Herpes simplex virus infection and homoeopathic management

Dr Dhanya Deepak Bhat¹ Dr Jyothi Vijaykumar²

ABSTRACT: Herpes simplex virus is ubiquitous, enveloped and double stranded DNA virus which is transmitted across mucosal membranes and non-intact skins that migrate to nerve tissues, where they persist in a latent state. Most commonly cause oro-facial, genital and herpetic whitlow, whereas most serious disorders occur are herpes keratitis, neonatal herpes and herpes encephalitis. It can be prevented by avoiding contact with affected people, correct use of contraceptives and by recommending Cesarean section for women who are at term and affected with genital herpes. Homoeopathic medicines play an important role in such infectious conditions for both treatment and prevention from future outbreak. Homoeopathic case studies are also conducted to ascertain the efficacy of homeopathic medicines in herpes simplex virus infection.

KEY WORDS: Herpes simplex virus infection, Prognosis, Homoeopathy

INTRODUCTION:
Herpes simplex viruses have worldwide distribution and are found in the most remote human populations. Worldwide rates of either HSV1 or HSV2 are between 60% and 95% in adults.HSV1 is more common than HSV2, where HSV1 rates are between 70% and 80% in population of low socioeconomic status and 40% to 60% in improved socioeconomic status. Prevalence of HSV2 in those between the ages of 15 and 50 is about 16% of population, with highest rates in sub-Sahara Africa and lowest in Western Europe and with greater rates among women and those in developing world. In U.S, 57.7% of the population is infected with HSV1 And 16.2% are infected with HSV2. Herpes simplex virus belongs to the family herpesviridae which consists of 80 distinct types of viruses that are found in every kind of animals.

HISTORICAL PERSPECTIVE:
The word herpes (from Greek, “to creep”) has been used in medicine since ancient times. Cold sores (herpes febirilis) were described by Romans physician Herodotus in AD100. Genital herpes was 1^st described by John Astruc, physician to king of France in 1736. In 18^th century it was so common among prostitutes, it was called “a vocational disease of women”.The term herpes appeared in Richard Boultn’s “A system of Rational and Practical Chirugery” in 1713, where the terms ‘herpes milaris’ and ‘herpes exedens’ also appeared. Herpes was not found to be virus until 1940’s. Infection in orolabial lesions was transmitted to other humans in late 19^th century. The disease was successfully transferred to rabbits in the early 20^th century, and HSV was grown in-vitro in 1925. In the 1960’s Nahmias and Dowdle reported two antigenic types of HSV with different sites of viral infection. Herpes antiviral therapy began in the early 1960’s with the experimental use of medications that interfere with viral replication called DNA inhibitors. Herpes simplex was merely a cold sore in an unusual place until 1970’s. In 1971, it was proposed that two different types of HSV caused infection, where HSV-1 commonly causes Labial or Pharyngeal infection, and transmission by non-genital contact. HSV-2 typically affects the genital area and transmitted by intimate sexual contact.

TRANSMISSION:

• Transmission of HSV infections, most frequently occurs through close contact with the person who is shedding virus at a peripheral site, at a mucosal surface, or in genital and oral secretions.
• Infection occurs by inoculation of virus into susceptible mucosal surfaces like oropharynx, cervix, and conjunctiva or through small cracks in the skin.
• As HSV is readily inactivated at room temperature and by drying, aerosol and fomite are unusual means of transmissions. Spread of HSV-1 infection from oral secretions to other skin areas is a hazard of certain occupations like dentists, respiratory care personnel, laboratory acquired and nosocomial outbreaks in hospital or nursery personnel.
• Transmission of HSV can occur in infants born to mother excreting HSV at delivery.
• The majority of cases occurred within five days of contact with short incubation period of primary infection.

PATHOPHYSIOLOGY:

