Prodromal symptoms of primary herpes labialis:

• Fever 
• Sore throat and mouth
• Submandibular or cervical lymphadenopathy
• Gingivostomatitis and odynophagia in children
• Painful vesicles on the lips, gingiva, palate, or the tongue, with erythema and swelling
• Ulceration and spontaneous healing in 2-3 weeks.

The duration of latency (when HSV-1 is dormant) is variable. Reactivation results in the development of  lesions in the face, orolabial and ocular mucosae, attended by pain and paresthesia, ulceration or crust formation, usually in the vermillion border. Untreated cases last approximately 1 week. Primary HSV-1 infection may be self-limiting or asymptomatic. Otherwise, young children may present with febrile herpetic stomatitis, with small blisters and 2 to 10 mm ulcers in the mouth, tongue, and lips [15]. Adults may complain of sore throat and cervical lymphadenopathy, resembling infectious mononucleosis.

Relapses are accompanied by skin rash on the lips, papules, vesicles, and crusts around the mouth. Healing may occur before blisters are formed in 25% of recurrent cases. Prodromal symptoms of reactivation are associated with itching, burning sensation and/or paresthesia prior to the appearance of erythema and papules [16]. Vesicles, pustulation, ulceration, scabbing or crust formation signify a late stage in the course of the disease. Peak viral titres occur in the first 24 h (when most lesions are in the vesicular stage). The infectious cycle gradually subsides with scab or crust formation after which the virus will recede into the latency phase [16] [17].

• Malaise

  No associated malaise, adenopathy or fever. – Carefully consider other sites: buccal (Stomatitis, Chapter 3), genital (Genital ulcers, Chapter 9), ophthalmic, and secondary bacterial infections. – Clean with soap and water 2 times daily until the lesions [medicalguidelines.msf.org]

  Fever, malaise, headache, and sore throat are presenting features. The vesicles rupture to form ulcerative lesions with grayish exudates on the tonsils and the posterior pharynx. [emedicine.medscape.com]

  Hepatitis E is caused by an enterically transmitted RNA virus and causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice. Fulminant hepatitis and death are rare, except during pregnancy. [msdmanuals.com]

  Generalized symptoms such as fever and malaise may develop, and lymph nodes in the groin may enlarge. Lesions may persist in this stage for a week or more, and complete healing may take four to six weeks. [britannica.com]

• Aphthous Stomatitis

  Aphthous stomatitis Other names Recurrent aphthous stomatitis, recurring oral aphthae, recurrent aphthous ulceration Canker sore on the lower lip Specialty Oral medicine, dermatology Frequency ~20% of people to some degree[1] Aphthous stomatitis is a [en.wikipedia.org]

  The prevalence was related to the place of living, income, and college, but not to gender, marital status, medical history, smoking, or aphthous stomatitis. [ncbi.nlm.nih.gov]

  RIH may appear similar to traumatic lesions (mechanical/thermal/chemical) or other types of oral mucosal disorders, such as aphthous stomatitis. [jcda.ca]

  But, in doubtful cases, various recurrent and acute conditions causing oral ulcerations such as acute necrotizing ulcerative gingivitis, herpangina, aphthous stomatitis, varicella zoster infection, erythema multiform, allergic stomatitis should be considered [omicsonline.org]

• Lip Blisters

  If they do have symptoms, they may include: fever irritability painful mouth ulcers and lip blisters poor appetite or reluctance to drink. The ulcers/blisters usually take 10 to 14 days to go away. The blisters never leave scars. [rch.org.au]

  Recurrences are milder than the primary infection, and are commonly known as cold sores or fever blisters. Fever blisters on the lips and face is called herpes simplex labialis. [dentalresource.org]

• Vesicular Rash

  Physical findings include a painful vesicular rash ranging from multiple lesions with primary infection to a few lesions with recurrent infection in the immune competent host. [cancertherapyadvisor.com]

Diagnosis of herpes labialis commences with physical examination of the characteristic lesions, history-taking and assessment of symptoms. Laboratory confirmation may be required in atypical or special cases e.g., immunocompromised or pregnant patients. 

Virus culture from the skin vesicles helps in typing of HSV. Virus isolation and identification from lesions, tears or saliva are done using polymerase chain reaction (PCR) [18]. Tzanck test entails microscopic examination of Giemsa-stained smears from freshly ruptured vesicle to detect the presence of multinucleate giant cells as in HSV or varicella-zoster virus infections. Seroconversion with specific antibody is confirmatory in primary HSV infections. Direct fluorescent antibody testing on air-dried smears is another laboratory test with approximately 75% positivity rate. 

