herpes zoster ( hz ) is a viral disease that causes vesicular rash , pain , and/or paresthesia according to the dermatome that is affected . hz is caused by reactivation of the varicella zoster virus ( vzv ) , which can remain latent in the dorsal root ganglia and cranial nerve ganglia following the initial infection . reactivation leads to proliferation of the virus in the sensory ganglia , followed by the infection spreading along the nerves to the skin , resulting in a vesicular rash and pain . the incidence of hz increases in old age , during human immunodeficiency virus infection , during steroid treatment , and after receiving immunosuppression treatment for an organ transplant or cancer . in rare cases , no lesions are formed on the skin , a condition known as zoster sine herpete ( zsh ) . diagnosis of hz based on the characteristic rash and vesicles that appear before and after the manifestation of neuropathy symptoms is relatively accurate . however , when there are atypical skin lesions , especially those occurring in the mouth or genitals of immunosuppressed patients , differential diagnosis is required . in addition , there are cases of zsh that need to be differentiated in order to determine whether the dermatomal pain is from vzv infection . laboratory tests for differential diagnosis consist of serological testing and extracting the virus from the affected tissue through tissue culture or molecular biology . after vzv infection , igg and igm antibodies appear 2 to 5 days after the rash and show the highest titers at 2 to 3 weeks . the vzv igm antibody levels then rapidly decrease and can not be detected at 1 year after infection , and the igg antibody levels gradually decrease , showing positive test results for several years . however , these reports of titer changes in vzv antibodies are usually based on patients with a primary infection of vzv ; consequently , there have been no reports that have specifically examined the titer changes in hz patients . the serological testing of vzv - specific antibodies has been widely used in the diagnosis of both acute and latent infections of hz . detecting vzv igm antibody by enzyme - linked immunosorbent assay ( elisa ) is simple and has a high sensitivity and specificity compared to the traditional method of directly separating the virus from the skin lesion . furthermore , elisa is known to be a more economical method with respect to cost and use of human resources in the laboratory . the elisa method for detecting vzv igm is especially useful during the diagnosis of a central nervous system infection , which requires the early administration of antiviral agents and is difficult to differentiate from other diseases when zsh is suspected because it lacks the typical rashes usually found in hz . however , there have been no clear reports of the positive rate of vzv igm antibodies over the time course of hz . consequently , there are limits to the diagnosis of hz through serological testing because it is difficult to differentiate whether negative results are because of a long time interval since the initial onset or to a non - hz infection . therefore , we conducted an observational study to evaluate the positive rate of vzv igm results over the time course after the onset of hz and estimate the vzv igm - positive period . this observational study was approved by the institutional review board of our hospital ( irb no . analysis was performed from august 2010 to july 2013 on the patients who visited the pain center of our hospital . the inclusion criteria were : diagnosis with hz owing to the typical dermatomal pain after rash and vesicle formation and receiving antiviral medications . the disease period after the onset of skin lesions in each patient was investigated , and serum from the venous blood of the patients was collected for the viral serological test . , hercules , ca ) , which uses an elisa principle , was used to measure the titer of the plasma vzv igm according to the guidelines of the manufacturer . an aliquot of serum diluted to a ratio of 1:101 in a volume of 100  l was placed in a well coated with anti - human igm monoclonal antibodies , then incubated for 45  minutes at 37c . afterward , it was washed 4 times with phosphate - buffered saline for 30  seconds . then , 100  l of antigen - labeled monoclonal antibodies was added and the mixture was incubated again for 45  minutes at 37c , followed by 4 washes with phosphate - buffered saline for 30  seconds each time . finally , 100  l of the substrate was added to the well and then incubated for 15  minutes at room temperature ( 24c    1c ) . within 30  minutes of adding 100  l of stop solution , the absorbance was measured using an evolis elisa analysis instrument ( bio - rad laboratories , inc . , ca ) . for every test , negative and positive reference materials were compared with each sample and used to calculate the absorbance ratio . when the absorbance ratio was 1.0 compared to the positive reference , the result was determined to be positive . when the absorbance ratio was below the positive reference ( i.e. , the absorbance ratio was < 1.0 ) , it was determined to be negative . the free statistical software program  r  version 2.15.0 ( the r foundation for statistical computing , vienna , austria ) was used for statistical analysis . before regression analysis , the normality of the vzv igm titer ( x variable ) and the period after the onset of hz ( y variable ) were tested using the shapiro wilks test , and if the assumptions of normality were not satisfied , these variables were transformed logarithmically . after logarithmic transformation of the x and y variables , regression analysis was performed between these variables . then , the estimated antibody - positive period ( x  1.0 ) was calculated from the regression equation model . this observational study was approved by the institutional review board of our hospital ( irb no . analysis was performed from august 2010 to july 2013 on the patients who