• Exposure to HSV at mucosal surfaces or abraded skin sites permits entry of the virus and initiation of its replication in cells of the epidermis and dermis.
• Initial HSV infection is often subclinical, without apparent lesions.
• In animal models and human subjects, both clinical acquisition and subclinical acquisition are associated with sufficient viral replication to permit infection of either sensory or autonomic nerve endings.
• After transversing the neuroepithelial gap and entering the neuronal cell, the virus or, more likely the nucleocapsid is transported intra-axonally to the nerve call bodies in ganglia.
• For HSV1 infection, trigeminal ganglia are most commonly infected, although extension to the inferior and superior cervical ganglia also occurs.
• For HSV2 infection, sacral nerve root ganglia are most commonly affected.
• Viral replication occurs in ganglia and contagious neural tissue during primary infection only.
• After initial inoculation of neural ganglion, virus spread to other mucosal skin surfaces by centrifugal migration of infectious virions through peripheral sensory nerves.
• This mode of spread explains the characteristics development of new lesions distant from initial crop of vesicles in patients with primary genital or orofacial HSV infection, the large surface area over which these vesicles may be visualized, and recovery of virus from neural tissue distant from neurons innervating the inoculation.
• Contagious spread of virus may also takes place via autoinoculation and allow further extension of disease.
• Viremia is present approximately 25% of primary HSV2 infections, and its presence may affect the natural history of HSV2 disease in terms of site, severity and frequency of reactivation.
• Recent studies suggest that reactivation is far more frequent and dynamic than previously recognized.
• Clinical studies demonstrate that host factors also influence a reactivation.
• Immunocompromised patients have more severe disease.
• Antibodies that develop following an initial infection with type of HSV prevents reinfection with type same virus type – a person with history of orofacial infection caused by HSV1 cannot contract herpes whitlow or genital infection caused by HSV1.
• If an oral HSV1 infection is contracted first, seroconversion will have occurred after 6 weeks to provide protective antibodies against a future HSV1 infection.

CLINICAL MANIFESTATION:

HSV infections cause several distinct medical disorders. Most common is:

• Muco-cutaneous infection which may affect the face and mouth – Orofacial herpes.
• Genital herpes.
• Infection on hands – Herpes whitlow.

Most serious disorders occur:

• Virus infects and damages the eye – Herpes keratitis.
• Virus invades the CNS and damages the brain – herpes encephalitis.
• Virus affects newborn – neonatal herpes.

Muco-cutaneous infection:

• Lesions may appear anywhere in the skin or mucosa, but are most frequent around or in the mouth or on the lips, conjunctiva, cornea and genitalia.
• After a prodromal period of discomfort/ itching, the clusters of small, tense vesicles appear on an erythematous base.
• Clusters vary in size (0.5 – 1.5cm) but may coalesce.
• Vesicles typically persist for a few days, then rupture and dry forming a thin yellowish crust.
• Healing generally occur 8 – 12 days after the onset.
• Lesions usually heal completely but recurrent lesions at the same site may cause atrophy and scarring.
• Skin lesions may develop secondary bacterial infection.
• Localized infection may spread in immunocompromised patients.

1. Orofacial herpes:
2. Herpes labialis:

• It usually occurs as secondary outbreak of HSV.
• It develops as cold sores/ ulcers on the vermilion border of the lip.

1. Acute herpetic gingivostomatitis:

• Usually results from primary infection with HSV1, typically in children.
• Occasionally through oral-genital contact, the HSV2 can also lead to gingivostomatitis, intraoral and gingival vesicles rupture, usually within several hours to 1 or 2 days.
• Fever and pain are often present, at times there may be difficulty in eating and drinking.

1. Herpes gladiatorum:

• Individuals that participate in contact sports, such as wrestling, rugby or soccer, sometimes acquire this condition caused by HSV1.
• It presents as skin ulceration on face, ears, and neck, accompanied by fever, headache, sore throat and swollen glands.
• It occasionally affects the eyes or eyelids.

2. Herpetic whitlow:

• It is swollen lesion of the distal phalanx of finger or thumb.
• It results from inoculation of HSV through the skin and is most common among health care workers.
• Occasionally infection occurs on the toes or on the nail cuticle.

3. Herpetic keratoconjunctivitis:

• Primary infection typically presents as swelling of the conjunctiva and eyelids.
• Infection of the corneal epithelium causes pain, tears, photophobia and corneal ulcers, that often have a branching pattern.

4. Genital herpes:

• It is most common STD in the developed countries.
• It is usually caused by HSV2 although 10% to 30% of cases involve HSV1, HSV2 is most common in women.
• Primary lesions develop within 4 to 7 days after contact.
• The vesicles usually erode to form ulcer that may coalesce.
• Lesions may occur on prepuce, glans penis and penile shafts in men and on labia, clitoris, Vagina, perineum and cervix in women.
• Infection may cause urinary hesitancy, dysuria, and urinary infection in counterparts.
• In some cases sacral neuralgia may occur.
• Scarring may follow healing and recurrences occur in 80% with HSV2 and 50% in HSV1 cases.
• Primary genital lesions are usually more painful, prolonged and widespread and are more likely to be bilateral and involve regional lymphadenopathy and constitutional symptoms than recurrent genital lesions.
• Recurrent lesions may have severe prodromal symptoms and may involve the buttocks, groin or thigh.
• People diagnosed with 1^st episode of genital herpes can expect to have several symptomatic recurrences within a year.

