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Herpes Zoster (Shingles) (Clinical)

Herpes zoster (also known as shingles) is a viral, reactivation infection caused by the varicella-zoster virus (VZV). Latent VZV remains dormant in the dorsal root ganglion after the primary infection phase of varicella (chickenpox). Age, stress, or immunocompromised states can trigger the reactivation of the virus. Herpes zoster clinically presents as a painful, unilateral rash in a single, dermatomal distribution. The diagnosis is primarily made from the history and physical examination. However, laboratory testing (such as PCR) can be performed if the diagnosis is unclear. Management includes antiviral therapy and symptomatic treatment. Effective vaccines exist for both primary varicella and herpes zoster.

Last updated: Mar 4, 2024

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition[1,6,8]

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 (also known as shingles Shingles 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) is a viral, reactivation Reactivation Herpes Simplex Virus 1 and 2 infection caused by the varicella-zoster virus Varicella-Zoster Virus Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Varicella-zoster infections are highly contagious and transmitted through aerosolized respiratory droplets or contact with infected skin lesions. Varicella-Zoster Virus/Chickenpox (VZV) manifesting as a unilateral, dermatomal Dermatomal Dermatologic Examination, painful, vesicular eruption.

Epidemiology[5,6,8]

  • Annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in the United States: 1.2 million people
  • Approximately 30% of the population will experience 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 during their lifetime.
  • More common in:
    • Older age
    • 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
    • Women
  • Only individuals previously affected with 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 develop shingles Shingles 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.

Etiology[8]

Causative organism: VZV

  • Also known as human herpesvirus 3 Human herpesvirus 3 Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Varicella-zoster infections are highly contagious and transmitted through aerosolized respiratory droplets or contact with infected skin lesions. Varicella-Zoster Virus/Chickenpox
  • Enveloped, 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
  • Belongs to the Herpesviridae Herpesviridae A family of enveloped, linear, double-stranded DNA viruses infecting a wide variety of animals. Subfamilies, based on biological characteristics, include: alphaherpesvirinae; betaherpesvirinae; and gammaherpesvirinae. Herpes Simplex Virus 1 and 2 family

Transmission: 

  • VZV causes 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, which can be spread via:
  • After recovery from 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, 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 remains dormant but can become reactivated later in life, leading to 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.
  • Contact with 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 lesions does NOT cause 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 but can cause 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 in exposed individuals without immunity.
  • After blisters crust Crust Dried exudate of body fluids (blood, pus, or sebum) on an area of damaged skin Secondary Skin Lesions over, they are no longer infectious.
Single varicella zoster virus herpes zoster

Transmission electron microscopic image showing the single varicella-zoster virus (VZV), also known as human herpesvirus 3, which causes chickenpox

Image: “Ultrastructural features exhibited by a single varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3), the cause of chickenpox.” by CDC. License: Public Domain

Risk factors[1,5,6]

  • Immunocompromised patient Immunocompromised patient 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. Herpes Zoster (Shingles):
    • Transplant
    • Immunosuppressive therapy
    • Human immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome 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 ( HIV HIV Anti-HIV Drugs), with highest risk in those with CD4 counts <200 cells/mm3
    • Autoimmune disorder Autoimmune Disorder Septic Arthritis
  • Active or chronic illness
  • Physical trauma
  • Family history Family History Adult Health Maintenance
  • Age (as patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship get older, T-lymphocyte–specific immunity to 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 wanes) 
  • Stress

Pathophysiology[1]

Varicella-zoster virus Varicella-Zoster Virus Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Varicella-zoster infections are highly contagious and transmitted through aerosolized respiratory droplets or contact with infected skin lesions. Varicella-Zoster Virus/Chickenpox causes 2 distinct syndromes:

Primary infection Primary infection Herpes Simplex Virus 1 and 2 ( 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): 

  • Transmitted through aerosols Aerosols Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents. Coxiella/Q Fever → targets mucoepithelial cells
  • Viremia Viremia The presence of viruses in the blood. Erythema Infectiosum → contagious, febrile illness occurs
  • After resolution, viral particles remain in the dorsal root ganglia or other sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology ganglia.
  • Host immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs suppresses replication 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 → lays dormant for years to decades (latency period)

