Herpetic gingivostomatitis

Age: Primary herpetic gingivostomatitis is common in children from 6 months to 5 years old. This virus is also common in young adults aged around 20–25.[5]

Immune system: The prevalence and severity of the disease is dependent on the host's immune response and the virulence of the virus.

Environment: As this virus is very contagious it has the potential to spread quickly in enclosed environments e.g. nurseries and orphanages.[5]

Epidemiology: Those living in developing countries are at a higher risk of HSV-1 infection. It has been reported that around a 1/3rd of children living in developing countries are HSV-1 positive by 5 years old and 70-80% of the population are infected by the age of adolescence. In developed countries only 20% of children are infected at the age of 5 and there is no significant increase in disease prevalence until 20–40 years old where the percentage of infected individuals ranges from 40-60% [9]

Socio-economic status: Those with a lower income have a higher risk of HSV-1 infection at a younger age.[5]

Race: Studies have demonstrated that in the USA 35% of African Americans by the age of 5 have presented with the disease whereas only 18% of White Americans are affected.[9]

The histological appearance of a herpetic infection on the mucosa includes degeneration of stratified squamous epithelial cells, the loss of intercellular connections and inflammatory infiltrate around the capillaries of the dermis layer.[10] An intact herpetic vesicle presents as an intraepithelial blister histologically. This vesicle is caused by rupture and distension of the virally epithelial cells by intracellular oedema and coalescence of disrupted cells.

Rupturing of the infected cells cause a great number of viral particles to be released, rendering them the ability to affect adjacent epithelial cells and even the sensory axons of the trigeminal nerve. Histologically, these infected cells have an eosinophilic cytoplasm and large, pale vesicular nuclei, appearing swollen under the microscope. The cytoplasms of the infected cells fuse, collectively forming giant cells with many nuclei. The balloon cells and multi-nucleated giant cells can often be identified in smears taken from an intact vesicle or from one which has been recently ruptured.[12]

The lamina propria shows a variable inflammatory infiltrate, the density of which depends on the stage and severity of the disease, and inflammatory cells also extend into the epithelium.[12]

Cowdry type A bodies are intranuclear inclusion bodies visible under light microscopy. They show electron dense glycoproteins and viral capsids.[13] Both Cowdry type A bodies can both be found in varicella zoster and herpetic gingivostomatitis, making it impossible to distinguish between both eosinophilic bodies. One way to distinguish between the herpes virus (and hence herpetic gingivostomatitis) and varicella virus is by direct immunohistochemistry using fluorescent antibodies.[5]

Diagnosis of HG is very much clinically based. Therefore, it is imperative to rule out other diseases that present similarly, bearing in mind the past medical history of the patient.

Some differential diagnoses to bear in mind when considering herpetic gingivostomatitis are:

1. Teething in infants: A study mentioned that "primary tooth eruption begins at about the time that infants are losing maternal antibody protection against the herpes virus. Also, reports on teething difficulties have recorded symptoms which are remarkably consistent with primary oral herpetic infection such as fever, irritability, sleeplessness, and difficulty with eating." Another study highlighted that "younger infants with higher residual levels of antibodies would experience milder infections and these would be more likely to go unrecognized or be dismissed as teething difficulty."[14]
2. Herpangina: It is a disease that is caused by the Coxackie A virus rather than a herpes virus.[15] In herpangina, ulcers are usually isolated to the soft palate and anterior pillar of the mouth.[15] In herpetic gingivostomatitis, lesions can be found in these locations, but they are almost always accompanied by ulcerations on the gums, lips, tongue or buccal mucosa and/or by hyperemia, hypertrophy or hemorrhage of the gums.[15]
3. Hand Foot and Mouth Disease: Similar to herpangina, hand foot and mouth disease occurs predominantly in children. It is caused by Coxsackie A and B virus, and lesions or blisters are found bilaterally on the hands, feet and mouth of the patient.[16]
4. Oral candidiasis: Also known as thrush, herpetic gingivostomatitis can often be differentiated from these microorganism/bacterial causing white plaques on the palate, buccal mucosa, tongue, oropharynx etc.[16]
5. Apthous stomatitis: They are commonly known as apthous ulcers, and are characterized by grey membranes and peripheral erythema. Lesions/ulcers for herpetic gingivostomatitis may also be found on the palate and keratinzied gingivae[17] hence aphthous ulcers can be ruled out.
6. Stevens–Johnson syndrome: Stevens–Johnson syndrome is characterized by early symptoms of malaise and fever, and shortly after that erythema, purpura and plaques on the skin, which often progresses to epidermal necrosis and sloughing in extreme cases.[16]
7. Infectious mononucleosis - Infectious Mononucleosis presents with a high fever and lymphadenopathy, which is may or may not be presented in the symptoms of herpetic gingivostomatitis.  However, upon closer oral examination, ulceration, petechiae and occasional gingivostomatitis may be spotted.[10]
8. Behcet's syndrome - It is an inflammatory disorder in which the presenting symptoms are recurrent aphthous ulcers, and severe cases may result in the patient having genital lesions, gastro-intestinal problems, and even arthritis.[10]
9. Varicella - Small ulcers on the back of the oral cavity and vesicular lesions on the scalp and trunk are common for Varicella.[10] It is ruled out as the location of the infections are unilateral, unlike herpetic gingivostomatitis which is bilateral.