5. Herpes encephalitis:

• It is the commonest form of sporadic viral encephalitis.
• HSV1 causes more than 95% of cases of HSV encephalitis.
• In children and young adults , primary HSV infection may result in encephalitis.
• Acquired virus enters the CNS by neurotrophic spread from periphery via olfactory bulb.
• Most of the adults with HSV encephalitis have clinical or serological evidence of HSV1 infection prior to onset of CNS symptoms.
• Patient may present with headache, seizures, confusion, stupor or coma.
• Late manifestations include olfactory or gustatory hallucinations, anosmia, temporal lobe seizures, aphasia, hemiparesis and abnormalities in behaviour.
• Rarely an affliction of memory may be present, but this becomes evident only later in the convalescent states of illness, as a patient awakens from stupor or coma.
• Swelling and herniation of one or both temporal lobes through tentorium may occur, leading to Deep coma and respiratory arrest during the first three days.

6. Neonatal herpes:

• Herpes infection in newborn is often a devastating disease associated with an extremely high mortality and morbidity.
• It can be acquired intrauterine, intrapartum or postpartum.
• It is most commonly caused by HSV2 but 15-30% of cases can be attributed by HSV1.
• The incubation period is 4 to 21 days after delivery.
• Neonatal HSV infection can be divided into 3 clinical groups – skin, eyes and mouth disease (SEM) is a localized infection.
• Presentation of infection differs according to type of infection, vesicular skin lesions are most predominant symptom.
• These lesions begin as papules which develop over a few days into ulcers.
• Vesicles appear anywhere on the body from head to toe.

DIAGNOSTIC TESTS:

• Primary orofacial herpes by HSV1 is readily identified by clinical examination. -The appearance and distribution of sores typically presents as multiple, round, superficial oral ulcers accompanied by acute gingivitis.

• Genital herpes can be more difficult to diagnose through clinical basis, since HSV2 infected persons have no classical symptoms.

Laboratory tests:            

• Viral culture test: By taking fluid sample or culture from lesions ideally within 3 days.
• Skin biopsy
• Polymerase chain reaction test for presence of viral DNA.

— Laboratory confirmation permits subtyping of virus, which may help to predict frequency of reactivation after 1^st episode oral or genital HSV infection, site of CNS infection, and likelihood of drug resistance.

• Serological tests for antibodies to HSV –

– More accurate when done 12 to 16 weeks after exposure.

– Newer ‘type-specific’ arrays test for antibodies to two different proteins, associated with herpes virus.

1. a) Glycoproteins gG-1 is associated with HSV1
2. b) Glycoprotein gG-2 is associated with HSV2

Various recommended tests include:

1) Herpe-select: Includes enzyme-linked immunosorbent essay on immunoblot, results take larger time.

2) Biokit HSV-2: Detects only HSV2, less expensive, results provide in less than 10 minutes.

3) Western-blot: This is gold standard, expensive and not widely available.

POSSIBLE COMPLICATIONS:

• In immunocompromised people, such as those with advanced HIV infection, HSV-1 can have more severe symptoms and more frequent recurrences, which can lead to severe complications such as encephalitis (brain infection) or keratitis (eye infection).
• HSV-2 and HIV have been shown to influence each other. HSV-2 infection increases the risk of acquiring a new HIV infection by approximately 60 – 90%.
• In advanced HIV disease, HSV-2 can lead to more serious, but rare, complications such as meningoencephalitis, esophagitis, hepatitis, pneumonitis, retinal necrosis, or disseminated infection.
• Neonatal herpes is rare, but is a serious condition that can lead to lasting neurologic disability or death.
• Recurrent symptoms of oral herpes may be uncomfortable and can lead to some social stigma and psychological distress. With genital herpes, these factors can have an important impact on quality of life and sexual relationships.

PREVENTION:

• People with active symptoms of oral herpes should avoid oral contact with others and sharing objects that have contact with saliva.
• Avoid contact with vesicular lesion or ulcer.
• Cesarean section is recommended for women who are at term and have genital lesions.
• The consistent and correct use of contraceptive can help to prevent the spread of genital herpes.
• Individuals with genital HSV infection should abstain from sexual activity whilst experiencing symptoms of genital herpes.

