New Treatment For Pox-Based Molluscum Contagiosum

I. Introduction to Molluscum Contagiosum

Molluscum Contagiosum are a common skin infection caused by the molluscum contagiosum virus (MOCV). [Sulzberger, 1948] Given the current global population, approximately 648 million people can be expected to have Molluscum this year, although the exact figure is unclear and may be less. [World, 2024] [Han, 2023] Approximately 6 million Americans, mostly children, are infected each year. [U.S., 2024] Molluscum are raised, round, firm, painless bumps on the skin that can range in size from a pinhead to a pencil eraser. These bumps can take on a pink color and often have a small dent or dot at the top. [Mayo, 2022] 

The infection can spread through skin-to-skin contact or contact with infected objects or toys. [Mayo, 2022] Swimming pools may present a high risk of infection, although the exact reason is unclear. [Swimming, 2018] It is more common in children, but it can affect people of any age. [Molluscum, 2023] In adults with a healthy immune system, molluscum contagiosum can be a sexually transmitted infection (STI). [Mayo, 2022]

If the bumps are scratched or injured, the infection can spread to nearby skin. Left untreated, the bumps usually disappear in 6 months to 2 years. [Mayo, 2022] However, the bumps and the skin around them may become inflamed, which is thought to be an immune system response to the infection. [Mayo, 2022] If scratched, these bumps can become infected and heal with scarring. [Oakley, 1997] If sores appear on the eyelids, pink eye (conjunctivitis) can develop. [Mayo, 2022]

To help prevent the spread of the virus, it's recommended to wash your hands regularly, avoid touching the bumps, don't share or borrow personal items, and avoid sexual contact if you have molluscum contagiosum on or near your genitals. [Mayo, 2022]

II. A Pox Virus; Molluscum Contagiosum (MOCV)

Since the eradication of smallpox, MOCV has become the principal poxvirus that infects humans. [Chen, 2013] With an incidence rate estimated to be 8000 persons per 100,000 globally, it is much more prevalent than emergent monkeypox, which, historically, has been concentrated in the tropical rainforest regions of Central and West Africa. At the height of the recent outbreak in the U.S., the incidence rate was approximately 8.37 per 100,000 people. [Han, 2023] [CDC, 2022] [Population, 2024] 

Poxviruses are members of the Poxviridae family, which cause a variety of illnesses in both humans and other animals. Their shape is brick-like or oval, with the longest dimension measuring up to 250-300 nm with hollow spikes scattered across their surface. These viruses contain deoxyribonucleic acid (DNA). [Editors, 1998]

In the early 80s and 90s two molecular genotypes or species (MOCV1 and 2) emerged from the data using the techniques available at the time. It was not, however, until 2023 that the possibility of the existence of other species of MOCV was fully investigated. All 66 of the MOCV genomes that were available underwent extensive phylogenomic and recombination analysis, which revealed that they can be divided into six phylogenetic subgroups (PG1-6) and three genotypes (MOCV1, 2, 3). [Zorec, 2023]

Despite genomic information being available on MOCV, there are still no vaccines against this infection that could prevent the development of molluscum, which would be especially important for high risk groups such as children, swimmers and contact sport participants such as wrestlers. [Davies, 2017]

III. Established Treatments for Molluscum

Physical Therapy

● Curettage: A procedure involving the scraping or removal of molluscum contagiosum lesions using a curette, a spoon-shaped instrument.

● Cryotherapy: Treatment method for molluscum contagiosum involving the freezing of the lesions using liquid nitrogen, causing them to blister and eventually fall off.

● Pulsed Dye Laser: A therapeutic approach employing a laser that delivers high-intensity light to target and eliminate blood vessels supplying nutrients to molluscum contagiosum lesions. [Chen, 2013]

Chemical Destructive Agents

● Phenol: applied topically to the lesions, where it acts as a caustic substance, causing controlled chemical burns and tissue destruction, ultimately leading to the removal of the infected tissue.

● Trichloroacetic Acid: applied directly to the lesions. TCA causes coagulation of proteins, leading to controlled tissue destruction and subsequent removal of the infected tissue. [Chen, 2013]

Chemical Non-Destructive Agents

● Cantharidin: A topical treatment for molluscum contagiosum involving the application of a solution containing cantharidin, a blistering agent derived from blister beetles, which causes the formation of blisters and subsequent detachment of the lesions.

● Podophyllotoxin: Utilized in treating molluscum contagiosum, podophyllotoxin is a topical antimitotic medication derived from certain plants, disrupting cell division in infected tissues and promoting the removal of lesions.

