Genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital HerpesinfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease are common sexually transmitted infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease caused by herpes simplexHerpes SimplexA group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection.Congenital TORCH InfectionsvirusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology (HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2) type 1Type 1Spinal Muscular Atrophy or 2. Herpes simplexHerpes SimplexA group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection.Congenital TORCH InfectionsvirusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virologytype 1Type 1Spinal Muscular Atrophy is more commonly associated with non-genital herpes, while HSV-2 is more commonly associated with genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes. Primary infectionPrimary infectionHerpes Simplex Virus 1 and 2 often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesiclesVesiclesFemale Genitourinary Examination on an erythematous base, dysuriaDysuriaPainful urination. It is often associated with infections of the lower urinary tract.Urinary Tract Infections (UTIs), and painful lymphadenopathyLymphadenopathyLymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. Primary infectionPrimary infectionHerpes Simplex Virus 1 and 2 can also be asymptomatic. Herpes infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease are unique in that the virusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology is able to remain dormant in the neuronal ganglia, which allows for recurrent infectionsRecurrent infectionsCommon Variable Immunodeficiency (CVID). Recurrent outbreaksOutbreaksSudden increase in the incidence of a disease. The concept includes epidemics and pandemics.Influenza Viruses/Influenza are usually less severe than the initial infection. Treatment is with antiviralAntiviralAntivirals for Hepatitis B therapy, primarily acyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles).
Genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes is a mucocutaneous ulcerative disease caused by either herpes simplexHerpes SimplexA group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection.Congenital TORCH InfectionsvirusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology (HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2) type 1Type 1Spinal Muscular Atrophy or 2.[1,2,10]
HSV-1:
Traditionally associated with gingivostomatitisGingivostomatitisHerpes Simplex Virus 1 and 2 (“cold soresCold soresStomatitis caused by herpesvirus hominis. It usually occurs as acute herpetic stomatitis (or gingivostomatitis), an oral manifestation of primary herpes simplex seen primarily in children and adolescents.Labial and Genital Herpes”) and non-genital infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
However, HSV-1 is now also associated with genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes. The reason is unknown but thought to be due to a decrease in the number of oral HSV-1 infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease, leading people to be more susceptible to genital HSV-1 infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease.[10]
Usually acquired in childhood
HSV-2:
Traditionally (and most commonly) associated with genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes
Usually acquired after pubertyPubertyPuberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems.Puberty
Types of infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease:
Primary infectionPrimary infectionHerpes Simplex Virus 1 and 2: a 1st infection with either HSV-1 or HSV-2 in an individual without evidence of a prior infection of either type (i.e., without any preexisting antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions)
Non-primary infection: a 1st infection with either HSV-1 or HSV-2 in an individual with evidence of a prior infection of the other type (i.e., with preexisting antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions to the opposite type)
Recurrent infection: an infection due to reactivationReactivationHerpes Simplex Virus 1 and 2 of a preexisting HSV-1 or HSV-2 infection after a period of latency (i.e., antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions from the current infection match the HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 type of preexisting antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions)
InfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease are more commonly acquired in females than in males
The WHO estimates:
Global prevalencePrevalenceThe total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time.Measures of Disease Frequency of HSV-2: 11%
Global incidenceIncidenceThe number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time.Measures of Disease Frequency of new infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease of HSV-2: 19.2 million in individuals ages 14‒49 years
The CDC estimates (in the United States):
IncidenceIncidenceThe number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time.Measures of Disease Frequency (HSV-1 and HSV-2): approximately 800,000 new cases/year
HSV-2:
PrevalencePrevalenceThe total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time.Measures of Disease Frequency: 12% of persons aged 14–49 years old
Most infected persons are unaware: approximately 88% of infected 14–49-year-olds have never been diagnosed
Very common in countries that have HIVHIVAnti-HIV DrugsepidemicsEpidemicsSudden outbreaks of a disease in a country or region not previously recognized in that area, or a rapid increase in the number of new cases of a previous existing endemic disease. Epidemics can also refer to outbreaks of disease in animal or plant populations.Influenza Viruses/Influenza
PrevalencePrevalenceThe total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time.Measures of Disease Frequency in HIVHIVAnti-HIV Drugs populations (in Africa): approximately 70%
Because genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes causes skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions breakdown and ulcerations, it is associated with an increased risk of HIVHIVAnti-HIV Drugs transmission.