visited the pain center of our hospital . the inclusion criteria were : diagnosis with hz owing to the typical dermatomal pain after rash and vesicle formation and receiving antiviral medications . the disease period after the onset of skin lesions in each patient was investigated , and serum from the venous blood of the patients was collected for the viral serological test . , hercules , ca ) , which uses an elisa principle , was used to measure the titer of the plasma vzv igm according to the guidelines of the manufacturer . an aliquot of serum diluted to a ratio of 1:101 in a volume of 100  l was placed in a well coated with anti - human igm monoclonal antibodies , then incubated for 45  minutes at 37c . afterward , it was washed 4 times with phosphate - buffered saline for 30  seconds . then , 100  l of antigen - labeled monoclonal antibodies was added and the mixture was incubated again for 45  minutes at 37c , followed by 4 washes with phosphate - buffered saline for 30  seconds each time . finally , 100  l of the substrate was added to the well and then incubated for 15  minutes at room temperature ( 24c    1c ) . within 30  minutes of adding 100  l of stop solution , the absorbance was measured using an evolis elisa analysis instrument ( bio - rad laboratories , inc . negative and positive reference materials were compared with each sample and used to calculate the absorbance ratio . when the absorbance ratio was 1.0 compared to the positive reference , the result was determined to be positive . when the absorbance ratio was below the positive reference ( i.e. , the absorbance ratio was < 1.0 ) , it was determined to be negative . version 2.15.0 ( the r foundation for statistical computing , vienna , austria ) was used for statistical analysis . before regression analysis , the normality of the vzv igm titer ( x variable ) and the period after the onset of hz ( y variable ) were tested using the shapiro wilks test , and if the assumptions of normality were not satisfied , these variables were transformed logarithmically . after logarithmic transformation of the x and y variables , regression analysis was performed between these variables . then , the estimated antibody - positive period ( x  1.0 ) was calculated from the regression equation model . the research was conducted on a group of 62 patients , and the time taken from a skin lesion outbreak to serological testing ranged from 2 days to 40 weeks . the sex , age , time from skin lesion outbreak to serological testing , and area of affected skin of the patients of the 62 patients , the vzv igm antibody appeared positive in 23 patients ( 37% ) and negative in 39 patients ( 63% ) . the vzv igm titer started to increase after the skin lesions appeared , showing maximum levels at 6 to 10 days following the rash , and all patients showed negative results after 10 weeks ( fig . the positive rate over the time course indicated that 83% of the patients were positive when tested within 1 week ( 5/6 ) ; 73% were positive when tested between 1 to 2 weeks ( 11/15 ) ; then the rate decreased to 36% when tested between 2 to 4 weeks ( 4/11 ) , and the positive rate was 0% when tested after 10 weeks ( fig . scatter plot of vzv igm antibody levels against the duration of rash according to serological test . the achieved regression equation model after logarithmic transformation was ( log [ y ] = 1.2665248116    log [ x ] ) ( r = 0.382 , p the estimated positive duration calculated from this equation was 3.5 weeks ( 95% confidence interval 2.84.6 weeks , fig . the estimated duration during which patients would test positive for vzv igm antibody was 3.5 weeks ( 95% confidence interval 2.84.6 weeks ) . hz is relatively easy to diagnose clinically because of its characteristic painful skin blisters , rash , and dermatomal pattern . the period from the start of pain to the occurrence of lesions has been reported to range from 7 days to > 100 days , and symptoms similar to the common cold , such as fatigue and headache , can appear a few days before the lesions occur . however , there may be a need for differential diagnosis of hz from other skin diseases , such as zosteriform herpes simplex , eczema herpeticum , and vesicular enterovirus eruption . furthermore , clinical diagnosis can be difficult when an atypical manifestation of hz occurs , such as one with no skin lesions , no pain in the case of a previous vaccination , or a reduction in the diseased area of skin . cases of hz that do not show the characteristic skin lesions are called zsh and have been estimated to have a prevalence of approximately 0.2% ; however , there have been no attempts to thoroughly investigate the prevalence of zsh . there are various laboratory tests for the diagnosis of hz , such as the tzanck smear test , virus culture , serological methods , immunofluorescence methods , and polymerase chain reaction ( pcr ) . these test methods have various strengths and weaknesses in terms of their sensitivity , specificity , convenience , reproducibility , required time , and cost . morphological studies , such as the tzanck smear test , are simple methods in which a diagnosis can be made by collecting a specimen from the blisters in the skin lesion , allowing fast verification of hz for skilled examiners . however , such tests can not be used when there are no skin lesions , and differential diagnosis from other viruses , such as herpes simplex virus , is impossible . pcr is a method that can be used to detect vzv dna in blister fluid , blood , and cerebrospinal fluid ; this method allows fast testing with very high sensitivity . it is especially helpful when there is a suspicion of zsh or a central nervous system infection , which requires the early administration of antiviral agents . however , the accuracy of the pcr method for detecting zsh remains controversial ; it has drawbacks , for example , when analyzing blister fluid , it is difficult to manipulate the test material , and this method can not be used when blisters are