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Herpes Simplex Virus 1 and 2

Herpes simplex Herpes Simplex A 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 virus Virus Viruses 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 (HSV) is a double-stranded DNA DNA A 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 virus Virus Viruses 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 belonging to the family Herpesviridae. Herpes simplex Herpes Simplex A 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 virus Virus Viruses 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 commonly causes recurrent infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease involving the skin Skin The 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 and mucosal surfaces, including the mouth, lips Lips The 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, eyes, and genitals. Typical mucocutaneous infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are characterized by an acute localized appearance of clusters of small, painful vesicles Vesicles Female Genitourinary Examination on an erythematous base. Although overlap exists, HSV-1 is classically associated with oropharyngeal lesions, whereas HSV-2 is mostly responsible for genital herpes Genital Herpes Genital 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, an STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs). Systemic and severe infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease including encephalitis Encephalitis Encephalitis 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, meningitis Meningitis Meningitis 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, and neonatal herpes may also occur. The diagnosis is made based on clinical presentation and history, which can be confirmed by the microscopic examination of a stained smear of a fresh vesicle Vesicle Primary Skin Lesions, nucleic amplification test using PCR PCR Polymerase 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), direct immunofluorescence, or serologic tests. The therapy for mucocutaneous lesions is usually symptomatic, but antiviral Antiviral Antivirals for Hepatitis B therapies involving acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles), valacyclovir Valacyclovir A 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), or famciclovir Famciclovir An 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 are useful if given early, and are always part of the therapy for serious systemic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.

Last updated: Oct 5, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Classification

Dna virus classification flowchart

DNA DNA A 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 virus Virus Viruses 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 identification Identification Defense Mechanisms:
Viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology can be classified in many ways. Most viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology, however, will either have a genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics formed by DNA DNA A 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 or RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure. Viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology with a DNA DNA A 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 genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics can be further characterized by whether that DNA DNA A 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 is single or double stranded. If the viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology are covered by a thin coat of cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane (usually taken from the host cell), they are called “enveloped” viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology. If that coat is absent, the viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology are called “naked” viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology. Some of the enveloped viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology translate their DNA DNA A 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 into RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure before it is incorporated into the host cell’s genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics.

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General Characteristics and Epidemiology

Basic features of herpes simplex Herpes Simplex A 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 virus Virus Viruses 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

  • Taxonomy:
    • Family: Herpesviridae
    • Subfamily: Alphaherpesvirinae Alphaherpesvirinae A subfamily of herpesviridae characterized by a short replication cycle. The genera include: simplexvirus; varicellovirus; marek’s disease-like viruses; and iltovirus. Antivirals for Herpes Virus
    • Genus: Simplexvirus
  • DNA DNA A 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 virus Virus Viruses 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
    • Double stranded
    • Linear
    • Encodes approximately 70 proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
  • Structure:
    • Core (contains genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics)
    • Icosahedral nucleocapsid
    • Tegument (contains viral proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis and enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes)
    • Envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology and glycoprotein spikes

Clinically relevant species

Two types have been recognized to cause infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:

  • HSV-1 (tropism for oral epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology)
  • HSV-2 (tropism for genital epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology)

Epidemiology

HSV-1:

  • Prevalent worldwide 
  • Affects approximately 66% of the population
  • Seroprevalence: 
    • Individuals 0–49 years of age: 
      • 47% in the US
      • Up to 90% in low-income countries
    • In children in the US:
      • 6–7 years: 26%
      • 12–13 years: 36%
  • No gender Gender Gender Dysphoria preference
  • Becoming more common as a cause of genital herpes Genital Herpes Genital 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
  • Most common cause of acute, nonepidemic viral encephalitis Encephalitis Encephalitis 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 in the US

HSV-2:

  • Prevalent worldwide
  • More common in low-income countries
  • Seroprevalence: 
    • Individuals who are 14–49 years old in the US: approximately 16%
    • Increases with age and the number of sexual partners
    • Gender Gender Gender Dysphoria:
      • Women: 21%
      • Men: 12%
    • Race:
      • Non-Hispanic Blacks: 39% 
      • Non-Hispanic Whites: 12%

Neonatal herpes infection: 

  • A rare complication of maternal genital herpes Genital Herpes Genital 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
  • Occurs in about 1 in 3,200 deliveries in the US
  • Most likely to occur in women who acquire primary genital herpes Genital Herpes Genital 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 and, thus, lack maternal antibodies Antibodies Immunoglobulins (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 at or near the time of delivery

Pathogenesis

Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli

Humans are the main reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli.

Transmission

HSV-1:

  • Close contact with oral secretions of individuals who are actively shedding the virus Virus Viruses 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
  • May also be transmitted via unapparent or asymptomatic lesions
  • Can be transmitted through oral sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria to uninfected partners

HSV-2:

  • Sexual contact:
    • Risk is higher with male than with female source partners.
    • 70% of successful transmissions occur during periods of asymptomatic viral shedding Viral shedding The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Hepatitis A Virus.
  • Contact with infected secretions
  • Perinatal transmission Perinatal transmission The 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:
    • Usually occurs during vaginal birth
    • In utero infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease can occur in primary infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.

