varicella
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VARICELLA
Main statements
The causative agent is DNA-containing Varicella-Zoster virus (VZV), from Herpesviridae family.
The source of infection is a person with varicella or herpes zoster. Within 24-48 hours before rash onset there are catarrhal changes in
oropharynx and vesicles on the soft palate. Reinfections of the disease are seen in 2-4%. The rash elements are macula-papule-vesicle-crust; polymorphism is
typical, the rash is often accompanied by hyperthermia. If mother develops the disease 5 days before or 5 days after delivery,
infection in the newborn results in very severe forms of the disease, with 30% mortality rate.
Encephalitis develops most often on the 5-10th day of the disease. Etiotropic agent is acyclovir. Vaccination of healthy children in Ukraine is not obligatory, but
recommended; the vaccine is registered.
Varicella (chicken pox) is an acute infectious disease with airborne route of
transmission, which is caused by virus from the family Herpesviridae. It is characterized
by presence of macula – papule – vesicular rash.
Etiology. The causative agent of the infection is Varicella-Zoster virus (VZV),
which belongs to Herpesviridae family, subfamily α, 3rd type virus, genus Varicellavirus.
The size of the elementary virion particles is within 150 – 200 nm. The virus is DNA-
containing. The virus is susceptible to environmental factors and can only replicate in
human cells. Beyond human body, in saliva droplets and on clothes the virus can survive
during 10-15 minutes. Direct sunlight and heating kill the virus within several minutes.
The varicella virus has tropism to skin and mucus epithelium and, to a lesser degree, to
nervous system cells.
Epidemiology. The varicella virus under natural conditions does not cause any
similar to chicken pox disease in any other animals, except human.
The source of infection in varicella can only be the person suffering from varicella
or zoster. The entrance route of the causative agent is upper respiratory tract mucus. Viral
localization on the mucosa should be considered the main mechanism of viral spreading.
Transmission of the virus through third person is considered impossible. Intrauterine
acquisition of varicella is possible in case of chicken pox in a pregnant woman.
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Varicella is a typical airborne infection. All the particularities of airborne
transmission are typical for mechanism of varicella transmission. After removal of the
infection source from the room, without any specific measures, the air in the room quickly
clears from the causative agent, as the virus is unstable in the environment.
It is considered that life-long immunity develops after an episode of varicella.
However, according to modern epidemiological studies, repeated cases of varicella are
diagnosed in 2-4% of patients.
Susceptibility to varicella in children without history of this disease is very high.
Contagiousness index is 95-98%.
Similar to other infections with airborne way of transmission, the highest incidence
of varicella is observed in cold seasons of the year. Maximal amount of cases is seen in
February, with minimal in August.
Varicella can be diagnosed at any age, but nowadays most of the cases develop in
children 2 to 7 years of age.
Pathogenesis. The site of entry for varicella virus is upper respiratory tract mucosa.
At the beginning of incubational period the virus replicates in regional lymph nodes and is
spreading with blood flow to liver, spleen and other organs of reticulo-endothelial system.
At the end of incubational period secondary viremia develops. The virus spreads to
epithelial cells of the skin and mucosa and causes the development of vesicles with serous
contain, which are multicameral at first, but later become unicameral.
The development of varicella vesicle begins with protoplasmic edema of spiny layer
of skin epithelium. With fluid collection the cell protoplasm is only preserved as septa,
forming a distinctive radial reticulum (stage of reticular dystrophy). Further accumulation
of the fluid leads to membrane and nucleus edema, until complete dilution of the nucleus.
The cell body becomes round, loses its thorns and connection with other cells, transforms
into a vesicle – balloon (stage of balloon dystrophy). At the early stages of the process
round eosinophilic inclusions, described by Tizer, are formed in nuclei of damaged cells.
Clinical manifestations. Incubational period at varicella is 11-21 days, after
immunoglobulin injection it is prolonged till 28 days. Maximal frequency of disease onset
is on the 15th day after contact. Rash at varicella often appears at once, without prodromal
phase. In rare cases subfebrile fever, malaise, restlessness, appetite decrease, sometimes
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vomiting and diarrhea can be seen 1-5 days before rash appearance. Sometimes prodromal
symptoms also include seizures and scarlet fever-like exanthema, so called “rash-
exanthema”.
Appearance of rash at varicella coincides with fever or can be several hours later.
