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Herpes Simplex Infection

Herpes simplex infection is a term encompassing a wide range of infections that can be caused by herpes simplex viruses (HSV-1 and HSV-2). Mucocutaneous, oropharyngeal, genital, central nervous system, disseminated and systemic forms have been identified in children, adults, pregnant women, and neonates. An early diagnosis, achieved through a meticulous workup and isolation of the virus in body fluids or from skin lesions, is imperative, as the infection can be life-threatening without adequate therapy.


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].
Cervical Lymphadenopathy
  • Generalised muscle pains and often rigors occur, with cervical lymphadenopathy and sometimes splenomegaly. Recurrent infections can occur and typically recurrences are in the same site.[bestpractice.bmj.com]
  • lymphadenopathy appear and last up to 2 weeks, and are seen in the pediatric population.[symptoma.com]
  • There may be associated fever, cervical lymphadenopathy, halitosis, lethargy, irritability and loss of appetite.[patient.info]
  • Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution. ETHICS AND DISSEMINATION: New Zealand Ethics Registration 15/NTB/93.[ncbi.nlm.nih.gov]
  • RESULTS: Nine days after the onset of symptoms, the oral and cutaneous lesions had started to heal and the patient no longer required pain medication.[ncbi.nlm.nih.gov]
  • Two trials evaluating treatment reported on time to healing, duration of viral shedding and relief of pain.[ncbi.nlm.nih.gov]
  • For genital herpes, the mean duration of attacks and pain, occurrence of crusting, and mean healing time with honey treatment were 53%, 50%, 49% and 59% better, respectively, than with acyclovir.[ncbi.nlm.nih.gov]
  • […] to pain resolution (days), defined as time from first experiencing pain to total resolution of pain. (5) Time to stage 4 from randomisation. (6) Time to stage 7 from stage 4. (7) Acceptability of treatments.[doi.org]
  • Abstract A 6 months old female infant presented with history of fever, cough and severe respiratory distress. There was past history of recurrent attacks of pneumonia. She succumbed to the illness after a hospital stay of 7 days.[ncbi.nlm.nih.gov]
  • Herpes simplex-1-induced lesions of the eyes and skin of the head, neck, trunk, or extremities, accompanied by lymphadenopathy, sore throat, fever, chills and headache, often described in wrestlers and rugby players herpes gladiatorum Traumatic herpes[medical-dictionary.thefreedictionary.com]
  • Characteristically, patients had behavioral changes, fever, confusion, speech disturbances, and, less frequently, seizures. The EEG was the most useful neurodiagnostic aid followed by technetium and computed axial tomographic scans.[doi.org]
  • She subsequently developed fever and redeveloped a rising C reactive protein (CRP).[ncbi.nlm.nih.gov]
  • If symptomatic, high fever, sore throat, and pharyngeal oedema may occur. Painful ulcers can appear a few days later on the pharyngeal and oral mucosa, and high fever and mouth pain last for several days.[bestpractice.bmj.com]
  • All players had a prodrome of fever, malaise, and anorexia with a weight loss of 3.6 to 9.0 kg. Two players experienced ocular lesions associated with cutaneous vesicular lesions of the face.[jamanetwork.com]
  • 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]
  • Symptoms can include painful, blistery cold sores on the face and neck, along with a sore throat, infected lymph nodes and malaise. It’s a tricky little bugger of a virus.[blogs.discovermagazine.com]
  • This includes fever, loss of appetite, muscle aches and a general feeling of being unwell (malaise). These symptoms do not usually appear with recurrences. HSV-2 infections are more likely than HSV-1 to recur.[healthhype.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]
  • Postmortem examination revealed hepatic necrosis, tonsillitis, pharyngitis and uterine cervicitis caused by herpes simplex virus (HSV) together with microthrombosis in lungs and glomerular arterioles, suggesting the diagnosis of fulminant HSV disseminated[ncbi.nlm.nih.gov]
  • If symptomatic, high fever, sore throat, and pharyngeal oedema may occur. Painful ulcers can appear a few days later on the pharyngeal and oral mucosa, and high fever and mouth pain last for several days.[bestpractice.bmj.com]