Immunodeficient patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship are at risk of developing more severe recurrent genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes with possible invasive systemic illness.
Global seroprevalence of herpes simplex virus type 2 infection
Image by Lecturio.
Etiology
Causative agent: herpes simplexHerpes SimplexA group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection.Congenital TORCH InfectionsvirusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology[1]
Enveloped
Double-stranded, linear DNADNAA deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).DNA Types and Structure
Replicates within the nucleusNucleusWithin a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus.The Cell: Organelles of host cells
Transmission[1,2,10]
The majority of infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease are transmitted by asymptomatic individuals.
Can occur via asymptomatic viral sheddingViral sheddingThe expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract.Hepatitis A Virus
Can occur with primary, non-primary, and recurrent outbreaksOutbreaksSudden increase in the incidence of a disease. The concept includes epidemics and pandemics.Influenza Viruses/Influenza
Person-to-person transmission during sexual activity, by direct contact with:
Mucosal surfaces
Genital secretions
Oral secretions
HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2herpetic lesionsHerpetic LesionsFemale Genitourinary Examination
Vertical transmissionVertical transmissionThe transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding.Congenital TORCH Infections (one of the TORCH infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease: toxoplasmosisToxoplasmosisToxoplasmosis is an infectious disease caused by Toxoplasma gondii, an obligate intracellular protozoan parasite. Felines are the definitive host, but transmission to humans can occur through contact with cat feces or the consumption of contaminated foods. The clinical presentation and complications depend on the host’s immune status. Toxoplasma/Toxoplasmosis, other agents, rubellaRubellaAn acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system.Rubella Virus, cytomegalovirusCytomegalovirusCMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus, and herpes simplexHerpes SimplexA group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection.Congenital TORCH Infections)
Less commonly, can be acquired from non-genital herpetic lesionsHerpetic LesionsFemale Genitourinary Examination that are found on the fingers, eyes, or lipsLipsThe lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves.Lips and Tongue: Anatomy of an infected individual
Men who have sexSexThe totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism.Gender Dysphoria with men (MSM)
Primary infectionPrimary infectionHerpes Simplex Virus 1 and 2 and non-primary infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease occur when the virusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology travels through tiny breaks or even microscopic abrasionsAbrasionsCorneal Abrasions, Erosion, and Ulcers in the skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions or mucous membranes in the mouth or genital areas.
Replication begins in cells of the epidermisEpidermisThe external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).Skin: Structure and Functions and dermisDermisA layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands.Skin: Structure and Functions.
Virions replicate within the nucleusNucleusWithin a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus.The Cell: Organelles, forming intranuclear inclusion bodies (Cowdry bodiesCowdry BodiesLabial and Genital Herpes) that may be visible on a Tzanck smearTzanck smearHerpes Simplex Virus 1 and 2.
SensorySensoryNeurons which conduct nerve impulses to the central nervous system.Nervous System: Histology and autonomic nerve endings are also infected.
Once infected, viral particles are transported to nerve cell bodies in the sacral ganglia (via retrograde transport). This transport is independent of virusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology multiplication and local inflammationLocal InflammationSurgical Site Infections.
Once in the ganglia, the virusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology is able to replicate and enter a dormant state known as latency.
Protected from the immune systemImmune systemThe body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Primary Lymphatic Organs, the virusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology is able to stay dormant.
Recurrent infection is due to HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2reactivationReactivationHerpes Simplex Virus 1 and 2.
ReactivationReactivationHerpes Simplex Virus 1 and 2 can occur due to psychological stressPsychological stressStress wherein emotional factors predominate.Acute Stress Disorder (related to activation by the stress hormonesHormonesHormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and TypesepinephrineEpinephrineThe active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels.Sympathomimetic Drugs and corticosteroneCorticosteroneAn adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid.Adrenal Hormones), physical illness, immunosuppression, or for no apparent reason.
Viral DNA replicationDNA replicationThe entire DNA of a cell is replicated during the S (synthesis) phase of the cell cycle. The principle of replication is based on complementary nucleotide base pairing: adenine forms hydrogen bonds with thymine (or uracil in RNA) and guanine forms hydrogen bonds with cytosine. DNA Replication begins in the ganglia.
