Are You Confident of the Diagnosis?
What you should be alert for in the history
Molluscum contagiosus, also known as molluscipoxvirus (MCV), can infect healthy children and adults. Risk factors for infection include atopic dermatitis, immunosuppression and sexual activity. History often reveals a new papule or “bump” that slowly grows over time. Incubation for MCV is typically 2-7 weeks but it has been reported at 1 week of age.
The most common location is the trunk, however the extremities, groin and face can also be involved. The palms and soles, as well as mucous membranes are usually spared. Spontaneous resolution can occur after several months-years, however most patients develop multiple lesions before this occurs.
Characteristic findings on physical examination
Infection with MCV results in discrete flesh-colored to pink dome-shaped smooth papules that typically range from 1-5 mm in diameter (Figure 1, Figure 2). A central dell or umbilication can often be appreciated which represents a central plug of dead epithelial cells and virus particles. This plug may be expressed with pressure to produce a white curd-like substance that is highly infectious.
Occassionally “molluscum dermatitis “ develops, consisting of erythema and scale surrounding the papules. The lesions may present as a single papule or in groups, but patients often develop multiple lesions secondary to autoinnoculation. The lesions are typically asymptomatic and do not scar upon resolution. Some do actually resolve with pinpoint areas of atrophy without treatment.
Expected results of diagnostic studies
Diagnosis is typically clinical, however tests are available. Giemsa stain of a crush preparation of the contents of the central plug will show intracytoplasmic molluscum inclusion bodies Histopathologic examination reveals inverted lobules with hyperplastic epidermis and enlarged cells above the basal lamina that contain eosinophilic intracytoplasmic inclusions (“Henderson-Paterson” or “molluscum” bodies) (Figure 3, Figure 4). Although rarely utilized, electron microscopy can be performed on biopsies that will show the characteristic brick-shaped viral particles inside the Henderson-Paterson inclusion bodies.
In general, the differential diagnosis for MCV inculdes verrucae (warts), pyogenic granulomas, appendageal tumors (syringomas, hydrocystomas and trichoepitheliomas), Langerhans cell histiocytosis, amelanotic melanomas, and basal cell carcinomas. In immunosuppressed individuals, other opportunistic fungal infections should be considered, such as histoplasmosis, cryptococcosis, coccidiodomycosis and penicillosis. More specifically, location and size direct the differential diagnosis.
In sexually transmitted cases, condyloma accuminata can closely resemble MCV. In cases associated with molluscum dermatitis, atopic dermatitis should be considered. Facial eruptions can mimic acneiform eruptions, especially when inflammation co-exists, and eyelid infections can be confused with a stye or chalazion. Giant molluscum are more easily confused with neoplasms such as basal cell carcinomas, keratoacanthomas, or appendageal tumors, and can also be confused with epidermal inclusion cysts.
Who is at Risk for Developing this Disease?
POPULATIONS MOST COMMONLY AFFECTED
MCV infection most commonly occurs in immunocompetent school-age children . Children with Darier’s disease, ichthyosis, atopic dermatitis, or a genetic or acquired immunodeficiency are at higher risk for infection or dissemination. In children, the most frequently infected part of the body is face, neck, trunk and extremities, but can occur on any part of the body including mucous membranes.
If the infection is seen in the close to the anus of children, sexual transmission can be a consideration. However, most cases near the genitals of children represent transmission by autoinoculation.
Individuals with atopic dermatitis are at a higher risk for MCV infection as well as more widespread skin involvement, prolonged course and molluscum dermatitis. Because of the associated pruritus with atopic dermatitis and molluscum dermatitis, these patients are also at a higher risk of autoinoculation. It is unclear if atopic dermatitis patients are at higher risk for MCV because of barrier dysfunction, frequent dermatitis or use of topical medications, however these patients should receive concurrent treatment for MCV along with their usual regimen for atopic dermatitis.
Adolescents and adults
MCV infection is less common in adults and adolescents and is often due to sexual transmission or contact sports. Sexually active adults typically present with lesions in the groin, upper thighs, or lower abdomen and can also have lesions on the genitals. Individuals involved in close-contact sports are at a higher risk of infection because of direct skin-to-skin contact and sharing equipment, including towels and sponges. Swimming pools have also been implicated as a source of infection.
Immunosuppressed individuals are at a higher risk for MCV infection as well as an atypical presentation of MCV infection. Lesions may be found more often on the face, eyelids and neck and may not have the characteristic umbilication. The lesions may also grow larger and coalesce into plaques, have a verrucous appearance or become ulcerative and disfiguring.
