Current Management for Molluscum Contagiosum

Current Treatment Practices for Molluscum Contagiosum

  • A Prospective Randomized Trial Comparing the Efficacy and Adverse Effects of Four Recognized Treatments of Molluscum Contagiosum in Children. Hanna D, Hatami A, Powell J, et al. Pediatr Dermatol. 2006;23(6):574-579.
  • Abstract: Molluscum contagiosum is a common viral disease of childhood presenting as small, firm, dome-shaped umbilicated papules. Although benign and generally self-limited, this condition is contagious and can lead to complications such as inflammation, pruritus, dermatitis, bacterial superinfection, and scars. No consensus has been established concerning the management of this condition. We conducted a prospective randomized study comparing four common treatments for molluscum contagiosum in 124 children aged 1 to 18 years. 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. Patients needing, respectively, one, two, or three visits for treatment of their mollusca were: 80.6%, 16.1%, and 3.2% for curettage, 36.7%, 43.3%, and 20.0% for cantharidin, 53.6%, 46.4%, and 0% for salicylic acid and glycolic acid, and 55.2%, 41.4%, and 3.4% for imiquimod. The rate of side effects was 4.7% for group 1, 18.6% for group 2, 53.5% for group 3, and 23.3% for group 4. Curettage was found to be the most efficacious treatment and had the lowest rate of side effects. It must be performed with adequate anesthesia and is a time-consuming procedure. Cantharidin is a useful bloodless alternative particularly in the office setting but has moderate complications due to blisters and necessitated more visits in our experience. The topical keratolytic used was too irritating for children. Topical imiquimod holds promise but the optimum treatment schedule has yet to be determined. Finally, we believe that the ideal treatment for mollusca depends on the individual patient preference, fear, and financial status, distance from the office, and whether they have dermatitis or blood-borne infections.
  • https://pubmed.ncbi.nlm.nih.gov/17156002/
  • Molluscum contagiosum: the importance of early diagnosis and treatment. Tyring SK. Am J Obstet Gynecol. 2003;189(3 Suppl):S12-S16.
  • Molluscum contagiosum is a viral infection that is becoming an increasing problem in sexually active individuals and in patients with human immunodeficiency virus. Although molluscum contagiosum lesions are generally self-limiting, it may take 6 months to 5 years for lesions to disappear. Furthermore, patients with weakened immune systems have increased difficulty in clearing lesions; therefore lesions typically persist for prolonged periods. Although there has been continued debate about whether molluscum contagiosum lesions should be treated or allowed to resolve spontaneously, many clinicians recommend treatment of genital molluscum contagiosum lesions to reduce the risk of sexual transmission, prevent autoinoculation, and increase patient quality of life. Treatment options for molluscum contagiosum include physician-administered and patient-administered therapies. Novel patient-administered treatment options allow administration in the privacy of a patient’s home, providing added convenience and reducing patient embarrassment or stress. With the novel treatment opportunities currently available or in development, physicians are able to improve patient quality of life while providing patients with a convenient, well-tolerated, easily administered treatment regimen. This review summarizes the clinical diagnosis of molluscum contagiosum and provides a critical assessment of several current and emerging treatment options.
  • https://www.ajog.org/article/S0002-9378(03)00793-2/fulltext

Cantharidin Mechanism of Action

  • The Mechanism of Cantharidin Acantholysis. Weakley DR, Eindinder, JM. The Journal of Investigative Dermatology. 35-41.
  • In an earlier paper, we reviewed the literature concerning cantharidin acantholysis and commented on the theories thus far proposed to explain its production. New data were presented, and it was concluded that no adequate biochemical explanation currently exists. Stoughton first emphasized that cantharidin probably acts by affecting some enzyme or enzyme system, and substantiated his theory by producing acantholysis with intradermal injections of papain as well as a proteolytic enzyme isolated from sterile feces of patients with ulcerative colitis. He also pointed out, however, that cantharidin acantholysis showed histologic differences from that produced by these enzymes. Further, he was unable to demonstrate the reaction products expected if such enzymes do indeed mediate the action of cantharidin on skin. The independent development in two laboratories of a dilute aqueous solution of disodium cantharidin (DSC) which readily produces both acantholysis and intraepidermal vesication in vitro has facilitated investigation of the specific biochemical lesion it causes. Many recent data indicate that a number of dermatologic diseases are probably manifestations of specific metabolic aberrations in the skin. Since the cantharidin-skin system used in the experiments reported here works equally well with human or mouse skin, it provided an unusual opportunity to perform biochemical studies on a model system producing acantholysis. Because of the close similarity between the histologic changes induced by cantharidin and those of pemphigus vulgaris, further investigation seemed warranted. The results of these experiments indicate that cantharidin acantholysis is closely linked to the oxidative metabolism of carbohydrate.
