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Viral Disease-Vesicular

Definition

Herpes simplex: Skin or mucous membrane infection, marked by vesicles on red base caused by Herpes simplex virus (HSV) and Herpesvirus hominis. Exists in acute and recurrent forms.

Herpes zoster (Shingles): Reactivated, self-limited infection of latent varicella-zoster virus in 1 to 2 nerve roots, inflamming the related sensory nerves. Manifest by eruption in a dermatomal pattern on the skin unilaterally, never crossing the midline.

Varicella (Chicken pox): Acute, primary infection of the skin with varicellazoster virus. Most common exanthem of the childhood diseases.

Hand, foot, and mouth disease: Contagious skin infection caused by enterovirus coxsackievirus A 16 or enterovirus 71. Typically affects the mouth and/or hands and feet.

History

Symptoms

Herpes simplex: Prodrome of itch, tingle, and/or burning at the infection site. Painful group of blisters on intraoral surfaces, lips, or face. Primary episode may include headache, fever, and tender swollen glands in the region of infection. These symptoms are less common in the recurrent setting. With herpes genitalis symptoms include severe pain, itching, dysuria, mucoid discharge, and tender inguinal lymph nodes.

Herpes zoster (Shingles): One-to 4-day prodrome with fever, headache, malaise, pain, and paresthesias (itching, tingling, burning). Unilateral, painful blisters with red bases in a narrow pattern. Regionally enlarged, tender lymph nodes.

Varicella (Chicken pox): Widespread pruritic papules, clear vesicles, and crusts together in any area of head, mouth, trunk.

Hand, foot, and mouth disease: Bright red-ringed papules, vesicle, ulcers in mouth, dysphagia. Red macules, papules, and grayish white vesicles of hands and feet. May have malaise, and low-grade fever with a sore throat.

Age

Herpes simplex: Children as young as 1-to 5-years old but incidence peaks rapidly after 15 years and slows by age 30 for primary disease.

Herpes zoster (Shingles): Any, but more than 60 percent over 50-years-old. Less than 10 percent under 20 years.

Varicella (Chicken pox): Any, but common in childhood. Neonates can acquire the disorder from mothers.

Hand, foot, and mouth disease: Infants and children.

Onset

Herpes simplex: Acute, with tingling, stinging prodrome for a few hours to 1 to 2 days in over 50 percent of patients for primary or recurrent disease. Infectious contact occurs 2 to 20 days before active signs of infection. Neurologic pain may precede each recurrence.

Herpes zoster (Shingles): Acute prodromal pains, paresthesias that are followed by skin lesions in approximately 4 days.

Varicella (Chicken pox): Acute after up to 14-day incubation. The patient remains asymptomatic for a few days before the outbreak. Viral prodrome is common with fever, myalgia, chills, arthralgias from 3 days before to a few days after eruptions.

Hand, foot, and mouth disease: Acute with oral lesions. Incubation is 3 to 5 days.

Duration

Herpes simplex: Acute, self-limited for 2 weeks or more in primary and 10 days or less in recurrent episodes.

Herpes zoster (Shingles): Prodrome and skin lesions in 4 days, vesicles to pustules in 3 to 4 days, crusts by tenth day, and resolution in most by 3 weeks. Postherpetic pain fairly common, especially in older patients that lasts 2 months to many years.

Varicella (Chicken pox): One to 3 weeks.

Hand, foot, and mouth disease: Self-limited, 7 to 10 days to healing.

Intensity

Herpes simplex: From one herpetiform (cluster) to a few in primary disease, to one or two lesions with recurrences. Recurrences average 2 to 3 times per year for oral herpes labialis and 4 to 8 times per year in genital herpes.

Herpes zoster (Shingles): Many vesicular groups, on red bases, in one to two dermatomes unilaterally is the most typical. Occasionally occur In one to two groups especially in young patients.

Varicella (Chicken pox): Sub clinical with few to no lesions Or generalized with full body and mucous membrane involvement. Hand, foot, and mouth disease: A few to a mouthful of painful erosions and few, several, or many red-base gray vesicles of toes, fingers, palms, and soles.

Aggravating Factors

Herpes simplex: UV irradiation, fever, systemic illness, emotional stress, fatigue, trauma, menses, pregnancy; all known to reactivate the virus.

Herpes zoster (Shingles): Compromised cellular immunity.

Varicella (Chicken pox): Immunocompromise, secondary bacterial infection, varicella pneumonia (rare), encephalitis, and Reye syndrome in children who have taken aspirin during the course of disease. Heat hastens outbreaks.

Hand, foot, and mouth disease: Epidemics due to enterovirus 71 occasionally lead to central nervous system disorders (aseptic meningitis, polio-like paralysis, and encephalitis). Children less than 3 years may also get a maculopapular rash in the diaper area, including the buttocks.