Causes recurrent symptoms of skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and FunctionsvesiclesVesiclesFemale Genitourinary Examination, ulcers, and crusting
Pathophysiology of herpes
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Clinical Presentation
Genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes infection can be symptomatic or asymptomatic/subclinical and is defined as either primary, non-primary, or recurrent. It cannot be determined on the basis of signs and symptoms alone whether an HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 infection is caused by HSV-1 or HSV-2.[1,2,7,8,13]
Primary[1,2,7,8,13]
Occurs in patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with no pre-existing antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions
More common in patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship who have recently become sexually active
IncubationIncubationThe amount time between exposure to an infectious agent and becoming symptomatic.Rabies Virus period: 2–12 days
Presentation is variableVariableVariables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups.Types of Variables:
PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship may develop aprodromeProdromeSymptoms that appear 24–48 hours prior to migraine onset.Migraine Headache:
Systemic features: feverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, headacheHeadacheThe symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders.Brain Abscess, malaiseMalaiseTick-borne Encephalitis Virus
Localized painPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways and itching
Tender lymphadenopathyLymphadenopathyLymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
Distribution in men: prepucePrepuceThe double-layered skin fold that covers the glans penis, the head of the penis.Penis: Anatomy and subpreputial areas of the penisPenisThe penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy
Distribution in women: vaginaVaginaThe vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery.Vagina, Vulva, and Pelvic Floor: Anatomy, vulvaVulvaThe vulva is the external genitalia of the female and includes the mons pubis, labia majora, labia minora, clitoris, vestibule, vestibular bulb, and greater vestibular glands. Vagina, Vulva, and Pelvic Floor: Anatomy, and cervixCervixThe uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium.Uterus, Cervix, and Fallopian Tubes: Anatomy
Healing usually takes place within 1 month and leaves no scarringScarringInflammation.
Non-primary[1,2]
Acquisition of HSV-1 in a patient with pre-existing antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions to HSV-2 (or vice versa)
Occurs due to reactivationReactivationHerpes Simplex Virus 1 and 2 of HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 infection
Recurrence is more common with HSV-2 and in immunodeficient patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship.
Presentation is usually less severe, with fewer lesions and shorter duration (7–10 days).
Frequency of recurrences typically depends on the severity of the initial infection (e.g., more severe symptoms during primary infectionPrimary infectionHerpes Simplex Virus 1 and 2 = more frequent recurrences)
Median rate of recurrence of after a symptomatic 1st episode: approximately 4 per year
Can occur as frequently as 10 times per year
Recurrence usually decreases over time.
Other forms of herpetic infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease[1]
Other forms of herpetic infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease associated with HSV-1 include:
Also known as cold soresCold soresStomatitis caused by herpesvirus hominis. It usually occurs as acute herpetic stomatitis (or gingivostomatitis), an oral manifestation of primary herpes simplex seen primarily in children and adolescents.Labial and Genital Herpes
Painful, fluid-filled lesions on an erythematous base
Herpetic lesionsHerpetic LesionsFemale Genitourinary Examination on the finger or handHandThe hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy
Most common in:
Children with active oral HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 lesions who suck their thumbs
Healthcare personnel or others who don’t wear gloves while feeding patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship who cannot feed themselves
More common in those participating in contact sports (e.g., wrestlers)
Crusted blister scabs from broken and healing vesicles of cold sores (“fever blisters,” herpes simplex labialis) which are a common viral infection. Cold sores start as a cluster of tiny, fluid-filled blisters on and around the lips. After the blisters break, a scab forms that can last for several days. Cold sores usually heal in 2 to 3 weeks without leaving a scar. Cold sores spread from person to person via close contact, such as kissing. These sores are usually caused by HSV-1 (HSV-1).
A diagnosis of genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes should be confirmed with laboratory testing. However, treatment may be initiated based on a clinical diagnosis if lesions are present, prior to the availability of test results.
A diagnostic clue is that the vesiclesVesiclesFemale Genitourinary Examination are painful and tend to be clustered into small groups, although the presentation can vary widely.
