History

Fact Explanation
Painful sores which may be recurrent [6] Herpes simplex viruses are belong to the herpes family of viruses. Two types of herpes viruses (HSV) are HSV-1 and HSV-2. HSV-1 is usually associated with orofacial disease, and HSV-2 is associated with genital disease. Primary infection is usually followed by the seroconversion and established in the nerve ganglia, [10] later it can be reactivated causing recurrences. [3] Genital sores are usually painful, occur on the penis, vagina, buttocks, or anus and inside the vagina in females. [6] Like oral herpes, these sores can appear anywhere on the skin.fluid-filled blisters may appear.May be single or multiple. May apper 2-20 days after the exposure to an infected person. [1,4] Before the appearance of the blisters, patient may feel these sensations over the skin.
History of exposure to an infected person [6] HSV is a highly contagious infection usually spread through direct contact. Sexual activities including oral, vaginal and anal sex place the individual at high risk of acquiring the infection. Having multiple sex partners, high risk partners and men sex with men increase the risk of getting HSV infection. Infected person may spread the infection to the others by above mentioned contacts. [6]
Oral lesions [8] Oral herpes is usually due to HSV-1 virus. [8] Most blisters appear on the lips or around the mouth. Sometimes may be extending to the face or the tongue.
Fever, bodyaches [10] Flu-like symptoms may be present, and may be due to the effect of inflammatory cytokines. Fever may also be due to the complications like meningitis, encephalitis etc. [10]
Micturition [6] and defecating problems Patients with enital herpes may have difficulty in urinating particularly due to the pain. [6] Proctitis due to rectal inflammation may cause difficulty in defecation particularly in men after sex with men.
Eye involvement [7] Herpes simplex virus can affects the eye mainly the anterior segment of the eye. [7] It causes pain, light sensitivity, discharge, and a gritty feeling in the eye. Scarring can lead even loss of vision.
Past history of same disease [6] HSV is a latent infection which can recur after sometime. Therefore signs and symptoms may reappear. [2]
Risk factors for HSV infection Female gender, having another sexually transmitted infection (STI) and having a weakened immune system due to malignancy, organ transplant, chemotherapy and HIV/AIDS may increase the risk getting the infection. [10]
New born affected with the disease: blindness, neonatal deaths [9] Newborn babies born to infected mothers will acquire infection while passing through the birth canal. [9] This may result in brain damage, blindness or death for the newborn. Recurrences in neonates is associated with high risk of mortality. [5]
References
  1. ESPY MJ, UHL JR, MITCHELL PS, THORVILSON JN, SVIEN KA, WOLD AD, SMITH TF. Diagnosis of Herpes Simplex Virus Infections in the Clinical Laboratory by LightCycler PCR J Clin Microbiol [online] 2000 Feb, 38(2):795-799 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC86206
  2. RAUTEMAA R, HELANDER T, MERI S. Herpes simplex virus 1 infected neuronal and skin cells differ in their susceptibility to complement attack Immunology [online] 2002 Jul, 106(3):404-411 [viewed 01 September 2014] Available from: doi:10.1046/j.1365-2567.2002.01421.x
  3. VYSE A, GAY N, SLOMKA M, GOPAL R, GIBBS T, MORGAN-CAPNER P, BROWN D. The burden of infection with HSV-1 and HSV-2 in England and Wales: implications for the changing epidemiology of genital herpes Sex Transm Infect [online] 2000 Jun, 76(3):183-187 [viewed 01 September 2014] Available from: doi:10.1136/sti.76.3.183
  4. SMIT C, PFROMMER C, MINDEL A, TAYLOR J, SPAARGAREN J, BERKHOUT B, COUTINHO R, DUKERS NH. Rise in seroprevalence of herpes simplex virus type 1 among highly sexual active homosexual men and an increasing association between herpes simplex virus type 2 and HIV over time (1984-2003) Eur J Epidemiol [online] 2007 Dec, 22(12):937-944 [viewed 05 July 2014] Available from: doi:10.1007/s10654-007-9178-2
  5. KIMURA H, FUTAMURA M, ITO Y, ANDO Y, HARA S, SOBAJIMA H, NISHIYAMA Y, MORISHIMA T. Relapse of neonatal herpes simplex virus infection Arch Dis Child Fetal Neonatal Ed [online] 2003 Nov, 88(6):F483-F486 [viewed 01 September 2014] Available from: doi:10.1136/fn.88.6.F483
  6. WALD ANNA, ZEH JUDITH, SELKE STACY, WARREN TERRI, RYNCARZ ALEXANDER J., ASHLEY RHODA, KRIEGER JOHN N., COREY LAWRENCE. Reactivation of Genital Herpes Simplex Virus Type 2 Infection in Asymptomatic Seropositive Persons. N Engl J Med [online] 2000 March, 342(12):844-850 [viewed 02 September 2014] Available from: doi:10.1056/NEJM200003233421203
  7. COOK SD. Herpes simplex virus in the eye. Br J Ophthalmol [online] 1992 Jun, 76(6):365-366 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC504287
  8. GARCEAU R, LEBLANC D, THIBAULT L, GIROUARD G, MALLET M. Herpes simplex virus type 1 is the leading cause of genital herpes in New Brunswick Can J Infect Dis Med Microbiol [online] 2012, 23(1):15-18 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374468
  9. STRAFACE G, SELMIN A, ZANARDO V, DE SANTIS M, ERCOLI A, SCAMBIA G. Herpes Simplex Virus Infection in Pregnancy Infect Dis Obstet Gynecol [online] 2012:385697 [viewed 02 September 2014] Available from: doi:10.1155/2012/385697
  10. SCHIFFER JT, COREY L. New Concepts in Understanding Genital Herpes Curr Infect Dis Rep [online] 2009 Nov, 11(6):457-464 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804398