Rash initially presents with maculae, often quite small, like points. They rapidly increase
in size, the central part elevates over the skin, and papules appear. Later vesicles appear in
the center of the elements. The newly appeared vesicles look like dewdrops. They are
quite large, round, with transparent contain and thin glossy covers. Redness around it can
be absent. The vesicles are situated on the infiltrated basis. Later the vesicles become
irregular in shape, their borders become scalloped. It can be clearly seen when the vesicles
start to dry and become flatter. The content of the vesicles becomes cloddy. Vesicles are
fragile, soft to palpation, can be easily disrupted. At piercing the vesicles empty very
quickly due to their one-chamber structure. Vesicles dry out in 1-2 days. Drying begins
from the center, the central parts sink down, get darker, and gradually the vesicles are
transformed into thick, brown crusts.
First elements of rash can appear on any part of the body, but in most of the cases
they appear first on trunk and scalp. At the beginning only one element can appear. After
maturation of some elements of rash new ones appear. At typical cases, single scattered
rash elements are followed by abundant rash. The latter is usually accompanied by fever
and itching. Abundant rash is usually dense, evenly distributed, it covers scalp and trunk.
The rash is usually less prominent on the face and distal parts of extremities. The
appearance of rash is not simultaneous, but in crops every 1-2 days. The first elements, as
it was pointed out before, in most of the cases develop through the stages of macula-
papule, and are transformed into vesicles very quickly. The development of further
elements takes place slower, the size of the elements is smaller, and they do not always
develop into vesicles. The new rash at varicella usually appears during 2-4 days. In some
cases the new rash can appear till 7-9th day, and sometimes till the 14th day of the disease.
Such stepwise appearance causes polymorphic character of varicella rash. There can be
maculae, papules, vesicles and crusts on the same part of the body skin. Such
polymorphism is called “false”, as the apparently different rash elements are in reality just
different stages of the same process.
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Term of crusts rejection depends largely on the skin care. With meticulous care the
crusts are rejected much quicker. The most often the crusts are rejected between the 12 th
and 22nd days of the disease. The size of the crust is the same as the size of the preceding
vesicle. During drying out of the vesicle the surrounding redness disappears, and the crust
becomes surrounded by normal skin. Its rejection takes place from borders. After rejection
of the crusts there can remain small, round discolorated spots with pigmented borders.
Sometimes the crusts are rejected with scars formation; most commonly they are situated
on the face. Appearance of scars after acne rash can cause itching and joining of secondary
bacterial complications.
Besides skin, varicella typically is also characterized by the rash on oral mucosa,
nasal mucosa, more seldom on mucosa, conjunctive and genitals. Enanthema is usually
accompanied by fever and exanthema.
Rare localizations of varicella enanthema include rash on laryngeal mucosa. This
rash often precedes the appearance of elements on the skin and causes hoarse voice, rough
barking cough. Sometimes laryngeal stenosis can develop.
Inborn varicella
Varicella during pregnancy can cause congenital varicella syndrome of the fetus,
which can present with isolated or multiple defects: extremities hypoplasia, microcephaly,
eyes defects (microphthalmia, cataract, chorioretinitis), CNS defects with disorders of
motor and sensory functions, paralysis, dysphagia, intrauterine growth retardation, skin
scars. Risk of these defects is 0.5% if varicella develops at 2-12 weeks of pregnancy and
up till 1.4% with varicella at 2-12 weeks of pregnancy; embryopathies are caused by
cytopathic action of the virus and incomplete organogenesis. At antenatal ultrasound
investigation the signs of fetus infection can be venriculomegaly, microcephaly, anomalies
of extremities, intrauterine development delay, dysmorphism, calcifications in inner
organs, especially in liver.
Varicella at 24-28 weeks of pregnancy does not present any danger for both mother
and infant, because passive transport of maternal antibody through placenta is enough for
the fetus protection.
If mother develops varicella within 5 days before or 5 days after delivery, the
newborn develops severe form of varicella. Due to the lack of time for specific antibody
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production and their transport through placenta there is massive dissemination of the virus.
