich et al. Analysis of the MCV genome has revealed that it encodes approximately 182 proteins, 105 of which have direct counterparts in orthopoxviruses (OPV).

• Restriction endonuclease analysis of the genomes has identified 4 types. MCV I and MCV II have genomes of 185 kilobases (kb) and 195 kb, respectively. MCV III and IV are very rare. No relationship exists between virus type and lesional morphology or anatomical distribution. MCV encodes an antioxidant protein (MC066L), selenoprotein, which functions as a scavenger of reactive oxygen metabolites and protects cells from UV or peroxide damage. The particular role of this protein is not known.

• In one study, type I caused 96.6% and type II caused 3.4% of infections in 147 patients, but no relationship was observed between virus type and lesional morphology or anatomical distribution.

Lab Studies:

• In most instances, diagnosis is easily established because of distinctive central umbilication of the dome-shaped lesion. Pseudocystic MC, giant MC, and MC associated with other lesions may be more difficult to diagnose clinically.

• If diagnosis is uncertain, lesions may be biopsied. Characteristic intracytoplasmic inclusion bodies (molluscum bodies or Henderson-Patterson bodies) are seen on histological examination.

• Express the pasty core of a lesion by crushing between 2 microscope slides and stain to reveal the particulate virions, which are present in abundance. Firm compression between the slides is required to release the virions with the stain in place. The use of Sedi-Stain (Clay-Adams, Parsippany, NJ 07054: crystal violet, safranin, and ammonium oxalate in 10% ethanol); Papanicolaou test; or Wright, Giemsa, or Gram stains can reveal the virions that make up the molluscum bodies.

• Measure serum antibodies by complement fixation, tissue culture neutralization, fluorescent antibody, and gel agar diffusion techniques; however, they are not well standardized and are seldom used except in research protocols.

• Polymerase chain reaction can be used to detect and categorize MCV in skin lesions.

• MCV cannot be grown in tissue culture; however, Buller et al demonstrated MCV replication in an experimental system using human foreskin grafted to athymic mice.

• Evaluate the patient for other STDs because sexually active patients may acquire other concomitant venereal diseases, such as syphilis and gonorrhea.

• Always consider testing for HIV infection in patients with facial lesions.

Histologic Findings: Lesions have a characteristic histopathology. In the fully developed lesion, a crater appears near the surface and gradually extends into lobules that contain hyalinized molluscum bodies (ie, Henderson-Paterson bodies), which can measure 35 mm in diameter. Molluscum bodies are membrane-bound sacks that contain numerous MC virions. Downward proliferation of the rete ridges with envelopment by the connective tissue forms the crater. Enlarged deep-purple keratinocytes develop above the basal cell layer of the epidermis. These enlarged keratinocytes contain viral particles, which increase in size as the cells progress upwards. Eventually, the bulk of the viral particles compress the nucleus to the side of the cell to form crescent-shaped nuclei. Intact lesions show little or no inflammatory changes.

Lesions with intradermal rupture of molluscum bodies show an intense dermal inflammatory infiltrate consisting of lymphocytes, histiocytes, and occasional multinucleated foreign body giant cells.

Medical Care:

• Before attempting any therapy, educate the patient or parents in-depth about the diagnosis, prognosis, risk of autoinoculation or infection of others, therapeutic options, and risks of therapy. More than one treatment session frequently is required. It is particularly important to provide this information at the first clinical visit when treating benign lesions, such as MC and common warts. A few extra minutes of explanation at this stage can prevent or mitigate numerous problems and questions during later visits. When lesions fail to respond to initial therapy, a temptation to be overzealous in treatment may exist. Patients and families are more understanding and less likely to demand aggressive therapy when reasonable goals and limitations of therapy are discussed thoroughly.
• In healthy patients, MC is generally self-limited and heals spontaneously after several months. Individual lesions are seldom present for more than 2 months. Although treatment is not required, it may help reduce autoinoculation or transmission to close contacts and improve clinical appearance.
• Therapeutic options can be divided into several broad categories, including benign neglect, direct lesional trauma, immune response stimulation, and antiviral therapy.
• The most appropriate therapeutic approach largely depends on the clinical situation. In healthy children, a major goal is to limit discomfort, and benign neglect or minor direct lesional trauma is appropriate. In adults who are more motivated to have their lesions treated, cryotherapy or curettage of individual lesions is effective and well tolerated. In immunocompromised individuals, MC may be very extensive and difficult to treat. The goal may be to treat the most troublesome lesions only. In severe cases, these patients may warrant more aggressive therapy with lasers, imiquimod, antiviral therapy, or combinations of these. Of course, effective antiretroviral therapy in patients with AIDS makes therapy of MC much more effective.
• Controlled studies that compare treatments have not been performed, and all treatments have benefits and disadvantages.

• Benign neglect
  • It is often reasonable to leave mollusca to resolve spontaneously, especially in young children for whom freezing or curettage may be painful and frightening. The dictum primum non nocere (first do no harm) has a special significance in children with minor self-limited conditions. Many physicians refuse to treat children with small numbers of mollusca.
  • Lesions on the eyelids and central face may be particularly distressing to parents and patients. When possible, treat lesions at other locations first, with the hope that the treatment may stimulate the facial lesions to resolve spontaneously. When facial lesions require treatment, the best option is to treat them frequently with minor physical trauma.
  • More aggressive therapy may be required in patients in whom the extent of disease is intolerable and in patients who are immunocompromised.

• Varying degrees of physical trauma to individual lesions are used and frequently quite successful. Physical trauma to individual MC lesions can be performed with cryotherapy, lasers, curettage, expression of the central core with tweezers, rupture of the central core with a needle or toothpick, electrodesiccation, or shave removal.

• Instruct the parents to tease out the firm white core at the center of lesions using a clean needle or toothpick. The process of irritating the lesion usually causes it to inflame and resolve within 1-2 weeks. This safe and easy approach can be performed by the parent, limiting the need for follow-up visits.

• In an office setting, curettage of individual lesions is easy and very effective. With a sharp curette and a quick firm motion, small individual lesions can be removed completely, with little or no bleeding. With practice and a sharp curette, the provider may perform this procedure with little or no discomfort. Older children, adolescents, and adults usually tolerate this procedure better.

• Other simple mechanical methods such as expression of the contents in the papule by squeezing it with forceps held parallel to the skin surface, or shaving off the lesions with a sharp scalpel are effective.

• Lesions also may be treated with light electrodesiccation. At very low voltage settings, anesthesia may not be required.

• Cryotherapy is the first-line treatment for many physicians, particularly in adolescents and adults. A brief freeze, which causes icing of the lesion and a thin rim of surrounding skin, is usually adequate. Treatment is repeated at intervals of 2-3 weeks until all lesions resolve. Achieve accurate spray of liquid nitrogen by using a disposable ear speculum. The small end is placed against the skin and liquid nitrogen is sprayed into the funnel created. Lesions also may be treated with cotton tip applicators chilled in liquid nitrogen and held against the lesion until a small amount of frosting occurs. Cryotherapy is painful and the smoke that rises off the cold applicator or the noise of the liquid nitrogen sprayer may be quite frightening to younger children.

• Pulsed dye laser (PDL) therapy has been shown to be more than 95% successful in treating individual lesions after one treatment. PDL treatment of molluscum contagiosum has been used successfully in patients with AIDS. A significant reduction in the number of molluscum contagiosum lesions following a single treatment with the PDL can be attained. Treated areas may remain disease-free for months. Although cost and availability are major limiting factors for routine use, it may be considered for treatment of extensive or resistant lesions. It also may be valuable in immunocompromised individuals with extensive disease.

• Treatment of MC in patients with AIDS remains a challenge. The combination of 2 or more therapeutic modalities, such as carbon dioxide laser, PDL, and TCA, can be of much help to improve the quality of life of these patients.

