Background

Molluscum contagiosum virus causes a benign viral infection that is largely (if not exclusively) a disease of humans. Molluscum contagiosum virus causes characteristic skin lesions consisting of single or, more often, multiple, rounded, dome-shaped, pink, waxy papules that are 2-5 mm (rarely up to 1.5 cm in the case of a giant molluscus) in diameter. The papules are umbilicated and contain a caseous plug. See the images below for examples. (See Presentation and Workup.)

Note the central umbilication in these classic lesions of molluscum contagiosum.

Approximately 10% of patients develop eczema around lesions. Eczema associated with

molluscum lesions spontaneously subsides following removal. Larger lesions may have several clumps of molluscum bodies rather than the more common single central umbilication. This may make them difficult to recognize as molluscum

contagiosum.

Molluscum contagiosum on the right axilla.

Molluscum contagiosum virus is an unclassified member of the Poxviridae family. 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. (See Etiology.)

Through restrictive endonuclease analysis of the genomes of isolates, molluscum contagiosum virus types I-IV have been identified. In a study of 147 patients, molluscum contagiosum virus I caused 96.6% of infections, and molluscum contagiosum virus II caused 3.4%; however, no relationship was observed between virus type and lesional morphology or anatomical distribution.[1] Molluscum contagiosum viruses III and IV are rare. In patients with human immunodeficiency virus (HIV) infection, molluscum contagiosum virus II causes most infections (60%). 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.

Complications
Complications of molluscum contagiosum 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. (See Prognosis, Treatment, and Medication.) Cellulitis is an unusual complication of molluscum contagiosum in patients who are HIV infected. [2] Secondary infection with Staphylococcus aureus has resulted in abscess formation, whereas Pseudomonas aeruginosa can cause necrotizing cellulitis.

Etiology
Transmission
The molluscum contagiosum virus may be inoculated along a line of minor skin trauma (eg, from shaving), resulting in lesions arranged in a linear pattern (see the image below). This process, termed autoinoculation, can also result from manipulation of lesions by the patient. Autoinoculation is different from the Koebner phenomenon, which is also called an isomorphic response. In the Koebner phenomenon, new lesions develop along a line of trauma and the etiology of the underlying condition is unknown. Psoriasis and lichen planus are examples of skin conditions that commonly koebnerize.

In a patient who had preexisting molluscum contagiosum, the virus was inoculated along a line of minor skin trauma, resulting in the development of the 3 new lesions.

Molluscum contagiosum virus transmission through direct skin contact between children sharing a bath and between athletes sharing gymnasium equipment and benches has been reported. An association between school swimming pool use and molluscum contagiosum infection has also been reported. [3, 4] 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 of these groups. Molluscum contagiosum is most common 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 (see the image below). 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.

Molluscum lesions may become quite numerous in intertriginous areas. This child has autoinoculated lesions to both inner thighs.

In adults, molluscum contagiosum most commonly is a sexually transmitted disease (STD). Healthy adults tend to have few lesions, which are limited to the perineum, genitalia, lower abdomen, or buttocks. Molluscum contagiosum in healthy children and adults is usually a self-limited disease. Widespread, persistent, and atypical molluscum contagiosum may occur in patients who are significantly immunocompromised or have acquired immunodeficiency syndrome (AIDS) with low CD4 T-lymphocyte counts (see the images below). Molluscum contagiosum may be the presenting complaint in patients with AIDS. Molluscum contagiosum virus infection in immunocompromised patients may be particularly resistant to therapy. Other opportunistic infections in these patients may closely resemble molluscum contagiosum.

Molluscum contagiosum rarely occurs on the face in an adult unless the patient is infected with HIV. When molluscum contagiosum occurs in individuals infected with HIV, facial lesions are common and frequently numerous.

Molluscum contagiosum lesions in individuals infected with HIV may number in the hundreds. In

addition, they may become quite large and prominent.

Multiple papules on the face of a man with HIV.

Case reports have detailed molluscum contagiosum eruptions in areas that were treated with tacrolimus 0.1% (Protopic).[5, 6, 7]

Infection
The molluscum contagiosum virus replicates in the cytoplasm of epithelial cells, producing cytoplasmic inclusions and enlargement of infected cells. This virus infects only 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, although viral

particles are noted in the basal layer, viral deoxyribonucleic acid (DNA) replication and the formation of new viral particles do not occur until the spindle and granular layers of the epidermis are involved. Infection may be accompanied by a latent period of as long as 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, molluscum contagiosum virus 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 patients with HIV infection generally have more widespread lesions. Prevalence of molluscum contagiosum virus 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 infrequently induces antibody formation. 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.