The symptoms appear 5-10 days after birth, newborns become severely ill and the
mortality is 30%. Newborns develop fever, respiratory distress, often there is pneumonia,
hepatitis. There is vesicular or hemorrhagic rash on the skin. Respiratory distress appears
on the 2-3rd day after first rash elements, and prognosis depends on the severity of
respiratory distress. The term between skin and respiratory symptoms is the same as the
term between rash and pneumonia in adults. Death is caused by severe lung damage and
disseminated intravascular coagulation syndrome (DIC).
If fetal infection occurs 5-21 days before delivery, the newborn will develop mild
form, with scarce vesicles. Similar clinical picture is seen if the newborn gets infected
within 7-29 days of age. Development and localization of rash is the same as in other age
groups. First elements can appear on trunk, then disseminating to other parts of the body.
Newborns present with more prominent polymorphism of the rash, with simultaneous
presence of maculae, vesicles, pustules and crusts on the skin.
Episode of varicella during pregnancy can cause development of shingles in the
child within first months of life. This reflects transplacental inoculation of the virus and its
penetration into nervous ganglia of the fetus with viral reactivation during first months of
life.
Shingles in a pregnant woman very seldom causes infection in the fetus.
Varicella in patients with oncohaematological diseases and immunodeficiency.
In 30-50% children with lymphoproliferative malignant diseases and solid tumors
without active antiviral therapy disseminated visceral form of varicella develops with
mortality more than 20%. The course of the disease is characterized by development of
pneumonia, hepatitis, encephalitis, severe coagulopathy, pancreatitis, esophagitis, necrotic
splenitis and enterocolitis. The disease is accompanied by severe abdominal and low back
pains.
The risk of visceral form of varicella is high when chemotherapy is performed in
incubational period and within first 5 days of the beginning of the disease. These children
are also highly susceptible to secondary bacterial infections complicating the course of
varicella. The children at high risk of generalized varicella are also organ transplantation
recipients, bone marrow recipients, children with T-cell immunodeficiency and with HIV
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infection. Main clinical presentations of varicella in these children are hepatitis and
thrombocytopenia.
There are cases of unusual clinical presentation of varicella in such children, which
are described in the literature and which present with hyperkeratosis and inner organ
involvement which lasts within several weeks and months after contact with varicella
patients.
Complications. Frequency of varicella complications is 5%, and up till 30-50% in
patients with compromised immunity. Varicella complications can develop due to damage
of vesicles entity, which will open the route for bacterial infections. Secondary infection
can result into abscesses, phlegmons, erysipelas, bullous streptococcal impetigo,
stomatitis, lymphadenitis. Most commonly they are caused by S. aureus and Str. pyogenes.
Purulent complications most commonly develop in weakened early age children, during
recovery from acute infectious diseases. Sometimes hematogenic dissemination of bacteria
leads to sepsis, pneumonia, arthritis, osteomyelitis, nephritis.
Nervous system complications at varicella most often develop on the 5-10 th days of
the disease. Sometimes it can happen on the 18-21st days. They are seen more often in
boys, at the age of 1-5 years. The frequency of these complications is 1 per 4000 cases of
varicella. 90% of all nervous system complications at varicella present with encephalitis.
This complication develops in 0.1-0.2% of all the patients with varicella. 13% of
encephalitis with determined etiology are due to varicella.
75% of encephalitis at varicella involve cerebellum and present with cerebellar
ataxia. Clinical signs and symptoms develop within 3-5 days and continue in general 2-4
weeks. 25% of varicella encephalitis also involve other brain structures into inflammatory
process (brain hemispheres, brain steam, basal ganglia, etc.). Symptoms of complication
usually develop on the 5-7th day after appearance of rash. Mortality from these
complications can reach 35%. Residuals such as paralysis, oligophrenia, repeated seizures
can take place in 12-15% of the patents.
Besides cerebellar ataxia and encephalitis, the following complications are also
possible at varicella: myelitis, encephalomyelitis, opticomyelitis, polyneuropathy, optic
nerve neuritis, serous meningitis.
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Special place among varicella complications belongs to demyelinization diseases of
nervous system, mediated by T-cell immune reaction to main protein, myelin. This
reaction is similar to allergic encephalomyelitis.
Varicella can be complicated by Reye’s syndrome, which has mortality 50-80% at
late diagnosis and treatment. Risk factor for Reye’s syndrome is usage of acetylsalicylic
acid and other drugs during varicella.
49% of patients with varicella show mild ALT elevation in blood serum due to virus
replication in liver.