  • https://www.sciencedirect.com/science/article/pii/S0022202X15497155
  • Cantharide acantholysis: endogenous protease activation leading to desmosomal plaque dissolution. Bertaux B, Prost C, Heslan M, et al. Br J Dermatol. 1988;118(2):157-165.
  • Using a method which allowed us to study the morphological consequences of the expression and the inhibition of proteases in living tissues, we demonstrated that the primary detectable cellular event in cantharide acantholysis is the dissolution of the dense plaque, leading to the detachment of tonofilaments from desmosomes. This process is inhibited by neutral serine protease inhibitors. This suggests that the desmosome-tonofilament complex, more precisely the desmosomal dense plaque, is the primary target of activated proteases during cantharide acantholysis, and can be disrupted by a specific epidermal protease-anti protease system. Cantharide acantholysis may be useful model for studying desmosomal turnover.
  • https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2133.1988.tb01769.x
    • Paid access
  • Cantharidin-Induced Acantholysis. Piérard-Franchimont C, Piérard GE. The American Journal of Dermatopathology. 1988 (Oct)419-423.
  • Cantharidin has been used to induce acantholysis in vivo. Intraepidermal clefting starts at the junction between the basal and epidermal layers, and later involves all of the levels of the stratum spinosum. As a response to early acantholysis, an increased number of epibasal cells synthesize DNA. This is not related to an increased binding of epidermal growth factor to these cells. In sum, the basal-epibasal junction is one of the weakest within the epidermis. The epibasal cells represent a reserve pool for proliferating keratinocytes that may be stimulated without necessarily binding an increased amount of epidermal growth factor.
  • https://journals.lww.com/amjdermatopathology/Abstract/1988/10000/Cantharidin_Induced_Acantholysis.6.aspx
    • Paid access.
  • Cantharidin-induced acantholysis: adhesion molecules, proteases, and related proteins. Yell JA, Burge SM, Dean D. British Journal of Dermatology. 130: 148-157.
  • Summary: Acantholysis is a feature of disorders such as Hailey‐Hailey disease and Darier’s disease. Immunocytochemical studies have shown internalization of desmosomal components after acantholysis. Basal cytokeratins show suprabasal expression in lesional Darier’s disease. The exact mechanisms of acantholysis are still unclear. Cantharidin induces blistering, with suprabasal keratinocyte acantholysis, possibly by protease activation. Plasmin has been implicated in the pathogenesis of acantholysis in Darier’s disease and Hailey‐Hailey disease. We examined the distribution of desmosomal components, proteases and cytokeratins in cantharidin blisters, to compare them with those previously found in Darier’s disease and Hailey‐Hailey disease. Two drops of cantharidin collodion were applied to the skin of five normal volunteers. A 4‐mm punch biopsy of the blister was taken, and snap frozen. Sections were stained with antibodies to desmosomal proteins (dp) 1/2, dp 3, desmosomal glycoproteins (dg) 1, 2/3, extracellular carbohydrate residues, using the lectins peanut agglutinin (PNA) and soybean agglutinin (SBA), proteases and cytokeratins. Acantholytic cells were stained diffusely with dp l/2: there was markedly reduced or absent peripheral staining for dp 3, dg l, dg 2/3, PNA and SBA. There was no clumping of stain. Plasminogen, fibrinogen and urokinase were expressed in some acantholytic cells. Basal keratin markers were expressed suprabasally in acantholytic cells. These results are similar to those previously obtained in Darier’s disease, but different from the staining obtained in Hailey‐Hailey disease. Extracellular glycosylated portions of adhesion molecules may be lost after acantholysis, perhaps as a result of conformational changes, internalization of extracellular domains, or proteolysis. The changes in the expression of plasminogen, fibrinogen, urokinase and cytokeratins in acantholytic cells in cantharidin‐induced blisters are, as in Darier’s disease and Hailey‐Hailey disease, probably secondary to acantholysis, and changes in the shape of cells. We conclude that cantharidin blisters may be a useful model for the study of acantholysis in Darier’s disease.
