DISCUSSION
The role of EBV as a potential inducer or exacerbator of autoimmune blistering disorders in children is debated, while there seems to be sufficient evidence to support its role as an infectious trigger factor in adults. In fact, DNA sequences of EBV have been found in 5% of skin biopsies of adult patients affected by bullous pemphigoid (BP).6F. Drago et al. detected DNA sequences of HHV, including EBV, in 27% of skin samples, further supporting the potential role of herpesviruses as elicitors of an autoimmune response in genetically predisposed patients. Regarding PV, the evidence supporting the role of EBV as a trigger is scarce4. In their study, Sagi et al. found no significant difference in EBV antibodies between patients with autoimmune blistering diseases (comprehending both BP and PV patients) and healthy controls. The authors concluded that their findings suggest a minor contribution of EBV in autoimmune blistering disorders.3Finally, to date, there are no reports of other autoimmune bullous diseases (such as linear IgA bullous dermatosis or epidermolysis bullosa acquisita) associated with EBV in adult patients.
On the other hand, EBV is more commonly associated with paraviral skin eruptions. In adolescents and young adults, primary EBV infection frequently results in infectious mononucleosis. In approximately 5% of patients affected by mononucleosis, the viral infection is associated with skin eruption characterized by heterogeneous lesions (such as macular, petechial, urticarial, scarlatiniform of erythema multiforme-like lesions).7A transient erythematous, maculopapular eruption involving trunk and upper extremities is also common in patients affected by mononucleosis who received antibiotic therapy in the previous 10 days.8In children, EBV is one of the most common infectious agents associated with Gianotti-Crosti syndrome (GCS). GCS (also referred to as papular acrodermatitis of childhood) is an acute, autolimited eruption involving acral skin sites. Clinically, GCS is characterized by symmetrical, monomorphic papular lesions tending to be asymptomatic. The most frequently involved sites are cheeks, buttocks, extensor aspects of arms, hands and thighs. Viral antigens have not been demonstrated in skin on ultrastructural or immunohistochemical studies.9GCS can rarely manifest with vesiculobullous lesions: a bullous form of GCS also falls within the differential diagnosis of paraviral bullous eruptions.
To date, there is only one case report of an EBV-induced autoimmune bullous disease in a child. Baldari et. al. reported the case of a 3-year-old girl developing chronic bullous disease of childhood (a variant of linear IgA bullous dermatitis) following recent EBV seroconversion. The authors hypothesized that EBV was able to stimulate the patient’s immune system (through immortalization of B lymphocytes and activation of T lymphocytes) ultimately leading to the development of an autoimmune disease.10Case reports of autoimmune bullous diseases in children induced by other Human-Herpes viruses (such as HSV and VZV) were also reported.2,11