Secondary infection ( shingles Shingles 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):

  • Host immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs fails to contain 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 → VZV reactivates
  • Spreads down the sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology nerve → 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 rash Rash Rocky Mountain Spotted Fever
  • Inflammatory response in the sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology ganglia:
    • Involves plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells and T lymphocytes T lymphocytes 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
    • Can result in neuronal damage → neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways
Pathogenesis of varicella-zoster virus herpes zoster

Pathogenesis of varicella-zoster virus (VZV):
The infection replicates viruses in mucoepithelial cells then spreads throughout the reticuloendothelial (RE) system and bloodstream, causing flu-like symptoms and chickenpox. After resolution of the primary infection, a latency period occurs and the virus remains dormant in the dorsal root ganglia. Reactivation of the infection results in shingles.

Image by Lecturio.

Clinical Presentation and Complications

Common presentation[6,9]

Acute neuritis Acute Neuritis Herpes Zoster (Shingles)

Rash Rash Rocky Mountain Spotted Fever:

  • Appears about 2–3 days (but can be longer) after the prodromal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Unilateral:
    • Occasionally, lesions may cross the midline (typically on the back).
  • Dermatomal Dermatomal Dermatologic Examination distribution
  • Initially appears as erythematous papules 
  • Progresses into bullae Bullae Erythema Multiforme or groups of vesicles Vesicles Female Genitourinary Examination:
    • Most lesions affect the area between dermatomes Dermatomes Spinal Cord: Anatomy T1 and L2.
    • In 15% of cases, the ophthalmic (1st) division of the trigeminal nerve Trigeminal nerve The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. The 12 Cranial Nerves: Overview and Functions is affected.
  • Becomes pustular or hemorrhagic within 3–4 days
  • Lesions start to crust Crust Dried exudate of body fluids (blood, pus, or sebum) on an area of damaged skin Secondary Skin Lesions in 7–10 days (no longer infectious). 
  • Scarring Scarring Inflammation and hypo- or hyperpigmentation Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. Malassezia Fungi may occur.

Systemic symptoms (< 20% of cases):

  • 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
  • Malaise Malaise Tick-borne Encephalitis Virus
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia

Disseminated 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[1,5]

The following are severe presentations, which may occur 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:

Cutaneous dissemination:

Visceral organ involvement:

  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Hepatitis
  • 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
  • May occur with or without a rash Rash Rocky Mountain Spotted Fever

Other presentations

Herpes zoster ophthalmicus Herpes zoster ophthalmicus Virus infection of the gasserian ganglion and its nerve branches characterized by pain and vesicular eruptions with much swelling. Ocular involvement is usually heralded by a vesicle on the tip of the nose. This area is innervated by the nasociliary nerve. Herpes Zoster (Shingles):[1,5]

  • Involves the ophthalmic division of the 5th cranial nerve (i.e., the trigeminal nerve Trigeminal nerve The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. The 12 Cranial Nerves: Overview and Functions, which innervates the forehead Forehead The part of the face above the eyes. Melasma, eyelid, eye, and part of the nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal))
  • Symptoms:
    • Unilateral pain Unilateral Pain Cluster Headaches
    • Hypesthesia
    • 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
    • Malaise Malaise Tick-borne Encephalitis Virus
    • 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
  • Hutchinson sign:[14,15]
    • Zoster lesions in the root, dorsum and/or on the tip of the nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal)
    • Indicates that the nasociliary branch of the trigeminal/5th cranial nerve is affected
    • ↑ Risk of ocular 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 and corneal denervation
  • Progression to:
    • 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
    • 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
    • Episcleritis
    • Keratitis Keratitis Inflammation of the cornea. Herpes Simplex Virus 1 and 2
    • Vision Vision Ophthalmic Exam loss

Ramsay Hunt syndrome Ramsay Hunt syndrome A syndrome characterized by facial palsy in association with a herpetic eruption of the external auditory meatus. This may occasionally be associated with tinnitus, vertigo, deafness, severe otalgia, and inflammation of the pinna. The condition is caused by reactivation of a latent herpesvirus 3, human infection which causes inflammation of the facial and vestibular nerves, and may occasionally involve additional cranial nerves. Herpes Zoster (Shingles) ( herpes zoster oticus Herpes zoster oticus A syndrome characterized by facial palsy in association with a herpetic eruption of the external auditory meatus. This may occasionally be associated with tinnitus, vertigo, deafness, severe otalgia, and inflammation of the pinna. The condition is caused by reactivation of a latent herpesvirus 3, human infection which causes inflammation of the facial and vestibular nerves, and may occasionally involve additional cranial nerves. Herpes Zoster (Shingles)):[1,5]

