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 May 31st, 2021

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 Herpes Infections of the Oral Region

Herpes Labialis is a common recurrent irritation for many children and parents alike. The Red Book, the bible of pediatric Infectious diseases, is the best resource for understanding Herpes viral infections. There are 8 primary herpes viruses that infect humans including: herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus, Epstein-Barr virus, cytomegalovirus,

Human herpesvirus-6, Human herpesvirus-7, and Kaposi's sarcoma herpes virus. They all are made of a double stranded DNA genome and have a common and unique feature of herpesvirus biology, they have a high incidence of asymptomatic transmission coupled to the ability to establish a latency phase which can be reactivated to cause recurrent or new episodes of disease during periods of physical and or mental stress. For the purposes of this piece, we will focus on HSV1/2 and primarily the annoying skin manifestations.

HSV-1 and HSV-2 infections are primarily called herpes labialis and herpes genitalis and are characterized by vesicular ulcers around the mouth, face and genital regions. These two viruses are deadly for newborns up to a month of age and for immunocompromised individuals. We are going to only focus on the milder version. The vesicles will look like a blister that gradually will dry out into crusted lesions and can last for 1 to 2 weeks during primary infections and recurrences. Lesions can tingle or burn during and before their appearance. They contain high amounts of virus promoting the immune system to send monocytes and other immune cells to attack. After a primary, i.e. HSV naive, infection occurs, the viral infection goes dormant in the local nerve ganglion where the immune system has a very difficult time clearing it.

During this latency phase, "It is important to note that these persons will nevertheless shed infectious viral particles from the mucosae, which could infect other individuals . On the other hand, up to one-third of the persons that have had clinical symptoms during primary infection show frequent reactivations, which occur on average six times a year."(Alvarez et. al. 2020)

Upon reactivation, the virus travels from the nerve to the local skin cells where they replicate inducing a reactivation as seen via new skin lesions near the nerve dormancy site. This is the time for a preventative event to occur. Therapy has been marginally useful at best for most patients. Antivirals like valacyclovir and acyclovir will reduce the length of time of vesicle activity by a day or so.

Overall, therapy seems unnecessary for minor herpes labialis unless a day or so of less lesion time has value to you. The antivirals on the other hand are very useful for someone that has disseminated disease as a baby or in an immunocompromised state. There are also emerging theories that some of the pediatric autoimmune neuropsychiatric syndromes, PANS, may be herpes viral induced and may in select cases benefit from a course of acyclovir or valacyclovir. This is still in the works of understanding but may be a real issue moving forward. (Swedo et. al. 2015)

Non pharmaceutical interventions are weak and poorly studied. One candidate, the amino acid L-lysine has been looked at for its antiviral properties. Fish, potato, yeast and yogurt are good sources. Some individuals have a good response to this therapy when dosed above 3 grams per day with a similar 1-2 day reduction of lesion time. (Mailoo et. al. 2017)

I think of Herpes labials as a problem of immune surveillance and viral suppression once contracted. If you are physically or mentally stressed, your innate and adaptive T helper type 1 cells are ineffective at controlling the persistent herpes virus. Thus, the bulk of our interventions should be focused on maintaining a robust immune system to suppress herpes viral replication and activity which comes through maintaining a robust immune surveillance system.

How should we do this?

Most of the science of immune activity and function follows the general adage that what is good for general cellular and human metabolism is great for immune surveillance and function.

The to do:

1) Reduce the volume and change the quality of the ingested food sources. Sugar, flour and saturated fats consumed together in high volume are the major triggers of insulin resistance and metabolic damage. Returning to a whole food, high fiber diet with no added sugars will profoundly change the inputs that cause insulin resistance and immune dysregulation. Saturated fat and fats in general except for trans fats are in and of themselves not dangerous in moderation and coupled with fiber and normal whole foods. The anti-inflammatory diet is the perfect place to start your new dietary journey.
2) Secondly, having periods of restriction from calories as a fast or a time restricted feeding pattern will give the system time to heal by turning off mTOR1, mechanistic or mammalian target of rapamycin which is a master metabolic switch. Eating in an 18:6 pattern is ideal for individuals past 18 years of age and likely younger as well. This means that you compress your meals into a 6-hour window. This allows for longer periods of caloric deprivation pushing the metabolic system to shift into breakdown mode as opposed to storage mode. For younger children, I encourage eating only when they are hungry. Only present high quality anti-inflammatory food types to eat and you are well on your way to health and childhood IR avoidance. Avoid, avoid, avoid sugar beverages as juice, soda, sweet tea, flavored milks, etc…..
3) Thirdly, moderate exercise is a powerful tool to change metabolic and immune problems by directly increasing the utilization of glucose and increasing white blood cell activity. Move often, daily and with purpose. Not much more to say here other than family-based activities are great for collective encouragement.
4) Learn to reduce chronic mental stress. Stress dramatically affects blood glucose levels raising them due to the release of stress hormones from the adrenal gland. Stress also turns on the inflammatory pathways systemically worsening the insulin resistance issue as well as immune function.
5) What herbs and supplements can be used to augment this process?
a. Omega 3 fatty acids are found primarily in fish oils and other foods like flax seeds. They are a major source of anti-inflammatory compounds called resolvins, protectins and defensins. I encourage small oily fish consumption including mackerel, salmon, sardines and trout. High quality fish oil supplements are also excellent.
b. Polyphenol supplements and foods. Polyphenols are chemicals that are found in berries, green leafy vegetables, nuts, seeds, beans, onions, cocoa and other plants. They are very potent sources of anti-inflammatory compounds and directly work against metabolic and immune problems.
c. Curcumin or turmeric is a special herb all on it’s own. It is a very potent anti-inflammatory compound as it blocks NFkB and it’s downstream inflammation. This will be very useful to prevent the progression the immune mediated inflammation and dysfunction.
d. Berberine has been shown in quality studies to increase AMPk and GLUT4 receptors counteracting SAD type diets and sloth. It also can modulate the intestinal microbiome shifting it more toward a healthy immune status.
e. Vitamins A/D and the mineral zinc are all necessary cofactors of enzymatic immune based reactions. Using the sun as the 30 minute source of vitamin D daily is part one. Vitamin A can be obtained through the consumption of fish, orange/red/yellow vegetables and fruits, eggs, liver and broccoli. Zinc is obtained through the consumption of meat, eggs, shellfish, pumpkin seeds and legumes. Supplementation with provider dosing is also useful.

To prevent recurrent HSV lesions,
Dr. M

Alvarez Frontiers Microbiology
Spear J of Virology
Swedo J of Child and Adolescent Psychopharmacology
Mailoo Int Medicine
Garber Sage journal
Dr Weil Herpes information
Yanuck Int Medicine
Veldhoen Nature Reviews Immunology
Irwin Nature Reviews Immunology
Saxton Cell