Herpes-Associated Erythema Multiforme: A Case Report and Review of Literature

VESICULOBULLOUS DISEASE:  A case report of Erythema Multiforme

Karin Davis, DMD, MPAS; Calvin Smith, III, MD; Leslie Halpern, DDS, MD, PhD, MPH; Billy Ballard, DDS, MD; Olumuyiwa Esuruoso, MD

Erythema Multiforme is an acute inflammatory skin disease where 90% of the minor cases follow outbreaks of herpes simplex. Herpes associated erythema multiforme is thought to be an immune mediated complication of the herpes simplex I virus.  Langerhans cells infected with HSV travel to the epidermis and transfer viral DNA fragments to epidermal keratinocytes. HSV genes expressed in the skin leads to recruitment of HSV specific CD4+ T helper 1 cells that produce IFN gamma in response to viral antigens.  Release of IFN gamma initiates an inflammatory cascade that leads to epidermal damage and the inflammatory infiltrate that characterize cutaneous lesions of EM. Clinical presentation entails the onset of macular, papular, urticarial, bullous, or purpuric symmetric lesions on extensor surfaces as well as oral mucous membrane involvement. Target lesions with clear centers and concentric erythematous rings may also be noted. 

Discussion

Erythema multiforme is an acute inflammatory skin disease. 90% of EM minor cases follow outbreaks of herpes simplex which is thought to be an immune mediated complication. Development of EM secondary to HSV is thought to involve a cell-mediated immune process directed against viral antigens deposited into the skin. Langerhans cells with HSV travel to epidermis and transfer viral DNA fragments to the epidermal keratinocytes.  HSV genes expressed in the skin leads to recruitment of HSV specific CD4+ T helper 1 cells that produce IFN gamma in response to viral antigens. Release of IFN gamma initiates an inflammatory cascade that leads to epidermal damage and the inflammatory infiltrate that characterize cutaneous lesions of EM.

Herpes Simplex Virus I is a double stranded dna-enveloped virus with a central core containing viral DNA, an inner core surrounded by envelope derived from both host cellular membranes and viral glycoproteins, and an icosahedral capsid composed of viral proteins. Lifetime seroprevalence for HSV I can be up to 80-90%.

Patients usually present with onset of symmetric erythematous skin lesions with history of recurrence that may be macular, papular, urticarial, bullous, or purpuric in nature. Target lesions with clear centers and concentric erythematous rings or “iris” lesions may also be noted. The condition usually lasts 2-6 weeks and often reoccurs.

Suppressive therapy with acyclovir-400mg bid for 6 months decreases the recurrence rate. Valacyclovir may be effective in cases unresponsive to acyclovir.

References

1. Wetter, DA. Pathogenesis, clinical features, and diagnosis of erythema multiforme. UpToDate. (Accessed March 2014.)
2. Marx R, Stern D. Immune-Based Disorders. Oral and Maxillofacial Pathology: A Rationale for Diagnosis and Treatment. Vol 1.  2^nd ed. Illinois: Quintessence Publishing: 2012.