  • Involves the geniculate ganglion and 8th cranial nerve
  • Triad of symptoms:
  • Additional features:
    • Dysgeusia Dysgeusia A condition characterized by alterations of the sense of taste which may range from mild to severe, including gross distortions of taste quality. Nitroimidazoles
    • Hearing abnormalities
    • Lacrimation
Herpes zoster ophthalmicus

Herpes zoster ophthalmicus with involvement of the left eye

Image: “External photograph showing herpes zoster ophthalmicus” by Sudharshan S et al. License: CC BY 2.0

Zoster sine herpete[5,9,13]

  • VZV causes pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (in dermatomal Dermatomal Dermatologic Examination distribution) without obvious 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/ vesicles Vesicles Female Genitourinary Examination.
  • Can be missed or misdiagnosed

Complications[1,6]

Postherpetic neuralgia Postherpetic neuralgia Pain in nerves, frequently involving facial skin, resulting from the activation the latent varicella-zoster virus. The two forms of the condition preceding the pain are herpes zoster oticus; and herpes zoster ophthalmicus. Following the healing of the rashes and blisters, the pain sometimes persists. Herpes Zoster (Shingles)

  • Most common complication 
  • Persistence of significant pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways for 90 days after rash Rash Rocky Mountain Spotted Fever development
  • Other symptoms:
  • Affects 10%–18% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with shingles Shingles 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
  • Risk increases with age.
    • Rarely seen in those < 40 years of age.
    • Severity and duration of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways also increase with age

Acute retinal necrosis Acute Retinal Necrosis Herpes Zoster (Shingles)

  • VZV infection is the most common cause.[16]
  • Features:
    • Acute iridocyclitis Iridocyclitis Acute or chronic inflammation of the iris and ciliary body characterized by exudates into the anterior chamber, discoloration of the iris, and constricted, sluggish pupil. Symptoms include radiating pain, photophobia, lacrimation, and interference with vision. Relapsing Fever
    • Vitritis 
    • Necrotizing retinitis
    • Occlusive retinal vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus
  • Presents with blurred vision Blurred Vision Retinal Detachment and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Complications:
    • Rapid loss of vision Vision Ophthalmic Exam 
    • Retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment

Other complications: 

  • Secondary bacterial 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 of 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
  • 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
  • Peripheral motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuropathy Neuropathy Leprosy
  • Guillain-Barré syndrome Guillain-Barré syndrome Guillain-Barré syndrome (GBS), once thought to be a single disease process, is a family of immune-mediated polyneuropathies that occur after infections (e.g., with Campylobacter jejuni). Guillain-Barré Syndrome
  • Stroke syndromes

Diagnosis

Shingles Shingles 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 diagnosis is primarily based on clinical presentation. Lesions may be atypical (e.g, hemorrhagic 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), or absent (zoster sine herpete). In other cases, the lesions can be difficult to distinguish from 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 (especially if lesions are in the face and genital areas). 

In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with atypical presentations or diagnostic uncertainty, the following tests can be used:[6,9,15]