Examination

Fact Explanation
Sores/vesicles [4] Red blisters will be appearing initially Affected sites would be penis, vagina, buttocks, anus and inside the vagina in females. Occasionally scrotum, thighs and urethra in males may be affected. Like oral herpes, these sores can appear anywhere on the skin. Usually vesicles [4] are tender. May appear as blisters and rupture of them causes ulcers. [1]Sores can last from 7 to 10 days. Later blisters will break open and often fluid will excreted and form a crust, before healing.
Oral herpes lesions [1] Most blisters appear on the lips or around the mouth. [1]
Febrile High temperature of 38°C (100.4°F) or over may be present. Fever may also be due to the complications like meningitis and encephalitis. [4]
Lymphadenopathy Swollen lymph nodes, are found in the region of the affected area. eg:- groin
Signs of meningeal irritation:neck stiffness, kernig sign and brudzinki sign Aseptic meningitis/ meningoencephalitis [4] is a rare complication of the disease.
Altered level of consciousness [4] Encephalitis is arecognized complication of HSV infection. [2,3]
References
  1. VYSE A, GAY N, SLOMKA M, GOPAL R, GIBBS T, MORGAN-CAPNER P, BROWN D. The burden of infection with HSV-1 and HSV-2 in England and Wales: implications for the changing epidemiology of genital herpes Sex Transm Infect [online] 2000 Jun, 76(3):183-187 [viewed 01 September 2014] Available from: doi:10.1136/sti.76.3.183
  2. Herpes encephalitis. Br Med J [online] 1968 Aug 10, 3(5614):331-332 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1991195
  3. KIMURA H, FUTAMURA M, ITO Y, ANDO Y, HARA S, SOBAJIMA H, NISHIYAMA Y, MORISHIMA T. Relapse of neonatal herpes simplex virus infection Arch Dis Child Fetal Neonatal Ed [online] 2003 Nov, 88(6):F483-F486 [viewed 01 September 2014] Available from: doi:10.1136/fn.88.6.F483
  4. SCHIFFER JT, COREY L. New Concepts in Understanding Genital Herpes Curr Infect Dis Rep [online] 2009 Nov, 11(6):457-464 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804398

