Chickenpox laboratory findings: Difference between revisions

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Latest revision as of 20:53, 29 July 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S [2]

Overview

The laboratory findings of chickenpox include blood tests that can be done to identify the response to acute infection (IgM) or previous infection and subsequent immunity (IgG). Prenatal diagnosis of fetal varicella infection can be performed using ultrasound at 5 weeks following primary maternal infection. A PCR test of the mother's amniotic fluid can also be performed, though the risk of spontaneous abortion due to the amniocentesis procedure is higher than the risk of the baby developing fetal varicella syndrome.

Laboratory Findings

Laboratory tests that are shown to be useful for the diagnosis of chickenpox include:

PCR is done by collecting skin vesicles fluid, scabs, saliva and cerebrospinal fluid if neurological symptoms or signs are present.^[1]
PCR done with a restriction enzyme can be used to hydrolyze and sequence specific segments of the viral genome. This can be used to determine whether VZV is resistant to acyclovir.^[1]
Antibody Testing
Viral detection
VZV DNA testing
Direct Fluorescent Antibody (DFA)
VZV culture

Antibody Testing

Laboratory tests detect and measure the level of VZV antibodies. The presence of IgM antibodies indicates acute infection.

IgM

It can be detected within 1-2 weeks post exposure.
The levels of IgM antibodies rise for a short period of time and then fall below detectable levels.
Post-Infection, the IgM levels rise only when the latent VZV is reactivated.

IgG

IgG antibodies are produced several weeks after the initial exposure.
IgG levels rise during active infection and then the levels become stable as the VZV infection gets resolves and as the virus gets inactivated.

Viral detection

Viral detection is done by finding VZV in a blood, vesicle fluid, or tissue sample. Detection is done by culturing the virus or by detecting its genetic material (VZV DNA).

VZV DNA testing

VZV DNA testing is sensitive and measures viral load.

Direct Fluorescent Antibody (DFA)

DFA test detects the presence of VZV in the cells in the skin lesion using a labeled antibody. It is rapid but less specific and sensitive than DNA testing.

VZV culture

Culture is not very reliable for VZV and can lead to false-negative results.

Microscopic Findings

Photomicrograph reveals the intranuclear inclusions produced by varicella virus grown in a tissue culture (500x mag). From Public Health Image Library (PHIL). ^[2]
Cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox (125x mag). From Public Health Image Library (PHIL). ^[2]
Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (125x mag). From Public Health Image Library (PHIL). ^[2]
Photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (500x mag). From Public Health Image Library (PHIL). ^[2]
Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (50x mag). From Public Health Image Library (PHIL). ^[2]
Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (50x mag). From Public Health Image Library (PHIL). ^[2]
Photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (500x mag). From Public Health Image Library (PHIL). ^[2]
Photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (1200x mag). From Public Health Image Library (PHIL). ^[2]
Photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (1200x mag). From Public Health Image Library (PHIL). ^[2]

References

↑ ^1.0 ^1.1 Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D; et al. (2015). "Varicella zoster virus infection". Nat Rev Dis Primers. 1: 15016. doi:10.1038/nrdp.2015.16. PMC 5381807. PMID 27188665.
↑ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 ^2.8 "Public Health Image Library (PHIL)".

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[pmid27188665-1] 1.0 ^1.1 Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D; et al. (2015). "Varicella zoster virus infection". Nat Rev Dis Primers. 1: 15016. doi:10.1038/nrdp.2015.16. PMC 5381807. PMID 27188665.

[PHIL-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 ^2.8 "Public Health Image Library (PHIL)".

[1]

[2]