  • 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):
    • Utilizes a sample from vesicular lesions to detect VZV 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[11]
      • Perform a vesicle Vesicle Primary Skin Lesions fluid swab on an ulcerated or oozing lesion, or a deroofed vesicular lesion. 
      • Also can be obtained from lesion crusts or by swabbing the dried lesion with a moistened swab 
      • To diagnose 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 of visceral organs, samples for 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) testing include: biopsies, cerebrospinal fluid Cerebrospinal Fluid A watery fluid that is continuously produced in the choroid plexus and circulates around the surface of the brain; spinal cord; and in the cerebral ventricles. Ventricular System: Anatomy (CSF), bronchoalveolar lavage Bronchoalveolar lavage Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. Pulmonary Fibrosis, intraocular fluids, and blood samples
    • Preferred method of testing due to high sensitivity
    • More rapid than other methods of testing
    • Can be used in all stages of the disease 
  • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus:[6]
    • VZV immunoglobulin ( Ig Ig X-linked Agammaglobulinemia) M and IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis
    • Indications:
      • When 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) is not possible and/or
      • In cases of suspected zoster sine herpete
    • VZV IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions can be positive in:
      • Primary infection Primary infection Herpes Simplex Virus 1 and 2 ( 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)
      • Reinfection
      • Reactivation Reactivation Herpes Simplex Virus 1 and 2 ( patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 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 can mount transient IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions response)
    • To distinguish from primary infection Primary infection Herpes Simplex Virus 1 and 2, obtain IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis avidity testing:
  • 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 (DFA):
    • Tests infected cells in lesion scrapings
    • Limited sensitivity 
    • Cannot be conducted on crusted lesions
  • Tzanck smear Tzanck smear Herpes Simplex Virus 1 and 2:
    • Lowest 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
    • Confirms a herpetic lesion, but does not differentiate herpes 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
    • Shows 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
  • HIV HIV Anti-HIV Drugs test should be performed on all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (undiagnosed HIV HIV Anti-HIV Drugs is found in > 0.1% of those with 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).[10,11]
Tzanck smear herpes zoster

Tzanck smear with 3 multinucleated giant cells

Image: “Positive Tzanck test, showing three multinucleated giant cells in center” by NIAID. License: Public Domain

Management and Prevention

Antiviral Antiviral Antivirals for Hepatitis B therapy

  • Antiviral Antiviral Antivirals for Hepatitis B therapy aims to:[10]
    • ↓ Severity and duration of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Aid in rapid healing of the lesions
    • Prevent the formation of new lesions
    • 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
    • Prevent complications 
  • Options:[9,10,15]
    • Oral guanosine analogues:
      • Drugs: 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
      • Disrupt VZV DNA replication DNA replication The entire DNA of a cell is replicated during the S (synthesis) phase of the cell cycle. The principle of replication is based on complementary nucleotide base pairing: adenine forms hydrogen bonds with thymine (or uracil in RNA) and guanine forms hydrogen bonds with cytosine. DNA Replication
    • Choice of drug depends on factors including cost, dosing schedule, contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation, and drug interactions.
      • 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) and 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 preferred owing to improved pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics → allows for less frequent dosing than acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles) (which has lower bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics).
      • Acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles): the cheapest agent; preferred for pregnant women.
    • Acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles) dose:
      • 800 mg orally 5 times daily for 7–10 days (for acute localized disease)
      • 10 mg/kg/dose IV every 8 hours (for disseminated disease), switching to oral acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles) with clinical improvement (total, 10–14 days)
    • 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) dose: 1,000 mg orally every 8 hours for 7 days
    • 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 dose: 500 mg orally every 8 hours for 7 days
  • In those with suspected or known kidney disease:
    • Renal function needs to be checked prior to initiation (as drugs may cause acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury).
    • Dose adjustment is required in those with moderate to severe renal impairment.
  • Treatment should be administered:
    • ≤ 72 hours after symptom onset:[9]
      • Minimal benefit when lesions have crusted over
      • In those with lesion onset of > 72 hours, medication can be given if new lesions are still appearing or neurologic/ophthalmic complications are noted.
    • During the eruption of new lesions
    • In all 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 (even if onset is > 72 hours)

Supportive care[10,12]

  • Analgesics:
    • Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen
    • NSAIDs NSAIDS Primary vs Secondary Headaches (e.g., ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs))
    • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants ( TCAs TCAs Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants) (e.g., amitriptyline Amitriptyline Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the reuptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines. Tricyclic Antidepressants)
    • Gabapentinoids:
      • Gabapentin Gabapentin A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of partial seizures; neuralgia; and restless legs syndrome. Second-Generation Anticonvulsant Drugs: start with 100–300 mg 1–3 times a day
      • Pregabalin Pregabalin A gamma-aminobutyric acid (gaba) derivative that functions as a calcium channel blocker and is used as an anticonvulsant as well as an anti-anxiety agent. It is also used as an analgesic in the treatment of neuropathic pain and fibromyalgia. Second-Generation Anticonvulsant Drugs: for adults, start with 50–150 mg/day in 2–3 doses
  • Corticosteroids Corticosteroids Chorioretinitis (e.g., prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants) for severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways or neurologic complications: prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants at a starting dose of 60 mg/day, tapering over 10–14 days
  • Antibiotics:
    • For suspected secondary bacterial infection
    • Provide staphylococcal and streptococcal coverage