Although most HSV patients have experienced full or partial recovery without treatment, antimicrobial therapy serves to alleviate symptoms and to interrupt the transmission cycle (prevention) by eliminating the causative agent. In isolated cases, the clinical manifestations subside spontaneously. Some antiviral drugs e.g., acyclovir, valacyclovir, or famciclovir can be prescribed if needed [19], especially in primary HSV infections. Symptomatic treatment is recommended for all mucocutaneous herpes infections, with systemic analgesics for pain. Oral and topical acyclovir have been shown to be effective by shortening the duration of relapse by one day. Acyclovir-resistant strains are resistant to penciclovir.

Penciclovir 1% cream when applied every 2 hours  for 4 days, starting when the first lesion appears, can decrease recurrence, with minimal toxicity effects. Famciclovir 1500 mg single oral dose or valacyclovir 2 gm every 12 hours for 1 day is recommended for recurrent herpes labialis. Docosanol 10% cream requires repeated applications 5 times a day until symptoms subside [20]. Application of a sunscreen or zinc oxide minimizes recurrence [20] [21].

In primary infection, all of the oral mucosa can be involved. Recurrence is confined to the mucosa of the hard palate or the lips in older children and adults [13]. Relapses decrease in frequency after age 35 [14]. After the primary infection the virus migrates to the trigeminal ganglion where it remains dormant for life until it is reactivated by some stimuli.

In general, HSV infections are self-limiting and resolve without dire consequences; however, recurrence is common. About 30%of patients experience recurrences. Lifelong recurrences are associated with persistent virus infection in the trigeminal ganglion.

Herpes labialis is caused by herpes simplex virus type 1 (HSV-1). Primary infection in adolescents may manifest before age 20, 80% of them are positive for anti-HSV antibodies. The virus produces painful lesions on the lip and mucous membranes, annoying reactions in immunocompetent patients, which subsides spontaneously in 10 days. Immunocompromised and previously uninfected individuals are highly susceptible to infection [1]. Genital lesions can develop through orogenital contact [2].

Herpes labialis affects more than 30% of people around the world [3] and accounts for a wide spectrum of ailments from annoyance to death. Records show an annual incidence rate of 1.6 per 1000 patients and an annual prevalence rate of 2.5 per 1000 patients [4]. Relapses occur in about 30% of all infected patients [5]. Data from different countries show HSV-1 serology between 56 to 85% in early adulthood [6] [7]. The epidemiology of HSV-1 has changed in recent years, thus, from the traditionally non-sexual transmission, it has become a preeminent cause of primary genital HSV infections [8].

Infection is initiated when HSV, a double-stranded DNA virus, enters the human body through abraded skin on the lips or intact oral mucosa [3]. HSV infects and replicates in epithelial cells which break up (cytolytic infection) releasing clear fluid with virus particles, then forming vesicles and merging with other cells becoming multinucleated giant cells.

HSV migrates to sensory nerve ganglia (trigeminal ganglion) where it remains as a latent lifelong virus infection and serving as a source of relapses [3]. Virus reactivation is triggered by stimuli such as trauma, immunodeficiency, fever, sunlight, menstruation, and sexual intercourse [3] [9] [10]. The role of emotional stress in HSV recurrence is not clear [11]. Reactivated virus returns to the oral epithelium to initiate a new infectious cycle. HSV infects and multiplies in both neurons and epithelial cells. Reactivated virus from the trigeminal ganglion affects the face, the oropharyngeal and ocular mucosae [12].

• Awareness and avoidance of known stimuli that predispose to recurrent episodes.
• Personal hygiene to prevent acquiring or passing the infection unknowingly [22].
• Avoiding contact with persons with active infections and vice versa [22] [23].
• Abstinence from oral and sexual contact.

Herpes simplex labialis is a common infection of the lips. It is manifested by ulcerations on the vermilion border of the lip and oral mucosa, which are highly contagious, cause pain, discomfort, or disfigurement and likely to recur since the virus which remains dormant in the trigeminal ganglion can become activated and initiate new infection.

• Herpes labialis (cold sores) is a common infectious condition of the lip and oral mucosa caused by herpes simplex virus type-1 (HSV-1), reported worldwide.
• Most patients experience full or partial recovery from primary HSV-1 infection spontaneously after 2 to 3 weeks. 
• Treatment with topical applications  (e.g., zinc oxide, zinc sulfate, anesthetic, antiviral cream) helps lessen pain and the duration of symptoms if applied early.
• Antiviral drugs can be prescribed if needed to mitigate the effects of HSV infection, to prevent complications and recurrences.
• About one-third of all patients will experience relapses due to reactivation of the virus from the trigeminal ganglion. HSV migrates to the  sensory nerve ganglia after a primary infection, thereupon, remaining dormant until it is reactivated by some stimuli, then, to initiate new infections in the orofacial mucosa. 
• Avoid contact with infected persons and vice versa (that is, transmitting the infection to others), through casual touch, kissing, or sexual intercourse.

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