Pathophysiology

Primary infection:

  • Primary infection: 
    • Occurs in individuals with no preexisting antibodies Antibodies Immunoglobulins (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 for HSV-1 or HSV-2
    • Different from non-primary 1st-episode: a herpes infection in a patient with preexisting antibodies Antibodies Immunoglobulins (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 alternate serotype
    • Example: 1st episode of a perioral lesion of HSV-1 in a patient who has preexisting antibodies Antibodies Immunoglobulins (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
      • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship exhibit attenuated symptoms and signs similar to those in reactivation lesions, with fewer lesions and less severe systemic symptoms.
  • Virus Virus Viruses 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 must encounter mucosal surfaces or broken skin Skin The 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 (intact skin Skin The 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 is resistant). 
  • Virus Virus Viruses 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 attaches to and enters epithelial cells through interactions between the viral surface glycoproteins Glycoproteins Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. Basics of Carbohydrates and cellular HSV receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (e.g., nectin-1).
  • Vesicular lesions of the epidermis Epidermis The 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 are produced → release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of infectious virions during the lytic/reproductive phase

Lifetime latency:

  • Definition: the persistence of viral genomes in cells that do not produce infectious virus Virus Viruses 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
  • Viral nucleocapsids are transported along sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology axons Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Nervous System: Histology to the neuronal cell bodies → establishment of latent infection:
    • Trigeminal ganglia in oropharyngeal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease 
    • Sacral ganglia in genital infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Virus Virus Viruses 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 remains latent in the nuclei of nerve cells.
  • Only latency-associated viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure transcripts (LATs) are synthesized (no viral proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis are produced). 
  • LATs appear to confer resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage by silencing lytic gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression through heterochromatin Heterochromatin The portion of chromosome material that remains condensed and is transcriptionally inactive during interphase. DNA Types and Structure formation, which prevents transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription.
  • HSV avoids cellular and humoral immune recognition Immune Recognition Yaws, Bejel, and Pinta by:
    • Inhibiting the class I MHC Class I MHC Genetic loci in the vertebrate major histocompatibility complex which encode polymorphic characteristics not related to immune responsiveness or complement activity, e.g., B loci (chicken), dla (dog), gpla (guinea pig), h-2 (mouse), rt-1 (rat), hla-a, -b, and -c class I genes of man. Adaptive Cell-mediated Immunity recognition pathway
    • Producing decoy receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors that bind BIND Hyperbilirubinemia of the Newborn the Fc Fc Crystallizable fragments composed of the carboxy-terminal halves of both immunoglobulin heavy chains linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (complement fixation, binding to the cell membrane via fc receptors, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme papain. Immunoglobulins: Types and Functions domain of Igs Igs Immunoglobulins (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 and inhibit  complement activation Complement Activation The sequential activation of serum complement proteins to create the complement membrane attack complex. Factors initiating complement activation include antigen-antibody complexes, microbial antigens, or cell surface polysaccharides. Systemic Lupus Erythematosus
    • Infecting dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions that help in antiviral Antiviral Antivirals for Hepatitis B immune responses

Reactivation:

  • Signifies the transition of a virus Virus Viruses 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 from its latent state to lytic replication state in the nerve ganglia
  • The virus Virus Viruses 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 moves by anterograde axonal transport to epithelial cells at the original infected site.
  • Replication occurs within epithelial cells:
  • Recurrent eruptions are usually: 
    • Less severe 
    • Occur less frequently over time
  • Occurs in immunocompetent individuals because HSV has multiple immune-evasion mechanisms
  • Factors favoring reactivation/frequency of reactivation:
    • Immunosuppressed states:
      • Transplant recipients
      • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cancer
      • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS who have low CD4 counts (HSV requires intact cellular immunity Cellular immunity Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role. Squamous Cell Carcinoma (SCC) to be normally contained)
    • Excessive sunlight
    • Febrile illnesses
    • Physical (e.g., dental procedures) or emotional stress 
    • Elderly
    • Unknown stimuli
Pathogenesis of hsv-1 and 2 infections herpes simplex virus

Diagram summarizing the pathogenesis of HSV-1 and -2 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

Image by Lecturio. License: CC BY-NC-SA 4.0

Pathology

Herpes simplex Herpes Simplex A 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 viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology cause cytolytic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease that form the basis of all pathologic changes: necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of infected cells together with the inflammatory response

  • Gross: 
    • Grouped vesicles Vesicles Female Genitourinary Examination on an erythematous base
    • Later become pustules and form crusts that heal without scarring Scarring Inflammation because cytopathic effects are limited to the epidermis Epidermis The 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
  • Microscopic:
    • Infected keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions become multinucleated (from cell fusion) and acantholytic (separated from each other).
    • Distinct intranuclear inclusions Intranuclear inclusions Circumscribed masses of foreign or metabolically inactive materials, within the cell nucleus. Some are viral inclusion bodies. Varicella-Zoster Virus/Chickenpox (“Cowdry type A inclusions” = viral replication proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis and virions that push chromatin Chromatin The material of chromosomes. It is a complex of dna; histones; and nonhistone proteins found within the nucleus of a cell. DNA Types and Structure to the edge of the nucleus Nucleus Within 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)
    • Epidermal necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage or full-thickness acantholysis Acantholysis Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris and darier disease. Varicella-Zoster Virus/Chickenpox (causes blistering)
    • Dermal nerve twigs may have acute and chronic perineural inflammation Inflammation Inflammation 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 with occasional Schwann cell Schwann Cell Neuroglial cells of the peripheral nervous system which form the insulating myelin sheaths of peripheral axons. Nervous System: Histology hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation and frank neuronal necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage.

