Key points
This is the first report of adult primary herpetic oropharyngitis in the
view point of the differences between the two types of herpes simplex
virus (HSV).
41 (25 type 1 and 16 type 2) HSV specific antigen positive cases among
68 immunoserologically confirmed adult HSV primary infection cases were
investigated.
Significantly low incidence of oral lesions and high incidence of nausea
were seen in HSV type 2 oropharyngitis cases, that might mean particular
correlation vagus nerve and HSV type 2.
Significantly increased white blood cell count and high C-reactive
protein value were seen in oropharyngitis by HSV type 2.
HSV type 2 possibly cause more severe symptoms and higher inflammatory
reactions than type 1, without oral lesions.
Key Words: Herpes simplex virus, oropharyngitis, primary infection
Objectives
Although primary infection with herpes simplex virus (HSV) type 1
usually occurs in children, it is sometimes seen in adults. Primary
herpetic oropharyngitis, which is oral and pharyngolaryngeal infection
caused by HSV, in adults is known to cause more severe symptoms than
that seen in children1, and hospitalization is often
recommended2. HSV type 2, which is well known as a
cause of genital herpes, is also known to cause oropharyngitis, as one
of the sexually transmitted diseases3. There have been
no studies on the differences between herpetic oropharyngitis caused by
HSV type 1 and 2.
Nakagawa et al. have already reported the first case series of primary
herpetic oropharyngitis in adults with immuneserological diagnostic
criteria, and suggested the possibility that there might be some
differences of the clinical symptoms between HSV type 1 and
24. In this study, we tried to investigate the
differences between HSV type 1 and 2 in more details.
Participants
All adult patients of acute-onset throat pain with white exudates or
stomatitis-like lesions in the oropharyngeal mucous membrane, who had
visited the Department of Otolaryngology at XXXX Hospital within the
16-year period from April, 2004 to March, 2020.
Design
We reviewed the clinical files of participants and selected cases that
met immune serological diagnostic criteria of Nakagawa et
al4, retrospectively. The immune serological
diagnostic criteria is shown in Table 1.
<Table 1 should be placed here>
In all selected cases, HSV-specific antigen was tested at the firs
visit, by direct immunofluorescence staining using fluorescein
isocyanate-labelled monoclonal antibody for glycoprotein (Denka Seiken,
Tokyo, Japan) on samples obtained from oropharyngeal mucosal white
lesion with a cotton swab.
Settings
Ethical considerations
Data gathering for this investigation was performed in the patients who
were already prescribed an otorhinolaryngologic evaluation; therefore,
it did not have need of additional diagnostic or therapeutic procedure.
All patient data were anonymized prior to data analysis. This study was
approved by the ethical organization of XXXX Hospital No. 20-4.
Statistical analyses
All P-values were two sided and P-values of 0.05 or less were considered
statistically significant. All statistical analyses were performed with
EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan),
which is a modified version of R (The R Foundation for Statistical
Computing, Vienna, Austria) commander designed to add statistical
functions frequently used in biostatistics5.
The authors have been following CARE guidelines.
Main outcome measures
The types, number, sex, age, clinical findings including
laryngofiberscopic examination, laboratory datas, and treatments of the
HSV-specific antigen-positive cases were reviewed.
Results
Fourty-one patients were positive for HSV-specific antigen (15 male, 26
female; age range, 17-65 years; (mean ± standard deviation) 26.7 ±
9.1years), among sixty-eight patients who met the criteria as primary
HSV oropharyngitis (27 male, 41 female; age range, 16-65 years; mean
27.2±8.8 years). Type 1 positive cases were 25 and type 2 were 16.
The difference in clinical features between type 1 and type 2 is shown
in Table 2.
<Table 2 should be placed here.>
Although white slightly raised mucosal lesions spreading widely in
pharynx were seen in all patients regardless of types, oral herpetic
lesions, like gingivitis, labialis, buccal mucosal lesion, glossitis,
were seen in 11 of 25 type 1 patients and 0 of 16 type 2 patients
(p<0.01). Nausea was complained by 6 patients in type 1 and 11
in type 2 (p<0.01). Increased white blood cell counts and
higher C-reactive protein(CRP) values were significantly seen in type 2
patients (p<0.05, p<0.01, respectively).
Female, older patients, higher admission rate, and longer inpatient
period were likely to be seen in type 2, there were no statistically
significant differences.
Conclusions
Oral lesions and digestive tract symptoms
A significant low incidence of oral lesions were seen in HSV type 2
infection. During primary HSV infection, the main site of viral
replication is not the local mucous membrane. HSV is transported
intra-axonally to the nerve-cell bodies in ganglia, where the majority
of viral replication occurs, after invasion to the endplate of sensory
nerve endings. Then HSV spread widely to other mucous membranes through
centrifugal migration by way of peripheral sensory
nerves6. If HSV enters the sensory nerves of
pharyngeal wall, viral replication should occur in the ganglia of
glossopharyngeal or vagus nerve, then causes pharyngitis. The fact that
significant less number of patients with HSV type 2 showed oral lesions
suggests that HSV type 2 possibly have the tendency to enter the
endplate of the glossopharyngeal or vagus nerve endings, not the
trigeminal nerve, which is well known as major affected nerve by HSV
type 1. The result that significant larger number of patients complained
nausea, which is considered as one of typical symptom of vagal
neuritis7, in type 2 infected patients reinforce this
supposition.
Moreover, HSV type 2 infection may have a potential to be misdiagnosed
as a bacterial pharyngitis/tonsillitis, because of its low incidence of
causing oral stomatitis, which is well known as a typical finding of HSV
infection.
Inflammatory reactions
HSV type 2 infection showed more severe inflammatory reactions,
increased white blood cell counts and higher CRP, than type 1. Higher
CRP in HSV type 2 may be related to the result that HSV type 2 viremia
is more likely seen than type 1 during primary
infections8,9. McMillan et al. reported that 33 type 1
and 2 type 2 HSV patients were seen among 613 pharyngitis in university
students at an university health cernter10. The fact
that a higher rate of type 2 seen in this study possibly indicate the
severity of type 2, because this study was based on an outpatient clinic
of an acute general hospital which treats more severe patients.
Increased white blood cell counts may also make type 2 HSV infection
mimic bacterial pharyngitis.
Clinical applicability
Severity of HSV infection has the great variation from asymptomatic
infection to severe oropharyngitis causing poor oral uptake. Inpatient
care with hydration and intravenous injection of antiviral agents should
be considered for the patients who cannot ingest food, water, or take
medicine orally, and who show poor general states2.
The results of this study showed the difference in the clinical symptoms
of HSV oropharyngitis by its types. If type 2 infection is suspected,
poor oral uptake, caused not only by throat pain related to severe
inflammatory reaction, but also by nausea, should be predicted, and
inpatient care will be considered. Moreover, suspicious of type 2
infection forces us to investigate their potentially infected partners.
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