  • https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2133.1994.tb02893.x
    • Paid access
  • Cantharidin blisters: a technique for investigating leukocyte trafficking and cytokine production at sites of inflammation in humans. Day RM, Harbord M, Forbes A, et al. J Immunol Methods. 2001; 257(1-2):213-220.
  • A skin blister technique is described which allows the investigation of acute inflammation in humans in vivo. Filter paper discs are placed on the skin, impregnated with cantharidin and covered with impermeable film held by adhesive tape. The assembly is easily applied, unobtrusive, stable and may be worn during normal activities. The blister formed at 24 h contains approximately 5×10(5)-5×10(6) cells, predominantly neutrophils and macrophages. Inflammatory cytokines and chemotactic factors are detectable in the blister fluid. The technique is useful for characterizing the acute inflammatory response in health and disease.
  • https://www.sciencedirect.com/science/article/abs/pii/S0022175901004677?via%3Dihub
    • Paid access
  • Production and resolution of cantharidin-induced inflammatory blisters. Maglio D, Nightingale CH, Nicolau DP. International journal of antimicrobial agents. 2003; 22. 77-80.
  • While inflammatory blisters have long been utilized as a means of evaluating antimicrobial disposition to aid in the development of new treatments for skin and skin structure infections, sparse data are available regarding the healing of the blisters once the experiment has been completed. We report the blister induction technique and resolution time in ten volunteers enrolled in a pharmacokinetic study using the cantharidin-induced inflammatory blister technique.
  • https://www.sciencedirect.com/science/article/abs/pii/S0924857903000840
    • Paid access.
  • Characterisation of Leukocytes in a Human Skin Blister Model of Acute Inflammation and Resolution. Jenner W, Motwani M, Veighey K, et al. PLOS ONE. 2014; 9(3): e89375.
  • There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predominant cells were CD16hi/CD66b+ PMNs followed by HLA-DR+/CD14+ monocytes/macrophages, CD11c+ and CD141+ dendritic cells as well as Siglec-8+ eosinophils. CD3+ T cells, CD19+ B cells and CD56+ NK cells were also present, but in comparatively fewer numbers. During resolution, 72 h following blister induction, numbers of PMNs declined whilst the numbers of monocyte/macrophages remain unchanged, though they upregulated expression of CD16 and CD163. In contrast, the overall numbers of dendritic cells and Siglec-8+ eosinophils increased. Post hoc analysis of these data revealed that of the inflammatory cytokines measured, TNF-α but not IL-1β or IL-8 correlated with increased PMN numbers at the onset. Volunteers with the greatest PMN infiltration at onset displayed the fastest clearance rates for these cells at resolution. Collectively, these data provide insight into the cells that occupy acute resolving blister in humans, the soluble mediators that may control their influx as well as the phenotype of mononuclear phagocytes that predominate the resolution phase. Further use of this model will improve our understanding of the evolution and resolution of inflammation in humans, how defects in these over-lapping pathways may contribute to the variability in disease longevity/chronicity, and lends itself to the screen of putative anti-inflammatory or pro-resolution therapies.
  • https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089375

Compounded Cantharidin for the Treatment of Molluscum Contagiosum

  • Topical Cantharidin in the Management of Molluscum Contagiosum: Preliminary Assessment of an Ether-free, Pharmaceutical-grade Formulation. Del Rosso JQ, Kircik L. J Clin Aesthet Dermatol. 2019;12(2):27-30.
  • Topical application of cantharidin, a vesicant that is naturally derived from the blister beetle, has a long track record of being used to treat primarily cutaneous molluscum contagiosum and Verrucae. Although not approved by the United States Food and Drug Administration, cantharidin has been available through a variety of compounding sources without standardization of manufacturing, formulation, or method of application. Randomized, controlled studies assessing safety and efficacy of topical cantharidin are limited, to date, with the majority of published evidence gleaned from collective clinical experience. A recent Phase II pilot study evaluating a specific formulation of cantharidin 0.7% solution [w/v] (VP-102) has demonstrated promising efficacy and safety results, with additional studies forthcoming, including the designated use of a patented application device that contains the solution.