Infections in this population typically persist for years and have a higher incidence of secondary bacterial infection. Giant molluscum (>1cm in diameter) are observed in HIV/AIDS patients and can be a marker for decreased CD4 lymphocyte counts. It has been reported that over 30% of patients with HIV/AIDS that have a CD4 count of less than 100 cells/mL are also co-infected with MCV.
MCV infection has a worldwide distribution but is sometimes seen more commonly in tropical climates, as well as in areas with poor hygeine, poverty and overcrowding. Annual incidence is reported between 2% and 10%, however this is likely an underestimate since many patients do not seek medical attention. The prevalence of MCV has risen significanly over the past two decades in the United States.
What is the Cause of the Disease?
MCV is a member of the Poxviridae family and exists as a large, brick-shaped, double-stranded DNA virus. Four major subtypes exist (MCV-1, MCV-2, MCV-3 and MCV-4). All subtypes appear clinically indistinguishable;, however, it has ben shown that MCV-1 is responsible for the majority of infections in children, whereas MCV-2 accounts for infection in immunocompromised individuals and sexually-transmitted infection.
Transmission of the virus occurs by direct contact with infected skin or indirectly by fomites. Swimming pools and shared bath towels have been implicated as sources of infection. Also, individuals who participate in close contact sports appear to be at higher risk for infection. Autoinnoculation and koebnerization of already infected patients is also common due to manipulation or scratching.
MCV is a benign infection in immunocompetent patients, and spontaneous resolution typically occurs in less than a year. However, due to the risk of spread and prolonged course, treatment is usually pursued. Lifelong immunity can occur after infection.
MCV infects epithelial cells and replicates in keratinocytes most often in the epidermis. Hypertrophy and hyperplasia is induced in infected cells, causing the replication rate to double. The MCV genome shares similarities with other members of the poxvirus family, with up to two-thirds of genes resembling those found in variola and vaccinia virus. Many viral genomically-encoded molecules have been implicated in the impaired immune response of the human host, including MC54, MC148, MC013L, MC159, MC80 and MC66.
Systemic Implications and Complications
The majority of MCV infections occur in healthy children, or in children with atopic dermatitis. Healthy adults and adolescents are also infected by MCV, but more commonly in a sexually-transmitted fashion, although non sexually-transmitted MCV infection does not necessarily warrant a work-up. However, prolonged or numerous MCV infections may be an indicator of immunosuppression.
Congenital and acquired immunodeficiencies could be considered in children with extensive MCV infections(if the lesions are more numerous and diffuse than seen in most patients in your clinical expierence). Initial work-up can include complete blood count (CBC), immunoglobulins, antibody titers to viral/bacterial antigens along with referral to immunology. Atopic dermatitis is often a concurrent condition in children and appropriate treatment measures should be taken to control the atopic dermatitis as well as the MCV infection.
Adults and Adolescents
Sexually transmitted MCV infections are the most common type of MCV transmission in this population. If sexual transmission is observed, testing for concurrent common sexually transmitted infections should be performed, including gonorrhoea, chlamydia and syphilis as indicated, in the appropriate clinical context.
Recalcitrant or atypical MCV infections may warrant an immunosuppression work-up in all age groups, but especially in adults. HIV with reflexive CD4 count testing is paramount in any patients with risk factors. HAART therapy to bring CD4 counts above 200 cells/mL has been shown to resolve MCV infections. Cidofovir is another option in patients with AIDS that are unresponsive to HAART therapy Immunosuppression caused by hereditary or acquired conditions should also be considered in recalcitrant cases, and initial work-up including CBC, immunoglobulins, antibody titers to viral/bacterial antigens along with consultation with immunology.
The evidence is limited for MCV treatment. A 2009 Cochrane review concluded insufficient evidence to recommend specific treatments for MCV. However, despite no general consensus or conclusive clinical trials for MCV therapies, there are still a number of options utilized by dermatologists.
An option for any immunocompetent individual is observation. MCV lesions are typically self-limiting over several months-years; however due to risk of spread, transmission, associated symptoms and cosmesis, treatment is usually pursued. Patients with atopic dermatitis and immunosuppression should receive treatment to prevent secondary infections and prolonged infections.
The extract of the blistering beetle, Cantharis vesicatoria was the treatment of choice for many dermatologists until recent FDA sanctions have made this substance more difficult for pharmacies to dispense. A wooden stick is used in-office to apply the vesicant to the lesions. They are allowed to air dry and the patient is instructed to wash the area thoroughly in 1 hour. Use in intertriginous areas and occlusion should be avoided due to the risk of increased inflammatory reactions.