Relatively common complication of varicella is acute thrombocytopenia with skin
petechiae, hemorrhages into vesicles, nasal hemorrhages, hematuria and gastrointestinal
hemorrhages. Clinical presentation of this complication is short-term, but level of blood
platelets can remain decreased within several weeks.
Kidney involvement at varicella develops seldom. Nephritis with hematuria, edema,
hypertension can develop during the first 3 weeks after rash. Interstitial pneumonia at
varicella is also possible, but it is more common in adults.
Ibuprofen can cause development of necrotic fasciitis at varicella; this anti-
inflammatory drug is not recommended at this infection.
Diagnosis. Diagnosis is based on typical clinical symptoms. In case of difficult
clinical diagnosis, the following laboratory methods are used: CBC shows leucopenia,
relative lymphocytosis and normal ERS since 48-72 hours from rash appearance.
Serological investigation shows 4-fold increase in antibody titers within 10-14 days. This
investigation is performed with the methods of reaction of complement fixation, reaction
of indirect hemagglutination, immunoenzyme analysis and radioimmune assay.
Specific IgG antibodies appear in blood serum since third day of the rash, and their
titer rapidly increases during recovery. Due to high frequency of false positive results, IgM
titers should not be measured in clinical practice.
Management. Etiotropic therapy of varicella is acyclovir. Indications for acyclovir
prescription at varicella are the following:
- patients with oncohaematological diseases;
- organ and marrow recipients;
- patients on corticosteroids;
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- children with inborn T-cell immunodeficiencies;
- children with HIV infection;
- inborn varicella;
- varicella with nervous system complications, hepatitis, thrombocytopenia,
pneumonia;
- severe forms of varicella.
Acyclovir is recommended to patients with varicella who have chronic diseases of
skin and lungs and those who receive salicylates, short-term corticosteroids, including
inhalatory forms.
Antiviral therapy is prescribed from the first day of the disease. Children with
immune deficiencies and with nervous system complications receive acyclovir
intravenously. Acyclovir dosage is 10 mg/kg or 500 mg/m2, three times a day. The course
of etiotropic therapy lasts 7 days or 48 hours after appearance of last rash elements.
Immunocompetent children with severe forms of varicella and immunocompromised
children with mild to moderate forms of the infection are given acyclovir orally. Acyclovir
dose for children under 2 years of age is 200 mg, from 2 to 6 years it is 400 mg and older
than 6 years it is 800 mg. This dosage is taken 4 times a day. Besides acyclovir, other
antiviral drugs as valaciclovir, famciclovir, ganciclovir are also effective at varicella.
For varicella treatment in newborns the dosage of acyclovir is 10-20 mg/day,
divided for three times per day; the course is 7 days. At severe forms of the disease high
doses are prescribed.
At severe, generalized forms of varicella, especially in newborns and children of the
first year of life, intravenous polyvalent immunoglobulin 0.4 g/kg/day, for 3-5 days, is
used, or specific varicella-zoster immunoglobulin in dose of 0.2 ml/kg.
At mild and moderate forms of varicella in immunocompetent patients the aim of
therapy is prophylaxis of secondary bacterial infections. It includes prevention of vesicles
rupture, clean linen and clothes of the patient, rash treatment with aniline dye solutions,
1% solution of potassium permanganate. In early age children aniline dyes should be used
carefully due to possible toxic effects.
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With the aim of prophylaxis of secondary bacterial infections in the mouth, after
meals it is recommended to rinse the mouth with 5% solution of boric acid, weak solutions
of potassium permanganate, furacilin or plain water.
Prophylaxis. Patient with varicella must be isolated for 5 days from appearance of
last rash elements. Isolation of contact children in groups is since the 11 th till the 21st day
from the contact. After immunoglobulin injection the term of isolation of contact children
increases till 28 days.
Passive immune prophylaxis of varicella is possible with high titer immunoglobulin
against varicella-zoster virus. Immunoglobulin is injected intramuscularly not later than
48-96 hours after contact, first of all to: children with immune deficiency, pregnant
women, children born to mothers who developed varicella within 5-10 days before
delivery and 2 day after, premature babies born before 28 weeks of pregnancy and with
body weight less than 1000g. Prophylaxis of varicella with regular immunoglobulin
without determination of specific antibody titer is considered to be ineffective.
