A 43-year-old African American female with history of Herpes Simplex Virus (HSV) induced Erythema Multiforme (EM) presented to the Emergency Department after six days of evolving oral blisters, cranio-caudal rash, odynophagia, nonproductive cough, and pruritus. Patient had been hospitalized six months prior with a biopsy supported diagnosis of EM. At that time serology confirmed HSV as the etiology of EM. The patient had adhered to her acyclovir suppression therapy up until re-admission. Initial vitals signs, laboratory studies, imaging findings, and ECG were all unremarkable. Physical examination demonstrated intraoral ulcerations, erythema along the vermillion border, and diffuse target shaped lesions at different stages throughout her body. Repeat biopsy confirmed a diagnosis of Erythema Multiforme Major. The Patient received high dose prednisone, intravenous acyclovir and supportive care (topical anesthetics, pain control, and fluids). Over the course of a 4-day admission the patient demonstrated clinical improvement as evidenced by rash resolution. Patient was discharged with an oral prednisone taper in addition to twice a day acyclovir regimen. On outpatient follow up, the patient had healed completely from this episode of EM.
Discussion:
Erythema Multiforme is a visually distinct skin and mucosal manifestation, which has associations with infections, medications, pregnancy, and autoimmune disease. The presence in biopsies of Herpes Simplex antigens from six months to two years after onset in EM has lead to continue acyclovir suppression therapy for up to two years when HSV infection is the suspected trigger.
The largest case series of recurrent EM is a retrospective review of 48 cases. It was noted that 63% of recurrent EM episodes involve oral mucosa and approximately 23% of cases identified HSV as the etiology. 48% of patients in this review required escalation in therapy to include immunosuppressants in addition to antiviral medications. Our case represents a unique situation in an uncommon disease: development of an EM flare while undergoing suppressive therapy with acyclovir. A literature review failed to reveal other cases of recurrent flare occurred while on suppressive antiviral therapy. The recurrence of EM while on suppressive therapy suggests an evolving autoimmune condition rather than a static process related to a single exposure. In cases where suppressive therapy with acyclovir fails to prevent recurrences, steroids can be used to achieve disease control.
Conclusions:
This case underscores the unpredictable nature of EM recurrence and the need to continue surveillance in patients who recently developed EM. During this surveillance period, escalation of therapy to include immunosuppressive drugs might be required to achieve control.