Viral characteristics
Molluscum contagiosum 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). 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 using 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. Molluscum contagiosum virus has been grown in human foreskin grafted to athymic mice but not in other laboratory animals. Humans are the host for the following 3 types of molluscum contagiosum virus:

Orthopoxvirus - This resembles variola (smallpox) and vaccinia, which are ovoid (300 x 250 nm) Parapoxvirus - These are orf and milkers nodule viruses, which are cylindrical (260 x 160 nm) Unclassified (with features that are intermediate between those of the orthopox and parapox groups) - These are intermediate in structure (275 X 200 nm); they include molluscum contagiosum virus and tanapox The primary structure and coding capacity of molluscum contagiosum virus was determined by Senkevich et al.[8] Analysis of the molluscum contagiosum virus genome has revealed that it encodes approximately 182 proteins, 105 of which have direct counterparts in orthopoxviruses. Restriction endonuclease analysis of the genomes has identified 4 types. Molluscum contagiosum virus I and molluscum contagiosum virus II have genomes of 185 kilobases (kb) and 195 kb, respectively. Molluscum contagiosum virus III and IV are very rare. No relationship between virus type and lesional morphology or anatomical distribution is known. Molluscum contagiosum virus encodes an antioxidant protein (MC066L), selenoprotein, which functions as a scavenger of reactive oxygen metabolites and protects cells from damage from ultraviolet (UV) light and peroxide. 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 anatomic distribution. [1]

Epidemiology
Occurrence in the United States
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/L, the prevalence of molluscum contagiosum is reported to be as high as 33%.

International occurrence
The molluscum contagiosum virus occurs throughout the world, and its incidence in most areas is not reliably known. It is more prevalent in tropical areas. In Mali, molluscum contagiosum is among the most frequent dermatoses in children, with an incidence of 3.6%.[9] In Australia, an overall seropositivity rate of 23% is reported. [10] 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 molluscum contagiosum is common in Papua New Guinea, Fiji, and certain parts of Africa. During a regional outbreak in East Africa, it was estimated that 17% of the village population and as many as 52% of children older than age 2 years developed lesions. Epidemiologic studies suggest that transmission may be related to poor hygiene and climatic factors such as warmth and humidity.

Race- and sex-related demographics

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.[11] Whether the noted difference was secondary to differences in access to medical care, other socioeconomic factors, or genetic predisposition is unclear.[12] Several studies have shown that males are affected by molluscum contagiosum more commonly than are females. Data from STD clinics in England and Wales revealed that more than twice as many men as women were diagnosed with the infection.

Age-related demographics
Molluscum contagiosum is rare in children younger than age 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 age 5 years and in young adults. The peak among the pediatric age group correlates with casual contact, whereas the peak in young adults correlates with sexual contact. [13, 14] 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 age 10 years was found to be 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.

Prognosis
The prognosis in molluscum contagiosum is generally excellent because the disease is usually benign and self-limited. Spontaneous resolution generally occurs by 18 months in immunocompetent individuals; however, lesions have been reported to persist for as long as 5 years. In healthy patients, treatments are usually effective, although lesions can be disfiguring and may 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. The duration of infection is uncertain in populations with HIV infection and in populations that are otherwise immunocompromised (eg, patients who have undergone renal transplant), because molluscum contagiosum may not be self-limiting in these cases.

Morbidity and mortality

Molluscum contagiosum is generally 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. Involvement of the margin of the eyelids may produce keratoconjunctivitis. No mortality has been associated directly with the molluscum contagiosum virus.

Patient Education
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. [15, 16] More than 1 treatment session is frequently required. Providing this information at the first clinical visit is particularly important when treating benign lesions, such as those of molluscum contagiosum and common warts. A few extra minutes of explanation at this stage can prevent or mitigate numerous problems and questions during later visits.[17] When lesions fail to respond to initial therapy, a temptation to be overzealous in treatment may occur. Patients and families are more understanding and less likely to demand aggressive therapy when reasonable goals and limitations of therapy are thoroughly discussed. Stress the benign nature of this ubiquitous disease to the patient and his or her parents. Limiting physical contact with infected areas of skin and good handwashing may reduce transmission. Instruct the patient to avoid scratching, which may result in autoinoculation. Keeping children out of school is not necessary; however, discourage physical contact and sharing of clothes and towels. In smaller children in whom physical contact is more difficult to prevent, keeping infected areas covered with clothing is reasonable. Cover exposed lesions with tape or an adhesive bandage. Infection of other children cannot be

completely prevented. 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 is usually sexually transmitted. Encourage safe sex and abstinence; however, whether condoms and other barrier methods provide adequate protection against transmission is unclear. Emphasize that not all STDs are as benign as molluscum contagiosum virus (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. Note that not all cases in adults are sexually transmitted. This diagnosis can cause significant relationship stress. For patient education information, see the Skin Conditions and Beauty Center, as well as Molluscum Contagiosum.

