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Case 5: Discussion

Virology and Epidemiology

Molluscum contagiosum is caused by a large, double-stranded DNA poxvirus. Attempts to cultivate molluscum contagiosum virus using conventional tissue culture or eggs have remained unsuccessful, although investigators have grown this virus in human foreskin grafted to athymic mice. More recent research has established the genetic sequence of molluscum contagiosum DNA. Nevertheless, the difficulty in isolating molluscum contagiosum virus has hampered a more precise understanding of the biology of this virus. The transmission of molluscum contagiosum virus occurs via skin-to-skin contact, including contact that occurs with sexual activity. An individual infected with molluscum contagiosum virus can also spread the infection via autoinoculation. The virus infects epidermal keratinocytes and viral replication occurs in the cytoplasm of these cells. This infection results in a significant loss of S-100 protein-positive dendritic cells in mid and upper layers of overlying epidermis thereby causing local modulation of cytokines and a decrease in the number of Langerhans cells[1,2]. The molluscum contagiosum virus uses multiple mechanisms in an attempt to evade the host immune response[1]. Although the exact incidence of molluscum in HIV-infected persons remains unknown, studies have estimated that 5 to 18% of untreated HIV-infected patients develop molluscum lesions at some point in their clinical course[3]. Among HIV-infected persons who have a CD4 count less than 200 cells/mm3, the incidence is higher, probably in the 25 to 35% range. Whether antiretroviral therapy has significantly altered the incidence of molluscum in HIV-infected persons remains unclear, but most clinicians have the impression that severe disfiguring molluscum now occurs much less frequently.

Clinical Findings

Among HIV-infected patients who develop molluscum contagiosum, most have advanced immune suppression, with several studies showing a mean CD4 count of approximately 100 cells/mm3[4,5]. The molluscum lesions typically first appear as multiple, painless, flesh-colored, papules that can appear anywhere on the body, but most often are located on the face, neck, and genital tract (Figure 1 and Figure 2)[1,4,6]. Up to 5% of HIV-infected patients with molluscum will have involvement of the eyelid (Figure 3)[7,8]. Often the lesions do not have the characteristic dome shape with central umbilication that is generally seen in the molluscum lesions that develop in healthy children. Patients with advanced HIV disease often have persistent molluscum lesions that gradually increase in size, with some patients developing giant, tumor-like, nodular lesions that can exceed 1 cm in diameter and become very deforming (Figure 4 and Figure 5)[1,6,9]. In particularly severe cases, the lesion can become necrotic[10]. The number of lesions generally varies inversely with CD4 cell count[4], with some patients with very advanced immune suppression developing several hundred lesions in a disseminated pattern (Figure 6)[11]. Disseminated molluscum can resemble the lesions seen with disseminated cryptococcal disease[12]. Several reports have described highly unusual manifestations of molluscum, including a penile horn[13]. Overall, compared with immune competent persons, molluscum lesions in HIV-infected persons with advance immune suppression are characterized by greater number, larger size, more rapid growth, and atypical locations. Although the cutaneous lesions in HIV-infected persons can cause dramatic cosmetic effects, molluscum does not cause systemic complications.

Diagnosis

In most cases, a clinician experienced in HIV care can make the diagnosis of molluscum on a clinical basis. To confirm the diagnosis, a thick white core can usually be expressed from the center of the lesion, then smeared on a slide to show the Henderson-Patterson (molluscum) bodies. If the clinical diagnosis remains in doubt, hematoxylin and eosin staining of a skin biopsy specimen can confirm the diagnosis. The characteristic histologic feature is the presence of large, eosinophilic, intracytoplasmic Henderson-Patterson inclusion bodies (Figure 7)[1,11]. These Henderson-Patterson bodies consist of a membrane sac that contains numerous viral particles. In addition, the histology typically shows epidermal hyperplasia, increased size of basophils, a deep purple basal keratinocytes. Specific immunohistochemical staining using S-100 protein reveals a significant decrease in the number of S-100 protein-positive dendritic cells in the mid to upper layers of the overlying epidermis[1]. If performed, electron microscopy shows multiple brick-shaped viral particles within the intracytoplasmic Henderson-Patterson bodies.

General Approach to Therapy

In contrast to healthy children with molluscum, in whom the course is usually self-limited, HIV-infected persons with advanced immunosuppression typically have persistent and progressive lesions. The primary goal of therapy is to improve the patient's cosmetic appearance, but therapy will also diminish the likelihood of spread by autoinoculation and decrease the risk of transmission to others. Multiple reports have described dramatic improvement in molluscum lesions following initiation of potent antiretroviral therapy[14,15,16]. Thus, the most important component of therapy is to maximize the patient's immune status with antiretroviral therapy. Several reports, however, have noted a temporary flare in the molluscum lesions after starting antiretroviral therapy in an apparent immune reconstitution manifestation[17,18].