Laboratory evaluation
Laboratory testing possibilities include both direct detection methods (i.e., testing the lesions themselves, which is the preferred method, if possible) and indirect serologic testing:
Polymerase chain reactionPolymerase chain reactionPolymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules.Polymerase Chain Reaction (PCR) (PCRPCRPolymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules.Polymerase Chain Reaction (PCR)):[7,9,10,12,13]
Test of choice in diagnosing genital HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2
Preferred if active lesions present; can also detect asymptomatic HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 shedding
A type of nucleic acid amplificationNucleic acid amplificationLaboratory techniques that involve the in-vitro synthesis of many copies of DNA or RNA from one original template.Septic Arthritis test (NAAT)
Samples should be taken from the base of the anogenital lesion (or rectal mucosa in cases of proctitisProctitisInflammation of the mucous membrane of the rectum, the distal end of the large intestine.Chronic Granulomatous Disease).
Has the greatest sensitivity and specificitySensitivity and SpecificityBinary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition.Epidemiological Values of Diagnostic Tests
Lesion should be unroofed and vesicular fluid cultured
Sensitivity is only approximately 50%; therefore, PCRPCRPolymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules.Polymerase Chain Reaction (PCR) is becoming more acceptable as a gold-standard diagnostic modality.
Reveals multinucleated giant cellsGiant cellsMultinucleated masses produced by the fusion of many cells; often associated with viral infections. In aids, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus.Giant Cell Arteritis, ground glass nuclei, nuclear molding, and, possibly, eosinophilic intranuclear inclusionsIntranuclear inclusionsCircumscribed masses of foreign or metabolically inactive materials, within the cell nucleus. Some are viral inclusion bodies.Varicella-Zoster Virus/Chickenpox (type A Cowdry bodiesCowdry BodiesLabial and Genital Herpes)
Direct fluorescent antibodyDirect Fluorescent AntibodyA form of fluorescent antibody technique utilizing a fluorochrome conjugated to an antibody, which is added directly to a tissue or cell suspension for the detection of a specific antigen.Congenital TORCH Infectionsor type-specific serologic tests:
Differentiates HSV-1 and -2
Identifies type-specific glycoproteinsGlycoproteinsConjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Basics of Carbohydrates called glycoprotein G1 (gG1) and G2 (gG2), which are found in HSV-1 and HSV-2, respectively
Initial enzyme immunoassaysImmunoassaysImmunoassays are plate-based techniques that can detect and quantify many types of molecules through antibody-antigen reactions. An immunoassay typically involves an analyte, a targeted antibody, and labels. Classification of immunoassays is based on the type of label utilized, which includes enzymes (ELISA), light-emitting molecules/tracers (e.g., chemiluminescence and fluorescence immunoassays), and radioactive isotopes (radioimmunoassays).Immunoassays (a common method of serologic testing) may require confirmatory testing with a Western blot.
Indications:[8-10,12,13]
All new HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease (to identify the type, which guides counseling)
Recurrent genital disease of unknown cause
Individuals with clinically suspicious ulcers but negative PCRPCRPolymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules.Polymerase Chain Reaction (PCR), NAAT, and/or culture results (or the tests were not done)
Investigating asymptomatic partners in potentially discordant relationships (which can guide counseling regarding transmission prevention)
Serologic screeningScreeningPreoperative Care is not recommended in asymptomatic adults (including pregnant women) in the general population who do not meet the above indications.[11,14]
Interpretation:
IgGIgGThe major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b.Hypersensitivity PneumonitisantibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions: indicate the individual has had an HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 infection with that type at some point in time
The presence of HSV-2 antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions implies an anogenital infection.
HSV-1 antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions alone have limited use in identifying the location of the infection.
Demonstrating seroconversionSeroconversionThe appearance of antibodies against causative agents in the blood of individuals during the course of an infection or following immunization.HIV Infection and AIDS:[8,10]
IgMIgMA class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin.Immunoglobulins: Types and FunctionsantibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions: unreliable. Up to 35% of individuals produce IgMIgMA class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin.Immunoglobulins: Types and FunctionsantibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions during recurrent outbreaksOutbreaksSudden increase in the incidence of a disease. The concept includes epidemics and pandemics.Influenza Viruses/Influenza, so their diagnostic value is limited.