History
Molluscum contagiosum 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. Parents may report recent exposure to other children affected with molluscum contagiosum at school, camp, or public recreational facilities (eg, gymnasiums, swimming pools). 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 and may have a positive family history of atopy (eg, eczema, asthma, hayfever). Children frequently have active atopic dermatitis. A report detailed an eruption of molluscum contagiosum in a patient who had undergone a renal transplant.[18] Case reports have detailed molluscum contagiosum eruptions in areas that were treated with tacrolimus 0.1% (Protopic). [5, 6, 7] Duration of the individual lesion and of the attack varies. 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.

Patients infected with HIV

Patients generally have a low CD4 count, with the severity of infection being inversely related to the count. Patients who are poorly compliant or noncompliant with highly active antiretroviral therapy (HAART) for the treatment of HIV are at an increased risk, as are patients who have multiple sexual partners. The frequency of unprotected sex also increases the risk of transmission.

Physical Examination
Lesions are discrete, nontender, flesh-colored, dome-shaped papules that show a central umbilication (which is more apparent when the lesion is frosted with liquid nitrogen). (See the image below.)

Presented here are the classic umbilicated papules of molluscum contagiosum lesions on the cheek of a child. Facial lesions occur frequently in children, although lesions generally are few.

Lesions are usually 2-5 mm (rarely up to 1.5 cm in the case of giant molluscus) in diameter 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 (see the image below). Beneath the umbilicated center is a white, curdlike core that contains molluscum bodies. Some lesions become confluent to form a plaque (agminate form).

Larger lesions may have several clumps of molluscum bodies rather than the more common single central umbilication. This may make them difficult to recognize as molluscum contagiosum.

Lesions may be located anywhere; however, a predilection for the face, trunk, and extremities is observed in children and a predilection for the groin and genitalia is observed in adults. Lesions are seldom found on the palms and are rarely documented on the soles, oral mucosa, or conjunctiva. Distribution is influenced by the mode of infection, type of clothing worn, and climate. In sexually active individuals, the lesions may be confined to the penis, pubis, and inner thighs (see the image below). Widespread and persistent molluscum contagiosum may occur in patients with AIDS and may be the presenting complaint.

Molluscum contagiosum on the shaft of the penis. Molluscum contagiosum in the genital region of adults is most commonly acquired as a sexually transmitted disease.

Molluscum contagiosum may be randomly associated with other lesions, such as epidermal cysts, nevocellular nevi, sebaceous hyperplasias, and Kaposi sarcoma. Pseudocystic molluscum contagiosum, giant molluscum contagiosum, and molluscum contagiosum associated with other lesions are responsible for frequent clinical misdiagnosis. Other characteristics of molluscum contagiosum to consider include the following:

Intertriginous areas - Hundreds of lesions may develop in intertriginous areas, such as the axillae and intercrural region Atopic dermatitis - Patients with atopic dermatitis occasionally develop large numbers of lesions, which are confined to areas of lichenified skin Eczema - Approximately 10% of patients develop eczema around the lesions, with this being 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 (see the first image below) Inflammatory changes - These result in suppuration, crusting, and eventual resolution of the lesion; this inflammatory stage does not usually represent secondary infection and seldom requires antibiotic therapy (see the second image

below)

Approximately 10% of patients develop eczema around lesions. Eczema associated

with molluscum lesions spontaneously subsides following removal. After trauma, or spontaneously after several months, 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.

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[19] ; at the time of molluscum contagiosum diagnosis, the CD4 count is low Immunocompromise - Lesions are especially common and extensive on the face and neck Sarcoidosis Lymphocytic leukemia Congenital immunodeficiency Selective immunoglobulin M (IgM) deficiency Thymoma Treatment with prednisone and methotrexate Disseminated malignancy Refractory atopic dermatitis

Diagnostic Considerations
The cutaneous manifestations of other opportunistic infections, such as cutaneous cryptococcosis, histoplasmosis, and aspergillosis, may mimic molluscum contagiosum and must be ruled out in immunocompromised hosts. (See the images below.)

This lesion of cutaneous coccidioidomycosis could be included among the differential diagnoses

of molluscum contagiosum. diagnoses of molluscum contagiosum.