Diseases caused by HSV-1

A number of conditions are caused by HSV. The infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease listed below are most commonly caused by HSV-1. Note: HSV-2 can also be (though often less commonly) associated with many of these diagnoses.

Asymptomatic infection

Only 20%‒25% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HSV-1 antibodies Antibodies Immunoglobulins (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 have a positive clinical history of oral-labial or genital infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.

Oral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

Gingivostomatitis:

  • Commonly caused in children by a primary infection
  • Signs and symptoms:
    • Fever Fever Fever 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
    • Painful vesicular lesions:
      • Occur on the oral and pharyngeal mucosa
      • Ulcerate rapidly
    • Gingivitis Gingivitis Inflammation of gum tissue (gingiva) without loss of connective tissue. Chédiak-Higashi Syndrome with extension Extension Examination of the Upper Limbs to the lips Lips The 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 and cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma
    • Pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis
    • Cervical lymphadenopathy Lymphadenopathy Lymphadenopathy 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
    • Systemic symptoms:
      • Fever Fever Fever 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
      • Malaise Malaise Tick-borne Encephalitis Virus
      • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus

Pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis:

  • Commonly caused in adults by a primary infection
  • Signs and symptoms:
    • Pharyngeal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Tonsillar exudate Tonsillar exudate Tonsillitis
    • Oral lesions:
      • Exudative
      • Ulcerative
    • Cervical lymphadenopathy Lymphadenopathy Lymphadenopathy 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
    • Systemic symptoms

Herpes labialis:

  • Recurrent reactivation infection
  • Signs and symptoms:
    • Prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache:
    • Lesions: 
      • Consist of vesicles Vesicles Female Genitourinary Examination or localized oral-labial ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers (“ cold sores Cold sores Stomatitis 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” or “ fever Fever Fever 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 blisters”)
      • Decrease in pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways after 24 hours
      • Healing and crust Crust Dried exudate of body fluids (blood, pus, or sebum) on an area of damaged skin Secondary Skin Lesions formation in 5–8 days
    • Rarely associated with systemic symptoms

Genital infection

  • Primary genital HSV-1 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Bilateral genital ulcerations
    • Tender lymphadenopathy Lymphadenopathy Lymphadenopathy 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 
    • Fever Fever Fever 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 
    • Headache Headache The 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 
    • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
    • Autonomic dysfunction Autonomic Dysfunction Anterior Cord Syndrome ( urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium or constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation)
    • Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology disturbances (hyperesthesia or anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts of the perineum Perineum The body region lying between the genital area and the anus on the surface of the trunk, and to the shallow compartment lying deep to this area that is inferior to the pelvic diaphragm. The surface area is between the vulva and the anus in the female, and between the scrotum and the anus in the male. Vagina, Vulva, and Pelvic Floor: Anatomy)
  • Reactivation of genital HSV-1:
    • More common in the 1st year after infection 
    • Multiple recurrences are rare (unlike genital HSV-2 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease).

Other cutaneous manifestations

Herpetic whitlow: 

  • Infection of the finger from inoculation of the virus Virus Viruses 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 through a break in the skin Skin The 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 
  • Seen in: 
  • Signs and symptoms:

Herpes gladiatorum: 

Erythema multiforme Erythema multiforme Erythema multiforme (EM) is an acute hypersensitivity reaction characterized by targetoid skin lesions with multiple rings and dusky centers. Lesions may be accompanied by systemic symptoms (e.g., fever) and mucosal lesions (e.g., bullae). Erythema Multiforme

Eczema Eczema Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE and a personal or family history of atopy. Skin dryness, erythema, oozing, crusting, and lichenification are present. Atopic Dermatitis (Eczema) herpeticum: 

  • HSV-1 infection superimposed on skin Skin The 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 lesions from atopic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema) (particularly in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on immunosuppressive therapy)
  • Signs and symptoms:
    • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and vesicular skin Skin The 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 lesions
    • Can spread rapidly if untreated

Eye infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

Eye infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease occur in < 5% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HSV-1 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, leading to vision Vision Ophthalmic Exam loss and/or blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity.

Keratitis:

  • Infection of the corneal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology
  • Leading cause of corneal blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity in high-income countries 
  • Signs and symptoms:
    • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 
    • Foreign-body sensation
    • Visual blurring 
    • Tearing
    • Chemosis Chemosis Conjunctivitis 
    • Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis 
    • ↓ Corneal sensation 
    • Characteristic dendritic lesions of the cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy
  • Recurrent infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are common. 
  • Stromal scarring Scarring Inflammation can result.