@@ Line 4: / Line 4: @@
 ==Overview==
-* Diagnosis of Chickenpox is usually based upon signs and symptoms of the affected individual.
+The laboratory findings of [[chickenpox]] include [[blood]] tests that can be done to identify the response to acute [[infection]] ([[IgM]]) or previous [[infection]] and subsequent [[Immunity (medical)|immunity]] ([[IgG]]). [[Prenatal]] diagnosis of [[Fetus|fetal]] [[Chickenpox|varicella infection]] can be performed using [[ultrasound]] at 5 weeks following primary [[maternal]] [[infection]]. A [[PCR]] test of the mother's [[amniotic fluid]] can also be performed, though the risk of [[spontaneous abortion]] due to the [[amniocentesis]] procedure is higher than the risk of the baby developing fetal [[Chickenpox|varicella syndrome]].
-* Laboratory tests are not routinely used to diagnose active cases of chickenpox and shingles, which are caused by the varicella zoster virus (VZV).
-* Children are nowadays vaccinated and most adults generally may have been infected with VZV in their early years.Hence, general population screening is not done usually.  Anyhow, testing for VZV or for the antibodies produced in response to VZV infection may be performed in when required for screening purposes.
-* Also, screening may be advised for newborns, pregnant women, prior to organ transplantation, and in those with HIV/AIDS.
-* Testing may be used to:
-** Determine if someone has been previously exposed to VZV either through past infection or
-** Vaccination and has developed immunity to the disease
 ==Laboratory Findings==
-* Laboratory tests can help confirm the diagnosis, if needed. They are:
+Laboratory tests that are shown to be useful for the diagnosis of [[chickenpox]] include:
-** Antibody Testing
+* [[Polymerase chain reaction|PCR]] is done by collecting [[skin]] [[Vesicle|vesicles]] [[fluid]], [[Scab|scabs]], [[saliva]] and [[cerebrospinal fluid]] if neurological symptoms or signs are present.<ref name="pmid27188665">{{cite journal| author=Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D et al.| title=Varicella zoster virus infection. | journal=Nat Rev Dis Primers | year= 2015 | volume= 1 | issue=  | pages= 15016 | pmid=27188665 | doi=10.1038/nrdp.2015.16 | pmc=5381807 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27188665  }} </ref>
-** Viral detection
+*[[Polymerase chain reaction|PCR]] done with a [[restriction enzyme]] can be used to [[hydrolyze]] and sequence specific segments of the [[Virus|viral]] [[genome]]. This can be used to determine whether [[Varicella zoster virus|VZV]] is resistant to [[acyclovir]].<ref name="pmid27188665">{{cite journal| author=Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D et al.| title=Varicella zoster virus infection. | journal=Nat Rev Dis Primers | year= 2015 | volume= 1 | issue=  | pages= 15016 | pmid=27188665 | doi=10.1038/nrdp.2015.16 | pmc=5381807 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27188665  }} </ref>
-** VZV DNA testing
+* [[Antibody]] Testing
-** Direct Fluorescent Antibody (DFA)
+* [[Virus|Viral]] detection
-** VZV culture
+* [[Varicella zoster virus|VZV]] [[DNA]] testing
+* Direct [[Fluorescent]] Antibody ([[Direct fluorescent antibody|DFA]])
+* [[Varicella zoster virus|VZV]] culture
 ===Antibody Testing===
-* When an individual is exposed to VZV, their immune system responds by producing antibodies to the virus. Laboratory tests detect and measure the level of two classes of VZV antibodies in the blood namely IgM and IgG.
+*Laboratory tests detect and measure the level of [[Varicella zoster virus|VZV]] [[antibodies]]. The presence of [[IgM]] antibodies indicates acute [[infection]].
 ====IgM====
-*First antibodies to be produced in response to the infection.
+*It can be detected within 1-2 weeks post exposure.
-*Can be detected within a week or two post exposure.
+*The levels of [[Immunoglobulin M|IgM antibodies]] rise for a short period of time and then fall below detectable levels.
-*The levels of IgM antibodies rises for a short period of time and then falls below detectable levels.
+*Post-Infection, the [[IgM]] levels rise only when the latent [[VZV]] is reactivated.
-*Post-Infection, in the future, the IgM levels rise only when the latent VZV is reactivated.
 ====IgG====
-*Produced several weeks after the initial exposure.
+*[[Immunoglobulin G|IgG antibodies]] are produced several weeks after the initial exposure.
-*IgG levels rise during active infection and then the levels become stable as the VZV infection gets resolves and as the virus gets inactivated.
+*[[IgG]] levels rise during active [[infection]] and then the levels become stable as the [[Varicella zoster virus|VZV]] infection gets resolves and as the [[virus]] gets inactivated.
-*Provides Long-Term protection
 ===Viral detection===
-* Viral detection is done by finding VZV in a blood, vesicle fluid, or tissue sample. Detection done by culturing the virus or by detecting it's genetic material (VZV DNA).
+* [[Virus|Viral]] detection is done by finding [[Varicella zoster virus|VZV]] in a [[blood]], [[vesicle]] [[fluid]], or [[tissue]] sample. Detection is done by culturing the [[virus]] or by detecting its [[genetic material]] ([[Varicella zoster virus|VZV]] [[DNA]]).
 ===VZV DNA testing===
-* Performed to detect VZV genetic material in a person's sample. This method is sensitive. It can identify and measure the amount of the virus.
+* [[Varicella zoster virus|VZV]] [[DNA]] testing is [[Sensitivity (tests)|sensitive]] and measures [[viral load]].
 ===Direct Fluorescent Antibody (DFA)===
-* DFA test visualizes the presence of VZV in the cells taken from an individuals's skin lesion using a special microscope and labeled antibody. Advantages of DFA test are that it is rapid, but less specific and sensitive than DNA testing.
+* [[Direct fluorescent antibody|DFA]] test detects the presence of [[Varicella zoster virus|VZV]] in the cells in the [[skin]] lesion using a labeled [[antibody]]. It is rapid but less [[Specificity (tests)|specific]] and [[Sensitivity (tests)|sensitive]] than [[DNA]] testing.
 ===VZV culture===
-* Culture is not very reliable for VZV and can lead to false-negative results.