The antiviral cidofovir can be applied topically in a 1%-3% compounded gel or cream base. This is applied to the lesions daily 5 days/week until resolution, typically 6-8 weeks. Severe inflammation can occur.
Cryotherapy causes destruction of tissue by direct contact with liquid nitrogen. The destruction may also cause release of viral particles from keratinocytes, eliciting an immune response that aides to clear the infection. Liquid nitrogen may be applied by spray or by cotton-tip applicators directly to the lesion and 2 mm of surrounding tissue. A thaw cycle of 15-20 seconds is desired and typically two cycles are performed per lesion.
This in-office procedure may need to be repeated at 2-3 week intervals and side effects include discomfort, with blistering, dyspigmentation, and sometimes scarring. It is considered an inexpensive and effective therapy for MCV.
Curretage is a physical ablative removal of the lesion performed after application of topical anesthesia. This destructive therapy does not yield as high of an immune response as other destructive methods, but can yield tissue in the case of unclear diagnosis. The utility of this method is limited in younger patients and multiple lesions.
Although manually expressing lesions is a common form of treatment, it is not recommended due to scarring and the potential for inadvertant transmission.
Phenol and Alcohol
Phenol (10%) and alcohol (70%) have been used topically as destructive means, but are not recommended because of scarring.
Podophyllotoxin (Podofilox) is a standardized solution or gel containing podophyllin, which is a plant resin that causes tissue necrosis by arresting mitosis. It can be applied at home with a recommendation of twice daily for 3 days followed by 4 days without therapy for up to 6 weeks. Treatment area should be restricted to less than 10cm2, with a daily maximum dose of 0.5mL to reduce systemic side effects. Local side effects are minimal but include pruritus, erythema and postinflammatory pigmentary changes.
Symptoms that are worrisome for systemic accumulation include gastrointestinal (GI) side effects (nausea, vomiting and diarrhea), neurological side effects (confusion, loss of reflexes and coordination) and psychiatric side effects (irritability and hallucinations. These are dangerous and can progress to seizures and cause neurological damage. Podophyllin is contraindicated in pregnant women.
KOH (5-10% solution) has been shown to be an effective therapy when applied twice daily until evidence of inflammation occurs. Side effects are irritation and dyspigmentation.
Pulsed Dye Laser (PDL)
PDL at 585/595nm selectively damages blood vessels and connective tissue, which may help to induce an immune response against MCV. As few as one treatment may be necessary; and the efficiency of treatment is optimal for patients with multiple lesions
Retinoid creams and liquids have variable results. Destructive effects and possible immunomodulation are postulated mechanisms for retinoid therapy. Typically 0.05% tretinoin is used once to twice daily.
Salicylic and Lactic Acid
Salicylic acid is a beta-hydroxy acid that causes desquamation of the epithelium. It can be a useful agent for MCV, especially in a patient that is willing to do home treatments. Preparations range from lower-strength liquid (17%, Compound W®, Wart-off®, Duofilm®, Duoplant® and Occlusal HP®) to patches (15%, Trans Ver Sal® and 21%, Trans Plantar®), and finally to plasters (40%, Mediplast® or Duofilm®).
Most formulations are a combination with lactic acid an alpha-hydroxy acid which is also a keratolytic. Treatment duration is variable and may cause local irritation, but should continue 2-3 weeks after clinical resolution to prevent recurrence.
Sliver nitrate is available in solution (0.5%, 10%, 25%, 50%) and topical applicators (75%, Lunar Caustic®). Contact with skin causes a chemical reaction that coagulates bacterial proteins and destroys tissue. Topical applicators are used for small lesions by first dipping into water and then pressing on the lesion for cauterization. Silver nitrate paste is also available. Patients often have resolution with one treatment and side effects are typically local irritation and brown discoloration at the site, which resolves within 1-2 weeks.
Bichloroacetic acid and trichloroacetic acid (35%, 80% solution) cause destruction via protein coagulation. Typically the solution is applied to MCV weekly in a physician’s office, taking note to avoid the surrounding normal skin. The lesion is then covered for 5 days and the cycle is repeated every week. Resolution can take many weeks and side effects are generally mild localized irritation but scarring may occur with an incorrect depth of acid penetration.
Intralesional injections of candida antigen (a killed yeast protein) is used as immunotherapy for MCV. The immune response from the candida antigen to the region infected with MCV is thought to help the body also mount an immune response to MCV. A small amount (typically 0.3mL) of candida antigen is injected directly into the lesion at monthly intervals as needed. This can also be used concurrently with destructive methods such as cryotherapy.