Acute retinal necrosis Acute Retinal Necrosis Herpes Zoster (Shingles):

Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis and blepharitis Blepharitis Blepharitis is an ocular condition characterized by eyelid inflammation. Anterior blepharitis involves the eyelid skin and eyelashes, while the posterior type affects the meibomian glands. Often, these conditions overlap. Blepharitis:

  • Unilateral
  • Vesicles Vesicles Female Genitourinary Examination on the lid margin 
  • Chemosis Chemosis Conjunctivitis 
  • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema of the eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis 
  • Tearing

Chorioretinitis Chorioretinitis Chorioretinitis is the inflammation of the posterior segment of the eye, including the choroid and the retina. The condition is usually caused by infections, the most common of which is toxoplasmosis. Some of these infections can affect the fetus in utero and present as congenital abnormalities. Chorioretinitis (posterior uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea)

  • From disseminated HSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease 
  • Seen in neonates or immunosuppressed individuals
  • Signs and symptoms:

Neurologic syndromes

Encephalitis Encephalitis Encephalitis 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:

  • Usually unilateral, involving the temporal lobe Temporal lobe Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the occipital lobe. Cerebral Cortex: Anatomy and insular cortex (board exam question)
  • High rate of morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status
  • Signs and symptoms:
    • Fever Fever Fever 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
    • Headache Headache The 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
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • Focal neurologic signs
    • Impaired consciousness

Aseptic meningitis Meningitis Meningitis 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:

  • More commonly associated with HSV-2 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Signs and symptoms:
    • Fever Fever Fever 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
    • Headache Headache The 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
    • Photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache
    • Meningismus Meningismus Subarachnoid Hemorrhage

Other manifestations:

  • Bell’s palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies: temporary inability to control the facial muscles Facial muscles The facial muscles (also called mimetic muscles) control facial expression and are supplied by the facial nerve. Most of them originate from the skull and attach to the skin around the facial openings, which serve as a method to group or classify them. Facial Muscles: Anatomy on the affected side of the face
  • Autonomic dysfunction Autonomic Dysfunction Anterior Cord Syndrome: presents as urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium during a primary genital infection
  • Transverse myelitis Transverse myelitis Inflammation which extends horizontally across the spinal cord, believed to be immune-mediated and triggered by infection; associated with signs and symptoms of motor, sensory, and/or autonomic dysfunction. Mononucleosis: a demyelinating inflammation Inflammation Inflammation 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 of both sides of 1 section of the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy

Respiratory tract infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

Epiglottitis Epiglottitis Epiglottitis (or “supraglottitis”) is an inflammation of the epiglottis and adjacent supraglottic structures. The majority of cases are caused by bacterial infection. Symptoms are rapid in onset and severe. Epiglottitis or laryngitis Laryngitis Laryngitis is an inflammation of the larynx most commonly due to infection or trauma that can be either acute or chronic. In this condition, the 2 folds of mucous membranes that make up the vocal cords become inflamed and irritated. The inflammation results in a distortion of the voice produced, resulting in a hoarse sound or aphonia. Laryngitis (herpetic croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup): 

HSV pneumonitis Pneumonitis Human Herpesvirus 6 and 7:

  • Rare
  • Usually occurs in immunocompromised immunocompromised A 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 patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Considered an AIDS-defining condition
  • Occurs following tracheobronchitis Tracheobronchitis Moraxella
  • Signs and symptoms:
    • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
    • Cough
    • Fever Fever Fever 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
    • Wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing

Gastrointestinal disease

HSV esophagitis Esophagitis Esophagitis is the inflammation or irritation of the esophagus. The major types of esophagitis are medication-induced, infectious, eosinophilic, corrosive, and acid reflux. Patients typically present with odynophagia, dysphagia, and retrosternal chest pain. Esophagitis:

  • Usually seen in immunocompromised immunocompromised A 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 hosts
  • Considered an AIDS-defining condition 
  • Spread by either: 
    • Direct extension Extension Examination of the Upper Limbs from the oropharynx Oropharynx The middle portion of the pharynx that lies posterior to the mouth, inferior to the soft palate, and superior to the base of the tongue and epiglottis. It has a digestive function as food passes from the mouth into the oropharynx before entering esophagus. Pharynx: Anatomy 
    • Reactivation and spread through the vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy to the mucosa
  • Signs and symptoms: 
    • Odynophagia Odynophagia Epiglottitis 
    • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia 
    • Retrosternal chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 

Fulminant hepatitis Fulminant hepatitis Echovirus

  • Rare 
  • Associated with disseminated disease
  • Caused by both HSV-1 and HSV-2
  • Only 30% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have typical skin Skin The 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 lesions.

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Diseases Caused by HSV-2

The conditions listed below are most commonly associated with HSV-2 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease. Again, keep in mind that HSV-1 can also be associated with many of these diagnoses.