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415708/
  • Beetle juice: a guide for the use of cantharidin in the treatment of molluscum contagiosum. Moye V, Cathcart S, Burkhart CN, et al. Dermatol Ther. 2013;26(6):445-451.
  • Molluscum contagiosum (MC) is an increasingly common cutaneous viral infection that primarily affects the pediatric population. MC lesions are benign, and most cases resolve within 6–9 months. Nonetheless, many patients and their parents seek active treatment of MC because of local pain, pruritus, embarrassment due to the lesions, or desire to reduce transmission to siblings. Individuals with atopic dermatitis are predisposed to severe and protracted MC, and immunocompromised patients may never clear the infection without treatment. Despite the availability of various therapies, no clear best treatment for MC has emerged. Cantharidin is a commonly used and effective therapy for MC that is generally well tolerated and has high rates of parental satisfaction. In this review, current literature regarding MC is summarized and particular focus is placed on the use of cantharidin for treating MC, including a review of the literature and detailed instructions for its use.
  • https://onlinelibrary.wiley.com/doi/full/10.1111/dth.12105
    • Paid access.
  • Safety of cantharidin: a retrospective review of cantharidin treatment in 405 children with molluscum contagiosum. Moye VA, Cathcart S, Morrell DS. Pediatr Dermatol. 2014;31(4):450-454.
  • Cantharidin is a widely used treatment for molluscum contagiosum (MC) that is often favored because of its speed of application and lack of pain at the time of application. Previous studies have supported its safety and reported high parental and dermatologist satisfaction with its use. Nonetheless, a lack of safety data has contributed to ambiguous U.S. Food and Drug Administration status that has made it increasingly difficult to obtain. All children treated with cantharidin for MC at a tertiary care center between January 1, 2005, and December 31, 2011, who had at least one follow-up visit or telephone call were included in the current study. Information related to treatment with cantharidin and adverse effects was abstracted from medical records. Of 512 children identified, 405 had at least one follow-up visit or telephone call after treatment and were included in this study. Cantharidin was applied to 9,688 lesions over 1,056 visits. Fifty-seven percent of children experienced blistering, an expected effect of therapy. Eleven percent of patients experienced adverse events. The most common adverse events were pain (7%) and significant blistering (2.5%). Other side effects were rare (<1%) and included pruritus, possible mild infection, significant irritation, id reactions, and bleeding. Eighty-six percent of parents reported satisfaction with cantharidin or opted to use it again. Cantharidin is a safe treatment modality for MC and should be considered when symptomatic infection necessitates treatment. The cantharidin application protocol used in this study may serve as a model protocol with a known side-effect profile.
  • https://onlinelibrary.wiley.com/doi/abs/10.1111/pde.12276.
    • Paid access.
  • Compounding in Dermatology Update. Agnetta V, Torres A, Desai S, et al. Journal of Drugs in Dermatology. 2020;19(2) :s18.
  • Medication compounding is defined as any alteration, mixing, or combining of two or more ingredients that make the drug more specific to the needs of the patient. Compounded medications are used widely in patient care to meet their individual medical needs and maximize treatment outcomes. The Food and Drug Administration (FDA) and the United States Pharmacopeia (USP) have been the leading organizations in creating the official rules and guidelines of drug compounding.
  • Ever since an outbreak of fungal meningitis in 2012 from contaminated steroid injections causing multiple deaths, safety in medication compounding has been a major source of concern resulting in a series of new compounding rules, regulations and guidelines set by the regulating agencies. These new standards were developed with the intention to maximize medication safety. Between 2012 and today, there have been multiple revisions and changes to the rules reflecting a very complex and dynamic issue on medication compounding.
  • While patient safety should and has always been the primary focus of the health providers, the FDA, and the USP, these strict and constantly changing complex rules pose many challenges to health practitioners when planning the treatment plan for their patients. Limitations to compounding particular medication mixtures can restrict treatment options leaving patients and providers with few or no good treatment alternatives and ultimately negatively affecting patient care.
  • https://jddonline.com/articles/dermatology/S1545961620S0015X
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