This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.ABSTRACT HYPOTHESIS It is expected that imiquimod cream, 5%, will be a safe and well-tolerated treatment for molluscum contagiosum in pediatric patients. Low concentrations of imiquimod and metabolites S-26704 and S-27700 in serum are expected in this pediatric MC study based on the results of previous external genital/perianal warts studies.
SPECIFIC AIMS The primary objective of this study is to evaluate the systemic exposure of imiquimod cream, 5% following single and multiple-dose administration in pediatric subjects aged 2 to 12 years with extensive MC. Secondary objectives include the evaluation of safety and tolerance of topically applied imiquimod cream, 5% in pediatric subjects with extensive MC disease.BACKGROUND AND SIGNIFICANCE Molluscum contagiosum (MC) is a common childhood viral infection with cutaneous manifestations characterized by discrete single or multiple, firm, umbilicated dome-shaped papules ranging in size from 1 mm to 1 cm. It is caused by the molluscum contagiosum virus (MCV), a pox virus of double-stranded deoxyribonucleic acid (DNA) that includes the variola species of the smallpox virus. Like the variola species, MCV relies exclusively on humans as hosts. Most patients typically present to the clinic with multiple lesions. Although MC lesions can involve any anatomic site, the most common locations include the trunk, axillae, antecubital and popliteal fossae, and crural folds. MC lesions can sometimes have an associated eczematous reaction around the papule that can cause discomfort and pruritis. Occasionally, MC can occur on the eyelid and mouth. Ocular MC has been reported to induce conjunctivitis in some patients and can be very difficult to treat. The incubation period and clinical course is poorly documented. MC lesions in most immunocompetent patients will eventually resolve without treatment, however, some lesions can take years to spontaneously clear.The diagnosis of MC is made clinically, but when necessary, a biopsy or crust preparation can be used to confirm the clinical diagnosis. Histologically, epithelial proliferation with intraepidermal globules with central and viral debris and 'molluscum bodies,' large eosinophilic globules within keratinocytes, are observed. The virions within the infected cells surround themselves with an ultrastructural thin membrane, which may act as a protective barrier against cells involved in immune surveillance. These mechanisms may explain why an absence of Langerhans cells and natural killer cells within MC lesions has been observed.MCV has a worldwide distribution but has been reported to be more common in tropical areas. Most people who are exposed to the MCV, however, do not develop clinical lesions. The incidence of clinical lesions appears to be most common in young children. The mode of transmission is believed to be direct contact with an infected individual and fomites. Transmission seems to be facilitated by mechanical trauma.Currently, there are no approved drug therapies for the treatment of MC. Treatment options include watchful waiting, physical ablation (eg, curettage, liquid nitrogen), and chemical ablation with cantharidin, podophyllin, silver nitrate, potassium hydroxide, or phenol. Although most lesions spontaneously resolve, this process can take as long as 2 years in some patients. Furthermore, some patients can infect other areas of skin through autoinoculation as well as spread the infection to others.Physical and chemical ablative therapies can result in scarring, however, even untreated lesions have also been reported to cause scarring. Therefore, a safe and effective therapeutic option for pediatric patients would fill an unmet clinical need for the treatment of MC.
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