pemphigus disease is classified as an autoimmune disease in which auto - antibodies act against surface glycoproteins of epithelial cells for some unknown reason . the most common type of this disease associated with the oral mucosal lesions is pemphigus vulgaris . oral lesions in most cases are the first symptoms , and treatment is extremely difficult . as a result , these lesions appear earlier and disappear later than all other types . nowadays , it is commonly believed that autoimmune diseases are the result of multiple factors . among the factors , the role of endogenous ( genetic ) and exogenous factors in the prompting autoimmune diseases has been more significant . exogenous factors include viruses and previous infections that could be effective in setting off , triggering , and even causing progression of autoimmune diseases . there are several reports indicating the possible role of viruses , particularly that of the herpes family . the prominent feature of herpes viruses is their role in causing infections that have the ability to survive in the host for a lifetime and activate periodically . several studies have been conducted aiming at isolating viruses and/or triggering an immune response against a possible viral cause of pemphigus . some confirmed the role of viruses in this disease , but others rejected such a role . in various studies , the role of viruses namely ebv , cmv , hsv1 and hsv2 in patients with pemphigus vulgaris has been confirmed . these studies have also proven the existence of the dna of viruses in the blood smear and peripheral skin lesions of patients with pemphigus using polymerase chain reaction ( pcr ) . the presence of the antibody of these viruses in the blood has also been confirmed [ 710 ] . according to some studies , viral cultures can be as valuable in the diagnosis of herpes simplex as pcr ; therefore , in patients with pemphigus resistant to treatment such viral cytological / serological examinations as well as pcr should be done . in addition to the role of these viruses in the occurrence of the disease , the findings of various research studies indicated that infections caused by these viruses , particularly by herpes simplex , can increase pemphigus mortality . viruses of the herpes group , especially hsv as well as cmv , can play an important role in development of oral lesions of pemphigus patients [ 1321 ] . clinically , measured igg antibody levels are generally considered to be indicative of an individual 's immune response to particular pathogens . a common example of this practice is titers drawn to demonstrate serological immunity to viruses . specific igg against viruses is produced one to two weeks after initial infection and increases to maximum titer in four to eight weeks and then decreases . considering the possible role of viruses , particularly herpes viruses in pemphigus and given that studying the relationship between the diseases and these viruses can play an important role in the diagnosis and treatment of these conditions , the goal of this study was to compare the level of igg antibodies against hsv2 , hsv1 , cmv and ebv in patients with pemphigus vulgaris and healthy controls . in this cross - sectional study , serum samples taken from 25 patients with pemphigus vulgaris and 27 healthy controls were evaluated . participants of the patient group were selected from people referring to the oral and maxillofacial department and alzahra hospital of isfahan university of medical sciences . oral lesions were studied and a detailed history of the patient 's lesions was assessed . after biopsy , the skin lesions or mucosal samples were sent to a pathology lab and diagnosis of pemphigus vulgaris was confirmed based on histopathological pattern and direct immunofluorescence . patients taking drugs such as captopril and d - penicillamine who fell into the category of drug - induced pemphigus and those diagnosed with cancer or leukemia , thymoma , and other malignancies that could cause paraneoplastic pemphigus were excluded from the study . the control group included healthy individuals who experienced no illnesses and were not taking any drugs . separated serums were isolated in separate tubes and were maintained at a temperature of 20c . measurement kits were used to assess anti - ebv ( igg ) , anti - cmv ( igg ) , anti - hsv2 ( igg ) , and anti - hsv1 ( igg ) ( fig . spss software and independent t - test were used for statistical analysis and p<0.05 was considered statistically significant . in this study , 25 patients with pemphigus vulgaris , including 11 males and 14 females with a mean age of 36.6 years ( range 25 to 48 years ) were studied . the control group of this study included 27 healthy individuals ; 15 males and 12 females with a mean age of 36.6 years ( range 25 to 45 years ) who were healthy and were not taking any medications . the mean levels of anti - ebv , anti - cmv , anti - hsv1 and anti - hsv2 igg in the study group are presented in table 1 . the difference in the mean levels of anti - ebv ( p=0.005 ) , anti - cmv ( p=0.0001 ) and anti - hsv2 igg was statistically significant ( p=0.001 ) , but this difference was not significant for anti - hsv1 igg ( p=0.36 ) . average anti - virus immunoglobulin g for epstein - barr virus , cytomegalovirus , herpes simplex virus type 1 and herpes simplex virus type 2 separately for each study group viral infections are the trigger factors of many autoimmune diseases such as type 1 diabetes mellitus , rheumatoid arthritis , lupus erythematosus , multiple sclerosis , sjogren 's syndrome , and hashimoto 's thyroiditis . several attempts have been made to isolate a virus from the blood , blister fluid and skin lesions in pemphigus patients , but no definitive results have been achieved from these studies . the purpose