This keratoacanthoma could be included among the differential

Molluscum contagiosum may be randomly associated with other lesions, such as epidermal cysts, nevocellular nevi, sebaceous hyperplasias, and Kaposi sarcoma. Pseudocystic molluscum contagiosum, giant molluscum contagiosum, and molluscum contagiosum associated with other lesions are responsible for frequent clinical misdiagnoses.

Infection of children through sexual abuse is possible; however, to a greater extent than warts, molluscum contagiosum virus is quite common on the genital, perineal, and surrounding skin of children. [20, 21] Regard abuse as unlikely, unless other suspicious features are present. Histologic or microscopic confirmation of molluscum contagiosum is indicated in patients who are immunocompromised because several life-threatening opportunistic infections may clinically mimic molluscum contagiosum. Conditions to consider in the differential diagnosis of molluscum contagiosum include the following:

Keratoacanthoma Verruca vulgaris (warts) Eccrine poroma Epidermal cyst Foreign body granuloma Lichen planus Flat warts (verruca plana) Pyoderma Perforating disorders (all very rare in children) to consider in the differential diagnosis of molluscum contagiosum include the following: Acquired reactive perforating dermatosis of renal failure Kyrle disease Perforating serpiginous elastoma Perforating folliculitis Verrucous perforating collagenoma Perforating granuloma annulare Differential diagnoses to consider in patients with AIDS include the following: Cutaneous cryptococcus[22] - Cutaneous cryptococcus presents as molluscumlike eruptions (on the face, it often has a very dramatic appearance); the patient may have few or no other symptoms associated with cryptococcal meningitis Cutaneous coccidioidomycosis Cutaneous histoplasmosis Cutaneous aspergillosis

Differentials
Basal Cell Carcinoma Condyloma Acuminatum Cryptococcosis Keratosis Pilaris Milia Pearly Penile Papules Pyogenic Granuloma Surgical Treatment of Basal Cell Carcinoma Varicella-Zoster Virus

Approach Considerations
In most instances, a diagnosis is easily established because of the distinctive, central umbilication of the dome-shaped lesion. Pseudocystic molluscum contagiosum, giant molluscum contagiosum, and molluscum contagiosum 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-Paterson bodies) are seen on histologic examination findings. Express the pasty core of a lesion by crushing the lesion between 2 microscope slides and staining it 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 crystal violet, safranin, and ammonium oxalate in 10% ethanol; the Papanicolaou test; or Wright, Giemsa, or Gram stains can reveal the virions that make up the Henderson-Paterson 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 (PCR) assay can be used to detect and categorize molluscum contagiosum virus in skin lesions. Molluscum contagiosum virus cannot be grown in tissue culture; however, Buller et al demonstrated molluscum contagiosum virus replication in an experimental system using human foreskin grafted to athymic mice.[23]

Evaluate the patient for other sexually transmitted diseases (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.

Squash preparation
Squash preparation is microscopic examination of cellular exudate. The cellular material contained within the central umbilication may be extracted manually, flattened between 2 microscope slides, and stained. Microscopic examination of this preparation reveals the Henderson-Paterson bodies.

Histologic Findings
Lesions in molluscum contagiosum have a characteristic histopathology. [24] The prototypical hematoxylin and eosin (H&E)stained histologic section in this disease reveals a cup-shaped indentation of the epidermis into the dermis (as seen in the images below). Downward proliferation of the rete ridges with envelopment by the connective tissue forms the crater.

This low-power view of a molluscum contagiosum lesion shows the classic cupshaped invagination of the epidermis into dermis. The Henderson-Paterson bodies are identified readily and stained purple to red in

this image. appearance.

Low-power histopathologic examination reveals an overall cup-shaped

Within the region of the indentation, the epidermis appears thickened (acanthosis), possibly measuring up to 6 times the thickness of the surrounding, uninvolved skin, and the cornified layer typically is disintegrated. The striking feature is the presence of intracytoplasmic, eosinophilic, granular inclusions within the keratinocytes of the basal, spinous, and granular layers of the epidermis. These inclusions, the Henderson-Paterson bodies, can measure 35m in diameter. Ultrastructural studies have shown that these bodies are membrane-bound sacs that contain numerous molluscum contagiosum virions. The viral particles increase in size as they progress up toward the granular layer, causing compression of the nucleus to the periphery of the infected keratinocytes. The surrounding dermis is relatively unremarkable. Intact lesions show little or no inflammatory change. (See the images below.)

This is a medium-power view of a molluscum contagiosum lesion. Magnification allows better demonstration of the intracytoplasmic molluscum bodies (staining purple-pink) within the keratinocytes.