SeroconversionSeroconversionThe appearance of antibodies against causative agents in the blood of individuals during the course of an infection or following immunization.HIV Infection and AIDS is best demonstrated by conversion of a negative test to a positive one on repeat testing 6‒12 weeks later.
Herpes infection with classic multinucleated giant cell on ThinPrep Pap smear
Image: “Herpes infection on ThinPrep Pap smear” by Ed Uthman. License: CC BY 2.0
Management
Management may slightly vary depending on practice location. The following information is based on US, European, and UK recommendations. Please consult your local clinical guidelines.
Should be started as soon as possible after lesion appearance
Courses for primary infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease are typically 5‒10 days.
1st-line oral therapy for uncomplicated disease (see table for specific dosing regimens):
Oral acyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles)
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles)
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus
Parenteral therapies for severe infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease:
IV acyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 5‒10 mg/kg every 8 hours
For acyclovir-resistant strains: foscarnetFoscarnetAn antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV.Antivirals for Herpes Virus
Indications for hospitalizationHospitalizationThe confinement of a patient in a hospital.Delirium and parenteral therapy:
Individuals should begin therapy when prodromal symptoms occur (tinglingTinglingPosterior Cord Syndrome, paresthesiasParesthesiasSubjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation.Posterior Cord Syndrome, or pruritusPruritusAn intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.Atopic Dermatitis (Eczema)).
Chronic suppressive therapy may be required for those with severe and frequent outbreaksOutbreaksSudden increase in the incidence of a disease. The concept includes epidemics and pandemics.Influenza Viruses/Influenza (> 4‒6 per year).
Supportive measures during outbreaksOutbreaksSudden increase in the incidence of a disease. The concept includes epidemics and pandemics.Influenza Viruses/Influenza:
Appropriate analgesiaAnalgesiaMethods of pain relief that may be used with or in place of analgesics.Anesthesiology: History and Basic Concepts, which may include topical lidocaineLidocaineA local anesthetic and cardiac depressant used as an antiarrhythmic agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine.Local Anesthetics
Urinating with the genitals submerged in water may alleviate severe dysuriaDysuriaPainful urination. It is often associated with infections of the lower urinary tract.Urinary Tract Infections (UTIs) due to labial lesions.
Saline or sitz baths
Petroleum jelly
Table: AntiviralAntiviralAntivirals for Hepatitis B dosing regimens for the treatment of HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
Organization
Primary infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
Recurrent episodic infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
For chronic suppressive therapy
WHO[7,8]
For adults, adolescents, pregnant women, and those with HIVHIVAnti-HIV Drugs and who are
immunocompromisedimmunocompromisedA human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation.Gastroenteritis. A 10-day course of 1 of the following:
Aciclovir 400 mg by mouth 3 times daily
Aciclovir 200 mg by mouth 5 times daily
Valaciclovir 500 mg by mouth 2 times daily
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 250 mg by mouth 3 times daily
For adults, adolescents, and pregnant women:
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth 3 times daily x 5 days
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 800 mg by mouth twice daily x 5 days
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 800 mg by mouth 3 times daily x 2 days
Valaciclovir 500 mg by mouth twice daily x 3 days
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 250 mg by mouth 3 times daily x 5 days
For people with HIVHIVAnti-HIV Drugs or immunocompromisedimmunocompromisedA human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation.Gastroenteritis:
Aciclovir 400 mg 3 times daily x 5 days
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg by mouth twice daily x 5 days
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 500 mg by mouth twice daily x 5 days
For individuals with > 4‒6 outbreaksOutbreaksSudden increase in the incidence of a disease. The concept includes epidemics and pandemics.Influenza Viruses/Influenza per year For adults, adolescents, and pregnant
women:
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth twice daily
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg by mouth once daily
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 250 mg by mouth twice daily
For people with HIVHIVAnti-HIV Drugs or immunocompromisedimmunocompromisedA human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation.Gastroenteritis:
Aciclovir 400 mg by mouth twice daily
Valaciclovir 500 mg by mouth twice daily
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 500 mg by mouth twice daily
U.S. CDC[9,10]
A 7‒10-day course of 1 of the following:
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth 3 times daily
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 1 g by mouth twice daily
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 250 mg by mouth 3 times daily
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 800 mg by mouth twice daily x 5 days
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 800 mg by mouth 3 times daily x 2 days
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 1 g by mouth once daily x 5 days
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg by mouth twice daily x 3 days
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 1 g by mouth twice daily x 1 day
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 500 mg once, followed by 250 mg twice daily x 2 days