Differential Diagnoses

Fact Explanation
Syphilis [4] Syphilis is a sexually transmitted disease with resulting from infection by Treponema pallidum. Syphilis can be divided into primary, secondary, latent, and tertiary stages. Lesions (chancres) are usually solitary, raised, firm, red papules and importantly they are painless. Mucocutaneous rash and generalized nontender lymphadenopathy may be present. Diagnosis require dark ground microscopy. VDRL is important for the scrrening. [4]
Chancroid [1] This lesion is caused by Haemophilus ducreyi, which is a small, gram-negative, facultative anaerobic bacillus. It causes painful genital ulcers associated with inguinal lymphadenopathy. Chancres differs from chancroids where the chancroids are painless. [1]
Impetigo [5] This is a common condition in children. [5] Localized red rash where skin may appear red or brown with blisters and pus will be evident, there may be associated lymphadenopathy. This is usually caused by either group A β-hemolytic streptococci or Staphylococcus aureus. [5] A bacterial culture of the skin is the investigation to diagnose the condition. Secondary bacterial infections complicating the vesicles may look similar to impetigo.
Candidiasis [2] Candida albicans is the predominant pathogen causing mucocutaneous candidiasis. [2] Immunocompromised states, broad-spectrum antibiotics, cytotoxic chemotherapies, and transplantation increase the risk of candidiasis. Rash initially starts with vesiculopustules later ruptures leaving erythematous area with scalloped edges. Satellite lesions are commonly found which may coalesce and extend into larger lesions. Females can have vaginal discharge with odour which may be itchy. Males will have lesions over the penis "balanitis". Oral thrush, nail infections are the other manifestations of candidiasis. Sometimes it causes invasive illnesses.
Herpes zoster [2] This is a latent infection where primary infection causes varicella (chickenpox),and then virus becomes latent in cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia which can later reactivates and causes a wide range of neurologic disease. Herpes zoster appears along a 1-3 dermatomes and gradually maculopapular rash evolves into vesicles. [2] Other features of reactivation includes postherpetic neuralgia, vasculopathy, myelopathy, retinal necrosis and cerebellitis. [3]
References
  1. WEISS HA, THOMAS SL, MUNABI SK, HAYES RJ. Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis Sex Transm Infect [online] 2006 Apr, 82(2):101-110 [viewed 14 July 2014] Available from: doi:10.1136/sti.2005.017442
  2. PFALLER MA, DIEKEMA DJ. Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem Clin Microbiol Rev [online] 2007 Jan, 20(1):133-163 [viewed 14 July 2014] Available from: doi:10.1128/CMR.00029-06
  3. MUELLER NH, GILDEN DH, COHRS RJ, MAHALINGAM R, NAGEL MA. Varicella Zoster Virus Infection: Clinical Features, Molecular Pathogenesis of Disease, and Latency Neurol Clin [online] 2008 Aug, 26(3):675-viii [viewed 05 July 2014] Available from: doi:10.1016/j.ncl.2008.03.011
  4. COLEMAN DL, MCPHEE SJ, ROSS TF, NAUGHTON JL. Secondary syphilis with pulmonary involvement. West J Med [online] 1983 Jun, 138(6):875-878 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1010855
  5. PEREIRA LB. Impetigo - review An Bras Dermatol [online] 2014, 89(2):293-299 [viewed 02 September 2014] Available from: doi:10.1590/abd1806-4841.20142283

Investigations - for Diagnosis

Fact Explanation
Tzank smears [3] This is used to evaluate the characteristic cytologic changes in HSV, such as epithelial cells with eosinophilic intranuclear inclusion bodies and multinucleated giant cells. Rapid diagnosis is possible and it does not need a specialized laboratory settings. [3]
Polymerase chain reaction (PCR) techniques [2] HSV DNA can be detected by polymerase chain reaction (PCR). It has the superior sensitivity to all other diagnostic methods for the detection of HSV infections, but routine there are limitations due to the problems of amplicon carryover contamination and the time-consuming gel electrophoresis. [1]
Viral culture [1] Tissue sample or scraping of the sores is used for the culture. This is a best method for detection of this virus from sources other than cerebrospinal fluid. [1]
References
  1. ESPY MJ, UHL JR, MITCHELL PS, THORVILSON JN, SVIEN KA, WOLD AD, SMITH TF. Diagnosis of Herpes Simplex Virus Infections in the Clinical Laboratory by LightCycler PCR J Clin Microbiol [online] 2000 Feb, 38(2):795-799 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC86206
  2. MITCHELL PS, ESPY MJ, SMITH TF, TOAL DR, RYS PN, BERBARI EF, OSMON DR, PERSING DH. Laboratory diagnosis of central nervous system infections with herpes simplex virus by PCR performed with cerebrospinal fluid specimens. J Clin Microbiol [online] 1997 Nov, 35(11):2873-2877 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC230078
  3. FOLKERS E, ORANJE AP, DUIVENVOORDEN JN, VAN DER VEEN JP, RIJLAARSDAM JU, EMSBROEK JA. Tzanck smear in diagnosing genital herpes. Genitourin Med [online] 1988 Aug, 64(4):249-254 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1194227/PMC86206