Lesions of molluscum contagiosum have a characteristic histopathology. Lobules containing hyalinized molluscum bodies, also known as Henderson-Paterson bodies, are diagnostic.

This molluscum contagiosum body is an intracytoplasmic inclusion body. Notice in the image that the keratinocyte nuclei are displaced to the periphery of the cell and that the intracytoplasmic inclusions have a

granular quality.

Cytoplasmic viral inclusions become progressively larger toward the

epidermal surface (hematoxylin and eosin, 200X) shaped appearance. Courtesy of Alvin Zelickson, MD.

Viral particles have a dumbbell-

In nonprototypical cases of molluscum contagiosum, in which intradermal rupture of molluscum bodies occurs, an intense, inflammatory dermal infiltrate consisting of lymphocytes, histiocytes, and occasional foreign body type, multinucleated giant cells may be observed. Rarely, metaplastic ossification may occur. Exceptionally, the inflammatory dermal infiltrate may be intense enough to simulate a cutaneous lymphoma (pseudolymphoma).

Approach Considerations
In healthy patients, molluscum contagiosum 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 to reduce autoinoculation or transmission to close contacts and improve clinical appearance. Intervention may also be indicated if lesions persist. Therapeutic modalities include topical application of various medications, radiation therapy, and/or surgery. Each technique may result in scarring or postinflammatory pigmentary changes. Frequently, multiple treatment sessions are necessary because of the recurrence of treated lesions and/or the appearance of new lesions by autoinoculation. The benefit of therapy must exceed the risk. Therapeutic options for molluscum contagiosum can be divided into broad categories, including the following:

Benign neglect Direct lesional trauma

Antiviral therapy Immune response stimulation

Choice of 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, molluscum contagiosum 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 a combination of these. Of course, effective antiretroviral therapy in patients with AIDS makes therapy of molluscum contagiosum much more effective. The US Food and Drug Administration (FDA) has approved none of the topical or intralesional agents for treatment of molluscum contagiosum. In a study of the treatment of molluscum contagiosum in children, Hanna et al determined that curettage was the most efficacious therapy. The investigators conducted a prospective, randomized trial that compared the efficacy and adverse effects of 4 recognized treatments of molluscum contagiosum in 124 children. [25]One group was treated with curettage, a second with cantharidin, a third with a combination of salicylic acid and lactic acid, and a fourth with imiquimod. Curettage was found to be the most efficacious treatment and had the lowest rate of side effects. However, it must be performed with adequate anesthesia and is a time-consuming procedure. Cantharidin had moderate complications due to blisters and was slightly less effective. The topical keratolytic used was too irritating for children. Topical imiquimod was more effective than cantharidin but is expensive, and an optimum treatment schedule has yet to be reported.

Follow-up
Repeat examination is recommended 2-4 weeks after treatment. Retreatment often is necessary. Consider combination therapy in patients whose lesions respond poorly.

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

Deterrence and prevention

Most cases in adolescents and adults are secondary to sexual contact. Abstinence and careful selection of sexual partners are important. Whether condoms are effective in preventing spread is unclear. Good personal hygiene is important in limiting transmission. Autoinoculation may result from trauma, such as shaving or the manipulation of lesions by the patient.

Pharmacologic Therapy
Clinical success has been reported with the use of the following topical agents, which may act as irritants, stimulating an immunologic response:

Imiquimod cream - An immune response modifier approved for the treatment of external genital and perianal warts in adults, imiquimod cream has been reported to be effective in the treatment of molluscum contagiosum[26, 27] ; imiquimod cream may be used in conjunction with cantharidin[28] Cantharidin - Several studies report that cantharidin, a chemovesicant that can be used in combination with imiquimod, is effective in treating molluscum contagiosum; to test the patient's response to therapy, treat only a few lesions on the initial visit[28] Tretinoin - This agent has reportedly been successful in the treatment of small molluscum contagiosum lesions Bichloracetic acid Trichloroacetic acid Salicylic acid Lactic acid Glycolic acid Silver nitrate Tretinoin, cantharidin, and imiquimod may be dispensed to the patient with application instructions and close follow-up, although some recommend application in the office. Bichloracetic acid, trichloroacetic acid, salicylic acid, lactic acid, glycolic acid, and silver nitrate must be applied in the office by the physician. Topical podophyllotoxin 0.5% cream self-administered twice daily for 3 weeks has been reported effective in a placebocontrolled, double-blind study.[29] Reports have suggested that subcutaneous interferon alfa administered intralesionally may be useful in immunocompromised children. A case report noted the efficacy of topical cidofovir in the treatment of disseminated molluscum in immunodepressed patients.[6] Cidofovir diphosphate was reported to inhibit molluscum contagiosum virus DNA polymerase activity. [30]

Benign Neglect
Leaving mollusca to spontaneously resolve is often reasonable, [31] 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 spontaneously resolve. When facial lesions require treatment, the best option is to treat them frequently with minor physical trauma. (See the image below.)