+* [[Culture medium|Culture]] is not very reliable for [[Varicella zoster virus|VZV]] and can lead to [[false-negative]] results.
-The choice of tests and samples collected depends on the person, their symptoms, and on the healthcare practitioner's clinical findings.
-==Determining Chickenpox Susceptibility==
+===Microscopic Findings===
-====IgG ELISA====
+<gallery>
-* Whole infected cell (wc) [[ELISA]] is the most commonly used test to determine if a person has [[antibodies]] to VZV from past varicella disease. Wc ELISA is done on [[blood]] samples. It can readily detect seroconversion to a natural infection with VZV. However, it is not sensitive enough to detect all seroconversions after vaccination. The more sensitive purified glycoprotein ELISA (gpELISA) or fluorescent antibody to membrane [[antigen]] (FAMA) tests have been used in research settings to detect seroconversion after vaccination. However, these are not available commercially.
-====IgG Avidity====
+Image: Chickenpox37.jpeg| Photomicrograph reveals the intranuclear inclusions produced by varicella virus grown in a tissue culture (500x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
-* IgG avidity has been used in research settings to determine if a person who is IgG positive for VZV was infected with the virus in the past or more recently. Avidity testing can be used to determine if the most recent VZV rash was due to primary [[infection]] (varicella) or reactivation ([[herpes zoster]]). People infected in the past tend to have antibodies with high affinity for binding to the antigen compared with people with a more recent infection who have a low affinity. As a result, low avidity is an indicator for VZV primary infection. This test is not available commercially.
-====Laboratory Confirmation of Vaccine-Adverse Event====
+Image: Chickenpox14.jpeg|Cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox (125x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
-* [[PCR]] [[genotyping]] of [[skin]] [[lesions]] can be used to distinguish [[rashes]] due to wild-type VZV from rashes caused by vaccine type (Oka)-strain VZV. Samples of [[blood]], [[cerebrospinal fluid]], or [[biopsy]] specimens may also be tested for vaccine-strain VZV to confirm a vaccine-adverse event. VZV-strain-specific testing is not available commercially; it is available at some laboratories, including the CDC National VZV Laboratory. Examples of possible varicella vaccine-adverse events for which PCR genotyping for VZV can be useful include varicella in a vaccinee 7–42 days after [[vaccination]], herpes zoster in a vaccinee >42 days post-vaccination, and suspected secondary vaccine-strain VZV transmission.
-===Interpretation of Laboratory Findings===
+Image: Chickenpox13.jpeg|Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (125x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
-====Confirmation of Suspected Varicella====
+Image: Chickenpox12.jpeg|Photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (500x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
-* The most sensitive method for confirming a diagnosis of varicella is the use of PCR to detect VZV in skin lesions ([[vesicles]], [[scabs]], [[maculopapular]] [[lesions]]). Vesicular lesions, if present, are the best for sampling.  Adequate collection of specimens from maculopapular lesions in vaccinated persons can be challenging. However a recent study comparing a variety of specimens from the same patients suggests that maculopapular lesions collected with proper technique can be highly reliable specimen types for detecting VZV.
-* IgM testing is considerably less sensitive than PCR testing of skin lesions.  Commercial IgM assay may not be reliable and false negative IgM results are not uncommon. A positive IgM ELISA result, although suggestive of a primary infection, does not exclude re-infection or reactivation of latent VZV. Careful clinical evaluation may be needed to determine if a [[rash]] is varicella or herpes zoster. Nevertheless, IgM testing is readily available and a positive result from a person with a rash is usually interpreted as laboratory confirmation of varicella. A single positive IgG ELISA result cannot be used to confirm a varicella case.
+Image: Chickenpox11.jpeg|Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (50x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
-* Paired [[acute]] and convalescent [[sera]] showing a four-fold rise in IgG antibodies have excellent specificity for varicella, but are not as sensitive as PCR of skin lesions for diagnosing varicella. Persons with prior history of vaccination or disease history may have very high baseline titers, and may not achieve a four-fold increase in the convalescent sera. The usefulness of this method for diagnosing varicella is further limited as it requires two office visits.
+Image: Chickenpox10.jpeg|Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (50x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
-====Establishing Laboratory Evidence of Immunity to Varicella====
+Image: Chickenpox09.jpeg|Photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (500x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
-* A positive IgG ELISA result indicates that a person has [[antibodies]] to VZV either from past varicella disease history or vaccination. This test cannot distinguish whether the antibodies were from a past episode of varicella or vaccination. It is a fairly sensitive and specific assay. However, none of the currently available commercial assays are sufficiently sensitive to detect immunity in all vaccinated persons.
+Image: Chickenpox08.jpeg|Photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (1200x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
+Image: Chickenpox07.jpeg|Photomicrograph reveals some of the cytoarchitectural histopathologic changes which you’d find in a human skin tissue specimen that included a chickenpox, or varicella zoster virus lesion (1200x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
+</gallery>
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