Genital infection

Primary genital HSV-2 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:

  • Average incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: 4 days (range 2–12 days)
  • Viremia Viremia The presence of viruses in the blood. Erythema Infectiosum is more common (24%) than in reactivation cases. 
  • Can be asymptomatic, or present with mild or severe symptoms:
    • Painful genital ulcers:
    • Dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs)
    • Fever Fever Fever 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
    • Tender local inguinal lymphadenopathy Lymphadenopathy Lymphadenopathy 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
    • Headache Headache The 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 

Non-primary 1st episode infection (reactivation): 

  • Frequency of recurrences:
    • Earlier and more frequent recurrences if the primary infection had lasted > 5 weeks
    • More common with HSV-2 than HSV-1
    • More common in immunosuppressed patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Signs and symptoms:
Penile blisters herpes simplex-2

Penile blisters (arrows) due to a recurring herpes simplex-2 virus Virus Viruses 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 (HSV-2) infection

Image: “Penile blisters (arrows), due to a recurring herpes simplex-2 (HSV-2) virus Virus Viruses 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 infection” by CDC/ Susan Lindsley. License: Public Domain

Extragenital manifestations

  • Aseptic meningitis Meningitis Meningitis 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
  • Benign Benign Fibroadenoma recurrent aseptic meningitis Meningitis Meningitis 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 (Mollaret’s meningitis Meningitis Meningitis 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):
    • > 3 episodes of meningitis Meningitis Meningitis 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 symptoms
    • Followed by spontaneous resolution
  • Sacral ANS ANS The ans is a component of the peripheral nervous system that uses both afferent (sensory) and efferent (effector) neurons, which control the functioning of the internal organs and involuntary processes via connections with the CNS. The ans consists of the sympathetic and parasympathetic nervous systems. Autonomic Nervous System: Anatomy dysfunction: causes urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium
  • Sacral radiculitis Radiculitis Ankylosing Spondylitis
    • Acute urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium with loss of sacral sensation
    • Occurs in severe primary infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Transient, but requires catheterization
  • Hepatitis
  • Proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease: more common in men who have sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria with men (MSM)

Diagnosis

  • PCR PCR Polymerase 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):
    • Preferred method of diagnosis
    • Can be used to detect viral DNA DNA A 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
    • Can be used to identify HSV serotypes
    • Extremely high sensitivity (98%) and specificity (99%) 
    • Positive findings early in the course of illness 
    • Samples can be obtained from:
  • Viral cultures: 
    • Less sensitive than PCR PCR Polymerase 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)
    • Depends on the quantity of virus Virus Viruses 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
  • Tissue biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
    • Sites:
      • Skin Skin The 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
      • Lung
      • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
      • Esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
    • Can be diagnosed based on histologic appearance and confirmed using immunohistochemical or molecular methods
  • Tzanck smear:
    • Procedure:
      • Specimen is obtained by scraping the base of a vesicle Vesicle Primary Skin Lesions.
      • Specimen is placed on a slide. 
      • Stained with Giemsa or toluidine blue
      • Typical cytopathic effects of HSV are observed.
    • Will show multinucleated giant cells Giant cells Multinucleated 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
    • Low sensitivity and specificity Sensitivity and Specificity Binary 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
    • Cannot differentiate between HSV serotypes
  • Direct fluorescent antibody Direct Fluorescent Antibody A 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 Infections testing:
  • Serologic testing: 
    • Limited applications
    • Titers do not correlate with positive cultures or the presence of lesions.
Image from a tzanck smear herpes simplex virus

Image from a Tzanck smear obtained from a penile lesion:
Multinucleated giant cells Giant cells Multinucleated 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 are seen, indicating a herpes infection.

Image: “Photomicrograph depicts a Tzanck stained penile lesion specimen” by CDC/ Joe Miller. License: Public Domain

Management

Medical therapy

Antivirals:

  • Mechanism of action: nucleoside derivatives that interfere with the synthesis Synthesis Polymerase Chain Reaction (PCR) of viral DNA DNA A 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 by inhibiting viral DNA DNA A 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 polymerase
  • Renal function should be monitored.
  • Uses:
    • Depends on severity (may not be needed for mild or minimally symptomatic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease)
    • Treatment of an active infection
    • Episodic therapy (started at the very 1st sign of prodromal symptoms)
    • Chronic suppression Suppression Defense Mechanisms (for frequent or severe recurrences)
    • Reduces but does not eliminate viral shedding Viral shedding The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Hepatitis A Virus
  • Systemic options:
    • Acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles)
    • Valacyclovir Valacyclovir A 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)
    • Famciclovir Famciclovir An 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
  • Topical options (for ocular infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease):

Analgesics:

  • Lidocaine Lidocaine A 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
  • Benzocaine Benzocaine A surface anesthetic that acts by preventing transmission of impulses along nerve fibers and at nerve endings. Local Anesthetics

Immunosuppressed patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship

  • Immunosuppressed patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have more severe symptoms, higher risk of complications, and greater risk for developing drug-resistant HSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.
  • Treated with similar regimens as immunocompetent patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, but with higher doses for suppressive therapy
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are HIV HIV Anti-HIV Drugs positive and not on antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs (ART) may be prone to immune reconstitution inflammatory syndrome (IRIS) when treated for HSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.
    • Clinical manifestations worsen initially after the initiation of ART.
    • Suppressive therapy may be given to prevent IRIS.