PROGNOSIS:

• Following active infection, herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system.
• The double –stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus of nerve cell body.
• Many HSV-infected people experience recurrence within the first year of infection.
• Prodrome proceeds development of lesions which include tingling (paresthesia), itching and pain where lumbosacral nerves innervate the skin.
• A 2009 study showed the protein VP16 plays role in reactivation of the dormant virus.
• Triggers include local injury to the face, lips, or mouth, and exposure to ultraviolet light.
• The frequency and severity of recurrent outbreaks vary greatly between people.
• Some individual outbreaks can be quite debilitating, with large, painful lesions persisting for several weeks, while others experience only minor itching or burning for a few days.
• Some evidence indicates genetics play a role in the frequency of cold sore outbreaks.

MANAGEMENT:

• Antiviral medications are used to reduce frequency, duration and severity of the out breaks.
• They effectively slow the replication rate of virus and provide opportunity for immune system to intervene.
• Various antivirals for controlling HSV are: Acyclovir, valacyclovir, famciclovir and penciclovir.
• The options for treatment of acyclovir resistant HSV infection include cidofovir and foscarnet, but both are very nephrotoxic.

FUTURE DIRECTIONS:

• Extensive research has gone into vaccines for both prevention and treatment of herpes infections.
• Unsuccessful clinical trials have been conducted for glycoprotein subunit vaccines.
• For therapy, only a single replication-competent HSV vaccine has undergone testing, competent vaccine proposals require further animal testing.

HOMEOPATHIC MANAGEMENT:

Arsenic album:

• Red herpetic skin around the mouth, with burning, worse from scratching and after midnight.
• Eruptions on mouth and lips with burning pain, hard knots and ulcers having thick scurf with lard like bottoms on the lips.
• Lips excoriated with sensation of tingling, swelling and bleeding of the lips.
• Mouth is reddish blue, inflamed and burning,
• Aphthae in the mouth.
• Eruptions of small red pimples which increase and change into gnawing ulcers, vesicular eruptions.
• Herpes, with vesicles, and violently burning especially at night.

Graphitis:

• Herpes in females with scanty menstruation, burning blisters on lower side and tip of the tongue, dryness of the skin.
• Eruption on face, in appearance as if the skin were raw.
• Ulcers on internal surface of the lips, fissures in ulcerated lips.
• Ulcerated corner of the mouth with cracked lips.
• Eruption of pimples on the prepuce, and on the penis with violent erections and uncontrollable sexual desire.
• Vesicles and pimples on the vulva and excoriation in between the thighs with soreness of the vagina.
• Unhealthy skin, every injury tending to ulceration.
• Eruption of pimples and nodules which itch very much.

Cantharis:

• Large, burning painful blisters with erysipelatous inflammation of the parts.
• Burning, tearing ulcerative pains, worse on right side and urinary complications.
• Burning redness and swelling of the face and lips, fissure and exfoliation of the lips.
• Inflammation of the mucous membrane of the mouth, aphthae in the mouth.
• Itching vesicles with burning pain on being touched.

Natrum muriaticum :

• Herpes occurring during fevers, eruptions on the lips and flexures of the joints,
• Vesicles on the tongue and itching pricking feeling on the skin.
• Itching and eruption of pimples on face and forehead.
• Lips dry, cracked or excoriated and ulcerated, with scabs, burning and smarting eruption.
• Fever blisters on the lips, ulcer on cheek.
• Sanguineous vesicles in the internal surface of upper lip, with burning pain when touched.
• Skin of nails especially about nails, dry and cracked.
• Exanthema on mouth and lips in intermittent fever where there are large exanthematous spots looking like large peas, on lips . Lips look puffy

Apis mellifica :

• Large confluent vesicles, burning stinging pains,
• Vesicular eruption on the lips, cold sores.
• Lips oedematous, hot and red.
• Swollen tongue, borders blistered, feel as if scalded and quite raw, Ulcers on left border.
• Dry tongue, cracked, sore, ulcerated, covered with vesicles.

Mercurius solubilis :

• Herpes on the prepuce with a tendency to suppuration.
• Ulcers on glands, itching of the genitals.
• Feverish heat and redness of cheeks with red and tettery spots on face.
• Swelling and ulceration of lips with burning when touched.
• Burning pain, vesicles, blisters, apthae and ulcers in the mouth.
• Voluptuous itching, tingling, tearing and shooting pain in glans and prepuce.
• Vesicles and ulcers with lard like, or cheesy, bases and raised margin, on glans and prepuce.
• Itching of genitals < from contact of urine.
• Inflammatory swelling of vagina, with a sensation as if it were raw and excoriated.
• Swelling of labia, with heat, hardness, shining redness, great sensitiveness to touch, burning, pulsative and shooting pains.

