Herpes Simplex Infection

Herpes simplex viruses (HSV-1 and HSV-2) are double-stranded DNA viruses that cause numerous types of infections in humans. Apart from primary infections (when the individual is exposed to the virus for the first time), their recurrent ability to cause infections is possible because they establish a life-long latency in neuronal cells after their acquisition through direct contact with previously infected individuals [1]. Due to the loss of maternal antibodies, the initial infection by HSV-1 occurs in early childhood, either by direct contact with saliva and other secretions, whereas HSV-2 is principally transmitted through sexual intercourse [1] [2] [3]. It is estimated that antibodies to HSV-1 are present in up to 80% of adults, illustrating that many patients go through the initial encounter with HSV asymptomatically, while approximately 14% of adults have been exposed to HSV-2 and develop specific antibodies [1]. In the literature, the following clinical entities have been described [1] [2] [3] [4] [5] [6] [7]:

• Mucocutaneous infections - Acute herpetic gingivostomatitis and herpetic pharyngitis are two of the most common forms of primary HSV-1 infection, in which constitutional symptoms, irritability, and cervical lymphadenopathy appear and last up to 2 weeks, and are seen in the pediatric population [7]. Typical vesicular ulcerative lesions, the hallmark of herpes simplex infection, appear in the oral, gingival, labial, or buccal mucosa, and the surrounding skin [2] [7]. Herpes labialis (cold sores), on the other hand, denotes HSV-1 infection in adults as a result of its reactivation from a latent state in the proximal neuronal cells. Herpetic keratitis (infection of the eye presenting with a sudden onset of pain, conjunctivitis, and visual deficits), Herpetic whitlow (an infection of the finger), and Herpes gladiatorum (infection of the skin) are other less common forms [2] [3] [7]. On the other hand, genital herpes, predominantly caused by HSV-2 (although an increasing number of reports show an almost equal prevalence of HSV-1 and HSV-2 as causative agents), manifests with fever, myalgias, and a range of genital symptoms (vaginal/urethral discharge, dysuria, inguinal lymphadenopathy and pain) [1] [5]. Symptoms last for about 10-12 days in the setting of a primary infection, whereas recurrent forms usually have a milder clinical course [1] [5].
• Infections of the central nervous system (CNS) - Two main entities in this group are meningitis, principally occurring as a complication of genital HSV-2 infection, and encephalitis, with preexisting mucocutaneous HSV-1 infections being the probable cause of dissemination to the CNS [3]. The sudden onset of fever, neurological deficits, and altered consciousness must include herpes encephalitis in the differential diagnosis, as much higher mortality rates are seen if the diagnosis is delayed.
• Disseminated and systemic infections - The immunocompromised population (individuals suffering from malignant diseases, acquired immunodeficiency syndrome, or AIDS, prolonged corticosteroid therapy, etc) are at a particular risk for infections of the esophagus, lungs, the liver, and the CNS [3] [4] [7].
• Neonatal infection - Life-threatening herpes simplex infection in the neonatal period is usually acquired during delivery or postnatal contact with individuals who are shedding the virus. The neonate can develop any of the above-mentioned entities, particularly mucocutaneous and CNS forms [2] [6] [7].

The diagnosis of a herpes simplex infection starts with a meticulous patient history and a thorough physical examination that will identify the course of symptoms and the appearance of typical skin lesions, respectively. Physicians should carefully examine the skin and establish clinical suspicion based on the obtained signs and order a targeted laboratory investigation to confirm HSV as the underlying cause. In children, serology testing may be useful if a primary infection is suspected, as enzyme-linked immunosorbent assay (ELISA) can distinguish between antibody classes and confirm a high titer of immunoglobulin M (IgM) antibodies in serum [1] [2] [3]. Conversely, titers of IgG are not indicative of a recent or recurrent infection, which is why more advanced methods are necessary for adults. Detection of viral genetic material in serum, cerebrospinal fluid (in the setting of a CNS infection) or from biopsy samples through a polymerase chain reaction (PCR) testing are the methods of choice [1] [5] [6] [7]. Additionally, direct microscopic examination of the obtained biopsy samples is an equally effective method, and the Tzanck smear will show multinucleated giant cells and inclusion bodies in the nucleus, known as Cowdry type A acidophilic intranuclear inclusion bodies [2] [3] [7]. If frequent recurrences are observed, or if a disseminated infection is confirmed, the role of patient history is pivotal in assessing preexisting risk factors or underlying diseases, and a diagnosis of HIV infection must be excluded through appropriate serological testing.

1. Sauerbrei A. Herpes Genitalis: Diagnosis, Treatment and Prevention. Geburtshilfe Frauenheilkd. 2016;76(12):1310-1317.
2. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
3. Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. Seventh edition. Philadelphia: Elsevier/Saunders; 2013.
4. Munawwar A, Singh S. Human Herpesviruses as Copathogens of HIV Infection, Their Role in HIV Transmission, and Disease Progression. J Lab Physicians. 2016;8(1):5-18.
5. Johnston C, Corey L. Current Concepts for Genital Herpes Simplex Virus Infection: Diagnostics and Pathogenesis of Genital Tract Shedding. Clin Microbiol Rev. 2016;29(1):149-161.
6. Corey L, Wald A. Maternal and Neonatal HSV Infections. The New England journal of medicine. 2009;361(14):1376-1385.
7. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015

• Genital Herpes
  User58774, 2019-05-18 23:51
• Erythema multiforme
  User32159, 2018-09-29 07:48
• I have confirmed herpes simplex.
  Guest, 2018-07-20 20:19