Local Destructive Measures and Topical Therapy

Specific treatment options for molluscum consist of local destructive measures or topical therapies (Figure 8). The local destructive measures include cryotherapy, curettage, and electrodessication. Among these options, cryotherapy is the most commonly used by non-dermatologists; treatments for molluscum consist of applying liquid nitrogen to the lesion for 5-10 seconds and repeating this process after the lesion thaws. Several courses of cryotherapy, spaced 2-3 weeks apart, usually provide high response rates, but cryotherapy is painful, it can cause significant blistering, and patients can end up with post-treatment pigment changes, a particularly problematic issue for facial lesions. Multiple topical agents have been shown to be highly effective in treating molluscum, including tretinoin (Avita, Renova, Retin-A), cantharidin (Cantharone, Cantharone Plus), podophyllin and podofilox (Condylox), acetic acid preparations, imiquimod (Aldara), and topical cidofovir (Vistide). Topical tretinoin generally works best when multiple small lesions are present. In a study involving 20 patients with disseminated facial molluscum, investigators compared cryosurgery (left side of face) with trichloroacetic acid 100% peels (right side of face) and found trichloroacetic acid treatment resulted in a 90% average reduction in lesion count versus a 55% average reduction with cryotherapy[22]. Imiquimod (Aldara) appears to produce very good results in treating molluscum, presumably working by altering the cytokine milieu in the region around the lesion[3,6,19]. Several reports have documented dramatic responses to topical cidofovir in patients with severe cases of HIV-associated molluscum[10,20], and one report described a patient who had improvement in molluscum lesions while receiving intravenous cidofovir for treatment of cytomegalovirus retinitis[21]. Unfortunately, no commercial preparations of topical cidofovir are manufactured.

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    Figure 1. Facial Molluscum Contagiosum

    This HIV-infected patient had multiple small, painless papular lesions of variable size present diffusely on the face. The patient had advanced HIV-related immune suppression.


    Figure 1
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    Figure 2. Genital Molluscum Contagiosum

    This HIV-infected individual developed multiple, persistent molluscum lesions in the genital region. One of the lesions has the characteristic dome-shaped contour with central umbilication.


    Figure 2
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    Figure 3. Periocular Molluscum Contagiosum

    This image shows an HIV-infected individual with multiple periocular molluscum contagiosum lesions.


    Figure 3
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    Figure 4. Giant Molluscum Contagiosum

    This image shows an HIV-infected individual who had advanced immune suppression and persistent molluscum on his face that gradually enlarged to form large nodular lesions.


    Figure 4
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    Figure 5. Giant Facial Molluscum Contagiosum

    This HIV-infected patient had extensive facial molluscum, including a giant molluscum lesion on the lateral aspect of his left eyebrow. This slide is courtesy of Ciro R. Martins, MD, Department of Dermatology, John's Hopkins University.


    Figure 5
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    Figure 6. Extensive Facial Molluscum Contagiosum

    Numerous molluscum lesions in a 33-year-old patient with AIDS and a CD4 count of 60 cells/mm3. This figure is from Cotell SL, Roholt NS. Images in clinical medicine. Molluscum contagiosum in a patient with the acquired immunodeficiency syndrome. N Engl J Med. 1998;338:888. Reproduced with permission from the Massachusetts Medical Society. Copyright © 1998 Massachusetts Medical Society. All rights reserved.


    Figure 6
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    Figure 7. Histologic Appearance of Molluscum Contagiosum

    This hematoxylin and eosin stained skin biopsy taken from a patient with AIDS and molluscum (see figure 6) shows lobules of keratinocytes that contain numerous large eosinophilic intracytoplasmic inclusion bodies (Henderson-Patterson, or molluscum bodies) [arrows]. Magnification x20. This figure is from Cotell SL, Roholt NS. Images in clinical medicine. Molluscum contagiosum in a patient with the acquired immunodeficiency syndrome. N Engl J Med. 1998;338:888. Reproduced with permission from the Massachusetts Medical Society. Copyright © 1998 Massachusetts Medical Society. All rights reserved.


    Figure 7
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    Figure 8. Treatment of Molluscum Contagiosum

    Abbreviations: qd = once daily; bid = twice daily; d = day; qhs = once at nighttime


    Figure 8