Rhus toxicodendron :

• Herpes upon hairy parts with burning and stinging, itching worse after scratching.
• Rheumatic pains with great weariness.
• Face red with burning heat, vesicular eruptions with yellow serum in vesicles.
• Herpetic, crusty eruptions around mouth and nose, with itching, jerking, and burning sensation.
• Triangular red tip tongue, with offensive smell in the mouth.
• Profuse eruption on male genital organs with inflammation of glans.
• Running vesicles on the glans and swelling of prepuce.
• Herpes, sometimes alternately with asthamatic sufferings and dysentry.

Sepia:

• Herpetic eruption around the lips, herpes during pregnancy
• Inflammation and herpetic eruptions on face with yellow scurfy pimples, thickly grouped.
• Itching and eruption on face and on forehead, sometimes merely like redness and roughness of skin.
• Yellow colour and herpetic eruption round mouth.
• Painful ulcer on internal surface of lips.
• Skin yellow, cracked which may extend deeply into tissues which < by washing in water.
• Dry itch, bad effects where itch is suppressed by Merc. or Sul.
• Brown vinous or reddish and herpetic spots on skin which is annular herpes.

Petroleum:

• Herpes on the perineum and genitals, itching worse in the open air.
• Burning pain, itching, redness, excoriation, itching pimples on genitals with diminished sexual desire.
• Swelling and induration of glands, itching excoriated and running spots on skin.
• Unhealthy skin every injury tends to ulceration.

Sulphur:

• Herpes around the mouth and nose with itching and burning, aggravated by warmth with hot palms and soles.
• Itching and moist blisters over the face chiefly above nose, round eyes and in eyelids.
• Yellowish herpetic spots on upper lip with burning sensation and continued heat.
• Vesicles, blisters and apthae in the mouth and tongue with pain when eating.
• Unhealthy skin, slightest injury followed by inflammation and ulceration.
• Herpetic spots of yellow or brownish colour.
• Skin dry, rough scaly voluptuous itching , feeling good by scratching.
• Itching of skin worse at morning and night, in bed and often with pain and bleeding of the part which has been scratched.

REVIEW OF LITERATURE:

1. As per latest (Dec 2020) article “A clinical case of homeopathic and isopathic treatment of human herpes simplex virus” by Dr. Alex A Volinsky. Author used a complex homeopathic preparation based on an alcohol solution of Ranunculus bulbosus and Ascelpias tuberosa in different solutions with isopathic treatment  and concluded as there were no exacerbations and symptoms of HSV for over 10 years and says that it is completely cured.
2. As per article “ Homeopathic treatment of Herpetic Gingivostomatitis in children : a Prospective Open Label Quasi Randomised controlled study” published in 2014 by Dr.Valee Suwatika, MD / Author concluded that homeopathic remedy Mercurius solubilis 30C is more effective in the treatment of Herpetic Gingivostomatitis in children.
3. As per full length research paper “ Evaluation of in vitro antiviral activity of Chelidonium majus Linnaeus against herpes simplex virus type – 1” published in 2011 by Seyed Hamidreza Monavari et.al. Author says that in this preliminary study, the extract of Chelidonium majus L. showed antiviral properties against Herpes simplex virus type 1. Also mentions that further studies are required to know the mechanism of action using suitable animal models.

REFERENCES:

1. API Text book of medicine.
2. Herpes simplex virus infections, Pathophysiology and Management https://www.researchgate.net/publication/305800727_Herpes_simplex_virus_infections_Pathophysiology_and_Management
3. Human herpes simplex virus categories, mode of transmission, treatment and preventive measures
   https://www.researchgate.net/publication/291766262_human_herpes_simplex_virus_categories_mode_of_transmission_treatment_and_preventive_measures
4. Homoeopathy in oral herpes labialis https://www.homeobook.com/homoeopathy-in-oral-herpes-labialis/
5. Cold Sores (Homeopathy) https://www.peacehealth.org/medical-topics/id/hn-2211000
6. Herpes simplex virus https://www.stlukes-stl.com/health-content/medicine/33/000079.htm
7. Homoeopathy for Herpes simplex treatment https://hpathy.com/cause-symptoms-treatment/herpes-simplex/
8. Skin diseases by Dr. M.E. Douglass.
9. A dictionary of practical materia medica by J.H. Clarke. https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus
10. https://emedicine.medscape.com/article/218580-treatment.

Dr Dhanya Deepak Bhat¹ Dr Jyothi vijaykumar^2
1PG Scholar, Department of Practice of Medicine, A.M. Shaikh Homoeopathic Medical College, Belagavi
²HOD, PG Guide, Professor, Department of Practice of Medicine, A.M. Shaikh Homoeopathic Medical College, Belagavi