Prevention of new HSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

  • Herpes labialis: 
    • Avoid contact with saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy or saliva-contaminated fomites Fomites Inanimate objects that carry pathogenic microorganisms and thus can serve as the source of infection. Microorganisms typically survive on fomites for minutes or hours. Common fomites include clothing, tissue paper, hairbrushes, and cooking and eating utensils. Adenovirus from family members and intimate partners (e.g., avoid kissing and sharing kitchen utensils and towels).
    • Healthcare workers: 
      • Universal precautions
      • Wear gloves during physical examination of a patient with active HSV lesions.
      • Eye and mouth protection when suctioning or during bronchoscopy Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Laryngomalacia and Tracheomalacia
  • Genital herpes Genital Herpes Genital 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:
    • Barrier use for oral and genital sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria is recommended.
    • Note: Precautions should be taken by pregnant partners who are HSV negative owing to the high risk of transmission to the neonate Neonate An infant during the first 28 days after birth. Physical Examination of the Newborn.
  • Herpes gladiatorum: 
    • Athletes must not participate in contact sports until all herpes lesions are in the dry, crust Crust Dried exudate of body fluids (blood, pus, or sebum) on an area of damaged skin Secondary Skin Lesions stage. 
    • Suppressive oral antiviral Antiviral Antivirals for Hepatitis B therapy has been suggested for all wrestlers regardless of HSV history, as it markedly reduces the risk of an outbreak (by 85%).

Comparison of Herpesviruses

The table presented below compares and contrasts HSV-1 and HSV-2:

Table: Comparision of herpes simplex Herpes Simplex A 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 viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology
Serotype HSV-1 HSV-2
Transmission
  • Respiratory secretions, saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy
  • Ubiquitous
  • 90% in childhood
  • Sexual contact, perinatal
  • 30% in adulthood
Lytic infection Mucoepithelial cells Mucoepithelial cells
Latency Trigeminal ganglia Sacral ganglia
Diseases
  • Gingivostomatitis
  • Herpes labialis
  • Keratitis
  • Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis
  • Herpetic whitlow
  • Encephalitis Encephalitis Encephalitis 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
  • Hepatitis
  • Esophagitis Esophagitis Esophagitis is the inflammation or irritation of the esophagus. The major types of esophagitis are medication-induced, infectious, eosinophilic, corrosive, and acid reflux. Patients typically present with odynophagia, dysphagia, and retrosternal chest pain. Esophagitis
  • Pneumonitis Pneumonitis Human Herpesvirus 6 and 7
  • Herpes genitalis Herpes Genitalis Infection of the genitals (genitalia) with herpes simplex virus in either the males or the females. Labial and Genital Herpes
  • Neonatal herpes
  • Aseptic meningitis Meningitis Meningitis 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
  • Proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease

Comparison of viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology in the Herpesviridae family

The table below compares the 9 herpesviruses considered endemic in humans. There are 115 different total known species of herpesviruses, which are grouped into 3 families: 