  • If symptomatic, fever, sore throat, and pharyngeal oedema may occur. Painful ulcers can appear a few days later on the pharyngeal and oral mucosa, and fever and mouth pain may last for several days.[bestpractice.bmj.com]
  • In the literature, the following clinical entities have been described: Mucocutaneous infections - Acute herpetic gingivostomatitis and herpetic pharyngitis are two of the most common forms of primary HSV-1 infection, in which constitutional symptoms,[symptoma.com]
  • Acute herpetic pharyngotonsillitis In adults, oropharyngeal HSV-1 infection causes pharyngitis and tonsillitis more often than gingivostomatitis. Fever, malaise, headache, and sore throat are presenting features.[emedicine.medscape.com]
  • In this case report we stress that HSV infections of the colon and small intestine should be considered in the differential diagnosis of diarrhea and intestinal bleeding in the early post-transplantation period.[ncbi.nlm.nih.gov]
  • It may lead to diarrhea, severe vision problems including blindness, infections of the stomach and intestines, and even death.[medbroadcast.com]
  • These consisted of rash (one case in each group), diarrhea (one in the vidarabine group), tremulousness (two in the vidarabine group and one in the acyclovir group), and vomiting (one in the acyclovir group). Laboratory Data Figure 2. Figure 2.[content.nejm.org]
  • Abstract A previously well 11-month-old infant presented with lethargy, a blanching rash, vomiting and diarrhoea. She was diagnosed with suspected gastroenteritis and discharged.[ncbi.nlm.nih.gov]
  • You get a headache, are nauseated, or vomit. Your eyes feel irritated or you feel like you have something in your eye. Your skin becomes itchy, swollen, or develops a rash after you take your medicine.[drugs.com]
  • These consisted of rash (one case in each group), diarrhea (one in the vidarabine group), tremulousness (two in the vidarabine group and one in the acyclovir group), and vomiting (one in the acyclovir group). Laboratory Data Figure 2. Figure 2.[content.nejm.org]
  • Primary HSV 1 Infection Clinical manifestations There is a 1 to 3 days viral prodromal of fever, loss of appetite, malaise and myalgia that may also be accompanied by headache and nausea.[myhealth.gov.my]
Aphthous Stomatitis
  • RIH may appear similar to traumatic lesions (mechanical/thermal/chemical) or other types of oral mucosal disorders, such as aphthous stomatitis.[jcda.ca]
Sore Mouth
  • Symptoms of herpes simplex mouth infection Your child might say he has a sore mouth. His lips, gums and throat might also be sore.[raisingchildren.net.au]
  • Abstract Herpes simplex type 1 produces a perilabial vesicular eruption that normally resolves without scarring. Three cases of herpetic infection associated with different dermatologic surgical procedures are presented.[ncbi.nlm.nih.gov]
  • METHODS: Two weeks following an eruption of herpes labialis, a 20-year-old white female patient developed acutely painful oral and labial ulcers accompanied by target skin lesions. A diagnosis of erythema multiforme (EM) was made.[ncbi.nlm.nih.gov]
  • The patient had herpes simplex before, and this was the second herpetic eruption.[ncbi.nlm.nih.gov]
  • If the patient's history includes wrestling, skin eruptions should be cultured for viruses," says Nicolette. "And parents should reinforce the value of exclusion in preventing spread of the disease to teammates."[webmd.com]
  • Mild, uncomplicated eruptions of herpes simplex require no treatment. Blisters may be covered if desired, for example with a hydrocolloid patch. Severe infection may require treatment with an antiviral agent.[dermnetnz.org]
Vesicular Rash
  • Vesicular rash over the scrotum and penis was noted in all patients (Fig 1 ).[pediatrics.aappublications.org]
  • Twenty-nine of the affected wrestlers (48 percent) recalled having an abrasion or break in the skin at the location of the vesicular rash before the rash developed. Laboratory Investigation Figure 3. Figure 3.[nejm.org]
  • Any vesicular rash in an infant up to eight weeks of age should be cultured and the infant immediately started on antiviral therapy with acyclovir (Zovirax) pending culture results.[aafp.org]
  • Equine coital exanthema. In: Coetzer JAW, Tustin RC, eds. Infectious diseases of livestock. 2nd ed. Cape Town: Oxford Press, 1992:860-7. 5 Marschang RE. Viruses infecting reptiles. Viruses 2011;3:2087-126. 6 Merin A, Pachankis JE.[ojcpcd.com]
Skin Ulcer
  • Mouth, eye and genital skin ulceration may occur. It typically lasts 7 to 10 days.[doi.org]


