Lichen planus as a Side Effect of HBV Vaccination

Dr. Alfredo Rebora Department of Dermatology, University of Genoa Viale Benedetto XV I–16132 Genova (Italy) Tel. +39 10 353 8414, Fax +39 10 353 8401 Ferrando et al. [1] in this tissue of Dermatology report a further case of lichen planus (LP) occurring after vaccination against hepatitis B virus (HBV). We are aware of 18 cases [2–11], including 2 observed by us and still unpublished (table 1). What could have been a coincidence in 1990 [2], should be now recognized as a genuine side effect of the HBV vaccine [12]. These observations deserve some comment. (1) Because of the diffusion of HBV vaccination, 18 cases in 7 years indicate that postvaccine LP is a rare event. Many cases may certainly go undetected or be dumped as ‘skin rashes’, but their theoretical importance may be underrated as well. (2) All cases have been described in Italy and in France. It is surprising that, given the number of HBV vaccinations worldwide, similar cases have not been reported elsewhere, particularly in the USA, where a good proportion of people are of Mediterranean stock. (3) Although a case-control study is needed to definitely exclude coincidence, we may assume that it is unlikely. The observation of 3 cases in children [9], in whom LP is extremely rare, the exacerbation after the 2nd dose [7] or after the booster dose in one of our unpublished cases, and the severity of the lesions in a patient previously infected by HBV [11], all support the causal role of vaccination. (4) A chronic graft-versus-host(GVHR)-like autoimmune reaction has been suggested as a pathogenetic mechanism. Except for Lefort et al. [8] and Ferrando et al. [1] cases, in which LP developed as early as 7 and 15 days respectively after the 1st dose, latency is in keeping with this interpretation. In chronic GVHR, the lichenoid eruption may develop up to months or even years after bone marrow transplantation. (5) Whenever studied, seroconversion followed vaccination in all cases except in Ferrando et al. [1]. In the original case [2], the HBsAb titer was low (16 IU/l) and even disappeared 1 year later. In the other cases, the titers ranged between 82 [8] and 582 IU/l [7]. In 2 cases [2 and one of our cases], also HBcAb was present, an antibody that cannot be induced by the vaccines. Because of the negative prevaccination serology, this was probably a false-positive finding. The absence of HBeAb makes very unlikely that the patient got infected in the interval between doses. An old infection was suggested when the eruption started after the 1st dose [7]. This would be the case only if the patient, infected before vaccination, did not seroconvert. (6) The vaccines are disparate. In 2 cases, the vaccines were obtained by inactivation of a plasma-derived HBsAg, while in the other cases they were recombinant proteins. All these vaccines share only protein S as a common component. HBsAg is a mosaic of epitopes (S, pre-S1 and pre-S2) each of which is immunogenic. While the plasma-derived vaccines contain all the epitopes, recombinant ones do not. In Pusel’s [4] and Aubin’s [5] cases, the vaccine did not contain the pre-S1 epitope. Recombivax [3] did not contain the pre-S2 epitope and Engerix B [7, 9, 10 and one of our upublished cases] neither pre-S1 nor pre-S2, but only S. LP, therefore, may well develop as an immune reaction to keratinocytes expressing S epitope. Likewise, in patients with chronic postviral hepatitis, LP would be a cytotoxic reaction to keratinocytes expressing HBs and not epitopes shared by the hepatocytes damaged by the virus as suggested [13]. More simply, the vaccine may stimulate the immune system nonspecifically triggering LP eruption as it does with other immune-related disorders, including lupus erythematosus [14]. However, we are unaware of lichenoid eruption