Lesions on the upper eyelid of a 3-year-old child.

More aggressive therapy may be required in patients in whom the extent of disease is intolerable and in patients who are immunocompromised.

Direct Lesional Trauma

Takematsu et al reported that disruption of the epidermal wall of Henderson-Paterson bodies induces acute inflammatory changes by activation of the alternative complement pathway on exposure to the tissue fluids; furthermore, the Henderson-Paterson bodies release proinflammatory cytokines and other neutrophil chemotactic factors upon decomposition.[32] This supports the observation that minor trauma to molluscum lesions frequently produces an inflammatory response and resolution of the lesion. The Henderson-Paterson bodies can be ruptured and a local inflammatory response created by various forms of physical trauma and caustic topical agents. Various caustic agents have been shown to be effective in treating molluscum contagiosum. Tretinoin, salicylic acid, and potassium hydroxide[33, 34] may be used. Cantharidin,[28, 35] silver nitrate,[36] trichloroacetic acid, and phenol also are options. Children may tolerate therapy with these agents better than curettage or cryotherapy. None of these caustic agents has been approved by the FDA for treatment of molluscum contagiosum.

Tretinoin cream
Tretinoin cream 0.1% or gel 0.025% is applied daily. Apply it to a region of skin with scattered lesions. It may produce eczema and may increase the number of lesions through autoinoculation; however, a small amount of tretinoin may be applied to individual lesions with the rough end of a broken toothpick. Rotate the toothpick, gently abrading the lesion and increasing the inflammatory response produced by the tretinoin. Treat lesions every few days until significant inflammation or resolution occurs.

Potassium hydroxide
Potassium hydroxide is a strong alkali that has long been known to digest proteins, lipids, and most other epithelial debris of skin scrapings to identify fungal infections. Topical 10% potassium hydroxide aqueous solution applied twice daily on each molluscum contagiosum lesion until all lesions undergo inflammation and superficial ulceration may be effective in clearing molluscum contagiosum in children.

Cantharidin
Cantharidin is a chemovesicant that is highly effective in treating molluscum contagiosum; however, this agent has lost favor with some physicians because of concerns regarding its safety. However, if cantharidin is used properly, it is very effective, safe, and well tolerated by children. In a study by Silverberg et al in which 300 patients were treated with cantharidin, 90% of patients experienced complete clearing after an average of 2.1 visits. Blisters occurred at sites of application in 92% of patients. Temporary burning, pain, erythema, or pruritus was reported in 6-37% of patients. No major adverse effects were reported, and no patients experienced secondary bacterial infection. A total of 95% of parents reported that they would proceed with cantharidin therapy again.[37] Cantharidin is not approved by the FDA for treatment of any condition; however, it has been used safely and effectively by dermatologists for many years.[38, 39] It is listed as acceptable therapy in the American Academy of Dermatology treatment guidelines for warts; however, because it has never been approved by the FDA for use in humans, it is no longer marketed as medical therapy in the United States. Cantharidin crystals and diluent can be purchased in the United States, and many dermatologists continue to use it. Cantharidin solution for the treatment of warts and molluscum is available in Canada and many other countries.

Salicylic acid

Seventeen percent salicylic acid in collodion (Compound W, Freezone, Wart-Off, Occlusal) is commonly used in treating verruca vulgaris. In most patients, repeated application to individual molluscum contagiosum lesions until an inflammatory response is generated is effective therapy.

Physical trauma
Varying degrees of physical trauma to individual lesions are used and are frequently quite successful. Physical trauma to individual molluscum contagiosum lesions can be performed with cryotherapy, lasers, curettage,[40, 41] expression of the central core with tweezers, rupture of the central core with a needle or a toothpick, [42, 43] electrodesiccation, shave removal, or duct tape occlusion.[44] Instruct the parents to tease out the firm, white core at the center of lesions using a clean needle or a 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 patient's 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 may also 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 23 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 with 1 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, PDL therapy may be considered for treatment of extensive or resistant lesions. It may also be valuable in immunocompromised individuals with extensive disease.[45, 46, 47, 48, 49] Treatment of molluscum contagiosum in patients with AIDS remains a challenge. The combination of 2 or more therapeutic modalities, such as carbon dioxide laser, PDL, and trichloroacetic acid, 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. Lesions may be sprayed with ethyl chloride until frosting has occurred and then scraped away with a curette. The application of local anesthetic cream, EMLA (a eutectic mixture of 5% lignocaine and prilocaine) or its equivalent, may permit painless treatment. The cream is best applied under occlusion 1-2 hours before the planned procedure.