  • Alpha (infect epithelial cells and produce latent infection in post-mitotic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology)
  • Beta (infect and produce latent infection in various cell types)
  • Gamma (produce latent infection mainly in lymphoid cells)
Table: Comparison of the 9 herpesviruses considered endemic in humans
HHV Common name Primary target cells Latency site Clinical presentation*
1
(alpha group)
HSV-1 Mucoepithelial cells Dorsal root ganglia
  • Gingivostomatitis
  • Keratitis
  • Herpetic whitlow
  • Encephalitis Encephalitis Encephalitis 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
  • Hepatitis
  • Esophagitis Esophagitis Esophagitis is the inflammation or irritation of the esophagus. The major types of esophagitis are medication-induced, infectious, eosinophilic, corrosive, and acid reflux. Patients typically present with odynophagia, dysphagia, and retrosternal chest pain. Esophagitis
  • Pneumonitis Pneumonitis Human Herpesvirus 6 and 7
2
(alpha group)
HSV-2
  • Genital herpes Genital Herpes Genital 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
  • Meningitis Meningitis Meningitis 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
  • Proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease
3
(alpha group)
VZV
  • Chickenpox Chickenpox A highly contagious infectious disease caused by the varicella-zoster virus. It usually affects children, is spread by direct contact or respiratory route via droplet nuclei, and is characterized by the appearance on the skin and mucous membranes of successive crops of typical pruritic vesicular lesions that are easily broken and become scabbed. Chickenpox is relatively benign in children, but may be complicated by pneumonia and encephalitis in adults. Varicella-Zoster Virus/Chickenpox
  • Herpes zoster Herpes Zoster Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Shingles (also known as herpes zoster) is more common in adults and occurs due to the reactivation of VZV. Varicella-Zoster Virus/Chickenpox
4
(gamma group)
EBV EBV Epstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus
  • Epithelial cells
  • B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions
Memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions
  • Infectious mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as “the kissing disease,” is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis
  • Hodgkin lymphoma Hodgkin lymphoma Hodgkin lymphoma (HL) is a malignancy of B lymphocytes originating in the lymph nodes. The pathognomonic histologic finding of HL is a Hodgkin/Reed-Sternberg (HRS) cell (giant multinucleated B cells with eosinophilic inclusions). The disease presents most commonly with lymphadenopathy, night sweats, weight loss, fever, splenomegaly and hepatomegaly. Hodgkin Lymphoma
  • Burkitt lymphoma Burkitt lymphoma A form of undifferentiated malignant lymphoma usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (Human herpesvirus 4) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative. Non-Hodgkin Lymphomas
  • Oral hairy leukoplakia Hairy leukoplakia Epithelial hyperplasia of the oral mucosa associated with epstein-barr virus and found almost exclusively in persons with HIV infection. The lesion consists of a white patch that is often corrugated or hairy. Epstein-Barr Virus
  • EBV-associated gastric cancer Gastric cancer Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Gastric Cancer
5
(beta group)
CMV
  • Monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation
  • Lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology
  • Epithelial cells
Hematopoietic progenitor cells in bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis
  • CMV mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as “the kissing disease,” is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis
  • CMV retinitis CMV retinitis Infection of the retina by cytomegalovirus characterized by retinal necrosis, hemorrhage, vessel sheathing, and retinal edema. Cytomegalovirus retinitis is a major opportunistic infection in AIDS patients and can cause blindness. Retinal Detachment
  • CMV colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis
  • CMV encephalitis Encephalitis Encephalitis 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
6A, 6B
(beta group)
HHV-6 HHV-6 Human herpesvirus (HHV)-6 and HHV-7 are similar double-stranded DNA viruses belonging to the Herpesviridae family. Human herpesviruses are ubiquitous and infections are commonly contracted during childhood. Human Herpesvirus 6 and 7 T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions Monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation Roseola
7
(beta group)
HHV-7 HHV-7 Human herpesvirus (HHV)-6 and HHV-7 are similar double-stranded DNA viruses belonging to the Herpesviridae family. Human herpesviruses are ubiquitous and infections are commonly contracted during childhood. Human Herpesvirus 6 and 7 T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions
8
(gamma group)
Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions‘s sarcoma-associated herpesvirus
  • Lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology
  • Epithelial cells
B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions sarcoma
*Bold in “clinical presentation” column: AIDS-defining illnesses
VZV: varicella zoster virus Virus Viruses 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