Imiquimod (Aldara, 5% cream) is a nonnucleoside heterocyclic amine that acts as an immunomodulator via activation of toll-like receptor 7 to induce cytokines. It also enhances the skin’s immune system by the production of intracellular INF-alpha, IL-12, TNF-alpha and TNF-gamma. It is used off-label for treatment of MCV. Erythema and irritation are the most common side effects, but may also be a sign of efficacy. Recommendations include application to affected areas up to 3 times a week before bed (to allow the 6-10 hours before washing off) as tolerated until resolution of the lesions or up to 16 weeks.
Although H2-antihistamines are typically used for gastric ulcer disease, evidence has shown that cimetidine may provide an antipruritic activity and may enhance cell-mediated immunity against MCV. Although its utility is unclear, it is a relatively safe medication for children and may be beneficial, especially in concurrent atopic dermatitis. Dosing of the medication is generally from 25mg/kg/day – 40mg/kg/day administered for several months.
IFN-alpha is typically reserved for immunocompromised patients with severe MCV. Intralesional or subcutaneous injections are available and the mechanism of action is likely related to immunomodulatory, cytotoxic and antiviral effects.
HAART and Systemic Antivirals
Both HAART therapy in HIV-infected patients and antiviral therapy in other immunosuppressed patients have shown benefit in treating MCV lesions in immunocompromised patients.
Optimal Therapeutic Approach for this Disease
First-line treatment in healthy individuals with few, discrete lesions is cantharidin (if available) and cryotherapy. Cantharidin requires a compliant patient because the medication must be washed off 4-6 hours after application. Cryotherapy can be more immediately painful for patients, but often causes resolution after one treatment.
If cryotherapy is not tolerated, other topical treaments can be considered such as podophyllotoxin, intralesional candida antigen or salicylic acid. For facial lesions, good results have been seen with trichloracetic acid (35%).
For recurrent lesions or patients who are often reinfected, adding cimetidine can be beneficial with low side effects. In healthy patients with multiple lesions or recurrent cases, topical imiquimod can be used. Curretage is ideal for a limited number of lesions and in patients who can tolerate local anesthesia. PDL is not commonly utilized, however may be an option if others fail. HAART and systemic anti-virals are an important component for HIV/immunocompromised patients.
The most important aspect of patient management is always education. Important messages to relay include the “benign” nature of MCV infections. The lack of definitve therapies for this infection is important to convey. Watchful waiting is always an option because of the self-limiting nature of the disease; however, treatment is usually pursued because of the risk of transmission, autoinoculation and social stigma.
Immunosuppression and cell-mediated immune deficiencies are rare underlying causes and should only be considered in relcacitrant or atypical cases. Educating families to help reduce spreading the infection among each other is also of importance. Reassurance that MCV is not officially classified as a sexually transmitted infection may also be emphasized to put parents at ease; however, as discussed above, other STI co-infections should be considered. According to the American Academy of Pediatrics, children need not be kept out of school or daycare.
Care of Lesions
MCV lesions should not be manipulated. The central plug is extremely infectious and transmission from under fingernails is a common form of autoinoculation. In children, fingernails should be cut short to prevent scratching.
Patients with atopic dermatitis present a difficult challenge and care should be taken to treat the underlying atopic dermatitis as well as the MCV. In general, lesions do not need to be covered; however, when undergoing treatment they can become irriatated and may be covered to both aid in treatment and prevent secondary infection, as well as transmission.
Hand and personal hygeine should be emphasized, as well as hygeine associated with sports and team practices. Sharing towels or equipment should be avoided, and showering after practices and frequent laundering of workout attire is critical. Personal clothing, bedding, and other such items of a patient with MCV infection should not be shared among household members. Laundry should be washed with water at least 71 degrees C.
Management and Follow-up
Depending on the treatment method utilized, patients may be seen in office every few weeks to every few months until resolution of the lesions. No follow-up is necessary for MCV infection per se, however, seeing patients as needed for recurrent infections is encouraged. Specialized care should be taken with atopic dermatitis patients; and monitoring for recalcitrant or aypical MCV infections is important in overall patient health since it can give clues about potential cell-mediated immune deficiencies or other forms of immunosuppression.
Unusual Clinical Scenarios to Consider in Patient Management
Atopic dermatitis and congenital cell-mediated immune deficiency, along with other causes of immunsuppression, often represent the cases of MCV that are more recalcitrant to treatment or have an atypical presentation. Although diagnosis is most commonly clinical, the differential is broad and other less-common diagnoses should be considered if unusual behavior of the lesions is noted (see differential diagnosis).