Immune Response Stimulation

Imiquimod cream, intralesional interferon alfa, [50] and topical injections of streptococcal antigen[51] have been shown to be effective in treating patients with resistant molluscum contagiosum. The high cost of these products limits their use to more extensive or resistant infections. Imiquimod cream applied 3 times per week for 16 weeks is an option in severe cases. The dosing schedule and length of treatment require further evaluation. [25, 27, 52, 53, 54, 55, 56, 57] Imiquimod is a novel topical immune response modifier that is a potent inducer of interferons. Various treatment regimens have been effective in treating molluscum contagiosum. In children [58, 59] and in some patients with AIDSassociated molluscum contagiosum,[60, 26] 1% cream applied 3 times daily or 5% cream applied at every bedtime for 4 weeks appears to be effective treatment. A newer compound, Veregen,is a sinecatechin. Its true mechanism of action is unknown. It is a botanical extract from green tea. The 15% ointment is applied topically 3 times a day. It is FDA approved for topical therapy for external genital warts and perianal warts, but it is used off label for molluscum as well as verruca plana. [61]

Antiviral Therapy
In immunocompromised patients, improvement of lesions has been observed in individual patients treated with ritonavir, cidofovir (intravenous and topical),[62, 63]and zidovudine. Not surprisingly, patients with AIDS and severe molluscum contagiosum improve with effective antiretroviral therapy.

Medication Summary
Molluscum contagiosum usually resolves within months in people with a normal immune system. Many treatments have been promoted for molluscum contagiosum. The common goal of most treatment methods is the destruction of lesions

and the development of a localized inflammatory reaction. Extensive controlled studies have not been performed and all treatments have advantages and disadvantages. A review for the Cochrane Database examined the effects of several topical, systemic, and homeopathic interventions. [64] Among the findings, the investigators determined that there was limited evidence for the efficacy of sodium nitrite coapplied with salicylic acid compared with salicylic acid alone. In addition, no statistically significant differences were found for topical povidone iodine plus salicylic acid compared with either povidone iodine or salicylic acid alone The investigators also found no statistically significant differences between treatment with placebo and therapy with potassium hydroxide or between placebo treatment and systemic treatment with cimetidine or calcarea carbonica, a homeopathic drug. The authors concluded no single intervention has been shown to be convincingly effective in treating molluscum contagiosum. However, various limitations were found in the studies reviewed, and the investigators cautioned that small study sizes may have caused some important treatment differences to be missed. None of the evaluated treatment options were associated with serious adverse effects.

Keratolytic Agents
Class Summary
These agents inhibit cell growth and destroy infected cells. They are applied directly to lesions. To decrease discomfort, treat a small number of lesions at each visit.

Salicylic acid (Compound W, Freezone, Wart-Off)

Adult Dosing & Uses

Dosing Forms & Strengths
topical liquid

6% 12.6% 15% 17% 26% 27.5% 40%

Plantar Warts/Calluses/Corn
Hydrate skin prior to application by soaking in warm water for 5 min, then dry skin thoroughly Liquid: Protect surrounding unaffected skin with petrolatum, then apply liquid to hyperkeratotic area Patches/plasters/strips: Apply as directed per individual product Product content varies, check individual labeling Salicylic acid produces desquamation and inflammation. Various liquid products that contain 17% salicylic acid as the caustic agent or as part of a mix of caustic agents used to treat molluscum contagiosum and warts are available. Most of these products include an adhesive such as collodion or a clear nail-polishlike material, which dries within seconds of application. This helps to concentrate the caustic agent on the lesion and minimize spread to the surrounding skin.

Tretinoin topical (Retin-A, Avita, Tretin-X)

Pediatric Dosing & Uses

Dosing Forms & Strengths
topical cream/gel

0.01% 0.02% 0.025% 0.0375% 0.04% 0.05% 0.1%

Acne Vulgaris (Except Renova)

<12 years old: Safety and efficacy not established 12 years or older: Apply small amount to area qHS (pea-sized amount)

Tretinoin is available in various bases and concentrations (0.025%, 0.05%, 0.1% cream; 0.01%, 0.025%, 0.1% gel; 0.05% solution). Applied to a region of skin with scattered lesions, tretinoin may produce eczema and increase the number of lesions through autoinoculation. However, a small amount of tretinoin may be applied to individual lesions with good effect.