Investigations - Fitness for Management

Fact Explanation
Full blood count Person might be presenting with fever [1] and need to exclude the other causes for the fever such as bacterial infections (leucocytosis- increased white blood cell count,), dengue-low platelets etc. On the other hand, patient may be having increased lymphocytes as this is a viral infection.
References
  1. VYSE A, GAY N, SLOMKA M, GOPAL R, GIBBS T, MORGAN-CAPNER P, BROWN D. The burden of infection with HSV-1 and HSV-2 in England and Wales: implications for the changing epidemiology of genital herpes Sex Transm Infect [online] 2000 Jun, 76(3):183-187 [viewed 01 September 2014] Available from: doi:10.1136/sti.76.3.183

Investigations - Followup

Fact Explanation
PCR [1] This can be used for the follow up, but is not practiced routinely due to the cost of the investigation. [1]
References
  1. ESPY MJ, UHL JR, MITCHELL PS, THORVILSON JN, SVIEN KA, WOLD AD, SMITH TF. Diagnosis of Herpes Simplex Virus Infections in the Clinical Laboratory by LightCycler PCR J Clin Microbiol [online] 2000 Feb, 38(2):795-799 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC86206

Investigations - Screening/Staging

Fact Explanation
Direct fluorescent antigen [1] Specimen from the ulcer base can be stained with a direct fluorescent antibody, and is able to distinguish HSV-1 from HSV-2. [1]
Serology [4] HSV-specific immunoglobulin M (IgM) antibodies Glycoprotein G antibody assay is important for differentiate the HSV type 1 and 2. Serological methods [4] such as antibody testing is the method used for the large group scrrening.
CT scan and MRI scan [2] HSV encephalitis may be associated with cerebral edema.
Cerebrospinal fluid analysis [3] Is required on a suspicious 0f an encephalitis. [3]
References
  1. ESPY MJ, UHL JR, MITCHELL PS, THORVILSON JN, SVIEN KA, WOLD AD, SMITH TF. Diagnosis of Herpes Simplex Virus Infections in the Clinical Laboratory by LightCycler PCR J Clin Microbiol [online] 2000 Feb, 38(2):795-799 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC86206
  2. HO DY, MOCARSKI ES, SAPOLSKY RM. Altering central nervous system physiology with a defective herpes simplex virus vector expressing the glucose transporter gene. Proc Natl Acad Sci U S A [online] 1993 Apr 15, 90(8):3655-3659 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC46360
  3. Herpes encephalitis. Br Med J [online] 1968 Aug 10, 3(5614):331-332 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1991195