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 500 mg by mouth twice daily x 3 days
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth twice daily
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg once daily (< 10 recurrences annually)
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 1 g by mouth once daily (≥ 10 recurrences annually)
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 250 mg by mouth twice daily
2017 European Guidelines (International Union against Sexually Transmitted
InfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease[12]
A 5‒10-day course of 1 of the following:
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth 3 times daily
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 200 mg by mouth 5 times daily
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg by mouth twice daily
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 250 mg by mouth 3 times daily
Preferred, short-course therapy:
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 800 mg by mouth 3 times daily x 2 days
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg by mouth twice daily x 3 days
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 1 g by mouth twice daily x 1 day
Alternative, 5-day courses:
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg 3 times daily x 3‒5 days
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 200 mg 5 times daily
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg twice daily
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 125 mg twice daily
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth twice daily
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg once daily (< 10 recurrences annually)
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 1 g by mouth once daily (> 10 recurrences annually)
BASHH[13]
A 5-day course of 1 of the following:
Preferred regimens:
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth 3 times daily
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg by mouth twice daily
Alternative regimens:
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 200 mg by mouth 5 times daily
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 250 mg by mouth 3 times daily
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg twice daily
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 200 mg 4 times daily
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg once daily
FamciclovirFamciclovirAn aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection.Antivirals for Herpes Virus 250 mg twice daily
HSV: herpes simplex virus
WHO: World Health Organization
CDC: Centers for Disease Control and Prevention
BASHH: British Association for Sexual Health and HIV
Management in pregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care[15,10,12]
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth 3 times daily x 7‒10 days
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 1 g by mouth twice daily x 7‒10 days
Episodic treatment:
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth 3 times daily x 5 days
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 800 mg by mouth twice daily x 5 days
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg by mouth twice daily x 3 days
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 1 g by mouth once daily x 5 days
AcyclovirAcyclovirA guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.Herpes Zoster (Shingles) 400 mg by mouth 3 times daily
ValacyclovirValacyclovirA prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes.Herpes Zoster (Shingles) 500 mg by mouth twice daily
Viral sheddingViral sheddingThe expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract.Hepatitis A Virus at the time of delivery significantly increases the risk of vertical transmissionVertical transmissionThe transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding.Congenital TORCH Infections to the infant and neonatal viral encephalitisViral encephalitisInflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of togaviridae infections; herpesviridae infections; adenoviridae infections; flaviviridae infections; bunyaviridae infections; picornaviridae infections; paramyxoviridae infections; orthomyxoviridae infections; retroviridae infections; and arenaviridae infections.Encephalitis.
All pregnant women with a history of genital HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 lesions should:
Have a genital exam (including visual examination of the cervixCervixThe uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium.Uterus, Cervix, and Fallopian Tubes: Anatomy) to look for ulcers at the onset of labor or rupture of membranes.
Cesarean deliveryCesarean DeliveryCesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery is recommended if lesions are present during labor.
Decreases but does not eliminate the risk of neonatal HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 infection
Routine screeningScreeningPreoperative Care with HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 cultures is not recommended in individuals with a history of disease.
Prevention[10,13]
Prevention is accomplished through patient education, the use of barrier contraceptive devices, and chronic suppressive therapy.
Encourage informing sexual partners and the use of barrier contraceptive devices: consistent condom use can decrease HSV-2 transmission by up to 96%!
Remember that antiviralAntiviralAntivirals for Hepatitis B therapy does not eradicate the latent virusVirusViruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology.
Recurrence is expected and will likely be less severe than the initial outbreak.
Transmission can occur during asymptomatic periods due to viral sheddingViral sheddingThe expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract.Hepatitis A Virus.
PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship should remain abstinent when lesions or prodromal symptoms present.