Management of complicated disease

  • Postherpetic neuralgia Postherpetic neuralgia Pain in nerves, frequently involving facial skin, resulting from the activation the latent varicella-zoster virus. The two forms of the condition preceding the pain are herpes zoster oticus; and herpes zoster ophthalmicus. Following the healing of the rashes and blisters, the pain sometimes persists. Herpes Zoster (Shingles):
    • TCAs TCAs Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants and gabapentinoids are the 1st-line therapy.
    • Topical drugs (capsaicin) to control mild-to-moderate pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics or intrathecal glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids only if other measures fail
  • Herpes zoster ophthalmicus Herpes zoster ophthalmicus Virus infection of the gasserian ganglion and its nerve branches characterized by pain and vesicular eruptions with much swelling. Ocular involvement is usually heralded by a vesicle on the tip of the nose. This area is innervated by the nasociliary nerve. Herpes Zoster (Shingles):[10,12,15]
    • Ophthalmology referral
    • Immunocompetent patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: oral antivirals
      • Under the ophthalmologist’s supervision, topical steroid drops can be given (to ↓ inflammatory response) for keratitis Keratitis Inflammation of the cornea. Herpes Simplex Virus 1 and 2 and 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.
      • In case of acute disseminated disease and/or with sight-threatening disease, use IV acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles).
    • 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: IV acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles) 
  • Acute retinal necrosis Acute Retinal Necrosis Herpes Zoster (Shingles):[15–17]
    • Initial: IV acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles) for 10–14 days
    • Followed by: oral 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 equivalent)
      • Prolonged oral treatment (≥ 14 weeks) reduces the risk of contralateral eye involvement.
      • Intraocular treatment with ganciclovir Ganciclovir An acyclovir analog that is a potent inhibitor of the herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from aids-associated cytomegalovirus infections. Antivirals for Herpes Virus has also been used by some as part of the initial regimen.
    • Empiric systemic corticosteroids Corticosteroids Chorioretinitis are given, especially if the patient has ↓ visual acuity Visual Acuity Clarity or sharpness of ocular vision or the ability of the eye to see fine details. Visual acuity depends on the functions of retina, neuronal transmission, and the interpretative ability of the brain. Normal visual acuity is expressed as 20/20 indicating that one can see at 20 feet what should normally be seen at that distance. Visual acuity can also be influenced by brightness, color, and contrast. Ophthalmic Exam.
  • Ramsay Hunt syndrome Ramsay Hunt syndrome A syndrome characterized by facial palsy in association with a herpetic eruption of the external auditory meatus. This may occasionally be associated with tinnitus, vertigo, deafness, severe otalgia, and inflammation of the pinna. The condition is caused by reactivation of a latent herpesvirus 3, human infection which causes inflammation of the facial and vestibular nerves, and may occasionally involve additional cranial nerves. Herpes Zoster (Shingles):[18]
    • Oral 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)/ acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles) and prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants
      • While the duration and dosage Dosage Dosage Calculation vary in the studies, the rate of recovery of facial nerve Facial nerve The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. The 12 Cranial Nerves: Overview and Functions function was 70% with combination therapy.
      • Best results were noted when medications were started within 5 days after symptom onset.
    • Severe symptoms ( hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss, tinnitus Tinnitus A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. Cranial Nerve Palsies): IV antiviral Antiviral Antivirals for Hepatitis B therapy

Prevention

Measures to prevent transmission:[6]

  • Cover the rash Rash Rocky Mountain Spotted Fever.
  • Avoid contact with:
  • Airborne and contact precautions in case of disseminated disease or if patient is 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

Vaccines:[6,10]