Alleviating Factors

Herpes simplex: Analgesics, antipyretics, antipruritics, compresses with boric acid solution or Burow's mupirocin or polysporin ointment. Herpes zoster (Shingles): Corticosteroids, nonsteroidal anti-inflammatories, narcotics, Burow's compresses, and acyclovir.

Varicella (Chicken pox): Antipruritics, antipyrexics, Burow's compresses, topical antibiotic, and for severe or complicating disease, acyclovir.

Hand, foot, and mouth disease: Symptomatic therapy.

Associated Factors Herpes simplex: Immunocompromised patients will have more severe or disseminated outbreaks. HSV infection is known to lead on occasion to erythema multiforme in 7 to 14 days, following herpetic infection

Herpes zoster (Shingles): Immunocompromise such as acquired immunodeficiency syndrome, leukemia, Hodgkin's disease, and other malignancies, immunosuppressive drugs and corticosteroids.

Varicella (Chicken pox): Communicable. Possibly developmentally deforming with congenital infection in first trimester of pregnancy. Most fetal infection resolves without residual.

Hand, foot, and mouth disease: Small epidemics seen in warmer months.

Physical Examination

General

Herpes simplex: Primary infection: Swollen tender regional lymph nodes. Clusters of vesicles on red base in oral cavity on any mucous membranes or on dry lips or skin of face. Occasionally any other area of the skin including fingers (herpetic whitlow) lasting up to 6 weeks; for type I infection. Type II infection presents as 10 to 15 papules progressing to red-based vesicles, to erosions, to grayish white ulcers on any area of male or female genitalia. Neonates can acquire the disease from mothers by vaginal delivery. Recurrent infection: Fewer clustered vesicles or ulcers, may be 10 percent of primary genital disease. Less prominent swollen, tender adenopathy; sites of which will be close or include area of the primary infection. Less recurrence of mucosal oral disease or whitlows.

Herpes zoster (Shingles): Unilateral, palm-sized groups of vesiocobullae on raised inflammed base in dermatome. Vesicles may become purpuric, necrotic and crusty, and leave scars. Can occur in the ophthalmic distribution of the trigeminal nerve and result in infections and complications in the eye. Regional lymph nodes are enlarged and tender. Possible, but rare in the mouth or vagina.

Varicella (Chicken pox): Single, small, widespread lesions progressing rapidly through papular stage to vesicles and pustules, followed typically by umbilication and crusting. Successive crops of vesicles erupt for 4 to 5 days and become crusted by 1 week. Not uncommon to have three successive crops of lesions and thus, any area of skin will manifest all stages of the disease at the same time. Occur anywhere on the body.

Hand, foot, and mouth disease: Widespread or densely grouped red-ringed vesicles, 2 to 8 mm in size. Progress quickly to painful denuded erosions on any intraoral membranes, including tongue, hard palate, and buccal mucosa. Red macules progress to gray vesicles with red ring. The skin lesions follow the oral lesions and are found on the sides and dorsum of the fingers, toes, hands, and feet, and may be on the soles and palms.

Pathophysiology

Herpes simplex: The virus enters at mucous membrane or injured skin site by contact with infected person, most commonly at the mouth or genitalia for adults. The virus replicates in epidermal and dermal cells and is transported to the neuronal nucleus and can spread distally to additional skin sites. Also, by unknown means, the virus enters a life long latent stage in the nuclei of neural ganglia. Periodic reactivation then leads to the recurrent episodes of infection and skin-mucous membrane manifestation or replication. Viral shedding is possible in the crust stage.

Herpes zoster (Shingles): Varicella-zoster virus, during varicella infection, clinically or subclinically invades the sensory nerves and migrates to the neural ganglia and becomes latent until some event reactivates the virus (e.g., immunosuppression, malignancy, or trauma). The infection travels along the sensory nerve causing inflammation, pain, and a vesicular eruption.

Varicella (Chicken pox): Very contagious virus acquired by direct contact with infected person who has varicella or herpes zoster by inhaling infected airborne droplets. Virus replicates in skin causing the typical vesicular eruption that progress to crusting. Contagion persists from 2 days before first crop of eruptions until all the lesions are crusted. The virus migrates along axons to become latent in nerve ganglia, and if and when reactivated, leads to herpes zoster (shingles) .

Hand, foot, and mouth disease: Highly contagious virus that directly invades the skin or migrates to the skin after direct contact with infected individual. Colonizes in the bowel and spreads by fecal-oral route.

Diagnostic Studies

Laboratory

Herpes simplex: Blood titres: For antibody for HSV to immunoglobulin G (IgG) and immunoglobulin M (IgM). Effective to identify acute and latent disease.

Herpes zoster (Shingles): Not applicable.

Varicella (Chicken pox): Not applicable.