Management - General Measures

Fact Explanation
Symptomatic treatment [2] Fever is one of the presenting features of HSV infection. [4] Fever may need antipyretics. Pain and itching may need symptom relief. [1] Keeping the affected area clean using either plain or salt watr, keeping an ice pack wrapped in a flannel and avoid wearing tight clothing etc will comfort the patient. Appropriate wound care is and treatment of secondary bacterial skin infections is also needed. Supportive maangement Rest, fever control, fluids and electrolyte balance is important. [1] Cool baths or cool compressive bandages can be prescribed. Regular bathing and cleaning of skin lesions are important. No dietary restrictions, but a soft, blended diet may be needed if sores are there in the mouth.
Vaccination [1] Type-specific vaccines containing heat-inactivated herpes simplex hominis virus type 1 or 2 is available for the treatment of herpes simplex genitalis particularly in recurrent disease. Disease free interval is extended by the vaccine. [1]
Management of mothers with genital herpes [4] Mothers with genital herpes may require caesarean section to avoid passing on herpes simplex to a newborn during the vaginal delivery. Pregnant women with a clinical episode or a recurrence may need acyclovir or valacyclovir though they are not officially approved during the pregnancy. [4]
Patient education [3] Oral herpes patients has to be advised not to engage in activities that causes spread of infection to the others such as kissing, oral sex, sharing items such as silverware, cups, towels, and lip balms. They should not be engaged in sex till during the period of active lesions. [5] They should be advised to wash the hands after touching a sore. Recurrent nature of the disease has to be emphasized.
Prevention [5] Barrier protection (condom) is advised with condoms to minimize exposure to genital HSV infections, [5] but not completely effective as the possibility of ulcers occurring outside of areas covered by the condom. Herpetic whitlow prevention needs wearing the gloves when handling the patients by health care workers. Educating about the safe sexual practices, avoiding sex with the high risk partners and limiting sexual activities to trusted one partner are important.
References
  1. NASEMANN T, WASSILEW SW. Vaccination for herpes simplex genitalis. Br J Vener Dis [online] 1979 Apr, 55(2):121-122 [viewed 31 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1045605
  2. THIN RN, NABARRO JM, PARKER JD, FIDDIAN AP. Topical acyclovir in the treatment of initial genital herpes. Br J Vener Dis [online] 1983 Apr, 59(2):116-119 [viewed 31 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1046152
  3. RAUTEMAA R, HELANDER T, MERI S. Herpes simplex virus 1 infected neuronal and skin cells differ in their susceptibility to complement attack Immunology [online] 2002 Jul, 106(3):404-411 [viewed 01 September 2014] Available from: doi:10.1046/j.1365-2567.2002.01421.x
  4. STRAFACE G, SELMIN A, ZANARDO V, DE SANTIS M, ERCOLI A, SCAMBIA G. Herpes Simplex Virus Infection in Pregnancy Infect Dis Obstet Gynecol [online] 2012:385697 [viewed 02 September 2014] Available from: doi:10.1155/2012/385697
  5. SCHIFFER JT, COREY L. New Concepts in Understanding Genital Herpes Curr Infect Dis Rep [online] 2009 Nov, 11(6):457-464 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804398

Management - Specific Treatments

Fact Explanation
Antiviral treatment-acyclovir [1] Acyclovir is a synthetic purine nucleoside analogue [3] that is used for the treatment of herpesviruses. Acyclovir monophosphate is the initial form that attacks the infected cells and is metabolized to the active form of triphosphate by cellular kinases. Variety of formulations and routes of administration are available.[1] It is effective in both in “early” lesion stage, prodrome or erythema, and in advanced, “late” stages—papule, vesicle, or ulcer. Treatment doses will be depend on location of the lesions and the nature of the disease as primary or reactivation. Oral administration of 400 mg of acyclovir five times/day for 5 days is usually used. Ointment is used for the accelerated healing of herpes labialis in immunocompromised patients. [2] Cream is used five times/day for 4 days (20 doses). Acyclovir causes significant reduction of virus shedding, healing time and the duration of pain. [1] It also reduces the frequency of recurrent episodes and prevents herpes-associated erythema multiforme. Life-threatening HSV infections in immunocompromised patients and HSV encephalitis, and visceral disease may need high-dose of intravenous antivirals. [3]
Other antivirals-penciclovir , valacyclovir [1] More expensive valacyclovir is a drug that is converted to the active drug acyclovir. More doses are required than the acyclovir. wg:- penciclovir creamhas to apply nine times/day for 4 days (36 doses) for get the same effect of acyclovir. [1] Drug resistant HSV is can be treated with foscarnet or cidofovir. [3]
References
  1. SPRUANCE SL, NETT R, MARBURY T, WOLFF R, JOHNSON J, SPAULDING T, THE ACYCLOVIR CREAM STUDY GROUP. Acyclovir Cream for Treatment of Herpes Simplex Labialis: Results of Two Randomized, Double-Blind, Vehicle-Controlled, Multicenter Clinical Trials Antimicrob Agents Chemother [online] 2002 Jul, 46(7):2238-2243 [viewed 31 August 2014] Available from: doi:10.1128/AAC.46.7.2238-2243.2002
  2. COLLUM LM, MCGETTRICK P, AKHTAR J, LAVIN J, REES PJ. Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration. Br J Ophthalmol [online] 1986 Jun, 70(6):435-438 [viewed 31 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1041036
  3. SCHIFFER JT, COREY L. New Concepts in Understanding Genital Herpes Curr Infect Dis Rep [online] 2009 Nov, 11(6):457-464 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804398