  • Indicated in adults ≥ 50 years of age and 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 adults ≥ 19 years of age 
  • Zoster vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination live (live-attenuated vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination):
    • Brand name: Zostavax
    • No longer available in the United States, but used in other countries 
    • Contraindicated 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
    • Effectivity decreases significantly over time; in the 1st 3 years following vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination, efficacy wanes to:
      • 41% in adults 70–79
      • 18% in adults 80+ 
  • Recombinant zoster vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination (recombinant glycoprotein E vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination)
    • Brand name: Shingrix
    • 2 doses administered 2–6 months apart
    • Do not give if the patient has active acute 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.
    • Not intended to prevent primary varicella (i.e., 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) 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
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have received Zostavax:
      • Studies have shown safety ≥ 5 years after the Zostavax vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination.
      • No theoretical or data concerns for shorter intervals
      • The Centers for Disease Control and Prevention (CDC) recommends waiting at least 8 weeks.
    • For pregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
      • No specific recommendation from the CDC regarding Shingrix in pregnant women
      • Consider delaying until after pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care.
      • No known risks in breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HIV HIV Anti-HIV Drugs: delay in vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination until there is virologic suppression Suppression Defense Mechanisms from 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 or CD4 count recovery is acceptable.[15]

Differential Diagnosis

  • 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: caused by the 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 and spreads via direct contact with herpetic lesions Herpetic Lesions Female Genitourinary Examination or mucosal surfaces. The primary infection Primary infection Herpes Simplex Virus 1 and 2 often presents with systemic, prodromal symptoms followed by dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs) (when genital area is involved), painful 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, and clusters of painful, fluid-filled vesicles Vesicles Female Genitourinary Examination on an erythematous base. Diagnosis is confirmed with laboratory testing, such as 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 DFA. Treatment includes antiviral Antiviral Antivirals for Hepatitis B therapy.
  • Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis: a common 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 infection affecting the deeper layers of the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions and subcutaneous tissue Subcutaneous tissue Loose connective tissue lying under the dermis, which binds skin loosely to subjacent tissues. It may contain a pad of adipocytes, which vary in number according to the area of the body and vary in size according to the nutritional state. Soft Tissue Abscess. The condition is most commonly caused by Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess and 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 pyogenes. Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis presents as an erythematous, edematous area, which is warm and tender to the touch. Diagnosis is clinical and management involves antibiotics tailored to the suspected organism.
  • Folliculitis: 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 the hair follicles caused by a bacterial or fungal infection. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with itchy, sore, erythematous papules/pustules around the hair follicles. The diagnosis is clinical. Management is usually supportive, but topical or oral antibiotic therapy may be required for severe cases.
  • Allergic contact dermatitis Contact dermatitis A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. Male Genitourinary Examination: 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 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 due to contact with an allergen. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship commonly present with a local, red, pruritic rash Rash Rocky Mountain Spotted Fever and blistering may occur. Diagnosis is made through history and examination, but 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 patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes testing can be used to determine a trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation. Management includes topical corticosteroids Corticosteroids Chorioretinitis and allergen avoidance.
  • Molluscum contagiosum Molluscum contagiosum Molluscum contagiosum is a viral infection limited to the epidermis and is common in children below 5 years of age. Lesions appear as grouped, flesh-colored, dome-shaped papules with central umbilication. Molluscum Contagiosum: a viral 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 infection caused by a poxvirus typically seen in children < 5 years of age. Lesions are grouped, flesh-colored, dome-shaped papules with central umbilication. The disease is mild in immunocompetent patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship and self-resolves within months. An immunocompromised patient Immunocompromised patient 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. Herpes Zoster (Shingles) may present with extensive lesions and systemic disease requiring treatment. The diagnosis is clinical. Cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma with liquid nitrogen Liquid Nitrogen Molluscum Contagiosum is the 1st-line in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship requiring therapy.

References

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  12. Werner, R. N., Nikkels, A. F., Marinović, B., et al. (2017). European consensus-based (S2k) guideline on the management of herpes zoster—guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment. Journal of the European Academy of Dermatology and Venereology, 31(1), 20–29. https://doi.org/10.1111/jdv.13957
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  14. Amano, E., Machida, A. (2021). Teaching neuroImages: Hutchinson sign in herpes zoster ophthalmicus. Neurology, 96(15), e2033–e2034. https://doi.org/10.1212/WNL.0000000000011285
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