Cantharidin
Cantharidin is a strong vesicant. It has not been approved by the FDA for the treatment of any condition but has been safely and effectively used by dermatologists for years. In the American Academy of Dermatology treatment guidelines for warts, it is listed as the second-line therapy following liquid nitrogen. However, because cantharidin has never been approved by the FDA for use in humans, it is no longer marketed in the United States. Cantharidin crystals and diluent can be purchased in the United States, and numerous dermatologists continue to use it. Cantharidin solution for the treatment of warts and molluscum is available in Canada and many other countries. The effectiveness results from the exfoliation of the lesion as a consequence of cantharidin's vesicant action. The lytic action does not go below the basement membrane of epidermal cells. As a result, unless the area becomes secondarily traumatized or infected, no scarring from topical application occurs.

Topical Skin Products

Class Summary
These agents induce cytokines, including interferon. They are typically reserved for use in patients with molluscum contagiosum that is refractory to cryotherapy or tretinoin.

Imiquimod 5% cream (Aldara, Zyclara)

Pediatric Dosing & Uses

Dosing Forms & Strengths
topical cream

3.75% (9.375mg drug/packet, 28 packets) 5% (12.5mg drug/packet, 12 packets)

External Genital Warts

<12 years: safety and efficacy not established 12 years or older

3.75% cream: Apply 1 packet of 3.75% cream as thin layer qDay HS; leave on skin for ~8 hr, then wash; apply for up to 8 weeks 5% cream: Apply 1 packet of creams as thin layer 3 times/week HS; leave on skin for 6-10 hr, then wash; apply for up to 16 weeks Do not occlude application site Imiquimod induces the secretion of interferon alfa and other cytokines; its mechanisms of action are unknown.

Antivirals, Other
Class Summary
Presumably, antiviral drugs may interfere with the ability of the molluscum contagiosum virus to replicate. Because of their expense and adverse effect potential, consider these products for use only in immunocompromised patients.
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Cidofovir (Vistide)
Cidofovir is a selective inhibitor of viral DNA production in cytomegalovirus and other herpes viruses. One case report showed improvement in 3 out of 3 patients with HIV and extensive co-infection with molluscum contagiosum virus.

Adult Dosing & Uses

Dosing Forms & Strengths
injectable solution

75mg/mL

Cytomegalovirus Retinitis
Induction treatment: 5 mg/kg IV over 1 hour, once/week x2 weeks Maintenance treatment: 5 mg/kg IV q2Weeks Serum creatinine (SCr) increase 0.3-0.4 mg/dL above baseline: Reduce to 3 mg/kg IV SCr increase >0.4 mg/dL above baseline: Discontinue therapy

Monitor: SCr, urine protein, WBC with differential prior to each dose, IOP, visual acuity

Concomitant Therapy
Must administer probenecid orally with each dose of cidofovir Probenecid dose: Must administer 2 g of probenecid 3 hours prior to each cidofovir dose and 1 g at 2 hours and again at 8 hours after completion of 1 hour cidofovir infusion (for a total of 4 g); ingestion of food prior to each dose of probenecid may reduce drug-related nausea and vomiting Hydration: Must receive at least 1 L of 0.9% (normal) saline solution IV prior to each infusion of cidofovir; should administer over 1-2 hours; may administer a second liter over 1-3 hours at start of cidofovir infusion or immediately following infusion if tolerated
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Ritonavir (Norvir)
Ritonavir is an antiretroviral protease inhibitor. In one case report, a patient with HIV and intractable molluscum contagiosum had resolution of lesions after treatment.

Adult Dosing & Uses

Dosing Forms & Strengths
capsule, tablet

100mg oral solution 80mg/mL

HIV Infection
Not typically used as sole protease inhibitor (PI), but as pharmacokinetic enhancer of other PIs Indicated in combination with other antiretroviral agents for the treatment of HIV-infection 300 mg PO BID intially; increase by 100 mg BID to 600 mg PO BID over 5 days as tolerated Use as booster with another protease inhibitor: 100-400 mg PO qDay or divided BID

Administration
Gradually increase to dose to avoid nausea/vomiting Tablet: Take with food Capsule and oral solution: Take with food if possible (may improve tolerability) May mix capsules/oral solution with chocolate milk, Ensure Tablets may be stored at room temperature Capsules must be stored in refrigerator; may be left at room temperature for up to 30 days

Herbal Formulations
Class Summary
These agents are over-the-counter, herbal alternatives. It is essential to be aware, however, that herbal formulations are not regulated by the FDA.

Australian lemon myrtle (Backhousia citriodora)

This is a 10% solution of essential oil of Australian lemon myrtle. [65]