not present . pcr using blood is also limited by the fact that vzv dna can only be discovered during the first few days of symptom manifestation . in addition , this method is difficult to apply generally to patients suspected of having hz in terms of its cost and patient compliance . the antibody serological test for hz virus consists of detecting the igg and igm antibodies for vzv , and it is used to differentially diagnose primary infection or recurrence of vzv , or to check the immune state . the igm antibody test , which reveals acute vzv infection , has a low sensitivity , cross - reacts with other herpes viruses , and has a high false - negative error rate when the titer of igg antibody is high . although the igm antibody test is accepted as an early diagnosis method for many other viral infections , the change in igm titer in vzv infection does not currently offer significant diagnostic value in many cases . this is because the change in igm titer is yet to be clearly defined , although there have been some reports that the titer appears 2 to 5 days after the lesions and shows the highest value after 2 to 3 weeks , rapidly decreasing to the point of being undetectable after 1 year . despite this issue , it can be a  diagnostic test of choice  when there are no skin lesions , as it offers fast test results and is less invasive and has lower cost than other methods . for these reasons , it remains useful , compared to methods that separate the virus from blisters . in our study , the positive rate of vzv igm was lower than expected at 37% . there have been a few studies on the positive rate of serological tests in patients with hz . according to research by sundqvist et al that investigated the frequency and specificity of the vzv igm response using elisa , 21 of 25 patients were shown to be positive , which is equivalent to a positive rate of 84% . dobec et al reported a positive rate of 47% for the detection of vzv igm in hz in a study to investigate the sensitivities of various laboratory approaches for the diagnosis of hz in 53 patients with typical morphology and distribution of the skin lesions . the positive rate of vzv igm antibody in hz patients has been reported to range from 10% to 70% according to the test method , test period , and clinical symptoms of the patients . early diagnosis using the vzv igm antibody test is not usually possible because it takes 2 to 5 days to form antibodies after the lesions appear . even in our research , 1 of the 6 patients who received the test within 1 week of a skin lesion presented negative results . the patient who presented negative results was tested 4 days after the appearance of a skin lesion . it is known that the disease period of postherpetic neuralgia before treatment is diverse , ranging from 0 to 312 months , and the mean disease period is known to be close to 1 month . therefore , in patients exhibiting neural segmental pain without a clear etiology and no history of surgery or injury , along with suspected hz and pain for approximately 1 month , the vzv igm antibody test can be useful in identifying sources of unexplainable pain such as zsh . the results of our study showed an estimated positive duration of 3.5 weeks for this test . the limitation of this research is that hz is caused by reactivation of vzv ; thus , to make an accurate serological diagnosis , the igg antibody should be measured twice during the acute period and the recovery period to observe the progress of the titer , but our study only measured the igm antibody titer once . however , an igm - positive result always signifies a recent infection ; therefore , it may be considered that an igm - positive result reflects a vzv infection . in addition , no comparison was performed between the vzv igm titer and the clinical symptoms of the patients . hence , it is thought that further research is necessary to evaluate the correlation between the degree of skin lesion and severity of pain with the titer . our study included 1 patient who showed the characteristic skin lesion and was clearly presumed to be hz , but was vzv igm - negative in the serological test ; therefore , there is need for a comparative study that includes other accurate test methods besides pcr . in conclusion , when hz is suspected , a vzv igm test within 3.5 weeks of onset can be helpful ; however , the diagnostic value of the test decreases after this period . therefore , for a patient with suspected vzv infection who suffers nerve segmental pain for unknown reasons , a serological test for vzv igm - specific antibody performed once within 3.5 weeks of pain onset would be easy , simple , and relatively cheap . this serological elisa test can ultimately be clinically useful for making a differential diagnosis of vzv from other causes of nerve segmental pain .
abstractlaboratory tests for herpes zoster ( hz ) are required to confirm varicella zoster virus ( vzv ) infection , especially when a skin lesion is not typical or apparent . the serological test for vzv igm antibody is simple and cost - effective ; however , the change in the vzv igm - positive rate over the time course of the disease has not been investigated . 
 therefore , we conducted an observational study to evaluate the positive rate of vzv igm results during the time course of hz and estimate the vzv igm - positive period.after obtaining serum from patients with typical hz , the vzv igm titer was examined using enzyme - linked immunosorbent assay methods . after logarithmic transformation of the vzv igm titer and the period after the onset of hz , regression analysis was performed with the 2 transformed variables.a total of 62 patients were included in this study , and vzv igm antibody was positive only in 23 patients ( 37% ) . 
 the estimated antibody - positive period after hz onset was 3.5 weeks ( 95% confidence interval 2.84.6 weeks).these findings suggest that the serological diagnosis of vzv igm to confirm hz is only useful within 3.5 weeks after the onset of symptoms .