Other treatments that have been reported include acidified nitrite, Australian lemon myrtle oil, benzoyl peroxide, bromogeramine, diphencyprone, Griseofulvin, milkweed, povidone iodine in combination with salicylic acid, yellow oxide of mercury, zinc oxide with colloidal oatmeal extracts, and calcarea carbonica.
Molluscum conjunctivits (and often associated keratitis) is caused by MCV lesions that occur near the eyelid margin. The lesions are often initially missed and patients will complain of persistent conjunctivitis despite multiple antibiotic and steroid eye drops. These lesions can be excised or curetted to provide quick resolution.
What is the Evidence?
Bard, S, Shiman, M, Bellman, B, Connelly, E. “Treatment of facial molluscum contagiosum with trichloracetic acid”. Pediatr Dermatol. vol. 26. 2009 Jul-Aug. pp. 425-6. (An overview of the utility of TCA to treat MCV on the face, highlighting proper technique.)
Clark, Y, Dohil, M. “Warts and molluscum- diagnosis and treatment”. Skin Aging. July 2010. pp. 30-35. (A succinct overview of the pathogenesis and treatment options for MCV.)
Dohil, M, Lin, P, Lee, J, Lucky, A, Paller, A, Eichenfield, L. “The epidemiology of molluscum contagiosum in children”. J Am Acad Dermatol. vol. 54. 2006. pp. 47-54. A retrospective chart review of 3 tertiary pediatric dermatology referral centers looking at epidemiology of MCV. Age, number of lesions, concurrent health problems (including atopic dermatitis) are discussed.)
Julapalli, MR, Levy, ML. “Viral and fungal skin iInfections”. Feigin and Cherry’s textbook of pediatric infectious diseases. 2009. pp. 1934-1935. (An excellent and succinct overview of MCV infections in the pediatric population)
Gould, D. “An overview of molluscum contagiosum: a viral skin condition”. Nurs Stand. vol. 22. 2008 Jun 18-24. pp. 45-8. (A good generalized overview of MCV. This is especially useful for patient management and education, providing advice for families on how to deal with the diagnosis, including transmission prevention at home.)
Lee, R, Schwartz, R. “Pediatric molluscum contagiosum: reflections on the last challenging poxvirus infection, Part 1”. Cutis. vol. 86. 2010 Nov. pp. 230-6. (Excellent overview of epidemiology, clinical presentation, and virulence of MCV.)
Lee, R, Schwartz, R. “Pediatric molluscum contagiosum: Reflections on the last challenging poxvirus infection, Part 2”. Cutis. vol. 86. 2010 Dec. pp. 287-92. (Excellent overview of MCV treatments, including both destructive and systemic.)
Lio, P. “Warts, molluscum and things that go bump on the skin: a practical guide”. Arch Dis Child Educ Pract Ed. vol. 92. 2007 Aug. pp. ep119-24. (A practical guide for the diagnosis and treatment of warts and molluscum in children. A good review for all first-line providers as well as dermatologists.)
Maronn, M, Salm, C, Lyon, V, Galbraith, S. “One-year experience with Candida antigen immunotherapy for warts and molluscum”. Pediatr Dermatol. vol. 25. 2008 Mar-Apr. pp. 189-92. (A retrospective chart review of Candida antigen treatment for warts and molluscum at MCW in 2005. Comparison of side effects, number of treatments needed and a good step-by-step regiment.)
Silverberg, N, Sidbury, R, Mancini, A. “Childhood molluscum contagiosum: experience with cantharidin therapy in 300 patients”. J Am Acad Dermatol. vol. 43. 2000. pp. 503-7. (An excellent overview of cantharidin treatment in pediatric MCV patients, including side effects and efficacy.)
Swiecki, M, Colonna, M. “Disparate antiviral responses in mollusum contagiosum virus-induced skin lesions”. J Invest Dermatol. vol. 131. 2011 Feb. pp. 288-90. (A molecular biology overview of MCV and its effects on the skin and immune system, highlighting variation in inflammatory lesions versus noninflammatory lesions.)
Van der Wouden, JC, van der Sande, R, van Suijlekom-Smit, LW, Berger, M, Butler, C, Koning, S. “Interventions for cutaneous molluscum contagiosum (Review)”. Cochrane Database Syst Rev. 2009 Oct 7. pp. CD004767(Cochrane review of all evidence on MCV treatments through 2010. A good overview that declares no conclusive evidence for a “best treatment” option but reviews many utilized treatments.)
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