Complications
The following complications are associated with HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 infection:[1,2,4,5,9,10]
MeningitisMeningitisMeningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
Accounts for 5% of all viral encephalitisViral encephalitisInflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of togaviridae infections; herpesviridae infections; adenoviridae infections; flaviviridae infections; bunyaviridae infections; picornaviridae infections; paramyxoviridae infections; orthomyxoviridae infections; retroviridae infections; and arenaviridae infections.Encephalitis in the United States
Most are due to HSV-2
EncephalitisEncephalitisEncephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis.Encephalitis
HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 causes 10%–20% of all sporadicSporadicSelective IgA Deficiencyviral encephalitisViral encephalitisInflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of togaviridae infections; herpesviridae infections; adenoviridae infections; flaviviridae infections; bunyaviridae infections; picornaviridae infections; paramyxoviridae infections; orthomyxoviridae infections; retroviridae infections; and arenaviridae infections.Encephalitis in the United States
> 95% caused by HSV-1
Neonatal herpes and encephalitisEncephalitisEncephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis.Encephalitis (can be caused by either HSV-1 or HSV-2)
In immunocompromisedimmunocompromisedA human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation.GastroenteritispatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship, HSVHSVHerpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals.Herpes Simplex Virus 1 and 2 may cause:
Vast skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions involvement
Systemic infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease with involvement of the central and peripheral nervous systems, gastrointestinal (GI) tract, and ocular system
Differential Diagnosis
The differential diagnosis of genital herpesGenital HerpesGenital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes includes the following conditions:
Caused by the Gram-negative spirocheteSpirocheteTreponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement.TreponemaTreponema pallidumTreponema pallidumThe causative agent of venereal and non-venereal syphilis as well as yaws.Treponema
Presents with painless, well-demarcated, indurated ulcerations
ChancroidChancroidChancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid:
Caused by the Gram-negative coccobacilli Haemophilus ducreyiHaemophilus ducreyiA species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid.Haemophilus
Presents as a deep, purulent ulcer with painful lymphadenopathyLymphadenopathyLymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
Granuloma inguinaleGranuloma inguinaleDonovanosis (also known as granuloma inguinale) is an STD caused by Klebsiella granulomatis and is mainly seen in tropical regions. The condition is characterized by chronic, progressive, ulcerating disease mostly affecting the genital region.Donovanosis:
Caused by KlebsiellaKlebsiellaKlebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species.Klebsiella granulomatis; not common in the United States
Chlamydia trachomatisChlamydia trachomatisType species of Chlamydia causing a variety of ocular and urogenital diseases.Chlamydia serovars L1-3: the causative agents of lymphogranuloma venereumLymphogranuloma venereumSubacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. But is more widespread in developing countries. It is distinguished from granuloma venereum, which is caused by calymmatobacterium granulomatis.Chlamydial Infections (LGVLGVSubacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. But is more widespread in developing countries. It is distinguished from granuloma venereum, which is caused by calymmatobacterium granulomatis.Chlamydial Infections)
Behcet’s syndrome:
Rare vasculitisVasculitisInflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body.Systemic Lupus Erythematosus syndrome
Presents with painful oral and genital lesions that often cause scarringScarringInflammation, ocular inflammationInflammationInflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, arthritisArthritisAcute or chronic inflammation of joints.Osteoarthritis, ulcers of the GI tract, and neurological symptoms
References
Corey L. (2018). Herpes simplex virus infections. In Jameson JL, et al. (Eds.), Harrison’s principles of internal medicine, 20th ed. Vol. 1, pp. 1345!1354. New York: McGraw-Hill.
Panwar H, Joshi D, Goel G, Asati D, Majumdar K, Kapoor N. (2017). Diagnostic utility and pitfalls of Tzanck smear cytology in diagnosis of various cutaneous lesions. Journal of Cytology 34(4):179–182. https://doi.org/10.4103/JOC.JOC_88_16
World Health Organization. (2021). Guidelines for the management of symptomatic sexually transmitted infections. Chapter 10: Genital ulcer disease syndrome. Retrieved July 18, 2022, from https://www.who.int/publications/i/item/9789240024168
Patel R, Kennedy OJ, Clarke E, et al. International Union against Sexually Transmitted Infections. (2017). 2017 European guidelines for the management of genital herpes. Int J STD AIDS. doi.org/10.1177/0956462417727194
Patel R, Green J, Clarke E, et al. (2014). 2014 UK national guideline for the management of anogenital herpes. Int J STD AIDS 26(11):763–776. doi: 10.1177/0956462415580512