● Salicylic Acid Gel: Employed as a topical treatment, salicylic acid gel for molluscum contagiosum works by breaking down the keratin in the skin, aiding in the removal of the lesions through gradual exfoliation.

● Benzoyl Peroxide Cream: Used topically for molluscum contagiosum, benzoyl peroxide cream functions as a keratolytic agent, assisting in the shedding of infected skin cells and facilitating the elimination of lesions.

● Retinoic Acid: Applied topically in the treatment of molluscum contagiosum, retinoic acid, a derivative of vitamin A, promotes cell turnover and helps reduce the severity of lesions by encouraging the shedding of infected skin cells. [Chen, 2013]

Other Therapies

● Photodynamic Therapy: An alternative treatment for molluscum contagiosum involving the application of a photosensitizing agent followed by exposure to light, which activates the agent to destroy infected cells, ultimately leading to lesion elimination.

● Electron Beam Therapy: A therapeutic approach for molluscum contagiosum utilizing targeted high-energy electron beams to irradiate and eliminate infected lesions, often considered in severe cases or when other treatments have been ineffective. [Chen, 2013]

Severe Cases and Combined Treatments

● Cancer Chemotherapeutic Drugs: In cases of severe molluscum contagiosum, certain cancer chemotherapeutic drugs may be employed as a treatment, aiming to disrupt the rapid division of infected cells and promote the regression of lesions. [Chen, 2013]

Considerations and Side Effects

The efficacy of these treatments varies, and some have side effects such as pain, burning, erythema, dyspigmentation, and scarring. The best treatment option for molluscum contagiosum virus infection in immunocompetent patients is still under debate, and waiting for spontaneous resolution without treatment is also an option. [Chen, 2013]

IV. Recent Treatment Innovations

ZELSUVMI™ (Berdazimer Sodium) Topical Medication

Ligand Pharmaceuticals Incorporated has announced that the U.S. Food and Drug Administration (FDA) has granted approval for ZELSUVMI?, a nitric oxide (NO) releasing polymer, as a first-in-class medication for treating Molluscum Contagiosum. It is expected to be available in the U.S. in the second half of 2024. [U.S., 2024]

ZELSUVMI™ is indicated for the topical treatment of Molluscum Contagiosum in adults and pediatric patients one year of age and older. It is the first and only topical prescription medication that can be applied by patients, parents, or caregivers at home, outside of a medical setting to treat Molluscum. [U.S., 2024] 

This approval follows successful Phase 3 trials, including B-SIMPLE 4 and B-SIMPLE 2, that demonstrated the medication's efficacy in reducing lesion counts and its tolerability when used once a day. The trials enrolled 1,598 patients, and the most commonly reported adverse reactions were application site reactions. [U.S., 2024] 

Mechanism of Action

The exact mechanism of action is unknown, [U.S., 2024] however NO plays a significant role in the immune response against viruses. Here are some key points about its general anti-viral mechanism:

Figure: Potential anti-MOCV mechanisms by NO generating ZELSUVMI?  

1. NO is a free radical produced during L-arginine metabolism. It has a well-described role in the immune system as a microbicide and tumor-killing mediator. [Uehara, 2015]

2. NO is produced by a variety of immune and non-immune cells and is involved in the regulation of several immune functions, such as T-cell polarization and suppression. [Uehara, 2015]

3. Viral infections generally promote NO production. Depending on its concentration, NO can trigger different effector mechanisms in immune responses. It can activate the second messenger cyclic guanosine monophosphate (cGMP), increase the cytoplasmic p53 tumor suppressor molecule, and modify host and viral molecules by nitrosylation. [Uehara, 2015]

4. Inhibition of Viral Protease Activity and Replication: The antiviral role of NO is also due to its inhibition of viral protease activity. It prohibits viral replication. [Saura, 1999]

5. Chemical alteration of DNA by Reactive Nitrogen and Oxygen Species is one of the main mechanisms of NO mediated antimicrobial action. [Garren, 2021]

6. The development of NO-based antiviral therapies, particularly gaseous NO inhalation and NO-donors, has proven to be an excellent antiviral therapeutic strategy. [AbdelMassih, 2021]

V. Conclusion

Despite established treatments such as physical therapy, chemical agents, and other therapies, the limitations and side effects associated with these approaches have fueled the search for innovative solutions. ZELSUVMI? addresses this need by offering a convenient, at-home application for patients, parents, or caregivers. The approval of this new medication provides hope for improved outcomes and convenience in the management of Molluscum Contagiosum, particularly for individuals in high-risk categories. As research continues and new treatment modalities emerge, ZELSUVMI? stands out as a notable advancement in the quest for effective and accessible solutions for Molluscum Contagiosum.

VI. Sources

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