of this study was to search for the presence or absence of a relationship between pemphigus vulgaris and viral infections , particularly herpes virus . comparison of the levels of anti - ebv igg showed highly significant levels of antibodies in patients with pemphigus in comparison with the controls . the results of our study were consistent with those of tufano et al ,   in 1999 , who observed the dna of the ebv in peripheral blood smears and skin biopsies of 15% and 5% of patients , respectively . barzilai and colleagues   also found that anti - ebv igg titer was higher in patients with pemphigus vulgaris compared with healthy controls , which conforms with the results of our study . these results support the hypothesis that ebv is truly associated with many autoimmune diseases including pemphigus vulgaris . regarding the level of anti - cmv igg , the results of our study also showed that antibody titer increased significantly in patients with pemphigus vulgaris in comparison with the control group . these results are also consistent with those of tufano et al ,   where the anti - cmv igm was found in 10% of pemphigus patients . .   showed anti - cmv antibody titer in 1565 sera from 23 different autoimmune diseases , including pemphigus vulgaris . although higher antibody titer against cmv was observed in several diseases tested , including pemphigus , the increase was significant only in systemic lupus erythematosus patients . in a study by kalra et al ,   16.6% of pemphigus vulgaris patients had anti - cmv igm , which indicated acute infection and the probable role of cmv infection in the initiation and exacerbation of pemphigus in these patients . therefore , it can be said that there is a strong relationship between cmv infection and the onset and exacerbation of pemphigus in genetically susceptible individuals . the results of our study on hsv1 antibody showed an increase in the level of antibody titer in patients with pemphigus compared with the control group , but this difference was not significant . likewise , numerous studies have reported the activation of pemphigus disease following herpes simplex infection . in the study by tufano et al , the presence of the dna of hsv1 and hsv2 was confirmed in 50% of peripheral blood smear cells and 71% of skin biopsies . also , in 95% of patients , anti - hsv igg was higher than 1:8 titers . however , to determine whether the obtained results are really significant or not , it is better to study a larger number of participants so that the minor differences between the two groups can be interpreted correctly . the results of our study were also consistent with those of the study by kalra et al ,   in which patients who had more than 50% of mucosal involvement were positive for hsv antigen in oral scrapings and patients with less than 50% mucosal lesions were negative for hsv antigen . kurata et al .   examined saliva for the presence of hsv dna after the onset of pemphigus vulgaris initially localized to the oral lesions ; they successfully detected high levels of hsv dna in the saliva samples from six of 16 patients with pemphigus vulgaris at the earliest stage . in addition , anti - hsv igg titers in patients with pemphigus vulgaris were significantly higher than those in patients with virologically confirmed hsv - induced disorders . this should also be mentioned that as far as the authors are concerned , all studies on hsv have been carried out without isolating hsv1 and hsv2 ; therefore , this study was the first to isolate hsv1 and hsv2 and their relationship with pemphigus vulgaris . the results of our study showed a significant rise in hsv2 antibody titer in pemphigus vulgaris patients compared to the control group . only one case has been reported by kalajian and callen   in 2007 , where the disease manifested genital lesions and following diagnostic procedures , pemphigus vulgaris with herpes infection was diagnosed . this clarifies the fact that hsv2 infection may play a role in the onset and exacerbation of pemphigus . results of the current study are also consistent with those obtained by kalajian and callen . since herpes family of viruses poses a potential risk on patients with skin diseases such as pemphigus , it is necessary to use the best diagnostic techniques to discover the symptoms of such infections in these patients and employ the most effective anti - viral treatment to cure them .
objectives : regarding the implication of viruses particularly herpes in pemphigus vulgaris , we sought to assess and compare the level of immunoglobulin g ( igg ) antibodies against herpes simplex virus types 1 and 2 ( hsv1 and hsv2 ) , cytomegalovirus ( cmv ) and epstein - barr virus ( ebv ) in patients with pemphigus vulgaris and healthy people.materials and methods : in this cross - sectional study , 25 patients with pemphigus vulgaris and 27 healthy individuals comprised the experimental and control groups , respectively . 
 serum samples were taken from both groups ; the levels of igg antibodies against hsv1 , hsv2 , cmv and ebv were measured using elisa.results:immunoglobulin g titer was higher for all four viruses in the patient group in comparison to the control group . 
 this difference was significant for anti - ebv ( p= 0.005 ) , anti - cmv ( p=0.0001 ) and anti - hsv2 ( p=0.001 ) but not significant for anti - hsv1 ( p= 0.36).conclusion : viruses including ebv , cmv , and hsv2 probably play a role in the pathogenesis of pemphigus in addition to the effects of genetics , toxins and other predisposing factors . in this study 
 , no statistically significant relationship was observed between hsv1 and pemphigus vulgaris , which was probably due to the high titer of anti - hsv1 igg in healthy individuals in the community . 
 more studies must be done in this regard .