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.

  • Copyright 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.[ncbi.nlm.nih.gov]
Intranuclear Inclusion Bodies
  • inclusion bodies, margination of chromatin and formation of multinucleated giant cells Cell fusion provides an efficient method for cell-to-cell spread of HSV A.[es.slideshare.net]
Viral Inclusion Body
  • General Pathology Corneal scrapings of HSV keratitis prepared with Giemsa stain may reveal the presence of intranuclear viral inclusion bodies. Multinucleated giant cells may also be found.[eyewiki.aao.org]


  • The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment.[ncbi.nlm.nih.gov]
  • TREATMENT: The patient received antituberculous drugs (ethambutol, isoniazid, pyrazinamide, rifampicin), amphotericin B, flucytosine, and valaciclovir, along with prolonged intensive care treatment and mechanical ventilation.[ncbi.nlm.nih.gov]
  • To examine the effects of interventions for the prevention or treatment or both, of herpes simplex virus in patients receiving treatment for cancer.[ncbi.nlm.nih.gov]


  • This article reports an uncommon case of GB Syndrome caused by HSV infection in a 2 yr-9 mth-old child and have analysed the natural history, etiopathology, treatment and prognosis of the disease.[ncbi.nlm.nih.gov]
  • The documented change from HSV-2 towards HSV-1 in cases of genital HSV infection may have implications as to prognosis, future usefulness of vaccines, present and future usefulness of new type-specific serological tests.[ncbi.nlm.nih.gov]
  • Herpes Simplex Diagnosis Herpes Simplex Prognosis Herpes Simplex History Herpes Simplex Mechanism[news-medical.net]
  • Prognosis Prognosis is usually good, but greatly varies depending on severity and number of recurrences of the disease.[eyewiki.aao.org]
  • Herpes_Simplex_Encephalitis It is still unclear whether the prognosis of HSE is affected to a great extent by specific chemotherapy. The outcome in HSE is dependent to a great extent on the quality of the general medical care.[virology-online.com]


  • Abstract The etiology of herpetic lesions on burn wounds generally is believed to be a reactivation of previous infection or possible exposure to the pathogens under an immunocompromised status.[ncbi.nlm.nih.gov]
  • None of the recognized etiologies of tissue compromise (bacterial infection, tension, host vascular disease, excessive inflammation, or edema) could be identified.[ncbi.nlm.nih.gov]
  • CONCLUSION: The use of molecular diagnostic modalities in clinical practice may aid in determining infectious etiologies in patients with atypical clinical manifestations.[ncbi.nlm.nih.gov]
  • CONCLUSIONS: Although the etiology of EM is still often unknown, infections with herpes simplex virus have been implicated as a possible precipitating factor. This case illustrates the association of the occurrence of EM with an HSV infection.[ncbi.nlm.nih.gov]
  • BACKGROUND: Herpes simplex virus (HSV) is thought to play an etiological role in the development of Alzheimer's disease (AD).[ncbi.nlm.nih.gov]


  • HSV: herpes simplex virus IV: intravenous PCR: polymerase chain reaction SEM: skin, eye, and mouth STI: sexually transmitted infection VZV: varicella-zoster virus Objectives After completing this article, readers should be able to: Characterize the epidemiology[dx.doi.org]
  • Characterize the epidemiology of herpes simplex virus (HSV) infection, including mode of transmission, incubation period, and period of communicability. 2. Recognize the difference in clinical manifestations of HSV1 and HSV2 infection. 3.[ncbi.nlm.nih.gov]
  • This article reviews the epidemiology, pathogenesis, and diagnostic features of HSV infections, providing the clinician with an up-to-date understanding of the available management strategies for mucocutaneous HSV-induced disease.[ncbi.nlm.nih.gov]
  • Together the two volumes provide the first comprehensive compilation and critical analysis of epidemiological data over a wide range of childrens and youth sports.[books.google.es]
Sex distribution
Age distribution


  • This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation.[ncbi.nlm.nih.gov]
  • Pathophysiology Add text here Primary prevention Prevention of herpetic infection includes avoidance of direct contact with known HSV.[eyewiki.aao.org]
  • Pathophysiology [ edit ] Herpes gladiatorum is transmitted by direct contact with skin lesions caused by a herpes simplex virus. [1] This is the main reason why the condition is often found in wrestlers.[en.wikipedia.org]
  • HSV infection is mediated through attachment via ubiquitous receptors to cells, including sensory neurons, leading to establishment of latency. [1] Pathophysiology HSV-1 and HSV-2 are characterized by the following unique biological properties: [1] Neurovirulence[emedicine.com]


  • OBJECTIVES: To assess the effects of interventions for the prevention of HSL in people of all ages.[ncbi.nlm.nih.gov]
  • There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections.[ncbi.nlm.nih.gov]
  • Prevention efforts have been limited by lack of an effective intervention for preventing primary infections and the unclear role of routine serologic testing.[ncbi.nlm.nih.gov]
  • OBJECTIVE: To determine which methods are most used by Quebec physicians performing deliveries with regard to the prevention of and screening for infections caused by the herpes simplex virus.[ncbi.nlm.nih.gov]
  • Grant Support: In part by National Institutes of Health Herpes Program Project Grant AI-30731 and Centers for Disease Control and Prevention Prevention Research Initiative UR6/CCU017828-02.[annals.org]



  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

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Last updated: 2018-06-21 22:47