• The discomfort of curettage or other mechanical removal may be reduced, as follows:
  • Lesions may be sprayed with ethyl chloride until frosting has occurred and scraped away with a curette.
  • The application of local anesthetic cream, EMLA (a eutectic mixture of 5% lignocaine and prilocaine) or equivalent, may permit treatment painlessly. The cream is best applied under occlusion 1-2 hours before the planned procedure.

Activity:

• Instruct the patient to avoid activities or sports involving physical contact between infected areas of skin and exposed skin of other participants.

The common goal of most treatment methods is the destruction of lesions. Extensive controlled studies have not been performed with these treatments. All treatments have advantages and disadvantages.

Before attempting any therapy, educate the patient and parents in-depth about the diagnosis, prognosis, risk of autoinoculation and infection of others, therapeutic options, and risks of therapy. It is important to provide this information at the first clinic visit.
 

Drug Category: Cytotoxic and caustic agents -- Inhibits cell growth and destroy infected cells. They are applied directly to lesions. To decrease discomfort, treat a small number of lesions at each visit.

Drug Category: Immune response modifiers, topical -- Induction of cytokines, including interferon. Typically reserved for use if refractory to cryotherapy or tretinoin.

Drug Category: Antiviral drugs -- Presumably, antiviral drugs may interfere with the ability of the MCV to replicate. Because of expense and adverse effect potential, only consider these products in immunocompromised patients.

Further Outpatient Care:

• Re-treatment often is necessary.

Deterrence/Prevention:

• Most cases in adolescents and adults are secondary to sexual contact. Abstinence and careful selection of sexual partners are important. It is unclear if condoms are effective in preventing spread.

• Good personal hygiene is important in limiting transmission.

• Autoinoculation may result from trauma, such as shaving or manipulation of lesions by the patient.

Complications:

• Complications include irritation, inflammation, and secondary infections.
• Lesions on eyelids may be associated with follicular or papillary conjunctivitis.

• Bacterial superinfection may occur but is seldom of clinical significance.

• Autoinoculation is possible.

• Infection may be transmitted to others.

• Immunocompromised individuals may have extensive cutaneous infections.

Prognosis:

• Prognosis is generally excellent because the disease usually is benign and self-limited.

• In healthy patients, treatments are usually effective.

• Lesions can be disfiguring and produce anxiety in the patient, family, and daycare facility or school.

• Recurrences occur in as many as 35% of patients after initial clearing. The significance of these recurrences is unknown. They may represent reinfection, exacerbation of ongoing disease, or new lesions arising after a prolonged latent period.

• The disease often becomes generalized in patients who are infected with HIV or are otherwise immunocompromised. A direct correlation has been found between increasing severity of the disease and lower CD4 counts.

Patient Education:

• Stress the benign nature of this ubiquitous disease to the patient and parents.

• Limiting physical contact with infected areas of skin and good hand washing may reduce transmission.

• Instruct the patient to avoid scratching, which may result in autoinoculation.

• It is not necessary to keep children out of school; however, discourage physical contact and sharing of clothes and towels. In smaller children in whom physical contact is more difficult to prevent, it is reasonable to keep infected areas covered with clothing. Cover exposed lesions with tape or Band-Aids. Infection of other children cannot be prevented completely. Because the disease is extremely common and of very little clinical significance, the decision to limit infected children from daycare centers must be approached on a case-by-case basis.

• In adolescent and adult patient populations, this disease usually is sexually transmitted. Encourage safe sex and abstinence; however, it is unclear whether condoms and other barrier methods provide adequate protection against transmission.

• Emphasize that not all STDs are as benign as MCV (eg, herpes simplex, gonorrhea, chlamydia, HIV). Stress adherence to abstinence until lesions resolve. In the patient with multiple sexual partners or other risk factors, HIV testing is strongly recommended.

• It is important to note that not all cases in adults are sexually transmitted. This diagnosis can cause significant relationship stress.