Hand, foot, and mouth disease: Viral culture: Retrieve able from vesicular fluid, throat secretions, and feces.

Radiology: Not applicable.

Other

Herpes simplex: Tzanck preparations: Performed by unroofing vesicle, scraping the base, smearing on slide, and allowed to air dry. Giemsa stain is performed to view for giant multinucleated epithelial cells.

Tissue culture: Is the best confirmatory test, but takes up to 3 days and not available in all laboratories.

Herpes zoster (Shingles): Tissue culture: Takes longer than HSV. May aid in diagnosis.

Varicella (Chicken pox): Tzanck preparation or tissue cultures verify. Usually not necessary.

Hand, foot, and mouth disease: Not applicable.

Differential Diagnosis

Traumatic

Herpes simplex: Bum blisters: Have no prodrome and have illicit able history.

Herpes zoster (Shingles): Not applicable, only as a possible reactivation trigger.

Varicella (Chicken pox)/Hand, foot, and mouth disease: Not applicable.

Infectious

Herpes simplex: Coxsackievirus infection: Usually isolated vesicles on hands, feet, and in mouth; not clustered.

Varicella-zoster: Larger blisters than vesicles and in unilateral dermatomal pattern of pain and outbreak with linear clusters. Not recurrent.

Syphilis: Generally larger, single ulcers without significant pain and not recurrent. RPR positive.

Chancroid: Ulcers enlarge from primary pustule and are raggedly irregular, culture positive for bacteria (Haemophilus ducreyi). Lymph nodes suppurate and drain.

Lymphogranuloma venereum: Painless papule, pustule, ulcer of penis, but large, double lymph node involvement in groin. Cultures positive for virulent strain of C. trachomatis.

Herpes zoster (Shingles): Zosteriform herpes simplex with neuralgia: Difficult to differentiate, but grows quickly on tissue culture and can recur.

Varicella: Widespread single, small papulovesicles.

HSV: Fewer, localized recurring lesions and less neuritis.

Varicella (Chicken pox): Herpes simplex: Small, localized involvement and only one stage evident at any given time. Same for herpes zoster. If dissemination, still do not have the wide variability of stages.

Eczema vaccinatum: History, usually in atopic patient, with known recent vaccination or exposure to the vaccinated person with cowpox vaccine for small pox. Rare as only the military may be using vaccine.

Hand, foot, and mouth disease: Herpetic gingivostomatitis and herpangina: Neither have the pronounced red ring around the lesion. Less Common on hard palate.

Metabolic

Hand, foot, and mouth disease: Aphthous stomatitis: Usually few lesions and less painful and without the bright red ring around lesion.

Herpes simplex/Herpes zoster (Shingles)/Varicella (Chicken pox): Not applicable.

Neoplastic: Not applicable.

Vascular

Herpes zoster (Shingles): Necrotizing vasculitis: Not dermatomal;bilateral.

Herpes simplex/Varicella (Chicken pox)/Hand, foot, and mouth disease: Not applicable.

Congenital

Herpes zoster (Shingles): Varicella infection in infants: Mother with a history of gestational varicella.

Herpes simplex/Varicella (Chicken pox)/Hand, foot, and mouth disease: Not applicable.

Acquired

Herpes simplex: Behcet's disease: Usually oral and genital ulcers, yellow rather than white ulcer; surface coagulum. Large lesions of genitals, usually the scrotum are deeper and heal with scars. Negative cultures or tests.

Crohn's disease: Bowel disease a major part of the history. Negative HSV culture. Genital and oral ulcers are more granulomatous.

Herpes zoster (Shingles): Not applicable.

Varicella (Chicken pox): Folliculitis infections or oil contact: Has no significant stages, only papulo-pustule.

Hand, foot, and mouth disease: Erythema multiforme: More diffuse and bullous than sharp red erosions of hand, foot, and mouth disease. More localized to gums and buccol mucosa.

Herpes simplex: Acyclovir 200 mg 2 three times a day or 1 to 5 times day for 7 days. Begun at the first sign of a new lesion or as early in infection as possible. Maintenance therapy to prevent recurrences is acyclovir 200 mg three times a day or 2 twice a day for 1 or more years. Recurrences are common after cessation of therapy but with less frequency.

Herpes zoster (Shingles): Acyclovir is given as early as possible in course of infection to markedly affect symptoms and duration. Acyclovir 800 mg 5 times daily for 5 to 7 days.Prednisone 20 to 60 mg every day or Q.O.D. can reduce symptoms and minimize the postherpetic neuralgia. Care should be taken with prednisone use in immunocompro mised as it can lead to dissemination of the disease.

Analgesia: Nonsteroidal anti-inflammatory drugs or narcotics are used to relieve symptoms.

Burow's compresses 15 to 30 minutes 3 to 4 times a day, followed by antibiotic ointment, may speed healing.