Differential Diagnosis

  • Recurrent aphthous ulcers (canker sores): a very common, probably immunologically related disease of the oral mucosa Oral mucosa Lining of the oral cavity, including mucosa on the gums; the palate; the lip; the cheek; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous epithelium covering muscle, bone, or glands but can show varying degree of keratinization at specific locations. Stomatitis (and less commonly, the genital mucosa), manifesting as small, discrete, painful ulcers that heal within 1–2 weeks. Recurrent aphthous ulcers are not preceded by vesicles Vesicles Female Genitourinary Examination and occur only on mucosal surfaces. Diagnosis is clinical, although testing can be conducted to evaluate for associated conditions (e.g., nutritional deficiencies, inflammatory bowel disease). Management includes trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation avoidance, symptomatic therapy, and treatment of underlying etiologies.
  • Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis: a bacterial infection caused by the spirochete Spirochete Treponema 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. Treponema Treponema pallidum Treponema pallidum The causative agent of venereal and non-venereal syphilis as well as yaws. Treponema, which is usually spread through sexual contact. Primary syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis can present with hard chancres that initially present as small red patches Patches Vitiligo. Unlike the vesicles Vesicles Female Genitourinary Examination in HSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, these chancres ( vesicles Vesicles Female Genitourinary Examination are absent) are painless. Diagnosis is made with serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus, dark-field examination, and immunostaining on biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Penicillin Penicillin Rheumatic Fever G is the antibiotic of choice.
  • Chancroid Chancroid Chancroid 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: an STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) caused by Haemophilus ducreyi Haemophilus ducreyi A species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid. Haemophilus. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop painful necrotizing genital ulcers and inguinal lymphadenopathy Lymphadenopathy Lymphadenopathy 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. Diagnosis is usually clinical, but PCR PCR Polymerase 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) and cultures can be used for confirmation. Management is with macrolide antibiotics.
  • Other genital, anal, or perianal ulcers: noninfectious causes that are not STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) related: yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology, trauma, carcinoma, aphthae, fixed drug eruption, and psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis.
  • Bacterial pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis: an infection of the pharynx Pharynx The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship typically experience a sore throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy and fever Fever Fever 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. Symptoms are not preceded by a grouped cluster of vesicles Vesicles Female Genitourinary Examination as those seen in HSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease. Diagnosis can include rapid streptococcal screens to detect group A Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus, bacterial cultures, and PCR PCR Polymerase 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) to exclude HSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease. Treatment includes penicillin Penicillin Rheumatic Fever or amoxicillin Amoxicillin A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. Penicillins.
  • Enterovirus Enterovirus A genus of the family picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated ‘human enterovirus’. Coxsackievirus infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (e.g, herpangina Herpangina Acute types of coxsackievirus infections or echovirus infections that usually affect children during the summer and are characterized by vesiculoulcerative lesions on the mucous membranes of the throat; dysphagia; vomiting, and fever. Coxsackievirus): acute febrile illnesses mostly caused by coxsackievirus Coxsackievirus Coxsackievirus is a member of a family of viruses called Picornaviridae and the genus Enterovirus. Coxsackieviruses are single-stranded, positive-sense RNA viruses, and are divided into coxsackie group A and B viruses. Both groups of viruses cause upper respiratory infections, rashes, aseptic meningitis, or encephalitis. Coxsackievirus A and B, and enterovirus Enterovirus A genus of the family picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated ‘human enterovirus’. Coxsackievirus 71. Herpangina Herpangina Acute types of coxsackievirus infections or echovirus infections that usually affect children during the summer and are characterized by vesiculoulcerative lesions on the mucous membranes of the throat; dysphagia; vomiting, and fever. Coxsackievirus is associated with small vesicular or ulcerative lesions on the posterior oropharyngeal structures ( enanthem Enanthem Varicella-Zoster Virus/Chickenpox). Clinical findings and PCR PCR Polymerase 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) are used to make the diagnosis. Management is symptomatic.
  • Infectious mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as “the kissing disease,” is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis: an infection caused by another herpesvirus, the EBV EBV Epstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus. Clinical manifestations include fever Fever Fever 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, tonsillar pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis, and lymphadenopathy Lymphadenopathy Lymphadenopathy 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. Unlike HSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as “the kissing disease,” is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis is not usually associated with clusters of vesicles Vesicles Female Genitourinary Examination. Diagnosis is clinical and confirmed using heterophile antibody testing or serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus. Management is supportive.
  • Stevens-Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome ( SJS SJS Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome): a rare, potentially lethal disease that attacks the skin Skin The 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 and mucous membranes. Stevens-Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome runs on a spectrum with the more severe form ( toxic epidermal necrolysis Toxic Epidermal Necrolysis Stevens-Johnson Syndrome (TEN)) and can be triggered by a reaction to a medication or to a preexisting bacterial or viral infection (including HSV) or illness. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with a flu-like prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache and the appearance of cutaneous bullae Bullae Erythema Multiforme, followed by sloughing on the face, thorax, and mucous membranes. Diagnosis is clinical and the management is largely supportive.
  • Bacterial skin Skin The 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 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease with superficial ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers: infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease that can mimic herpetic whitlow. Bacterial skin Skin The 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 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease with superficial ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers are not preceded by a vesicle Vesicle Primary Skin Lesions and often involve subepidermal tissues. It is important to differentiate these conditions, as antibiotics and drainage are not necessary for herpetic whitlow.
  • Proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease: besides HSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, the differential diagnosis in MSM includes Neisseria gonorrhoeae Neisseria gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria, Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia, and T. pallidum infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease. The presentation of proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease can mimic inflammatory bowel disease. Diagnosis is by PCR PCR Polymerase 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), cultures, serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus, dark-field examination, and immunostaining on biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma.

References

  1. Wald, A., Johnston, C. (2020). Treatment and prevention of herpes simplex virus type 1 in immunocompetent adolescents and adults. UpToDate. Retrieved February 1, 2021, from https://www.uptodate.com/contents/treatment-and-prevention-of-herpes-simplex-virus-type-1-in-immunocompetent-adolescents-and-adults
  2. Miller, S. (2019). Herpesviruses. In Riedel, S, Morse, S.A., Mietzner, T., Miller, S. (Eds.), Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28th ed, pp. 473–482.
  3. Corey, C. (2018). Herpes Simplex Virus Infections. In Jameson, J.L., et al. (Ed.), Harrison’s Principles of Internal Medicine, 20th ed. Vol 1, pp. 1345–1354.
  4. Frank, K.M., McAdam, A.J. (2020). Infectious Diseases. In Kumar, V., Abbas, A.K., Aster, J.C., (Eds.). Robbins & Cotran Pathologic Basis of Disease, 10 ed. pp. 354–355.
  5. Johnston, C., Wald, A. (2019). Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection. In Mitty, J. (Ed.), UpToDate. Retrieved May 24, 2021, from https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-herpes-simplex-virus-type-1-infection
  6. Saleh, D., Yarrarapu, S.N.S., Sharma, S. (2021). Herpes simplex type 1. [online] StatPearls. Retrieved May 24, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK482197/
  7. Mathew, Jr, J., Sapra, A. (2021). Herpes simplex type 2. [online] StatPearls. Retrieved May 24, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK554427/
  8. Ayoade, F.O., Balan, S., Todd, J.R. (2021). Herpes simplex. In Bronze, M.S. (Ed.), Medscape. Retrieved May 24, 2021, from https://emedicine.medscape.com/article/218580-overview

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