Currently live vaccine against varicella is developed and used in 80 countries of the
world. Introduction of varicella vaccine in some countries considerable influenced the
varicella morbidity there.
European office of WHO recommends obligatory vaccination to selected patients
with leukemia in remission and those waiting for organ transplantation without previous
history of varicella.
National vaccination schedule of Ukraine includes varicella vaccination as
recommended to healthy children after 12 months of age, children before entering primary
school and health care workers with high risk of infection and without previous history of
varicella. This vaccine is obligatory for children with HIV infection.
Activities for varicella prophylaxis in pregnant women are very important,
considering high prevalence of the disease and periodic outbreaks in different regions.
Pregnant women without previous history of varicella or who lack this information should
be tested for VZV immunity: antibody level with immunoenzyme analysis. However, as a
rule, 85-90% of people who did not have any episode of varicella in the past still have
immunity to VZV. Pregnant women without immunity should be given VZV
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immunoglobulin in case of contact. Immunoglobulin prophylaxis is most effective if
administered within 96 hours after contact with the virus.
Newborns from mothers who developed varicella within 5 days before or 2 days
after delivery should immediately be injected with 125 IU of VZV immunoglobulin and
should be started with acyclovir in dosage 10 mg/kg/day. Immunoglobulin administration
does not decrease frequency of varicella in newborns but provides much milder form of
the disease in comparison to children without immunoglobulin prophylaxis.
If mother is diagnosed with varicella just before or during delivery, the newborn
should be isolated from other children till transformation of all the vesicles into crusts in
mother. The child should stay with the mother in maternity house. There is no single
opinion regarding breastfeeding if mother has varicella. It is considered that due to high
risk of viral transmission through milk, the first 5 days of rash breastfeeding should be
abstained from. Other clinicians have the opinion that breastfeeding should be interrupted
only in case of vesicles on the breasts, especially around nipples.
Questions for self-control
1. Etiology of varicella, characteristics of the causative agent.2. Epidemiological particularities of varicella, source of infection.3. Pathogenesis of varicella.4. Clinical presentation of typical form of varicella.5. Inborn varicella.6. Particularities of varicella in newborns and infants.7. Laboratory diagnosis of varicella.8. Nervous system involvement at varicella.9. Main approaches to varicella treatment (main antiherpetic drugs: drug characteristics, dosage).10. Prophylactic activities in varicella nidus.
Tests for self-control1. Causative agent of varicella is the following:A. Herpes simplex virus B. ParamyxovirusC. Varicella-Zoster virusD. Cytomegalovirus E. Epstein-Barr virus2. Minimal incubation period at varicella is:A. 3 days B. 5 daysC. 9 daysD. 11 daysE. 21 days 3. Particularities of rash at varicella:A. Appears on the 3-4th day of the diseases beginning
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B. “False” polymorphism is typicalC. Step-wise appearance D. It is not accompanied by itching E. It is seen in approximately 50% of patients4. What pattern of fever is typical for varicella?A. PermanentB. Remitting C. Wave-like D. Two-wavedE. New elements are accompanied by fever episodes. 5. Choose the most severe complication of varicella:A. Pneumonia B. CroupC. OtitisD. Encephalitis E. Phlegmona6. In newborns and infants with varicella the rash appears:A. On the first dayB. On the 2-5th dayC. On the 6-7th day D. On the 3-4th dayE. Rash can be absent7. Terms of isolation of patients with varicella?A. After 2 negative evaluations for Varicella-zoster virusB. Till clinical recoveryC. Since beginning of the disease till the 5th day after last vesicles appearance D. After 1 negative evaluation for Varicella-zoster virus E. Till 5 days after beginning of rash 8. Which part of brain is most often involved at varicella encephalitis:A. Brain hemispheres B. Brain stem C. CerebellumD. Meninges E. Basal ganglia9. Etiotropic antiviral therapy at varicella is not indicated at?A. Severe forms of varicella B. CNS complicationsC. Inborn varicellaD. Patients with HIV infection and AIDS E. Presence of bacterial complications 10. Which therapy is appropriate for treatment of typical mild varicella?A. Symptomatic therapy B. Interferon C. Normal human immunoglobulin D. Acyclovir E. Antibacterial drugs
Test answers
1-C, 2-D, 3-B, 4-E, 5-D, 6-B, 7-C, 8-C, 9-E, 10-A.
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