Varicella (Chicken pox): For severe or complicating disease use acyclovir 800 mg 5 times day for 7 days in adults. Otherwise use antipruritics. Antipyrexics are used as needed for fevers and muscle joint symptoms, but do not use salicylates in children under 14.

Burow's compresses 1:40 for 15 to 20 minutes 3 to 4 times daily is used for symptomatic relief. Treat secondary bacterial infection with systemic antibiotics as directed (see Bacterial Skin Infection). It is important to treat the symptoms to minimize itch, excoriation, and scarring.

Hand, foot, and mouth disease: Symptomatic only with analgesics, acetaminophen, topical xylocaine viscous, and diphenhydramine elixir swished and swallowed.

Pediatric Considerations

HSV: Maternal infection with HSV type 2 (and occasionally type 1) during pregnancy or parturition is associated with intrauterine infection and more commonly neonatal disease. It is characterized by disseminated viremia with multisystem involvement or may be localized to the brain, skin, eyes, and oropharynx. Signs may be present at birth but vesicles may appear up to 7 days after birth. Mortality rates are high in neonates with systemic infection. In infants and children, 60 percent of HSV infections appear as gingivostomatitis almost always due to type 1. The primary episode often appears in infants under 6 months. Presenting symptoms include irritability, salivation, refusal to eat, foul odor, and fever (often; 1030 F). It can last 7 to 14 days and is self-limited. Symptomatic and supportive therapy is important.

In infants, stomatitis may lead to severe dehydration, shock, electrolyte imbalance, and hypoproteinemia. For older children, local analgesics (viscous lidocaine or benzocaine lozenges) may help. Cold fluids or semisolids foods may be tolerated when other food is refused. On the skin, the lesion consists of groups of vesicles on an erythematous base. These rupture, scab, and heal within 7 to 10 days. In children the vesicles may become secondarily infected and in that case only, antibiotics are useful.

Viral exanthems: In the pediatric age group numerous, viral infections exist that are associated with dermatologic manifestations. A variety of different patterns are seen in these viral exanthems including a generalized maculopapular eruption that mimics measles (morbilliform), peetechial eruptions, vesiculobullous eruptions, scarlet feverlike eruptions (scarlatiniform), and oral eruptions. These include measles, rubella, erythema infectiosum, roseola infantum, varicella, and many others. A more complete discussion is beyond the scope of this book and the reader is referred to textbooks on pediatric infectious diseases for further information. Aspirin, as an antipyrexic, should not be used in the pediatric age group.

Obstetrical Considerations

Herpes gestation is: An autoimmune condition that occurs during pregnancy and the postpartum period. It is a pruritic condition involving vesicles on normal-appearing and erythematous skin. Lesions usually first appear on the abdomen. There is an associated possibility of up to 30 percent fetal mortality rate, and an increased incidence of premature deliveries. High potency topical steroids and diphenhydramine may be of help. Usually however, oral prednisone is needed to adequately treat the condition throughout the pregnancy.

HSV: HSV complicates 1 to 2 percent of all pregnancies. The main risk of infection posed to the fetus from a mother infected with HSV occurs during the delivery. If a mother is experiencing aprimary active outbreak (attack), a vaginal delivery creates a 50 percent chance of HSV transmission to the baby. This leads to the recommendation of delivery by cesarean section if the woman has genital herpetic lesions present. Up to 60 percent of women delivering infected infants may be asymptomatic and 1 to 2 percent of all individuals (pregnant and nonpregnant) chronically shed the virus in saliva and genital secretions. Woman can also carry an active herpes infection of the cervix and have no symptomatology. It is interesting to note that infants who were delivered vaginally to mothers with active recurrent HSV only had a 5 percent risk of transmission of the infection to the neonate. There is also an approximately 12 percent infection rate in fetuses with intact amniotic membranes. HSV infection in the neonate is often catastrophic with an approximately 50 percent mortality rate. Therefore, serological testing is recommended. Primary HSV maternal infection has also been found to increase the risk of prematurity and intrauterine growth retardation. Acyclovir use in pregnancy has not yet been defined as being safe for the fetus. Its use should be limited to severe life threatening maternal primary HSV infections. Disseminated maternal infection is more likely in a woman who is pregnant.

Herpes zoster: In contrast to chicken pox, mothers who develop herpes zoster during pregnancy seldom pose a risk of congenital infection to the infant.

Varicella: Pregnant women who are at all unsure of their immune status in regards to varicella should avoid individuals with varicella infections.If a pregnant woman does develop varicella, the frequency of congenital infection is rare. If it does occur, however, the fetus can develop a syndrome of limb hypoplasia chorioretinitis, cutaneous scars, cataracts, cortical atrophy, and microcephaly. If a mother contracts chicken pox immediately prior to or shortly after delivery, the infant can then be administered varicellazoster immunoglobulin.

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