Role of herpes simplex virus 1 & 2, interferon-γ and tumor necrosis factor-α in the pathogenesis of erythema multiforme.

Abstract

Background: It was hypothesized that herpes simplex virus (HSV) might play an important role in erythema multiforme (EM) pathogenesis (as high incidence of EM is preceeded by HSV infection); and this role might involve the proinflammatory cytokines: interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Objective: Of this work was to study the role of HSV in inducing EM in attempt to differentiate herpes simplex associated EM (HAEM) from other EM syndromes for more specific treatment, better understanding the pathogenesis of EM; and to study the role of IFN- and TNF-α as important proinflammatory cytokines in the EM immune reactions. Subjects: Forty five patients presented with EM selected from the outpatient Dermatology Clinic at Ain Shams University Hospital, and thirty (age & sex matched) control subjects were included in this work. Patients were divided into 3 groups “HAEM” group, drug induced EM “DIEM”; and idiopathic group. Controls were selected and grouped into 2 groups: diseased control group which includes 15 patients with dermatological diseases other than EM and this group included 6 psoriatic patients, 5 patients with lichen planus, and 4 with chronic eczema. The other 15 were healthy volunteers. All groups were subjected to HSV DNA detection by PCR technique in lesional, non-lesional and blood samples using primers with a common nucleotide sequence for both HSV types 1 & 2. In addition, IFNγ mRNA was detected by the use of RT-PCR with primers for IFNγ mRNA and TNFα was detected by using the ELISA technique. Results of this work show that 73% of HAEM patients had positive results for detection of HSV DNA in their lesional samples and 67% in the non-lesional tissues. Also, in the idiopathic group, the frequency of detection was 73% in the lesional and 60% in the non-lesional tissues. On the other hand, the frequency of detection in the DIEM and in the diseased control group was 13% in the lesional-skin and no detection in the non-lesional tissues. These results showed a highly significant statistical difference between each of the HEAM and the idiopathic group on one hand and each of the DIEM and both the control groups on the other hand, as regards HSV detection in tissues. Where as HSV DNA detection in blood samples showed no significant difference suggesting that HSV DNA detection in tissues by the PCR technique has a higher significance than detection in blood that require a quantitative assay for diagnosis of active HSV infection. As for INF-γ detection, there was a positive correlation between its detection in tissues and the HSV DNA detected in both the HAEM and the idiopathic groups but not in the DIEM or the control groups. On the other hand. TNFα was detected in 100% of samples in the DIEM group. Conclusion: HSV plays a definite role in inducing HAEM, which should be considered as a different entity than DIEM. INF-γ and TNF-α are important cytokines in the pathogenesis of HAEM and DIEM. Recommendation: antiviral therapy must be given as a prophylaxis after HSV in known EM patients to decrease the number of EM attacks.

New Egyptian Journal of Microbiology Vol. 17 (2) 2007: pp. 27-39