A collaborative team comprised of researchers from Italy and the USA have set out to study the proposed relationship between urticaria and viral infection. High level HHV-6 reactivation is often seen in individuals that suffer from severe hypsersensitivity conditions such as DIHS and DRESS. Acute urticaria occurs in 15% to 25% of people at some point in their life, being associated with transudation of fluid from skin blood vessels and release of mediators from cutaneous mast cells and basophils. Chronic urticaria occurs in 1% of the general population overall, but the reported etiology is “unknown” in 80-90% of cases. The release of mast cell-derived mediators may be caused by both immune and non-immune mechanisms. However, nearly all of the numerous studies reporting evidence for infectious agents triggering acute or recurrent acute urticaria were retrospective observational studies without appropriate controls or individual case reports.
While reports of specific herpesvirus infections are frequent in these publications, reports of associated urticaria are few. Thus, this collaboration investigated the association of herpes simplex virus (HSV) types 1 and 2, Epstein-Barr virus (EBV), CMV and human herpesvirus-6 (HHV-6) with acute or recurrent acute urticaria. In an age-matched case-control study, the first of its kind, the group identified a highly significant correlation between specific herpesvirus infections and acute or recurrent acute urticaria. Specific infections were diagnosed in 26 of 37 cases and among 9 of 37 control children (70% vs 24%; P=0.0002). Of infected cases, 25 had viral infections, six had viral-bacterial co-infections, six were infected with two viruses, and one had M. pneumoniae infection. Two or more infections occurred in 7 of 17 cases (41%) with recurrent urticaria compared with 2 of 20 cases (10%) with only one episode of urticaria (P =0.05). The cases, compared to the age matched controls, had a higher prevalence of herpesvirus infections: single or concomitant herpesvirus infections occurred in 24 cases and in 4 controls (65% vs 11 %, p=0.0003).
Although this preliminary study lacks the power of a large-scale clinical surveillance, the initial findings suggest herpesviruses may be a crucial component of the process involved in the development of acute or recurrent acute urticaria. This study is further contributory to the idea that HHV-6 reactivation may be involved in the etiology of allergic reactions (Hashizume 2013). Currently, no viral testing is done for persistent urticaria. The “French Investigators for Skin Adverse Reaction to Drug” (FISARD) has recently proposed that physicians treat life-threatening cases of DRESS with IV immunoblobulins and/or antiviral therapy. The group, led by Dr. Vincent Descamps, made this recommendation based on the important role of virus (especially HHV-6) and immune response to virus in patients who present with a ‘picture’ of DRESS but without any evidence of a drug trigger (often observed in transplant patients and emergency room patients). Dr. Descamps has also proposed recently that autoimmunity and thyroid dysfunction may be attributable to HHV-6 reactivation, and has suggested a role for saliva testing in the detection of herpesvirus reactivation in patients with drug hypersensitivity.
Since significant HHV-6 reactivation is frequent in patients with hypersensitivity reactivation, one question that requires urgent study is the possibility that viral activity could be exacerbated by high dose steroid therapy, and ultimately contribute to the late flare and organ failure. HHV-6 reactivation can cause liver and kidney failure in transplant patients under high levels of immunosuppression, but no studies have been conducted to date on the viral load in affected organs in DRESS/VRESS. For more information, read the full paper, and visit the following pages from the HHV-6 Foundation: HHV-6 & Rash / Roseola. HHV-6 & Hypersensitivity (DIHS/DRESS)